WO2017203301A1

WO2017203301A1 - Operation of a deep brain stimulation (dbs) lead

Info

Publication number: WO2017203301A1
Application number: PCT/GB2017/051541
Authority: WO
Inventors: Binith CHEERAN
Original assignee: Oxford University Innovation Ltd
Current assignee: Oxford University Innovation Ltd
Priority date: 2016-05-27
Filing date: 2017-05-30
Publication date: 2017-11-30
Anticipated expiration: 2018-11-27
Also published as: GB201609377D0

Abstract

A method of determining operation of a deep brain stimulation (DBS) lead 102, 104 comprising a plurality of electrodes 106, 108 is provided. The method comprises detecting an electrophysical signal at two or more of the electrodes and deriving a value representative of the electrophysical signal at each electrode. The method further comprises comparing the derived values and calculating a mathematical function or ratio representative of the magnitudes of the derived values. The method additionally comprises, on the basis of the calculated mathematical function or ratio, evaluating whether all or a subset of the electrodes should be activated for DBS. The method may further comprise mathematically fitting the derived values. A system for determining operation of a deep brain stimulation (DBS) lead using the method is also provided.

Description

Operation of a deep brain stimulation (DBS) lead

Technical Field The present invention relates to a method of and system for determining operation of a deep brain stimulation (DBS) lead. The present invention also relates to a method of performing deep brain stimulation (DBS).

Background to the Invention

A variety of neurological conditions, such as Parkinson's Disease, can be treated with deep brain stimulation (DBS). This has been shown to be effective in reducing the symptoms associated with the condition, e.g. tremors, stiffness and mobility problems, leading to a better quality of life for the person affected by the condition. DBS is a surgical procedure where electrodes are implanted into a patient's brain. The electrodes are electrically connected to a pulse generator that is implanted in the patient's body e.g. in their chest. Activating the pulse generator causes the electrodes to deliver high frequency stimulation to the targeted area. This stimulation changes some of the electrical signals in the brain that cause the symptoms of Parkinson's and other neurological conditions. Advantageously, DBS is a non-destructive and reversible type of surgery. This becomes important where it transpires that the electrodes have been implanted incorrectly, at the wrong position in the brain, causing undesirable, possibly unpleasant, side effects. Ceasing the pulses, and therefore the stimulation, also ceases the (potentially adverse) effects that the stimulation has been providing. However, if the neurological condition still needs to be treated, correcting how the stimulation is applied, and possibly repositioning the implanted electrodes, can be difficult. It is clearly desirable to avoid repeat attempts at implantation due to the risks associated with brain lead insertion. The electrodes are typically located along and at or near the end of a lead (or probe) that is implanted into the patient's brain. Assuming the lead and electrode are positioned correctly, pulses can be used to stimulate nearby neurons. Figure 1 shows a frequency-time log power spectrum where the dark peaks around 22 Hz are representative of high or over-activity in the brain. DBS is applied at a time interval, as shown by the bars on the time axis and it can be seen that, where DBS is utilized, the activity reduces. I.e. this demonstrates the advantageous effect DBS can have on the brain of a person suffering with a neurological condition. For example, DBS is believed to help to modulate the oscillatory activity which occurs between the cortex and the basal ganglia. High frequency DBS is believed to suppress the excess activity at low frequencies e.g. between about 13 and 35 Hz (the beta frequency band) that occurs in Parkinson's Disease.

Up until recently, ring electrodes have been used, as shown in Figure 2. Here, a lead 10 comprises a series of ring electrodes 12 that extend the entire circumference of the cylindrical lead. Electrical connections 14 provide for conveying the generated pulses to one or more of the electrodes 12. In the example shown, the lowermost electrode is providing stimulation. The electrode 12 emits stimulation current I in all directions, as depicted by the arrows. Different sites in the brain will need to be targeted, depending on the condition and/or symptoms to be treated. For example, for treating Parkinson's, the subthalamic nucleus (STN) or the globus pallidus interna (GPi) are commonly targeted. When a DBS lead that is implanted in the brain is activated, it emits an electric field into the surrounding area which, if positioned well, will stimulate the correct part of the brain and provide beneficial effects. However, even correct positioning of the lead 10, and especially incorrect positioning of the lead 10, can provide stimulation to parts of the brain that should not be stimulated. That can lead to adverse effects on the patient.

Split or segmented or non circumferential electrode leads have also been developed, for example as depicted in Figures 3 and 4. Here, electrode portions 16 are provided around the periphery of the lead 10. When activated, the electric field produced is directional, rather than annular, dependent upon the size and positions of the electrode portions 16. This can help avoid stimulating areas of the brain that should not be stimulated (because that would cause unwanted side effects). It is possible to selectively activate one or more of the electrode portions 16.

The lead 10 of Figure 2, where there are four electrode rings 12, provides 4!=24 stimulation permutations or patterns. The lead 10 of Figure 3, where there are 8 electrode portions 16, provides 161=40,320 stimulation permutations or patterns. New/proposed DBS leads may have 40 electrode portions, giving a total number of permutations/patterns equal to 40!, or 8.1591528e+47. Whilst such DBS leads could probably provide near perfect stimulation to control various symptoms, when correct and appropriate DBS stimulation parameters are applied, it would take too long for the neurologist to test all the possible permutations on the patient, meaning that the process is simply unfeasible. Manual selection will be practically unfeasible if the DBS lead has more than 8 electrodes. An initial screening survey conducted for every newly implanted lead, assessing one electrode or contact at a time, will take more than twice as long with double the number of electrodes, and perhaps longer in practice, because a patient cannot be continuously examined for the duration required. As such, whilst multi-electrode leads offer the ability to be able to provide directional stimulation that is potentially beneficial, increasing the number of electrodes compared to standard non-directional ring or paddle electrodes causes major issues. Aspects and embodiments of the present invention have been devised with the foregoing in mind.

Summary of the invention According to a first aspect of the present invention there is provided a method of determining operation of a deep brain stimulation (DBS) lead comprising a plurality of electrodes. The method may comprise detecting an electrophysical signal (e.g. relevant to a particular disease state) at two or more of the electrodes. The method may comprise deriving a value representative of the electrophysical signal at each electrode. The method may comprise comparing the derived values and calculating a mathematical relationship or ratio representative of the relative magnitudes of the derived values. The method may comprise, on the basis of the calculated mathematical function or ratio, evaluating whether all or a subset of the electrodes should be activated for DBS. Preferably the method is, at least in part, computer- implemented.

Advantageously, the method facilitates use of a multi-electrode DBS lead that may have a high number of permutations/patterns in which the electrodes could be operated. The invention advantageously enables an assessment to be made of whether segmented electrodes need to be selected for providing DBS stimulation. The present invention provides for indicating, based on a calculated mathematical function or ratio, whether directional stimulation is needed at all. If not, non-circumferential electrodes at the same transverse level along the longitudinal axis of the DBS lead can be treated as one electrode and activated together to produce an annular electrical field. This reduces the number of permutations to be tested. A further advantage is that the patient is not put under any duress in making this determination - it is done based on signals sensed in the brain i.e. it can be done without applying any stimulation (which could have the potential to cause unwanted side effects).

In an embodiment, the method further comprises fitting the derived values using a mathematical function. The derived values, representative of signals detected at one or more of the electrodes, may be taken together with information about the respective electrode(s). For example, the location of the electrode(s) on the lead, or their relative location(s), may be used. This would define a relationship of the derived values against e.g. a distance or separation, or relative distance or separation. A mathematical fit can then be performed to that data.

The mathematical function may be a conic section or quadric surface. In an embodiment, the method further comprise determining an eccentricity from the fitted conic section or quadric surface.

The method may further comprises determining whether one, some or all of the electrodes should be used for DBS based on the information from the mathematical function or fit e.g. the calculated value of eccentricity. The evaluation of whether some or all of the individual electrodes need to be activated - i.e. whether directional rather stimulation is appropriate - can be made based on the fit parameters. Predetermined criteria may be set for enabling that determination to be made. Where an eccentricity is derived, a calculated value of eccentricity equal to or slightly greater than 0 may be indicative that DBS can be performed using all electrodes. A calculated value of eccentricity greater than zero or above a preset threshold value may be indicative that DBS should be performed using a subset of electrodes only. The comparison with the threshold may be automatically or manually performed. An output, e.g. textual, numeric, visual, graphical etc. may be provided to indicate whetehr directional stimulation is required, The method may further comprise determining a particular subset of electrodes to be used in DBS based on the mathematical function/fit parameters, the derived conic section/quadric surface and/or the eccentricity. I.e. based on identifying which electrodes detected the signals initially, a determination may be made as to which electrodes are needed to provide directional stimulation. These may be the same electrodes, or different.

In a further embodiment, comparing the derived values and calculating the mathematic relationship or ratio comprises plotting the derived values on a graph. Preferably the derived values are plotted radially on the same graph. Each derived value may be plotted at a position along a radially extending axis, and the axes are separated by angles representative of the separation of the electrodes at which the corresponding signals were detected. I.e. a number of axes equal to the number of electrodes may be plotted in x-y space, and the derived values for each electrode may be plotted on the relevant axis. The position of the value along each axis gives a relative relationship between the values derived for each electrode. The radially extending axes may be spaced equidistantly on the graph. This is particularly useful for segmented electrodes within a single "band" at the same longitudinal position along the DBS lead.

Where data is available for more than one "band" or "level" of electrodes spaced at intervals along the longitudinal axis of the DBS lead, the data for each "band" can be plotted at intervals along a third ("z") axis, at a location on the z-axis corresponding to the distance between the electrode bands. That would enable a 3D fit to the data to be made.

In another embodiment, the same calculations and fits are performed, but without actually plotting the data graphically.

Aspects and embodiments of the invention thus use derived mathematical properties of fitting measured data to decide on and/or guide (either manually or automatically) field shaping. A determination can thus be made as to whether directional stimulation is needed on the basis of brain signal measurements.

In an embodiment, detecting an electrophysical signal comprises detecting a local field potential (LFP). Preferably, LFP signals in the beta oscillation range (approximately 13-35Hz) emitted by the subthalamic nucleus (STN) of a person's brain are detected. Alternatively, other neurophysiological signals could be detected e.g. seizure activity. It is beneficial to use the information signals emitted by the brain, but these first have to be interpreted in terms of a meaningful value. A useful value is electrical power. As such, in another embodiment, deriving the values representative of the LFP signal comprises deriving the power.

In an embodiment, the method further comprises displaying or outputting one or more of the derived values e.g. power, the calculated mathematical function or ratio e.g. the conic section or quadric surface, the fit parameters (of e.g. the conic section or quadric surface) and the eccentricity or other derived characteristic. The display or output may be e.g. to a screen, printout or otherwise and may be textual, graphical, visual, audible or otherwise.

According to a second aspect of the present invention there is provided a system for determining operation of a deep brain stimulation (DBS) lead. The system may comprise a deep brain stimulation (DBS) lead comprising a plurality of electrodes, the electrodes being operational to emit a stimulation pulse and/or to detect an electrophysical signal. The system may also comprise a pulse generator operational to command one or more of the electrodes to emit a stimulation pulse and/or to detect an electrophysical signal. A remote control module operational to program the pulse generator to command one or more of the electrodes may also be provided. Software may also be provided, configured to run at the remote control module or other processor to perform the method of any of the first aspect.

In an embodiment, the DBS lead is of circular cross section and the electrodes are distributed around the circumference thereof in a pattern and/or in bands e.g. longitudinally separated along the DBS lead.

In another embodiment, the pulse generator and remote control module are configured for wireless communication and, optionally or preferably, by radio. Other suitable forms of communication may also/instead be used.

The same or different electrodes or contacts may be used for sensing and for stimulation. The electrodes may be configured to detect local field potentials (LFPs). In an embodiment, the electrodes are configured to detect local field potentials (LFPs) in the beta oscillation range (approximately 13-35Hz) emitted by the subthalamic nucleus (STN) of a person's brain. The electrodes may be configured to detect other signals and/or at other frequencies.

According to a third aspect of the present invention, there is provided a method of performing deep brain stimulation (DBS). The method may comprise inserting a DBS lead into a brain or using a DBS lead inserted into a brain. The DBS lead may comprise a plurality of electrodes. The method may also comprise coupling the DBS lead to a remote control module. The method may further comprise performing the method of the first aspect. The method may further comprise using the control module to generate electrical stimulation signals at one or more of the electrodes.

Aspects and embodiments of the invention may be implemented on a computer. There may be provided a computer program, which when run on a computer, causes the computer to perform any method disclosed herein. The computer program may be a software implementation, and the computer may be considered as any appropriate hardware, including a digital signal processor, a microcontroller, and an implementation in read only memory (ROM), erasable programmable read only memory (EPROM) or electronically erasable programmable read only memory (EEPROM), as non-limiting examples. The software implementation may be an assembly program.

The computer program may be provided on a computer readable medium, which may be a physical computer readable medium, such as a disc or a memory device, or may be embodied as a transient signal. Such a transient signal may be a network download, including an internet download.

According to a fourth aspect there is provided a computer program configured to, when executed on a computing device, cause the computing device to perform the method according to the first aspect. Features of the aspects and embodiments described above and below may be used interchangeably and/or in combination, even if not expressly stated.

Aspects and embodiments of the invention will now be described with reference to the Figures of the accompanying drawings in which:

Figure 5 is a schematic view of a system according to an embodiment of the invention; Figure 6 shows an exemplary DBS lead useable in embodiments of the invention, in (a) side and (b) end views; Figure 7 shows a power distribution graph obtained from measurements from a DBS lead (left) and a fitted power distribution graph for that DBS lead (right);

Figure 8 shows a power distribution graph obtained from measurements from another DBS lead (left) and a fitted power distribution graph for that DBS lead (right); and

Figure 9 shows a power distribution graph obtained from measurements from a DBS lead having three bands of electrodes.

Detailed description of embodiments of the invention

Referring to Figure 5, there is shown a system 100 operable for applying deep brain stimulation (DBS) to a patient and for determining what stimulation should be applied. In the embodiment shown, the system comprises two DBS leads 102, 104. The DBS leads 102, 104 are implantable into a patient's brain in accordance with conventional techniques (or other techniques yet to be developed). It will be appreciated that it is not necessary to have two DBS leads - sometimes a single lead can be used for unilateral stimulation; other times multiple leads are used e.g. for treating pain or epilepsy. Each lead comprises a plurality of electrodes 106, 108. In the embodiment of Figure 5, each lead 102, 104 has eight segmented electrodes 106, 108 respectively, but it will be appreciated that any number of electrodes can be provided. Whilst aspects and embodiments of the invention are particularly useful for leads with a high number of segmented electrodes, they are also applicable to leads with a smaller number of segmented electrodes and to ring electrodes etc.

Each electrode 106, 108 is electrically connected to an implantable pulse generator 1 10. This is preferably achieved via one or more wires 112, provided internally of the leads 106, 108. The wires run inside the leads 102, 104 to connect to each electrode 106, 108. The pulse generator 1 10 is typically implanted in a person's body e.g. in their chest, but this need not be the case e.g. during testing of the system. The pulse generator is operable to provide electrical stimulation pulses with parameters (e.g. duration, amplitude, frequency) that can be set dependent upon requirements.

The pulse generator 110 can communicate with a remote control module 112, which is not implanted in the patient's body. A suitable communication link may be radio, but other means of wireless communication are also envisaged. The remote control module 112 can be operated to control the pulses provided by the pulse generator 1 10 and/or to change the programming of the pulse generator 110. Once programmed, the communications link between the control module 112 and the pulse generator 110 is terminated, and the pulse generator will provide pulsed stimulation at a preset intensity, for a preset duration and/or at preset intervals.

Programming is conventionally achieved by manually screening each electrode to determine the benefit to the patient and avoid side-effects that occur at various electrical stimulation parameters. Then, a determination is made of an electrode or a montage of electrodes to be used to optimise the benefit. With more electrodes to test, as with directional DBS leads, the burden on medical service resources and patient discomfort is significantly greater. Aspects and embodiments of the invention assist in optimising this monopolar survey. To make the determination as to whether or not directional stimulation is needed, the implanted leads 102, 104 are also used to record electrophysiological signals.

Different signals can in principle be used, originating from different areas of the brain and from varying distances from the implantation site. Conveniently, the electrodes 106, 108 can detect/record local field potentials (LFPs). Alternatively, additional specialised non-circumferential detectors can be provided on the DBS lead e.g. at the tip of the DBS lead 102, 104.

An LFP is an electrophysiological signal generated by the summed electric current from neuronal assemblies in the brain. Voltage is produced across the local extracellular space by action potentials and graded potentials in neurons in the area, and varies as a result of synaptic activity. "Potential" refers to electrical potential, or voltage, and this can be recorded with the electrodes 106, 108 of the DBS leads 102, 104 when implanted into a patient. LFPs are therefore closely related to the activity of individual neurons. As such, LFPs are useful parameters to record and analyse. Other useful neurophysiological signals, for example seizure activity, can also be detected through DBS leads. Figure 6 shows an exemplary DBS lead 102, 104 that can be used in embodiments of the invention. In the embodiment shown, the lead 102, 104 has segmented electrodes 106 or 108 arranged in a band b around the circumference of the lead 102, 104. This lead 102, 104 has two bands of electrodes and two circumferential or ring electrodes, but it will be appreciated that aspects and embodiments of the invention can utilise a variety of different leads with electrodes varying in number and arrangement. The key is that there are a plurality of electrodes. The invention may be put into effect using LFPs detected by two, three, four or more electrodes. Three or four may be preferable. In an embodiment the plurality of electrodes 106, 108 may be located in the same band b i.e. in the same transverse plane t relative to the longitudinal direction I of the electrode 102, 104. In another embodiment the plurality of electrodes 106, 108 may be located in different bands b i.e. in different transverse planes t relative to the

longitudinal direction I of the electrode 102, 104

In the embodiment of Figure 6, the DBS lead 102, 104 has three electrodes 106, 108 per band b: 106a, 106b, 106c, or 108a, 108b, 108c. Figure 6a shows a side view of the DBS lead 102, 104 and Figure 6b shows an end view, from the direction of the arrow shown in Figure 6a. Figure 6b clearly shows the three electrodes.

A LFP in the beta oscillation range is detected at the electrodes 106 or 108 on a DBS lead 102 or 104, respectively. Figure 7a shows a plot of values derived from signals received at each of electrodes 106a, 106b, 106c, or 108a, 108b, 108c. The plot is a power plot, derived from the LFP measurements. The power axes increase radially outwardly from the central point where the three axes converge. The central point may represent zero power, or some other value. The axes may be scaled as required, and may change depending on the patient or on the measurement being taken. Because there are three electrodes 106a, 106b, 106c, or 108a, 108b, 108c, the centres of those electrodes in the band b are radially separated across the transverse width of the DBS lead 102, 104 by 120°. This is shown in Figures 6b and 7a. Of course, for two electrodes the separation between electrode centres is 180°, for four electrodes it is 90°, for five electrodes it is 72° etc. I.e. the separation is 360 n where n is the number of electrodes 106, 108. The actual detected/derived power from each electrode 106a, 106b, 106c, or 108a, 108b, 108c is represented on the plot as Ma, Mb, Mc respectively.

The plot shows a series of concentric circles depicting equal power values for each of the three electrodes 106a, 106b, 106c, or 108a, 108b, 108c. In the example shown, it can be seen that all three electrodes 106a, 106b, 106c, or 108a, 108b, 108c have recorded substantially the same LFP or power. The measurement points are therefore equidistant from the axes convergence point.

Figure 8a also shows a plot of measurements from the lead of Figure 6. Here, the electrodes 106a, 106b, 106c, or 108a, 108b, 108c have detected different LFPs, meaning the measurement points are not all equidistant along the axes from the centre of the plot. Electrode 106b/108b detected a larger LFP than electrodes 106a/108a or 106C/108C.

A conic section can be fitted for the three measurement points Ma, Mb, Mc. Most often, all three measurements Ma, Mb, Mc will be able to be plotted on the plot. In that case, the fitted conic section will be a circle or an ellipse. However, it is conceivable that sometimes not all three measurements might be present on the plot e.g. if one of the measurements might give a reading off the scale of the plot, or one of the electrodes might not working. In that case, the fitted conic section will be a parabola, or will not be able to be fitted from the data.

Figure 7b shows a conic section C fitted through the measurement points Ma, Mb, Mc from Figure 7a. Since all measurement points were equidistant from the plot centre, the resulting conic section is a circle.

Figure 8b shows a conic section C fitted through the measurement points Ma, Mb, Mc from Figure 8a. Since all measurement points were not equidistant from the plot centre, the resulting conic section is an ellipse.

The eccentricity of the fitted conic section can be determined. For the example of Figure 7b, the conic section is a circle which has an eccentricity e=0. For the example of Figure 8b, the conic section is an ellipse which has an eccentricity e≠0. In that case the eccentricity has a value 0<e≤1. In practice, the eccentricity might be unlikely to equal 1 , so mostly the eccentricity will have a value 0<e<1.

Where data is available for more than one "band" or "level" of electrodes, spaced at intervals along the longitudinal axis of the DBS lead, the data can be displayed by adding a third ("z") axis value, at a location on the z-axis corresponding to the distance between the electrode bands. For example, if a DBS lead has a "1-3-3-1" configuration (a first circumferential electrode, two bands of three segmented electrodes and a fourth circumferential electrode), LFP data will be available for all electrodes, and they can all be represented on the same plot, by adding a z-value equal to the spacing between levels (which may typically be about 0.5 - 1.5mm spacing).

In another embodiment, LFP measurements are taken from electrodes in more than one band b. In that case the plot would be three-dimensional. An example is shown in Figure 9. Here, power measurements (represented by the solid spots) from three bands bi , b₂, b₃ of three electrodes are represented. The vertical separations z=d₁₂, d₂3 between adjacent radial (x,y) plots are representative of the distance between the adjacent bands b1 , b2 and b3. A quadric surface Q may be fitted e.g. an ellipsoid. In that case the eccentricity is the eccentricity of a designated section of it.

The ellipse fit may be performed using a known fitting method, e.g. MathWorks fitellipse, LMS, RANSAC, PRANSAC or any other suitable method.

More than one method of ellipse fitting is possible. The method of ellipse fitting can be selected based on the physiological target, the physiological signal recorded, electrical characteristics of the lead, and the system or technical capabilities of each DBS system.

The method of aspects and embodiments of the invention allows for an estimation of signal field (the volume and shape of tissue generating signal), and not just the direction from which the maximum signal is being generated. This allows for estimation of stimulation energy (through a electric field estimation model of stimulation) required to closely match the signal field, avoiding the need for or providing a starting point for programming of stimulation systems. Technical limitations of DBS devices mean that coverage of the signal field may be superior when matching the size and shape of the signal field rather than direction alone. Direction (centroid of stimulation field), size of stimulation field and shape of stimulation field co-vary with current systems and cannot be varied independently. The mathematical properties of the fitted conic section C or quadric surface - i.e. the derived eccentricity value e - can be used to predict the likelihood that a clinician programmer of the DBS lead needs to explore directional stimulation.

Where a value of e closer to 1 has been obtained, i.e. where some or all of the electrodes have measured different LFP values, this may indicate that it would not be necessary or might not be beneficial to activate all of those electrodes. The direction from which the LFP is originating is where the DBS stimulation needs to be directed. As such, it would be better to only activate certain electrodes, and not all of them. Activating all electrodes could, instead, cause adverse effects, as stimulation pulses could be directed towards other parts of the brain that do not need or should not be stimulated.

On the other hand, where a value of e closer to 0 has been obtained, i.e. where all electrodes have measured equal, or substantially equal, LFP values, this indicates that activation of all of those electrodes for DBS is acceptable. For example, the DBS lead 102, 104 may have been implanted in a very good location, close to the STN that is desired to be stimulated, such that the DBS lead 102, 104 is receiving LFP signals equally from the STN. That in turn implies that DBS stimulation signals emitted from all electrodes would also be received at the STN and therefore full activation of all electrodes would be acceptable and beneficial to the patient.

For situations in between, the eccentricity can be considered as a probability for needing directional stimulation. A preset threshold could be defined, and/or the clinician can use their judgment. Thresholds/ranges can be provided for each DBS lead type combination, as the thresholds for using directionality will vary with the equipment being used.

As such, the calculated eccentricity or other mathematical properties (e.g. taking the power values, calculating a ratio between the power values, normalising the power values against each other or a threshold etc.) can be used to determine whether directional stimulation is needed. It can also be used to determine the direction of the stimulation. For example, the angle subtended by the major axis can be used to predict where the centroid of the volume tissue to be activated lies relative to the lead 102, 104. The area or volume of the conic section or quadric surface can be used to assess the adequacy of the implant location.

Aspects and embodiments of the invention thus enable prediction of whether more extensive testing of directional (current steering) electrodes is needed. Furthermore, Aspects and embodiments of the invention can guide field shaping when programming directional stimulation, based on electrophysiological data collected from the directional lead itself. This can guide either manual or automated programming. Referring back to the discussion above, new/proposed DBS leads may have 40 electrode portions, giving a total number of permutations/patterns equal to 40!, or 8.1591528e+47. Using aspects and embodiments of the present invention can indicate, based on calculated eccentricity values of 0, or near 0, that directional stimulation is not needed. Where directional stimulation is not needed, any non- circumferential electrodes at the same transverse level can be treated as one electrode and activatged together to produce an annular electric field. This reduces the number of permutations to be tested. Sometimes, none of these permutations need be tested. That means the patient is not put under any duress, since the determination is made by looking at LFP values received by the DBS leads only - it is not necessary to also test the DBS stimulation in the patient (which could have the potential to cause unwanted side effects). In other cases, aspects and embodiments of the present invention can be used to provide an indication of the direction in which stimulation should be applied. That means that only a subset of the 40 (or other number) electrodes have to be tested. Being able to eliminate a substantial number of electrodes to reduce the factorial calculation will drastically reduce the test time on the patient. This is clearly beneficial for the patient, and for hospital resources, clinician time spent etc.

A further benefit of aspects and embodiments of the present invention is that the eccentricity value derived is a ratio, that may be between and including 0 and 1. As such, it is standardized for use by different clinicians. It is also believed to be reliable for both mild and strong forms of Parkinson's Disease.

Additionally, the patient's situation (and the eccentricity derivable from measurements) could change over time. This could be caused by physical changes in the brain, disease progression, scarring around the lead, movement of the implanted lead etc.

Aspects and embodiments of the present invention allow for an easy assessment to be made as to whether or not the current DBS stimulation regime is appropriate. For example, if full DBS stimulation (all electrodes) has been used for a patient, but they start to experience undesirable side effects, new LFP recordings can be obtained from the chronically implanted lead (as enabled by existing devices such as the Medtronic PC&S or similar devices in the future). Eccentricity values can be re-calculated to determine whether it is the stimulation that is causing those side effects - i.e. whether full stimulation is still appropriate - or whether directional stimulation would be better. In the latter case, the patient can be tested to determine appropriate directional stimulation at that time.

Although the appended claims are directed to particular combinations of features, it should be understood that the scope of the disclosure of the present invention also includes any novel feature or any novel combination of features disclosed herein either explicitly or implicitly or any generalisation thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention.

Features which are described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

For the sake of completeness it is also stated that the term "comprising" does not exclude other elements or steps, the term "a" or "an" does not exclude a plurality, and any reference signs in the claims shall not be construed as limiting the scope of the claims.

Claims

1. A method of determining operation of a deep brain stimulation (DBS) lead comprising a plurality of electrodes, the method comprising:

detecting an electrophysical signal at two or more of the electrodes;

deriving a value representative of the electrophysical signal at each electrode; comparing the derived values and calculating a mathematical function or ratio representative of the relative magnitudes of the derived values; and

on the basis of the calculated mathematical function or ratio, evaluating whether all or a subset of the electrodes should be activated for DBS.

2. The method of claim 1 , further comprising fitting the derived values using a mathematical function.

3. The method of claim 2, wherein the mathematical function is a conic section or quadric surface.

4. The method of claim 3, further comprising determining an eccentricity from the fitted conic section or quadric surface.

5. The method of claim 4, further comprising determining whether one, some or all of the electrodes should be used for DBS based on the calculated value of eccentricity.

6. The method of claim 5, wherein a calculated value of eccentricity equal to or slightly greater than 0 is indicative that DBS can be performed using all electrodes.

7. The method of claim 5 or 6, wherein a calculated value of eccentricity greater than zero or above a preset threshold value is indicative that DBS should be performed using a subset of electrodes only.

8. The method of any of claims 5 to 7, further comprising determining a particular subset of electrodes to be used in DBS based on the derived conic section/quadric surface and/or eccentricity.

9. The method of any preceding claim, wherein comparing the derived values and calculating the mathematic relationship or ratio comprises radially plotting the derived values on a graph.

10. The method of claim 9, wherein each derived value is plotted at a position along a radially extending axis, and the axes are separated by angles representative of the separation of the electrodes at which the corresponding signals were detected.

1 1. The method of claim 10, wherein the radially extending axes are spaced equidistantly on the graph.

12. The method of any preceding claim, wherein detecting an electrophysical signal comprises detecting a local field potential (LFP) in the beta oscillation range (approximately 13-35Hz) emitted by the subthalamic nucleus (STN) of a person's brain.

13. The method of claim 12, wherein deriving the values representative of the LFP signal comprises deriving the power.

14. The method of any preceding claim, further comprising displaying or outputting one or more of the derived values, the calculated mathematical function or ratio, the fit parameters and the eccentricity.

15. A system for determining operation of a deep brain stimulation (DBS) lead, the system comprising:

a deep brain stimulation (DBS) lead comprising a plurality of electrodes, the electrodes being operational to emit a stimulation pulse and/or to detect an electrophysical signal;

a pulse generator operational to command one or more of the electrodes to emit a stimulation pulse and/or to detect an electrophysical signal;

a remote control module operational to program the pulse generator to command one or more of the electrodes; and

software configured to run at the remote control module or other processor to perform the method of any of claims 1 to 14.

16. The system of claim 15, wherein the DBS lead is of circular cross section and the electrodes are distributed around the circumference thereof in a pattern and/or in bands.

17. The system of claim 16 or 17, wherein the pulse generator and remote control module are configured for wireless communication and, optionally or preferably, by radio.

18. The system of any of claims 15 to 17, wherein the electrodes are configured to detect local field potentials (LFPs) and, optionally or preferably, wherein the electrodes are configured to detect local field potentials (LFPs) in the beta oscillation range (approximately 13-35Hz) emitted by the subthalamic nucleus (STN) of a person's brain.

19. A method of performing deep brain stimulation (DBS), the method comprising: inserting a DBS lead into a brain or using a DBS lead inserted into a brain, the

DBS lead comprising a plurality of electrodes;

coupling the DBS lead to a remote control module;

performing the method of any of claims 1 to 14; and

using the control module to generate electrical stimulation signals at one or more of the electrodes.

20. A computer program configured to, when executed on a computing device, cause the computing device to perform the method according to any of claims 1 to 14.

21. A system substantially as hereinbefore described with reference to Figure 6 of the accompanying drawings.