WO2010078441A2 - Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor - Google Patents

Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor Download PDF

Info

Publication number
WO2010078441A2
WO2010078441A2 PCT/US2009/069843 US2009069843W WO2010078441A2 WO 2010078441 A2 WO2010078441 A2 WO 2010078441A2 US 2009069843 W US2009069843 W US 2009069843W WO 2010078441 A2 WO2010078441 A2 WO 2010078441A2
Authority
WO
WIPO (PCT)
Prior art keywords
electrode
gel
electrode assembly
skin
adapter
Prior art date
Application number
PCT/US2009/069843
Other languages
French (fr)
Other versions
WO2010078441A3 (en
Inventor
Marom Bikson
Abhishek Datta
Varun Bansal
Jinal Patel
Johnson Ho
Preet Minhas
Jorge Vega
Dan Steingart
Lucas Parra
Original Assignee
Research Foundation Of The City University Of New York
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Research Foundation Of The City University Of New York filed Critical Research Foundation Of The City University Of New York
Priority to EP09837170.1A priority Critical patent/EP2384221B1/en
Priority to KR1020117017917A priority patent/KR101685124B1/en
Priority to AU2009334503A priority patent/AU2009334503B2/en
Priority to BRPI0918700A priority patent/BRPI0918700B8/en
Priority to JP2011543727A priority patent/JP5559197B2/en
Priority to MX2011007037A priority patent/MX2011007037A/en
Priority to CA2748007A priority patent/CA2748007C/en
Priority to US13/142,140 priority patent/US9440063B2/en
Publication of WO2010078441A2 publication Critical patent/WO2010078441A2/en
Publication of WO2010078441A3 publication Critical patent/WO2010078441A3/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0408Use-related aspects
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0087Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/009Sachets, pouches characterised by the material or function of the envelope
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0408Use-related aspects
    • A61N1/0456Specially adapted for transcutaneous electrical nerve stimulation [TENS]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0472Structure-related aspects
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0472Structure-related aspects
    • A61N1/0492Patch electrodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0472Structure-related aspects
    • A61N1/0492Patch electrodes
    • A61N1/0496Patch electrodes characterised by using specific chemical compositions, e.g. hydrogel compositions, adhesives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/20Applying electric currents by contact electrodes continuous direct currents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014External stimulators, e.g. with patch electrodes

Definitions

  • the present invention generally relates to methods, apparatus and compositions for administering neurocramal stimulation, and more particularly to methods, apparatus and compositions for applying neuro-cranial stimulation to particularized areas of the cranium with reduced discomfort and pain
  • Non-invasive neuro-cranial stimulation is an application of current through one or more electrodes on the neck or head for the purpose of changing function of nervous system
  • the purpose may be therapeutic including the treatment of neuropsychiat ⁇ c diseases, epilepsy, depression, Parkinson's disease, Alzheimer's Disease, neuro-degenerative disorders, obesity, and Obsessive-Compulsive-Disorder
  • the purpose may also be to enhance or accelerate cognitive performance, learning, or perception related tasks
  • Non-invasive neuro-cranial stimulation inherently involves passing current through an electrode into or across the skin
  • Transcranial direct current stimulation tDCS
  • tDCS Transcranial direct current stimulation
  • NINCS can lead to a wide range of discomfort in the subject receiving electrical stimulation
  • Discomfort can include any perception of tingling, pain, burning, or an otherwise undesirable sensation
  • skin irritation may occur, with such manifestations as flaking, redness, inflammation, burns, or any change in skin properties Discomfort and irritation may occur together or separately TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Irritation is most pronounced during or right after stimulation, but may be manifested a while after stimulation
  • Irritation and discomfort are not desired during NINCS for several reasons Irritation and discomfort cause pain or discomfort to the subject, complicate the desired effect of stimulation, and can lead to adverse health effects Further, irritation and discomfort may prevent optimal application of NINCS and reduce a subject's desire to receive NINCS
  • tDCS a type of NINCS
  • Conventional tDCS employs the passage of a constant direct current (nominally 260 uA - 3 mA) between an anode and cathode electrode, at least one of which is placed over the scalp
  • a constant direct current nominally 260 uA - 3 mA
  • the spatial focahty (targeting) of tDCS is considered pivotal for efficacy and safety Decreasing electrode scalp contact area is considered to improve spatial focality But for a given electrode current, reducing contact area increases current density, which in turn may increase hazards
  • the prior art electrodes fail to address minimizing skin irritation and pain dunng electro-stimulation activities like NINCS, particularly tDCS It is an object of the invention to optimize electrode parameters to minimize skin irritation and pain, with a specific focus on engineering small, more focal electrodes
  • an electrode assembly for neuro-cranial stimulation comprising an adapter including a receiver for attachment of an electrode, and a holder for use with an electrode and conductive gel or paste having a holder reservoir for storing TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the holding reservoir having rigid or semi- ⁇ gid wall restricting the flow of the gel or paste, and attaching means for attachment of the holder to the scalp of a subject
  • compositions for neurocranial stimulation gels that reduce or prevent irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness
  • a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pam, or redness dunng cranial neurostimulation compnsing selecting an appropriate combination of (1) gel and (2) solid conductor which support, control, or limit electrolyte depletion or formation at the cathode or anode
  • a method to reduce lrntation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during neurocranial stimulation comprising the steps of selecting a suitable electrode-skin contact area, selecting a suitable metal electrode material, selecting an electrode shape, selecting a rigid or semi-rigid holder, selecting an appropriate gel, selecting a chemical to apply to the gel or the skin, selecting a temperature for the gel/skin, combining the electrode and gel in the holder, wherein said holder determines the shape and volume of the gel, the position of the electrode relative to the gel, and the portion of skin exposed to the gel, TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • an apparatus for applying transcranial current through the scalp using a plurality of electrodes each electrode comprising at least one ngid or semi-rigid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of a gel, at least one electrical stimulation electrode with a proximal end and a distal end, the distal end making contact with a portion of the gel, and gel or paste contacting the scalp and containing no electrolytes, minimal electrolytes, or one or more electrolytes, and a cap or mesh positioned on the scalp and connected to the semi-rigid shell
  • an apparatus for applying transcranial current through the scalp using a plurality of electrodes each electrode comprising at least one semi-rigid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of the secondary gel, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the primary gel containing no electrolytes, minimal electrolytes, or one more electrolytes, a secondary gel contacting a portion of the primary gel and the scalp, wherein the secondary gel may contain no electrolytes or one or more electrolytes
  • an apparatus for applying transcranial current through the scalp using a plurality of units each unit comprising at least one semi-rigid shell with a distal end contacting the scalp and proximal end, a electrode mount with one portion contacting the semi-rigid shell and one portion contact the electrical stimulation electrode, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the gel, TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
  • a transcranial stimulation electrode comprising: an electrically conductive backing and an electrically conductive hydrogel matrix coated thereupon, said matrix being adapted to make contact with the skin of the patients and being sufficiently flexible to conform to the contours of the body.
  • electroencephalography uses small head electrodes and involves measuring brain potentials rather than applying brain-stimulating electrical currents.
  • These small electrodes have not been used or discussed before for neurocranial stimulation, because it was considered that the application of desired neurocranial stimulation current levels with small head electrodes would result in current densities sufficiently high to cause significant pains and/or discomfort.
  • the small head electrodes disclosed in the prior art could be modified for effective use in neurocranial stimulation, under particular design conditions which form a part of their invention as described herein.
  • Electrodes have been used for the purpose of drug delivery through the skin (transdermal drug delivery). These electrodes have not generally been used for electrical stimulation, electrotherapy, or neurocranial stimulation, but may also be suitable when modified according to principles of the present invention for neurocranial stimulation. Applicants incorporate by reference herein the following patents TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the term "about”, in the context of concentrations of components of the formulations, typically means +/- 20% of the stated value, more typically +/- 10% of the stated value, more typically +/- 5% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0 5% of the stated value Throughout this disclosure, certain embodiments may be disclosed in a range format It should be understood that the desc ⁇ ption in range format is mainly for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges Accordingly, the desc ⁇ ption of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual nume ⁇ cal values within that range For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc , as well as
  • Fig 1 illustrates an adapter element of an electrode assembly in accordance with the present invention
  • TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Fig 2 illustrates the adapter of Fig 1 in combination with a cap element provided in an unlocked position
  • Fig 3 illustrates the adapter of Fig 2 with the cap element provided in a locked position
  • Fig 4 illustrates the adapter of Fig 1 in combination with an accessory element
  • Fig 5 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
  • Fig 6 illustrates the adapter of Fig 5 in combination with another cap element provided in an unlocked position
  • Fig 7 illustrates the adapter and cap of Fig 6 with the cap provided in a locked position
  • Fig 8 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
  • Fig 9 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
  • Fig 10 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
  • Fig 11 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
  • Fig 12 illustrates the adapter of Fig 11 in combination with an accessory element
  • Fig 13 illustrates an adapter of an electrode assembly in combination with another accessory element
  • Figs 14(a) and 14(b) illustrate the adapter of Fig 1 with a preloaded gel, electrode, shield and cap
  • Fig 15 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
  • Figs 16(a) and 16(b) illustrate another adapter of an electrode assembly in accordance with principles of the present invention
  • Fig 17 illustrates the adapter of Fig 14 without the cap and with an additional shield TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Fig 18 illustrates the adapter of Fig 14 with an additional shield
  • Figs 19(a) and 19(b) illustrate an electrode according to the present invention
  • Fig 20 illustrates an electrode according to the present invention
  • Fig 21 illustrates an electrode according to the present invention
  • Fig 22 illustrates a mounting plate for an electrode assembly mounting apparatus according to the present invention
  • Figs 23 and 24 illustrate semi-circular band for electrode assembly mounting apparatus according to the present invention
  • Fig 25 illustrates a cross band design for an electrode assembly mounting apparatus according to the present invention
  • Fig 26 illustrates a circular band design for an electrode assembly mounting apparatus according to the present invention
  • Figs 27(a) - 28 illustrate electrode assembly mounting apparatus according to the present invention that include flexible arms that receive and position the electrode assemblies
  • Figs 29 and 30 illustrate electrode potential results for trials employing electrode assemblies having pellet type electrodes
  • Fig 31 illustrates electrode potential results for trials employing electrode assemblies having rubber-type electrodes according to the present invention
  • Fig 32 illustrates electrode potential results for trials employing electrode assemblies having Ag/AgCl disc electrodes according to the present invention
  • Fig 33 illustrates electrode potential results for trials employing electrode assemblies having Ag/AgCl Ring electrodes according to the present invention
  • Fig 34 illustrates pain developed during cathodal stimulation in va ⁇ ous subjects when stimulation is applied using variety of gels and variety of electrodes according to the present invention
  • Fig 35 illustrates pain developed during anodal stimulation in various subjects when stimulation is applied using variety of gels and variety of electrodes according to the present invention
  • Fig 36 presents bar graphs showing average run time of different electrodes with different electrolyte gels according to the present invention TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Fig 37 presents tables showing electrochemical behavior and summary of time and pain performance using a variety of gels and variety of electrodes according to the present invention
  • electrodes for transcranial direct current stimulation have taken the form or large square sponges
  • High current densities at specific areas on the head are desirable for efficacy of the electrical stimulation protocol, and current electrodes do not optimize these parameters
  • Small electrodes are ideal for the attainment of that efficacy and advancement of the field
  • the objective of this invention as accomplished herein is a practical small medical electrode suitable for neurocranial electrical stimulation and, in a preferred embodiment, transcranial direct current stimulation
  • the main goal is the ability to deliver desired levels of current in a way that is safe and comfortable for the patient
  • Previous electrode designs are unsuitable for several reasons Large electrodes must be made flexible to accommodate the curvature of the skin This results in poor control of the skin interface, for example the amount of gel or other material between the metal electrode and skin This has shown to result in current hot-spots and injury Small electrodes have been attempted, but previous designs of small electrodes were TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • electrodes are presented which fix the electrode position relative to the skm, maintain a minimum distance between metal and skin, and are able to improve and replicate the functionality of large electrodes in a safe and effective way
  • an electrode assembly for neuro-cranial stimulation comprising an adapter including a receiver for attachment of an electrode and a holder for use with an electrode and conductive gel or paste having a holder reservoir for stonng the gel or paste, the holding reservoir having rigid or semi-ngid wall restricting the flow of the gel or paste, and attaching means for attachment of the holder to the scalp of a subject
  • electrodes In order to ensure skin safety and comfort during transcranial stimulation, electrodes must be designed properly as descnbed in this invention It is also necessary to ensure electrode voltages do not increase to too high a level This design requires the balance of several engineenng factors We have found three properties which are cntical for effective, safe electrode apparatuses
  • gel-skin contact area should be within a desired range
  • the area should be minimized as to localize the location of current entry, and in order to practically control the uniformity of contact
  • the area should be maximized in order to reduce discomfort by distributing the current, and the area may be maximized in relation to (scaled by) the amount of current that will be passed
  • the distance between the nearest components of electrode and skin should be maximized, while the overall head-gear and electrode profile is not too high (i e standing far off of the head) that it is not practical
  • Classical electrodes used on the head for example those used for EEG, he directly on or very close to the surface of the scalp
  • electrodes and their holders be designed so that there is sufficient separation between the scalp and TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the contact area between the metal electrode and the gel should be maximized within the given constraints of the holder volume and electrode size If the electrode contacts only one surface of the gel material, the electrode-gel interface is an essentially a 2-dimensional interface However, if the metal electrode is immersed in the gel, this becomes a 3-D interface, thus greatly increasing surface area For example, a pellet electrode can be fit into a small diameter cylindrical plastic holder The plastic holder has a small skin contact area, but its depth allows the use of longer pellets with increased surface area Though, in our ⁇ ng design the electrode contact area is actually less than the skin contact area
  • the electrode holder is a ⁇ gid or semi-rigid material exposed at two ends, which is able to hold a volume of gel and an electrode
  • the electrode holding reservoir is cylindrical, conical, square, rectangular, circular, or a more complex permutation of these shapes
  • the holder is a cylinder or hyperboloid of a suitable volume for holding both the electrode and gel material
  • the material out of which the holder is made can be any rigid or semi-rigid material suitable to hold in place both a gel and an electrode
  • the holder is made out of a material selected from the group consisting of, but not limited TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
  • the holder is made out of semi-rigid plastic.
  • Fig. 1 illustrates an adapter 100 of an electrode assembly according to the present invention.
  • the adapter 100 comprises a body 101 including an interior compartment 102 having an interior surface that is substantially hyperbolical.
  • the interior compartment 102 includes a first compartment 102a for positioning an electrode of the electrode assembly, and a second compartment 102b for receiving a conductive gel of the electrode assembly.
  • the compartments 102a, 102b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 102b to flow into the first compartment 102a for the purpose of coming into physical contact with the electrode.
  • the first compartment 102a further comprises indentations 103 each including a land surface 103a for carrying a bottom surface of the electrode, grooves 104 for receiving tabs 110a of a cap 110 as illustrated in Fig. 2, and a channel 105 that defines a passageway through which an electrical conductor of the electrode may extend away from the first compartment 102a.
  • each tab 110a of the cover 110 may be inserted into a vertical portion 104a of a corresponding groove 104 to enable the cap 110 to be sealably positioned within a top portion of the first compartment 102a.
  • the cap 110 includes a surface HOb which is shaped to conformally and sealably contact a corresponding surface portion of the top portion of the first compartment 102a upon insertion into the first compartment 102a.
  • tabs 110c may be manipulated to rotate the cap 110 so that the tabs HOa move outwardly along horizontal portions 104b of the grooves 104 toward a closed position of the cap 110.
  • Fig. 4 illustrates an accessory 410 to be mounted on to the adapter 100.
  • Each tab 410a of an accessory 410 may be inserted into a vertical portion 104a of a corresponding groove 104 to enable the accessory 410 TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the accessory 410 comp ⁇ ses a body 401 including an inte ⁇ or surface 402
  • the interior surface 402 is divided into a first compartment 402a for positioning an electrode of the electrode assembly, and a second compartment 402b for receiving the conductive gel of the electrode assembly
  • the compartments 402a, 402b and 102a are in fluid communication with one another
  • Fig 5 illustrates an adapter 500 of an electrode assembly according to the present invention
  • the adapter 500 comp ⁇ ses a body 501 including an inte ⁇ or surface 502 having two compartments a first compartment 502a for positioning an electrode of the electrode assembly, and a second compartment 502b for receiving a conductive gel of the electrode assembly
  • Compartments 502a and 502b are divided by an indentation 503 from the surface 501
  • These indentations 503 form a land surface 504 on the interior surface 502 for carrying a bottom surface of electrode
  • Two protrusions 505a are designed for holding of the electrode at a distance from the side surface of electrode In
  • the cap in Fig 6 has protrusions 511 Two vertical extruded bars 511a and horizontal extrusions 511bare positioned underneath protrusions 505b du ⁇ ng locking of the cap 510 on adapter 500
  • each extrusion 511b of the cap 510 may be inserted underneath a protrusion 505b to enable the cap 510 to be securely and tightly positioned on an upper portion of first compartment 502a
  • the cap 510 includes a surface 513 which is shaped to conformally and sealably contact a corresponding surface portion of the top portion of the first compartment 502a upon insertion into the first compartment 502a
  • tabs 514 may be manipulated to rotate the cap 510 so that the tabs 510a move outwardly along horizontal protrusions 505b of the extrusion 505 toward a closed position of the cap 510
  • the protrusions 505b extend slightly downwardly along the honzontal direction so that, as the tabs 511b move outwardly along the protrusions 505b, the surface 513 is pressed against TCO Ref09A0008 Attorney Docket No 02830
  • Fig 8 illustrates an adapter 800 of an electrode assembly according to the present invention
  • the adapter 800 comprises a body 801 including an interior surface 802 that has 2 large compartments upper compartment 802a with large radius for the positioning of electrode and a lower compartment 802b with small radius for receiving conductive gel
  • the compartment 802a, 802b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 802b to enter the first compartment 802a for the purpose of coming into physical contact with the electrode
  • a horizontal extrusion 804 extends into the center of upper compartment 802a
  • a vertical extrusion 803 extends from horizontal extrusion
  • Compartments 802c and 802b are in fluid communication with one another A bottom surface of an electrode sits on the top surface of 804
  • Outward angular extrusions 805 extend from the extruded body 803 for tightening and holding the electrode at a central hole of electrode The extrusions
  • Fig 9 illustrates an adapter 900 of an electrode assembly according to the present invention
  • the adapter 900 comp ⁇ ses a body 901 including an interior cylindrical surface 902
  • the cylindrical surface 902 defines a first compartment 902a for positioning an electrode of the electrode assembly, and a second compartment 902b for receiving a conductive gel of the electrode assembly
  • the compartments 902a, 902b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 902b to enter the first compartment 902a for the purpose of coming into physical contact with the electrode
  • the first compartment 902a further comp ⁇ ses indentations 903 each including a land surface 903a for carrying a bottom surface of the electrode and a channel 904 that defines a passageway through which an electrode may be inserted into the first compartment 902a
  • the electrode in the adapter 900 may be mounted TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • a groove 905 on the outer wall of adapter 900 may be used to hold the adapter 900 tightly in position within a mounting apparatus
  • Fig 10 illustrates an adapter 1000 of an electrode assembly according to the present invention
  • the adapter 1000 comprises a body 1001 including an interior cylindrical surface 1002
  • the cylindrical surface 1002 defines a first compartment 1002a for positioning an electrode of the electrode assembly, and a second compartment 1002b for receiving a conductive gel of the electrode assembly
  • the compartments 1002a, 1002b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1002b to enter the first compartment 1002a for the purpose of coming into physical contact with the electrode
  • the first compartment 1002a further comprises extrusions 1003 each including a land surface 1003a for carrying a bottom surface of the electrode and vertical bars 1003b for holding electrode in position
  • a channel 1004 defines a passageway through which an electrical conductor of the electrode may extend away from the first compartment 1002a
  • An electrode in the adapter 1000 may be mounted from top portion of first compartment 1002a
  • a groove 1005 on the outer wall of adapter 1000 includes 3 flap like extrusions 1006 on the top which assist in mounting of adapter 1000 on a mounting apparatus
  • Fig 11 illustrates an adapter 1100 of an electrode assembly according to the present invention
  • the adapter 1100 comprises a body 1101 including an interior cylindrical surface 1102
  • the cylindrical surface 1102 defines a first compartment 1102a for positioning an electrode of the electrode assembly, and a second extended wide compartment 1102b for receiving a large volume of conductive gel and of the electrode assembly
  • the compartments 1102a, 1102b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1102b to enter the first compartment 1102a for the purpose of coming into physical contact with the electrode
  • the first compartment 1102a further comprises indentations 1103 each including a land surface 1103a for carrying a bottom surface of the electrode and bars 1104 for holding the electrode Tabs 1105 protrude from a top part of bars 1104 for TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • accessory 1110 includes an interior cylindrical surface 1112 with extrusions 1113 that includes a horizontal extrusion 1113a for positioning another electrode and vertical bars 1113b for holding electrodes
  • the cylindrical surface 1112 defines a first compartment 1112a for positioning an electrode of the electrode assembly, and a second compartment 1112b for receiving conductive gel
  • the compartments 1102a, 1112b and 1112a are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1112b to enter the first compartment 1112a and 1102a for the purpose of coming into physical contact with both of the electrode
  • Fig 13 illustrates an adapter 1300 of an electrode assembly according to the present invention
  • the adapter 1300 comp ⁇ ses two different bodies a lower body 100 and an upper body 1301
  • An inner surface 1302 defines a first compartment 1302a for positioning three different electrodes of the electrode assembly, and a second compartment 1302b for receiving a conductive gel of the electrode assembly
  • the compartments 1302a, 1302b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1302b to enter the first compartment 1302a for the purpose of coming into physical contact with the electrode
  • the first compartment 1302a further comprises three slots 1303 each including a land surface 1303a for carrying a bottom surface of the electrode Electrodes can be mounted from the top of the accessory 1300 into each of three slots 1303
  • Figs 14(a) and 14(b) illustrate an adapter 1400 of an electrode assembly according to the present invention
  • the adapter 1400 comprises an adapter 100 in which compartment 102b is prefilled with the conductive gel 1403 and covered with a removable plastic shield 1401 on the bottom surface of 100
  • the compartment 102a of adapter 100 is preloaded with an electrode 1404 and covered with a tightening holder cap 110 on the top portion of compartment 102a
  • Fig 15 illustrates an adapter 1500 of an electrode assembly according to the present invention
  • the adapter 1500 comprises an adapter 100 in which outer surface TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the groove 1501 is designed to attach the adapter 100 within an associated aperture in a mounting apparatus be rotating the adapter 1500 clockwise or anticlockwise within the aperture
  • Figs 16(a) and 16(b) illustrate an adapter 1600 of an electrode assembly according to the present invention
  • the adapter 1600 comprises an adapter 100 in which outer surface 101 comprises two grooves 1601 on each side of the surface 101 for sliding into an associated aperture in a mounting apparatus
  • Fig 17 illustrates an adapter 1700 of an electrode assembly according to the present invention
  • the adapter 1700 comp ⁇ ses an adapter 100 in which compartment 102b is prefilled with the conductive gel 1703 and covered with a removable plastic shield 1701 on the bottom surface of 100
  • the compartment 102a of adapter 100 is in addition preloaded with the electrode 1704 and covered with a removable plastic shield 1702 on the top portion of compartment 102a
  • Fig 18 illustrates an adapter 1800 of an electrode assembly according to the present invention
  • the adapter 1800 comprises an adapter 100 in which compartment 102b is prefilled with the conductive gel 1802 and covered with a removable plastic shield 1801 on the bottom surface of 100
  • the compartment 102a of adapter 100 is covered with a tightening holder cap 110 and the side surface 101 of adapter body 100 is also covered with a removable plastic shield 1803 from where the electrode 1804 can be slid into the holder 100 from the side
  • an adapter is made which is a cap to be placed on top of the plastic holder
  • the adapter locks in place by fitting with tabs on the two components
  • the tabs are on the adapter
  • the electrode holder is engineered with grooves on its inner surface in order to lock the adapter in place
  • an alternate TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the tabs are located on the outer surface of the electrode holder, and the grooves are located in the adapter
  • the electrode is pushed from the top of the holder into a set of ridges at a defined distance
  • the electrode adapter has a side opening at the level of the ⁇ dges, and the electrode may be slid into place from the side
  • a headgear may be used as discussed below
  • the electrode holder may be modified to allow secure attachment to the head-gear This includes the use of lock mechanisms, snap mechanisms, and screw mechanisms
  • the hardware for securing the electrode holder to the head-gear may be designed such that when the electrode holder is secured it is modified or functionally activated to allow stimulation
  • gel is sealed in the electrode holder and a seal is punctured when the electrode holder is attached to the head-gear
  • the size of the optimal electrode holder depends on the ranges of values that are optimal for gel-scalp contact area and the distance between the electrode and the skin
  • the gel-scalp contact area is less than 7 cm 2 and greater than 0 07 cm 2
  • the area is less than 3 cm 2 and greater than 1 cm 2
  • the dimensions of the orifice at the bottom of the electrode holder follow logically from the above dimensions, and are constructed as exposing the same area as the gel-scalp contact surface area
  • the safety objectives of the invention additionally necessitate that the holder be built high enough (i e in a large enough distance along the axis normal to the scalp) that it allows an optimal distance between the electrode and the skin
  • the distance between the electrode and the skin is between 025 cm and 1 3 cm In a preferred embodiment, the distance is between 0 5 cm and 0 8 cm
  • the total volume of the optimal holder is determined by the ideal area of the gel-skin contact o ⁇ fice, the distance (height) needed to accommodate the ideal distance between the electrode and the skin, and the inner contour and shape of the holder
  • the dimensions of the inner holder should be such that they can also TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the volume of the gel is between 0 1 ml and 10 ml In a preferred embodiment, the volume of the gel is between 0 5 mL and 5 mL, and preferably between 0 5 mL and 1 5 mL
  • the properties of the metal electrode are specifically considered
  • the electrode can be a ring, disk, pellet, or other shape
  • the electrode is a nng, designed to have the optimal surface area for taking up a defined space in the electrode holder
  • the metal-gel contact area is greater than 50% of the gel-skin contact area
  • the metal-gel contact area is greater than 100% of the gel-skm contact area
  • the metal-gel contact area is increased relative to the gel-skin contact area by increasing the exposed vertical projection of the metal in the gel
  • the increased vertical projection takes the form of the pellet electrode design
  • the maximal vertical dimension of the metal is greater than 3 times the horizontal diameter
  • the maximum electrode vertical dimension is less than the maximum horizontal dimension
  • the electrode metal gel contact area includes the top and bottom of said metal electrode thereby approximately doubling the contact area between the metal and gel (compared to a metal electrode sitting on top of a gel)
  • the surface of the metal electrode is convoluted to increase TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
  • the metal-gel contact area including the use of ridges, spikes, roughening, and curves.
  • the metal-gel contact area is increased through the process of sintering.
  • AgCl is used in the sintering process.
  • the center of the electrode is hollow to increase gel-metal contact area.
  • the hollow electrode is built into the wall of the electrode holder.
  • the electrode holder is constructed such that it allows maximal electrode surface area exposed to the gel by allowing multiple electrodes.
  • the adaptor has an extra accessory "sleeve" that allows for two electrodes to be used concurrently in the same holder, doubling surface area exposure.
  • an adapter is constructed with three openings to allow three separate electrodes to fully contact the gel in a single holder, thus increasing surface area exposure three-fold.
  • Figs. 19(a) - 21 depict several exemplary electrodes according to the present invention.
  • Figs. 19(a)and 19(b) illustrates an electrode 1900 according to the present invention.
  • the electrode 1900 comprises triangular spikes 1901 on the bottom surface to increase the metal surface area in contact with the gel.
  • Fig. 20 illustrates an electrode 2000 with its height increased for example by a factor of 3 to increase the gel to metal contact surface area. Electrode 2000 is mounted in the electrode adapter 100. Electrode 2000 has the same top 2001 and bottom 2002 surface area.
  • Fig. 21 illustrates an electrode 2100 designed in a spiral shape to increase the overall surface area in contact with the gel.
  • the electrode 2100 is configured to be immersed completely into the gel compartment 102b.
  • another embodiment of the invention entails a holder reservoir that has multiple compartments which may contain different gels
  • the solid conductor of the electrode may be metal, rubber, conductive rubber, Ag/AgCl, Ag, Gold In a preferred embodiment the solid-conductor is sintered Ag/AgCl
  • the electrode assembly of the invention includes a cylindrical, semi-rigid plastic electrode holder that exposes roughly 2 cm 2 of surface area to the scalp, combined with a sintered AgCl nng electrode that is inserted by guided ridges roughly 0 5 cm above the scalp orifice into the side of the electrode holder, and fully submerged in 1 ml gel of the preferred composition discussed in a later aspect below
  • connection between the electrode and the scalp should be sufficiently secure such that the electrode gel maintains contact with the metal electrode and with the scalp
  • the former is achieved by a plastic holder, as discussed in detail above
  • the latter requires a connection of the electrode assembly, or preferably multiple electrode assemblies, to the head
  • the most practical method for this use is a type of "head gear" to hold the plastic assemblies in place on the scalp
  • the technology to hold the plastic inset to the head is thus critical and as discussed herein may be optimized for the most practical use
  • a flexible cap with fixed position holes, is used to position an array of electrodes in fixed positions of the head
  • pre-set (EEG) positions it is preferred for both stimulation efficacy and safety to have the ability to place the electrodes in various specific positions on the scalp, depending on the specific stimulation application This is necessary to ensure specific targeting of brain regions, as well as to account for variations in head size and contour between individuals
  • the head (mounting) gear described here is designed to fit with the TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • plastic holders described in this invention although is applicable to electrodes and holders not described herein
  • multiple electrode assemblies are attached by a flexible band that wraps either from front-to-back or side-to-side across the head
  • This band contains both individual spaces for electrode assemblies, as well as slots for connection of sub-bands to splay across the rest of the head, each with their own places for electrode assemblies at fixed distances along the band
  • the main band is wrapped completely around the head and connected with a clasp
  • Fig 26 depicts an exemplary circular band design for an electrode assembly mounting apparatus according to the present invention
  • a head gear 2600 includes an adjustable plastic head band 2601 and fabric C shaped cross band 2604 which also include a circular fabric disc shaped area 2605 on the inter-section of 2604 bands
  • a circular knob 2603 is preferably provided to increase or decrease the length of head band All around the length of the head band 2601 there are protrusions 2602 to hold the cross bands 2604 in proper position
  • Cross band 2604 includes holes 2606 on a marginal end of each band that fit with the protrusions 2602 of the head band 2601
  • a disc shaped section 2605 has holes 2607 to accommodate electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously described)
  • the cross bands 2604 can be adjusted along different protrusions 2602 of the head band 2601 to accurately position the disc shaped area 2605 on head
  • the band is in a semi-circle shape, fixed on the head by bands diverging from the central main band
  • Figs 23 and 24 depict exemplary semi-circular band designs for electrode assembly mounting apparatus according to the present invention
  • Fig 23 illustrates a flexible head band 2301 with the webbing buckle 2302 on one end, to adjust the length of the band on the head
  • Various sub- band attachments 2303 may preferably be attached on to the holes 2305 of the band 2301 for modular positioning of the electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously desc ⁇ bed)
  • the adapters may be mounted on to different holes 2305 of the head band or of sub-bands 2304 TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Fig 24 illustrates a plastic "double C configuration" cross band 2400
  • An extra flexible band 2403 may be attached between two main bands of the cross band 2400
  • the cross band 2400 has numerous holes 2404 all along the surface for mounting of different kinds of electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously described) Electrodes may effectively be positioned anywhere on the head using different holes 2404 on cross band 2400
  • two main bands form a "cross" on top of the head, the ends of each movable arm of the cross containing movable electrode holders
  • Fig 25 depicts an exemplary cross band design for a head-fixing means according to the present invention
  • a plastic cross band 2501 comp ⁇ ses two plastic arms 2501a and 2501b crossing each other at the center
  • Two arms 2501a and 2501b can be moved along the center
  • a center portion of the two arms 2501a and 2501b provides a receptacle 2504 to attach an additional electrode adapter (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously descnbed)
  • an additional electrode adapter for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously descnbed
  • Electrode adapters for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously desc ⁇ bed
  • the head-fixing means entails a "mounting plate” design, which contains two bands to hold the unit in place, and 2 or more plates, each with specific flexible or predefined spaces for electrode assemblies, diverging from the main bands
  • the plates are connected to each other by hinges, therefore allowing for adjustment of individual plates to accommodate head size and contour to allow precise positioning
  • Fig 22 depicts an exemplary mounting plate design for an electrode assembly mounting apparatus according to the present invention
  • Fig 22 illustrates a circular plastic plate 2200 with numerous holes 2202 for modular positioning of the electrodes
  • the electrode plate is preferably made of three or more different parts attached to each other by hinge joints 2203, which allow a free movement of different plates 2200
  • Flexible band 2201 is also TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the plate has an orifice at the center 2207 to attach a small flexible band 2206
  • the small flexible band has holes on the marginal end to attach with the tabs 2205 along the internal margin of the o ⁇ fice 2207 of the plate 2200
  • Figs 27(a) - 28 depict variants of the semi-circular and circular band designs, respectively, in which the sub bands are replaced by flexible arms that are each attached to the semi-circular or circular band at a proximal end, receive an electrode assembly at a distal end and may be manipulated to flexibly position the electrode assemblies on the cranial skin surface of a user
  • Figs 27(a) and 27(b) illustrate a plastic semicircular head band 2700 with 5 flexible and movable arms 2701 radiating from the upper surface 2700a of the head band 2700
  • Each of the arms has a C shaped plastic cup 2702, which holds another plastic piece 2703
  • Each plastic piece 2703 holds an electrode adapter (for example, any of the adapters 100, 800, 1300, 1400, 1500, 1700 or 500 previously desc ⁇ bed)
  • an electrode adapter for example, any of the adapters 100, 800, 1300, 1400, 1500, 1700 or 500 previously desc ⁇ bed
  • Fig 28 illustrates a circular adjustable plastic head band 2800 with a groove 2802 all along the length of the head band 2800
  • Small plastic slider 2801 tabs protrude from the groove 2802 and can be manipulated to slide protruding flexible arms within the groove 2802
  • Each of the arms preferably have a C shaped plastic cup 2702, that holds another plastic piece 2703
  • Each plastic piece 2703 holds an electrode adapter (for example, any of the electrode adapters 100, 800, 1300, 1400, 1500, 1700 or 500 previously desc ⁇ bed)
  • the electrodes can be positioned on any location of the head
  • a flexible EEG cap is modified to allow arbitrary electrode positioning
  • a sub-band is placed at specific points on a flexible EEG cap
  • the electrode is attached to the scalp using a tape, glue, a clip or a ridge TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • brain stimulation techniques include Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation, Deep Brain Stimulation, Vagus Nerve Stimulation, Epicranial Stimulation, Transcutaneous Electrical Stimulation, and Transcranial Electrical Stimulation
  • a power source is connected to one Neurocranial electrode and other electrode on the body.
  • the additional electrode on the body may take on a range of forms known to those in the art or may adopt the technologies developed for Neurocranial stimulation
  • a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during neurocranial stimulation comprising using with a neurocranial stimulation device an electrode apparatus detailed in the present invention
  • the invention is related to any neurocranial stimulation technique, although the invention is also especially useful for transcranial stimulation, and in a particular application is transcranial direct current stimulation
  • the method comprises using the electrode apparatus described above, including a selected electrode, electrode holder with a gel and containment adapter as described in the invention, and a specific means of attachment of the head as described above
  • compositions for neurocranial stimulation gels that reduce or prevent irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness
  • the optimal gel to allow for efficient delivery of current while maintaining good protection against pain or discomfort during neurocranial stimulation has certain core components, including 1) A polymer, which functions includes support properties, 2) surfactants or surface acting agent, functioning to act on the skin to increasing permeability and/or change skin resistivity, 3) humectants, functioning to maintain gel hydration, 4) salts, functioning to increase electrical conductivity, 5) water, and 6) preservatives or other chemicals
  • core components including 1) A polymer, which functions includes support properties, 2) surfactants or surface acting agent, functioning to act on the skin to increasing permeability and/or change skin resistivity, 3) humectants, functioning to maintain gel hydration, 4) salts, functioning to increase electrical conductivity, 5) water, and 6) preservatives or other chemicals
  • These are the general components of a suitable gel, and is understood that the performance of the gel relates to its total properties after fabrication
  • Each of these components as ingredients may serve the function of another component, for example a surfactant with salt content
  • Fig 37 shows a sample of gels tested, their general composition features and other physical properties are noted While these gels all have similar features and can be used with metal electrodes, only the CChTV gels were able to show a minimal pain response for each electrode used (also see Figures 34 and 35 of this patent)
  • gels known in the art as conducting gels for electrode applications such as Signa gel, Spectra 360, Tensive, Redux, 1090 BioGel, and Lectron are suitable as a foundation or base composition for a gel, but require additional specific added components, detailed here, in order to function effectively with minimal pain or discomfort
  • Gels may use humectants to maintain gel hydration
  • Humectants include materials such as propylene glycol, and can be formulated with or without ethanol Propylene glycol may also serve as a preservative Propylene glycol may result in skin redness and its concentration should be regulated
  • propylene glycol is included at a concentration of 1 ⁇ M to 10 mM In a preferred embodiment, propylene glycol is included at a concentration of 1 ⁇ M to 1 mM In a still preferred embodiment, propylene glycol is included at a concentration of 1 ⁇ M to 50 ⁇ M
  • Oil solubihzing surfactants including ionic and non-ionic surfactants may be included in the gel Agents that solubilize the oil layer on the skin and or penetrate the skin may be used They may be particularly useful in lowering skin resistance Examples include sodium hexametaphosphate, t ⁇ sodium phosphate, and products such as TWEEN and SPAN made by Atlas Chemicals
  • the gel contains 0 5 to 5% sodium hexametaphosphate
  • a 1% composition of sodium hexametaphosphate in the gel is preferred
  • hydroxycellulose may be used at the polymer or polymer agent
  • the polymer that is used may be dissolved in a base liquid Suitable liquids include water, alcohol, acetone, dimethlysulfoxide (DMSO), dimethyl formide (DMF), or a polar solvent Water, alcohol, and mixtures thereof are preferred Additional agents, such as cross-linking agents, may be added to adjust gel properties including viscosity
  • a base liquid Suitable liquids include water, alcohol, acetone, dimethlysulfoxide (DMSO), dimethyl formide (DMF), or a polar solvent
  • Water, alcohol, and mixtures thereof are preferred Additional agents, such as cross-linking agents, may be added to adjust gel properties including viscosity
  • the polymer may be set or cross-linked via photons, thermal TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • a viscosity of 10,000 to 1,000,000 CPS is used, and more preferably the viscosity is within 150,000 to 200,000 CPS
  • the viscosity of the gel changes upon delivery due to dehydration, temperature changes, or skin contact
  • the viscosity increases from during a temperate change from approximately 25 degrees Celsius to 37 degrees Celsius
  • the viscosity decreases on contact with air, skin, or the holder surface
  • the changes in viscosity may be mediated or triggered by exposure to the air or to the skin as described in this invention
  • the gel contains an alcohol
  • the gel solidifies with an increase in temperature, in another with a decrease
  • electrolyte is key to the formulation of the gel
  • the electrolyte is any material that will ionize in the liquid
  • the electrolyte may contain ions that are in the metal electrode or in biological tissue
  • suitable matenals include lomzable salts, salts of acids or bases, or buffer solutions
  • inorganic salts include potassium chloride, sodium sulfate and organic acids or salts such as citric acid potassium citrate, or potassium acetate
  • added salts include NaCl added as a salt and/or present in a saline base More than one salt may be used NaCl supplements may be used including addition of 0 1 to 50 grams of NaCl per 100 grams of base
  • the electrolyte concentration is 001 to 15% by weight in water, and preferably between 0 25 to 4%, and more preferably 0 5 to 2 5%
  • the gel contains NaCl at a concentration of around 2% by weight
  • the gel may include various additive agents such as perfumes, colorants, and preservatives Suitable materials are those conventional in the art Specialized additional agents which act to protect or restore the skin include potassium bitartrate, coconut oil, sulfated castor oil, Aloe Vera, aloe barbadensis leaf juice, glycerin, synthetic beeswax, cetearyl alcohol, calcium acetate, and vitamins E, A, & D Local anesthetics may be added to the gel include Lidocaine, Benzocaine, or derivatives thereof In one embodiment, 6% Benzocaine is incorporated in the gel In a preferred embodiment, Lanacane, which includes 6% Benzocaine, is diluted in the gel at 1-50% by weight, or more preferred around 2 - 10% In another preferred embodiment, 2 5% Lidocaine and/or 2 5% P ⁇ locaine are incorporated in the gel In another embodiment, Lidocaine/P ⁇ locaine 2 5/2 5% Cream as sold by Fou
  • the electrode gel of the invention comprises Polymer, Humectants, Reverse Osmosis water, Surface active agent, Color, Sodium chloride (0 5% Saline Base plus NaCl supplement (CCNY-4)
  • the gel additionally contains around 2 5% lidocaine or benzocaine as an anesthetic (CCNY-5)
  • a fifth aspect of the invention provides specific combinations of (1) gel and (2) solid conductor of the electrode that allow for the reduction or prevention of irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during cranial neurostimulation
  • the electrode assembly may require steps beyond simply limiting gel pH or temperature
  • a particularly effective strategy is to specifically match the electrode with the gel(s) used for neurocranial stimulation
  • the gel/electrode combination used is predicted to support the active electrolyte formation or depletion of the solid conductor based on electrochemical knowledge
  • the gels have an ideal salt content
  • the gels were designed with an ideal level of Cl-, discussed below
  • the gel electrical conductivity is 0 5 S/m to 10 S/m
  • the conductivity is 1 S/m to 6 S/m
  • the electrical conductivity is 4 S/m to 5 S/m
  • the gel thermal TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the thermal conductivity is 001 W/m C to 005 W/m C In the most preferred embodiment the thermal conductivity is 0025 W/m C to 0035 W/m C
  • a metal electrolyte MX is converted to M + X- (aq) through the addition of one electron at the "negative” electrode and M is converted to MX by accepting X- (aq) ion and releasing electrons at the "positive electrode”
  • MX is converted to M+ + X (aq) through the removal of one electron at the "positive” electrode and M is converted to MX by accepting M+ (aq) ion and accepting electrons at the "negative electrode”
  • X may be a hahde such as chlo ⁇ ne or iodine
  • M may be any metal such that MX is any electrical conductive substance and the conversion of M to MX and MX to M is an electrochemically reversible or irreversible reaction
  • both the positive and negative metal electrodes are AgCl and the ion is Cl In a preferred embodiment
  • a corrosion resistant metal electrode such as but not limited to stainless steel alloys, gold, aluminum, nickel, copper
  • a corrosion resistant metal electrode such as but not limited to stainless steel alloys, gold, aluminum, nickel, copper
  • a conductive carbon pad, weave or mesh acts as a current collector where a neutral salt MX forms M+ and X- when dissolved in water
  • H 2 gas will evolve at the "negative" electrode and species X will deposit/evolve at the "positive" electrode, where species X may be chlo ⁇ ne or iodine
  • the metal electrode is platinum
  • the surface area of Pt contacting containing gel is greater than 0 5 cm 2 per 40 coulombs of charge transfer
  • the electrode should have a porosity between 0% (fully dense) and 50% with a mean pore size between 1 ⁇ m and 100 ⁇ m TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • more than one gel or electrolyte layer are used.
  • charge is transferred such that Xn- is passed through a gel, paste, or hydrated film electrolyte, through the skin and other bodily tissue and re-emerges through the skin to a second gel, paste or hydrated film electrolyte
  • a counter ion, Mn+ must exist, and may also carry charge
  • M and X is selected from ions commonly present in biological fluid or tissue
  • X is Cl and M is Ag
  • the concentration of X in the gel is selected to approximate the concentration of X present in biological tissue, such as skin, or biological fluid
  • Ag+ Cl- concentration is between 10 mM and 200 mM
  • the concentration of X in the gel is selected to exceed the concentration of X normally present in biological tissue
  • the [Ag] and [Cl] concentration in the gel is 200 mM to 2 M
  • two or more ions commonly found in biological fluid or tissue are present in the gel
  • the concentration of ions approximates the concentration of ion normally present in biological fluid or tissue
  • 5 ions in the gel approximate the concentration of 5 ions in biological tissue or fluid
  • the ions may correspond to the more dominant or active ions in tissue or more mobile ions
  • the ions may include Na, K, Cl, Ca, and Mg
  • X- is passed through a gel, paste or hydrated film electrolyte, transported to the skin where X- transfers charge through the skin to species Y, where X is deposited or evolved and species Y become Y- through necessary charge balance Species Y- is then transported through skin and bodily tissue to a second gel, paste or hydrate film electrolyte where species Y is evolved or deposited and species X converters to species X- through necessary charge balance Species X- is then transported to a second electrode and undergoes an electrochemical reaction as described above
  • M+ may be passed through a gel, paste or hydrated film electrolyte, transported to the skin where M+ transfers charge through the skin to species N, where M is deposited or evolved and species N becomes N- TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • X- is selected from ions not normally present in the body at significant concentrations
  • X- is chloride ion or iodine ion
  • the charge transfer density of X and Y is great than 1 coulombs per 0 5 cm2 of gel skin contact area but less than 100 coulombs per 05 cm2 of dell skin contact area
  • ions not normally present in significant quantities in biological tissue or fluid are omitted from the gel hi a still preferred embodiment, the activity or ions in the gel that are not present in significant quantities in biological tissue is less than 1 mM The inclusion or omission of ions normally present in biological
  • the electrolyte medium is a paste consisting of cellulose, any cellulose derivative or modification, or any natural fiber mixed with a brine solution consisting of any concentration of salt MX in water where M is sodium, potassium, magnesium or silver and X is chlorine or iodine where the concentration of salt in the b ⁇ ne is between 10 and 200 mM and the ratio of brine to lotion is such that a minimum viscosity of 100 CPS and a maximum viscosity of 100,000 CPS is maintained while maintaining a conductivity on the order of 10-3 S/cm or greater
  • the electrolyte medium is a paste consisting of cellulose, any cellulose derivative or modification, or any natural fiber mixed with a brine solution consisting of any concentration of salt MX in water where M is sodium, potassium, magnesium or silver and X is chlorine or iodine where the concentration of salt in the b ⁇ ne is between 10 and 200 mM and the ratio of brine to lotion is such that a minimum viscosity of 100 CPS and a maximum viscosity of 100,000 CPS is maintained while maintained a conductivity on the order of 10-3 S/cm or greater TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • any hydrophihc film or membrane (including but not limited to natural sponge, polyethylene oxide, any fluo ⁇ nated high molecular weight polymer with a molecular weight exceeding 100,000) hydrated with a b ⁇ ne solution consisting of any concentration of salt MX in water where M is sodium, potassium, magnesium or silver and X is chlorine or iodine where the concentration of salt in the brine is between 10 and 200 mM and the ratio of b ⁇ ne to lotion is such that a minimum viscosity of 100 CPS and a maximum viscosity of 100,000 CPS is maintained while maintained a conductivity on the order of 10-3 S/cm or greater
  • the film may be set or crosshnked via photons, thermal treatment or chemical treatment such as, but not limited to, deprotonation, oxidation or reduction
  • a supporting electrolyte in the form of ocean or sea water (100 mM to 500 mM solutions) which may be but not limited to NaCl, MgC12 or KCl in addition to the brine solutions discussed above
  • the support material for the electrolyte and electrode is specifically designed for the purposes of the invention
  • a non-reactive and non-conductive ceramic such as but not limited to A12O3 or TiO2 where the holder may or not be porous If porous the pore size will be between 30 ⁇ m and 500 ⁇ m
  • a non-reactive and non-conductive polymer such as but not limited to PVDF, PVC, Acrylic or ABS where the holder may or not be porous If porous the pore size will be between 30 ⁇ m and 500 ⁇ m
  • a composite of non-reactive and non-conductive polymers and ceramics where the polymers may be but are not limited to PVDF, PVC, Acrylic or ABS and the ceramics may be but are not limited to A12O3 or TiO2 where the holder may or not be porous If porous the pore size will be between 30 ⁇ m and 500 ⁇ m
  • Solid conductors suitable for use in the combination include those commonly used in the art for the application or monitoring of current across the skin Examples of such suitable conductors of the electrode include rubber, Ag, and Ag/ AgCl In a preferred embodiment, the electrode solid conductor is sintered AgCl TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the combination consists of gels and electrolytes that are, when combined, predicted to support the active electrolyte formation or depletion of the solid conductor based on electrochemical knowledge
  • the electrodes/gel combination is expected to support the formation and depletion of AgCl at the anode and cathode, respectively
  • the combination consists of an Ag or Ag/ AgCl solid conductor with CCNY-4 gel
  • a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during neurocranial stimulation comprising the steps of selecting a suitable electrode-skin contact area, selecting a suitable metal electrode material, selecting an electrode shape, selecting a rigid or semi-rigid holder, selecting an appropriate gel, selecting a chemical to apply to the gel or the skin, selecting a temperature for the gel/skin, combining the electrode and gel in the holder, wherein said holder determines the shape and volume of the gel, the position of the electrode relative to the gel, and the portion of skin exposed to the gel, preparing the skin, attaching the assembly to the head of an individual with suitable attachment means, checking the electrode resistance, and/or selecting a conditioning electrical waveform to apply to the skin,
  • the electrode shape is selected from the group consisting of — Pellet, Ring, recessed surface, saw shaped surface, concave surface, convex surface, a horse-shore shape, a square, a diaphragm, and Disc
  • the electrode shape is a ring
  • the ⁇ ng outer diameter is greater than 3 times the ring thickness
  • the inner ring diameter is greater than 50% of the outer ⁇ ng diameter TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the electrode shape is a pellet In a more preferred embodiment, the pellet length is greater than 3 times the pellets diameter
  • the gel is selected from the group consisting of modified existing electrode gels, the base existing gel including Signa, Spectra, Tensive, Lectron II and Redux
  • the gel is either a modified version of Signa containing additional salt, or is CCNY-4
  • the gel is CCNY-4
  • the temperature is selected from the range consisting of -10-45 degrees centigrade In a preferred embodiment, the temperature is selected from the range of 10 to 37 degrees centigrade
  • the electrical waveform is selected from the group consisting of DC, Interrupted DC, Symmetrical A C, Asymmetrical A C, Unbalanced triphasic, ramped, noise
  • the current is direct current, applied via the method of transcranial direct current stimulation (tDCS)
  • the skin preparation is selected from the group consisting of applying a skin treatment such as a chemical that may be earned is a delivery material such as a gel or cream, or electrically treating the skin, or mechanically altering the skin including through abrasion and scratching, or changing skin temperature
  • the resistance is selected from the group consisting of 100 ohm to 5 mega ohm, or more preferably 200 ohm to 1 mega ohm, or more preferably 300 ohm to 1 mega ohm, or more preferably 200 ohm to 600 ohm, or more preferably 100 ohm to 600 ohm, or more preferably 400 ohm to 600 ohm
  • the shape of the holder is selected from the group consisting of circular, cylindrical, conical, square In a preferred embodiment, the shape is a cylinder, or a hyperboloid permutation of a cylinder
  • an apparatus for applying transcranial current through the scalp using a plurality of electrodes each electrode comprising at least semi-rigid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of a gel, at least one electrical stimulation electrode with a proximal end and a distal end, the distal end making TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the apparatus has a semi-rigid shell which is attached to the head by a means provided in the invention, including a banding apparatus, a plate apparatus, a cross apparatus, or a flexible cap or mesh
  • said electrode has a cylindrical shape
  • the electrode has a shape selected from the group consisting of disk or nng shape
  • said gel has high-resistivity while in another embodiment the gel has low-resistivity
  • said shell has a circular distal end, while in another embodiment said shell has a square distal end
  • said electrode is a metal while in another embodiment said electrode is a ceramic
  • said electrode is silver while in another embodiment, said electrode is silver chloride
  • said semi-rigid shell includes a metal component while in another embodiment, said semi- ⁇ gid shell includes insulating material obstructing a portion of the distal end
  • said semi-rigid shell has a distal end with an aperture of least 1
  • said semi-rigid shell has an adjusting and attaching mechanisms for adjusting said semi-rigid shell to an optimal position on the said cap of mesh to suit an individual patient
  • said semi-rigid shell has a distal end with an area increased to reduce current density
  • the said semi- ⁇ gid shell has a distal end with a mesh to reduce current density
  • an apparatus for applying transcranial current through the scalp using a plurality of electrodes each electrode comprising at least one semi- ⁇ gid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of the secondary gel, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the primary gel containing no electrolytes or one more electrolytes, TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • a secondary gel contacting a portion of the primary gel and the scalp, wherein the secondary gel may contain no electrolytes or one or more electrolytes
  • said secondary gel has high- resistivity, while in another embodiment said secondary gel has low-resistivity
  • said electrical stimulation electrode is in contact with a portion of the secondary gel, while in another embodiment where said electrical stimulation electrode is not in contact with a portion of the secondary gel
  • said semi-ngid shell include separate compartments for the primary gel and the secondary gel, while in another embodiment, said semirigid shell include includes a single compartment for the primary gel and the secondary gel
  • an apparatus for applying transcranial current through the scalp using a plurality of units each unit comprising at least one semi-rigid shell with a distal end contacting the scalp and proximal end, a electrode mount with one portion contacting the semi-rigid shell and one portion contact the electrical stimulation electrode, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the gel, and a gel or paste contacting the scalp and containing no electrolytes or one ore more electrolytes
  • said semi-ngid shell encases a portion of said electrode mount while in another embodiment said electrode mount encases entire semi-rigid shell
  • said electrode mount is in contact with said gel or paste, while in another embodiment said semi-ngid shell is in contact with said gel or paste
  • said semi-electrode mount is circular or tubular
  • semi-electrode mount makes contact with said gel or paste on its inner surface while in another embodiment said semi-electrode mount makes contact with said gel or paste on its outer surface
  • said matrix is a hydrophobic polymer containing water in the amount of about 10% to 70% of the matrix
  • said matrix is substantially free of acid or of a salt of a strong acid
  • said matrix is substantially free of chloride salt
  • said matrix has a high resistivity compared to the scalp, while in another embodiment, said matrix has a low resistivity compared to the scalp In one embodiment, said matrix contacts the scalp in an area less than 1 cm2
  • a transcranial stimulation electrode comprising an electrically conductive backing and an electrically conductive hydrogel matrix coated thereupon, said matrix being adapted to make contact with the skin of the patients and being sufficiently flexible to conform to the contours of the body
  • the present invention facilitates non-invasive neurocranial stimulation by reducing or eliminating irritation or discomfort caused during electro-stimulation
  • stimulation can lead to irritation or discomfort
  • mechanisms by which stimulation can lead to irritation or discomfort including but not limited to 1) heating, 2) electrical stimulation of axons, 3) pH changes, 4) temperature changes, 5) electroporation or electro-permeation, 6) electrolysis 7) electrophoresis, 8) iontophoresis, 9) electro-osmosis
  • a device to generate electrical energy which is delivered to electrodes located on the head of a subject via electrically conductive wires
  • the device may control applied voltage and/or current
  • the current is in units of amperes (A) and may be on the scale of milli-Amperes (mA)
  • the current travels down the elect ⁇ cal wires to the electrode where it first enters a solid (semi) ⁇ gid conductor - for example a silver disk
  • the current density (in units of A/m2) desc ⁇ bes how the current spreads through the solid conductor - this spread is not uniform (i e current density is not the same TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the current density in one part of the solid conductor is not the same as the current density in other parts of the solid conductor Often current tends to concentrates along the edges of the conductor After reaching up to the conductor, the current (which is spread across the solid conductor) crosses into the conductive gel There is an interface between the solid conductor and the gel (this interface is elsewhere referred to as the "electrode” but in this document “electrode” refers to the entire head assembly)
  • the current density at this interface is particularly important Generally it is desired that the current density be as low as possible and as uniform as possible (i e no "hot spots") - although it is recognized that this may not always be the case
  • the current then moves though the gel where it continues to "spread out", the measure of this spreading is the value of current density in the gel Again, the current density in the gel is not uniform throughout the gel, as the current density in one part of the gel is different than the current density in another part of the gel
  • the gel contacts the skin There is an interface between the gel and the skin
  • the gel is composed of a material with a chemical composition and mate ⁇ al properties
  • the semi-ngid holder is composed of a material with a chemical composition and mate ⁇ al properties
  • the solid-conductor is composed of a mate ⁇ al TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the following material properties of the gel may be changed to reduce irritation or discomfort
  • the concentration of Cl is important in neurocranial stimulation
  • Addition of sodium chlo ⁇ de increase chloride as well as sodium concentration
  • Addition of the above chemicals increases sodium but not chlo ⁇ de concentration
  • Gel analgesic effect specifically by adding to the gel analgesics such as desc ⁇ bed in this invention
  • the following material properties of the solid conductor may be changed to reduce irntation or discomfort
  • Solid-conductor resistance (proximal to distal end) in the range of 1 ⁇ to l,000 K ⁇ or l0 ⁇ - l K ⁇
  • the solid conductor may be metal, rubber, conductive rubber, Ag/ AgCl, Ag, Gold
  • the solid-conductor is sintered Ag/AgCl In another preferred embodiment the solid conductor is conductive rubber In another preferred embodiment the ratio of the resistivity on the solid conductor and gel is controlled TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the electrode is composed of a metal, a gel, and holder for the solid-conductor and gel
  • the holder is an electrical insulator
  • the holder contacts the scalp or other part the head or neck
  • the holder generally forms a well or series of wells, in which the gel is inserted, in such a way that the holder defines the shape of the gel
  • the solid-conductor contacts the gel and generally is held in place by the holder
  • the holder generally also attached to an electrode cap or band with position the electrode on the head
  • a couple images show some examples of geometries and preferred embodiments that will reduce irritation or discomfort du ⁇ ng NINCS
  • the fin is part of the holder
  • the fin design includes one or more planes, the planes are vertical to the surface of the scalp, and serve two inter-related functions 1) they divide the gel intro compartments, 2) they position the electrode over these compartments in such a manner that a portion of the electrode contacts each of these compartments
  • the fins may be parallel plains or may be radially symmetrical around the electrode center, or some other pattern
  • Each fin may be rectangular shaped or may have a different shape
  • Some features of these geometries include - One or more ring metal solid- conductors, where the outer diameter ranges from 1 to 1000 mm or 11-12 mm and the inner diameter ranges from 1 to 1000 mm or 6- 7 mm A pellet solid-conductor with diameter ranging from 1 to 1000 mm or 1 5-2 5 mm and depth ranging from 1 to 1000 mm or 2-4 mm A disk solid-conductor with diameter ranging from 1 to 1000 mms or 11-12 mm
  • the holder divides the gel intro compartments, with the number of compartments ranging from 1 to 100, preferably one compartment for a single gel, or between 2 7, or more preferably 2 to 5 for combinations of gels
  • the holder divides the gel intro compartments and a different or same gel is applied to each compartment
  • the holder fixes the distance of the proximal solid- conductor surface to the scalp surface, where the distance ranges from 0 1 to 100 mm or 2-5 mm
  • the holder fixes the position of the solid-conductor using a fin design, where the number of fins ranges from 1 to 1000 and from 2 to 7 and from 3 to 5 TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the electrode surface is modified with needles, micro-needles, micro- architecture, nano-features, or nanotubes
  • the solid-conductor is a ⁇ ng, positioned on a 3- fin radially symmetrical electrode holder In another preferred embodiment, a single holder accommodates two solid-conductors On another preferred embodiment, the solid-conductor surface area is increased by change the surface shape of the solid conductor including adding indent or extensions including curved extensions Chemical pre-treatment:
  • the skin or electrode may be pre-treated by application of a chemical
  • the chemical may be applied before the treatment for days, hours, or seconds
  • the chemical may be applied to the skin or to the electrode
  • the chemical may be applied by a variety of means including brushing, squeezing, injection, or pouring
  • the chemical may be allowed to permeate the skin or the gel
  • the chemical may be applied during NINCS
  • the chemical may be applied after NINCS
  • the chemical may be dissolved or mixed in a liquid carrier
  • the pre-conditioning cream is applied below the electrode
  • the pre-conditioning cream is applied >5 minutes before the main stimulation phase
  • the resistivity of the pre-conditioning cream is selected to be higher than the resistivity of the gel In this case, the conditioning cream will modify the current spread including increasing the uniformity of current entry
  • the resistivity of the pre-conditioning cream is selected to be less than the resistivity of the gel In this case, the cream will not significantly increase the overall resistance to current flow, thus minimizing the contribution to electrode potential
  • the cream will form an interface to both the gel and the skin with changes as described below
  • the appropriate pre-conditioning cream can be matched to the gel used as described in this invention, and based on the design specifications and constraints as described in this invention
  • the preconditioning cream includes the primary ion earner in the gel
  • the pre-conditioning cream excludes the primary ion carrier in the gel TCO Ref09A0008 Attorney
  • the factors will also take into account if the primary ion carrier in the gel has been matched to a primary ion earner in the tissue or skin
  • the properties of the pretreatment cream are essentially those of the electrode gels described above in this document Therefore, in the embodiment the pre-treatment creams are the same composition as optimal electrode gels, but are applied to the scalp prior to stimulation
  • the chemical may changes the properties of the skin or may changes the properties of the electrode or may change how current moves between different materials and into and through the skin
  • Some of the goals of chemical pre-treatment are to alter skin resistance, alter skin resistivity, make the skin more uniform in resistivity, remove resistivity hot spot or cold spots, block skin pores, open skin pores, change the properties of skin pores (including sweat glands and hair follicles), change the properties of blood vessels in the skin including dilation response, change the properties of axons the skin including firing threshold, the properties of muscle cell including firing threshold and mechanical responses
  • the chemical may be a substance that blocks or opens sweat pores Chemicals include
  • Buffering agents or pH-balancing creams such as Acid Mantle that help restore acid balance of the skin
  • This cream can be used under the one that produces a basic product, to maintain a balance Additionally, it may be useful to use different creams or topical solutions under the anode and cathode based on the properties of the creams,
  • Pain ointments such as Hydrocortisone 1% cream with Zinc Oxide, one of the main ingredients in creams to reduce irritation
  • a combination of zinc oxide cream (Balmex, Desitin), vaseline, and aluminum acetate (burrow's solution) can also be made to reduce irritation
  • Anti-inflammatory agents such as Cellex-C Sunshade SPF 30+, or anesthetic or analgesic creams or ointments, such as benzocaine, lidocaine, pnlocaine, or lanacane TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the chemical may be a pH buffer such as - NaH2PO4
  • the chemical may be penetration enhancer to reduce the skin impedance like stearic acid, propylene glycol, linoleic acid, ethanol, sodium lauryl sulfate, oleic acid, stearic acid
  • the chemical may be activated or transported by electricity either du ⁇ ng NEvJCS or during electrical pretreatment
  • the chemical may have high conductivity ranging from 1 to 1 ,000,000 or preferably greater than 40,000, or most preferably 40,000- 60,000 ⁇ mhos/cm or
  • the chemical may be an anesthetic such as topical solution
  • the chemical may reduce pain or irritation such as Tronolane
  • the chemical may be a muscle relaxant such as Relaxaid
  • the chemical may induce temperature changes such as BenGay
  • the chemical is applied to the surface of the skin and then the electrode is positioned over that surface
  • the chemical is applied to the electrode on the surface which will contact the skin, and the electrode is then positioned on the skin
  • electrical current may be applied prior to the actual stimulation protocol, effectively sensitizing the subject
  • the current is applied through the same electrode that is subsequently used for stimulation
  • separate electrodes may be used for electncal pre-treatment
  • Electrical pre-treatment may be applied before the treatment for days, hours, or seconds Additionally, electrical pretreatment may be applied du ⁇ ng or after NINCS
  • the electncal pre-treatment step works by selecting an approp ⁇ ate waveform for pre-treatment
  • the pre-treatment electrical waveform may or may not be same as NINCS
  • Using a pre-treatment waveform different than that of NINCS may be beneficial in the following ways 1) the pre-treatment waveform does not itself cause any skin irritation or discomfort but changes skin or electrode conditions such that TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the pre-treatment waveform does not change brain function but rather changes skin properties
  • the electrical pre-treatment waveform used may be DC in the amplitude range of 0 1 to 1 mA and applied for 0 1 to 60 minutes
  • the electrical pre-treatment waveform may be AC in the amplitude range of 0 1 to 1 mA the frequency range of 0 01 to 500 kHz and applied for 0 1 to 60 minutes
  • the electrical pre-treatment waveform may pulsed with frequency range 0 01 to 500 kHz, and pulse width of 0 1 us to 100 seconds, and an inter-pulse interval 0 1 us to 100 seconds
  • the electrical pre-treatment waveform may be noise or noisy including white noise, Gaussian noise, 1/f noise, thermal noise, short noise
  • the electrical pre-treatment waveform may be a ramp with a slope of 1 mA per minute to 1 mA per ms
  • the electrical pre-treatment waveform may be Gaussian with standard deviation of value 0 to 10 or 0 to 10000
  • the electrical pre-treatment waveform may a combination of the above and may involve repetitive pre-s ⁇ mulation
  • the electrical pre-treatment waveform may involve getting subject feed-back
  • a low level of conditioning DC current is applied prior to stimulation
  • the conditioning DC current is below 05 mA and may be below 0 1 mA
  • the conditioning DC current is applied for 1 minute to 30 minutes
  • the conditioning DC current may be ramped up and down slowly including at a rate of 0 1 mA per minute
  • the NINCS therapy current is applied (which may also be DC current but will generally be of higher and more brain effective amplitudes - in this case the conditioning current may be the same polarity or of opposite polarity to the DC electrical therapy current)
  • the interval between the DC conditioning current and the NINCS electrical therapy current can vary between 0 and 10 minutes
  • the resistance of the electrode may be tested - this resistance reading may inform if another additional conditioning current in necessary prior to NINCS electrical therapy stimulation (see also feed-back monitoring below)
  • the electrical pre-treatment waveform increased monotomcally
  • the intensity of the pre-treatment waveform increases and then decreases prior to the main stimulation phase
  • a still TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the intensity of the pre-treatment electrical waveform returns to zero
  • the waveform is sinusoidal
  • the sinusoidal waveform has a zero average intensity
  • the sinusoidal waveform has a non-zero average intensity where that average intensity may be positive or negative and may be matched to the intensity and polarity of the main electrical treatment stage
  • the waveform is a sinusoidal with modulated amplitude
  • the sinusoidal frequency is greater that 1000 Hz
  • the sinusoidal frequency is greater than 10000 Hz
  • the waveform is composed of two or more sign waves
  • the difference in frequencies between the two waveforms is greater than 100 Hz
  • the difference in frequencies between the two waveforms is less than 100 Hz
  • the electrical pre-treatment waveform incorporates pulses Feed-back monitoring:
  • the conditions of the electrode and/or skin may be monitored before, during, or after stimulation The conditions are monitored by sensing a parameter These readings may be used to turn off NINCS or adjust NINCS properties including all the properties described above
  • the device or sensor which monitors a condition or parameter may be integrated into the NINCS device itself, or may be a separate device, or may have some overlapping components
  • the parameter monitored may be displayed to the subject / operator for example using a digital display, or indicator lights, or an audio monitor
  • the parameter may be stored for later retrieval for example of a storage device
  • the parameter or combination or parameters may be processed using an algorithm or mathematical function This algorithm or mathematical function could incorporate addition, subtraction, averaging, averaging over time, filter, low-pass filtering, high- pass filtering, liner or non-linear operations, user defined operations
  • the output of this algorithm and the parameter form a reading that may be used to change NINCS parameters TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • NINCS For each reading there may be a 'threshold' value which is used to determine if NINCS should begin, stop, be interrupted, be changed, or if a warning should be provided to the subject or operators
  • the electrode voltage and electrode current are monitored and stimulation is stopped if either voltage or current exceed a threshold, if the rate of voltage change or current change exceed a threshold, if the current* voltage exceed a threshold, or if the rate of change of the current* voltage exceeds a threshold
  • the stimulation may stop instantaneously or may be gradually reduced
  • a warning may be provided to the subject or operator
  • the stimulation may stop automatically or after the subject or operator activates a manual switch or trigger
  • the electrode voltage and electrode current are monitored and stimulation is decreased if either voltage or current exceed a threshold, if the rate of voltage change or current change exceed a threshold, if the current*voltage exceed a threshold, or if the rate of change of the current*voltage exceeds a threshold
  • the stimulation current and/or voltage are automatically reduced to be maintained below the threshold
  • a warning may be provided to the subject or operator The subject or operator may choose to override the otherwise automatic reduction by activation of a manual switch or trigger
  • the resistance of the electrode is monitored.
  • the resistance may be monitored by application of a test voltage or current pulse
  • the test voltage or current pulse may be sufficiently small such that no brain modulation or skin irritation results
  • the test voltage or current pulse may be DC or AC
  • the resistance may act as a threshold for feed-back to determine is NINCS may begin or may continue
  • the resistance of the electrode may be passed through a mathematical function to determine the resistance quality
  • the resistance of an electrode may be compared again another value such as the resistance of another electrode
  • the impedance of the electrode is monitored
  • the impedance may be monitored by application of series of test voltages or current pulses
  • the series of test voltages or current pulses may be sufficiently small such that not brain modulation or skin irritation results
  • the series of test voltages or current pulses may be DC or AC of different frequencies
  • the impedance may act as a threshold for feed-back to determine is NINCS may begin or may continue
  • impedance of the electrode may be passed through a mathematical function to determine the impedance quality.
  • the impedance of an electrode may be compared again another value such as the resistance of another electrode.
  • a temperature probe is inserted into the gel or portion of the electrode and monitors temperature.
  • the temperature probe may be a thermocouple or a thermistor or optical.
  • a pH probe is inserted into the gel or portion of the electrode and monitors pH.
  • the pH probe may be an electrochemical or solid- state or optical.
  • the electrode voltage with a threshold for change ranging from 1 to 1000 V, and 50 to 150 V.
  • the electrode voltage change over time ranging from 0.001 V per hour to 1000 V per second.
  • the electrode current, with a threshold for change ranging from 0.1 to 1000 mA, and 1 mA to 20 mA.
  • Electrode configurations materials and geometry
  • Each electrode- gel configuration was independently evaluated as an anode or cathode.
  • Plastic holders for all electrodes were used to position electrodes over the skin and standardize gel volume used.
  • Plastic holders for all pellet electrodes held ⁇ 90 ⁇ 5 mm 3 of gel volume with a gel-skin contact area of -25 ⁇ 2.5 mm 2 .
  • Customized holders for ring/disc electrodes contained ⁇ 280 ⁇ 10 mm 3 of gel and provided ⁇ 95 ⁇ 5 mm 2 gel-skin contact area.
  • a constant current stimulator (CX 6650, Schneider Electronics, Gleichen, Germany) was used to apply direct current for all trials, with a maximum driving voltage capability of 66 7 Volts A current intensity of 2 mA was used for up to 22 minutes, with automatic on and off ramps of 10 sec to avoid "stimulation break" effects
  • the stimulator automatically terminates stimulation at an output potential (total potential across both electrodes and agar/tissue) of 66 7 V, which was used as a cut-off point in all trials P ⁇ or to and after stimulation, total cell resistance (see below) of the agar gel or forearm skin was measured using a RMS digital multimeter (FLUKE 177, FLUKE Corporation, Everett, WA, USA), stimulation was only initiated when the total cell resistance was less than 8 M ⁇ Electrode Potential, pH, and Temperature Studies
  • the electrodes were mounted with gel on a flat block of agar made with 150 mM (physiological) NaCl
  • the rationale was to measure changes at only one "active" anode or cathode electrode without contribution from the two return electrodes
  • the two return electrodes generally sintered Ag/AgCl disc or ⁇ ng TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Electrode potential generally refers to the total potential over the entire assembly of electrodes, gel, and skin
  • a calibrated micro pH electrode (Orion 9810BN, Thermo Scientific, Waltham, MA, USA) and a digital pH meter (SMlOO, Milwaukee Instruments Inc , Rocky Mount, NC, U S A ) were used to measure pH in the active electrode's gel at the agar surface, at va ⁇ ous exposure durations
  • the stimulation was turned off, the solid conductor was removed from the gel, and the micro pH electrode was inserted into the gel within 5 seconds pH was recorded after exposure durations of 1 mm, 5 mm, 10 mm, 15 mm and 20 mm pH studies were conducted on four solid-conductors (Ag pellet, Ag/AgCl sintered pellet, Rubber pellet, Ag/ AgCl sintered ring) in combination with three electrolyte gels (Signa Gel, Lectron II Gel, CCNY4 Gel)
  • a Type T Thermocouple Thermometer (BAT-10, Physitemp Instruments, Clifton, NJ, USA) was used on the bottom surface of
  • the stimulator automatically stopped stimulation if a total potential of 66 7 V (cut-off voltage) was achieved In cases when stimulation was TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • the "stimulation time” was scored as 22 minutes and the maximum pH and temperature changes during the 22 minutes were noted In cases when a potential of 667 V was reached prior to 22 minutes, the “stimulation time” was scored as the time when the potential reached 66 7V, the maximum pH and temperature at this "stimulation time” was then noted
  • Subjective Sensation Eight healthy subjects (6 males and 2 females, 19-35 years) participated in each experiment All gave written informed consent before being included in the study The study was approved by the IRB board of the City College of New York Sensation tests were restricted to four solid-conductors (Ag pellet, Ag/AgCl sintered pellet, Rubber pellet, Ag/ AgCl sintered ⁇ ng) and three gels (Signa, Lectron II, and CCNY4) The experiments were conducted on the distal or proximal forearm, as arbitrarily preferred by the subjects For sensation studies, the rationale was to determine the effect of the "active" electrode (either cathode or anode) Two Ag/AgCl ⁇ ng electrodes were used as "return" electrodes Return electrodes were positioned on opposite sides of the active electrode Each return electrode was immersed in ⁇ 280 ⁇ 10 mm 3 volume of Signa Gel Regions of skin with visible irritation or cuts prior to stimulation were avoided There were no steps taken to otherwise prepare the skin prior to stimulation
  • Stimulation was applied for up to 22 minutes with subjects scoring pain (on a 1 to 10 analog scale) every minute beginning two minutes before, every minute du ⁇ ng, and ending two minutes after stimulation
  • subjects were prompted to descnbe the sensations ("burning", "prickling” etc ) P ⁇ or to stimulation each subject indicated a personal termination value (at or below 5) at which stimulation would be stopped by the operator
  • each subject could request to stop the stimulation at any point of the expe ⁇ ment, regardless of the current pain score or nature of perception If stimulation was stopped p ⁇ or to 22 minutes of exposure, the pain score at termination was noted Greater than 1 hour of delay was allowed between expe ⁇ ments, and the stimulation site (e g arm) was changed for consecutive experiments Participants were blinded to the type and combination of solid-conductor and gels tested After stimulation any skin lesions or redness was noted Results Electrode Potential TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Electrode potential across conductive agar was recorded during 2 mA DC stimulation During clinical stimulation it is desirable to minimize electrode potential for several reasons including 1) voltage limits on constant current stimulators, 2) increased ⁇ sk for skin injury including through electrochemical reactions (limited by electrode over-potential) and heating Cathodal stimulation with rubber pellets resulted in variable voltage increases whereas electrode potential remained less than IV for all other solid-conductors Anodal stimulation with all solid-conductors resulted in increased and variable electrode potential values
  • Electrode potential results for anodal stimulation experiments are summarized, we report both the average potential and variability across trials (5 trials per electrode/gel combination) These potentials can also be interpreted as reflecting changes in the resistance at the electrode site during DC anodal stimulation When the stimulator potential reached 66 7 V (driving voltage capacity of CX 6650), stimulation was automatically stopped and this was recorded as the maximum exposure duration ("stimulation time") for that trial, otherwise the exposure duration was scored as 22 minutes
  • Figs 29 and 30 illustrate the electrode potential results for trials employing electrode assemblies having pellet type electrodes
  • Fig 29 illustrates a current-induced polarization of a AG pellet type electrode assembly shown as apparent voltage across anode over time 2 mA DC current with indicated gels was passed, and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines shows average The electrode assembly shown is used only to indicate the general design
  • Fig 30 illustrates a current-induced polarization of a Ag-AgCl pellet type electrode assembly shown as apparent voltage across an anode electrode assembly over time 2 mA DC current with indicated gels was passed, and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines shows average The electrode assembly shown is used only to indicate the general design
  • Fig 31 illustrates the electrode potential results for trials employing electrode assemblies having a rubber type electrodes
  • a current-induced polarization of a rubber pellet type electrode assembly is shown as apparent voltage across an anode electrode TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
  • Fig 32 illustrates the electrode potential results for trials employing an electrode assembly having a disc type electrode Current induced polarization of an Ag-AgCl disk type electrode assembly is shown as apparent voltage across anode over time A 2 mA DC current with indicated gels was passed and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines show an average The electrode assembly shown is used only to indicate the general design
  • Fig 33 illustrates the electrode potential results for trials employing an electrode assembly having a ⁇ ng type electrode Current induced polarization of an Ag-AgCl ring type electrode assembly is shown as apparent voltage across an anode electrode assembly over time 2 mA DC current with the indicated gels was passed, and the change in voltage with time was measured Back dotted curves show five repeats while solid lines show averages The electrode assembly shown is used only to indicate the general design
  • Fig 36 presents a summary of run times by electrode type according to the trials of Figs 31 - 33 Average potential run time profiles during anodal stimulation for designed electrode assemblies 22 minutes represents the maximum time tested For each electrode, the run times are indicated for seven gels from left to right Electro Gel, Lectron, Redux, Signa, Spectra, Tensive, CCNY4
  • Fig 37 presents a summary of pain and electrochemical performance of designed Neurocranial electrode assemblies 2 mA of current was used in all cases
  • a summary of average pain scores (high, and average over stimulation period) across subjects is provided, together with a percentage of subjects electing to stop stimulation prior to 22 minutes, a percentage of subjects with redness under electrodes following stimulation, and indications of peak changes in temperature and in pH of the gel
  • anodic stimulation could be consistently applied only with Lectron II gel and after stimulations a removable, black paste-like residue was observed along the surface of the electrode Using the Rubber pellet, some variability in exposure time was observed across various trials and gels, in addition, a relatively wide deposition layer was observed on the rubber after stimulation This layer was easily deterged and an apparently intact and unaffected rubber solid-conductor surface remained Using both Ag/AgCl sintered ⁇ ng and Ag/ AgCl disk electrodes, 22 minutes of stimulation could be consistently applied, in combination with any gel, with Ag/AgCl disk having the lowest average electrode potentials Gel pH and Temperature
  • the electrode interface can proceed, no significant electrochemical processes initiate.
  • dissolution of silver chloride and reduction of the silver ions facilitates faradaic charge delivery across the electrode.
  • This layer may "chemically insulate" the electrode from further reactions, which in turn may explain the increase in the electrode over-potential and decrease in run time.
  • This hypothesis is supported by our observation that after removing this layer, running a second stimulation supports run times comparable to the novel case of the Ag pellet electrode. However, running a second stimulation without removing the AgCl layer, results in run times of less than a minute. The failure of Ag/ AgCl pellets to support anodic stimulation may indicate 1) the formation of a similar chemical insulation layer; or 2) insufficient reservoir of available Ag.

Abstract

An electrode assembly for neuro-cranial stimulation includes an electrode, a conductive gel, and an adapter including an interior compartment for positioning the electrode relative to the adapter and for receiving and retaining the conductive gel. The conductive gel contacts the electrode along an electrode-gel interface. An orifice at one end of the interior compartment and adjacent to a positioning surface of the adapter for positioning the electrode assembly against a skin surface of a user enables the conductive gel is able to contact the skin surface of the user to define a gel-skin interface, such that a minimum distance between the electrode-gel interface and the gel-skin interface is maintained between 0,25 cm and 1.3 cm. An electrode assembly mounting apparatus is provided for adjustably positioning a plurality of electrode assemblies against target positions on the cranium.

Description

TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
METHODS FOR REDUCING DISCOMFORT DURING ELECTROSTIMULATION, AND COMPOSITIONS AND APPARATUS
THEREFOR
Cross-Reference to Related Application
The present application claims priority to U S Provisional Patent Application No 61/141,469, filed on December 30, 2008 and entitled "A Method for Reducing Discomfort During Electrostimulation & Electrodes Therefor "
Field of the Invention
The present invention generally relates to methods, apparatus and compositions for administering neurocramal stimulation, and more particularly to methods, apparatus and compositions for applying neuro-cranial stimulation to particularized areas of the cranium with reduced discomfort and pain
Background of the Invention
Non-invasive neuro-cranial stimulation is an application of current through one or more electrodes on the neck or head for the purpose of changing function of nervous system The purpose may be therapeutic including the treatment of neuropsychiatπc diseases, epilepsy, depression, Parkinson's disease, Alzheimer's Disease, neuro-degenerative disorders, obesity, and Obsessive-Compulsive-Disorder The purpose may also be to enhance or accelerate cognitive performance, learning, or perception related tasks
Non-invasive neuro-cranial stimulation (NINCS) inherently involves passing current through an electrode into or across the skin Transcranial direct current stimulation (tDCS) is an example of non-invasive neurocramal stimulation in which direct current is applied directly to the scalp in order to pass current to specific brain regions NINCS can lead to a wide range of discomfort in the subject receiving electrical stimulation Discomfort can include any perception of tingling, pain, burning, or an otherwise undesirable sensation Additionally, skin irritation may occur, with such manifestations as flaking, redness, inflammation, burns, or any change in skin properties Discomfort and irritation may occur together or separately TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
They typically occur just under or around the electrode, but may occur between electrodes or elsewhere Discomfort is typically expeπenced during or immediately after stimulation, but may be felt at longer time points after stimulation has been ceased Irritation is most pronounced during or right after stimulation, but may be manifested a while after stimulation
Irritation and discomfort are not desired during NINCS for several reasons Irritation and discomfort cause pain or discomfort to the subject, complicate the desired effect of stimulation, and can lead to adverse health effects Further, irritation and discomfort may prevent optimal application of NINCS and reduce a subject's desire to receive NINCS
Conventional tDCS (a type of NINCS) employs the passage of a constant direct current (nominally 260 uA - 3 mA) between an anode and cathode electrode, at least one of which is placed over the scalp The spatial focahty (targeting) of tDCS is considered pivotal for efficacy and safety Decreasing electrode scalp contact area is considered to improve spatial focality But for a given electrode current, reducing contact area increases current density, which in turn may increase hazards
From the perspective of tDCS safety, it is important to consider 1) injurious effects of electrical currents on the brain, and 2) pruritic, painful, or injurious effects of electrical currents on the skin Brain injury and skin effects are not necessaπly linked, and therefore should be considered independently For example, stimulation causing skin irritation may not have any adverse effect on brain function, and brain injury may not be concomitant with skin irritation
The prior art electrodes fail to address minimizing skin irritation and pain dunng electro-stimulation activities like NINCS, particularly tDCS It is an object of the invention to optimize electrode parameters to minimize skin irritation and pain, with a specific focus on engineering small, more focal electrodes
Summary of the Invention
According to a first aspect of the invention, there is provided an electrode assembly for neuro-cranial stimulation comprising an adapter including a receiver for attachment of an electrode, and a holder for use with an electrode and conductive gel or paste having a holder reservoir for storing TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
the gel or paste, the holding reservoir having rigid or semi-πgid wall restricting the flow of the gel or paste, and attaching means for attachment of the holder to the scalp of a subject
According to a second aspect of the invention, there is provided a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness dunng neurocranial stimulation compnsing a neurocranial stimulation device and electrode apparatus detailed in the present invention
According to a third aspect of the invention, there are provided compositions for neurocranial stimulation gels that reduce or prevent irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness
According to a fourth aspect of the invention, there is provided a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pam, or redness dunng cranial neurostimulation compnsing selecting an appropriate combination of (1) gel and (2) solid conductor which support, control, or limit electrolyte depletion or formation at the cathode or anode
According to a fifth aspect of the invention, there are provided specific combinations of (1) gel and (2) solid conductor of the electrode that allow for the reduction or prevention of lrntation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during cranial neurostimulation
According to a sixth aspect, there is provided a method to reduce lrntation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during neurocranial stimulation comprising the steps of selecting a suitable electrode-skin contact area, selecting a suitable metal electrode material, selecting an electrode shape, selecting a rigid or semi-rigid holder, selecting an appropriate gel, selecting a chemical to apply to the gel or the skin, selecting a temperature for the gel/skin, combining the electrode and gel in the holder, wherein said holder determines the shape and volume of the gel, the position of the electrode relative to the gel, and the portion of skin exposed to the gel, TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
preparing the skin, attaching the assembly to the head of an individual with suitable attachment means, checking the electrode properties such as resistance, and/or selecting a conditioning electrical waveform to apply to the skin,
According to an seventh aspect, there is provided an apparatus for applying transcranial current through the scalp using a plurality of electrodes, each electrode comprising at least one ngid or semi-rigid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of a gel, at least one electrical stimulation electrode with a proximal end and a distal end, the distal end making contact with a portion of the gel, and gel or paste contacting the scalp and containing no electrolytes, minimal electrolytes, or one or more electrolytes, and a cap or mesh positioned on the scalp and connected to the semi-rigid shell
According to an eighth aspect, there is provided an apparatus for applying transcranial current through the scalp using a plurality of electrodes, each electrode comprising at least one semi-rigid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of the secondary gel, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the primary gel containing no electrolytes, minimal electrolytes, or one more electrolytes, a secondary gel contacting a portion of the primary gel and the scalp, wherein the secondary gel may contain no electrolytes or one or more electrolytes
According to a ninth aspect, there is provided an apparatus for applying transcranial current through the scalp using a plurality of units, each unit comprising at least one semi-rigid shell with a distal end contacting the scalp and proximal end, a electrode mount with one portion contacting the semi-rigid shell and one portion contact the electrical stimulation electrode, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the gel, TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
and a gel or paste contacting the scalp and containing no electrolytes or one or more electrolytes.
According to a tenth aspect, there is provided a transcranial stimulation electrode comprising: an electrically conductive backing and an electrically conductive hydrogel matrix coated thereupon, said matrix being adapted to make contact with the skin of the patients and being sufficiently flexible to conform to the contours of the body.
In a different field, electroencephalography uses small head electrodes and involves measuring brain potentials rather than applying brain-stimulating electrical currents. These small electrodes have not been used or discussed before for neurocranial stimulation, because it was considered that the application of desired neurocranial stimulation current levels with small head electrodes would result in current densities sufficiently high to cause significant pains and/or discomfort. As a result of extensive experimentation described further herein, applicants discovered that the small head electrodes disclosed in the prior art could be modified for effective use in neurocranial stimulation, under particular design conditions which form a part of their invention as described herein. Applicants incorporate by reference herein the following patents which describe prior art electroencephalography electrodes : US 6640122, US 6574513, US 6445940, US 6201982, US 6175753, US 6161030, US 4171696, US 4537198, US 4683892, US 5357957, US 5479934, US 5511548, US 5630422, US 5730146, US 5740812, US 5800351, US 6047202, US 6067464, US 537198, US 4632120, US4709702, US 4770180, US 4836219, US 4967038, US 5038782, US 5273037, US 5291888, US 5293867, US 5348006, US 5357957, US 5404875, US 5479934, US 5564433, US 5740812, US 5800351, US 5813993, US 6067464, US 6161030, US 6167298, US 6175753, US 6201982, US 6301493, US 6381481, US 4683892, US 4709702, US 5038782, US 5479934, US 6067464, US 6155974, US 4067321, US 4632120,US 4709702, US 4936306 and US 5222498.
Other electrodes have been used for the purpose of drug delivery through the skin (transdermal drug delivery). These electrodes have not generally been used for electrical stimulation, electrotherapy, or neurocranial stimulation, but may also be suitable when modified according to principles of the present invention for neurocranial stimulation. Applicants incorporate by reference herein the following patents TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
which describe this pπor art US 4177817, US 4196737, US 5282843, US 4736752, US 3817252, US 4503863, US 4535779, US 7392096, US 6343226,US 4736752, US 4367755 and US 7421299
Definitions
The following words and terms used herein shall have the meaning indicated
Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, un- recited elements
As used herein, the term "about", in the context of concentrations of components of the formulations, typically means +/- 20% of the stated value, more typically +/- 10% of the stated value, more typically +/- 5% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0 5% of the stated value Throughout this disclosure, certain embodiments may be disclosed in a range format It should be understood that the descπption in range format is mainly for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges Accordingly, the descπption of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numeπcal values within that range For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc , as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6 This applies regardless of the breadth of the range
Brief Description of Drawings
The foregoing and other features of the present invention will be more readily apparent from the following detailed description and drawings of illustrative embodiments of the invention, in which
Fig 1 illustrates an adapter element of an electrode assembly in accordance with the present invention TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
Fig 2 illustrates the adapter of Fig 1 in combination with a cap element provided in an unlocked position
Fig 3 illustrates the adapter of Fig 2 with the cap element provided in a locked position
Fig 4 illustrates the adapter of Fig 1 in combination with an accessory element
Fig 5 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
Fig 6 illustrates the adapter of Fig 5 in combination with another cap element provided in an unlocked position
Fig 7 illustrates the adapter and cap of Fig 6 with the cap provided in a locked position
Fig 8 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
Fig 9 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
Fig 10 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
Fig 11 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
Fig 12 illustrates the adapter of Fig 11 in combination with an accessory element
Fig 13 illustrates an adapter of an electrode assembly in combination with another accessory element
Figs 14(a) and 14(b) illustrate the adapter of Fig 1 with a preloaded gel, electrode, shield and cap
Fig 15 illustrates another adapter of an electrode assembly in accordance with principles of the present invention
Figs 16(a) and 16(b) illustrate another adapter of an electrode assembly in accordance with principles of the present invention
Fig 17 illustrates the adapter of Fig 14 without the cap and with an additional shield TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
Fig 18 illustrates the adapter of Fig 14 with an additional shield
Figs 19(a) and 19(b) illustrate an electrode according to the present invention
Fig 20 illustrates an electrode according to the present invention
Fig 21 illustrates an electrode according to the present invention
Fig 22 illustrates a mounting plate for an electrode assembly mounting apparatus according to the present invention
Figs 23 and 24 illustrate semi-circular band for electrode assembly mounting apparatus according to the present invention
Fig 25 illustrates a cross band design for an electrode assembly mounting apparatus according to the present invention
Fig 26 illustrates a circular band design for an electrode assembly mounting apparatus according to the present invention
Figs 27(a) - 28 illustrate electrode assembly mounting apparatus according to the present invention that include flexible arms that receive and position the electrode assemblies
Figs 29 and 30 illustrate electrode potential results for trials employing electrode assemblies having pellet type electrodes
Fig 31 illustrates electrode potential results for trials employing electrode assemblies having rubber-type electrodes according to the present invention
Fig 32 illustrates electrode potential results for trials employing electrode assemblies having Ag/AgCl disc electrodes according to the present invention
Fig 33 illustrates electrode potential results for trials employing electrode assemblies having Ag/AgCl Ring electrodes according to the present invention
Fig 34 illustrates pain developed during cathodal stimulation in vaπous subjects when stimulation is applied using variety of gels and variety of electrodes according to the present invention
Fig 35 illustrates pain developed during anodal stimulation in various subjects when stimulation is applied using variety of gels and variety of electrodes according to the present invention
Fig 36 presents bar graphs showing average run time of different electrodes with different electrolyte gels according to the present invention TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
Fig 37 presents tables showing electrochemical behavior and summary of time and pain performance using a variety of gels and variety of electrodes according to the present invention
Like reference numerals are used in the drawing figures to connote like elements of the invention
Detailed Description of the Invention
Medical electrodes have, in the past, taken many shapes and forms Electrodes used in monitoring apparatuses, such as EKG and EEG, where little or no current is passed across the electrodes, have commonly round contact surfaces, whereas electrodes used in stimulation apparatus devices tend to be larger and have rectangular surfaces For example, electrodes for transcranial direct current stimulation have taken the form or large square sponges High current densities at specific areas on the head are desirable for efficacy of the electrical stimulation protocol, and current electrodes do not optimize these parameters Small electrodes are ideal for the attainment of that efficacy and advancement of the field However, it has commonly been believed that the use of small electrodes, or specifically higher current densities, would result in skin pain and injury
We discovered that using appropπately designed small electrodes, high currents (high current densities) could be applied to the skin safely and comfortably This discovery challenges conventional perceptions widely held by experts in the field
The objective of this invention as accomplished herein is a practical small medical electrode suitable for neurocranial electrical stimulation and, in a preferred embodiment, transcranial direct current stimulation The main goal is the ability to deliver desired levels of current in a way that is safe and comfortable for the patient Previous electrode designs are unsuitable for several reasons Large electrodes must be made flexible to accommodate the curvature of the skin This results in poor control of the skin interface, for example the amount of gel or other material between the metal electrode and skin This has shown to result in current hot-spots and injury Small electrodes have been attempted, but previous designs of small electrodes were TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
unsuitable for various reasons In some designs a flexible (adhesive) back is used, which does not strictly regulate the metal skin distance And in other previous designs, a "low profile" configuration results in insufficient distance between the metal and the skin In the invention contained herein, electrodes are presented which fix the electrode position relative to the skm, maintain a minimum distance between metal and skin, and are able to improve and replicate the functionality of large electrodes in a safe and effective way
According to a first aspect of the invention, there is provided an electrode assembly for neuro-cranial stimulation comprising an adapter including a receiver for attachment of an electrode and a holder for use with an electrode and conductive gel or paste having a holder reservoir for stonng the gel or paste, the holding reservoir having rigid or semi-ngid wall restricting the flow of the gel or paste, and attaching means for attachment of the holder to the scalp of a subject
In order to ensure skin safety and comfort during transcranial stimulation, electrodes must be designed properly as descnbed in this invention It is also necessary to ensure electrode voltages do not increase to too high a level This design requires the balance of several engineenng factors We have found three properties which are cntical for effective, safe electrode apparatuses
First, gel-skin contact area should be within a desired range The area should be minimized as to localize the location of current entry, and in order to practically control the uniformity of contact However, the area should be maximized in order to reduce discomfort by distributing the current, and the area may be maximized in relation to (scaled by) the amount of current that will be passed
Second, the distance between the nearest components of electrode and skin should be maximized, while the overall head-gear and electrode profile is not too high (i e standing far off of the head) that it is not practical Classical electrodes used on the head, for example those used for EEG, he directly on or very close to the surface of the scalp However, when applying large currents to the scalp, such as in neurocranial stimulation, there is a potential hazard from direct contact of the electrode with the skin Therefore, it is of cntical importance that electrodes and their holders be designed so that there is sufficient separation between the scalp and TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
electrode Additionally, one must also consider that the skin is not flat but rather flexible and so will protrude into the electrode assembly to a varying degree depending on the size of the opening The desired apparatus, and those holders described in this invention, therefore have a specific depth which physically positions the electrode away from the skin by utilizing a holder that a) holds the electrode at a certain height and b) keeps the skin from protruding into the electrode area Note that (b) can be done by either limiting the area of the electrode (pellet) or using fins (ring) The reasons for maintaining this distance are several fold including buffering electrochemical products, preventing contact between electrode and skin, and allow current to distribute evenly throughout the gel
Third, the contact area between the metal electrode and the gel should be maximized within the given constraints of the holder volume and electrode size If the electrode contacts only one surface of the gel material, the electrode-gel interface is an essentially a 2-dimensional interface However, if the metal electrode is immersed in the gel, this becomes a 3-D interface, thus greatly increasing surface area For example, a pellet electrode can be fit into a small diameter cylindrical plastic holder The plastic holder has a small skin contact area, but its depth allows the use of longer pellets with increased surface area Though, in our πng design the electrode contact area is actually less than the skin contact area
Specific examples of electrodes embodying these important concepts necessary to optimize voltage and safety, and the descπptive embodiments mentioned below, are illustrated in the drawing figures In essence, the electrode holder is a πgid or semi-rigid material exposed at two ends, which is able to hold a volume of gel and an electrode
In one embodiment, the electrode holding reservoir is cylindrical, conical, square, rectangular, circular, or a more complex permutation of these shapes In a preferred embodiment, the holder is a cylinder or hyperboloid of a suitable volume for holding both the electrode and gel material
The material out of which the holder is made can be any rigid or semi-rigid material suitable to hold in place both a gel and an electrode In one embodiment, the holder is made out of a material selected from the group consisting of, but not limited TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
to, plastic, sponge, or ceramic. In a preferred embodiment, the holder is made out of semi-rigid plastic.
For example, Fig. 1 illustrates an adapter 100 of an electrode assembly according to the present invention. The adapter 100 comprises a body 101 including an interior compartment 102 having an interior surface that is substantially hyperbolical. The interior compartment 102 includes a first compartment 102a for positioning an electrode of the electrode assembly, and a second compartment 102b for receiving a conductive gel of the electrode assembly. The compartments 102a, 102b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 102b to flow into the first compartment 102a for the purpose of coming into physical contact with the electrode.
The first compartment 102a further comprises indentations 103 each including a land surface 103a for carrying a bottom surface of the electrode, grooves 104 for receiving tabs 110a of a cap 110 as illustrated in Fig. 2, and a channel 105 that defines a passageway through which an electrical conductor of the electrode may extend away from the first compartment 102a.
As illustrated in Fig. 3, each tab 110a of the cover 110 may be inserted into a vertical portion 104a of a corresponding groove 104 to enable the cap 110 to be sealably positioned within a top portion of the first compartment 102a. The cap 110 includes a surface HOb which is shaped to conformally and sealably contact a corresponding surface portion of the top portion of the first compartment 102a upon insertion into the first compartment 102a. As illustrated in Figs. 1 and 3, upon insertion into the first compartment 102a, tabs 110c may be manipulated to rotate the cap 110 so that the tabs HOa move outwardly along horizontal portions 104b of the grooves 104 toward a closed position of the cap 110. As can be seen with reference to Fig. 1, the portions 104b extend slightly downwardly along the horizontal direction so that, as the tabs 110a move outwardly along the portions 104b, the surface HOb is pressed against the corresponding surface portion of the top portion of the first compartment 102a to generate a reciprocal force that effectively fixes or locks the cap 110 to the body 101 in the closed position. Fig. 4 illustrates an accessory 410 to be mounted on to the adapter 100. Each tab 410a of an accessory 410 may be inserted into a vertical portion 104a of a corresponding groove 104 to enable the accessory 410 TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
to be locked on to the adapter 100 The accessory 410 compπses a body 401 including an inteπor surface 402 The interior surface 402 is divided into a first compartment 402a for positioning an electrode of the electrode assembly, and a second compartment 402b for receiving the conductive gel of the electrode assembly The compartments 402a, 402b and 102a are in fluid communication with one another Fig 5 illustrates an adapter 500 of an electrode assembly according to the present invention The adapter 500 compπses a body 501 including an inteπor surface 502 having two compartments a first compartment 502a for positioning an electrode of the electrode assembly, and a second compartment 502b for receiving a conductive gel of the electrode assembly Compartments 502a and 502b are divided by an indentation 503 from the surface 501 These indentations 503 form a land surface 504 on the interior surface 502 for carrying a bottom surface of electrode Two protrusions 505a are designed for holding of the electrode at a distance from the side surface of electrode In this case, the electrode can be mounted from the top so that the bottom surface of electrode sits on land surface 504 while protrusions 505a isolate the electrode from any movement from two opposite sides Protrusions 505b and 505c are shaped to conformally and sealably lock a cap 510 as illustrated in Fig 6 onto the adapter 500
The cap in Fig 6 has protrusions 511 Two vertical extruded bars 511a and horizontal extrusions 511bare positioned underneath protrusions 505b duπng locking of the cap 510 on adapter 500
As illustrated in Figs 5 - 7, each extrusion 511b of the cap 510 may be inserted underneath a protrusion 505b to enable the cap 510 to be securely and tightly positioned on an upper portion of first compartment 502a The cap 510 includes a surface 513 which is shaped to conformally and sealably contact a corresponding surface portion of the top portion of the first compartment 502a upon insertion into the first compartment 502a As illustrated in Figs 6 and 7, upon insertion into the first compartment 502a, tabs 514 may be manipulated to rotate the cap 510 so that the tabs 510a move outwardly along horizontal protrusions 505b of the extrusion 505 toward a closed position of the cap 510 As can be seen with reference to Fig 6, the protrusions 505b extend slightly downwardly along the honzontal direction so that, as the tabs 511b move outwardly along the protrusions 505b, the surface 513 is pressed against TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
the corresponding surface portion of the top portion of the first compartment 502a to generate a reciprocal force that effectively fixes or locks the cap 510 to the body 501 in the closed position
Fig 8 illustrates an adapter 800 of an electrode assembly according to the present invention The adapter 800 comprises a body 801 including an interior surface 802 that has 2 large compartments upper compartment 802a with large radius for the positioning of electrode and a lower compartment 802b with small radius for receiving conductive gel The compartment 802a, 802b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 802b to enter the first compartment 802a for the purpose of coming into physical contact with the electrode
From the inner surface of 802, a horizontal extrusion 804 extends into the center of upper compartment 802a A vertical extrusion 803 extends from horizontal extrusion
804 and includes a compartment 802c Compartments 802c and 802b are in fluid communication with one another A bottom surface of an electrode sits on the top surface of 804 Outward angular extrusions 805 extend from the extruded body 803 for tightening and holding the electrode at a central hole of electrode The extrusions
805 move inwardly in response to the push of the electrode onto the body 803 to tightly hold the electrode in position
Fig 9 illustrates an adapter 900 of an electrode assembly according to the present invention The adapter 900 compπses a body 901 including an interior cylindrical surface 902 The cylindrical surface 902 defines a first compartment 902a for positioning an electrode of the electrode assembly, and a second compartment 902b for receiving a conductive gel of the electrode assembly The compartments 902a, 902b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 902b to enter the first compartment 902a for the purpose of coming into physical contact with the electrode
The first compartment 902a further compπses indentations 903 each including a land surface 903a for carrying a bottom surface of the electrode and a channel 904 that defines a passageway through which an electrode may be inserted into the first compartment 902a Alternatively, the electrode in the adapter 900 may be mounted TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
from top portion of 902a A groove 905 on the outer wall of adapter 900 may be used to hold the adapter 900 tightly in position within a mounting apparatus
Fig 10 illustrates an adapter 1000 of an electrode assembly according to the present invention The adapter 1000 comprises a body 1001 including an interior cylindrical surface 1002 The cylindrical surface 1002 defines a first compartment 1002a for positioning an electrode of the electrode assembly, and a second compartment 1002b for receiving a conductive gel of the electrode assembly The compartments 1002a, 1002b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1002b to enter the first compartment 1002a for the purpose of coming into physical contact with the electrode
The first compartment 1002a further comprises extrusions 1003 each including a land surface 1003a for carrying a bottom surface of the electrode and vertical bars 1003b for holding electrode in position A channel 1004 defines a passageway through which an electrical conductor of the electrode may extend away from the first compartment 1002a An electrode in the adapter 1000 may be mounted from top portion of first compartment 1002a A groove 1005 on the outer wall of adapter 1000 includes 3 flap like extrusions 1006 on the top which assist in mounting of adapter 1000 on a mounting apparatus
Fig 11 illustrates an adapter 1100 of an electrode assembly according to the present invention The adapter 1100 comprises a body 1101 including an interior cylindrical surface 1102 The cylindrical surface 1102 defines a first compartment 1102a for positioning an electrode of the electrode assembly, and a second extended wide compartment 1102b for receiving a large volume of conductive gel and of the electrode assembly The compartments 1102a, 1102b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1102b to enter the first compartment 1102a for the purpose of coming into physical contact with the electrode
The first compartment 1102a further comprises indentations 1103 each including a land surface 1103a for carrying a bottom surface of the electrode and bars 1104 for holding the electrode Tabs 1105 protrude from a top part of bars 1104 for TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
holding an accessory element 1110 as illustrated in Fig 12 A bottom portion 1111 of the accessory 1110 fits on the top portion 1106 of adapter 1100
As illustrated in Fig 12, accessory 1110 includes an interior cylindrical surface 1112 with extrusions 1113 that includes a horizontal extrusion 1113a for positioning another electrode and vertical bars 1113b for holding electrodes The cylindrical surface 1112 defines a first compartment 1112a for positioning an electrode of the electrode assembly, and a second compartment 1112b for receiving conductive gel The compartments 1102a, 1112b and 1112a are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1112b to enter the first compartment 1112a and 1102a for the purpose of coming into physical contact with both of the electrode
Fig 13 illustrates an adapter 1300 of an electrode assembly according to the present invention The adapter 1300 compπses two different bodies a lower body 100 and an upper body 1301 An inner surface 1302 defines a first compartment 1302a for positioning three different electrodes of the electrode assembly, and a second compartment 1302b for receiving a conductive gel of the electrode assembly The compartments 1302a, 1302b are in fluid communication with one another, thereby permitting the conductive gel provided in the second compartment 1302b to enter the first compartment 1302a for the purpose of coming into physical contact with the electrode
The first compartment 1302a further comprises three slots 1303 each including a land surface 1303a for carrying a bottom surface of the electrode Electrodes can be mounted from the top of the accessory 1300 into each of three slots 1303
Figs 14(a) and 14(b) illustrate an adapter 1400 of an electrode assembly according to the present invention The adapter 1400 comprises an adapter 100 in which compartment 102b is prefilled with the conductive gel 1403 and covered with a removable plastic shield 1401 on the bottom surface of 100 The compartment 102a of adapter 100 is preloaded with an electrode 1404 and covered with a tightening holder cap 110 on the top portion of compartment 102a
Fig 15 illustrates an adapter 1500 of an electrode assembly according to the present invention The adapter 1500 comprises an adapter 100 in which outer surface TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
101 has a spiral groove 1501 The groove 1501 is designed to attach the adapter 100 within an associated aperture in a mounting apparatus be rotating the adapter 1500 clockwise or anticlockwise within the aperture
Figs 16(a) and 16(b) illustrate an adapter 1600 of an electrode assembly according to the present invention The adapter 1600 comprises an adapter 100 in which outer surface 101 comprises two grooves 1601 on each side of the surface 101 for sliding into an associated aperture in a mounting apparatus
Fig 17 illustrates an adapter 1700 of an electrode assembly according to the present invention The adapter 1700 compπses an adapter 100 in which compartment 102b is prefilled with the conductive gel 1703 and covered with a removable plastic shield 1701 on the bottom surface of 100 The compartment 102a of adapter 100 is in addition preloaded with the electrode 1704 and covered with a removable plastic shield 1702 on the top portion of compartment 102a
Fig 18 illustrates an adapter 1800 of an electrode assembly according to the present invention The adapter 1800 comprises an adapter 100 in which compartment 102b is prefilled with the conductive gel 1802 and covered with a removable plastic shield 1801 on the bottom surface of 100 The compartment 102a of adapter 100 is covered with a tightening holder cap 110 and the side surface 101 of adapter body 100 is also covered with a removable plastic shield 1803 from where the electrode 1804 can be slid into the holder 100 from the side
It may be practical for certain adapters to be added for additional functionality For instance, large electrodes can suffer from gel or salt solution leaking outside of the electrode area, or from drying dunng stimulation This partly results from the fact that large electrodes must be flexible Therefore, specific adapters may be added to the electrode holder for containment of the components or to fix the position of the components
In one embodiment, a firm plastic inset, placed firmly against the scalp, prevents this leakage In another embodiment, an adapter is made which is a cap to be placed on top of the plastic holder In a preferred embodiment, the adapter locks in place by fitting with tabs on the two components In a particularly preferred embodiment, the tabs are on the adapter, and the electrode holder is engineered with grooves on its inner surface in order to lock the adapter in place In an alternate TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
embodiment, the tabs are located on the outer surface of the electrode holder, and the grooves are located in the adapter
In order to fit the given electrode holder in the gel volume and hold it in place, various methods have been engineered into the holder to practical access and control over electrode position In one embodiment, the electrode is pushed from the top of the holder into a set of ridges at a defined distance In another embodiment, the electrode adapter has a side opening at the level of the πdges, and the electrode may be slid into place from the side
In order to affix the electrode holder to the body, cranium, or scalp, a headgear may be used as discussed below To attach the electrode holder to the head-gear the electrode holder may be modified to allow secure attachment to the head-gear This includes the use of lock mechanisms, snap mechanisms, and screw mechanisms In addition, the hardware for securing the electrode holder to the head-gear may be designed such that when the electrode holder is secured it is modified or functionally activated to allow stimulation In one embodiment, gel is sealed in the electrode holder and a seal is punctured when the electrode holder is attached to the head-gear
As mentioned above, the size of the optimal electrode holder depends on the ranges of values that are optimal for gel-scalp contact area and the distance between the electrode and the skin In one embodiment, the gel-scalp contact area is less than 7 cm2 and greater than 0 07 cm2 In a preferred embodiment, the area is less than 3 cm2 and greater than 1 cm2 The dimensions of the orifice at the bottom of the electrode holder follow logically from the above dimensions, and are constructed as exposing the same area as the gel-scalp contact surface area
The safety objectives of the invention additionally necessitate that the holder be built high enough (i e in a large enough distance along the axis normal to the scalp) that it allows an optimal distance between the electrode and the skin In one embodiment, the distance between the electrode and the skin is between 025 cm and 1 3 cm In a preferred embodiment, the distance is between 0 5 cm and 0 8 cm
Therefore, the total volume of the optimal holder is determined by the ideal area of the gel-skin contact oπfice, the distance (height) needed to accommodate the ideal distance between the electrode and the skin, and the inner contour and shape of the holder The dimensions of the inner holder should be such that they can also TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
accommodate a suitable volume of the gel to be used during stimulation In one embodiment, the volume of the gel is between 0 1 ml and 10 ml In a preferred embodiment, the volume of the gel is between 0 5 mL and 5 mL, and preferably between 0 5 mL and 1 5 mL
As noted above we discovered that small electrodes can pass significant currents with minimal voltage and sensation However, the electrodes must also be bigger than a minimum size for both pain and voltage considerations In moving from a smaller to larger electrode design, we observed dramatic improvements in the voltage capacity of the electrodes, and the increase in voltage capacity was not related to the gel-skin contact area but rather the metal-gel contact area Therefore, methods to increase the metal-gel interface area have been employed in the electrode assemblies of the invention
In one embodiment, the properties of the metal electrode are specifically considered The electrode can be a ring, disk, pellet, or other shape In a preferred embodiment, the electrode is a nng, designed to have the optimal surface area for taking up a defined space in the electrode holder Along these lines, one can envision a more convoluted permutation of the electrode to increase electrode-to-gel surface area contact, thereby making use of the insights of this invention In one embodiment, the metal-gel contact area is greater than 50% of the gel-skin contact area In another embodiment, the metal-gel contact area is greater than 100% of the gel-skm contact area In a preferred embodiment, the metal-gel contact area is increased relative to the gel-skin contact area by increasing the exposed vertical projection of the metal in the gel
In one preferred embodiment, the increased vertical projection takes the form of the pellet electrode design In another preferred embodiment, the maximal vertical dimension of the metal is greater than 3 times the horizontal diameter In another preferred embodiment, the maximum electrode vertical dimension is less than the maximum horizontal dimension
In another preferred embodiment, the electrode metal gel contact area includes the top and bottom of said metal electrode thereby approximately doubling the contact area between the metal and gel (compared to a metal electrode sitting on top of a gel) In another embodiment, the surface of the metal electrode is convoluted to increase TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
the metal-gel contact area including the use of ridges, spikes, roughening, and curves. In a still preferred embodiment, the metal-gel contact area is increased through the process of sintering. In a still preferred embodiment, AgCl is used in the sintering process.
In another preferred embodiment, the center of the electrode is hollow to increase gel-metal contact area. Such an embodiment is also described here as the ring electrode. In another preferred embodiment, the hollow electrode is built into the wall of the electrode holder.
In another embodiment, the electrode holder is constructed such that it allows maximal electrode surface area exposed to the gel by allowing multiple electrodes. In one preferred embodiment, the adaptor has an extra accessory "sleeve" that allows for two electrodes to be used concurrently in the same holder, doubling surface area exposure. In another preferred embodiment, an adapter is constructed with three openings to allow three separate electrodes to fully contact the gel in a single holder, thus increasing surface area exposure three-fold.
Figs. 19(a) - 21 depict several exemplary electrodes according to the present invention.
Figs. 19(a)and 19(b) illustrates an electrode 1900 according to the present invention. The electrode 1900 comprises triangular spikes 1901 on the bottom surface to increase the metal surface area in contact with the gel.
Fig. 20 illustrates an electrode 2000 with its height increased for example by a factor of 3 to increase the gel to metal contact surface area. Electrode 2000 is mounted in the electrode adapter 100. Electrode 2000 has the same top 2001 and bottom 2002 surface area.
Fig. 21 illustrates an electrode 2100 designed in a spiral shape to increase the overall surface area in contact with the gel. The electrode 2100 is configured to be immersed completely into the gel compartment 102b.
The designs described above imply a single compartment for the gel and subsequently immersed electrode. However, it may be desirable to have multiple gels, for conductance purposes or for more complex management of pH, temperature, TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
or potential build-up As such, another embodiment of the invention entails a holder reservoir that has multiple compartments which may contain different gels
It is appreciated that different electrode materials can have different physicochemical effects dunng stimulation, and therefore some may be more desirable than others for both minimizing voltage build-up and pain sensation Therefore, the solid conductor of the electrode may be metal, rubber, conductive rubber, Ag/AgCl, Ag, Gold In a preferred embodiment the solid-conductor is sintered Ag/AgCl
Thus, in a particularly preferred embodiment, the electrode assembly of the invention includes a cylindrical, semi-rigid plastic electrode holder that exposes roughly 2 cm2 of surface area to the scalp, combined with a sintered AgCl nng electrode that is inserted by guided ridges roughly 0 5 cm above the scalp orifice into the side of the electrode holder, and fully submerged in 1 ml gel of the preferred composition discussed in a later aspect below
To obtain reliable stimulation, and thus a consistent safety profile dunng neurocranial stimulation, the connection between the electrode and the scalp should be sufficiently secure such that the electrode gel maintains contact with the metal electrode and with the scalp The former is achieved by a plastic holder, as discussed in detail above The latter requires a connection of the electrode assembly, or preferably multiple electrode assemblies, to the head The most practical method for this use is a type of "head gear" to hold the plastic assemblies in place on the scalp The technology to hold the plastic inset to the head is thus critical and as discussed herein may be optimized for the most practical use
In some measurement devices such as EEG, a flexible cap, with fixed position holes, is used to position an array of electrodes in fixed positions of the head In fact, with such measurement, the use of pre-defined fixed positions across subjects is preferred In contrast, while one could envision the use of pre-set (EEG) positions for stimulation, it is preferred for both stimulation efficacy and safety to have the ability to place the electrodes in various specific positions on the scalp, depending on the specific stimulation application This is necessary to ensure specific targeting of brain regions, as well as to account for variations in head size and contour between individuals The head (mounting) gear described here is designed to fit with the TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
plastic holders described in this invention, although is applicable to electrodes and holders not described herein
In one embodiment, multiple electrode assemblies are attached by a flexible band that wraps either from front-to-back or side-to-side across the head This band contains both individual spaces for electrode assemblies, as well as slots for connection of sub-bands to splay across the rest of the head, each with their own places for electrode assemblies at fixed distances along the band
In a preferred embodiment, the main band is wrapped completely around the head and connected with a clasp
Fig 26 depicts an exemplary circular band design for an electrode assembly mounting apparatus according to the present invention
A head gear 2600 includes an adjustable plastic head band 2601 and fabric C shaped cross band 2604 which also include a circular fabric disc shaped area 2605 on the inter-section of 2604 bands A circular knob 2603 is preferably provided to increase or decrease the length of head band All around the length of the head band 2601 there are protrusions 2602 to hold the cross bands 2604 in proper position Cross band 2604 includes holes 2606 on a marginal end of each band that fit with the protrusions 2602 of the head band 2601 A disc shaped section 2605 has holes 2607 to accommodate electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously described) The cross bands 2604 can be adjusted along different protrusions 2602 of the head band 2601 to accurately position the disc shaped area 2605 on head
In another preferred embodiment, the band is in a semi-circle shape, fixed on the head by bands diverging from the central main band
Figs 23 and 24 depict exemplary semi-circular band designs for electrode assembly mounting apparatus according to the present invention
For example, Fig 23 illustrates a flexible head band 2301 with the webbing buckle 2302 on one end, to adjust the length of the band on the head Various sub- band attachments 2303 may preferably be attached on to the holes 2305 of the band 2301 for modular positioning of the electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously descπbed) The adapters may be mounted on to different holes 2305 of the head band or of sub-bands 2304 TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
Fig 24 illustrates a plastic "double C configuration" cross band 2400 An extra flexible band 2403 may be attached between two main bands of the cross band 2400 The cross band 2400 has numerous holes 2404 all along the surface for mounting of different kinds of electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously described) Electrodes may effectively be positioned anywhere on the head using different holes 2404 on cross band 2400
In another preferred embodiment, two main bands form a "cross" on top of the head, the ends of each movable arm of the cross containing movable electrode holders
Fig 25 depicts an exemplary cross band design for a head-fixing means according to the present invention A plastic cross band 2501 compπses two plastic arms 2501a and 2501b crossing each other at the center Two arms 2501a and 2501b can be moved along the center A center portion of the two arms 2501a and 2501b provides a receptacle 2504 to attach an additional electrode adapter (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously descnbed) At the marginal end of each arm 2501a and 2501b there are movable C shaped plastic holders 2503 to hold another plastic attachment 2502 Electrode adapters (for example, adapters 100, 800, 1300, 1400, 1500, 1700 or 500 as previously descπbed)may be mounted on the plastic attachment 2502
In another embodiment, the head-fixing means entails a "mounting plate" design, which contains two bands to hold the unit in place, and 2 or more plates, each with specific flexible or predefined spaces for electrode assemblies, diverging from the main bands The plates are connected to each other by hinges, therefore allowing for adjustment of individual plates to accommodate head size and contour to allow precise positioning In a particularly preferred embodiment, there are three plates connected to the central bands
Fig 22 depicts an exemplary mounting plate design for an electrode assembly mounting apparatus according to the present invention
For example, Fig 22 illustrates a circular plastic plate 2200 with numerous holes 2202 for modular positioning of the electrodes The electrode plate is preferably made of three or more different parts attached to each other by hinge joints 2203, which allow a free movement of different plates 2200 Flexible band 2201 is also TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
attached with the plate for holding of the plate across the head The plate has an orifice at the center 2207 to attach a small flexible band 2206 The small flexible band has holes on the marginal end to attach with the tabs 2205 along the internal margin of the oπfice 2207 of the plate 2200
Figs 27(a) - 28 depict variants of the semi-circular and circular band designs, respectively, in which the sub bands are replaced by flexible arms that are each attached to the semi-circular or circular band at a proximal end, receive an electrode assembly at a distal end and may be manipulated to flexibly position the electrode assemblies on the cranial skin surface of a user
Figs 27(a) and 27(b) illustrate a plastic semicircular head band 2700 with 5 flexible and movable arms 2701 radiating from the upper surface 2700a of the head band 2700 Each of the arms has a C shaped plastic cup 2702, which holds another plastic piece 2703 Each plastic piece 2703 holds an electrode adapter (for example, any of the adapters 100, 800, 1300, 1400, 1500, 1700 or 500 previously descπbed) By moving different arms 2701 electrodes can be positioned on any location of the head
Fig 28 illustrates a circular adjustable plastic head band 2800 with a groove 2802 all along the length of the head band 2800 Small plastic slider 2801 tabs protrude from the groove 2802 and can be manipulated to slide protruding flexible arms within the groove 2802 Each of the arms preferably have a C shaped plastic cup 2702, that holds another plastic piece 2703 Each plastic piece 2703 holds an electrode adapter (for example, any of the electrode adapters 100, 800, 1300, 1400, 1500, 1700 or 500 previously descπbed) By moving different arms 2701 within the groove 2802, the electrodes can be positioned on any location of the head
In another embodiment, a flexible EEG cap is modified to allow arbitrary electrode positioning In a preferred embodiment, a sub-band is placed at specific points on a flexible EEG cap
In yet another embodiment, the electrode is attached to the scalp using a tape, glue, a clip or a ridge TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
We describe head-gear formed of bands and apertured regions, suitable for positioning of electrode assemblies for neuro-cranial electrodes It is possible to use the described method for Neurocranial stimulation with other techniques for brain stimulation known to those in the art, while making necessary modifications to the Neurocranial system or the other stimulation techniques as necessary Other such brain stimulation techniques include Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation, Deep Brain Stimulation, Vagus Nerve Stimulation, Epicranial Stimulation, Transcutaneous Electrical Stimulation, and Transcranial Electrical Stimulation In a separate embodiment, one may also actively combine Neurocranial stimulation with stimulation with electrodes positioned on the cranium or elsewhere on the body, such as extra-cephalic electrodes In one particular embodiment, a power source is connected to one Neurocranial electrode and other electrode on the body The additional electrode on the body may take on a range of forms known to those in the art or may adopt the technologies developed for Neurocranial stimulation
According to a second aspect of the invention, there is provided a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during neurocranial stimulation comprising using with a neurocranial stimulation device an electrode apparatus detailed in the present invention The invention is related to any neurocranial stimulation technique, although the invention is also especially useful for transcranial stimulation, and in a particular application is transcranial direct current stimulation In ideal embodiments, the method comprises using the electrode apparatus described above, including a selected electrode, electrode holder with a gel and containment adapter as described in the invention, and a specific means of attachment of the head as described above
According to a third aspect of the invention, there are provided compositions for neurocranial stimulation gels that reduce or prevent irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness
Gels have been used with cranial electrodes in the past, however they have been mainly in momtoπng applications such as EEG, or for general low-current stimulation These types of gels were not designed for the high currents and TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
application times necessary for effective neurocranial stimulation (e g up to 2 mA for greater than 20 minutes), and it is generally thought that these gels would not be sufficient to protect the patient from pain or discomfort However, we unexpectedly observed that gels are able to allow these high currents and long times of stimulation with minimal discomfort In this invention are provide specific compositions which we found were effective to allow for delivery of the desired current to the scalp with minimal pain or discomfort
Additionally, while it was has logically been expected that physical changes of the electrode and gel (such as changes in potential, pH, and temperature during electrical stimulation) could be a predictor of pain and sensitivity in the subject undergoing the stimulation, we have discovered that, unexpectedly, pain can be expeπenced by the subject even in the absence of a pH or temperature change in the gel during stimulation And limiting the increase in electrode voltage can reduce pH and temperature changes - but does not necessarily preclude pain For instance, Lectron II gel seems to have the broadest protection against electrode potential buildup and pH change, but leads to greater pain sensation than our CCNY-4 gel Therefore, properties other than pH and temperature must be considered for a safe and effective gel for the neurocranial applications of this invention
We have found that the optimal gel to allow for efficient delivery of current while maintaining good protection against pain or discomfort during neurocranial stimulation has certain core components, including 1) A polymer, which functions includes support properties, 2) surfactants or surface acting agent, functioning to act on the skin to increasing permeability and/or change skin resistivity, 3) humectants, functioning to maintain gel hydration, 4) salts, functioning to increase electrical conductivity, 5) water, and 6) preservatives or other chemicals These are the general components of a suitable gel, and is understood that the performance of the gel relates to its total properties after fabrication Each of these components as ingredients may serve the function of another component, for example a surfactant with salt content, or a polymer with hydration properties As another example, salt may be omitted if conductivity is provided by another substance such as the polymer or surfactant As such, this list can be interpreted either as key ingredients or as a list of core functions that should be achieved TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
However, although examples of formulations with these properties can be found in regards to medical electrodes, we have unexpectedly found that specific formulations are particularly suitable and appropπate for our applications Fig 37 shows a sample of gels tested, their general composition features and other physical properties are noted While these gels all have similar features and can be used with metal electrodes, only the CChTV gels were able to show a minimal pain response for each electrode used (also see Figures 34 and 35 of this patent) We have found that common electrode gels can be used as a foundation for the gel, but are not sufficient to prevent pain or discomfort during neurocranial stimulation with high current Therefore, gels known in the art as conducting gels for electrode applications, such as Signa gel, Spectra 360, Tensive, Redux, 1090 BioGel, and Lectron are suitable as a foundation or base composition for a gel, but require additional specific added components, detailed here, in order to function effectively with minimal pain or discomfort
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
and delivery of gel components in a desirable or undesirable fashion Still another undesirable example includes electrical delivery of toxic substances On the contrary, a desirable example might include the specific delivery of analgesic substances Yet another special consideration is synergistic or antagonistic actions of the electricity and gel components on the skin A synergistic example includes decreased skin resistance by the surfactant and the electrical stimulation Further examples and illustrations are presented in the embodiments Based on these findings, it is thus evident that a medical electrode gel must be especially designed for our application Each of the specific types of ingredients or functions must be optimized
Gels may use humectants to maintain gel hydration Humectants include materials such as propylene glycol, and can be formulated with or without ethanol Propylene glycol may also serve as a preservative Propylene glycol may result in skin redness and its concentration should be regulated In one embodiment, propylene glycol is included at a concentration of 1 μM to 10 mM In a preferred embodiment, propylene glycol is included at a concentration of 1 μM to 1 mM In a still preferred embodiment, propylene glycol is included at a concentration of 1 μM to 50 μM
Oil solubihzing surfactants including ionic and non-ionic surfactants may be included in the gel Agents that solubilize the oil layer on the skin and or penetrate the skin may be used They may be particularly useful in lowering skin resistance Examples include sodium hexametaphosphate, tπsodium phosphate, and products such as TWEEN and SPAN made by Atlas Chemicals In one embodiment, the gel contains 0 5 to 5% sodium hexametaphosphate In a preferred embodiment, a 1% composition of sodium hexametaphosphate in the gel is preferred
Appropriate gel viscosity must be adjusted relative the specialized plastic holder The polymer may be formulated using various techniques familiar to those skilled in the art but must be designed to allow current passage In a particular embodiment, hydroxycellulose may be used at the polymer or polymer agent
The polymer that is used may be dissolved in a base liquid Suitable liquids include water, alcohol, acetone, dimethlysulfoxide (DMSO), dimethyl formide (DMF), or a polar solvent Water, alcohol, and mixtures thereof are preferred Additional agents, such as cross-linking agents, may be added to adjust gel properties including viscosity The polymer may be set or cross-linked via photons, thermal TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
treatment or chemical treatment such as, but not limited to, deprotonation, oxidation or reduction In one embodiment a viscosity of 10,000 to 1,000,000 CPS is used, and more preferably the viscosity is within 150,000 to 200,000 CPS In another embodiment, the viscosity of the gel changes upon delivery due to dehydration, temperature changes, or skin contact In a preferred embodiment, the viscosity increases from during a temperate change from approximately 25 degrees Celsius to 37 degrees Celsius In another preferred embodiment, the viscosity decreases on contact with air, skin, or the holder surface The changes in viscosity may be mediated or triggered by exposure to the air or to the skin as described in this invention For example by using an adapter composing a sealing member affixed to the positioning surface and extending over the orifice of the adaptor, this sealing member being configured to be peeled off or pierced In one embodiment, the gel contains an alcohol In another embodiment, the gel solidifies with an increase in temperature, in another with a decrease In a separate embodiment, a solvent in the gel vaporize with lower pressure, leaving any solids behind, resulting in a change in viscosity Additional ingredients may also be used to adjust viscosity or other relevant properties of the gel, for example "dilatants" where the viscosity increases with agitation The resulting high viscosities will restrict the free movement of the seal Thixotropic fluids which lower gel viscosity with agitation Addition or presence of plastic fluids which change viscosity
An electrolyte is key to the formulation of the gel Here, the electrolyte is any material that will ionize in the liquid The electrolyte may contain ions that are in the metal electrode or in biological tissue Examples of suitable matenals include lomzable salts, salts of acids or bases, or buffer solutions Examples of inorganic salts include potassium chloride, sodium sulfate and organic acids or salts such as citric acid potassium citrate, or potassium acetate
Previously, electrode designs were made to increase the resistivity of the electrode abutting the skin or tissue, since it was considered that an increased conductivity of the electrode/gel relative to the skin/tissue resulted in current concentration at the electrode edges and associated pain/discomfort problems Modeling studies supporting this including for DC stimulation However, we have TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
found that, unexpectedly, gels with increased conductivities (for example, increased CI- conductivity) often resulted in less discomfort
In a preferred embodiment, added salts include NaCl added as a salt and/or present in a saline base More than one salt may be used NaCl supplements may be used including addition of 0 1 to 50 grams of NaCl per 100 grams of base In a particularly preferred embodiment the electrolyte concentration is 001 to 15% by weight in water, and preferably between 0 25 to 4%, and more preferably 0 5 to 2 5% In the most preferred embodiment, the gel contains NaCl at a concentration of around 2% by weight
In addition to the core concepts mentioned above, the gel may include various additive agents such as perfumes, colorants, and preservatives Suitable materials are those conventional in the art Specialized additional agents which act to protect or restore the skin include potassium bitartrate, coconut oil, sulfated castor oil, Aloe Vera, aloe barbadensis leaf juice, glycerin, synthetic beeswax, cetearyl alcohol, calcium acetate, and vitamins E, A, & D Local anesthetics may be added to the gel include Lidocaine, Benzocaine, or derivatives thereof In one embodiment, 6% Benzocaine is incorporated in the gel In a preferred embodiment, Lanacane, which includes 6% Benzocaine, is diluted in the gel at 1-50% by weight, or more preferred around 2 - 10% In another preferred embodiment, 2 5% Lidocaine and/or 2 5% Pπlocaine are incorporated in the gel In another embodiment, Lidocaine/Pπlocaine 2 5/2 5% Cream as sold by Fougera is incorporated in the gel at 1-50% by weight In another embodiment, Amantle as sold by Doak Dematologics is incorporated in the gel at 1-50% by weight
We have determined key properties, and a specific gel having these properties, that can be used for minimal pain or discomfort during neurocranial stimulation Therefore, in the most preferred embodiment, the electrode gel of the invention comprises Polymer, Humectants, Reverse Osmosis water, Surface active agent, Color, Sodium chloride (0 5% Saline Base plus NaCl supplement (CCNY-4) In an alternate preferred embodiment, the gel additionally contains around 2 5% lidocaine or benzocaine as an anesthetic (CCNY-5)
According to a fourth aspect of the invention, there is provided a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
or redness during cranial neurostimulation compπsing selecting an appropriate combination of (1) gel and (2) solid conductor which support electrolyte depletion or formation at the cathode or anode
Accordingly, a fifth aspect of the invention provides specific combinations of (1) gel and (2) solid conductor of the electrode that allow for the reduction or prevention of irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during cranial neurostimulation
It is clear from the above discussions of gels, that design of the electrode assembly may require steps beyond simply limiting gel pH or temperature We have found that a particularly effective strategy is to specifically match the electrode with the gel(s) used for neurocranial stimulation In the embodiments, the gel/electrode combination used is predicted to support the active electrolyte formation or depletion of the solid conductor based on electrochemical knowledge
In terms of matching the electrolyte gel to the electrode being used, it is commonly believed that any metal/gel configuration that supports the electrode electrolyte formation or depletion at an electrode will minimize voltage For a pertinent example of a preferred electrode made of AgCl, it is commonly thought that AgCl formation/depletion will minimize electrode voltage
However, we have made new discoveries in this regard We have found that some configurations that supported this reaction "too much" actually worked less to reduce pain than configurations that didn't support the reaction to the same level For example, using one gel with no Cl- (Lectron II) resulted in reduced potentials (and hence increased run times) compared to other gels with Cl- (Signa), and Lectron II was nominally less supportive of these reactions that need Cl-
Thus, combined with the findings above on conductance, we have designed gels with an optimized level of electrical conductivity In a preferred embodiment, the gels have an ideal salt content In a still more preferred embodiment, the gels were designed with an ideal level of Cl-, discussed below In the preferred embodiment, the gel electrical conductivity is 0 5 S/m to 10 S/m In a still preferred embodiment the conductivity is 1 S/m to 6 S/m In the most preferred embodiment, the electrical conductivity is 4 S/m to 5 S/m In another embodiment, the gel thermal TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
conductivity is 001 W/m C to 005 W/m C In the most preferred embodiment the thermal conductivity is 0025 W/m C to 0035 W/m C
Further exploration of electrochemical systems intended for use (i e the electrodes and gels) informs on specific gel parameters under given electrode systems In one embodiment, a metal electrolyte MX is converted to M + X- (aq) through the addition of one electron at the "negative" electrode and M is converted to MX by accepting X- (aq) ion and releasing electrons at the "positive electrode" In another embodiment, MX is converted to M+ + X (aq) through the removal of one electron at the "positive" electrode and M is converted to MX by accepting M+ (aq) ion and accepting electrons at the "negative electrode" In the embodiments, X may be a hahde such as chloπne or iodine, and M may be any metal such that MX is any electrical conductive substance and the conversion of M to MX and MX to M is an electrochemically reversible or irreversible reaction In a preferred embodiment both the positive and negative metal electrodes are AgCl and the ion is Cl In a particularly preferred embodiment the surface area of AgCl contacting the Cl containing gel is greater than 0 5 cm2 per 40 coulombs of charge transfer In another particularly preferred embodiment the metal in the positive and negative electrodes is not the same In one such embodiment, one electrode is Ag and the other is AgCl The electrode should have a porosity between 0% (fully dense) and 50% with a mean pore size between 1 μm and 100 μm
In another embodiment, a corrosion resistant metal electrode (such as but not limited to stainless steel alloys, gold, aluminum, nickel, copper) plate or mesh or a conductive carbon pad, weave or mesh acts as a current collector where a neutral salt MX forms M+ and X- when dissolved in water Upon placing a potential upon the electrodes, H2 gas will evolve at the "negative" electrode and species X will deposit/evolve at the "positive" electrode, where species X may be chloπne or iodine In one embodiment the metal electrode is platinum In a particularly preferred embodiment the surface area of Pt contacting containing gel is greater than 0 5 cm2 per 40 coulombs of charge transfer The electrode should have a porosity between 0% (fully dense) and 50% with a mean pore size between 1 μm and 100 μm TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
In some applications, more than one gel or electrolyte layer are used In one embodiment, charge is transferred such that Xn- is passed through a gel, paste, or hydrated film electrolyte, through the skin and other bodily tissue and re-emerges through the skin to a second gel, paste or hydrated film electrolyte A counter ion, Mn+, must exist, and may also carry charge In one preferred embodiment M and X is selected from ions commonly present in biological fluid or tissue
In a particularly preferred embodiment of the above descriptions of one or more gels, X is Cl and M is Ag In one preferred embodiment the concentration of X in the gel is selected to approximate the concentration of X present in biological tissue, such as skin, or biological fluid In one particularly preferred embodiment Ag+ Cl- concentration is between 10 mM and 200 mM In another preferred embodiment, the concentration of X in the gel is selected to exceed the concentration of X normally present in biological tissue In a still preferred embodiment, the [Ag] and [Cl] concentration in the gel is 200 mM to 2 M In another preferred embodiment two or more ions commonly found in biological fluid or tissue are present in the gel In a particularly preferred embodiment, the concentration of ions approximates the concentration of ion normally present in biological fluid or tissue In a still further preferred embodiment, 5 ions in the gel approximate the concentration of 5 ions in biological tissue or fluid These ions may correspond to the more dominant or active ions in tissue or more mobile ions The ions may include Na, K, Cl, Ca, and Mg In one preferred embodiment the peak or average current density of X- in the gel is greater than 0 1 mA per cm2 and less than 10 mA per cm2
In another embodiment, X- is passed through a gel, paste or hydrated film electrolyte, transported to the skin where X- transfers charge through the skin to species Y, where X is deposited or evolved and species Y become Y- through necessary charge balance Species Y- is then transported through skin and bodily tissue to a second gel, paste or hydrate film electrolyte where species Y is evolved or deposited and species X converters to species X- through necessary charge balance Species X- is then transported to a second electrode and undergoes an electrochemical reaction as described above Accordingly, M+ may be passed through a gel, paste or hydrated film electrolyte, transported to the skin where M+ transfers charge through the skin to species N, where M is deposited or evolved and species N becomes N- TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
through necessary charge balance Species N- is then transported through skin and bodily tissue to a second gel, paste or hydrate film electrolyte where species N is evolved or deposited and species M converters to species M+ through necessary charge balance Species M+ is then transported to a second electrode and undergoes an electrochemical reaction as descπbed above In one preferred embodiment X- is selected from ions not normally present in the body at significant concentrations In a still preferred embodiment X- is chloride ion or iodine ion In one preferred embodiment the charge transfer density of X and Y is great than 1 coulombs per 0 5 cm2 of gel skin contact area but less than 100 coulombs per 05 cm2 of dell skin contact area In another preferred embodiment, to prevent the above reactions, ions not normally present in significant quantities in biological tissue or fluid are omitted from the gel hi a still preferred embodiment, the activity or ions in the gel that are not present in significant quantities in biological tissue is less than 1 mM The inclusion or omission of ions normally present in biological tissue is ultimately determined by overall design factors outline above including the reduction of generated voltages, undesired electrochemical products, and irritation A shown in this invention, the design and selection of gel composition in an appropπate manner is necessary for safe and effective neurocranial stimulation
In another embodiment the electrolyte medium is a paste consisting of cellulose, any cellulose derivative or modification, or any natural fiber mixed with a brine solution consisting of any concentration of salt MX in water where M is sodium, potassium, magnesium or silver and X is chlorine or iodine where the concentration of salt in the bπne is between 10 and 200 mM and the ratio of brine to lotion is such that a minimum viscosity of 100 CPS and a maximum viscosity of 100,000 CPS is maintained while maintaining a conductivity on the order of 10-3 S/cm or greater
In another embodiment the electrolyte medium is a paste consisting of cellulose, any cellulose derivative or modification, or any natural fiber mixed with a brine solution consisting of any concentration of salt MX in water where M is sodium, potassium, magnesium or silver and X is chlorine or iodine where the concentration of salt in the bπne is between 10 and 200 mM and the ratio of brine to lotion is such that a minimum viscosity of 100 CPS and a maximum viscosity of 100,000 CPS is maintained while maintained a conductivity on the order of 10-3 S/cm or greater TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
In another embodiment any hydrophihc film or membrane (including but not limited to natural sponge, polyethylene oxide, any fluoπnated high molecular weight polymer with a molecular weight exceeding 100,000) hydrated with a bπne solution consisting of any concentration of salt MX in water where M is sodium, potassium, magnesium or silver and X is chlorine or iodine where the concentration of salt in the brine is between 10 and 200 mM and the ratio of bπne to lotion is such that a minimum viscosity of 100 CPS and a maximum viscosity of 100,000 CPS is maintained while maintained a conductivity on the order of 10-3 S/cm or greater The film may be set or crosshnked via photons, thermal treatment or chemical treatment such as, but not limited to, deprotonation, oxidation or reduction
To improve electrochemical performance while maintaining a low level of discomfort, specific additional electrolytes may be used In one embodiment a supporting electrolyte in the form of ocean or sea water (100 mM to 500 mM solutions) which may be but not limited to NaCl, MgC12 or KCl in addition to the brine solutions discussed above
The support material for the electrolyte and electrode is specifically designed for the purposes of the invention In one embodiment be a non-reactive and non- conductive ceramic such as but not limited to A12O3 or TiO2 where the holder may or not be porous If porous the pore size will be between 30 μm and 500 μm In another embodiment be a non-reactive and non-conductive polymer such as but not limited to PVDF, PVC, Acrylic or ABS where the holder may or not be porous If porous the pore size will be between 30 μm and 500 μm In another embodiment be a composite of non-reactive and non-conductive polymers and ceramics, where the polymers may be but are not limited to PVDF, PVC, Acrylic or ABS and the ceramics may be but are not limited to A12O3 or TiO2 where the holder may or not be porous If porous the pore size will be between 30 μm and 500 μm
Solid conductors suitable for use in the combination include those commonly used in the art for the application or monitoring of current across the skin Examples of such suitable conductors of the electrode include rubber, Ag, and Ag/ AgCl In a preferred embodiment, the electrode solid conductor is sintered AgCl TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
As outlined above, the combination consists of gels and electrolytes that are, when combined, predicted to support the active electrolyte formation or depletion of the solid conductor based on electrochemical knowledge In a preferred embodiment, the electrodes/gel combination is expected to support the formation and depletion of AgCl at the anode and cathode, respectively In a particularly preferred embodiment, the combination consists of an Ag or Ag/ AgCl solid conductor with CCNY-4 gel
According to a sixth aspect, there is provided a method to reduce irritation, sensation, discomfort, injury, burns, perception, inflammation, pain, or redness during neurocranial stimulation comprising the steps of selecting a suitable electrode-skin contact area, selecting a suitable metal electrode material, selecting an electrode shape, selecting a rigid or semi-rigid holder, selecting an appropriate gel, selecting a chemical to apply to the gel or the skin, selecting a temperature for the gel/skin, combining the electrode and gel in the holder, wherein said holder determines the shape and volume of the gel, the position of the electrode relative to the gel, and the portion of skin exposed to the gel, preparing the skin, attaching the assembly to the head of an individual with suitable attachment means, checking the electrode resistance, and/or selecting a conditioning electrical waveform to apply to the skin,
In one embodiment according to the invention, the electrode shape is selected from the group consisting of — Pellet, Ring, recessed surface, saw shaped surface, concave surface, convex surface, a horse-shore shape, a square, a diaphragm, and Disc In a preferred embodiment, the electrode shape is a ring In a still preferred embodiment, the πng outer diameter is greater than 3 times the ring thickness In yet another preferred embodiment, the inner ring diameter is greater than 50% of the outer πng diameter TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
In another preferred embodiment, the electrode shape is a pellet In a more preferred embodiment, the pellet length is greater than 3 times the pellets diameter
In another embodiment, the gel is selected from the group consisting of modified existing electrode gels, the base existing gel including Signa, Spectra, Tensive, Lectron II and Redux In a preferred embodiment the gel is either a modified version of Signa containing additional salt, or is CCNY-4 In a particularly preferred embodiment, the gel is CCNY-4
In another embodiment, the temperature is selected from the range consisting of -10-45 degrees centigrade In a preferred embodiment, the temperature is selected from the range of 10 to 37 degrees centigrade
In another embodiment, the electrical waveform is selected from the group consisting of DC, Interrupted DC, Symmetrical A C, Asymmetrical A C, Unbalanced triphasic, ramped, noise In a preferred embodiment, the current is direct current, applied via the method of transcranial direct current stimulation (tDCS)
In another embodiment, the skin preparation is selected from the group consisting of applying a skin treatment such as a chemical that may be earned is a delivery material such as a gel or cream, or electrically treating the skin, or mechanically altering the skin including through abrasion and scratching, or changing skin temperature
In another embodiment, the resistance is selected from the group consisting of 100 ohm to 5 mega ohm, or more preferably 200 ohm to 1 mega ohm, or more preferably 300 ohm to 1 mega ohm, or more preferably 200 ohm to 600 ohm, or more preferably 100 ohm to 600 ohm, or more preferably 400 ohm to 600 ohm
In another embodiment, the shape of the holder is selected from the group consisting of circular, cylindrical, conical, square In a preferred embodiment, the shape is a cylinder, or a hyperboloid permutation of a cylinder
According to a seventh aspect, there is provided an apparatus for applying transcranial current through the scalp using a plurality of electrodes, each electrode comprising at least semi-rigid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of a gel, at least one electrical stimulation electrode with a proximal end and a distal end, the distal end making TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
contact with a portion of the gel, and gel or paste contacting the scalp and containing no electrolytes or one or more electrolytes, and a cap or mesh positioned on the scalp and connected to the semi-rigid shell
In an embodiment according to the invention, the apparatus has a semi-rigid shell which is attached to the head by a means provided in the invention, including a banding apparatus, a plate apparatus, a cross apparatus, or a flexible cap or mesh In another embodiment, said electrode has a cylindrical shape In yet another embodiment, the electrode has a shape selected from the group consisting of disk or nng shape In one embodiment, said gel has high-resistivity while in another embodiment the gel has low-resistivity In one embodiment, said shell has a circular distal end, while in another embodiment said shell has a square distal end In one embodiment, said electrode is a metal while in another embodiment said electrode is a ceramic In one embodiment said electrode is silver while in another embodiment, said electrode is silver chloride In one embodiment, said semi-rigid shell includes a metal component while in another embodiment, said semi-πgid shell includes insulating material obstructing a portion of the distal end In yet another embodiment, said semi-rigid shell has a distal end with an aperture of least 1 cm2
In one embodiment according to the invention, said semi-rigid shell has an adjusting and attaching mechanisms for adjusting said semi-rigid shell to an optimal position on the said cap of mesh to suit an individual patient In another embodiment, said semi-rigid shell has a distal end with an area increased to reduce current density In another embodiment, the said semi-πgid shell has a distal end with a mesh to reduce current density
According to an eighth aspect, there is provided an apparatus for applying transcranial current through the scalp using a plurality of electrodes, each electrode comprising at least one semi-πgid shell with a distal end contacting the scalp and a proximal end with a portion of the shell encompassing a portion of the secondary gel, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the primary gel containing no electrolytes or one more electrolytes, TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
a secondary gel contacting a portion of the primary gel and the scalp, wherein the secondary gel may contain no electrolytes or one or more electrolytes
In one embodiment according to the invention, said secondary gel has high- resistivity, while in another embodiment said secondary gel has low-resistivity In one embodiment, said electrical stimulation electrode is in contact with a portion of the secondary gel, while in another embodiment where said electrical stimulation electrode is not in contact with a portion of the secondary gel In one embodiment, said semi-ngid shell include separate compartments for the primary gel and the secondary gel, while in another embodiment, said semirigid shell include includes a single compartment for the primary gel and the secondary gel
According to a ninth aspect, there is provided an apparatus for applying transcranial current through the scalp using a plurality of units, each unit comprising at least one semi-rigid shell with a distal end contacting the scalp and proximal end, a electrode mount with one portion contacting the semi-rigid shell and one portion contact the electrical stimulation electrode, at least one electrical stimulation electrode with a proximal and distal end making contact with a portion of the gel, and a gel or paste contacting the scalp and containing no electrolytes or one ore more electrolytes
In one embodiment, said semi-ngid shell encases a portion of said electrode mount while in another embodiment said electrode mount encases entire semi-rigid shell In one embodiment, said electrode mount is in contact with said gel or paste, while in another embodiment said semi-ngid shell is in contact with said gel or paste In one embodiment, said semi-electrode mount is circular or tubular In one embodiment, semi-electrode mount makes contact with said gel or paste on its inner surface while in another embodiment said semi-electrode mount makes contact with said gel or paste on its outer surface In one embodiment, said matrix is a hydrophobic polymer containing water in the amount of about 10% to 70% of the matrix In another embodiment, said matrix is substantially free of acid or of a salt of a strong acid In yet another embodiment, said matrix is substantially free of chloride salt In TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
one embodiment, said matrix has a high resistivity compared to the scalp, while in another embodiment, said matrix has a low resistivity compared to the scalp In one embodiment, said matrix contacts the scalp in an area less than 1 cm2
According to a tenth aspect, there is provided a transcranial stimulation electrode comprising an electrically conductive backing and an electrically conductive hydrogel matrix coated thereupon, said matrix being adapted to make contact with the skin of the patients and being sufficiently flexible to conform to the contours of the body
The present invention facilitates non-invasive neurocranial stimulation by reducing or eliminating irritation or discomfort caused during electro-stimulation There are several mechanisms by which stimulation can lead to irritation or discomfort including but not limited to 1) heating, 2) electrical stimulation of axons, 3) pH changes, 4) temperature changes, 5) electroporation or electro-permeation, 6) electrolysis 7) electrophoresis, 8) iontophoresis, 9) electro-osmosis These mechanisms may be linked or independent There are other mechanisms that may lead to irritation or discomfort
We found that there are several methods to reduce discomfort or irritation duπng NINCS The methods are 1) Optimizing gel or solid-conductor properties, 2) Optimizing electrode and electrode holder geometry and physical properties, 3) Chemical pre-treatment, 4) Electrical pre-treatment, and 5) Feed-back monitoring Each of these methods may be applied independently or in combination with others Typical NINCS Setup:
There is provided a device to generate electrical energy which is delivered to electrodes located on the head of a subject via electrically conductive wires The device may control applied voltage and/or current The current is in units of amperes (A) and may be on the scale of milli-Amperes (mA) The current travels down the electπcal wires to the electrode where it first enters a solid (semi)πgid conductor - for example a silver disk The current spreads out from the wire into the solid conductor The current density (in units of A/m2) descπbes how the current spreads through the solid conductor - this spread is not uniform (i e current density is not the same TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
everywhere) The current density in one part of the solid conductor is not the same as the current density in other parts of the solid conductor Often current tends to concentrates along the edges of the conductor After reaching up to the conductor, the current (which is spread across the solid conductor) crosses into the conductive gel There is an interface between the solid conductor and the gel (this interface is elsewhere referred to as the "electrode" but in this document "electrode" refers to the entire head assembly) The current density at this interface is particularly important Generally it is desired that the current density be as low as possible and as uniform as possible (i e no "hot spots") - although it is recognized that this may not always be the case The current then moves though the gel where it continues to "spread out", the measure of this spreading is the value of current density in the gel Again, the current density in the gel is not uniform throughout the gel, as the current density in one part of the gel is different than the current density in another part of the gel The gel contacts the skin There is an interface between the gel and the skin At this interface, it is again important that the current density be as low as possible and not have any "hot spots" where the current density is very high The current then enters and moves across the skin There is a specific current density in the skin, which as in the gel, is not necessarily uniform, leading to current density hot spots in the skin Generally, it is desirable to avoid these current density hotspots in the skin by making the current density in the skin as low and as uniform as possible The previous text has described the journey that the current makes through the electrode The specifics on this journey will depend on the shapes of the materials used, the types of materials used, and also the condition of the skin The important things are how to make the electrode and how to prepare the skin By controlling these parameters, the current density can be controlled in a manner that decreases or prevents irritation and discomfort Current density is not the only explanation for that cause irritation and discomfort and it is not the only parameter that needs to be controlled, but it is one parameter that is likely important Changing Properties of the GeI, Semi-Rigid Holder, or Solid-conductor:
The gel is composed of a material with a chemical composition and mateπal properties The semi-ngid holder is composed of a material with a chemical composition and mateπal properties The solid-conductor is composed of a mateπal TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
with chemical composition and material properties These factors may be controlled and selected to reduce skin lrntation/discomfort during NINCS
One can decide and make the materials well before the experiment In specific cases, it is possible to change the materials or material properties right before NINCS or even during NINCS
The following material properties of the gel may be changed to reduce irritation or discomfort
Gel conductivity, specifically between 30,000 to 60,000 or more than 40,000 μmhos/cm Gel ionic content, specifically NaCl, KCl and CaC12
Gel temperature, specifically in the range of 0 and 37 degrees C
Gel viscosity, specifically in the range of 1,000 to 1,000,0000 or 180,000 - 260,000 CPS
Adding the chemicals to the gel like sodium acetate, sodium hydroxide, sodium citrate etc As descπbed in this invention, the concentration of Cl is important in neurocranial stimulation Addition of sodium chloπde increase chloride as well as sodium concentration Addition of the above chemicals increases sodium but not chloπde concentration
Gel antioxidant capacity, specifically adding to the gel antioxidants as described in this invention
Gel analgesic effect, specifically by adding to the gel analgesics such as descπbed in this invention
The following material properties of the solid conductor may be changed to reduce irntation or discomfort
Solid-conductor resistance (proximal to distal end) in the range of 1 Ω to l,000 KΩ or l0 Ω- l KΩ
The solid conductor may be metal, rubber, conductive rubber, Ag/ AgCl, Ag, Gold
In one preferred embodiment the solid-conductor is sintered Ag/AgCl In another preferred embodiment the solid conductor is conductive rubber In another preferred embodiment the ratio of the resistivity on the solid conductor and gel is controlled TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
Change Electrode Geometry:
The electrode is composed of a metal, a gel, and holder for the solid-conductor and gel Generally, the holder is an electrical insulator The holder contacts the scalp or other part the head or neck The holder generally forms a well or series of wells, in which the gel is inserted, in such a way that the holder defines the shape of the gel The solid-conductor contacts the gel and generally is held in place by the holder The holder generally also attached to an electrode cap or band with position the electrode on the head A couple images show some examples of geometries and preferred embodiments that will reduce irritation or discomfort duπng NINCS
Some of these embodiments incorporate a fin design The fin is part of the holder The fin design includes one or more planes, the planes are vertical to the surface of the scalp, and serve two inter-related functions 1) they divide the gel intro compartments, 2) they position the electrode over these compartments in such a manner that a portion of the electrode contacts each of these compartments The fins may be parallel plains or may be radially symmetrical around the electrode center, or some other pattern Each fin may be rectangular shaped or may have a different shape
Some features of these geometries include - One or more ring metal solid- conductors, where the outer diameter ranges from 1 to 1000 mm or 11-12 mm and the inner diameter ranges from 1 to 1000 mm or 6- 7 mm A pellet solid-conductor with diameter ranging from 1 to 1000 mm or 1 5-2 5 mm and depth ranging from 1 to 1000 mm or 2-4 mm A disk solid-conductor with diameter ranging from 1 to 1000 mms or 11-12 mm
The holder divides the gel intro compartments, with the number of compartments ranging from 1 to 100, preferably one compartment for a single gel, or between 2 7, or more preferably 2 to 5 for combinations of gels
The holder divides the gel intro compartments and a different or same gel is applied to each compartment The holder fixes the distance of the proximal solid- conductor surface to the scalp surface, where the distance ranges from 0 1 to 100 mm or 2-5 mm
The holder fixes the position of the solid-conductor using a fin design, where the number of fins ranges from 1 to 1000 and from 2 to 7 and from 3 to 5 TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
The electrode surface is modified with needles, micro-needles, micro- architecture, nano-features, or nanotubes
In one preferred embodiment, the solid-conductor is a πng, positioned on a 3- fin radially symmetrical electrode holder In another preferred embodiment, a single holder accommodates two solid-conductors On another preferred embodiment, the solid-conductor surface area is increased by change the surface shape of the solid conductor including adding indent or extensions including curved extensions Chemical pre-treatment:
To reduce irritation or discomfort dunng NINCS, prior to NINC the skin or electrode may be pre-treated by application of a chemical The chemical may be applied before the treatment for days, hours, or seconds The chemical may be applied to the skin or to the electrode The chemical may be applied by a variety of means including brushing, squeezing, injection, or pouring The chemical may be allowed to permeate the skin or the gel The chemical may be applied during NINCS The chemical may be applied after NINCS The chemical may be dissolved or mixed in a liquid carrier
In one embodiment, 02-2 ml of a pre-conditioning cream is applied below the electrode In a preferred embodiment, the pre-conditioning cream is applied >5 minutes before the main stimulation phase In another preferred embodiment, the resistivity of the pre-conditioning cream is selected to be higher than the resistivity of the gel In this case, the conditioning cream will modify the current spread including increasing the uniformity of current entry In another preferred embodiment, the resistivity of the pre-conditioning cream is selected to be less than the resistivity of the gel In this case, the cream will not significantly increase the overall resistance to current flow, thus minimizing the contribution to electrode potential The cream will form an interface to both the gel and the skin with changes as described below For these reasons, the appropriate pre-conditioning cream can be matched to the gel used as described in this invention, and based on the design specifications and constraints as described in this invention For example, in one preferred embodiment, the preconditioning cream includes the primary ion earner in the gel In another preferred embodiment, the pre-conditioning cream excludes the primary ion carrier in the gel TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
The factors will also take into account if the primary ion carrier in the gel has been matched to a primary ion earner in the tissue or skin
In another embodiment, the properties of the pretreatment cream are essentially those of the electrode gels described above in this document Therefore, in the embodiment the pre-treatment creams are the same composition as optimal electrode gels, but are applied to the scalp prior to stimulation
The chemical may changes the properties of the skin or may changes the properties of the electrode or may change how current moves between different materials and into and through the skin
Some of the goals of chemical pre-treatment are to alter skin resistance, alter skin resistivity, make the skin more uniform in resistivity, remove resistivity hot spot or cold spots, block skin pores, open skin pores, change the properties of skin pores (including sweat glands and hair follicles), change the properties of blood vessels in the skin including dilation response, change the properties of axons the skin including firing threshold, the properties of muscle cell including firing threshold and mechanical responses The chemical may be a substance that blocks or opens sweat pores Chemicals include
Buffering agents or pH-balancing creams such as Acid Mantle that help restore acid balance of the skin This cream can be used under the one that produces a basic product, to maintain a balance Additionally, it may be useful to use different creams or topical solutions under the anode and cathode based on the properties of the creams,
Pain ointments such as Hydrocortisone 1% cream with Zinc Oxide, one of the main ingredients in creams to reduce irritation A combination of zinc oxide cream (Balmex, Desitin), vaseline, and aluminum acetate (burrow's solution) can also be made to reduce irritation,
Agents such as Aloe Vera that help reduce chronic redness and inflammation,
Burn ointments such as Foille,
Anti-inflammatory agents such as Cellex-C Sunshade SPF 30+, or anesthetic or analgesic creams or ointments, such as benzocaine, lidocaine, pnlocaine, or lanacane TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
The chemical may be a pH buffer such as - NaH2PO4
The chemical may be penetration enhancer to reduce the skin impedance like stearic acid, propylene glycol, linoleic acid, ethanol, sodium lauryl sulfate, oleic acid, stearic acid
The chemical may be activated or transported by electricity either duπng NEvJCS or during electrical pretreatment The chemical may have high conductivity ranging from 1 to 1 ,000,000 or preferably greater than 40,000, or most preferably 40,000- 60,000 μmhos/cm or The chemical may be an anesthetic such as topical solution The chemical may reduce pain or irritation such as Tronolane The chemical may be a muscle relaxant such as Relaxaid
The chemical may induce temperature changes such as BenGay
In one preferred embodiment, the chemical is applied to the surface of the skin and then the electrode is positioned over that surface
In another preferred embodiment, the chemical is applied to the electrode on the surface which will contact the skin, and the electrode is then positioned on the skin
Electrical pre-treatment:
To reduce irritation or discomfort during NINCS, electrical current may be applied prior to the actual stimulation protocol, effectively sensitizing the subject In the simplest embodiment, the current is applied through the same electrode that is subsequently used for stimulation However, separate electrodes may be used for electncal pre-treatment
Electrical pre-treatment may be applied before the treatment for days, hours, or seconds Additionally, electrical pretreatment may be applied duπng or after NINCS
The electncal pre-treatment step works by selecting an appropπate waveform for pre-treatment The pre-treatment electrical waveform may or may not be same as NINCS Using a pre-treatment waveform different than that of NINCS may be beneficial in the following ways 1) the pre-treatment waveform does not itself cause any skin irritation or discomfort but changes skin or electrode conditions such that TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
subsequent NINCS does not induced irritation or discomfort, 2) the pre-treatment waveform does not change brain function but rather changes skin properties
The electrical pre-treatment waveform used may be DC in the amplitude range of 0 1 to 1 mA and applied for 0 1 to 60 minutes The electrical pre-treatment waveform may be AC in the amplitude range of 0 1 to 1 mA the frequency range of 0 01 to 500 kHz and applied for 0 1 to 60 minutes The electrical pre-treatment waveform may pulsed with frequency range 0 01 to 500 kHz, and pulse width of 0 1 us to 100 seconds, and an inter-pulse interval 0 1 us to 100 seconds
The electrical pre-treatment waveform may be noise or noisy including white noise, Gaussian noise, 1/f noise, thermal noise, short noise
The electrical pre-treatment waveform may be a ramp with a slope of 1 mA per minute to 1 mA per ms The electrical pre-treatment waveform may be Gaussian with standard deviation of value 0 to 10 or 0 to 10000
The electrical pre-treatment waveform may a combination of the above and may involve repetitive pre-sπmulation The electrical pre-treatment waveform may involve getting subject feed-back
In one preferred embodiment a low level of conditioning DC current is applied prior to stimulation The conditioning DC current is below 05 mA and may be below 0 1 mA The conditioning DC current is applied for 1 minute to 30 minutes The conditioning DC current may be ramped up and down slowly including at a rate of 0 1 mA per minute After this conditioning DC the NINCS therapy current is applied (which may also be DC current but will generally be of higher and more brain effective amplitudes - in this case the conditioning current may be the same polarity or of opposite polarity to the DC electrical therapy current) The interval between the DC conditioning current and the NINCS electrical therapy current can vary between 0 and 10 minutes In the interval between the conditioning DC current and the NINCS electrical therapy current, the resistance of the electrode may be tested - this resistance reading may inform if another additional conditioning current in necessary prior to NINCS electrical therapy stimulation (see also feed-back monitoring below)
In one preferred embodiment the electrical pre-treatment waveform increased monotomcally In another preferred embodiment, the intensity of the pre-treatment waveform increases and then decreases prior to the main stimulation phase In a still TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
preferred embodiment the intensity of the pre-treatment electrical waveform returns to zero In a still preferred embodiment, the waveform is sinusoidal In one such embodiment, the sinusoidal waveform has a zero average intensity In another such embodiment, the sinusoidal waveform has a non-zero average intensity where that average intensity may be positive or negative and may be matched to the intensity and polarity of the main electrical treatment stage In another preferred embodiment the waveform is a sinusoidal with modulated amplitude In one such embodiment, the sinusoidal frequency is greater that 1000 Hz In another such embodiment, the sinusoidal frequency is greater than 10000 Hz In another preferred embodiment the waveform is composed of two or more sign waves In one such embodiment, the difference in frequencies between the two waveforms is greater than 100 Hz In another such embodiment, the difference in frequencies between the two waveforms is less than 100 Hz In another preferred embodiment, the electrical pre-treatment waveform incorporates pulses Feed-back monitoring:
To prevent or reduce skin irritation or discomfort, the conditions of the electrode and/or skin may be monitored before, during, or after stimulation The conditions are monitored by sensing a parameter These readings may be used to turn off NINCS or adjust NINCS properties including all the properties described above
The device or sensor which monitors a condition or parameter may be integrated into the NINCS device itself, or may be a separate device, or may have some overlapping components
The parameter monitored may be displayed to the subject / operator for example using a digital display, or indicator lights, or an audio monitor The parameter may be stored for later retrieval for example of a storage device The parameter or combination or parameters may be processed using an algorithm or mathematical function This algorithm or mathematical function could incorporate addition, subtraction, averaging, averaging over time, filter, low-pass filtering, high- pass filtering, liner or non-linear operations, user defined operations The output of this algorithm and the parameter form a reading that may be used to change NINCS parameters TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
For each reading there may be a 'threshold' value which is used to determine if NINCS should begin, stop, be interrupted, be changed, or if a warning should be provided to the subject or operators
In one preferred embodiment the electrode voltage and electrode current are monitored and stimulation is stopped if either voltage or current exceed a threshold, if the rate of voltage change or current change exceed a threshold, if the current* voltage exceed a threshold, or if the rate of change of the current* voltage exceeds a threshold The stimulation may stop instantaneously or may be gradually reduced A warning may be provided to the subject or operator The stimulation may stop automatically or after the subject or operator activates a manual switch or trigger
In another preferred embodiment the electrode voltage and electrode current are monitored and stimulation is decreased if either voltage or current exceed a threshold, if the rate of voltage change or current change exceed a threshold, if the current*voltage exceed a threshold, or if the rate of change of the current*voltage exceeds a threshold The stimulation current and/or voltage are automatically reduced to be maintained below the threshold A warning may be provided to the subject or operator The subject or operator may choose to override the otherwise automatic reduction by activation of a manual switch or trigger
In another preferred embodiment, the resistance of the electrode is monitored The resistance may be monitored by application of a test voltage or current pulse The test voltage or current pulse may be sufficiently small such that no brain modulation or skin irritation results The test voltage or current pulse may be DC or AC The resistance may act as a threshold for feed-back to determine is NINCS may begin or may continue The resistance of the electrode may be passed through a mathematical function to determine the resistance quality The resistance of an electrode may be compared again another value such as the resistance of another electrode
In another preferred embodiment, the impedance of the electrode is monitored The impedance may be monitored by application of series of test voltages or current pulses The series of test voltages or current pulses may be sufficiently small such that not brain modulation or skin irritation results The series of test voltages or current pulses may be DC or AC of different frequencies The impedance may act as a threshold for feed-back to determine is NINCS may begin or may continue The TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
impedance of the electrode may be passed through a mathematical function to determine the impedance quality. The impedance of an electrode may be compared again another value such as the resistance of another electrode.
In another preferred embodiment, a temperature probe is inserted into the gel or portion of the electrode and monitors temperature. The temperature probe may be a thermocouple or a thermistor or optical.
In another preferred embodiment, a pH probe is inserted into the gel or portion of the electrode and monitors pH. The pH probe may be an electrochemical or solid- state or optical. The electrode voltage with a threshold for change ranging from 1 to 1000 V, and 50 to 150 V. The electrode voltage change over time ranging from 0.001 V per hour to 1000 V per second. The electrode current, with a threshold for change ranging from 0.1 to 1000 mA, and 1 mA to 20 mA.
Examples Methods Electrode configurations: materials and geometry
Five types of solid-conductors were tested in the study: 1) "Ag pellet" (2117 - Silver Wire; Surepure Chemetals, Florham Park, NJ, USA); 2)"Ag/AgCl sintered pellet" (550015-pellet electrode; A-M systems Inc, Carlsborg, WA.USA); 3) "Rubber pellet" (116A-GSR-5, rubber electrode; Austin Medical equipment, Westchester, TX, USA; all pellets were 2mm(D) x 4mm(L) resulting in ~ 30 ± 2.5 mm2 solid- conductor-gel contact area); 4) "Ag/AgCl sintered ring" (EL-TP-RNG Sintered; Stens Biofeedback Inc, San Rafael, CA; with outer and inner periphery diameter as 12 mm and 6 mm respectively, resulting in a ~ 140 ± 5 mm2 solid-conductor-gel contact area); and 5) "Ag/AgCl sintered disc" (550025, Disc Electrode A-M Systems; with 8 mm diameter resulting in ~ 85 ± 5 mm2 electrode-gel contact area). Each electrode- gel configuration was independently evaluated as an anode or cathode. Plastic holders for all electrodes were used to position electrodes over the skin and standardize gel volume used. Plastic holders for all pellet electrodes held ~90 ± 5 mm3 of gel volume with a gel-skin contact area of -25 ± 2.5 mm2. Customized holders for ring/disc electrodes contained ~280 ± 10 mm3 of gel and provided ~95 ± 5 mm2 gel-skin contact area. TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
The following gels were tested 1) "Signa Gel" (Parker Laboratories Inc , Fairfϊeld, NJ, USA), 2) "Spectra 360" (Parker Laboratories Inc ), 3) "Tensive" (Parker Laboratoπes Inc ), 4) "Redux" (Parker Laboratories Inc ), 5) "1090 BioGel" (UFI Inc , Morro Bay, CA, USA), 6) "Lectron II" (Pharmaceutical Innovations Inc , Newark, NJ, USA), and 7) "CCNY-4" (custom made) All gels were at room temperature at the time of application The electrical conductivity values of the gels, measured by a portable digital conductivity meter (Model 2052, VWR International LLC, Bridgeport, NJ, USA), were (in units of μmhos/cm) CCNY4 ~ (45,000 ± 10,000), Signa ~ (40,000 ± 10,000), Redux ~ (35,000 ± 10,000), Lectron II ~ (15,000 ± 7,500), 1090 BioGel ~ (15,000 ± 7,500), Tensive ~ (6,000 ± 3,000), and Spectra ~ (1,500 ± 500) The thermal conductivity values of the gels, measured by a thermal properties meter (Model KD2, Decagon, Pullman Washington, USA), were (in units of W/m°C) CCNY4 ~ (0 0326 ± 00043), Signa ~ (0 0285 ± 0 0034), Redux ~ (0 0326 ± 0 0043), Lectron II ~ (0 0285 ± 00008), 1090 BioGel ~ (0 0280 ± 00008), Tensive ~ (0 0295 ± 0 0024), and Spectra ~ (0 0274 ± 0 0007) DC Stimulation and Resistance
A constant current stimulator (CX 6650, Schneider Electronics, Gleichen, Germany) was used to apply direct current for all trials, with a maximum driving voltage capability of 66 7 Volts A current intensity of 2 mA was used for up to 22 minutes, with automatic on and off ramps of 10 sec to avoid "stimulation break" effects The stimulator automatically terminates stimulation at an output potential (total potential across both electrodes and agar/tissue) of 66 7 V, which was used as a cut-off point in all trials Pπor to and after stimulation, total cell resistance (see below) of the agar gel or forearm skin was measured using a RMS digital multimeter (FLUKE 177, FLUKE Corporation, Everett, WA, USA), stimulation was only initiated when the total cell resistance was less than 8 MΩ Electrode Potential, pH, and Temperature Studies
For studies measuring electrode potential, pH, and temperature changes, the electrodes were mounted with gel on a flat block of agar made with 150 mM (physiological) NaCl For these studies, the rationale was to measure changes at only one "active" anode or cathode electrode without contribution from the two return electrodes The two return electrodes, generally sintered Ag/AgCl disc or πng TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
electrodes, were each immersed in an excess of -400 ± ϊθ mm3 Signa Gel The total cell resistance reflected the resistance between the active electrode and the two return electrodes which are connected in parallel In this report, "electrode potential" generally refers to the total potential over the entire assembly of electrodes, gel, and skin
In all experiments, 2 mA of DC current was applied for up to 22 minutes, between one active anode or cathode electrode and the two return electrodes For experiments quantifying electrode potential, current was passed between the active and return electrodes, and voltage was simultaneously measured The reference electrode was an 8 mm sintered Ag/AgCl disc electrode immersed in Signa Gel of volume in excess of ~ 400 ± 10 mm3 Therefore, the total measured voltage is a summation of voltage drops across the active electrode (including electrode, active electrode-gel interface, active electrode gel), agar gel (from the active to reference electrode), and reference electrode (across which current is not passed) it is expected that the only voltage that will change substantially as a result of stimulation is the voltage across the active electrode Thus the measured voltages in these experiments largely reflect the electrode-gel interface "over-potential" at the active electrode
A calibrated micro pH electrode (Orion 9810BN, Thermo Scientific, Waltham, MA, USA) and a digital pH meter (SMlOO, Milwaukee Instruments Inc , Rocky Mount, NC, U S A ) were used to measure pH in the active electrode's gel at the agar surface, at vaπous exposure durations To measure the pH, the stimulation was turned off, the solid conductor was removed from the gel, and the micro pH electrode was inserted into the gel within 5 seconds pH was recorded after exposure durations of 1 mm, 5 mm, 10 mm, 15 mm and 20 mm pH studies were conducted on four solid-conductors (Ag pellet, Ag/AgCl sintered pellet, Rubber pellet, Ag/ AgCl sintered ring) in combination with three electrolyte gels (Signa Gel, Lectron II Gel, CCNY4 Gel) For temperature experiments, a Type T Thermocouple Thermometer (BAT-10, Physitemp Instruments, Clifton, NJ, USA) was used on the bottom surface of the gel during stimulation
As indicated above, the stimulator automatically stopped stimulation if a total potential of 66 7 V (cut-off voltage) was achieved In cases when stimulation was TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
applied for 22 minutes, the "stimulation time" was scored as 22 minutes and the maximum pH and temperature changes during the 22 minutes were noted In cases when a potential of 667 V was reached prior to 22 minutes, the "stimulation time" was scored as the time when the potential reached 66 7V, the maximum pH and temperature at this "stimulation time" was then noted
Subjective Sensation Eight healthy subjects (6 males and 2 females, 19-35 years) participated in each experiment All gave written informed consent before being included in the study The study was approved by the IRB board of the City College of New York Sensation tests were restricted to four solid-conductors (Ag pellet, Ag/AgCl sintered pellet, Rubber pellet, Ag/ AgCl sintered πng) and three gels (Signa, Lectron II, and CCNY4) The experiments were conducted on the distal or proximal forearm, as arbitrarily preferred by the subjects For sensation studies, the rationale was to determine the effect of the "active" electrode (either cathode or anode) Two Ag/AgCl πng electrodes were used as "return" electrodes Return electrodes were positioned on opposite sides of the active electrode Each return electrode was immersed in ~ 280 ± 10 mm3 volume of Signa Gel Regions of skin with visible irritation or cuts prior to stimulation were avoided There were no steps taken to otherwise prepare the skin prior to stimulation
Stimulation was applied for up to 22 minutes with subjects scoring pain (on a 1 to 10 analog scale) every minute beginning two minutes before, every minute duπng, and ending two minutes after stimulation In addition, subjects were prompted to descnbe the sensations ("burning", "prickling" etc ) Pπor to stimulation each subject indicated a personal termination value (at or below 5) at which stimulation would be stopped by the operator In addition, each subject could request to stop the stimulation at any point of the expeπment, regardless of the current pain score or nature of perception If stimulation was stopped pπor to 22 minutes of exposure, the pain score at termination was noted Greater than 1 hour of delay was allowed between expeπments, and the stimulation site (e g arm) was changed for consecutive experiments Participants were blinded to the type and combination of solid-conductor and gels tested After stimulation any skin lesions or redness was noted Results Electrode Potential TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
Electrode potential across conductive agar was recorded during 2 mA DC stimulation During clinical stimulation it is desirable to minimize electrode potential for several reasons including 1) voltage limits on constant current stimulators, 2) increased πsk for skin injury including through electrochemical reactions (limited by electrode over-potential) and heating Cathodal stimulation with rubber pellets resulted in variable voltage increases whereas electrode potential remained less than IV for all other solid-conductors Anodal stimulation with all solid-conductors resulted in increased and variable electrode potential values
Electrode potential results for anodal stimulation experiments are summarized, we report both the average potential and variability across trials (5 trials per electrode/gel combination) These potentials can also be interpreted as reflecting changes in the resistance at the electrode site during DC anodal stimulation When the stimulator potential reached 66 7 V (driving voltage capacity of CX 6650), stimulation was automatically stopped and this was recorded as the maximum exposure duration ("stimulation time") for that trial, otherwise the exposure duration was scored as 22 minutes
Figs 29 and 30 illustrate the electrode potential results for trials employing electrode assemblies having pellet type electrodes
Fig 29 illustrates a current-induced polarization of a AG pellet type electrode assembly shown as apparent voltage across anode over time 2 mA DC current with indicated gels was passed, and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines shows average The electrode assembly shown is used only to indicate the general design
Fig 30 illustrates a current-induced polarization of a Ag-AgCl pellet type electrode assembly shown as apparent voltage across an anode electrode assembly over time 2 mA DC current with indicated gels was passed, and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines shows average The electrode assembly shown is used only to indicate the general design
Fig 31 illustrates the electrode potential results for trials employing electrode assemblies having a rubber type electrodes A current-induced polarization of a rubber pellet type electrode assembly is shown as apparent voltage across an anode electrode TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
assembly over time 2 mA DC current with the indicated gels was passed, and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines shows average The electrode assembly shown is used only to indicate the general design
Fig 32 illustrates the electrode potential results for trials employing an electrode assembly having a disc type electrode Current induced polarization of an Ag-AgCl disk type electrode assembly is shown as apparent voltage across anode over time A 2 mA DC current with indicated gels was passed and the change in voltage with time was measured Back dotted curves shows five repeats while solid lines show an average The electrode assembly shown is used only to indicate the general design
Fig 33 illustrates the electrode potential results for trials employing an electrode assembly having a πng type electrode Current induced polarization of an Ag-AgCl ring type electrode assembly is shown as apparent voltage across an anode electrode assembly over time 2 mA DC current with the indicated gels was passed, and the change in voltage with time was measured Back dotted curves show five repeats while solid lines show averages The electrode assembly shown is used only to indicate the general design
Fig 36 presents a summary of run times by electrode type according to the trials of Figs 31 - 33 Average potential run time profiles during anodal stimulation for designed electrode assemblies 22 minutes represents the maximum time tested For each electrode, the run times are indicated for seven gels from left to right Electro Gel, Lectron, Redux, Signa, Spectra, Tensive, CCNY4
Fig 37 presents a summary of pain and electrochemical performance of designed Neurocranial electrode assemblies 2 mA of current was used in all cases A summary of average pain scores (high, and average over stimulation period) across subjects is provided, together with a percentage of subjects electing to stop stimulation prior to 22 minutes, a percentage of subjects with redness under electrodes following stimulation, and indications of peak changes in temperature and in pH of the gel
Using the Ag/AgCl sintered pellets, the full 22 minutes of anodic stimulation could not be applied in combination with any gel Using the Ag pellet, 22 minutes of TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
anodic stimulation could be consistently applied only with Lectron II gel and after stimulations a removable, black paste-like residue was observed along the surface of the electrode Using the Rubber pellet, some variability in exposure time was observed across various trials and gels, in addition, a relatively wide deposition layer was observed on the rubber after stimulation This layer was easily deterged and an apparently intact and unaffected rubber solid-conductor surface remained Using both Ag/AgCl sintered πng and Ag/ AgCl disk electrodes, 22 minutes of stimulation could be consistently applied, in combination with any gel, with Ag/AgCl disk having the lowest average electrode potentials Gel pH and Temperature
For pH and temperature measurements we investigated three gels two with chloride (Signa and CCNY-4) and one nominally chloride free (Lectron II), each gel was independently tested in combination with four solid-conductors (Ag pellet, Ag/AgCl sintered pellet, Rubber pellet, Ag/AgCl sintered ring) All measurements were conducted on agar gel (150 mM of NaCl) Both Anodal and Cathodal stimulations were tested independently In the cases where the total cell potential (including electrode potential) exceeded the stimulator cut-off (66 7 V), measurements were limited to the maximum exposure time allowed pnor to cut-off
Cathodal stimulation, which results in minimal electrode potential values did not induce significant temperature increases in the gel under any condition tested For anodal stimulation, in cases where no electrode potential change occurred (e g Ag/AgCl sintered πng with any gel) no temperature changes were observed in the gel Across all three tested gels, temperature πses were observed under anodal stimulation with both Ag pellet and Ag/AgCl sintered pellet solid conductors, where electrode potential changes were also maximal During stimulation with Rubber pellet, there was significant tπal-to-tπal variability in the temperature changes induced, however, as voltage increase was observed, temperature increased monotonically (though not linearly) with voltage and time Temperature changes in gel under electrode may thus be avoided by limiting changes in electrode potential For a fixed electrode configuration (pellet), a change in potential was qualitatively related with a change in temperature TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
No pH changes were found across all tested electrodes, for either polarity, while using Lectron II gel In the case of Ag/ AgCl sintered pellet and Ag/ AgCl ring, no pH changes were observed, under either cathodal or anodal stimulation, for all three gels Using Ag pellet, no pH changes were observed during anodal stimulation, while pH alkahzation was observed with Signa and CCNY-4 gel during cathodal stimulation Rubber pellets only with Signa and CCNY-4 gel, resulted in acidic gel pH with anodal stimulation and basic gel pH in cathodal stimulation even in the absence of a voltage change Thus, while increase in temperature is linked to increased electrode potential, pH changes is not directly linked to electrode potential, and are matenal specific, pH changes can be avoided using appropriate solid- conductor and gel combinations Subjective Sensation
Fig 34 illustrates subjective pain results for trials employing cathodal stimulation Subjective sensation scores of four subjects during 22 minutes of cathodal stimulation (t=0 to 22), for each electrode assembly
Fig 35 illustrates subjective pain results for trials employing anodal stimulation Subjective sensation scores of four subjects dunng 22 minutes of anodal stimulation (t=0 to 22), for each electrode assembly
N-way (gel, polarity and electrode) ANOVA was applied to the pain ratings ANOVA revealed a significant effect of gel (F(1,8) = 10 37, p = 0001) and electrode (F(1,8) = 3 38, p = 019) on pain ratings There was no effect of polarity (F(1,8) = 0 05, p = 831) or interaction effects of gel-polarity (F(1,8) = 0 72, p = 488), gel- electrode (F(1,8) = 0 33, p = 922), polarity-electrode (F(1,8) = 0 13, p = 944) and gel-electrode-polaπty(F(1,8) = 0 37, p = 897) Overall, Signa gel and CCNY-4 were better tolerated than Lectron II There was no significant difference between anodal verses cathodal stimulation
Across subjects, stimulation polarity, electrode gel, and configurations, subjective sensation was highest when stimulation was ramped on or off As expected for any relative individual pain scoring, there were differences in absolute levels between subjects as well as differences in conditions tolerated A majority of subjects indicated that sensation was restricted only to the "active" test electrode (anode or cathode), but in a few cases subjects indicated sensation under the return electrode(s), TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
this was not an exclusion cπteπa There was no evident correlation between pH or temperature changes to that of the subject sensation, for example Ag/ AgCl sintered ring electrodes resulted in no temperature or pH changes but did induce discomfort in some subjects
Examination of the skin after stimulation indicated slight redness Overall, in cathodal stimulations there are higher chances of observing skin irritation in the form of small bumps or black dots (<1 mm) and apparent roughening of the skin under the electrode Observation of lesions was not apparently correlated to subjective pain sensation or any physical gel changes All effects on the skin were reversible and disappeared within few hours No subject reported a lasting irritation of pain
In comparing between forearm and agar gel stimulations, the total cell potentials recorded were not significantly different Therefore results obtained for the forearm and agar gel with respect to total cell potential are comparable We observed no consistent relationship between the changes in electrode potential and skin sensation during stimulation (or redness post-stimulation) The average resistance of the tissue pπor to stimulation with Ag/ AgCl πng electrode ranged from 100 kΩ to 8 MΩ, with an average value of 675 95 ± 1100 kΩ After the stimulation, the tissue resistance significantly reduced to a range of 3 kΩ to 800 kΩ, with an average value of 68 62 ± 272 3 kΩ Therefore, the average percentage drop of resistance post- stimulation was 92 56% ± 67% Electrochemistry of surface DC stimulation
We propose the following electrochemical scheme when electrode/gel conditions exist to support AgCl depletion/formation at the cathode/anode, electrical stimulation can proceed with minimal over-potential and no pH or temperature change When during the course of stimulation AgCl depletion/formation is no longer supported, electrode over-potential increases which leads to additional chemical reactions, which, in turn, may ultimately lead to heating and pH changes Over- potentials do not necessarily lead to (or are sufficient for) such changes, but are necessary for additional chemical reactions
For DC stimulation, a common approach is to use Ag/AgCl non-polanzing electrode With Ag/AgCl electrodes, as long as faradaic charge-transfer reactions at TCO Ref:09A0008 Attorney Docket No. 02830/2213322-WOO
the electrode interface can proceed, no significant electrochemical processes initiate. At the cathode, dissolution of silver chloride and reduction of the silver ions facilitates faradaic charge delivery across the electrode.
Figure imgf000062_0002
Figure imgf000062_0003
At the cathode, AgCl is thus depleted from the electrode surface. Under our tested conditions using all Ag/ AgCl electrodes (both pellet and ring), the availability of AgCl was apparently sufficient to allow this cathodic reaction for 22 minutes at 2 mA and hence minimal over-potential was generated; this proceeded independent of gel composition (e.g. the baseline concentration of Cl- in the gel being irrelevant, as it is a product). For similar reason, no pH or temperature changes were observed during cathodal stimulation with any AgCl electrodes, independent of gel composition. At the anode electrode site AgCl is formed
Figure imgf000062_0001
In contrast to the above described cathodal process; this anodal process requires Cl- availability in the gel and Ag at the solid-conductor surface. One might then predict that anodal stimulation with Ag pellet and Cl- rich gel would produce the least over-potential and longest run times because reaction (2) is supported. However, results show that high over potentials developed during anodal stimulation with Ag pellet and 22 minute run times were achieved only with nominally Cl- free (Lectron II) gels. Our hypothesis in this special case is that due to the rate of reaction (2) there is a rapid formation of AgCl on the metal electrode, which may appear as a black layer on the electrode. This layer may "chemically insulate" the electrode from further reactions, which in turn may explain the increase in the electrode over-potential and decrease in run time. This hypothesis is supported by our observation that after removing this layer, running a second stimulation supports run times comparable to the novel case of the Ag pellet electrode. However, running a second stimulation without removing the AgCl layer, results in run times of less than a minute. The failure of Ag/ AgCl pellets to support anodic stimulation may indicate 1) the formation of a similar chemical insulation layer; or 2) insufficient reservoir of available Ag.
Ag/AgCl pellets do not completely support this reaction and hence over- potentials develop. We used micro-temperature and pH sensors to detected TCO Ref09A0008 Attorney Docket No 02830/2213322-WOO
physical/chemical changes in the gels under the electrodes during stimulation We cannot rule out that in during stimulation across skin, hot-spots of temperature or pH changes may occur, for example in sweat glands, which could not be measured in the present study At the gel, we observed pH changes only with pellet electrodes and specific combination of metal conductor/gel pH changes reflect for electrochemical reactions at the solid-conductor/gel interface and the ability of the gel to buffer pH changes When pH changes were observed, the anode site became more acidic and the cathode site more basic, this observation is consistent with oxidation of water at the anode site (formation of H+) and reduction of water at the cathode site (formation ofOH-, reviewed in Mernll et al , 20O5),
Figure imgf000063_0001
Acidification at the anode and alkalization at the cathode, are consistent with our observations using un-optimized configurations, and previous pH measurements using various types of electrodes In all cases where the electrode/gel combination was expected to support AgCl formation or depletion, pH changes were not observed This is consistent with the reduction/oxidation of water requiring higher electrode over- potential to initiate AgCl formation/depletion In cases where the respective AgCl reaction was not supported, changes in pH were not necessarily observed, reinforcing the importance of the specific electrode design Rubber electrodes cannot support either AgCl deletion at the cathode (1) or AgCl formation at the anode (2) The chemical reactions occurring at the rubber-gel interface are poorly defined, and though they may support prolonged stimulation, there was trial-to-tπal variability in induced potential and associated temperature and pH changes While the invention has been particularly shown and described herein with reference to preferred embodiments thereof, it will be understood by those skilled in the art as described herein that various changes in form and details may be made to the discloses embodiments without departing from the spiπt and scope of the invention Accordingly, the invention is to be limited only by the scope of the claims and their equivalents

Claims

ClaimsWe claim:
1. An electrode assembly for neuro-cranial stimulation comprising: an electrode; a cottducth e gek and an adapter including: an interior compartment for positioning the electrode relame to the adapter and for receiving and retaining the conductive gel, whereby the conductiv e gel contacts the electrode along an electrode-gel interface, and an orifice in communication with tiic interior compartment and adjacent to a positioning surface of the adapter for positioning the electrode assembly against a skin surface of a user, through which orifice the conducthe gel is able to contact the skin surface of the user to define a gel-skin interlace, wherein the positioning surface defined a plane that extends laterally across the orifice and the adapter is further configured so that a minimum distance between the electrode-gel interface and piane during use is between 0.25 cm and 1.3 cm.
2. The electrode assembly of claim 1, wherein an area of the plane within the orifice is between 25 πmr and 95 rant.
3. The electrode assembly of claim I. wherein a contact area of the electrode-gel interface is between 30 and 140 mm2.
4. The electrode assembly of claim 1 , wherein a ratio of a contact area of the electrode-gel interface and the piane within the orifice is between 0.3 and 5.6.
5. The electrode assembly of claim 1, wherein an area of the plane within the orifice defines a circle or an oval
6. The electrode assembly of claim I. wherein one or more surfaces of the electrode define at least one shape selected from the group consisting of rings, thickened rings, discs, pellets, elongated pellets, recessed surfaces, saw-shaped surfaces, conca\ e surfaces, horse shoe-shaped surfaces, helix-shaped surfaces, squares, rectangles, plates, meshes and diaphragms,
7. The electrode assembly of claim 6, wherein the one or more surfaces of the electrode are provided with surface features that increase a surface area of the electrode.
8. The electrode assembly of claim I. wherein the electrode comprises at least one materia! selected from the group consisting of metals, alloyed metals, rubber, conductive rubber, Ag/AgCl, Ag, and Au,
9. The electrode assembly of claim 1 , wherein the electrode is a ring, electrode comprising sinteied AgCI.
10. The electrode assembly of claim 9, wherein the sintered AgCl electrode has a porosity of less than 50% with a mean pore size between 1 μm and ! 00 μm.
1 1. The electrode assembly of claim 1 , wherein the adapter comprises rigid material.
12. The electrode assembly of claim 1 1. wherein the adapter comprises a non- conduethe plastic material
13. The electrode assembly of claim 1, further comprising a first sealing member affixed to the positioning surface and extending cner the orifice of the adapter, the first sealing member being configured to be peeled off or pierced to enable the conduethe gei to contact the skin surface of the user to define the gel-skin interface.
14. The electrode assembly of claim 13, wherein an open end of the interior compartment of the adapter that is distal iy positioned relative to the orifice comprises a second sealing member, and the first sealing member and the second sealing member are configured to confine the conductive gel within the interior compartment.
15. the electrode assembly of claim 1, wherein the conductive gel has a
Figure imgf000066_0001
between 0.5 inL and 5 ml.
16. The electrode assembly of claim 1 , wherein the conductive gei has a conducmity between 30.000 to 60,000 μmho cm.
17 The electrode assembly of claim 1 , wherein the coudυcth e gel comprises at least one salt selected from the group consisting of NaCL KCi and CaCb-
18 The electrode assembly of claim 17, wherein a total gel Cl concentration is greater than I50 mM
19 The eleciKxie assembly of claim 18, wherein the total gel Cl concentration is greater than 200 røM
20 Fhe electrode assembly of claim 1, wherein the conductive gel has a viscosity between 180,000 to 260.000 cPs
21. The electrode assembly of claim 1 , wherein the conductive gel further comprises an additive
22. The electrode assembly of claim 21, wherein the addithe comprises an antioxidant.
23. The electrode assembly of claim 21. \\ herein the addithe comprises an analgesic
24 Ihe electrode assembly of claim 23, whet em the analgesic is selected from the group consisting of Lidocame, Benzocaine, and Prilocaine.
25 The electrode assembly of claim 2K w herein the additive comprises a pH buffer.
26. the electrode assembly of claim 21 , wherein the addith e comprises a penetration enhancer selected from the group consisting of steaπc acid, propylene glycol, unoiesc acid, ethanoi. sodium Iauryl sulfate, and oleic acid.
27. the electrode assembly of claim 1, wherein the interior compartment comprises one or more locating tabs for positioning the electrode.
28 The electrode assembly of claim 1, wherein the adapter further comprises a cap member configured for enclosing the electrode in the interior compartment
2(X The eiecttode assembly of claim 28. wherein the electrode is fixedly
Figure imgf000067_0001
idee! to the cap membeϊ
30. the electrode assembly of claim 1, wherein the adapter is further configured for positioning a plurality of electrodes within the interior compartment
31 Fhe electrode assembly of claim 1 , wherein the adapter further comprises an aceessojy piece for holding at least another electrode, the accessory piece being attached to the adapter and in communication with the interior compartment of the adapter whereby the eonducth e gel further extends to contact the other electrode
32. The electrode assembly of claim 1 , wherein the interior compartment comprises one or more fins in proximity to the orifice that extend w ithm the interior compartment
33 fhe electrode assembly of claim 32, \\ herein the one or more fins are configured to position at least a surface of the electiode
34. The electrode assembly of claim 1 , wherein an outer surface of the adapter includes one or more locating features.
35. An apparatus for neuro-cranial stimulation comprising- one or more electrode assemblies as claimedin claim 1, one or more bands configured to be seemed to the cranium of a user two or more apertures provided in one oi more apertured elements each configured to be secured to the one or more bands wherein a positioning of the one or raoie electrode assemblies on the cranium of the user is adjustable by one or more of a repositioning of at least one of the one or moie bands or by a movement of the one or more electiode assemblies to alternate ones of the two or more apertures
36 The apparatus of claim 35, wherein the one or more electrode assemblies comprise a minimum of four electiode assemblies and a maximum of fne electiode assemblies
37 The apparatus of claim 35 wherein the apparatus is configured to adjustably position the electrode assemblies within 1 cm of am target positon on the cranium of the user
38 The apparatus of claim 35 wherein the positioning surfaces of the two or mote electrode assemblies are capable of being securedly positioned against the skin surface of the user without an adhesive provided to one or more of the positioning surface or the skin surface of the user
39 The apparatus of claim 35 wherein the one or mot e apet tut ed elements comprise two or more semicircular plates hingedly joined to form a single circular articulatable plate.
40 The appaiatus oi claim 15 wherein the one oτ mote apet tut ed elements comprise one oi more apertured bands
41 The apparatus of claim 39, whetein the one or more apertured bands comprise two oi more bands ha\nig electrode tups for receiving the two oi more electiode assemblies, wherein the electrode cups are pi\ otably mourned at ends of the two or more bands.
42. An apparatus for neuro -cranial stimulation comprising: one or more electrode assemblies as claimed in claim 1; a base band configured for encircling a base of the user's cranium; and one or more flexible linear extensions extending upwardly from the base band and including electrode cups at ends of the flexible linear extensions for receiving the two or more electrode assemblies, the two or more flexible linear extensions being movable to adjustably position each of the two or more electrode assemblies against a cranial portion of the skin surface of the user,
43 The appaiatus of claim 42, wherein the two or more flexible lineai extensions are movable to position each of the two or more electrode assemblies against a cranial portion of the skin surface of the user without applying an adhesive to one or more of the electrode assembly or the cranial portion of the skin surface.
44. A method for performing neuro-craniaf stimulation, the method comprising the steps of; selecting one or more electrode assemblies each comprising-. an electrode for receiving electrical energy from a regulated current source, a conductive gel, and an adapter including; an interior compartment for positioning the electrode relathe to the adapter and for receiving and retaining the conductive gel, whereby the conducthe gel contacts the electrode along an electrode-gel interface, and an orifice in communication with the interior compartment and adjacent to a positioning surface of the adapter; and positioning the positioning surface of each electrode assembly against a cranial portion of the skin surface of the user, whereby the conductive gel material contacts the skin surface of the cranium alonti a yel-skin interface at the orifice, such that a minimum distance between the electrode- gei interface and the gel-skui interface ts between 0 25 era and 1 3 cm
45. The method of claim 44, wherein in the positioning step each electrode assembly is positioned against the cranial portion of the skin surface of the user without applying an adhesive to one or more of the electrode assembly or the cranial portion of the sKiα surface.
46 The method of claim 43, furthei comprising the steps of connecting the one or more electrode assemblies to a power source; and generating a predetermined current tluough the one oτ mote or more electrode assemblies foτ a predetei mined time period
47. the method of claim 44. wherein a cross-sectional area of the orifice of each electrode assembly Is between 25 mm3 and 95 mrrf and a current demit;, at the Hqiiid/'yei-skin interface of the electrode assembly is between 0.1 mΛ per era" and IO mΛ per era"
48. The method of claim 44. further comprising the step of pre-treatmg the skin surface υf Ihe cranium prior to the positioning step
49. The method of claim 48, wherein the pre-treatmg step further comprises the step of applying a chemical to one oi more of the corsduethe gel or the skin surface.
50. The method of claim 49. wherein the chemical comprises one or more of an antioxidant an analgesic or a rubefacient.
51. the method of claim 48, wherein the pre- treating step further comprises the step of apμi) ing a pre-treatinont
Figure imgf000070_0001
to the skin surface
52. The method of claim 51, wherein the pre-trcatment
Figure imgf000070_0002
comprises one of. a DC current between 0.1 to 1 mΛ, applied for 0.1 to 60 minutes, or an AC current between 0.1 to 1 rnA, having a frequency between 0.01 to 500 kHz . and applied for 0.1 to 60 minutes.
53. The method of claim 52, wherein the pre-treatment waveform comprises the AC current having frequency of 0.01 to 500 kHz. a pulse width of 0.1 us to 100 seconds, and an inter-pulse interval 0.1 us to 100 seconds.
54. The method of claim 51 , wherein the pre-treatment waveform comprises at least one of: electrical noise selected from the group consisting of white noise, Gaussian noise, I T noise, thermal noise, and short noise.
55 The method of claim 51 , wherein the electrical pre~treafmenl waveform comprises a current ramped with a slope of between 1 mA per minute to ! raA per ins.
56. The method of claim 55, wherein the electrical pre-treatment waveform comprises Gaussian waveform with a standard de\ iation of between 0 to 10000.
57. The method of claim 44. further comprising the step of monitoring an electrode resistance for at least one of the one or more electrode assemblies.
58. The method of claim 44, wherein the at least one or more electrode assemblies comprise at least two or more electrode assemblies, and the method further comprises the step of monitoring a voltage applied across at least two of the at least two or more electrode assemblies.
59. The method of claim 44, further comprising the step of monitoring a pH of the eondueth e gel
60. An electrode assembly for neuro-cranial stimulation comprising: an electrode; a condυctive liquid or gel; and an insulator, wherein: the conductive liquid or gel contacts the electrode along an electrode- liquid gel Interface and reaches an exterior surface of the electrode assembly for contacting the skin surface of a user at a liquid/gel-skin interface, and the insulator is configured to position the electrode so that a minimum distance between the electrode-liquid gel interface and the exterior surface of the electrode assembly for contacting the skin surface is no less than 0.25 cm.
61. A method for performing neυro-cranial stimulation, the method comprising the steps of: selecting two or more electrode assemblies each comprising: an electrode; a conductive liquid or gei; and an insulator, wherein the conductive liquid or ge! contacts the electrode along an electrode-liquid gel interface and reaches an exterior surface of the electrode assembly for contacting the skin surface of a user at a iiquid/gei-skiu interface; positioning the positioning surface of each electrode assembly against a crania! portion of the skin surface of the υ^er, whereby the conductive gel material contacts the skin surface of the cranium along a liquid/gel-skin interface at the orifice, such that a minimum distance between the electrode-Iiquiel'gel interlace and the liquid gel-skin interface is between 0.25 cm and 13 cm; connecting the two or more electrode assemblies in anode/cathode pairs: and generating a predetermined current through each anode/cathode pair for a predetermined time period, wherein a cross-sectional area of the orifice is between 25 mnr and 95 mrsr and a current density at the liquid gei-skin interface is between 0.1 raA per ctrf and IO mA per cm2.
PCT/US2009/069843 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor WO2010078441A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP09837170.1A EP2384221B1 (en) 2008-12-30 2009-12-30 Apparatus for reducing discomfort during electrostimulation
KR1020117017917A KR101685124B1 (en) 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor
AU2009334503A AU2009334503B2 (en) 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor
BRPI0918700A BRPI0918700B8 (en) 2008-12-30 2009-12-30 electrode sets and devices for neurocranial stimulation
JP2011543727A JP5559197B2 (en) 2008-12-30 2009-12-30 Method for reducing discomfort during electrical stimulation, and composition and device therefor
MX2011007037A MX2011007037A (en) 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor.
CA2748007A CA2748007C (en) 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor
US13/142,140 US9440063B2 (en) 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14146908P 2008-12-30 2008-12-30
US61/141,469 2008-12-30

Publications (2)

Publication Number Publication Date
WO2010078441A2 true WO2010078441A2 (en) 2010-07-08
WO2010078441A3 WO2010078441A3 (en) 2010-10-21

Family

ID=42310603

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/069843 WO2010078441A2 (en) 2008-12-30 2009-12-30 Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor

Country Status (9)

Country Link
US (1) US9440063B2 (en)
EP (1) EP2384221B1 (en)
JP (1) JP5559197B2 (en)
KR (1) KR101685124B1 (en)
AU (1) AU2009334503B2 (en)
BR (1) BRPI0918700B8 (en)
CA (1) CA2748007C (en)
MX (1) MX2011007037A (en)
WO (1) WO2010078441A2 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013022840A1 (en) * 2011-08-05 2013-02-14 Ndi Medical, Llc Systems for and methods of transcranial direct current electrical stimulation
WO2013113130A1 (en) 2011-06-07 2013-08-08 Swisstom Ag Electrode sensor kit, electrode assembly, and topical preparation for establishing electrical contact with skin, use thereof, and method of electro-impedance tomography (eit) imaging using these
EP2629842A2 (en) * 2010-10-19 2013-08-28 Research Foundation Of The City University Of New York Electrode assembly
US8818515B2 (en) * 2012-01-13 2014-08-26 Research Foundation Of The City University Of New York Voltage limited neurostimulation
WO2014166749A1 (en) * 2013-04-10 2014-10-16 Ebs Technologies Gmbh Measurement electrode arrangement
US9095266B1 (en) * 2010-08-02 2015-08-04 Chi Yung Fu Method for treating a patient
USD776822S1 (en) 2015-09-22 2017-01-17 The United States Of America As Represented By The Secretary Of The Air Force Uniform current distribution electrode for noninvasive brain stimulation

Families Citing this family (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9037247B2 (en) * 2005-11-10 2015-05-19 ElectroCore, LLC Non-invasive treatment of bronchial constriction
US20090024049A1 (en) 2007-03-29 2009-01-22 Neurofocus, Inc. Cross-modality synthesis of central nervous system, autonomic nervous system, and effector data
US8392253B2 (en) 2007-05-16 2013-03-05 The Nielsen Company (Us), Llc Neuro-physiology and neuro-behavioral based stimulus targeting system
KR20100038107A (en) 2007-07-30 2010-04-12 뉴로포커스, 인크. Neuro-response stimulus and stimulus attribute resonance estimator
US8386313B2 (en) 2007-08-28 2013-02-26 The Nielsen Company (Us), Llc Stimulus placement system using subject neuro-response measurements
US8392255B2 (en) 2007-08-29 2013-03-05 The Nielsen Company (Us), Llc Content based selection and meta tagging of advertisement breaks
US9357240B2 (en) 2009-01-21 2016-05-31 The Nielsen Company (Us), Llc Methods and apparatus for providing alternate media for video decoders
US8270814B2 (en) 2009-01-21 2012-09-18 The Nielsen Company (Us), Llc Methods and apparatus for providing video with embedded media
US8464288B2 (en) 2009-01-21 2013-06-11 The Nielsen Company (Us), Llc Methods and apparatus for providing personalized media in video
US20100268287A1 (en) * 2009-03-13 2010-10-21 The Johns Hopkins University Methods and devices for increasing learning and effects of training in healthy individuals and patients after brain lesions using dc stimulation and apparatuses and systems related thereto
US20100250325A1 (en) 2009-03-24 2010-09-30 Neurofocus, Inc. Neurological profiles for market matching and stimulus presentation
US8655437B2 (en) 2009-08-21 2014-02-18 The Nielsen Company (Us), Llc Analysis of the mirror neuron system for evaluation of stimulus
US10987015B2 (en) 2009-08-24 2021-04-27 Nielsen Consumer Llc Dry electrodes for electroencephalography
US20110106750A1 (en) 2009-10-29 2011-05-05 Neurofocus, Inc. Generating ratings predictions using neuro-response data
US8209224B2 (en) 2009-10-29 2012-06-26 The Nielsen Company (Us), Llc Intracluster content management using neuro-response priming data
US9560984B2 (en) 2009-10-29 2017-02-07 The Nielsen Company (Us), Llc Analysis of controlled and automatic attention for introduction of stimulus material
US8335716B2 (en) 2009-11-19 2012-12-18 The Nielsen Company (Us), Llc. Multimedia advertisement exchange
US8335715B2 (en) 2009-11-19 2012-12-18 The Nielsen Company (Us), Llc. Advertisement exchange using neuro-response data
GB2477567A (en) * 2010-02-09 2011-08-10 Roi Cohen Kadosh Apparatus for improving numerical ability
US8684742B2 (en) 2010-04-19 2014-04-01 Innerscope Research, Inc. Short imagery task (SIT) research method
US8655428B2 (en) 2010-05-12 2014-02-18 The Nielsen Company (Us), Llc Neuro-response data synchronization
US8750857B2 (en) * 2010-06-04 2014-06-10 Qualcomm Incorporated Method and apparatus for wireless distributed computing
US9037224B1 (en) * 2010-08-02 2015-05-19 Chi Yung Fu Apparatus for treating a patient
US8392250B2 (en) 2010-08-09 2013-03-05 The Nielsen Company (Us), Llc Neuro-response evaluated stimulus in virtual reality environments
US8392251B2 (en) 2010-08-09 2013-03-05 The Nielsen Company (Us), Llc Location aware presentation of stimulus material
US8396744B2 (en) 2010-08-25 2013-03-12 The Nielsen Company (Us), Llc Effective virtual reality environments for presentation of marketing materials
WO2012079778A1 (en) * 2010-12-13 2012-06-21 Stx-Med Sprl Headband for external occipital neurostimulation
US20140081369A1 (en) * 2011-05-11 2014-03-20 Alejandro Covalin Headache-treatment device with gel dispensing kit and method
US8934954B2 (en) * 2011-08-23 2015-01-13 Impeto Medical Assessment of sudomor function for peripheral diabetic neuropathy evaluation
US9569986B2 (en) 2012-02-27 2017-02-14 The Nielsen Company (Us), Llc System and method for gathering and analyzing biometric user feedback for use in social media and advertising applications
US9292858B2 (en) 2012-02-27 2016-03-22 The Nielsen Company (Us), Llc Data collection system for aggregating biologically based measures in asynchronous geographically distributed public environments
US9451303B2 (en) 2012-02-27 2016-09-20 The Nielsen Company (Us), Llc Method and system for gathering and computing an audience's neurologically-based reactions in a distributed framework involving remote storage and computing
US8989835B2 (en) 2012-08-17 2015-03-24 The Nielsen Company (Us), Llc Systems and methods to gather and analyze electroencephalographic data
US9320450B2 (en) 2013-03-14 2016-04-26 The Nielsen Company (Us), Llc Methods and apparatus to gather and analyze electroencephalographic data
EP2981326B1 (en) * 2013-03-15 2018-05-23 Neurolief Ltd. Headset for treatment and assessment of medical conditions
US9913973B2 (en) * 2013-04-23 2018-03-13 Yani Skincare, LLC Transcranial direct current brain stimulation apparatus
US20150025590A1 (en) * 2013-07-17 2015-01-22 Chih-Lung Cheng Physical health cap application system
CA2920835A1 (en) 2013-08-20 2015-02-26 Anutra Medical, Inc. Syringe fill system and method
US9486618B2 (en) 2013-08-27 2016-11-08 Halo Neuro, Inc. Electrode system for electrical stimulation
KR20160046887A (en) 2013-08-27 2016-04-29 헤일로우 뉴로 아이엔씨. Method and system for providing electrical stimulation to a user
US9782585B2 (en) 2013-08-27 2017-10-10 Halo Neuro, Inc. Method and system for providing electrical stimulation to a user
US9889290B2 (en) 2013-08-27 2018-02-13 Halo Neuro, Inc. Electrode system for electrical stimulation
JP6570516B2 (en) * 2013-09-17 2019-09-04 ノービンタム メディカル テクノロジー ゲーエムベーハー Device for accessing human veins
GB2524816B (en) * 2014-04-03 2016-03-30 Sooma Oy System and method for transcranial stimulation of a subject
US9622702B2 (en) 2014-04-03 2017-04-18 The Nielsen Company (Us), Llc Methods and apparatus to gather and analyze electroencephalographic data
USD774182S1 (en) 2014-06-06 2016-12-13 Anutra Medical, Inc. Anesthetic delivery device
USD763433S1 (en) 2014-06-06 2016-08-09 Anutra Medical, Inc. Delivery system cassette
USD750768S1 (en) 2014-06-06 2016-03-01 Anutra Medical, Inc. Fluid administration syringe
WO2016009424A1 (en) * 2014-07-13 2016-01-21 Nibs Neuroscience Technologies Ltd. Electrode headset grid and use thereof in the non-invasive brain stimulation and monitoring
US20160074649A1 (en) * 2014-09-16 2016-03-17 Nuraleve Inc. Cranial Position Determination System
AU2015319772B2 (en) * 2014-09-17 2020-06-11 Neurolief Ltd. Headset for neurostimulation and sensing of body parameters
FR3028743B1 (en) * 2014-11-21 2021-02-19 Univ Centre Hospitalier DEVICE FOR MEASURING SIGNALS OF THE BRAIN ACTIVITY OF AN INDIVIDUAL
EP3253445A4 (en) 2015-02-03 2018-02-21 Nibs Neuroscience Technologies Ltd. Early diagnosis and treatment of alzheimer disease and mild cognitive impairment
WO2016134271A1 (en) * 2015-02-19 2016-08-25 Massachusetts Institute Of Technology Systems and methods for selective memory enhancement and/or disruption
US9936250B2 (en) 2015-05-19 2018-04-03 The Nielsen Company (Us), Llc Methods and apparatus to adjust content presented to an individual
WO2017026386A1 (en) * 2015-08-07 2017-02-16 株式会社カネカ Patch
GB2541947A (en) * 2015-09-07 2017-03-08 Cerestim Ltd Electrode apparatus
EP3368146B1 (en) 2015-10-26 2021-04-07 Halo Neuro, Inc. Electrode positioning system
WO2017105930A1 (en) * 2015-12-15 2017-06-22 Sullivan Michael J Systems and methods for non-invasive treatment of head pain
USD809474S1 (en) * 2015-12-30 2018-02-06 Mybrain Technologies Audio headset for bio-signals acquisition
GB201601536D0 (en) 2016-01-27 2016-03-09 Neurolief Ltd Resilient head mounted device for neurostimulation and sensing of body parameters
EP3413966A4 (en) 2016-02-08 2019-11-27 Halo Neuro, Inc. Method and system for improving provision of electrical stimulation
US10506974B2 (en) 2016-03-14 2019-12-17 The Nielsen Company (Us), Llc Headsets and electrodes for gathering electroencephalographic data
US10485443B2 (en) 2016-06-20 2019-11-26 Halo Neuro, Inc. Electrical interface system
CN109414578B (en) * 2016-06-27 2022-06-28 积水化成品工业株式会社 Gel sheet
US10765363B2 (en) * 2016-09-30 2020-09-08 Cognionics, Inc. Headgear for dry electroencephalogram sensors
EP3592218B1 (en) 2017-03-08 2024-01-17 Halo Neuro, Inc. System for electrical stimulation
DE202018001803U1 (en) 2017-05-19 2018-06-27 Cefaly Technology Sprl External trigeminal nerve stimulation for the acute treatment of migraine attacks
EP3684463A4 (en) 2017-09-19 2021-06-23 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US10507324B2 (en) 2017-11-17 2019-12-17 Halo Neuro, Inc. System and method for individualizing modulation
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
WO2019133997A1 (en) 2017-12-31 2019-07-04 Neuroenhancement Lab, LLC System and method for neuroenhancement to enhance emotional response
JP7006283B2 (en) * 2018-01-12 2022-02-10 オージー技研株式会社 Electrical stimulator
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
CN113382683A (en) 2018-09-14 2021-09-10 纽罗因恒思蒙特实验有限责任公司 System and method for improving sleep
USD908664S1 (en) * 2019-06-02 2021-01-26 Sens.Ai Inc. Headset with biometric sensors
IL291688B1 (en) * 2019-09-27 2024-01-01 Niche Biomedical Inc Method and system for targeted and adaptive transcutaneous spinal cord stimulation
US11865328B2 (en) 2020-03-02 2024-01-09 The Regents Of The University Of Michigan Neuropsychological and neurological rehabilitation headgear device
CN114129741A (en) * 2021-12-16 2022-03-04 深圳市美的连医疗电子股份有限公司 Medical conductive paste and preparation method thereof
JP7152818B1 (en) 2022-01-21 2022-10-13 東和株式会社 Biomedical electrode device

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4537198A (en) * 1983-05-03 1985-08-27 Sue Corbett Electrode cap
US4920979A (en) 1988-10-12 1990-05-01 Huntington Medical Research Institute Bidirectional helical electrode for nerve stimulation
US5344440A (en) * 1990-11-21 1994-09-06 Stephen Richard L Method and apparatus for stimulating growth and healing of living tissues
US5540736A (en) * 1993-08-02 1996-07-30 Haimovich; Yechiel Transcranial electrostimulation apparatus having two electrode pairs and independent current generators
FR2738473B1 (en) * 1995-09-08 1998-01-02 Centre Nat Rech Scient ELECTRO-PHYSIOLOGY DEVICE
US5921925A (en) * 1997-05-30 1999-07-13 Ndm, Inc. Biomedical electrode having a disposable electrode and a reusable leadwire adapter that interfaces with a standard leadwire connector
US6161030A (en) * 1999-02-05 2000-12-12 Advanced Brain Monitoring, Inc. Portable EEG electrode locator headgear
US6567702B1 (en) * 1999-10-15 2003-05-20 The Board Of Trustees Of The Leland Stanford Junior University Eliciting analgesia by transcranial electrical stimulation
US7239919B2 (en) * 2001-04-27 2007-07-03 Biophysical Mind Technologies, Ltd. Diagnosis, treatment and research of mental disorder
US8118722B2 (en) * 2003-03-07 2012-02-21 Neuronetics, Inc. Reducing discomfort caused by electrical stimulation
US7153256B2 (en) * 2003-03-07 2006-12-26 Neuronetics, Inc. Reducing discomfort caused by electrical stimulation
JP2006006666A (en) * 2004-06-25 2006-01-12 Olympus Corp Electrode device for brain wave detection, brain wave detector, cap and package
US7857746B2 (en) * 2004-10-29 2010-12-28 Nueronetics, Inc. System and method to reduce discomfort using nerve stimulation
US20070225585A1 (en) * 2006-03-22 2007-09-27 Washbon Lori A Headset for electrodes
US7949403B2 (en) * 2007-02-27 2011-05-24 Accelerated Care Plus Corp. Electrical stimulation device and method for the treatment of neurological disorders
EP2211712B1 (en) * 2007-11-06 2016-05-04 Bio-signal Group Corp. Device and method for performing electroencephalography
WO2009128810A1 (en) * 2008-04-15 2009-10-22 Research Foundation Of The City University Of New York Apparatus and method for neurocranial electrostimulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of EP2384221A4 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9095266B1 (en) * 2010-08-02 2015-08-04 Chi Yung Fu Method for treating a patient
US10080506B2 (en) 2010-08-02 2018-09-25 Chi Yung Fu Method for processing brainwave signals
EP2629842A2 (en) * 2010-10-19 2013-08-28 Research Foundation Of The City University Of New York Electrode assembly
EP2629842A4 (en) * 2010-10-19 2014-08-27 Univ City New York Res Found Electrode assembly
US9956395B2 (en) 2010-10-19 2018-05-01 Research Foundation Of The City University Of New York Electrode assembly
WO2013113130A1 (en) 2011-06-07 2013-08-08 Swisstom Ag Electrode sensor kit, electrode assembly, and topical preparation for establishing electrical contact with skin, use thereof, and method of electro-impedance tomography (eit) imaging using these
JP2014518740A (en) * 2011-06-07 2014-08-07 スイストム・アーゲー Electrode sensor kit, electrode assembly and topical preparation for establishing electrical contact with skin, use thereof, and imaging method by electrical impedance tomography (EIT) using them
WO2013022840A1 (en) * 2011-08-05 2013-02-14 Ndi Medical, Llc Systems for and methods of transcranial direct current electrical stimulation
US20130204315A1 (en) * 2011-08-05 2013-08-08 Ndi Medical, Llc Systems for and methods of transcranial direct current electrical stimulation
US8818515B2 (en) * 2012-01-13 2014-08-26 Research Foundation Of The City University Of New York Voltage limited neurostimulation
WO2014166749A1 (en) * 2013-04-10 2014-10-16 Ebs Technologies Gmbh Measurement electrode arrangement
USD776822S1 (en) 2015-09-22 2017-01-17 The United States Of America As Represented By The Secretary Of The Air Force Uniform current distribution electrode for noninvasive brain stimulation

Also Published As

Publication number Publication date
AU2009334503A1 (en) 2011-07-21
AU2009334503B2 (en) 2013-09-12
EP2384221B1 (en) 2014-01-22
US20110319975A1 (en) 2011-12-29
EP2384221A4 (en) 2012-09-05
BRPI0918700A2 (en) 2020-08-04
WO2010078441A3 (en) 2010-10-21
KR101685124B1 (en) 2016-12-09
US9440063B2 (en) 2016-09-13
MX2011007037A (en) 2011-07-20
JP2012513851A (en) 2012-06-21
CA2748007C (en) 2020-03-10
KR20110118647A (en) 2011-10-31
EP2384221A2 (en) 2011-11-09
BRPI0918700B1 (en) 2021-01-26
CA2748007A1 (en) 2010-07-08
BRPI0918700B8 (en) 2021-06-22
JP5559197B2 (en) 2014-07-23

Similar Documents

Publication Publication Date Title
CA2748007C (en) Methods for reducing discomfort during electrostimulation, and compositions and apparatus therefor
Minhas et al. Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS
Keller et al. Electrodes for transcutaneous (surface) electrical stimulation
RU2323017C2 (en) Method and device for carrying out controlled delivery of active substances into skin
US9931499B2 (en) Method and apparatus for providing topical anesthesia prior to and during a cosmetic procedure
Green et al. Laser patterning of platinum electrodes for safe neurostimulation
US20070016277A1 (en) Lip augmentation device
AU2002363106A1 (en) Device and method for controlled delivery of active substance into the skin
Wang et al. Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex
CA2532786A1 (en) Method, apparatus, and kit for onychomycosis treatment using electrokinetic transport of substances
McAdams Biomedical electrodes for biopotential monitoring and electrostimulation
Newton et al. Skin pH following high voltage pulsed galvanic stimulation
RU156348U1 (en) DEVICE FOR STIMULATING REFLECTOR ZONES
CA2948955A1 (en) A stimulation electrode
Patel et al. Kilohertz electrical stimulation nerve conduction block: effects of electrode material
Schmidt et al. Intracortical capacitor electrodes: preliminary evaluation
KR20010070120A (en) Skin contact type Aluminum medical implement
US20210268275A1 (en) Plate electrodes
RU2495684C1 (en) Apparatus for body functional status correction
Dutta et al. Effect of electrode profile and conductivity on current density and cutaneous sensation during transcranial DC stimulation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09837170

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 2748007

Country of ref document: CA

Ref document number: 2009837170

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2011543727

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2009334503

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: MX/A/2011/007037

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2009334503

Country of ref document: AU

Date of ref document: 20091230

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20117017917

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 13142140

Country of ref document: US

ENP Entry into the national phase

Ref document number: PI0918700

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20110630