US20050149123A1 - Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders - Google Patents
Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders Download PDFInfo
- Publication number
- US20050149123A1 US20050149123A1 US11/073,683 US7368305A US2005149123A1 US 20050149123 A1 US20050149123 A1 US 20050149123A1 US 7368305 A US7368305 A US 7368305A US 2005149123 A1 US2005149123 A1 US 2005149123A1
- Authority
- US
- United States
- Prior art keywords
- brain
- activity
- stimulation
- wavelet
- seizure
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N2/00—Magnetotherapy
- A61N2/002—Magnetotherapy in combination with another treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/12—Devices for heating or cooling internal body cavities
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36082—Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00017—Electrical control of surgical instruments
- A61B2017/00022—Sensing or detecting at the treatment site
- A61B2017/00039—Electric or electromagnetic phenomena other than conductivity, e.g. capacity, inductivity, Hall effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00017—Electrical control of surgical instruments
- A61B2017/00022—Sensing or detecting at the treatment site
- A61B2017/00084—Temperature
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/007—Heating or cooling appliances for medical or therapeutic treatment of the human body characterised by electric heating
- A61F2007/0075—Heating or cooling appliances for medical or therapeutic treatment of the human body characterised by electric heating using a Peltier element, e.g. near the spot to be heated or cooled
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/12—Devices for heating or cooling internal body cavities
- A61F2007/126—Devices for heating or cooling internal body cavities for invasive application, e.g. for introducing into blood vessels
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Neurology (AREA)
- Developmental Disabilities (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Neurosurgery (AREA)
- Child & Adolescent Psychology (AREA)
- Physics & Mathematics (AREA)
- Thermal Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Electrotherapy Devices (AREA)
Abstract
A device and method of use for treating a medical disorder by surgically implanting into a patient at least one sensor element capable of detecting and conveying cell signals; attaching a management unit such that a micro controller of the management unit is connected to at least one sensor element; and connecting the management unit via a lead bundle to at least one treatment device. The treatment device may be an electrical stimulation device, a magnetic stimulation device, a heat transfer device, or a medication delivery device. Responsive to signals from the one or more sensor elements, mathematical algorithms of the management unit use wavelet crosscorrelation analysis to prompt delivery of at least one treatment modality, such heat transfer, current pulses, magnetic stimulation or medication. The medical disorder may arise from the brain, central nervous system or organs and tissues outside of the central nervous system.
Description
- This application claims priority to U.S. provisional patent applications Nos. 60/160,328, filed Oct. 19, 1999, and 60/201,188, filed May 2, 2000, which are hereby incorporated by reference.
- 1. Field of the Invention
- The invention pertains to a method of treating a medical disorder using heat transfer, electrical stimulation, and/or delivery of medication so as to stop or prevent abnormal cell activity, thus treating the disorder to improve function of an affected body tissue. The method improves effectiveness of stimulation for treating disorders of function of brain or elsewhere in central nervous system, or in peripheral nerve. The method may be used to treat epilepsy, for treatment of brain disorders other than epilepsy, for spinal disorders, and for disorders of other body organs and tissues.
- 2. Description of Related Art
- Epilepsy is a significant medical problem, as nearly 1% of the United States population is affected by this disease at any given time, constituting about 2.6 million people. In 1991 dollars, the direct costs for the treatment of epilepsy in the United States were 1.8 billion dollars and the indirect costs amounted to 8.5 billion dollars. Thus, the disorder is a significant health problem and a need exists for improved treatments to control the disease and alleviate its burden on society as a whole.
- Epileptic seizures occur because of an abnormal intensity and synchronized firing of brain cells. The fundamental neuronal disturbance during a seizure consists of large amplitude, sustained depolarization (depolarizing shift), on top of which rides a protracted volley of action potentials. The depolarizing shift (DS) is a complex phenomenon whose triggering mechanism is not fully understood. One hypothesis is that DS is a postsynaptic potential, amplified by slow calcium currents. Electrical activity is normally terminated toward the end of depolarization at which time potassium conductance is increased, making cells refractory to further stimulus (hyperpolarization). Generalized seizures can begin over essentially the entire brain at one time, while others, known as focal or partial seizures, begin in a localized area of the brain and then spread. Thus, both widespread and localized mechanisms appear to be involved in the occurrence of seizures. As an example, seizures manifest themselves as seizure discharges affecting the cerebral cortex, the outer most layer of the brain, though paradoxically, stimulation of the thalamus and other subcortical regions, located deeper within the brain, have been shown to not only initiate but also control or even prevent seizures. Evidence suggests that the thalamus and the substantia nigra are involved in the development of certain kinds of seizures. Even more widespread mechanisms might be involved, as evidenced by the successful use of vagal nerve stimulation for treatment of some seizures. The vagus nerve is located in the neck and extends to the brain stem from which it has widespread connections throughout the brain, including branches to the thalamus. Studies have shown that chronic vagal nerve stimulation can reduce seizures by 50% or more in a third of treated patients. The vagal nerve simulator has recently been released as a commercial product. Information thus far indicates that it is moderately effective, but only rarely controls seizures completely.
- Direct electrical stimulation has been applied to the cortex of humans for mapping purposes since the 1930s, but a complication of cortical stimulation can be the unwanted occurrence of afterdischarges. Recently, investigators have shown, however, that brief pulses of stimulation (BPS) can terminate afterdischarges (ADs), if appropriately applied. Preliminary data also suggests that stimulus is often more effective when exerted at peak negativity of AD waveform, and that phase of waveform at which stimulation is most effective varies. If one accepts ADs as one model for epilepsy in humans, this raises the possibility that appropriately applied stimulation could abort spontaneous seizure activity in human brain. This may be explained again using the analogy of cardioverter defibrillator where a single pulse stimulus is applied to chest. Stimulus, if synchronized to R wave, depolarizes the whole heart muscle at the same time and lets a single pulse source (SA node) take over. However, if not synchronized to the repolarization wave, stimulus will induce cardiac fibrillation, since some parts of tissue are in process of recovery from previous depolarization and therefore will be susceptible to another depolarizing stimulus. This asynchrony may cause the chaos called “cardiac fibrillation”. It results from excitation of some parts of tissue while the rest is electrically silent for a few milliseconds before it “fires up”. Therefore, successful cortical stimulation needs to be applied soon before (presumed) single generator spreads, and stimulation will be more likely to be successful if synchronized to portion of wave that is most sensitive to stimulation. With cardiac defibrillator, electrical shock, given to heart in synchrony with R wave of QRS complex, depolarizes whole tissue, and lets normal pacemaker resume its rhythm. Electrical stimuli pace, cardiovert, or defibrillate heart by changing transmembrane potential. Electrically induced neuronal synchrony also could play a role in effects of brief pulse stimulation on ADs in brain, perhaps by changing neuronal membrane potentials of a group of cells in stimulated region.
- Electrical stimulation has been in use to terminate acute and chronic medical conditions such as cardiac arrhythmias (cardioverter defibrillator, pacemaker), tremor (thalamic stimulation), and seizures (vagus nerve stimulation, thalamic stimulation). Electrical stimulation provides a non-surgical means for impairing generation of localized seizures. Thus, acute cortical stimulation applied directly to site of epileptiform discharge at onset of event could become a treatment for seizures, just as in experimental animal models, medication application to a seizure focus can suppress or eliminate seizure activity.
- Repetitive electrical stimulation, given in an appropriate manner and in an appropriate location in either archicortex or neocortex, is well known to produce long-term depression of cortical responsiveness as well as inhibition of kindling. A single pulse can desynchronize, and thus diminish amplitude of, population spikes in rat CA1 hippocampus. Low-frequency stimulation of amygdala for 15 minutes suppresses occurrence of generalized kindled seizures in rats. Stimulation of perforant pathway (but not hippocampus) of patients with implanted depth electrodes results in greater paired pulse suppression on epileptogenic side. Appropriately delivered transcortical magnetic stimulation can reduce cortical excitability in volunteers. A trial is underway to determine whether periodic transcortical magnetic stimulation might reduce seizure frequency. Electroconvulsive therapy (ECT) can transiently abort non-convulsive status epilepticus. In patients with spike-and wave-discharges, motor evoked potential amplitude can decrease during slow wave, and may either decrease or remain unchanged during spike. The mechanisms proposed to account for these phenomena include inhibitory mechanisms, possibly located in specific cortical layers or cerebral pathways, and possibly mediated by outward potassium currents, by properties of calcium channels, or by GABA receptors.
- In some patients, seizures are sufficiently localized such that removal of a particular area of brain may result in complete seizure control. Electrical stimulation provides a non-surgical means for impairing generation of localized seizures. In experimental animal models, drug application to a seizure focus can suppress or eliminate seizure activity.
- Hypothermia is known to have a protective effect on brain both in experimental animal preparations and in humans. This protective effect on brain is one reason for employing hypothermia in medical procedures, such as cardiac surgery. Hypothermia alters electrical activity of cortex in models of brain ischemia, and decreases production of excitatory neurotransmitters glutamate and dopamine. Hypothermia also appears to reduce occurrence, frequency, and amplitude of cortical potentials and suppresses seizure activity. Cooling is thought to prevent or abort seizures by reducing cortical excitability. Cooling brain tissue can be safely accomplished when properly undertaken. For example, irrigation of temporal horn of lateral ventricle with ice-cold liquid to cool hippocampus has been successful in acutely altering memory functions in humans with no apparent adverse effects.
- It is well known that temperature affects nerve conduction and responsiveness. For example, peripheral nerve conduction velocity decreases, and wave duration increases, during hypothermia. This may be because cooling increases sodium permeability less than it subsequently inactivates sodium permeability and increases potassium permeability during recovery process; slowing of recovery process increases amplitude. Decreased conduction velocity and increased wave duration “disperses” potentials that arrive more centrally, and this in turn result in a decrease in responsivity of spinal and cerebral neurons. One study found, in man, that conduction decrease occurred at a rate of 1.84 meters/sec/degree between 36° C. and 23° C. Another found the decrease to be 1.98 meters/sec/degree between 35.5° C. and 23.5° C. Similar findings have been reported by others. Stevenson et al. showed augmentation of spinal cord evoked response with hypothermia, but depression of responses in thalamic relay, midbrain reticular neurons. Others have reported an increase in duration but not amplitude of action potentials recorded intracellularly from individual afferent fibers and interneurons in dorsal columns and dorsal roots.
- In multiple sclerosis, the “hot bath test” has long been used as a clinical test: a warm bath can bring out symptoms of multiple sclerosis. Conduction block of multiple sclerosis is increased by higher temperatures. Conversely, conduction block can be overcome by reducing temperature.
- In muscle diseases such as amyotrophic lateral sclerosis and myasthenia gravis, cooling can increase surface area of M wave. Cooling can improve weakness of myasthenia gravis and myasthenic syndrome. In myasthenia gravis, for example, drooping of eyes due to eye muscle weakness can be improved by placing an ice pack over them. During electromyography, jitter that occurs with myasthenia gravis decreases in response to cooling. On the other hand, weakness of paramyotonia congenita increases with lower temperatures.
- Patients who have an aura prior to seizures, and who have an implanted vagus nerve stimulator can manually activate the stimulator, which successfully aborts seizures in some cases. However, to be of maximum benefit, stimulation (of whatever type) must occur as early as possible during seizures. Recordings with implanted electrodes often demonstrate seizure patterns exist before a patient is aware of an impending seizure. Early reaction to, or prevention of, seizure onset necessitates detection of abnormal discharges as soon as possible. Numerous of approaches toward detection of seizures have been explored. A number of methods have been tried in an attempt to predict seizure onset. These methods have included assessing amplitude, frequency, and other characteristics of raw EEG waves, as well as more advanced signal processing techniques, including some based on time-frequency localization, image processing, and identification of time-varying stochastic systems. In one attempt, using these methods, accuracy was 100%, compared to the current standard of visual recognition. Detection was sufficiently rapid to allow prediction of clinical onset in 92% of seizures by a mean of 15.5 sec. Methods based on non-linear analysis and chaos theory have been used as well. Previously, an EEG seizure detector based on an artificial neural network was developed, with input quantifying amplitude, slope, curvature, rhythmicity, and frequency components of EEG in a 2 sec epoch. An advantage of this approach is that computer detection may be modified to fit seizure pattern, or patterns, of an individual patient. Alternatively, several rule based or template matching methods for seizure detection may be employed, as well as methods using neural networks modeling seizures as chaotic attractors. All of the approaches just mentioned can sample the EEG continuously, thus providing possibility for delivering treatment if a change in EEG is detected.
- Therefore, although a number of detection methods have been tried, no one method has been entirely successful. Moreover, many methods are computationally intensive, so that calculation using an implantable microchip is not feasible. Finally, the methods described in essence consider activity occurring at single sites, with sites analyzed one by one. However, pathologic activities such as epileptic seizures involve the brain over more extended regions, so that an optimal predictive technique would assess the brain both spatially and temporally.
- U.S. Pat. No. 5,713,923 to Ward et al. (Ward '923) discloses techniques for treating epilepsy using a combination of electrical stimulation of brain and drug infusion to neural tissue. Stimulation may be directed to increase output of inhibitory structures, such as cerebellum, thalamus, or brain stem, or may inactivate epileptogenic areas. These methods tend to be based on chronic stimulation of brain inhibitory systems, with the goal of decreasing the background propensity to epileptogenesis. Historically, stimulation of inhibitory structures alone has not been particularly successful in seizure management. Ward '923 uses an implantable electrode to sense seizure onset, which permits regulatable stimulation of brain during initial seizure activity. The combination of drug infusion with brain stimulation as disclosed in Ward '923, however, would fail to be effective in many types of seizures. Many drugs are not particularly stable at body temperature, rendering them unsuitable for long term storage in an implanted infusion device. Certain risks exist for patients receiving combined therapy of Ward '923, including an increased risk for seizure propagation due brain stimulation as well as drug related side effects. Thus, while suitable for controlling some seizures, a substantial population of patients have seizures which cannot be treated using the methodology of Ward '923.
- The Medtronic ITREL stimulator (Medtronic Inc., Minneapolis, Minn., USA) uses asymmetric pulse phases so that, for example, the positive phase could be of higher amplitude and shorter duration, and the negative phase of lower amplitude and lower duration. It does not utilize the dynamic feedback as a means of insuring charge balance.
- U.S. Pat. No. 5,716,377 to Rise, U.S. Pat. No. 5,735,814 to Elsberry, U.S. Pat. No. 5,782,798 to Rise, and U.S. Pat. No. 5,792,186 to Rise disclose methods of treating other brain disorders using methodologies similar to Ward '923. These methodologies have the same combinations of advantages and disadvantages as does Ward '923, with disadvantages overcome by the present invention. U.S. Pat. No. 5,938,689 to Fischell discloses methods of electrode placement and configuration but does not disclose means of activity sensing or detection, or methods of brain stimulation. U.S. Pat. No. 6,016,449 to Fischell (Fischell '449) discloses a multiple electrode closed loop, responsive system for treatment of brain diseases. Fischell '449 envisions detection using electrodes near or within brain and then, after event detection, responding by stimulating brain or other parts of body, or by releasing medication. However, predictions of seizure occurrence and the optimal timing and locality of treatment are not suitably provided for by Fischell '449.
- Therefore, a need exists to improve therapeutic options available to persons with medical disorders associated with detectable abnormal cell activity, such as epilepsy.
- An object of the invention relates to a method of treating a medical disorder comprising surgically implanting into a patient at least one sensor element capable of detecting and conveying cell signals; attaching a management unit such that a micro controller of the management unit is connected to at least one sensor element; and connecting the management unit via a lead bundle to at least one treatment device; whereby responsive to signals from said one or more sensor elements, mathematical algorithms of the management unit prompt delivery of at least one treatment to tissues or cells responsible for the medical disorder. Abnormal tissue or cell activity is detected as signals via activity sensor elements, and analyzed using one or more mathematical assessment techniques, as needed, including quantification of waveform amplitude, slope, curvature, rhythmicity, time-lag, and frequency, as well as assessment techniques based on wavelets, such as wavelet cross-correlation analysis and time-lag analysis. The sensor elements may be activity sensor elements, capable of sensing electrical activity, chemical activity, electrical and chemical activities, or the activity sensor elements may be temperature sensor elements.
- Responsive to signals from the one or more sensor elements, mathematical algorithms of the management unit prompt delivery of at least one treatment to tissues or cells responsible for the medical disorder. Thus, for example, responsive to signals from the one or more sensor elements, the management unit may prompt stimulation portions of the treatment device to deliver to tissues or cells electrical current, or alternatively magnetic flux, at appropriate times and of appropriate duration, thereby altering activity of, for example, tissues or cells of the brain, spinal cord, or peripheral nerve. Likewise, for example, the management unit may cause a heat pump to alter tissue temperature using a heat sink, thereby increasing or decreasing temperature of predetermined portion of patient's brain, organ or other body part.
- In a preferred embodiment the method pertains to preventing or aborting the occurrence of a seizure by stimulating brain tissues or cells, at or near the area of seizure onset (“seizure focus”), or a brain structure that modulates (e.g. causes or influences the occurrence of) seizures.
- In another preferred embodiment, the invention relates to a method of reducing or preventing occurrence of a seizure comprising cooling brain tissue at or near a seizure focus or a brain structure that modulates (e.g. causes or influences the occurrence of) seizures.
- In another preferred embodiment, the invention relates to a method of reducing or preventing occurrence of a seizure comprising delivery of said medication at or near a seizure focus or a brain structure that modulates seizures. The medication may be any therapeutic capable of pharmacologically altering and/or correcting abnormal cell activity. Such therapeutics include, for example, hormones, hydantoins, deoxybarbiturates, benzodiazepines, glutamate receptor agonists, glutamate receptor antagonists, γ-aminobutyric acid receptor agoinsts, γ-aminobutyric acid receptor antagonists, dopamine receptor agonists, dopamine receptor antagonists and anesthetics.
- In another preferred embodiment, the invention relates to a method of reducing or preventing occurrence of a seizure comprising cooling brain tissue and electrically stimulating brain at or near a seizure focus or a brain structure that modulates seizures.
- In yet another preferred embodiment, the invention relates to a method of reducing or preventing occurrence of a seizure comprising cooling brain tissue and infusing said medication into brain at or near a seizure focus or a brain structure that modulates seizures.
- In still another preferred embodiment, the invention relates a method of reducing or preventing occurrence of a seizure comprising cooling brain tissue and electrically stimulating brain tissue and infusing a medication into brain at or near a seizure focus or a brain structure that modulates seizures. This structure might be near, part of, or remote from region or regions where seizure is originating.
- Yet another preferred embodiment provides for treatment of brain disorders such as intractable pain, psychiatric disorders and movement disorders. Examples of such ailments include dystonia or tremor, manic-depressive illness, panic attacks, and psychoses. The invention also provides for the control of effects of central nervous system trauma, swelling and inflammation, such as swelling of brain or spinal tissue due to trauma, hemorrhage, encephalitis or localized myelitis, mass lesions, such as tumors, cysts, and abscesses, and intractable migraine headaches.
- Yet another preferred embodiment provides for treatment of spinal or peripheral nerve disorders such as pain, disorders manifested by altered or decreased sensation, or movement disorders. Examples of such disorders include cervical spondylosis, lumbar stenosis, multiple sclerosis, and spinal myoclonus.
- Yet another preferred embodiment provides for treatment of swelling or inflammation of bone, cartilage, connective tissue, integument, or tissues in body cavities. Examples of when such disorders might occur include trauma and infection. Likewise, the invention provides for treatment of swelling, inflammation or localized pain in non-central nervous system organs, such as heart, lungs, liver, spleen, stomach, gall bladder, pancreas, duodenum, intestines, endocrine organs, extremities, muscles and peripheral nerves.
- Another object of the invention relates to the use of certain waveforms and pulse trains to control electrical stimulation for the treatment of brain disorders, comprising a method of treating a brain disorder by electrical stimulation of brain tissue. The method comprises surgically cutting an aperture into a patient's skull, thereby exposing a predetermined portion of patient's brain; surgically implanting into said aperture stimulating electrodes and electrical sensor elements; surgically implanting an electrical stimulator control unit in a body cavity of said patient such that a micro controller of the electrical stimulator control unit is connected to one or more electrical sensor elements and one or more stimulating electrodes that contact brain tissue; and connecting the electrical stimulator control unit to said stimulating electrodes via a lead bundle. Responsive to signals from one or more electrical sensor elements, mathematical algorithms of the electrical stimulator control unit determine abnormal brain activity, causing the stimulating electrodes to deliver one or more electrical pulses to the brain. This sequence of events halts the abnormal brain activity and therefore prevents, aborts or disrupts the seizure generating process.
- In a preferred embodiment, seizures are reduced or prevented by electrically stimulating the brain at or near a seizure focus or a structure that might be near, part of, or remote from the region or regions where the seizure is originating and stimulation of which would result in inhibition, prevention, disruption or termination of the seizure.
- The invention provides for placing electrodes in or on the brain area(s) of seizure foci and using mathematical algorithms to detect seizure onset. Once seizure onset is detected, electrical stimulation is initiated to reduce abnormal brain cell firing. The electrodes detecting seizure occurrence could be situated on the cortical surface, deeply within the cortex inaccessible to a surface electrode, or in deeper, subcortical areas of the brain such as the thalamus. The sensors detecting seizure onset would also record phase at which stimulation occurred, and brain responses to stimulation, so that the most appropriate phase at which to stimulate can be determined.
- The activity sensor could sense EEG activity. Other activities also could be sensed, according to the invention, with examples of activities including ionic changes, enzyme activity changes, hormonal changes, pH changes, changes in osmolality or osmolarity, cellular function changes, and optical changes. For example, optical changes in tissue and/or fluids could be sensed locally, or remotely with fiber optics, using light emitting diodes and photo sensors, e.g. photodiodes or photo transistors.
- This embodiment of the invention is distinguished from other techniques in several ways. The stimulation pulses may be biphasic with equivalent positive and negative phases, or may be asymmetric biphasic pulses (ABP). The device may use a single pulse (whether or not an ABP) that is time locked, i.e. phased locked to the background activity such that the pulse is delivered when a predetermined point in the cycle of rhythmic EEG activity at a predetermined sensor is reached. Notwithstanding the above-mentioned, a train of free running pulses also may be used. A train of pulses may be time locked, i.e. phase locked to the EEG activity such that the pulse is delivered when a predetermined point in the cycle of rhythmic EEG activity at a predetermined sensor is reached. Charge balance is maintained on a pulse by pulse basis by means of dynamic feedback. Methods based upon wavelet-crosscorrelation analysis can be used to assess brain activity, both to predict or detect the likely occurrence of unwanted brain activity and to determine when best to administer a treatment, such as stimulation, so as to prevent or abort the unwanted activity.
- The traditional methods of electrical stimulation for neuronal tissue always use symmetric waveforms to balance positive and negative electrical charge during stimulation. Charge balance also can be achieved with asymmetric pulses whose positive and negative phases have equal areas-under-the-curve, as is the case the Medtronic ITREL-II (Medtronic, Inc., Minneapolis, Minn., USA). Charge balance is needed to prevent damage due to gas generation and/or deposition of electrode material into the tissue. The device used according to the invention maintains charge balance by ensuring the product of current and pulse duration is the same for both positive and negative pulses, but allows for the pulses of one chosen polarity to be much larger than those of the opposite polarity. A direct consequence of this condition is that the high amplitude pulses are necessarily shorter than the opposite low amplitude pulses. This arrangement of high and low amplitude pulses is chosen so that only the high amplitude pulses have any significant effect, being above a physiological threshold. The low amplitude pulses would be below this threshold and so have no effect. The result, in theory, is a device that causes an effect with only one chosen polarity of current. This results in DC-like stimulation, without the damaging effects of DC current such as gas generation and electrode material deposition.
- Traditional symmetric bipolar stimulation uses equal and opposite currents and the effect of each individual polarity will interfere with those of the opposite polarity to some extent. It is interesting to note that physiological systems at the cell level use highly asymmetric signals similar to those proposed here.
- The invention embodies multiple variations of a technique that may be applied singly or in combination, depending upon the circumstances of a given situation. Control of an individual event may require only one of these methods, or may require a combination of two or more procedures. For example, a single pulse may be delivered or a train of pulses may be delivered until a seizure is prevented, terminated disrupted, or aborted. Similarly, some patients may require a negative pulse, others a positive pulse, others a balanced pulse with an initial positive phase, others a balanced pulse with an initial negative phase to treat their conditions. In still others, phase might not matter. The assessment algorithms that are a part of this invention would analyze the phase relationships and responses to stimulation so that treatment could be optimized. Notwithstanding the above, stimulation could be delivered to or beneath the skin elsewhere in the body in circumstances where such stimulation could prevent or abort occurrence of a seizure.
- It is a further object of the invention to provide a device for treating a medical disorder that includes at least one sensor element capable of detecting and conveying cell signals; a management unit positioned such that a micro controller of the management unit connects to the at least one sensor element; an electrical stimulation device connected to the management unit via a lead bundle such that a stimulation switch sends one or more current pulses to the electrical stimulation device and optionally at least one treatment device.
- This device is designed such that responsive to signals from said at least one sensor element, mathematical algorithms of the management unit perform, as needed, one or more mathematical analyses comprising quantification of waveform amplitude, slope, curvature, rhythmicity, time-lag or frequency as well as analyses based on wavelets, such as wavelet-crosscorrelation analysis to prompt delivery of one or more current pulses and optionally at least one additional treatment to cells responsible for the medical disorder. Thus, in one embodiment, in response to input from a sensor element implanted near the location of a seizure focus, the management unit would be capable of performing wavelet-crosscorrelation analysis and prompting delivery of one or more current pulses through the electrical stimulation device. The device can also include one or more additional treatment devices, for example, designed to deliver medication, heat or cooling.
- These and other features and advantages of the invention will become apparent from the detailed description below and from the accompanying drawings.
-
FIG. 1 shows a cross section of the brain withsensor elements -
FIG. 2 shows heat pump array of Peltier junctions combined withsensor elements heat pump 1 in response to abnormal electrical brain activity. -
FIG. 3 shows the main internal components of the stimulation control unit and the lead that connects this to the sensing and stimulating electrodes. Also shown are components ofHTMU 8 that analyze signals fromsensor elements heat pump 1 when required, as well components of stimulation control unit and lead that connects this to sensing and stimulating electrodes. -
FIG. 4 schematically diagrams four possible asymmetric biphasic pulse trains useful according to the invention, namely normal, reversed, alternate and random pulse trains. -
FIG. 5 shows a single asymmetric biphasic pulse (ABP) and physiological thresholds relative to that pulse. A pulse train is a succession of these pulses delivered at regular intervals. A symmetric pulse train and a single pulse also are shown. - Definitions
- The term central nervous system is defined herein to include tissue of the brain and spinal cord.
- The terms treating and treatment are defined as controlling, reducing or alleviating symptoms of a medical condition.
- An embodiment of the invention relates to hypothermia in combination with brain stimulation as a treatment of brain disorders, such as epilepsy. This may be accomplished by stimulating a brain structure that modulates seizures. Modulation is defined herein as increasing or decreasing neuronal excitability of a brain region responsible for producing seizures. Brain structures targeted for stimulation may be inhibitory or excitatory in nature. For example, output of inhibitory structures, such as cerebellum, thalamus, or brain stem, may be increased (“excited”) via brain stimulation. Output of said inhibitory structures would then inhibit firing of cells in a seizure focus located elsewhere.
- Another aspect of the invention is to target regions in which a treatment could directly block epileptogenic activity. Such targets include hippocanpus, neocortex, and subcortical and brain stem regions. Different targets are expected to be important in different types of brain disorders. For example, patients having unilateral hippocampal onset epilepsy may consider hippocampal removal, but surgery exposes some of these patients to potential memory impairment. Such patients may benefit from lower risk treatment procedures of the invention. In other patients suffering from bilateral hippocampal disease, hypothermia and electrical stimulation might be an effective treatment, as unilateral hippocampal removal would not be useful and bilateral removal is not possible due to memory concerns.
- Treatment may be accomplished by treating brain areas constantly, or at fixed intervals. For example, stimulation driven by feedback from brain monitoring of seizure patterns or pre-seizure patterns is also suitable according to the invention, such that treatment to prevent perpetuation or spread of seizure patterns may be administered upon detection of seizure activity. For example, altered neural discharges in hippocampus, amygdala, neocortex or elsewhere may be present at onset of a seizure. Such patterns often occur locally, but may spread before a seizure clinically manifests. The method of the invention permits detecting, mitigating or eliminating such patterns. Patients often experience auras as perceived warnings of impending seizures. In fact, auras are very small seizures that do not progress to alter consciousness. The method of the invention also enables blocking the spread of such auras. Consequently, a patient would be able to drive and engage in other normal daily activities. The method of the invention is directed toward interfering with synchronization of ictal firing. Synchronization or recruitment of multiple brain areas into a seizure pattern is very much related to spread of seizure activity in brain. Thus, either chronic stimulation or feedback-based episodic stimulation could impair synchronization and thus prevent seizure development.
- An aspect of the invention entails systematically evaluating neocortical pre-ictal and ictal firing patterns and determining methods of interfering with these patterns. These patterns and activities have been extensively monitored through clinical epilepsy monitoring centers. Firing patterns differ among patients such that no one pattern can be expected to occur in all patients with epilepsy. Systematic evaluation of firing pattern in each patient, and determination of whether more than one firing pattern occurs in each patient, will allow optimization of treatment for each patient. Brain cell activity may be monitored, and abnormal activity detected by electrical or chemical sensing elements (activity sensing elements) contacting brain structures to detect abnormal neuronal firing patterns.
- Placement of electrodes to target seizure foci may be patient specific, according to the invention. EEG recordings indicate that some seizures begin at cortical surface, while others originate deep within internal brain structures, such as hippocampus, amygdala, and thalamus. Although seizures may occur as purely subcortical phenomena, most epileptologists believe such seizures probably also manifest in cortex, but are triggered by, for example, thalamo-cortical circuits. Thus, both cortical and subcortical stimulation could abort, or control, seizures, but different sites would have to be stimulated in different patients to be effective. In addition to above-mentioned brain structures, other subcortical regions, such as caudate nucleus, may be important areas for seizure initiation or propagation, and thus may be target areas for therapeutic intervention. Acute and chronic animal models of epilepsy, such as kindling and cobalt/estrogen/penicillin models, suggest that brain stimulation and/or direct medication infusion will successfully control brain disorders in humans. An aspect of the invention is to target regions in which treatment could directly block epileptogenic activity. Such targets include hippocampus, neocortex, and subcortical and brain stem regions. Different targets are expected to be important in different types of brain disorders. For example, patients having unilateral hippocampal onset epilepsy may consider hippocampal removal, but surgery exposes some of these patients to potential memory impairment. Such patients may benefit from lower risk treatment procedures of the invention. In other patients suffering from bilateral hippocampal disease, electrical stimulation might be an effective treatment, as unilateral hippocampal removal would not be useful and bilateral removal is not an option due to memory concerns. The invention is directed towards electrical stimulation using implanted electrodes, however, magnetic stimulation could be used as an alternative without violating the spirit of the invention.
- To assist both in predicting seizure occurrence and in determining optimal timing and location of treatment, the invention provides for the use of wavelets. The use of wavelets provides progressively higher time resolution for changes at higher frequency scales. This in turn means that rapid subtle changes at higher frequencies are better characterized. Similar changes at higher frequencies are better characterized. Similarly, changes at low frequencies also can be optimally characterized. The invention also provides cross-correlation analysis. Wavelet cross-correlation analysis enables degree of waveform similarity between two different time series to be determined. It provides a quantitative measure of relatedness of two signals, usually from different recording sites, as they are progressively shifted in time with respect to each other. Furthermore, it can reveal common components that occur at same moment in time, or at a constant delay. However, it has been pointed out that data segments analyzed using crosscorrelation functions should not include non-stationarities. Therefore the invention uses a different method, denoted as wavelet-crosscorrelation analysis, developed for analyzing dynamics of epileptiform discharges. Wavelet transform of a signal can be computed by projecting it onto a wavelet basis. A given basic wavelet g(t) is scaled by a in the time domain and is shifted by b in order to generate a basic family ga,b(t), where t is time. Wavelet transform Wf(a,b) of a signal f(t) is as follows:
where {overscore (ga,b(t))} represents conjugate complex of ga,b(t). - The Gaussian wavelet
was employed as a basic wavelet, where constant Ω is given by 2π, and e is exponential. This is chosen because Gaussian function has least spread in domains of both time and frequency and Gaussian wavelet is suitable for singularity detection in form of non-orthogonal wavelets. - For non-stationary situations, a new crosscorrelation method, called wavelet-crosscorrelation analysis, has been found to overcome limitations of classical crosscorrelation analysis. This method can be used to analyze brain activity so as to predict when a seizure might occur, and also to determine when best to stimulate the brain so as to alter unwanted brain activities such as afterdischarges or seizures. Wavelet-crosscorrelation analysis was used to obtain wavelet-correlation coefficients (WCC), time lag (TL) and absolute value of TL (ATL) between two electrodes. For Analysis-1, WCC and ATL were compared in
epoch 1 which was prior to LS,epoch 2 which was after LS but before BPS, andepoch 3 which was after BPS. For Analysis-2, WCC and ATL were compared during four conditions duringepoch 1. These were when BPS subsequently terminated ADs within two seconds (1A), terminated ADs within two to five seconds (1B) did not terminate ADs within five seconds (1C), and when ADs did not appear (1D). We found that BPS efficacy in terminating ADs were predicted by (1) low correlation and (2) slow propagation speed between electrode pairs in the 2-10 second period before stimulation. Therefore, wavelet-crosscorrelation analysis can help predict conditions during which BPS can abort ADs. - The wavelet-crosscorrelation function can be written as:
where τ is a time delay of wavelet coefficients in wavelet space. WCx,y(a, τ) is -
- complex-valued and consists of a real part RWCx,y(a, τ) and an imaginary part
- IWCx,y(a, τ). RWCx,y(a, τ) can be used to express strength of correlation between two signals x and y.
- The wavelet-crosscorrelation coefficient WRx,y(a, τ) (WCC) from real part of wavelet-crosscorrelation function RWCx,y(a, τ) is
- The time lag τmax x,y,a(TL) that gives maximum wavelet-crosscorrelation coefficient is
τmax x,y,a=arg max WR x,y(a,τ),(−L a ≦τ≦L a),
where La[msec] corresponds to half-length of one wave for each scale, a. The invention utilizes this method of the novel purpose of predicting seizure onset, of determining optimal time to administer treatment, and determining optimal method of delivering treatment. - The invention also provides for placement of a catheter or similar tubing into brain for direct delivery of said medication or medications, as described hereinabove, to a seizure focus or a brain structure which modulates seizure activity. The invention uses direct infusion of said medication(s) into or onto brain to reduce or prevent occurrence of seizures. Examples of said medications include nucleic acids, hydantoins, deoxybarbiturates, benzodiazepines, glutamate receptor agonists, glutamate receptor antagonists, γ-aminobutyric acid receptor agonists, γ-aminobutyric acid receptor antagonists, dopamine receptor agonists, dopamine receptor antagonists and anesthetics, electrolytes such as sodium, potassium or magnesium, and hormones. Suitable drugs for use in the methods and devices of the invention also include drugs affecting NMDA receptors. AMPA receptors, and metabotropic receptors. These and other suitable medications will be familiar to those of skill in the art.
- The invention also provides for control of brain disorders such as intractable pain, psychiatric disorders such as manic-depressive illness, panic attacks and psychosis, and movement disorders such as dystonia or tremor.
- Another aspect of the invention is control of central nervous system swelling and inflammation. In this regard, implantable heat transfer device behaves essentially as a controlled internal cold “compress”. Cold therapy is well-known for treatment of swelling and the invention provides for a finely regulated means for achieving cold therapy. For example, swelling of brain or spinal tissue due to trauma, hemorrhage, encephalitis or myelitis, or mass lesions (such as tumors, cysts, and abscesses) may be reduced or eliminated by changing temperature of affected tissue according to the invention. Likewise, intractable migraine headaches may be controlled by temperature changes according to the invention. As noted hereinabove, a goal of treatment could be either increased or decreased temperature, and would depend upon disorder under treatment. As noted hereinabove, heat exchange could be combined with infusion of said medication, or said electrical stimulation.
- The method for treating brain or spinal tissue swelling and/or inflammation by controlling temperature would be executed essentially as described for brain cooling to regulate seizures. Briefly, the method would comprise surgically cutting a heat transfer aperture into a patient's skull or spine, thereby exposing a predetermined portion of patient's brain or spinal cord. A heat pump having one or more tissue or cell activity sensor elements and one or more temperature sensor elements would be surgically implanted into said heat transfer aperture. Heat transfer management unit would be attached such that a micro controller of heat transfer management unit would be connected to one or more electrical sensor elements and one or more temperature sensor elements would contact brain or spinal cord tissue. Heat transfer management unit would be connected to said heat pump via a lead bundle. Responsive to signals from one or more sensor elements, mathematical algorithms of heat transfer management unit would determine abnormal brain or spinal cord activity, causing heat pump to transfer heat from brain or spinal cord to a heat sink, thereby effecting cooling. Responsive to signals from one or more sensor elements, treatment with said medications or said electrical stimulation also could be delivered.
- The invention also is envisioned as a means to control swelling, inflammation or localized pain and to promote healing in non-central nervous system organs. Regional or local temperature changes, directed to thoracic and abdominal organs, including liver and intestine, as well as to skeletal muscle, bone, cartilage, tendons, and other connective tissues may control pain, swelling, or inflammation associated with these organs. To this end, a heat pump and a heat transfer management unit may be surgically implanted in, for example, a patient's abdomen, utilizing essentially same methodology described herein for directed brain hypothermia. Briefly, a procedure would be initiated by cutting an incision into a patient's musculature, fascia and body cavity linings and skin, thereby exposing a predetermined portion of said organ. Thereafter, a heat pump having one or more activity sensor elements and one or more temperature sensor elements would be surgically implanted through this incision. A heat transfer management unit would be attached such that a micro controller of heat transfer management unit is connected to one or more activity sensor elements and one or more temperature sensor elements in contact with organ tissue. A lead bundle would connect heat transfer management unit to said heat pump. Responsive to signals from one or more activity or temperature sensor elements, mathematical algorithms of heat transfer management unit detect abnormal organ cell activity. Such abnormal activity causes micro controller in heat transfer management unit to direct heat pump to alter temperature (for example, to initiate cooling) in order to quash, for example, nociceptor activity associated with swelling, inflammation and pain.
- Responsive to signals from one or more sensor elements, treatment with said medications or said electrical stimulation also could be delivered.
- As noted hereinabove, the invention is also envisioned as a method of controllably warming an organ. Warming may be accomplished by heat transfer to an organ, such as the brain, using a surgically implanted activity sensor and a surgically implanted heat transfer and detection apparatus essentially as described hereinabove for brain cooling. For example, abnormally low brain cell firing may be detected and monitored by electrical sensor units. Other characteristics of cells, tissues, organ or region, comprising alterations in ionic composition, pH, osmolality, osmolarity, cellular composition also could be detected. The heat transfer management unit may be surgically implanted into a patient's body cavity, or may optionally be located external to a patient's body. Responsive to signals from one or more sensor elements, mathematical algorithms of heat transfer management unit would determine abnormal activity, or abnormalities of microenvironment of organ, causing heat pump to transfer heat to or from brain tissue from a heat source, thereby altering temperature of patient's brain. An advantage of this method would be to permit controllable warming based upon level of brain activity, and would avoid changing tissue temperature too rapidly. Examples of settings for use of the invention include surgical hypothermia. Treatment with said medications or electrical stimulation could also be delivered.
- As an example, referring to
FIG. 1 in which numerals represent like parts, (1st time numbers are used) neural cooling is achieved by usingheat pump 1 to remove heat from brain intoheat sink 9.Heat sink 9 comprises a sac of high heat conductivity compound, such as silicon oxide paste.Heat sink sac 9 comprises a thin, biologically inert flexible material that permits substantial heat flow.Heat sink 9 covers a larger area than HTA, thereby allowing heat dissipation from body through a large part of scalp. Sink has a large area in relation to the HTA and high thermal conductivity, and thus enables more heat to dissipate from body for a given increase in temperature output fromheat pump 1 than would otherwise occur. This configuration, in turn, improves efficiency ofheat pump 1. Principles just described would apply in an analogous manner when an increased temperature is therapeutically desired. - Details of
heat pump 1 are shown inFIG. 2 . A solid state heat pump using the Peltier effect is illustrated. However, other small mechanical and/or chemical treatment devices are suitable for heat exchange, as long as appropriate elements of such treatment devices could be incorporated into a patient's body and power supply and environmental requirements of these devices may be satisfied post-implantation. Alternatively, portions of treatment devices could be located external to body, for example in a waist-pack, around neck and suspended over the chest, or as a backpack. External portions of the device could communicate with internal portions of the device, for example using telemetry. External portions of such devices may provide power to internal portions, or may assist in heat transfer.Peltier junctions ceramic plates upper junctions 15 heats these junctions, whilelower junctions 14 near brain surface become cold. Thus, the Peltier effect pumps heat from lower junctions to upper junctions away from brain to effect cooling. Reversal of current direction causes heat flow to brain. Complete assemblies of Peltier junction heat pumps are well known and are readily available. Electrical current for heat pump I is supplied throughleads 2 that are routed throughlead bundle 7 that in turn connects toHTMU 8. - In a preferred embodiment of this invention,
activity sensors 4 and atemperature sensor 18 are added to lowerceramic plate 17 resting on brain surface. Activity sensor could sense EEG activity. Other activities also could be sensed, according to the invention, with examples of activities comprising EEG changes, ionic changes, celluar changes, blood flow changes, enzyme changes, hormonal changes, pH changes, changes in osmolality or osmolarity, cellular function and changes and optical changes.Activity sensors 4 have leads 6 connecting sensors to leadbundle 7, which in turn connects toHTMU 8. Similarly,temperature sensor 18 has a lead 19, that is routed to leadbundle 7 and thereafter toHTMU 8.Activity sensors 4 exhibit dual functions in that they may provide electrical stimulation to brain as well as sensing electrical or other brain activity. Sensors determine nature of ongoing epileptiform brain activity and in particular determine positivity or negativity of activity. Stimulation could then be delivered at point in waveform at which epileptiform activity is most likely to stop in response to stimulation. This point could differ from person to person. Moreover, a patient could have more than one seizure type, either in terms of measured brain activity, or clinically, or both, so that more than one manner of treatment would be needed, according to type of seizure occurring. Sensors would determine appropriate point in waveform at which to stimulate and stimulation switch 27 could then be activated at that time. Portions of sensor or sensors could be located external to the body. Accordingly, such portions could be in a waist-pack, around neck and suspended over chest, or as a backpack, with external portions of the device communicating with internal portions of the device, for example by telemetry. External portions, for example, could provide power to internal portions, or could perform certain calculations externally, then providing results to internal portions of device. - Referring to
FIGS. 1-3 ,FIG. 1 showsheat pump 1 placed in an HTA surgically cut into patient's skull. Heat pump hassensor elements FIG. 2 . In addition,activity sensor elements 3 resting on surface of brain, or located within brain substance, monitor background brain activity. These could sense one or more types of activity or activities, comprising EEG changes, ionic changes, cellular changes, blood flow changes, enzyme changes, hormonal changes, pH changes, changes in osmolality or osmolarity, cellular changes. Signals generated byactivity sensor element 3 are used by micro controller 22 (shown inFIG. 3 ) inHTMU 8 to determine when cooling, and possibly heating, may be necessary for controlling seizures. One or more ofsensor elements Sensor elements lead bundle 7, which, in turn, connects toHTMU 8. Electrical and temperature sensor leads 5, 6, 19 feed into alead bundle 7 that in turn connects toHTMU 8.HTMU 8 may be implanted in patient's abdomen, a subcutaneous pocket, or a subclavicular pocket. - Electrical stimulation or delivery of said medication can likewise occur. Each can occur separately, can occur together with the other, or can occur together with heat pumping to control seizures. Magnetic stimulation could be used as an alternative to electrical stimulation.
Temperature sensor 18 serves two functions. First,temperature sensor 18 may trigger heat pumping to prevent a seizure should EEG, brain temperature, or other changes as described above indicate a seizure is imminent. Second,temperature sensor 18 regulates amount of heat pumping achieved to prevent tissue damage. Although brain cooling is generally neuro-protective, too much brain cooling may result in tissue damage. - The details of
HTMU 8 are show inFIG. 3 . Sensor signal leads 5, 6, 19 are fed toamplifiers 20 and then connect to analog todigital converter 21.Micro controller 22 then analyzes digital representations of sensor signals. When a seizure appears imminent,micro controller 22 operates a solid state switch (SSW) 24 to feed power toheat pump 1, or to electrical stimulator, or medication delivery system thereby preventing a seizure from occurring.Micro controller 22 uses a variablemark space waveform 26 to operate SSW. This configuration allows variable levels of power to be applied to heat pump while at same time reducing power wasted in regulating element,SSW 24. -
Power source 25 is contained inHTMU 8 and may comprise a primary battery or a rechargeable cell. Additional power may be provided by a subcutaneous coil orinduction loop 10, connected toloop receiver 23 inHTMU 8 bylead 11.Loop receiver 23 serves to direct additional power from induction loop, and commands and configures changes formicro controller 22. Additional power and/or commands and configuration changes come from an external unit that would transmitted by magnetic induction. Data may also be transmitted from implanted device to external unit in a similar fashion. - Seizures may be controlled by electrical stimulation, infusion of said medication, or beat pumping, singly or in combination. Electrical stimulation or infusion of said medication may be directed to any brain area associated with seizures, including neocortex, hippocampus, amygdala thalamus, hypothalamus, caudate or other nuclei of basal ganglia, cerebellum and brain stem.
Stimulation switch 27 is provided for this purpose, according to the invention.Switch 27 is activated bymicro controller 22, which sends a current pulse throughlead 60 to stimulatingelectrode 61, or to a remotestimulating electrode 62 vialead 63. - The invention provides for multiple techniques that could be applied singly or in combination depending upon situation of specific seizure. Control of an individual event may require only one of these methods, or may require a combination of two or more procedures involving, for example, a single pulse may be delivered or a train of pulses may be delivered until seizure is stopped. Similarly, some patients might require a negative pulse, others a positive pulse, others a balanced pulse with an initial positive phase, others a negative pulse with an initial negative phase. In still others, phase might not matter. Assessment algorithms that are a part of this invention would analyze phase relationships and responses to stimulation so that treatment could be optimized. Treatment could be delivered within the skull, or in or beneath the skin elsewhere in the body under circumstances wherein such stimulation could prevent or abort seizure occurrence.
- Medications could be delivered to brain via an implanted catheter or similar tubing in same manner. Accordingly,
micro controller 22 activates pump andrefillable reservoir 71 which delivers a quantity of said medication throughtubing 70 onto or into brain 28 (shown inFIG. 1 ). A refillable reservoir and pump 71 on surface of head permits replenishment of said medication in a manner analogous to functions of certain types of shunts. Pump in refillable reservoir is controlled bymicro controller 22 via connectinglead 72. - Pulses could vary in their morphology, according to the invention. An example of a train on these pulses is shown in
FIG. 4 waveform 50. Integral product of current and time for each of these component pulses is identical, thus guaranteeing charge balance. In another preferred embodiment on this invention shown inFIG. 4 , order of pulses may be reversed 51, alternating 52 or random 53. That isrecovery pulse 82, shown inFIG. 5 , maybe delivered first, followed byactive pulse 81,waveform 51. In case of alternating order,active pulse 81 is followed byrecovery pulse 82, thenrecovery 82 followed by active 81, then active 81 followed byrecovery 82, thenrecovery 82 followed byactive pulse 81, and so on as inwaveform 52. For random orderingactive pulse 81 may come before or afterrecovery pulse 82 as inwaveform 53. In all cases, for everyactive pulse 81, there will always be arecovery pulse 82 either just before or just after. For reference purposes, a symmetricbiphasic pulse -
Sensor electrodes FIG. 1 at a location that gives earliest indication of seizure activity or other changes in brain activity. Sensors could sense one or many kinds of activity, selected from a list comprising EEG changes, ionic changes, cellular changes, blood flow changes, enzyme changes, hormonal changes, pH changes, changes in osmolality or osmolarity, cellular function changes and optical changes. These sensors are connected byleads bundle 7. Stimulatingelectrodes electrodes bundle 7 byleads - The
lead bundle 7 connects to Stimulation and Medication Delivery System (SMDS) 8 (FIG. 3 ). Sensor leads 5 and 6 connect to anamplifier 20 that amplifies signal sufficiently so thatmicro controller 22 can analyze EEG signals and detect seizure onset. When a seizure is detected, micro controller operates solid state switch to generate one or more pulses as show inFIG. 4 . These pulses are connected tocapacitors 65 that will ensure that there is no net charge imbalance during period of stimulation for times spans that are long compared to time constant of capacitor and stimulation electrode impedance combination. - The invention is further illustrated by following non-limiting examples.
- Afterdischarges and the effect of brief pulse stimulation (BPS) on afterdischarges (ADs) were studied. No single, typical form of ADs was noted. Such pulse stimulation occurs for clinical reasons, in order to help localize areas of brain controlling movement, sensation, language, and other functions, but may produce activity of epileptiform morphology called afterdischarges. Such afterdischarges can be taken as a model of epilepsy. Effect of BPS was not dependent upon pretreatment with anticonvulsant medication, relative time of ADs, or treatment latency. In addition, BPS was effective in all lobes stimulated, for all types of ADs, and both in regions that did and did not produce interictal epileptiform discharges; however, degree of effectiveness depended on these variables. For example, BPS was most effective anteriorly and least effective posteriorly. BPS were more likely to stop ADs if ADs consisted of continuous rhythmic epileptiform activity than to stop ADs that were rapidly repeated spikes. BPS of shorter durations (e.g., 0.5 to 1 second) were more effective than those of longer durations (e.g., 1.5 to 2 seconds). BPS was less effective if stimulation occurred at electrodes where interictal epileptiform discharges were found.
- Wavelet-crosscorrelation analysis was used to obtain wavelet-correlation coefficients (WCC), time lag (TL) and absolute values of TL (ATL) between two electrodes. For Analysis-1, comparisons were made between WCC and ATL in
epoch 1, which was prior to LS,epoch 2 which was after LS but before BPS, andepoch 3 which was after BPS. For Analysis-2, comparisons were made between WCC and ATL during four conditions duringepoch 1. These were when BPS subsequently terminated ADs within two seconds (1A), terminated ADs within two to five seconds (1B) did not terminate ADs within five seconds (1C), and when ADs did not appear (1D). We found that BPS efficacy in terminating ADs was predicted by (1) low correlation and (2) slow propagation speed between electrode pairs in 2-10 second period before stimulation. Therefore, wavelet-crosscorrelation analysis aids in predicting conditions during which BPS can abort ADs. When used according to the invention, similar analyses could help predict when BPS or other interventions would abort clinical seizures. - The value of wavelet cross-correlation analysis was assessed in 57 events in which afterdischarges (ADs) appeared in response to stimulation of brain cortical tissue in humans. Mean durations of
epoch epochs epochs - The results suggested that activity propagated from one electrode to another with a time lag. Short time lags (less than 10 milliseconds) occurred less frequently during
epoch 2, but that time lags of 10 milliseconds occurred more frequently duringepoch 2. - In summary, results indicated that there were significant differences in WCC and TL when comparing among different epochs. These differences can be utilized to determine when seizures are likely to occur and to determine where they are originating and direction of propagation. The example pertains to results utilizing EEG analysis, but those skilled in the art will see that the methods of the invention could be utilized to analyze other data obtained from sensors placed on brain or elsewhere.
- The effects of cooling neural tissue on seizure development were investigated using an EAAC1 knockout rat model of epilepsy. EACC1 antisense DNA was continuously infused into left ventricle of a test animal for 10 days using a pump located on animal's back. Diffuse glutamate toxicity was thereby effected in brain of knockout rat. Diffuse glutamate activity produced seizures, manifested by activity arrest, staring, and rhythmic 2-3/sec epileptiform EEG patterns, all indicative of seizure activity. Thereafter, test animal was anesthetized and a cooling unit adhered to rat's head. Due to thinness of rat crania, cooling of brain was achieved through intact rat skull. EEG tracings were made at baseline (28.8° C.) and at hypothermic (25.2° C.) temperatures. An overall reduction in seizure activity was observed after cooling, marked by return of normal exploratory behavior and normal EEG tracings.
-
Sensor electrodes FIG. 1 at a location that gives the earliest indication of seizure activity. These sensors could be located as shown, or anywhere else in the brain or body where sensors could best detect evidence of seizure onset. These sensors are connected byleads bundle 7. The stimulatingelectrodes electrodes lead bundle 7 byleads lead bundle 7 connects to stimulation and medication delivery system (SMDS) 8, shown inFIG. 3 . The sensor leads 5 and 6 connect to anamplifier 20 that amplifies the signal sufficiently so that themicro controller 22 can analyze the EEG signals and detect seizure onset. When a seizure is detected, the micro controller operatessolid state switch 27 to generates one or more ABPs as show inFIGS. 4-5 . These pulses are connected tocapacitors 65 that will ensure that there is no net charge imbalance during the period of stimulation for time spans that are long compared to the time constant of the capacitor and stimulation electrode impedance combination. - A further refinement to this device uses feedback to dynamically balance the charge of each ABP. The
micro controller 22 senses the voltage at the stimulationelectrodes using connections 66 to the stimulation leads 2. The micro controller is programmed to adjust the amplitude of each phase of the stimulation pulse, via the solid state switch, so that charge balance is ensured at the end of each pulse. Thecapacitors 65 only ensure charge balance at times much longer than the time constant given by the product of the capacitance and stimulation electrode impedance. This time constant is necessarily much longer than the pulse width in order to preserve the original pulse shape. In other words, the charge balance afforded by the capacitor is only achieved at times longer than the time constant of the capacitor electrode combination, which in turn is much longer than the widths of the ABPs. - The use of brief bursts of pulse stimulation to abort seizure activity is further described in Lesser et al.,
Neurology 53, 2073-2081 (1999), the entire contents of which is incorporated herein by reference. - While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to those of ordinary skill in the art that various changes and modifications can be made therein without departing from the spirit and scope of the invention.
Claims (12)
1-34. (canceled)
35. A method of treating epilepsy, comprising:
monitoring at least one sensor that detects electrical activity in the brain;
performing a wavelet cross-correlation analysis on data obtained from said monitoring to determine whether an epileptic seizure is likely to occur or to determine whether one or more treatments selected from the group consisting of electrical stimulation, heating, cooling, and medicament is likely to prevent or abort epileptic seizure activity; and
if the wavelet cross-correlation analysis indicates that one or more of said treatments is likely to prevent or abort epileptic seizure activity, administering the treatments.
36. The method of claim 35 , wherein the one or more treatments comprise pulses of electrical stimulation.
37. The method of claim 35 , wherein the pulses of electrical stimulation are administered so as to maintain charge balance.
38. The method of claim 35 , wherein the medicament is a member selected from the group consisting of drugs, electrolytes, and fluids.
39. The method of claim 35 , wherein the drugs are selected from the group consisting of nucleic acids, hormones, hydantoins, deoxybarbiturates, benzodiazepines, glutamate receptor agonists, glutamate receptor antagonists, γ-aminobutyric acid receptor agonists, γ-aminobutyric acid receptor antagonists, dopamine receptor agonists, dopamine receptor antagonists, drugs affecting NMDA receptors, drugs affecting AMPA receptors, drugs affecting metabotropic receptors, and anesthetics.
40. The method of claim 35 , wherein the one or more treatments comprise electrical stimulation in combination with cooling.
41. A method of analyzing brain activity, comprising:
monitoring at least one sensor that detects electrical activity in the brain;
performing a wavelet cross-correlation analysis on data obtained from said monitoring; and
based on the wavelet cross-correlation analysis, predicting when abnormal electrical activity will occur.
42. The method of claim 41 , wherein the abnormal electrical activity represents epileptic seizure activity.
43. The method of claim 41 , further comprising, based on the wavelet cross-correlation analysis, determining where the abnormal electrical activity originates in the brain.
44. The method of claim 41 , further comprising, based on the wavelet cross-correlation analysis, determining the direction of propagation of the abnormal electrical activity.
45. A method of treating a medical disorder, comprising:
monitoring at least one sensor that senses physiological activity in one or more organs or organ systems;
performing a wavelet cross-correlation analysis on data obtained from said monitoring to determine whether an abnormal state caused by the medical disorder exists, said wavelet cross-correlation analysis comprising:
performing a wavelet transform on data obtained from said monitoring to generate wavelet-transformed data, and
performing a cross-correlation analysis on said wavelet-transforrned data; and
if the abnormal state exists, administering one or more treatments selected from the group consisting of electrical stimulation, heating, cooling, and medicament to the one or more affected organs.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/073,683 US20050149123A1 (en) | 1999-10-19 | 2005-03-08 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16032899P | 1999-10-19 | 1999-10-19 | |
US20118800P | 2000-05-02 | 2000-05-02 | |
US09/691,051 US6882881B1 (en) | 1999-10-19 | 2000-10-19 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
US10/413,520 US7228171B2 (en) | 1999-10-19 | 2003-04-15 | Signal analysis, heat flow management, and stimulation techniques to treat medical disorders |
US11/073,683 US20050149123A1 (en) | 1999-10-19 | 2005-03-08 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/691,051 Division US6882881B1 (en) | 1999-10-19 | 2000-10-19 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
US10/413,520 Continuation-In-Part US7228171B2 (en) | 1999-10-19 | 2003-04-15 | Signal analysis, heat flow management, and stimulation techniques to treat medical disorders |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050149123A1 true US20050149123A1 (en) | 2005-07-07 |
Family
ID=29554118
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/691,051 Expired - Fee Related US6882881B1 (en) | 1999-10-19 | 2000-10-19 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
US11/073,683 Abandoned US20050149123A1 (en) | 1999-10-19 | 2005-03-08 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/691,051 Expired - Fee Related US6882881B1 (en) | 1999-10-19 | 2000-10-19 | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders |
Country Status (1)
Country | Link |
---|---|
US (2) | US6882881B1 (en) |
Cited By (50)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080119900A1 (en) * | 1998-08-05 | 2008-05-22 | Dilorenzo Daniel John | Providing Output Indicative of Subject's Disease State |
US20090005843A1 (en) * | 2007-06-29 | 2009-01-01 | Washington University In St. Louis | Depth cooling implant system |
US20090012436A1 (en) * | 2006-02-17 | 2009-01-08 | Koninklijke Philips Electronics N.V. | Orthosis and treatment method |
US20090082832A1 (en) * | 2007-09-25 | 2009-03-26 | Boston Scientific Neuromodulation Corporation | Thermal Management of Implantable Medical Devices |
US20090149926A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | System for thermal modulation of neural activity |
US20090149911A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | System for electrical modulation of neural conduction |
US20090149799A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Method for chemical modulation of neural activity |
US20090149798A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Implant system for chemical modulation of neural activity |
US20090149914A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Method for reversible chemical modulation of neural activity |
US20090192568A1 (en) * | 2007-12-26 | 2009-07-30 | Boston Scientific Neuromodulation Corporation | Methods and systems for treating seizures caused by brain stimulation |
US20090192575A1 (en) * | 2008-01-29 | 2009-07-30 | Rafael Carbunaru | Thermal management of implantable medical devices |
US7676263B2 (en) | 2006-06-23 | 2010-03-09 | Neurovista Corporation | Minimally invasive system for selecting patient-specific therapy parameters |
US7747325B2 (en) | 1998-08-05 | 2010-06-29 | Neurovista Corporation | Systems and methods for monitoring a patient's neurological disease state |
US20100305632A1 (en) * | 2009-05-26 | 2010-12-02 | Barun Maskara | Temperature assisted stimulation |
US20100312318A1 (en) * | 2008-12-02 | 2010-12-09 | D Ambrosio Raimondo | Methods and devices for brain cooling for treatment and prevention of acquired epilepsy |
US20100324631A1 (en) * | 2009-06-18 | 2010-12-23 | Forschungszentrum Juelich Gmbh | Device and method for stimulating neuronal tissue by means of optical stimuli |
US20100331762A1 (en) * | 2007-02-08 | 2010-12-30 | Neuropace, Inc. | Refillable Reservoir Lead Systems |
US20110004282A1 (en) * | 2007-02-08 | 2011-01-06 | Neuropace, Inc. | Drug Eluting Lead Systems |
US8036736B2 (en) | 2007-03-21 | 2011-10-11 | Neuro Vista Corporation | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US8165668B2 (en) | 2007-12-05 | 2012-04-24 | The Invention Science Fund I, Llc | Method for magnetic modulation of neural conduction |
US8165669B2 (en) | 2007-12-05 | 2012-04-24 | The Invention Science Fund I, Llc | System for magnetic modulation of neural conduction |
US8180446B2 (en) | 2007-12-05 | 2012-05-15 | The Invention Science Fund I, Llc | Method and system for cyclical neural modulation based on activity state |
US8195287B2 (en) | 2007-12-05 | 2012-06-05 | The Invention Science Fund I, Llc | Method for electrical modulation of neural conduction |
US8295934B2 (en) | 2006-11-14 | 2012-10-23 | Neurovista Corporation | Systems and methods of reducing artifact in neurological stimulation systems |
US8538512B1 (en) * | 2007-04-23 | 2013-09-17 | Neurowave Systems Inc. | Method for amplifying abnormal pattern signal in observed brain activity of a subject for diagnosis or treatment |
US8588933B2 (en) | 2009-01-09 | 2013-11-19 | Cyberonics, Inc. | Medical lead termination sleeve for implantable medical devices |
US8725243B2 (en) | 2005-12-28 | 2014-05-13 | Cyberonics, Inc. | Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders |
US8762065B2 (en) | 1998-08-05 | 2014-06-24 | Cyberonics, Inc. | Closed-loop feedback-driven neuromodulation |
US8786624B2 (en) | 2009-06-02 | 2014-07-22 | Cyberonics, Inc. | Processing for multi-channel signals |
US8849390B2 (en) | 2008-12-29 | 2014-09-30 | Cyberonics, Inc. | Processing for multi-channel signals |
US8868172B2 (en) | 2005-12-28 | 2014-10-21 | Cyberonics, Inc. | Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders |
US9042988B2 (en) | 1998-08-05 | 2015-05-26 | Cyberonics, Inc. | Closed-loop vagus nerve stimulation |
US9259591B2 (en) | 2007-12-28 | 2016-02-16 | Cyberonics, Inc. | Housing for an implantable medical device |
US9375573B2 (en) | 1998-08-05 | 2016-06-28 | Cyberonics, Inc. | Systems and methods for monitoring a patient's neurological disease state |
US9415222B2 (en) | 1998-08-05 | 2016-08-16 | Cyberonics, Inc. | Monitoring an epilepsy disease state with a supervisory module |
US9421373B2 (en) | 1998-08-05 | 2016-08-23 | Cyberonics, Inc. | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
WO2016132228A3 (en) * | 2015-02-16 | 2016-10-20 | Nathan Intrator | Systems and methods for brain activity interpretation |
WO2016182894A1 (en) * | 2015-05-08 | 2016-11-17 | Duke University | Systems and methods for spinal cord stimulation |
US9522081B2 (en) | 2008-12-02 | 2016-12-20 | University Of Washington | Methods and devices for brain cooling for treatment and/or prevention of epileptic seizures |
US9622675B2 (en) | 2007-01-25 | 2017-04-18 | Cyberonics, Inc. | Communication error alerting in an epilepsy monitoring system |
US9643019B2 (en) | 2010-02-12 | 2017-05-09 | Cyberonics, Inc. | Neurological monitoring and alerts |
US9788744B2 (en) | 2007-07-27 | 2017-10-17 | Cyberonics, Inc. | Systems for monitoring brain activity and patient advisory device |
US9898656B2 (en) | 2007-01-25 | 2018-02-20 | Cyberonics, Inc. | Systems and methods for identifying a contra-ictal condition in a subject |
US11273283B2 (en) | 2017-12-31 | 2022-03-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11364361B2 (en) | 2018-04-20 | 2022-06-21 | Neuroenhancement Lab, LLC | System and method for inducing sleep by transplanting mental states |
US11406317B2 (en) | 2007-12-28 | 2022-08-09 | Livanova Usa, Inc. | Method for detecting neurological and clinical manifestations of a seizure |
US11452839B2 (en) | 2018-09-14 | 2022-09-27 | Neuroenhancement Lab, LLC | System and method of improving sleep |
US11717686B2 (en) | 2017-12-04 | 2023-08-08 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to facilitate learning and performance |
US11723579B2 (en) | 2017-09-19 | 2023-08-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement |
US11786694B2 (en) | 2019-05-24 | 2023-10-17 | NeuroLight, Inc. | Device, method, and app for facilitating sleep |
Families Citing this family (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4047382B2 (en) * | 1995-08-04 | 2008-02-13 | マイクロコーティング テクノロジーズ | Chemical vapor deposition and powder formation using near-supercritical and supercritical fluid solution spraying |
US20030100931A1 (en) * | 2001-11-28 | 2003-05-29 | Keith Mullett | Brain signal feedback for pain management |
US20030149450A1 (en) * | 2002-02-01 | 2003-08-07 | Mayberg Marc R. | Brainstem and cerebellar modulation of cardiovascular response and disease |
AU2003294595A1 (en) * | 2002-12-09 | 2004-06-30 | Medtronic, Inc. | Modular implantable medical device |
US7596408B2 (en) * | 2002-12-09 | 2009-09-29 | Medtronic, Inc. | Implantable medical device with anti-infection agent |
US7317947B2 (en) * | 2003-05-16 | 2008-01-08 | Medtronic, Inc. | Headset recharger for cranially implantable medical devices |
US7263401B2 (en) | 2003-05-16 | 2007-08-28 | Medtronic, Inc. | Implantable medical device with a nonhermetic battery |
US20050003268A1 (en) * | 2003-05-16 | 2005-01-06 | Scott Erik R. | Battery housing configuration |
US20050004637A1 (en) * | 2003-05-16 | 2005-01-06 | Ruchika Singhal | Explantation of implantable medical device |
US20050102006A1 (en) * | 2003-09-25 | 2005-05-12 | Whitehurst Todd K. | Skull-mounted electrical stimulation system |
WO2005062829A2 (en) * | 2003-12-19 | 2005-07-14 | Advanced Bionics Corporation | Skull-mounted electrical stimulation system and method for treating patients |
US9011329B2 (en) | 2004-04-19 | 2015-04-21 | Searete Llc | Lumenally-active device |
US8337482B2 (en) | 2004-04-19 | 2012-12-25 | The Invention Science Fund I, Llc | System for perfusion management |
US8353896B2 (en) | 2004-04-19 | 2013-01-15 | The Invention Science Fund I, Llc | Controllable release nasal system |
US8024036B2 (en) | 2007-03-19 | 2011-09-20 | The Invention Science Fund I, Llc | Lumen-traveling biological interface device and method of use |
US8092549B2 (en) * | 2004-09-24 | 2012-01-10 | The Invention Science Fund I, Llc | Ciliated stent-like-system |
US8512219B2 (en) * | 2004-04-19 | 2013-08-20 | The Invention Science Fund I, Llc | Bioelectromagnetic interface system |
US8361013B2 (en) * | 2004-04-19 | 2013-01-29 | The Invention Science Fund I, Llc | Telescoping perfusion management system |
US7850676B2 (en) * | 2004-04-19 | 2010-12-14 | The Invention Science Fund I, Llc | System with a reservoir for perfusion management |
US7596399B2 (en) * | 2004-04-29 | 2009-09-29 | Medtronic, Inc | Implantation of implantable medical device |
US20050245984A1 (en) * | 2004-04-30 | 2005-11-03 | Medtronic, Inc. | Implantable medical device with lubricious material |
US20080045882A1 (en) * | 2004-08-26 | 2008-02-21 | Finsterwald P M | Biological Cell Acoustic Enhancement and Stimulation |
US8836513B2 (en) | 2006-04-28 | 2014-09-16 | Proteus Digital Health, Inc. | Communication system incorporated in an ingestible product |
US8802183B2 (en) | 2005-04-28 | 2014-08-12 | Proteus Digital Health, Inc. | Communication system with enhanced partial power source and method of manufacturing same |
US8730031B2 (en) | 2005-04-28 | 2014-05-20 | Proteus Digital Health, Inc. | Communication system using an implantable device |
US9198608B2 (en) | 2005-04-28 | 2015-12-01 | Proteus Digital Health, Inc. | Communication system incorporated in a container |
EP3827747A1 (en) | 2005-04-28 | 2021-06-02 | Otsuka Pharmaceutical Co., Ltd. | Pharma-informatics system |
US8912908B2 (en) | 2005-04-28 | 2014-12-16 | Proteus Digital Health, Inc. | Communication system with remote activation |
US8150522B2 (en) * | 2005-08-19 | 2012-04-03 | The Trustees Of The University Of Pennsylvania | Active control of epileptic seizures and diagnosis based on critical systems-like behavior |
JP5714210B2 (en) * | 2005-09-01 | 2015-05-07 | プロテウス デジタル ヘルス, インコーポレイテッド | Implantable wireless communication system |
US7734352B2 (en) * | 2005-09-19 | 2010-06-08 | Second Sight Medical Products, Inc. | Sub-threshold stimulation to precondition neurons for supra-threshold stimulation |
US7729773B2 (en) * | 2005-10-19 | 2010-06-01 | Advanced Neuromodualation Systems, Inc. | Neural stimulation and optical monitoring systems and methods |
WO2007109076A1 (en) * | 2006-03-15 | 2007-09-27 | Cherik Bulkes | Composite waveform based method and apparatus for animal tissue stimulation |
US20120035439A1 (en) | 2006-04-12 | 2012-02-09 | Bran Ferren | Map-based navigation of a body tube tree by a lumen traveling device |
US9084901B2 (en) | 2006-04-28 | 2015-07-21 | Medtronic, Inc. | Cranial implant |
JP2009544338A (en) | 2006-05-02 | 2009-12-17 | プロテウス バイオメディカル インコーポレイテッド | Treatment regimen customized to the patient |
DE202006010486U1 (en) * | 2006-07-06 | 2007-01-18 | Pogorelik, Solomon, Dr. | Anti-sleeping device for e.g. drivers comprises a cooling body, a Peltier element fixed to the body and a control unit connected to the Peltier element and having a random generator to continuously impinge the Peltier element with a voltage |
US20080039904A1 (en) * | 2006-08-08 | 2008-02-14 | Cherik Bulkes | Intravascular implant system |
EP2083680B1 (en) | 2006-10-25 | 2016-08-10 | Proteus Digital Health, Inc. | Controlled activation ingestible identifier |
EP2069004A4 (en) | 2006-11-20 | 2014-07-09 | Proteus Digital Health Inc | Active signal processing personal health signal receivers |
US8267983B2 (en) | 2007-01-11 | 2012-09-18 | Scion Neurostim, Llc. | Medical devices incorporating thermoelectric transducer and controller |
US8696724B2 (en) * | 2007-01-11 | 2014-04-15 | Scion Neurostim, Llc. | Devices for vestibular or cranial nerve stimulation |
ES2930588T3 (en) | 2007-02-01 | 2022-12-19 | Otsuka Pharma Co Ltd | Ingestible Event Marker Systems |
KR101528748B1 (en) | 2007-02-14 | 2015-06-15 | 프로테우스 디지털 헬스, 인코포레이티드 | In-body power source having high surface area electrode |
US8734499B2 (en) * | 2007-03-29 | 2014-05-27 | Cardiac Pacemakers, Inc. | Systems and methods for thermal neuroinhibition |
WO2008137452A1 (en) * | 2007-05-04 | 2008-11-13 | Kenergy Royalty Company, Llc | Implantable high efficiency digital stimulation device |
US8115618B2 (en) | 2007-05-24 | 2012-02-14 | Proteus Biomedical, Inc. | RFID antenna for in-body device |
US8738139B2 (en) | 2007-08-01 | 2014-05-27 | Bruce Lanning | Wireless system for epilepsy monitoring and measurement |
FI2192946T3 (en) | 2007-09-25 | 2022-11-30 | In-body device with virtual dipole signal amplification | |
AU2009221781B2 (en) | 2008-03-05 | 2014-12-11 | Otsuka Pharmaceutical Co., Ltd. | Multi-mode communication ingestible event markers and systems, and methods of using the same |
US20090281623A1 (en) * | 2008-05-12 | 2009-11-12 | Medtronic, Inc. | Customization of implantable medical devices |
MY154234A (en) | 2008-07-08 | 2015-05-15 | Proteus Digital Health Inc | Ingestible event marker data framework |
US8788042B2 (en) | 2008-07-30 | 2014-07-22 | Ecole Polytechnique Federale De Lausanne (Epfl) | Apparatus and method for optimized stimulation of a neurological target |
US9393432B2 (en) | 2008-10-31 | 2016-07-19 | Medtronic, Inc. | Non-hermetic direct current interconnect |
US8788064B2 (en) | 2008-11-12 | 2014-07-22 | Ecole Polytechnique Federale De Lausanne | Microfabricated neurostimulation device |
WO2010056438A2 (en) | 2008-11-13 | 2010-05-20 | Proteus Biomedical, Inc. | Shielded stimulation and sensing system and method |
US7974705B2 (en) | 2008-11-13 | 2011-07-05 | Proteus Biomedical, Inc. | Multiplexed multi-electrode neurostimulation devices |
EP2346391A4 (en) * | 2008-11-18 | 2012-08-15 | Proteus Biomedical Inc | Sensing system, device, and method for therapy modulation |
US8055334B2 (en) | 2008-12-11 | 2011-11-08 | Proteus Biomedical, Inc. | Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same |
WO2013012869A1 (en) | 2011-07-21 | 2013-01-24 | Proteus Digital Health, Inc. | Mobile communication device, system, and method |
US9659423B2 (en) | 2008-12-15 | 2017-05-23 | Proteus Digital Health, Inc. | Personal authentication apparatus system and method |
TWI424832B (en) | 2008-12-15 | 2014-02-01 | Proteus Digital Health Inc | Body-associated receiver and method |
US9439566B2 (en) | 2008-12-15 | 2016-09-13 | Proteus Digital Health, Inc. | Re-wearable wireless device |
JP2012514799A (en) | 2009-01-06 | 2012-06-28 | プロテウス バイオメディカル インコーポレイテッド | Methods and systems for ingestion related biofeedback and individual pharmacotherapy |
US8560073B2 (en) * | 2009-03-23 | 2013-10-15 | Flint Hills Scientific, Llc | System and apparatus for automated quantitative assessment, optimization and logging of the effects of a therapy |
WO2011075574A1 (en) | 2009-12-18 | 2011-06-23 | Scion Neurostim, Llc | Devices and methods for vestibular and/or cranial nerve stimulation |
WO2012083126A1 (en) | 2010-12-16 | 2012-06-21 | Scion Neurostim, Llc | Systems, devices and methods for bilateral caloric vestibular stimulation |
TWI517050B (en) | 2009-11-04 | 2016-01-11 | 普羅托斯數位健康公司 | System for supply chain management |
EP2506920B1 (en) | 2009-12-01 | 2016-07-13 | Ecole Polytechnique Fédérale de Lausanne | Microfabricated surface neurostimulation device and method of making the same |
SG182825A1 (en) | 2010-02-01 | 2012-09-27 | Proteus Biomedical Inc | Data gathering system |
WO2011121089A1 (en) | 2010-04-01 | 2011-10-06 | Ecole Polytechnique Federale De Lausanne (Epfl) | Device for interacting with neurological tissue and methods of making and using the same |
TWI557672B (en) | 2010-05-19 | 2016-11-11 | 波提亞斯數位康健公司 | Computer system and computer-implemented method to track medication from manufacturer to a patient, apparatus and method for confirming delivery of medication to a patient, patient interface device |
US8641646B2 (en) * | 2010-07-30 | 2014-02-04 | Cyberonics, Inc. | Seizure detection using coordinate data |
US9744074B2 (en) | 2010-12-16 | 2017-08-29 | Scion Neurostim, Llc | Combination treatments |
US10512564B2 (en) | 2010-12-16 | 2019-12-24 | Scion Neurostim, Llc | Combination treatments |
US10537467B2 (en) | 2010-12-16 | 2020-01-21 | Scion Neurostim, Llc | Systems, devices and methods for bilateral caloric vestibular stimulation |
US9439599B2 (en) | 2011-03-11 | 2016-09-13 | Proteus Digital Health, Inc. | Wearable personal body associated device with various physical configurations |
WO2015112603A1 (en) | 2014-01-21 | 2015-07-30 | Proteus Digital Health, Inc. | Masticable ingestible product and communication system therefor |
US9756874B2 (en) | 2011-07-11 | 2017-09-12 | Proteus Digital Health, Inc. | Masticable ingestible product and communication system therefor |
US9235683B2 (en) | 2011-11-09 | 2016-01-12 | Proteus Digital Health, Inc. | Apparatus, system, and method for managing adherence to a regimen |
US8706237B2 (en) | 2012-02-19 | 2014-04-22 | Medtronic, Inc. | Brain stimulation response profiling |
WO2014039925A2 (en) * | 2012-09-07 | 2014-03-13 | Yale University | Brian cooling system |
US11744481B2 (en) | 2013-03-15 | 2023-09-05 | Otsuka Pharmaceutical Co., Ltd. | System, apparatus and methods for data collection and assessing outcomes |
WO2014151929A1 (en) | 2013-03-15 | 2014-09-25 | Proteus Digital Health, Inc. | Personal authentication apparatus system and method |
EP3047618B1 (en) | 2013-09-20 | 2023-11-08 | Otsuka Pharmaceutical Co., Ltd. | Methods, devices and systems for receiving and decoding a signal in the presence of noise using slices and warping |
JP2016537924A (en) | 2013-09-24 | 2016-12-01 | プロテウス デジタル ヘルス, インコーポレイテッド | Method and apparatus for use with electromagnetic signals received at frequencies that are not accurately known in advance |
US10084880B2 (en) | 2013-11-04 | 2018-09-25 | Proteus Digital Health, Inc. | Social media networking based on physiologic information |
EP3476430B1 (en) | 2014-05-16 | 2020-07-01 | Aleva Neurotherapeutics SA | Device for interacting with neurological tissue |
US11311718B2 (en) | 2014-05-16 | 2022-04-26 | Aleva Neurotherapeutics Sa | Device for interacting with neurological tissue and methods of making and using the same |
US9474894B2 (en) | 2014-08-27 | 2016-10-25 | Aleva Neurotherapeutics | Deep brain stimulation lead |
US9925376B2 (en) | 2014-08-27 | 2018-03-27 | Aleva Neurotherapeutics | Treatment of autoimmune diseases with deep brain stimulation |
US9403011B2 (en) | 2014-08-27 | 2016-08-02 | Aleva Neurotherapeutics | Leadless neurostimulator |
AU2016316683B2 (en) | 2015-09-04 | 2020-07-23 | The Johns Hopkins University | Low-profile intercranial device |
US10772561B2 (en) * | 2016-04-01 | 2020-09-15 | Thomas Alan Donaldson | Sensors to determine neuronal activity of an organism to facilitate a human-machine interface |
KR102051875B1 (en) | 2016-07-22 | 2019-12-04 | 프로테우스 디지털 헬스, 인코포레이티드 | Electromagnetic detection and detection of ingestible event markers |
US10912648B2 (en) | 2016-08-30 | 2021-02-09 | Longeviti Neuro Solutions Llc | Method for manufacturing a low-profile intercranial device and the low-profile intercranial device manufactured thereby |
US11589992B2 (en) | 2018-01-09 | 2023-02-28 | Longeviti Neuro Solutions Llc | Universal low-profile intercranial assembly |
US10702692B2 (en) | 2018-03-02 | 2020-07-07 | Aleva Neurotherapeutics | Neurostimulation device |
CN112533561B (en) * | 2018-03-07 | 2023-10-27 | Soovu实验室公司 | Systems and methods for improving pain relief by stimulating thermal fibers |
Citations (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3170465A (en) * | 1962-06-26 | 1965-02-23 | James E Henney | Internal body heating devices |
US4592359A (en) * | 1985-04-02 | 1986-06-03 | The Board Of Trustees Of The Leland Stanford Junior University | Multi-channel implantable neural stimulator |
US4719919A (en) * | 1983-01-21 | 1988-01-19 | Ramm Associates, A Partnership | Implantable hyperthermia device and system |
US4987896A (en) * | 1981-03-28 | 1991-01-29 | Yoshiro Nakamatsu | Apparatus for increasing the activity of the human brain |
US4989601A (en) * | 1988-05-02 | 1991-02-05 | Medical Engineering & Development Institute, Inc. | Method, apparatus, and substance for treating tissue having neoplastic cells |
US5314458A (en) * | 1990-06-01 | 1994-05-24 | University Of Michigan | Single channel microstimulator |
US5540737A (en) * | 1991-06-26 | 1996-07-30 | Massachusetts Institute Of Technology | Minimally invasive monopole phased array hyperthermia applicators and method for treating breast carcinomas |
US5611767A (en) * | 1991-06-14 | 1997-03-18 | Oncocath, Inc. | Radiation treatment of tumors using inflatable devices |
US5713923A (en) * | 1996-05-13 | 1998-02-03 | Medtronic, Inc. | Techniques for treating epilepsy by brain stimulation and drug infusion |
US5716377A (en) * | 1996-04-25 | 1998-02-10 | Medtronic, Inc. | Method of treating movement disorders by brain stimulation |
US5735814A (en) * | 1996-04-30 | 1998-04-07 | Medtronic, Inc. | Techniques of treating neurodegenerative disorders by brain infusion |
US5782798A (en) * | 1996-06-26 | 1998-07-21 | Medtronic, Inc. | Techniques for treating eating disorders by brain stimulation and drug infusion |
US5792186A (en) * | 1996-04-25 | 1998-08-11 | Medtronic, Inc. | Method and apparatus for treating neurodegenerative disorders by electrical brain stimulation |
US5795581A (en) * | 1995-03-31 | 1998-08-18 | Sandia Corporation | Controlled release of molecular components of dendrimer/bioactive complexes |
US5916242A (en) * | 1996-11-04 | 1999-06-29 | Schwartz; George R. | Apparatus for rapid cooling of the brain and method of performing same |
US5925070A (en) * | 1996-04-04 | 1999-07-20 | Medtronic, Inc. | Techniques for adjusting the locus of excitation of electrically excitable tissue |
US5938689A (en) * | 1998-05-01 | 1999-08-17 | Neuropace, Inc. | Electrode configuration for a brain neuropacemaker |
US5995868A (en) * | 1996-01-23 | 1999-11-30 | University Of Kansas | System for the prediction, rapid detection, warning, prevention, or control of changes in activity states in the brain of a subject |
US6016449A (en) * | 1997-10-27 | 2000-01-18 | Neuropace, Inc. | System for treatment of neurological disorders |
US6594524B2 (en) * | 2000-12-12 | 2003-07-15 | The Trustees Of The University Of Pennsylvania | Adaptive method and apparatus for forecasting and controlling neurological disturbances under a multi-level control |
-
2000
- 2000-10-19 US US09/691,051 patent/US6882881B1/en not_active Expired - Fee Related
-
2005
- 2005-03-08 US US11/073,683 patent/US20050149123A1/en not_active Abandoned
Patent Citations (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3170465A (en) * | 1962-06-26 | 1965-02-23 | James E Henney | Internal body heating devices |
US4987896A (en) * | 1981-03-28 | 1991-01-29 | Yoshiro Nakamatsu | Apparatus for increasing the activity of the human brain |
US4719919A (en) * | 1983-01-21 | 1988-01-19 | Ramm Associates, A Partnership | Implantable hyperthermia device and system |
US4592359A (en) * | 1985-04-02 | 1986-06-03 | The Board Of Trustees Of The Leland Stanford Junior University | Multi-channel implantable neural stimulator |
US4989601A (en) * | 1988-05-02 | 1991-02-05 | Medical Engineering & Development Institute, Inc. | Method, apparatus, and substance for treating tissue having neoplastic cells |
US5314458A (en) * | 1990-06-01 | 1994-05-24 | University Of Michigan | Single channel microstimulator |
US5611767A (en) * | 1991-06-14 | 1997-03-18 | Oncocath, Inc. | Radiation treatment of tumors using inflatable devices |
US5540737A (en) * | 1991-06-26 | 1996-07-30 | Massachusetts Institute Of Technology | Minimally invasive monopole phased array hyperthermia applicators and method for treating breast carcinomas |
US5795581A (en) * | 1995-03-31 | 1998-08-18 | Sandia Corporation | Controlled release of molecular components of dendrimer/bioactive complexes |
US5995868A (en) * | 1996-01-23 | 1999-11-30 | University Of Kansas | System for the prediction, rapid detection, warning, prevention, or control of changes in activity states in the brain of a subject |
US5925070A (en) * | 1996-04-04 | 1999-07-20 | Medtronic, Inc. | Techniques for adjusting the locus of excitation of electrically excitable tissue |
US5792186A (en) * | 1996-04-25 | 1998-08-11 | Medtronic, Inc. | Method and apparatus for treating neurodegenerative disorders by electrical brain stimulation |
US5716377A (en) * | 1996-04-25 | 1998-02-10 | Medtronic, Inc. | Method of treating movement disorders by brain stimulation |
US5735814A (en) * | 1996-04-30 | 1998-04-07 | Medtronic, Inc. | Techniques of treating neurodegenerative disorders by brain infusion |
US5978702A (en) * | 1996-05-13 | 1999-11-02 | Medtronic, Inc. | Techniques of treating epilepsy by brain stimulation and drug infusion |
US5713923A (en) * | 1996-05-13 | 1998-02-03 | Medtronic, Inc. | Techniques for treating epilepsy by brain stimulation and drug infusion |
US5782798A (en) * | 1996-06-26 | 1998-07-21 | Medtronic, Inc. | Techniques for treating eating disorders by brain stimulation and drug infusion |
US5916242A (en) * | 1996-11-04 | 1999-06-29 | Schwartz; George R. | Apparatus for rapid cooling of the brain and method of performing same |
US6016449A (en) * | 1997-10-27 | 2000-01-18 | Neuropace, Inc. | System for treatment of neurological disorders |
US5938689A (en) * | 1998-05-01 | 1999-08-17 | Neuropace, Inc. | Electrode configuration for a brain neuropacemaker |
US6594524B2 (en) * | 2000-12-12 | 2003-07-15 | The Trustees Of The University Of Pennsylvania | Adaptive method and apparatus for forecasting and controlling neurological disturbances under a multi-level control |
Cited By (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9042988B2 (en) | 1998-08-05 | 2015-05-26 | Cyberonics, Inc. | Closed-loop vagus nerve stimulation |
US20080119900A1 (en) * | 1998-08-05 | 2008-05-22 | Dilorenzo Daniel John | Providing Output Indicative of Subject's Disease State |
US8762065B2 (en) | 1998-08-05 | 2014-06-24 | Cyberonics, Inc. | Closed-loop feedback-driven neuromodulation |
US7930035B2 (en) * | 1998-08-05 | 2011-04-19 | Neurovista Corporation | Providing output indicative of subject's disease state |
US8781597B2 (en) | 1998-08-05 | 2014-07-15 | Cyberonics, Inc. | Systems for monitoring a patient's neurological disease state |
US7853329B2 (en) | 1998-08-05 | 2010-12-14 | Neurovista Corporation | Monitoring efficacy of neural modulation therapy |
US9421373B2 (en) | 1998-08-05 | 2016-08-23 | Cyberonics, Inc. | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US9415222B2 (en) | 1998-08-05 | 2016-08-16 | Cyberonics, Inc. | Monitoring an epilepsy disease state with a supervisory module |
US9375573B2 (en) | 1998-08-05 | 2016-06-28 | Cyberonics, Inc. | Systems and methods for monitoring a patient's neurological disease state |
US9320900B2 (en) | 1998-08-05 | 2016-04-26 | Cyberonics, Inc. | Methods and systems for determining subject-specific parameters for a neuromodulation therapy |
US9113801B2 (en) | 1998-08-05 | 2015-08-25 | Cyberonics, Inc. | Methods and systems for continuous EEG monitoring |
US7747325B2 (en) | 1998-08-05 | 2010-06-29 | Neurovista Corporation | Systems and methods for monitoring a patient's neurological disease state |
US8725243B2 (en) | 2005-12-28 | 2014-05-13 | Cyberonics, Inc. | Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders |
US9592004B2 (en) | 2005-12-28 | 2017-03-14 | Cyberonics, Inc. | Methods and systems for managing epilepsy and other neurological disorders |
US9044188B2 (en) | 2005-12-28 | 2015-06-02 | Cyberonics, Inc. | Methods and systems for managing epilepsy and other neurological disorders |
US8868172B2 (en) | 2005-12-28 | 2014-10-21 | Cyberonics, Inc. | Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders |
US20090012436A1 (en) * | 2006-02-17 | 2009-01-08 | Koninklijke Philips Electronics N.V. | Orthosis and treatment method |
US7676263B2 (en) | 2006-06-23 | 2010-03-09 | Neurovista Corporation | Minimally invasive system for selecting patient-specific therapy parameters |
US9480845B2 (en) | 2006-06-23 | 2016-11-01 | Cyberonics, Inc. | Nerve stimulation device with a wearable loop antenna |
US8855775B2 (en) | 2006-11-14 | 2014-10-07 | Cyberonics, Inc. | Systems and methods of reducing artifact in neurological stimulation systems |
US8295934B2 (en) | 2006-11-14 | 2012-10-23 | Neurovista Corporation | Systems and methods of reducing artifact in neurological stimulation systems |
US9622675B2 (en) | 2007-01-25 | 2017-04-18 | Cyberonics, Inc. | Communication error alerting in an epilepsy monitoring system |
US9898656B2 (en) | 2007-01-25 | 2018-02-20 | Cyberonics, Inc. | Systems and methods for identifying a contra-ictal condition in a subject |
US8190270B2 (en) * | 2007-02-08 | 2012-05-29 | Neuropace, Inc. | Refillable reservoir lead systems |
US20120109253A1 (en) * | 2007-02-08 | 2012-05-03 | Neuropace, Inc. | Refillable Reservoir Lead Systems |
US8160720B2 (en) * | 2007-02-08 | 2012-04-17 | Neuropace, Inc. | Refillable reservoir lead systems |
US20110004282A1 (en) * | 2007-02-08 | 2011-01-06 | Neuropace, Inc. | Drug Eluting Lead Systems |
US8423156B2 (en) | 2007-02-08 | 2013-04-16 | Neuropace, Inc. | Drug eluting lead systems |
US20100331762A1 (en) * | 2007-02-08 | 2010-12-30 | Neuropace, Inc. | Refillable Reservoir Lead Systems |
US8036736B2 (en) | 2007-03-21 | 2011-10-11 | Neuro Vista Corporation | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US9445730B2 (en) | 2007-03-21 | 2016-09-20 | Cyberonics, Inc. | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US8543199B2 (en) | 2007-03-21 | 2013-09-24 | Cyberonics, Inc. | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US8538512B1 (en) * | 2007-04-23 | 2013-09-17 | Neurowave Systems Inc. | Method for amplifying abnormal pattern signal in observed brain activity of a subject for diagnosis or treatment |
US20090005843A1 (en) * | 2007-06-29 | 2009-01-01 | Washington University In St. Louis | Depth cooling implant system |
US8202308B2 (en) | 2007-06-29 | 2012-06-19 | Matthew D. Smyth | Depth cooling implant system |
US9788744B2 (en) | 2007-07-27 | 2017-10-17 | Cyberonics, Inc. | Systems for monitoring brain activity and patient advisory device |
US20090082832A1 (en) * | 2007-09-25 | 2009-03-26 | Boston Scientific Neuromodulation Corporation | Thermal Management of Implantable Medical Devices |
US8170658B2 (en) | 2007-12-05 | 2012-05-01 | The Invention Science Fund I, Llc | System for electrical modulation of neural conduction |
US8160695B2 (en) | 2007-12-05 | 2012-04-17 | The Invention Science Fund I, Llc | System for chemical modulation of neural activity |
GB2467882B (en) * | 2007-12-05 | 2012-12-05 | Searete Llc | System for thermal modulation of neural activity |
US10092692B2 (en) | 2007-12-05 | 2018-10-09 | Gearbox, Llc | Method and system for modulating neural activity |
US8233976B2 (en) | 2007-12-05 | 2012-07-31 | The Invention Science Fund I, Llc | System for transdermal chemical modulation of neural activity |
US8195287B2 (en) | 2007-12-05 | 2012-06-05 | The Invention Science Fund I, Llc | Method for electrical modulation of neural conduction |
US8170660B2 (en) | 2007-12-05 | 2012-05-01 | The Invention Science Fund I, Llc | System for thermal modulation of neural activity |
US8180446B2 (en) | 2007-12-05 | 2012-05-15 | The Invention Science Fund I, Llc | Method and system for cyclical neural modulation based on activity state |
US9789315B2 (en) | 2007-12-05 | 2017-10-17 | Gearbox, Llc | Method and system for modulating neural activity |
US20090149914A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Method for reversible chemical modulation of neural activity |
US8630706B2 (en) | 2007-12-05 | 2014-01-14 | The Invention Science Fund I, Llc | Method and system for reversible chemical modulation of neural activity |
US8165668B2 (en) | 2007-12-05 | 2012-04-24 | The Invention Science Fund I, Llc | Method for magnetic modulation of neural conduction |
US8180447B2 (en) | 2007-12-05 | 2012-05-15 | The Invention Science Fund I, Llc | Method for reversible chemical modulation of neural activity |
US8165669B2 (en) | 2007-12-05 | 2012-04-24 | The Invention Science Fund I, Llc | System for magnetic modulation of neural conduction |
US20090149926A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | System for thermal modulation of neural activity |
US20090149911A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | System for electrical modulation of neural conduction |
US8170659B2 (en) | 2007-12-05 | 2012-05-01 | The Invention Science Fund I, Llc | Method for thermal modulation of neural activity |
US20090149799A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Method for chemical modulation of neural activity |
US20090149798A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Implant system for chemical modulation of neural activity |
US8989858B2 (en) | 2007-12-05 | 2015-03-24 | The Invention Science Fund I, Llc | Implant system for chemical modulation of neural activity |
US9014802B2 (en) | 2007-12-05 | 2015-04-21 | The Invention Science Fund I, Llc | Method and system for modulating neural activity in a limb |
US9020591B2 (en) | 2007-12-05 | 2015-04-28 | The Invention Science Fund I, Llc | Method and system for ultrasonic neural modulation in a limb |
US9020592B2 (en) | 2007-12-05 | 2015-04-28 | The Invention Science Fund I, Llc | Method and system for blocking nerve conduction |
WO2009073208A1 (en) * | 2007-12-05 | 2009-06-11 | Searete Llc | System for thermal modulation of neural activity |
GB2467882A (en) * | 2007-12-05 | 2010-08-18 | Searete Llc | System for thermal modulation of neural activity |
US9358374B2 (en) | 2007-12-05 | 2016-06-07 | Gearbox, Llc | Method and system for blocking nerve conduction |
US8600512B2 (en) | 2007-12-26 | 2013-12-03 | Boston Scientific Neuromodulation Corporation | Methods and systems for treating seizures caused by brain stimulation |
US20090192568A1 (en) * | 2007-12-26 | 2009-07-30 | Boston Scientific Neuromodulation Corporation | Methods and systems for treating seizures caused by brain stimulation |
US9031656B2 (en) | 2007-12-26 | 2015-05-12 | Boston Scientific Neuromodulation Corporation | Methods and systems for treating seizures caused by brain stimulation |
US11406317B2 (en) | 2007-12-28 | 2022-08-09 | Livanova Usa, Inc. | Method for detecting neurological and clinical manifestations of a seizure |
US9259591B2 (en) | 2007-12-28 | 2016-02-16 | Cyberonics, Inc. | Housing for an implantable medical device |
US20090192575A1 (en) * | 2008-01-29 | 2009-07-30 | Rafael Carbunaru | Thermal management of implantable medical devices |
US8165694B2 (en) | 2008-01-29 | 2012-04-24 | Boston Scientific Neuromodulation Corporation | Thermal management of implantable medical devices |
US20100312318A1 (en) * | 2008-12-02 | 2010-12-09 | D Ambrosio Raimondo | Methods and devices for brain cooling for treatment and prevention of acquired epilepsy |
US9522081B2 (en) | 2008-12-02 | 2016-12-20 | University Of Washington | Methods and devices for brain cooling for treatment and/or prevention of epileptic seizures |
US8591562B2 (en) * | 2008-12-02 | 2013-11-26 | University Of Washington | Methods and devices for brain cooling for treatment and prevention of acquired epilepsy |
US8849390B2 (en) | 2008-12-29 | 2014-09-30 | Cyberonics, Inc. | Processing for multi-channel signals |
US9289595B2 (en) | 2009-01-09 | 2016-03-22 | Cyberonics, Inc. | Medical lead termination sleeve for implantable medical devices |
US8588933B2 (en) | 2009-01-09 | 2013-11-19 | Cyberonics, Inc. | Medical lead termination sleeve for implantable medical devices |
US20100305632A1 (en) * | 2009-05-26 | 2010-12-02 | Barun Maskara | Temperature assisted stimulation |
US8463377B2 (en) * | 2009-05-26 | 2013-06-11 | Cardiac Pacemakers, Inc. | Temperature assisted stimulation |
US8786624B2 (en) | 2009-06-02 | 2014-07-22 | Cyberonics, Inc. | Processing for multi-channel signals |
US8721695B2 (en) * | 2009-06-18 | 2014-05-13 | Forschungszentrum Juelich Gmbh | Device and method for stimulating neuronal tissue by means of optical stimuli |
US20100324631A1 (en) * | 2009-06-18 | 2010-12-23 | Forschungszentrum Juelich Gmbh | Device and method for stimulating neuronal tissue by means of optical stimuli |
US9643019B2 (en) | 2010-02-12 | 2017-05-09 | Cyberonics, Inc. | Neurological monitoring and alerts |
US9955905B2 (en) | 2015-02-16 | 2018-05-01 | NeuroSteer Ltd. | Systems and methods for brain activity interpretation |
WO2016132228A3 (en) * | 2015-02-16 | 2016-10-20 | Nathan Intrator | Systems and methods for brain activity interpretation |
US11911171B2 (en) | 2015-02-16 | 2024-02-27 | Neurosteer Inc. | Systems and methods for brain activity interpretation |
WO2016182894A1 (en) * | 2015-05-08 | 2016-11-17 | Duke University | Systems and methods for spinal cord stimulation |
US11723579B2 (en) | 2017-09-19 | 2023-08-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement |
US11717686B2 (en) | 2017-12-04 | 2023-08-08 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to facilitate learning and performance |
US11273283B2 (en) | 2017-12-31 | 2022-03-15 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11318277B2 (en) | 2017-12-31 | 2022-05-03 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11478603B2 (en) | 2017-12-31 | 2022-10-25 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
US11364361B2 (en) | 2018-04-20 | 2022-06-21 | Neuroenhancement Lab, LLC | System and method for inducing sleep by transplanting mental states |
US11452839B2 (en) | 2018-09-14 | 2022-09-27 | Neuroenhancement Lab, LLC | System and method of improving sleep |
US11786694B2 (en) | 2019-05-24 | 2023-10-17 | NeuroLight, Inc. | Device, method, and app for facilitating sleep |
Also Published As
Publication number | Publication date |
---|---|
US6882881B1 (en) | 2005-04-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6882881B1 (en) | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders | |
WO2001028622A2 (en) | Techniques using heat flow management, stimulation, and signal analysis to treat medical disorders | |
Sun et al. | Responsive cortical stimulation for the treatment of epilepsy | |
US9707390B2 (en) | Apparatus for modulation of effector organs | |
Durand et al. | Suppression and control of epileptiform activity by electrical stimulation: a review | |
US6248126B1 (en) | Technique for using heat flow management to treat brain disorders | |
US9707391B2 (en) | Method for modulation of effector organs | |
US10537728B2 (en) | Vagal nerve stimulation to avert or treat stroke or transient ischemic attack | |
JP2023014177A (en) | Devices for treatment of medical disorders | |
Skarpaas et al. | Intracranial stimulation therapy for epilepsy | |
EP3331601B1 (en) | Neuromodulation device | |
US7228171B2 (en) | Signal analysis, heat flow management, and stimulation techniques to treat medical disorders | |
Jobst | Brain stimulation for surgical epilepsy | |
Li et al. | Electrical control of epileptic seizures | |
US20240108880A1 (en) | Vagal nerve stimulation for treating central nervous sytem disorders | |
US7813804B1 (en) | Methods and systems for treating a nerve compression syndrome | |
US20150374994A1 (en) | Systems for treating post-traumatic stress disorder | |
EP3319685B1 (en) | Apparatus for modulation of effector organs | |
US20190201692A1 (en) | Treatment of conditions associated with impaired glucose control |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |