Methods and systems for neural response measurement during charging of a neuromodulation device

Abstract

Disclosed is an implantable device comprising a charging component configured to perform wireless charging of an energy storage device of the implantable device. The implantable device further comprises a measurement amplifier configured to amplify a signal between a first input node and a second input node of the measurement amplifier subsequent to provision of a neural stimulus to evoke a neural response from a neural pathway, the signal comprising the evoked neural response. The implantable device further comprises one or more control elements connected to the first input node and the second input node of the measurement amplifier. The implantable device further comprises a control unit, where the control unit is configured to measure a characteristic of the evoked neural response of the amplified signal. The control unit is further configured to operate the one or more control elements to maintain, during an autozeroing phase comprising a period of time immediately preceding the measurement of the characteristic of the evoked neural response from the amplified signal, a fixed potential at the first input node and a fixed potential at the second input node of the measurement amplifier.

Description

METHODS AND SYSTEMS FOR NEURAL RESPONSE MEASUREMENT DURING CHARGING OF A NEUROMODULATION DEVICE

[0001] The present application claims priority from Australian Provisional Patent Application No.2024904280 filed on 23 December 2024, the contents of which are incorporated herein by reference in their entirety.TECHNICAL FIELD

[0002] The present invention relates to systems, devices, and methods for performing neuromodulation on a patient, such as for example via a neuromodulation device powered by an energy storage device (e.g., a battery), and in particular to mitigating a noise effect of wireless charging of the energy storage device on measurement of a neural response by the neuromodulation device.BACKGROUND OF THE INVENTION

[0003] There are a range of situations in which it is desirable to apply neural stimuli in order to alter neural function, a process known as neuromodulation. For example, neuromodulation is used to treat a variety of disorders including chronic pain, movement disorders, and voiding disorders. A neuromodulation device applies an electrical pulse (stimulus) to neural tissue (fibres, or neurons) in order to generate a therapeutic effect. In general, the electrical stimulus generated by a neuromodulation device evokes a neural response known as an action potential in a neural fibre which then has either an inhibitory or excitatory effects on neural networks. Inhibitory effects can be used to modulate an undesired process such as the transmission of pain, or excitatory effects may be used to cause a desired effect such as the contraction of a muscle.

[0004] When used to relieve neuropathic pain originating in the trunk and limbs, the electrical pulse is applied to the dorsal column (DC) of the spinal cord, a procedure referred to as spinal cord stimulation (SCS). Such a device typically comprises an implanted electrical pulse generator, and a power source such as a battery that may be transcutaneously rechargeable by wireless means, such as inductive transfer. An electrode array is connected to the pulse generator, and is implanted adjacent the target neural fibre(s) in the spinal cord, typically in the dorsal epidural space above the dorsal column. An electrical pulse of sufficient intensity applied to the target neural fibres by a stimulus electrode causes the depolarisation of neurons in the fibres, which in turn generates an action potential in the fibres. Action potentials propagate along the fibres in an orthodromic direction (in afferent fibres this means towards the head, or rostral) and in an antidromic direction (in afferent fibres this means towards the cauda, or caudal). Action potentials propagating along A0 (A-beta) fibres beingstimulated in this way may inhibit the transmission of pain from a region of the body innervated by the target neural fibres (the dermatome) to the brain. To sustain the pain relief effects, stimuli are applied repeatedly, for example at a stimulus frequency in the range of 30 Hz - 100 Hz.

[0005] For effective and comfortable neuromodulation, it is necessary to maintain stimulus intensity above a recruitment threshold. Stimuli below the recruitment threshold will fail to recruit sufficient neurons to generate action potentials with a therapeutic effect. In some neuromodulation applications, response from a single class of fibre is desired, but the stimulus waveforms employed can evoke action potentials in other classes of fibres which cause unwanted side effects. In pain relief, it is therefore desirable to apply stimuli with intensity below a discomfort threshold, above which uncomfortable or painful percepts arise due to over-recruitment of A0 fibres or recruitment of undesired fibre classes. When recruitment is too large, A0 fibres produce uncomfortable sensations. Stimulation at high intensity may even recruit AS (A-delta) fibres, which are sensory nerve fibres associated with acute pain, cold and heat sensation. It is therefore desirable to maintain stimulus intensity within a therapeutic range between the recruitment threshold and the discomfort threshold.

[0006] The task of maintaining appropriate neural recruitment is made more difficult by electrode migration (change in position over time) or postural changes of the implant recipient (patient), either of which can significantly alter the neural recruitment arising from a given stimulus, and therefore the therapeutic range. The spinal cord itself moves within the cerebrospinal fluid (CSF) with respect to the dura and the electrode array. During postural changes, the distance between the spinal cord and the electrode can change significantly. This effect is so large that postural changes alone can cause a previously comfortable and effective stimulus regime to become either ineffectual or painful.

[0007] Another control problem facing neuromodulation devices of all types is achieving neural recruitment at a sufficient level for therapeutic effect, but at minimal expenditure of energy. The power consumption of the stimulation paradigm has a direct effect on battery requirements which in turn affects the device’s physical size and lifetime. For rechargeable devices, increased power consumption results in more frequent charging and, given that batteries only permit a limited number of charging cycles, this ultimately reduces the implanted lifetime of the device.

[0008] Attempts have been made to address such problems by way of feedback or closed-loop control, such as using the methods set forth in International Patent Publication No. WO2012 / 155188 by the present applicant, the content of which is incorporated herein by reference. Feedback control seeks to compensate for relative nerve / electrode movement by controlling the intensity of the delivered stimuli to maintain neural recruitment at or near a target value. The intensity of a neural response evoked by a stimulus may be used as a feedback variable representative of the amount ofneural recruitment. A signal representative of the neural response may be sensed by a measurement electrode in electrical communication with the recruited neural fibres, and processed to obtain the feedback variable. Based on the response intensity, the intensity of the applied stimulus may be adjusted to bring the response intensity closer to the target value.

[0009] It is therefore desirable to accurately measure the intensity and other characteristics of a neural response evoked by the stimulus. The action potentials generated by the depolarisation of a large number of fibres by a stimulus sum to form a measurable signal known as an evoked compound action potential (ECAP). Accordingly, an ECAP is the sum of responses from a large number of single fibre action potentials. The ECAP generated from the depolarisation of a group of similar fibres may be sensed by a measurement electrode as a positive peak potential, then a negative peak, followed by a second positive peak. This morphology is caused by the region of activation passing the measurement electrode as the action potentials propagate along the individual fibres.

[0010] Approaches proposed for obtaining a neural response measurement are described by the present applicant in International Patent Publication No. WO2012 / 155183, the content of which is incorporated herein by reference.

[0011] However, neural response measurement can be a difficult task as a neural response component in the sensed signal will typically have a maximum amplitude in the range of microvolts. In contrast, a stimulus applied to evoke the response is typically several volts, and manifests in the sensed signal as crosstalk of that magnitude. Moreover, stimulus generally results in electrode artefact, which may manifest in the sensed signal as a decaying output of the order of several millivolts after the end of the stimulus. As the neural response can be contemporaneous with the stimulus crosstalk or the stimulus artefact, neural response measurements present a difficult challenge of measurement amplifier design. For example, to resolve a 10 pV ECAP with 1 pV resolution in the presence of stimulus crosstalk of 5 V requires an amplifier with a dynamic range of 134 dB, which is impractical in implantable devices. In practice, many non-ideal aspects of a circuit lead to artefact, and as these aspects mostly result in a time-decaying artefact waveform of positive or negative polarity, their identification and elimination can be laborious.

[0012] Evoked neural responses are less difficult to measure when they appear later in time than the artefact, or when the signal-to-artefact ratio is sufficiently high. The artefact decays over a time of 1 to 2 ms after the stimulus and so, provided the neural response is measured after this time window, a neural response measurement can be more easily obtained. This is the case in surgical monitoring where there are large distances (e.g. more than 12 cm for nerves conducting at 60 ms'1) between thestimulus and measurement electrodes so that the propagation time from the stimulus site to the measurement electrodes exceeds 2 ms, which is longer than the typical duration of stimulus artefact.

[0013] However, to characterize the responses from the dorsal column, high stimulation currents are required. Similarly, any implanted neuromodulation device will necessarily be of compact size, so that for such devices to monitor the effect of applied stimuli, the stimulus electrode(s) and measurement electrode(s) will necessarily be in close proximity (e.g. less than 5 cm). In such situations the measurement process must overcome artefact directly.

[0014] The difficulty of this problem is further exacerbated when attempting to implement CAP detection in an implanted device. Typical implanted devices have a power budget that permits a limited number, for example in the hundreds or low thousands, of processor instructions per stimulus, in order to maintain a desired battery lifetime. Accordingly, if a CAP detector for an implanted device is to be used regularly (e.g. ten to fifty a second), then care must be taken that the detector should consume only a small fraction of the power budget.

[0015] A functional feedback loop can also produce useful data for live operation or post-analysis, such as observed neural response intensity and applied stimulus intensity. However, device operation at tens of Hz over the course of hours or days quickly produces large volumes of such data which far exceed an implanted device’s data storage capacities.

[0016] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present Background is solely for the purpose of providing a context for the present technology. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present technology as it existed before the priority date of each claim of the present disclosure.SUMMARY OF THE INVENTION

[0017] According to a first aspect of the present technology, there is provided an implantable device comprising: a charging component configured to perform wireless charging of an energy storage device of the implantable device; a measurement amplifier configured to amplify a signal between a first input node and a second input node of the measurement amplifier subsequent to provision of a neural stimulus to evoke a neural response from a neural pathway, the signal comprising the evoked neural response; one or more control elements connected to the first input node and the second input node of the measurement amplifier; and a control unit configured to: measure a characteristic of the evoked neural response of the amplified signal; and operate the one or more control elements to maintain, during an autozeroing phase comprising a period of time immediately preceding the measurement of the characteristic of the evoked neural response from the amplified signal, a fixedpotential at the first input node and a fixed potential at the second input node of the measurement amplifier.

[0018] In some implementations of the first aspect, each fixed potential is common to the first input node and the second input node of the measurement amplifier.

[0019] In some implementations, the fixed and common potential is one of a ground potential of the implantable device; and a system potential of the implantable device.

[0020] In some implementations, the signal is provided to the first input node of the measurement amplifier by a first measurement electrode and to the second input node of the measurement amplifier by a second measurement electrode.

[0021] In some implementations, the control unit is further configured to operate the one or more control elements to electrically disconnect each of the first and second measurement electrodes from the respective first and second input nodes of the measurement amplifier during the autozeroing phase.

[0022] In some implementations, the control unit is further configured to operate the one or more control elements to electrically reconnect each of the first and second measurement electrodes to the respective first and second input nodes of the measurement amplifier following a buffer period of time commencing at the termination of the autozeroing phase.

[0023] In some implementations, the control unit is further configured to operate the one or more control elements to electrically disconnect each of the first and second measurement electrodes from the respective first and second input nodes of the measurement amplifier during a stimulation phase preceding the autozeroing phase, the stimulation phase comprising a period of time in which the neural stimulus is provided.

[0024] In some implementations, the control unit is further configured to control a stimulus source, wherein the stimulus source is configured to deliver the neural stimulus to the neural pathway via one or more stimulation electrodes comprising at least one return electrode.

[0025] In some implementations, the control unit is configured to operate the one or more control elements to, at or immediately following commencement of the autozeroing phase, electrically connect the first input node and the second input node of the measurement amplifier to respective first and second return electrodes of the one or more stimulation electrodes, the first and second return electrodes being connected to a fixed and common potential.

[0026] In some implementations, the respective first and second return electrodes are the same return electrode.

[0027] In some implementations, the control unit is further configured to operate the one or more control elements to electrically disconnect the first input node and the second input node of the measurement amplifier from the respective first and second return electrodes, at or immediately following termination of the autozeroing phase.

[0028] In some implementations, the measurement amplifier comprises a plurality of stages, and wherein the autozeroing phase persists while at least one of the plurality of stages is subject to autozeroing.

[0029] In some implementations, a first stage of the measurement amplifier ceases autozeroing after a first period of time of the autozeroing phase, and wherein one or more other stages of the measurement amplifier are still subject to autozeroing at an end of the first period of time.

[0030] In some implementations, the control unit is configured to store the fixed potentials on respective input capacitors of the measurement amplifier during the autozeroing phase.

[0031] In some implementations, the one or more control elements comprise one or more electrical switches.

[0032] According to a second aspect of the present technology, there is provided a method for measuring a characteristic of an evoked neural response by an implantable device, the method comprising: measuring a characteristic of an evoked neural response of a signal between a first input node and a second input node of a measurement amplifier of the implantable device subsequent to provision of a neural stimulus to evoke the neural response from a neural pathway; and maintaining, during an autozeroing phase comprising a period of time immediately preceding the measurement of the characteristic of the evoked neural response, a fixed potential at the first input node and a fixed potential at the second input node of the measurement amplifier.

[0033] In some implementations of the second aspect, each fixed potential is common to the first input node and the second input node of the measurement amplifier.

[0034] In some implementations, the signal is provided to the first input node of the measurement amplifier by a first measurement electrode and to the second input node of the measurement amplifier by a second measurement electrode, and wherein the method further comprises: electrically disconnecting each of the first and second measurement electrodes from the respective first and second input nodes of the measurement amplifier during at least the autozeroing phase.

[0035] In some implementations, the method further comprises electrically reconnecting each of the first and second measurement electrodes to the respective first and second input nodes of the measurement amplifier following a buffer period of time commencing at the termination of the autozeroing phase.

[0036] In some implementations, the neural stimulus is delivered via one or more stimulation electrodes comprising at least one return electrode.

[0037] In some implementations, the method further comprises, at or immediately following commencement of the autozeroing phase, electrically connecting the first input node and the second input node of the measurement amplifier to respective first and second return electrodes of the one or more stimulation electrodes, the first and second return electrodes being connected to a fixed and common potential.

[0038] In some implementations, the method further comprises electrically disconnecting the first input node of the measurement amplifier and the second input node of the measurement amplifier from the respective first and second return electrodes, at or immediately following termination of the autozeroing phase.

[0039] In some implementations, the method further comprises storing the fixed potentials on respective input capacitors of the measurement amplifier during the autozeroing phase.

[0040] In some implementations, the maintaining takes place during wireless charging of an energy storage device of the implantable device.

[0041] According to a third aspect of the present technology, there is provided a neural stimulation device configured to measure a neural response evoked in a neural pathway in response to a neural stimulus, the neural stimulation device comprising a controller configured to: amplify, using a measurement amplifier, a signal provided at one or more input nodes of the measurement amplifier subsequent to provision of the neural stimulus, the signal comprising the evoked neural response; and operate one or more control elements of the neural stimulation device to maintain, during autozeroing of the measurement amplifier, respective fixed potentials at the one or more input nodes of the measurement amplifier.

[0042] In some implementations, the measurement amplifier has a first input node maintained at a first fixed potential and a second input node maintained at a second fixed potential.

[0043] In some implementations, the first fixed potential and the second fixed potential are common or substantially common.

[0044] The present technology has been developed primarily for use in or with neuromodulation of the spinal cord and will be described hereinafter mostly with reference to this application. However, it will be appreciated that the present technology is not limited to this particular field of use, and may be applied in other neuromodulation contexts, including but not limited to sacral nerve stimulation, pudendal nerve stimulation, deep brain stimulation, stimulation of other parts of the peripheral and central nervous system. It will further be appreciated that the present technology may be applied fortreatment of conditions other than chronic pain, including but not limited to movement disorders, Crohn’s disease, rheumatoid arthritis, diabetes, Reynaud’s phenomenon, pelvic floor disorders, chronic inflammatory conditions, migraine, stroke, or depression.BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Notwithstanding any other implementations which may fall within the scope of the present invention, one or more implementations of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0046] Fig. 1 schematically illustrates an implanted spinal cord stimulator, according to one implementation of the proposed technology;

[0047] Fig. 2 is a block diagram of the stimulator of Fig. 1;

[0048] Fig. 3 is a schematic illustrating interaction of the implanted stimulator of Fig. 1 with a bundle of target nerve fibres;

[0049] Fig. 4a illustrates an idealised activation plot for one posture of a patient undergoing neural stimulation;

[0050] Fig. 4b illustrates the variation in the activation plots with changing posture of the patient;

[0051] Fig. 5 is a schematic illustrating elements and inputs of a closed-loop neural stimulation (CLNS) system implementable by the electronics module of Fig. 2, according to one implementation of the proposed technology;

[0052] Fig. 6 illustrates the typical form of an electrically evoked compound action potential (ECAP) of a healthy subject;

[0053] Fig. 7 is a block diagram of a neural stimulation therapy system including the implanted stimulator of Fig. 1 according to one implementation of the proposed technology;

[0054] Fig. 8 is an illustration of the stimulus pulses delivered by a stimulation program with four interleaved stimulation sets (stimsets);

[0055] Fig. 9 is a schematic illustrating elements and inputs of a multi-stimset closed-loop neural stimulation (CLNS) system implementable by the electronics module of Fig. 2, according to one implementation of the proposed technology;

[0056] Fig. 10 is a block diagram illustrating the data flow of a neural stimulation therapy system such as the system of Fig. 7;

[0057] Fig. 1 la is a schematic illustrating a configuration for wireless charging of an energy storage device of an implantable neuromodulation device;

[0058] Fig. 1 lb is a schematic of a circuit model of charging circuitry and measurement circuitry of the implantable neuromodulation device of Fig. Ila;

[0059] Fig. 12 is a schematic of a circuit model of an implantable neuromodulation device, according to some implementations of the proposed technology;

[0060] Fig. 13a is a schematic of a first example circuit of the model of the implantable neuromodulation device depicted in Fig. 12, according to some implementations of the proposed technology;

[0061] Fig. 13b is a schematic of a second example circuit of the model of the implantable neuromodulation device depicted in Fig. 12, according to some implementations of the proposed technology;

[0062] Fig. 13c is a schematic of a third example circuit of the model of the implantable neuromodulation device depicted in Fig. 12, according to some implementations of the proposed technology;

[0063] Fig. 13d is a schematic of a fourth example circuit of the model of the implantable neuromodulation device depicted in Fig. 12, according to some implementations of the proposed technology;

[0064] Fig. 14a is a flow diagram of a method for measuring a characteristic of an evoked neural response according to some implementations of the proposed technology;

[0065] Fig. 14b is a timing graph of operational phases of the implantable neuromodulation device used for measuring a characteristic of an evoked neural response according to the method of Fig. 14a;

[0066] Fig. 15 is a flow diagram of a method for operating a neuromodulation device to maintain a fixed potential at the input(s) of a measurement amplifier for the method of measuring a characteristic of an evoked neural response of Fig. 14a;

[0067] Fig. 16a is a schematic of an example circuit model of an implantable neuromodulation device with a three-stage measurement amplifier configured to measure a characteristic of an evoked neural response, at a time prior to the end of the stimulation phase, according to some implementations of the proposed technology;

[0068] Fig. 16b is a schematic of the example circuit of Fig. 16a at the commencement of the autozeroing phase, according to some implementations of the proposed technology;

[0069] Fig. 16c is a schematic of the example circuit model of Fig. 16b after a first period of the autozeroing phase, according to some implementations of the proposed technology;

[0070] Fig. 16d is a schematic of an example circuit model of Fig. 16c after one or more subsequent periods of time following the first period of the autozeroing phase, according to some implementations of the proposed technology;

[0071] Fig. 17a is a graph of a set of evoked neural responses measured from an implantable neuromodulation device implemented according to the circuit model of Fig. 11b, in the absence of charging of the implantable neuromodulation device;

[0072] Fig. 17b is a graph of a set of evoked neural responses measured from an implantable neuromodulation device implemented according to the circuit model of Fig. 1 lb, during charging of the implantable neuromodulation device;

[0073] Fig. 18a is a graph of a feedback variable histogram for performing closed-loop neural stimulation (CLNS) using evoked neural responses of an implantable neuromodulation device implemented according to the circuit model of Fig. 1 lb, in the absence of charging of the implantable neuromodulation device;

[0074] Fig. 18b is a graph of a feedback variable histogram 1802 for performing CLNS using evoked neural responses of an implantable neuromodulation device implemented according to the circuit model of Fig. 1 lb, during charging of the implantable neuromodulation device;

[0075] Fig. 19a is a graph of a stimulation current histogram of stimulation currents provided by an implantable neuromodulation implemented according to the circuit model of Fig. 1 lb, and performing CLNS using a feedback variable conforming to the histogram of Fig. 18a,;

[0076] Fig. 19b is a graph of a stimulation current histogram of stimulation currents provided by an implantable neuromodulation implemented according to the circuit model of Fig. 1 lb, and performing CLNS using a feedback variable conforming to the histogram of Fig. 18b;

[0077] Fig. 20a is a graph of a set of evoked neural responses measured from an implantable neuromodulation device implemented according to the circuit model of Fig. 12, in the absence of charging of the implantable neuromodulation device, according to some implementations of the proposed technology;

[0078] Fig. 20b is a graph of a set of evoked neural responses measured from an implantable neuromodulation device implemented according to the circuit model of Fig. 12, during charging of the implantable neuromodulation device, according to some implementations of the proposed technology;

[0079] Fig. 21a is a graph of a feedback variable histogram for performing CLNS using evoked neural responses of an implantable neuromodulation device implemented according to the circuit model of Fig. 12, in the absence of charging of the implantable neuromodulation device, according to some implementations of the proposed technology; and

[0080] Fig. 21b is a graph of a feedback variable histogram 1802 for performing CLNS using evoked neural responses of an implantable neuromodulation device implemented according to the circuitmodel of Fig. 12, during charging of the implantable neuromodulation device, according to some implementations of the proposed technology.DETAILED DESCRIPTION OF THE PRESENT TECHNOLOGY

[0081] Fig. 1 schematically illustrates an implanted spinal cord stimulator 100 in a patient 108, according to one implementation of the present technology. Stimulator 100 comprises an electronics module 110 housed within a conductive case, implanted at a suitable location. In one implementation, stimulator 100 is implanted in the patient’s lower abdominal area or posterior superior gluteal region. In other implementations, the electronics module 110 is implanted in other locations, such as in a flank or sub-clavicularly. The electronics module 110 is configured to electrically connect to an electrode assembly, typically comprising an electrode array 150 implanted within the epidural space and connected to the module 110 by a suitable lead. The electrode array 150 may comprise one or more electrodes such as electrode pads on a paddle lead, circular (e.g., ring) electrodes surrounding the body of a percutaneous lead, conformable electrodes, cuff electrodes, segmented electrodes, or any other type of electrodes capable of forming unipolar, bipolar or multipolar electrode configurations for stimulation and measurement. The electrodes may pierce or affix directly to the tissue itself.

[0082] Numerous aspects of the operation of implanted stimulator 100 may be programmable by an external computing device 192, which may be operable by a user such as a clinician or the patient 108. Moreover, implanted stimulator 100 serves a data gathering role, with gathered data being communicated to external device 192 via a transcutaneous communications channel 190. Communications channel 190 may be active on a substantially continuous basis, at periodic intervals, at non-periodic intervals, or upon request from the external device 192. External device 192 may thus provide a clinical interface configured to program the implanted stimulator 100 and recover data stored on the implanted stimulator 100. This configuration is achieved by program instructions collectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the clinical interface.

[0083] Fig. 2 is a block diagram of the stimulator 100. Electronics module 110 contains a battery 112 and a telemetry module 114. In implementations of the present technology, any suitable type of transcutaneous communications channel 190, such as infrared (IR), radiofrequency (RF), capacitive or inductive transfer, may be used by telemetry module 114 to transfer power or data to and from the electronics module 110 via communications channel 190. Module controller 116 has an associated memory 118 storing one or more of clinical data 120, clinical settings 121, control programs 122, and the like. Controller 116 is configured by control programs 122, sometimes referred to as firmware,to control a pulse generator 124 to generate stimuli, such as in the form of electrical pulses, in accordance with the clinical settings 121. Electrode selection module 126 switches the generated pulses to the selected electrode(s) of electrode array 150, for delivery of the pulses to the tissue surrounding the selected electrode(s). Measurement circuitry 128, which may comprise an amplifier or an analog-to-digital converter (ADC), is configured to process signals comprising neural responses sensed by measurement electrode(s) of the electrode array 150 as selected by electrode selection module 126.

[0084] Fig. 3 is a schematic illustrating interaction of the implanted stimulator 100 with a bundle of target nerve fibres 180 in the patient 108. In the implementation illustrated in Fig. 3 the target fibres 180 may be located in the spinal cord, however in alternative implementations the stimulator 100 may be positioned adjacent any target neural tissue including a peripheral nerve, visceral nerve, sacral nerve, parasympathetic nerve, or a brain structure. Electrode selection module 126 selects a stimulus electrode 2 of electrode array 150 through which to deliver a pulse from the pulse generator 124 to surrounding neural tissue including target fibres 180. A pulse may comprise one or more phases, e.g. a monophasic pulse comprises one phase, and a biphasic stimulus pulse 160 comprises two phases. Electrode selection module 126 also selects a return electrode 4 of the electrode array 150 for stimulus current return in each phase, to maintain a zero net charge transfer. An electrode may act as both a stimulus electrode and a return electrode over a complete multiphasic stimulus pulse. The use of two electrodes in this manner for delivering and returning current in each stimulus phase is referred to as bipolar stimulation. Alternative implementations may apply other forms of bipolar stimulation, or may use a greater number of stimulus or return electrodes. By contrast, in monopolar stimulation, current is returned through the conductive case of the stimulator 100, which may therefore be configured and function as an electrode though it is not physically part of the electrode array 150. The set of stimulus electrodes and return electrodes (collectively referred to as stimulation electrodes) is referred to as the stimulus electrode configuration. Electrode selection module 126 is illustrated as connecting to a ground 130 of the pulse generator 124 to enable stimulus current return via the return electrode 4. However, other connections for current return may be used in other implementations.

[0085] Delivery of an appropriate stimulus via stimulation electrodes 2 and 4 to the target fibres 180 evokes a neural response 170 comprising an evoked compound action potential (ECAP) which will propagate along the target fibres 180 as illustrated at a rate known as the conduction velocity. The ECAP may be evoked for therapeutic purposes, which in the case of a spinal cord stimulator for chronic pain may be associated with paresthesia at a desired location. To this end, the electrodes 2 and 4 are used to deliver stimuli periodically at any therapeutically suitable stimulus frequency, forexample 30 Hz, although other frequencies may be used including frequencies as high as the kHz range. In alternative implementations, stimuli may be delivered in a non-periodic manner such as in bursts, or sporadically, as appropriate for the patient 108. To program the stimulator 100 to the patient 108, a clinician may cause the stimulator 100 to deliver stimuli of various configurations which seek to produce a sensation that may be experienced by the patient as paresthesia. When a stimulus electrode configuration is found which evokes paresthesia in a location and of a size which is congruent with the area of the patient’s body affected by pain and of a quality that is comfortable for the patient, the clinician or the patient nominates that configuration for ongoing use. The therapy parameters may be loaded into the memory 118 of the electronics module 110 as the clinical settings 121.

[0086] Fig. 6 illustrates the typical form of an ECAP 600 of a healthy subject, as sensed by a single measurement electrode referenced to the system ground 130 or referenced to an indifferent electrode. Such configurations are referred to as single-ended ECAP measurement. The shape and duration of the single-ended ECAP 600 shown in Fig. 6 is predictable because it is a result of the ion currents produced by the ensemble of fibres depolarising and generating action potentials (APs) in response to stimulation. The evoked action potentials (EAPs) generated synchronously among a large number of fibres sum to form the ECAP 600. The ECAP 600 generated from the synchronous depolarisation of a group of similar fibres comprises a positive peak Pl, then a negative peak Nl, followed by a second positive peak P2. This shape is caused by the region of activation passing the measurement electrode as the action potentials propagate along the individual fibres.

[0087] The ECAP may be recorded differentially using two measurement electrodes, as illustrated in Fig. 3. Differential ECAP measurements are less subject to common-mode noise on the surrounding tissue than single-ended ECAP measurements. Depending on the polarity of recording, a differential ECAP may take an inverse form to that shown in Fig. 6, i.e. a form having two negative peaks Nl and N2, and one positive peak Pl. Alternatively, depending on the distance between the two measurement electrodes, a differential ECAP may resemble the time derivative of the ECAP 600, or more generally the difference between the ECAP 600 and a time-delayed copy thereof.

[0088] The ECAP 600 may be characterised by any suitable characteristic(s) of which some are indicated in Fig. 6. The amplitude of the positive peak Pl is Ap\ and occurs at time Tp . The amplitude of the positive peak P2 is Ap2and occurs at time Tp2. The amplitude of the negative peak Nl is Ari\ and occurs at time Tip. The peak-to-peak amplitude is Ap + Arp. A recorded ECAP will typically have a maximum peak-to-peak amplitude in the range of microvolts and a duration of 2 to 3 ms. A characteristic of an evoked neural response (e.g., a characteristic of an ECAP) may comprise one ormore of, but not limited to: an amplitude of a first positive peak Pl; an amplitude of a second positive peak P2; an amplitude of the negative peak Nl; and a peak-to-peak amplitude.

[0089] The stimulator 100 is further configured to measure the intensity of ECAPs 170 propagating along target fibres 180, whether such ECAPs are evoked by the stimulus from stimulation electrodes 2 and 4, or otherwise evoked. To this end, any electrodes of the array 150 may be selected by the electrode selection module 126 to serve as recording electrode 6 and reference electrode 8, whereby the electrode selection module 126 selectively connects the chosen electrodes to the inputs of the measurement circuitry 128. Thus, signals sensed by the measurement electrodes 6 and 8 subsequent to the respective stimuli are passed to the measurement circuitry 128, which may comprise a differential amplifier and an analog-to-digital converter (ADC), as illustrated in Fig. 3. The recording electrode and the reference electrode are referred to as the measurement electrode configuration. The measurement circuitry 128 for example may operate in accordance with the teachings of the above-mentioned International Patent Publication No. WO2012 / 155183.

[0090] Signals sensed by the measurement electrodes 6, 8 and processed by measurement circuitry 128 are further processed by an ECAP detector implemented within controller 116, configured by control programs 122, to obtain information regarding the effect of the applied stimulus upon the target fibres 180. In some implementations, the sensed signals are processed by the ECAP detector in a manner which measures and stores one or more characteristics from each evoked neural response or group of evoked neural responses contained in the sensed signal. In one such implementation, the characteristics comprise a peak-to-peak ECAP amplitude in microvolts (pV). For example, the sensed signals may be processed by the ECAP detector to determine the peak-to-peak ECAP amplitude in accordance with the teachings of International Patent Publication No. WO2015 / 074121, the contents of which are incorporated herein by reference. Alternative implementations of the ECAP detector may measure and store an alternative characteristic from the neural response, or may measure and store two or more characteristics from the neural response.

[0091] Stimulator 100 applies stimuli over a potentially long period such as days, weeks, or months and during this time may store characteristics of neural responses, clinical settings, target response intensity, and other operational parameters in memory 118. To effect suitable SCS therapy, stimulator 100 may deliver tens, hundreds or even thousands of stimuli per second, for many hours each day. Each neural response or group of responses generates one or more characteristics such as a measure of the intensity of the neural response. Stimulator 100 thus may produce such data at a rate of tens or hundreds of Hz, or even kHz, and over the course of hours or days this process results in large amounts of clinical data 120 which may be stored in the memory 118. Memory 118 is howevernecessarily of limited capacity and care is thus required to select compact data forms for storage into the memory 118, to ensure that the memory 118 is not exhausted before such time that the data is expected to be retrieved wirelessly by external device 192, which may occur only once or twice a day, or less.

[0092] An activation plot, or growth curve, is an approximation to the relationship between stimulus intensity (e.g. an amplitude of the current pulse 160) and intensity of neural response 170 evoked by the stimulus (e.g. an ECAP amplitude). Fig. 4a illustrates an idealised activation plot 402 for one posture of the patient 108. The activation plot 402 shows a linearly increasing ECAP amplitude for stimulus intensity values above a threshold 404 referred to as the ECAP threshold. The ECAP threshold exists because of the binary nature of fibre recruitment; if the field strength is too low, no fibres will be recruited. However, once the field strength exceeds a threshold, fibres begin to be recruited, and their individual evoked action potentials are independent of the strength of the field. The ECAP threshold 404 therefore reflects the field strength at which significant numbers of fibres begin to be recruited, and the increase in response intensity with stimulus intensity above the ECAP threshold reflects increasing numbers of fibres being recruited. Below the ECAP threshold 404, the ECAP amplitude may be taken to be zero. Above the ECAP threshold 404, the activation plot 402 has a positive, approximately constant slope indicating a linear relationship between stimulus intensity and the ECAP amplitude. Such a relationship may be modelled in piecewise linear form as:<

[0093] where 5 is the stimulus intensity, d is the ECAP amplitude, T is the ECAP threshold and S is the slope of the activation plot (referred to herein as the patient sensitivity) above the ECAP threshold T. The sensitivity S and the ECAP threshold T are the key parameters of the activation plot 402.

[0094] Fig. 4a also illustrates a discomfort threshold 408, which is a stimulus intensity above which the patient 108 experiences uncomfortable or painful stimulation. Fig. 4a also illustrates a perception threshold 410. The perception threshold 410 is a value of stimulus intensity that corresponds to an ECAP amplitude that is barely perceptible by the patient. There are a number of factors which can influence the position of the perception threshold 410, including the posture of the patient. Perception threshold 410 may correspond to a stimulus intensity that is greater than the ECAP threshold 404, as illustrated in Fig. 4a, if patient 108 does not perceive low levels of neural activation. Conversely, the perception threshold 410 may correspond to a stimulus intensity that is less than the ECAP threshold 404, if the patient has a high perception sensitivity to lower levels of neural activation than can be detected in an ECAP, or if the signal-to-noise ratio of the ECAP is low.

[0095] For effective and comfortable operation of an implantable neuromodulation device such as the stimulator 100, it is desirable to maintain stimulus intensity within a therapeutic range. A stimulus intensity within a therapeutic range 412 is above the ECAP threshold 404 and below the discomfort threshold 408. In principle, it would be straightforward to measure these limits and ensure that stimulus intensity, which may be closely controlled, always falls within the therapeutic range 412. However, the activation plot, and therefore the therapeutic range 412, varies with the posture of the patient 108.

[0096] Fig. 4b illustrates the variation in the activation plots with changing posture of the patient. A change in posture of the patient may cause a change in impedance of the electrode-tissue interface or a change in the distance between electrodes and the spinal cord. While the activation plots for only three postures, 502, 504 and 506, are shown in Fig. 4b, the activation plot for any given posture can lie between or outside the activation plots shown, on a continuously varying basis depending on posture. Consequently, as the patient’s posture changes, the ECAP threshold changes, as indicated by the ECAP thresholds 508, 510, and 512 for the respective activation plots 502, 504, and 506. Additionally, as the patient’s posture changes, the patient sensitivity also changes, as indicated by the varying slopes of activation plots 502, 504, and 506. In general, as the distance between the stimulus electrodes and the spinal cord increases, the ECAP threshold increases and the sensitivity decreases. The activation plots 502, 504, and 506 therefore correspond to increasing distance between stimulus electrodes and spinal cord, and decreasing patient sensitivity.

[0097] To keep the applied stimulus intensity within the therapeutic range as patient posture varies, in some implementations an implantable neuromodulation device such as the stimulator 100 may adjust the applied stimulus intensity based on a feedback variable that is determined from one or more measured ECAP characteristics. In one implementation, the device may adjust the stimulus intensity to maintain the measured ECAP amplitude at or near a target response intensity. For example, the device may calculate an error between a target ECAP amplitude and a measured ECAP amplitude, and adjust the applied stimulus intensity to bring the measured ECAP amplitude closer to the target ECAP amplitude, such as by adding the scaled error to the current stimulus intensity. A neuromodulation device that operates by adjusting the applied stimulus intensity to maintain a feedback variable at or near a target value is said to be operating in closed-loop mode and will also be referred to as a closed-loop neural stimulation (CLNS) device. By adjusting the applied stimulus intensity to maintain the measured ECAP amplitude at or near an appropriate target response intensity, such as a target ECAP amplitude 520 illustrated in Fig. 4b, a CLNS device will generally keep the stimulus intensity within the therapeutic range as patient posture varies.

[0098] A CLNS device comprises a pulse generator that takes a stimulus intensity value and converts it into neural stimuli comprising a sequence of electrical pulses according to a predefined stimulation pattern. The stimulation pattern is parametrised by multiple stimulus parameters including stimulus amplitude, pulse width, number of phases, order of phases, number of stimulus electrode poles (two for bipolar, three for tripolar etc.), and stimulus rate or frequency. At least one of the stimulus parameters, for example the stimulus amplitude, is controlled by the pulse generator to implement the received stimulus intensity value. For example, all stimulus parameters may be held constant except stimulus amplitude which is determined in proportion to the received stimulus intensity value. Alternatively, all stimulus parameters may be held constant except pulse width which is determined in proportion to the received stimulus intensity value.

[0099] In an example CLNS system, the user sets a target response intensity, and the CLNS device performs proportional -integral-differential (PID) control. In some implementations, the differential and proportional contributions are disregarded and the CLNS device uses a first order integrating feedback loop. The pulse generator generates stimulus in accordance with a stimulus intensity parameter, which evokes a neural response in the patient. The intensity of an evoked neural response (e.g. an ECAP) is measured by the CLNS device and compared to the target response intensity.

[0100] The measured neural response intensity, and its deviation from the target response intensity, is used by the feedback loop to determine possible adjustments to the stimulus intensity parameter to maintain the neural response at or near the target response intensity. If the target response intensity is properly chosen, the patient receives consistently comfortable and therapeutic stimulation through posture changes and other perturbations to the stimulus / response behaviour.

[0101] Fig. 5 is a schematic illustrating elements and inputs of a closed-loop neural stimulation (CLNS) system 300, implementable by the electronics module 110 of Fig. 2, according to one implementation of the present technology. The system 300 comprises a pulse generator 312 which converts a stimulus intensity parameter s, in concert with a set of predefined stimulus parameters, into a neural stimuli comprising a sequence of electrical pulses delivered via the stimulation electrodes (not shown in Fig. 5). According to one implementation, the predefined stimulus parameters comprise the number and order of phases, the number of stimulus electrode poles, the pulse width, the stimulus rate or frequency, and the pulse generator 312 determines the stimulus amplitude in proportion to the stimulus intensity parameter 5.

[0102] The generated stimulus crosses from the electrodes to the spinal cord, which is represented in Fig. 5 by the dashed box 308. The box 309 represents the evocation of a neural response y by the stimulus as described above. The box 311 represents the evocation of an artefact signal a, which isdependent on stimulus intensity and other stimulus parameters, as well as the electrical environment of the measurement electrodes. Various sources of measurement noise / / , as well as the artefact a, may add to the evoked response^ at the summing element 313 to form the sensed signal r, including: electrical noise from external sources such as 50 Hz mains power; electrical disturbances produced by the body such as neural responses evoked not by the device but by other causes such as peripheral sensory input; EEG; EMG; and electrical noise from measurement circuitry 318.

[0103] The neural recruitment arising from the stimulus is affected by mechanical changes, including posture changes, walking, breathing, heartbeat and so on. Mechanical changes may cause impedance changes, or changes in the location and orientation of the nerve fibres relative to the electrode array(s). As described above, the intensity of the evoked response provides a measure of the recruitment of the fibres being stimulated. In general, the more intense the stimulus, the more recruitment and the more intense the evoked response. An evoked response typically has a maximum amplitude in the range of microvolts, whereas the voltage resulting from the stimulus applied to evoke the response is typically several volts.

[0104] Measurement circuitry 318, which may be identified with measurement circuitry 128, amplifies the sensed signal r (potentially including evoked neural response, artefact, and measurement noise), and samples the amplified sensed signal r to capture a “signal window” 319 comprising a predetermined number of samples of the amplified sensed signal r. The ECAP detector 320 processes the signal window 319 and outputs a measured neural response intensity d. In one implementation, the neural response intensity comprises a peak-to-peak ECAP amplitude. The measured response intensity d (an example of a feedback variable) is input into the feedback controller 310. The feedback controller 310 comprises a comparator 324 that compares the measured response intensity dto a target ECAP amplitude as set by the target ECAP controller 304 and provides an indication of the difference between the measured response intensity d and the target ECAP amplitude. This difference is the error value, e.

[0105] The feedback controller 310 calculates an adjusted stimulus intensity parameter, s, with the aim of maintaining a measured response intensity d equal to the target ECAP amplitude. Accordingly, the feedback controller 310 adjusts the stimulus intensity parameter 5 to minimise the error value, e. In one implementation, the controller 310 utilises a first order integrating function, using a gain element 336 and an integrator 338, in order to provide suitable adjustment to the stimulus intensity parameter 5. According to such an implementation, the current stimulus intensity parameter .s may be determined by the feedback controller 310 ass = f Kedt (2)

[0106] where K is the gain of the gain element 336 (the controller gain). This relation may also be represented as8s = Ke (3)

[0107] where 6 is an adjustment to the current stimulus intensity parameter .s.

[0108] A target ECAP amplitude is input to the feedback controller 310 via the target ECAP controller 304. In one implementation, the target ECAP controller 304 provides an indication of a specific target ECAP amplitude. In another implementation, the target ECAP controller 304 provides an indication to increase or to decrease the present target ECAP amplitude. The target ECAP controller 304 may comprise an input into the CLNS system 300, via which the patient or clinician can input a target ECAP amplitude, or indication thereof. The target ECAP controller 304 may comprise memory in which the target ECAP amplitude is stored, and from which the target ECAP amplitude is provided to the feedback controller 310.

[0109] A clinical settings controller 302 provides clinical settings to the system 300, including the feedback controller 310 and the pulse generator 312. In one example, the clinical settings controller 302 may be configured to adjust the controller gain K of the feedback controller 310 to adapt the feedback loop to patient sensitivity. The clinical settings controller 302 may comprise an input into the CLNS system 300, via which the patient or clinician can adjust the clinical settings. The clinical settings controller 302 may comprise memory in which the clinical settings are stored, and are provided to components of the system 300.

[0110] In some implementations, two clocks (not shown) are used, being a stimulus clock operating at the stimulus frequency (e.g. 60 Hz) and a sample clock for sampling the sensed signal r (for example, operating at a sampling frequency of 16 kHz). As the ECAP detector 320 is linear, only the stimulus clock affects the dynamics of the CLNS system 300. On the next stimulus clock cycle, the pulse generator 312 generates a stimulus in accordance with the adjusted stimulus intensity 5. Accordingly, there is a delay of one stimulus clock cycle before the stimulus intensity is updated in light of the error value e.

[0111] Fig. 7 is a block diagram of a neural stimulation system 700. The neural stimulation system 700 is centred on a neuromodulation device 710. In one example, the neuromodulation device 710 may be implemented as the stimulator 100 of Fig. 1, implanted within a patient (not shown). The neuromodulation device 710 is connected wirelessly to a remote controller (RC) 720. The remote controller 720 is a portable computing device that provides the patient with control of their stimulation in the home environment by allowing control of the functionality of the neuromodulation device 710, including one or more of the following functions: enabling or disabling stimulation; adjustment ofstimulus intensity or target response intensity; and selection of a stimulation control program from the control programs stored on the neuromodulation device 710.

[0112] The charger 750 is configured to recharge a rechargeable power source of the neuromodulation device 710. The recharging is illustrated as wireless in Fig. 7 but may be wired in alternative implementations.

[0113] The neuromodulation device 710 is wirelessly connected to a Clinical System Transceiver (CST) 730. The wireless connection may be implemented as the transcutaneous communications channel 190 of Fig. 1. The CST 730 acts as an intermediary between the neuromodulation device 710 and the Clinical Interface (CI) 740, to which the CST 730 is connected. A wired connection is shown in Fig. 7, but in other implementations, the connection between the CST 730 and the CI 740 is wireless.

[0114] The CI 740 may be implemented as the external computing device 192 of Fig. 1. The CI 740 is configured to program the neuromodulation device 710 and recover data stored on the neuromodulation device 710. This configuration is achieved by program instructions collectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the CI 740.Multi-stimset neural stimulation

[0115] For some patients, it is beneficial for a neural stimulation therapy program to comprise multiple stimulation sets. A stimulation set (“stimset”) is a set of stimulus and return electrodes, or more precisely a stimulus electrode configuration (SEC), along with the stimulus parameters that govern the stimulation pulses delivered via that SEC.

[0116] Fig. 8 is an illustration 800 of the stimulus pulses delivered by a stimulation program with four interleaved stimsets. The stimulus pulse train delivered according to each stimset is illustrated on a separate, but vertically aligned, horizontal axis representing time. All the stimulus pulse trains are delivered at the same stimulus frequency. (It is not a requirement that all the stimulus pulse trains for the respective stimsets are delivered at the same stimulus frequency; however it is so represented in Fig. 8 for ease of illustration.) The first stimulus pulse 810, delivered according to the first stimset, is illustrated as a biphasic, anodic-first stimulus pulse, though many other stimulus pulse types are contemplated. The second, third, and fourth stimulus pulses 820, 830, and 840, delivered according to the second, third, and fourth stimsets in the program respectively, are also biphasic, anodic-first stimulus pulses with different pulse widths and different amplitudes. Each stimulus pulse is illustrated as delayed in time by a constant amount (the inter-stimulus interval, or ISI, 815) from the stimulus pulse delivered according to the preceding stimset. However, this is not to be interpreted as limiting,since the intervals between the pulses in the various stimsets may be different. Because all the stimulus pulse trains in Fig. 8 are delivered at the same stimulus frequency, the four stimulus pulses 810, 820, 830, 840 form a cycle that repeats indefinitely without any change to the relative timing of the pulses from the different stimsets. The fifth stimulus pulse 850 is a subsequent pulse in the pulse train delivered according to the first stimset and is therefore illustrated on the same time axis as the first stimulus pulse 810, and the cycle repeats thereafter. The stimulus period 890 is the period of repetition of the full cycle and is equal to the reciprocal of the stimulus frequency. In one implementation, the ISI 815 is the stimulus period 890 divided by the number of stimsets, so that the stimuli are evenly spaced throughout the stimulus period 890.

[0117] Also illustrated is an evoked neural response in the form of an evoked compound action potential (ECAP) 860 as sensed by a predetermined measurement electrode configuration (MEC) on a common time axis with the stimulus pulses. The illustrated ECAP 860 is evoked by the fourth stimulus pulse 840. A closed-loop neural stimulation (CLNS) system programmed with multiple interleaved stimsets, as illustrated in Fig. 8, may be based on measurements of the ECAP 860. That is to say, closed-loop adjustments to the stimulus parameters of all stimsets may all be based on measurements of the ECAP 860 evoked by a single stimset, referred to as the applied stimset. In Fig.8, the final stimset in the cycle is the applied stimset.

[0118] If the ISI 815 is short, ECAPs evoked by the first three stimulus pulses 810, 820, and 830 are potentially obscured by stimulus crosstalk or artefact from the stimulus pulses 820, 830, and 840. Therefore, if the ISI 815 is short, only the final stimset in the cycle may evoke a measurable ECAP. If the ISI 815 is greater than the refractory period and sufficiently long that ECAPs evoked by the earlier stimsets are not obscured by stimulus crosstalk and artefact from the other stimulus pulses in the cycle, any of the stimsets in the cycle may evoke a measurable ECAP and may therefore be the applied stimset.

[0119] Fig. 9 is a schematic illustrating elements and inputs of a multi-stimset CLNS system 900, implementable by the electronics module 110, according to one implementation of the present technology . The multi-stimset CLNS system 900 is the same as the CLNS system 300 of Fig. 5, with like numbers indicating like elements, with the addition of three further stimsets. The four stimsets are labelled A, B, C, and D and are delivered by pulse generators 312A, 312B, 312C, and 312D (the latter of which corresponds to the pulse generator 312 in the CLNS system 300) according to respective stimulus intensity parameters sA, sB, sc, and sD, and via respective SECs. The pulses delivered by the pulse generators 312A, 312B, 312C, and 312D correspond to the stimulus pulses 810, 820, 830, and 840 of Fig. 8. Stimset D, delivered by the pulse generator 312D, is delivered lastin the cycle and is the applied stimset, from which the ECAP is measured. In the implementation of Fig. 8, the stimulus intensity parameter sDfor stimset D is scaled by ratios RA, RB, and Rc to obtain the stimulus intensity parameters sA, sB, and scfor stimsets A, B, and C respectively at the end of each cycle. The ratios RA, RB, and Rcare fixed at the ratios of the respective stimulus intensities sA, sB, and scat which the respective stimsets were originally programmed, to the originally programmed stimulus intensity sDof the applied stimset D. In such an implementation, the stimulus intensity parameters sA, sB, and scalways remain in fixed ratio with the applied stimulus intensity parameter sDand with each other. This is referred to as ratiometric adjustment. So for example, if the originally programmed stimulus intensities were 1 mA, 2 mA, 4 mA, and 6 mA for the four stimsets A, B, C, and D respectively, the ratios RA, RB, and Rcare fixed at programming time at 1 / 6, 1 / 3, and 2 / 3 respectively and form part of the clinical settings 121 of the multi-stimset program. If during therapy the feedback controller 310 adjusts the applied stimset intensity parameter sDto 6.6 mA, the stimulus intensity parameters sA, sB, and scof the non-applied stimsets are automatically adjusted to 1.1 mA, 2.2 mA, and 4.4 mA respectively. The clinical settings controller 302 provides the respective stimulus parameters to the pulse generators 312A, 312B, 312C, and 312D.

[0120] It may be seen from Fig. 9 that the adjustments to the stimulus intensity parameters after each stimulus cycle are all in fixed proportion. A ratiometric multi-stimset CLNS system therefore emulates a CLNS system with four separate feedback loops driven by the four stimsets, wherein each loop has the same controller gain. A ratiometric multi-stimset CLNS system is effective to maintain the responses evoked by each stimset at a constant neural response intensity on the condition that when the patient moves to a new posture, the threshold and slope of all activation plots, both for applied and non-applied stimsets, move in a proportional manner. (See Fig. 4b for examples of activation plots for a given stimset in different postures.)Assisted Programming System

[0121] As mentioned above, obtaining patient feedback about their sensations is important during programming of closed-loop neural stimulation therapy, but mediation by trained clinical engineers is expensive and time-consuming. It would therefore be advantageous if patients could program their own implantable device themselves, or with some assistance from a clinician. However, interfaces for current programming systems are non-intuitive and generally unsuitable for direct use by patients because of their technical nature. The Assisted Programming System (APS) is a programming system that is as intuitive for non-technical users as possible while avoiding discomfort to the patient.

[0122] In some implementations, the APS comprises two elements: the Assisted Programming Module (APM), which forms part of the CPA, and the Assisted Programming Firmware (APF), whichforms part of the control programs 122 executed by the controller 116 of the electronics module 110. The APF is configured to complement the operation of the APM by responding to commands issued by the APM to the electronics module 110, possibly via a CST such as the CST 730 of Fig. 7, to deliver specified stimuli to the target neural tissue, and by returning, via the CST 730, data comprising measurements of neural responses to the delivered stimuli. The data obtained from the electronics module 110 under the control of the APF is analysed by the APM to determine the clinical settings for the neural stimulation therapy to be delivered by the electronics module 110.

[0123] In other implementations, all the processing of the APS is done by the APF. In other words, the data obtained from the patient is not passed to the APM, but is analysed by the controller 116 of the electronics module 110, configured by the APF, to determine the clinical settings 121 for the neural stimulation therapy to be delivered by the electronics module 110.

[0124] In implementations of the APS in which the APM analyses the data from the patient, the APS instructs the electronics module 110 to capture and return signal windows to the CI 740 via the CST 730. In such implementations, the electronics module 110 captures the signal windows using the measurement circuitry 128 and bypasses the ECAP detector 320, storing the data representing the raw signal windows temporarily in memory 118 before transmitting the data representing the captured signal windows to the APM for analysis.

[0125] Following the programming, the APS may load the determined program onto the electronics module 110 to govern subsequent neural stimulation therapy. In one implementation, the program comprises clinical settings 121, also referred to as therapy parameters, that are input to the electronics module 110 by, or stored in, the clinical settings controller 302. The patient may subsequently control the electronics module 110 to deliver the therapy according to the determined program using a remote controller for the electronics module 110 such as the remote controller 720 as described above. The determined program may also, or alternatively, be loaded into the instruction memory of a clinical interface for validation and modification by the CPA. Validation and modification of the determined program may also be carried out by the APS itself.Data flow

[0126] Fig. 10 is a block diagram illustrating the data flow 1000 of a neural stimulation therapy system such as the system 700 of Fig. 7 according to one implementation of the present technology. Neuromodulation device 1004, once implanted within a patient, applies stimuli over a potentially long period such as weeks or months and records neural responses, clinical settings, target response intensity, and other operational parameters, discussed further below. Neuromodulation device 1004 may comprise a Closed-Loop Neural Stimulation (CLNS) device, in that the recorded neuralresponses are used in a feedback arrangement to control clinical settings on a continuous or ongoing basis. To effect suitable SCS therapy, neuromodulation device 1004 may deliver tens, hundreds or even thousands of stimuli per second, for many hours each day. The feedback loop may operate for most or all of this time, by obtaining sensed signals subsequent to every stimulus, or at least obtaining such sensed signals regularly. Each sensed signal generates a feedback variable such as a measure of the amplitude of the evoked neural response, which in turn results in the feedback loop changing at least one stimulus parameter for a following stimulus. Neuromodulation device 1004 thus produces such data at a rate of tens or hundreds of Hz, or even kHz, and over the course of hours or days this process results in large amounts of clinical data. This is unlike past neuromodulation devices such as open-loop SCS devices which lack any ability to record any neural response.

[0127] When brought in range with a receiver, neuromodulation device 1004 transmits data, e.g. via telemetry module 114, to a clinical programming application (CPA) 1010 installed on a clinical interface. In one implementation, the clinical interface is the CI 740 of Fig. 7. The data can be grouped into two main sources: (1) Data collected in real-time during a programming session; (2) Data downloaded from a stimulator after a period of non-clinical use by a patient. CPA 1010 collects and compiles the data into a clinical data log file 1012.

[0128] All clinical data transmitted by the neuromodulation device 1004 may be compressed by use of a suitable data compression technique before transmission by telemetry module 114 or before storage into the memory 118 to enable storage by neuromodulation device 1004 of higher resolution data. This higher resolution allows neuromodulation device 1004 to provide more data for postanalysis and more detailed data mining for events during use. Alternatively, compression enables faster transmission of standard-resolution clinical data.

[0129] The clinical data log file 1012 is manipulated, analysed, and efficiently presented by a clinical data viewer (CDV) 1014 for field diagnosis by a clinician, field clinical engineer (FCE) or the like. CDV 1014 is a software application installed on the Clinical Interface (CI). In one implementation, CDV 1014 opens one Clinical Data Log file 1012 at a time. CDV 1014 is intended to be used in the field to diagnose patient issues and optimise therapy for the patient. CDV 1014 may be configured to provide the user or clinician with a summary of neuromodulation device usage, therapy output, and errors, in a simple single-view page immediately after log files are compiled upon device connection.

[0130] Clinical Data Uploader 1016 is an application that runs in the background on the CI, that uploads files generated by the CPA 1010, such as the clinical data log file 1012, to a data server. Database Loader 1022 is a service which runs on the data server and monitors the patient data folderfor new files. When Clinical Data Log files are uploaded by Clinical Data Uploader 1016, database loader 1022 extracts the data from the file and loads the extracted data to Database 1024.

[0131] The data server further contains a data analysis web API 1026 which provides data for third-party analysis such as by the analysis module 1032, located remotely from the data server. The ability to obtain, store, download and analyse large amounts of neuromodulation data means that the present technology can: improve patient outcomes in difficult conditions; enable faster, more cost effective and more accurate troubleshooting and patient status; and enable the gathering of statistics across patient populations for later analysis, with a view to diagnosing aetiologies and predicting patient outcomes.Effect of wireless charging on neural response measurement

[0132] Neuromodulation devices, including implantable neuromodulation devices such as the stimulator 100, rely on an ability to accurately measure characteristics of a neural response signal (such as an ECAP) evoked on a stimulated neural pathway. This is particularly important in modes of operation where the measurement of a characteristic of the evoked neural response signal is used to adjust the amplitude of an applied stimulus such as to keep the stimuli within a desired therapeutic range (e.g., as performed during CLNS where the evoked neural response measurements are used to calculate a feedback variable controlling the applied stimulus).

[0133] Implantable neuromodulation devices are typically powered by an internal energy storage device, such as a battery. The energy storage device requires charging, at least intermittently, to maintain a level of stored charge that is capable of powering the neuromodulation device.

[0134] Fig. Ila illustrates a configuration for wireless charging of an energy storage device of the stimulator 100. Electronics module 110 of the stimulator 100 comprises a charging component 140 configured to transfer energy to an energy storage device 104 (e.g., a battery) of the module 110 using a charging signal 106. The charging signal 106 is an electromagnetic signal emitted from a charging device 102 (also referred to as a “charger”). The charging component 140 receives the charging signal 106. An electrical connection between the charging component 140 and the energy storage device 104 results in wireless charging of the energy storage device 104 in response to exposure of the charging component 140 to the charging signal 106.

[0135] In some implementations, the charging component is a charging coil 140. The charging coil 140 may be formed from a Litz wire, or other type of multi-strand wire, comprising for example at least 100 strands of wire per cable. In some implementations, the module 110 includes a sensor (not shown) configured to detect the electromagnetic charging signal 106, and therefore the presence of the charger 102 or other emitting device, within a charging distance of the module 110. For example,the sensor may be a component that senses the voltage or current induced by the charging signal 106 emitted from the charger 102.

[0136] The ability of the stimulator 100 to accurately measure a characteristic of an evoked neural response is affected by the wireless charging of the energy storage device 104. Fig. 1 lb illustrates an example model 1100 of charging circuitry 1140 and measurement circuitry 128 of the stimulator 100. The measurement circuitry 128 comprises a measurement amplifier 1101 having a first input node 1102 and a second input node 1104. The first input node 1102 has a first voltage FW1and the second input node 1104 has a second voltage VN2at respective input connection points (e.g., points at which an electrode is connected to the measurement circuitry 128 for the delivery of a sensed signal to a respective input terminal 1142 and 1144 of the measurement amplifier 1101). Each input node 1102 and 1104 has a respective input capacitor 1103 and 1105 in the model 1100 depicted by Fig. 1 lb.

[0137] As shown in Fig. 11b, the first and second input nodes 1102 and 1104 are connected to the respective first and second input terminals 1142 and 1144 of the measurement amplifier 1101 via the respective input capacitors 1103 and 1105. In some implementations, each input node 1102 and 1104 may be directly connected to the respective input terminal 1142 and 1144 of the measurement amplifier 1101 (i.e., without any input element(s) providing a connection path between each of the input nodes and the respective input terminal). One or more measurement electrodes 6, 8 are in contact with the neural tissue 1120 and are connected to measurement amplifier 1101 via respective input nodes 1102, 1104.

[0138] The charging circuitry 1140 comprises a charging coil 140 and a rectifier circuit 142, configured to charge the energy storage device 104 with an electrical current generated by induction of the charging coil 140 with the electromagnetic charging signal 106. As shown in Fig. 11b, the charging coil 140 is typically located in close proximity to the measurement electrodes 6, 8 or to the connections at the respective input nodes 1102 and 1104 of the measurement amplifier 1101 (e.g., to provide a compact physical layout of the module 110).

[0139] During a charging operation, the charger 102 emits the charging signal 106, typically as a high frequency signal (e.g., in the 400 to 450 kHz range) to induce a current in charging coil 140. As a result, during the charging operation at least part of the charging coil 140 generates a high amplitude voltage signal at the frequency of the charging signal 106. The voltage in the coil 140 capacitively couples with conductive elements, such as the measurement electrodes 6, 8 or the connections themselves, at each input node 1102, 1104 via capacitive couplings represented as capacitances Cpand Cp’ respectively. The wireless charging of the energy storage device 104 therefore causes a noise signal to appear at the input nodes 1102, 1104 of the measurement amplifier 1101.

[0140] Measurement amplifier 1101 may be a differential amplifier configured to amplify a difference FW1— VN2between the voltages FW1and VN2occurring at the first and second input nodes 1102 and 1104, to generate an output voltage between outputs 1106 and 1108 that is proportional to the difference. In this case, if the noise signal at the input nodes 1102 and 1104 is a differential signal then the induction of the charging coil 140 may produce an undesired noise contribution in the measurement of a characteristic of the evoked neural response (as derived from the output voltage between outputs 1106 and 1108).

[0141] Various approaches have been previously implemented to address the problem of performing neuromodulation with an implantable device that is configured for wireless charging, including limiting or preventing a noise effect of the charging from influencing evoked neural response measurements. In one approach, as presented in International Patent Publication No. WO2012155183, an implantable pulse generator device is configured with an amplifier having inputs that are disconnected from measurement electrodes during a stimulus phase in which the neural stimulus is provided to the neural tissue. However, this does not prevent a noise signal from developing at the inputs of the measurement amplifier during, or just prior to commencement of, the measurement phase. Further, even if measurement electrodes are disconnected from the inputs of the amplifier, a noise signal can still be induced at the inputs via other electrical components (e.g., the electrode-to-amplifier connectors) leading to an undesired noise contribution to the evoked neural response measurements.

[0142] In a further approach, as presented in International Patent Publication No. WO2022032352, an implantable pulse generator device is configured to selectively operate in one of a charging mode and a measurement mode such that the implantable pulse generator device does not receive an electromagnetic charging signal 106 from a charger 102 during the measurement of neural response signals. That is, the implantable pulse generator device and the charger are synchronized to avoid charging of the energy storage device during ECAP measurement. However, in some applications it is not practical or possible to synchronize the operations of the implantable pulse generator device and the charger, and it is instead desired or required to perform measurements of evoked neural responses simultaneously with the charging of the energy storage device.

[0143] It is therefore desired to provide systems, devices, and methods that overcome or substantially ameliorate at least some of the above-mentioned drawbacks, and / or any other deficiencies, of the prior art, or that at least provide a useful alternative.Overview of the disclosed technology

[0144] Disclosed herein are methods, devices, and systems for measuring a characteristic of an evoked neural response during wireless charging of a neuromodulation device by fixing a potential at each respective input of an amplifier (referred to as a “measurement amplifier”) configured to amplify a voltage associated with the neural response. In some examples, the measurement amplifier has two inputs that are exposed to a time-varying noise signal generated by wireless charging (e.g., via the induction of a charging coil, also referred to as “inductive charging”) of an energy storage device of the neuromodulation device. In other examples, only one input of the measurement amplifier is exposed to the noise signal, for example as a result of the other input being substantially shielded or protected against coupling with the charging component.

[0145] It is particularly desirable to mitigate the impact of the noise signal on the measurement amplifier during an autozeroing phase. The autozeroing phase refers to an operational phase of the measurement amplifier that occurs in a period of time immediately preceding measurement of a characteristic of an evoked neural response from an amplified signal sensed by the measurement amplifier. During at least the autozeroing phase of the measurement amplifier, the neuromodulation device operates to mitigate a noise contribution of the wireless charging on the measurement of the characteristic of the neural response (i.e., as a random offset contributing to the output of the measurement amplifier) by maintaining one or more fixed potentials at the input node(s) of the measurement amplifier. For example, the neural stimulation device may maintain a fixed and optionally common potential at each respective input node of the measurement amplifier. This maintenance advantageously allows the neuromodulation device to accurately measure evoked neural response characteristics, such as ECAP values, without any interruption to the wireless charging of the energy storage device. This maintaining, which in some implementations takes place only during intervals of wireless charging, may also take place outside of wireless charging intervals without any adverse effects on the measurement of evoked neural response characteristics.

[0146] Measurement of a characteristic of an evoked neural response may be performed by the neuromodulation device (also referred to as an “implantable device” or an “implantable neuromodulation device” when the device is suitable for implantation in a patient), or a neural stimulation system using a neuromodulation device, during wireless charging of an energy storage device of the neuromodulation device. A measurement amplifier of the device is configured to amplify a signal between a first input node of the measurement amplifier and a second input node of the measurement amplifier subsequent to a provided neural stimulus, where the signal comprises the evoked neural response. In some implementations, the device includes a stimulus source (e.g. a pulse generator) configured to provide neural stimuli via one or more stimulus electrodes to evoke theneural response from a neural pathway. The stimulus source is controlled to provide the neural stimulus to neural tissue of the neural pathway, and the characteristic of the evoked neural response of the amplified sensed signal is measured, for example by the control unit of the device. One or more control elements are configured to control one or more potentials at the one or more input nodes of the measurement amplifier, including for example a first potential and a second potential at the respective first input node and second input node of the measurement amplifier. For example, the one or more control elements may be connected to the first input node and the second input node of the measurement amplifier. A control unit of the neuromodulation device is configured to measure the characteristic of the evoked neural response of the amplified signal. The control unit is also configured to operate the one or more control elements to maintain the first input node at a fixed potential and the second input node of the measurement amplifier at a fixed potential. This advantageously mitigates a noise contribution of the wireless charging on the measurement of a characteristic of the evoked neural response.

[0147] According to one implementation, the fixed potentials are a single fixed and common potential. That is, the voltage at each respective input node of the measurement amplifier is maintained at substantially the same value (i.e., the fixed and equal potential) during the autozeroing phase of the neurostimulation. The fixed and common potential may be provided in a variety of configurations. For example, the fixed and common potential is provided as a ground potential of the neuromodulation device. Alternatively, the fixed and common potential is provided as another reference potential, such as a system potential of the implantable device. For example, the fixed and common potential may be a supply voltage provided by a voltage supply rail. Alternatively, the fixed and common potential is provided as a tissue potential of the neural pathway receiving the neural stimulus, while the tissue itself is being held at a fixed potential.

[0148] The control unit of the neuromodulation device is configured to provide the fixed and common potential by electrically connecting the first and second input nodes of the measurement amplifier to a potential-defining element, at or immediately following commencement of the autozeroing phase.

[0149] For example, the control unit of the neuromodulation device may be configured to electrically connect the first and second input nodes of the measurement amplifier to: a ground potential; a voltage supply rail; or to respective first and second return electrodes of electrode array 150, where the return electrodes are connected to a fixed potential. In some implementations, each input node of the measurement amplifier is electrically connected to the same return electrode. It will be appreciated that any other configuration may be implemented to maintain the input nodes of the measurementamplifier at a fixed and common potential of an arbitrary value, subject to limits on the range of input voltages that can be processed by the measurement amplifier.

[0150] The fixed and common potential has a value that, when maintained at the first input node and the second input node of the measurement amplifier during the autozeroing phase, mitigates a noise contribution of the wireless charging on the measurement of a characteristic of the evoked neural response signal. Specifically, the presence of a random DC offset resulting from sampling of the noise signal at or immediately following the termination of the autozeroing phase is eliminated, since the potential at each of the first and second input nodes is held constant. In this case, since the fixed potential is common to each input node of the measurement amplifier, the contribution of the charging noise to the differential output of the amplifier is equal to zero (or substantially equal to zero when there is a small difference in the potentials maintained at the respective input nodes). That is, the neural response signal measurements obtained from the output of the measurement amplifier are substantially unaffected by the wireless charging, since the measurement amplifier is autozeroed while the voltage at the first and second input nodes is maintained at the same value.

[0151] Sensing of the evoked neural responses may be performed by a plurality of measurement electrodes connected to the measurement amplifier. For example, the signal is provided to the first input node of the measurement amplifier by a first measurement electrode and to the second input node of the measurement amplifier by a second measurement electrode. In some implementations, the control elements are operated to electrically disconnect the measurement electrodes from the respective input nodes of the measurement amplifier during the autozeroing phase. This advantageously prevents the input nodes of the measurement amplifier from being disturbed by the effects of noise and artefacts that may be induced in the measurement electrodes, such as, for example, by the charging signal or other electromagnetic fields to which the measurement electrodes are exposed. In some implementations, the control elements are operated to electrically disconnect each of the measurement electrodes from the measurement amplifier during the delivery of the neural stimulus (i.e., in a stimulation phase preceding the autozeroing phase).

[0152] In some implementations, the control elements are operated to electrically disconnect each input node of the measurement amplifier from the respective potential-defining element that provides the fixed and common potential (e.g., one of the ground; the voltage supply rail; and the respective first and second return electrodes), at or immediately following termination of the autozeroing phase. In this manner, the proposed techniques advantageously vary the electrical connections of the input nodes of the measurement amplifier in accordance with the separate stimulation, autozeroing, and measurement phases of operation. This reduces or prevents the introduction of random noisecontributions caused by wireless charging on the measurement amplifier output, thereby enabling the neuromodulation device to accurately measure ECAP values, such as to perform CLNS therapy, without interrupting the charging of its energy storage device.

[0153] According to another implementation, the control unit is configured to operate the one or more control elements to maintain respective fixed, but not necessarily common or substantially common, potentials at each respective input node of the measurement amplifier. The measurement amplifier may be a differential amplifier or a non-differential amplifier, where wireless charging produces a noise signal at one or more input nodes of the amplifier. By maintaining the potential of each input node at the respective fixed value, the proposed techniques permit mitigation of a contribution of the noise signal to the measured neural response values. For example, in the case of a differential amplifier, the noise contribution is a predetermined offset in the voltage output of the amplifier. Therefore, the value of the offset can be controlled by setting the first and second fixed potentials at the respective first and second input nodes to particular values, for example to prevent the noise contribution from causing a clipping of the neural response signal. The effect of the offset on the output of the measurement amplifier can then be compensated for (e.g., by processing the output voltage values) thereby enabling accurate measurement of a characteristic of the evoked neural responses.Neuromodulation device with fixed measurement amplifier input node potentials

[0154] Fig. 12 illustrates a circuit model 1200 of an implantable neuromodulation device (e.g., a stimulator) 100 according to implementations of the proposed technology. Neuromodulation device 100 comprises a charging component 140 configured to wirelessly charge an energy storage device 104, for example via an electromagnetic charging signal 106 emitted by an external charger 102.

[0155] Neuromodulation device 100 is configured to perform measurement of evoked neural responses during a charging operation performed by charging component 140. In response to emission of the charging signal 106 by the charger 102, the charging component 140 induces a noise signal on the measurement electrodes 6, 8, or on electrical connectors at the first and second input nodes 1102 and 1104 of the measurement amplifier 1101, via capacitive couplings represented as capacitances Cpand Cp’ respectively.

[0156] In some implementations, the neuromodulation device 100 includes a stimulus source (not shown) configured to provide neural stimuli, via one or more stimulation electrodes including at least one return electrode, to evoke a neural response from a neural pathway.

[0157] The neuromodulation device 100 further comprises one or more control elements 1201 connected to one or more input nodes of the measurement amplifier 1101. In the example circuit ofFig. 12, the measurement amplifier 1101 has first and second input nodes 1102 and 1104 connected to a respective first set 1202 and second set 1204 of the one or more control elements 1201. Input voltages FW1and VN2sensed at first and second measurement amplifier input nodes 1102 and 1104 produce corresponding input terminal voltages Vinland Vin2at input terminals 1142 and 1144. The measurement amplifier 1101 produces output voltages Voutl= — AmVN1and Vout2= — i4m7W2at output lines 1106 and 1108, where Amis the measurement amplifier gain. The differential output of the measurement amplifier 1101 is given by Vout= Vout2— Voutl= -4m(wi— VN2).

[0158] In some implementations, the one or more control elements 1201 comprise one or more electrical switches that are operated by control circuitry of the neuromodulation device 100, including for example control unit 116. The electrical switches are operable to permit or prevent a flow of electrical current between: an input node 1102, 1104 of the measurement amplifier; and a potentialdefining element 1212, 1214, to maintain a fixed potential at the respective input nodes of the measurement amplifier 1101, the potential being determined by the potential-defining element 1212, 1214. In some implementations, each of the one or more electrical switches has a low impedance such that, when the switch is closed, a fixed potential provided by the potential-defining element is passed to the respective input node of the measurement amplifier without any substantial drop over the switch itself (as shown in the examples described herein).

[0159] First and second measurement electrodes 6 and 8 are in contact with the neural tissue 1120 of the neural pathway receiving the neural stimulus. The first input node 1102 and the second input node 1104 of the measurement amplifier 1101 are configured for electrical connection to the first measurement electrode 6 and the second measurement electrode 8 respectively. In some implementations, the electrical connection of the first measurement electrode 6 and second measurement electrode 8 to the respective first input node 1102 and the respective second input node 1104 of the measurement amplifier 1101 is controlled via the one or more control elements 1201. In some implementations, the electrical connection of the first measurement electrode 6 and second measurement electrode 8 to the respective first input node 1102 and the respective second input node 1104 of the measurement amplifier 1101 is fixed. In some such implementations, the fixed potential provided by the potential-defining element 1212, 1214 may be applied to the respective first input node 1102 and the respective second input node 1104 of the measurement amplifier 1101 and to each of the first measurement electrode 6 and second measurement electrode 8.

[0160] The control unit 116 of the neuromodulation device 100 operates the one or more control elements 1201 to maintain, during the autozeroing phase, a fixed potential at each respective input node 1102, 1104 of the measurement amplifier 1101, to permit mitigation of a noise contribution ofthe wireless charging on the measurement of a characteristic of the neural response. This advantageously allows the neuromodulation device 100 to accurately measure a characteristic of an evoked neural response, such as an ECAP characteristic value, from the output of the measurement amplifier 1101 without interruption to, or by, the wireless charging of the energy storage device 104 (i.e., irrespective of the presence of inductive noise generated by the charging component 140 during charging).Example configurations using device reference potentials

[0161] Fig. 13a illustrates a first example circuit 1300 of the model 1200 depicted in Fig. 12, in which fixed and common reference potentials of the neuromodulation device 100 are maintained at the input nodes of the measurement amplifier 1101. In the first example circuit 1300, the one or more control elements 1301 comprise: a first electrical switch 1302 configured to electrically connect the first input node 1102 of the measurement amplifier 1101 to one of a set of potential-defining elements 1310; and a second electrical switch 1304 configured to electrically connect the second input node 1104 of the measurement amplifier 1101 to the same one of the set of potential-defining elements 1310.

[0162] The set of potential-defining elements 1310 comprise one or more elements that each provide a reference potential, including in this example, a ground node 1312 set to a ground potential (e.g., 0 V), and a voltage supply rail 1314 set to a system potential (e.g., VDDHV). Electrical switch 1309 is operable (e.g., by the control unit 116, or other control circuitry of the neuromodulation device 100) to toggle the potential provided to each of the first input node 1102 and the second input node 1104 of the measurement amplifier 1101, via the switches 1302 and 1304, between the reference potentials of the potential-defining elements 1310. In some implementations, the set of potential-defining elements 1310 comprises elements other than a ground node and a voltage supply rail. For example, the set of potential-defining elements 1310 may be configured to selectively provide a fixed and common potential of any arbitrary value to the input nodes 1102 and 1104 of the measurement amplifier 1101, via the first and second switches 1302 and 1304.

[0163] The control unit 116 is configured to operate the first and second switches 1302 and 1304 synchronously, such that both of the input nodes 1102 and 1104 are together either electrically connected to (i.e., when the switches 1302 and 1304 are closed), or electrically disconnected from (i.e., when the switches 1302 and 1304 are open), the potential-defining elements 1310.

[0164] In the first example circuit 1300 of Fig. 13a, the one or more control elements 1301 further comprise: a third electrical switch 1302’ configured to electrically connect the first input node 1102 of the measurement amplifier 1101 to the first measurement electrode 6; and a fourth electrical switch 1304’ configured to electrically connect the second input node 1104 of the measurement amplifier1101 to the second measurement electrode 8. The control unit 116 is configured to operate the third and fourth switches 1302’ and 1304’ synchronously, such that both of the input nodes 1102 and 1104 are together either electrically connected to (i.e., when the switches 1302’ and 1304’ are closed), or electrically disconnected from (i.e., when the switches 1302’ and 1304’ are open), the respective measurement electrodes 6 and 8. This enables the control unit 116 to advantageously prevent any distortion of an otherwise fixed potential, as provided by an electrical connection to a potentialdefining element of set 1310, at the input nodes 1102 and 1104 due to noise or residual voltages on the measurement electrodes 6 and 8.

[0165] By operating the first and second electrical switches 1302 and 1304, and optionally the third and fourth switches 1302’ and 1304’, the control unit 116 is therefore able to maintain a fixed and common potential (i.e., a reference potential provided by potential-defining element set 1310) at the first input node 1102 and the second input node 1104 of the measurement amplifier 1101. The reference potential is maintained at the first input node 1102 and the second input node 1104 of the measurement amplifier 1101 during autozeroing of the measurement amplifier 1101.

[0166] As shown in Fig. 13a, measurement amplifier 1101 has a first feedback impedance 1322 connected between a first output line 1106 and first input terminal 1142; and a second feedback impedance 1324 connected between a second output line 1108 and second input terminal 1144. During autozeroing of the measurement amplifier 1101, the first output line 1106 and second output line 1108 are respectively shorted to first input terminal 1142 and second input terminal 1144, via the closing of a first electrical switch 1332 and a second electrical switch 1334 respectively (referred to herein as “autozeroing (AZ) switches”). In response to the closing of the AZ switches 1332 and 1334, the amplifier input terminals 1142 and 1144 act as virtual ground nodes. In accordance with the proposed techniques, autozeroing of measurement amplifier 1101 therefore samples the fixed and common reference potential at each input node 1102 and 1104 and stores that potential on the input capacitors 1103 and 1105 for later use in determining the differential output voltage Vout. This prevents the output voltage Voutfrom being distorted by a random DC offset that may otherwise be generated from sampling the voltages at the input nodes 1102 and 1104 when these input voltages are driven by a noise signal of the induced charging (i.e., instead of being maintained at the fixed reference potential).

[0167] Fig. 13b illustrates a second example circuit 1300’ of the model 1200 depicted in Fig. 12, in which fixed, but not necessarily common, reference potentials of the neuromodulation device 100 are maintained at the input nodes 1102, 1104 of the measurement amplifier 1101. In the second example circuit 1300’, the one or more control elements 1301 comprise: a first electrical switch 1302configured to electrically connect the first input node 1102 of the measurement amplifier 1101 to one of a first set of potential-defining elements 1310; and a second electrical switch 1304 configured to electrically connect the second input node 1104 of the measurement amplifier 1101 to one of a second set of potential-defining elements 1311.

[0168] The first and second sets of potential-defining elements 1310 and 1311 each provide separate first and second reference potentials to first and second input nodes 1102 and 1104, via the first and second switches 1302 and 1304. For example, the first set of potential-defining elements 1310 comprises a ground node 1312 set to a ground potential (e.g., 0 V), and a voltage supply rail 1314 set to a system potential (e.g., VDDHV). The second set of potential-defining elements 1311 comprises a ground node 1313, and a voltage supply rail 1315.

[0169] In the second example circuit 1300’, the control unit 116 is configured to operate separate electrical switches 1309 and 1307 (referred to as first and second “potential-defining switches”) to independently control the reference potential that is provided to each of the first input node 1102 and the second input node 1104 of the measurement amplifier 1101, when the corresponding first and second switches 1302 and 1304 are closed. For example, the first potential-defining switch 1309 may be operated to cause the first set of potential-defining elements 1310 to provide a ground potential (e.g., 0 V) via ground node 1312, or a system potential (e.g., VDDHV) via voltage supply rail 1314, to the first input node 1102, when the first switch 1302 is closed. Likewise, the second potentialdefining switch 1307 may be operated to cause the second set of potential-defining elements 1311 to provide a ground potential (e.g., 0 V) via ground node 1313, or a system potential (e.g., VDDHV) via voltage supply rail 1315, to the second input node 1104, when the second switch 1304 is closed. Each of the first and second potential-defining switches 1309 and 1307 can be actuated by the control unit 116 to a selected state to collectively achieve any arbitrary combination of reference potentials for provision to the first and second input nodes 1102 and 1104.

[0170] As for the first example circuit 1300, each set of potential-defining elements 1310 and 1311 may comprise other elements configured to provide a fixed potential of any arbitrary value to the input nodes 1102 and 1104 of the measurement amplifier 1101, via the first and second switches 1302 and 1304. This permits control over a difference between the fixed potentials maintained at the first input node 1102 and the second input node 1104 of the measurement amplifier 1101.

[0171] In some implementations, the control unit 116 is configured to maintain the potential-defining switches 1309 and 1307 in a respective selected state as long as the corresponding first and second switches 1302 and 1304 are closed (i.e., such that the reference potential provided to the respective input node of the measurement amplifier 1101 is not altered). The control unit 116 is configured tooperate the first and second switches 1302 and 1304, and optionally the third and fourth switches 1302’ and 1304’, analogously to the first example circuit 1300. That is, both the input nodes 1102 and 1104 are respectively together either electrically connected to, or electrically disconnected from: the first and second sets of potential-defining elements 1310 and 1311, based on the states of the first and second switches 1302 and 1304; and, optionally, the measurement electrodes 6 and 8, based on the states of the third and fourth switches 1302’ and 1304’.

[0172] For the second example circuit model 1300’, autozeroing of measurement amplifier 1101 involves sampling the fixed reference potential provided at each of the first input node 1102 and the second input node 1104 (as fixed “first and second reference potentials”), and the storage of the fixed first and second reference potentials on the respective input capacitors 1103 and 1105 for use in determining the differential output voltage Vout. Although the fixed first and second reference potentials may not necessarily be equal, the values of the first and second reference potentials are known, thereby allowing control over the offset that will appear in the output voltage Vout. For example, the fixed first and second reference potentials can be controlled to prevent clipping of the output voltage Voutof the measurement amplifier 1101. As for the first example circuit 1300, this prevents the output voltage from being distorted by a random DC offset that may otherwise be generated from sampling the voltages at the input nodes 1102 and 1104 when these input voltages are driven by an induced charging noise signal (i.e., instead of being maintained at the respective fixed reference potential).Example configurations using return electrodes

[0173] Fig. 13c illustrates a third example circuit 1300” of the model 1200 depicted in Fig. 12, in which a fixed potential is maintained at the first input node 1102 and the second input node 1104 of the measurement amplifier 1101. The fixed potential at each respective input node 1102 and 1104 of the measurement amplifier 1101 is maintained by connection to a respective first return electrode 1352 and a second return electrode 1354 following the delivery of the neural stimulus, such as for example by the application of a stimulus current by a stimulus source.

[0174] In the third example circuit 1300”, the one or more control elements 1301 comprise a first electrical switch 1302 and a second electrical switch 1304 configured to electrically connect the first input node 1102 and the second input node 1104 of the measurement amplifier 1101 to a respective first return electrode 1352 and a second return electrode 1354. First and second return electrodes 1352 and 1354 are in contact with first and second tissue regions 1122 and 1124 and are also connected to a fixed potential, such as a ground potential as illustrated in Fig. 13c. In some implementations, thefirst and second return electrodes 1352 and 1354 are return electrodes used by the neuromodulation device 100 to deliver the neural stimulus to the neural tissue 1120.

[0175] The control unit 116 is configured to operate the first and second switches 1302 and 1304 synchronously, such that both the first input node 1102 and the second input node 1104 are together either electrically connected to, or electrically disconnected from, the respective first return electrode 1352 and second return electrode 1354 based on the state of the first and second switches 1302 and 1304. The electrical connection of the first and second input nodes 1102 and 1104 to the respective first and second return electrodes 1352 and 1354 provides a fixed potential at the first input node 1102, and a fixed potential at the second input node 1104. In some implementations, the fixed potentials of the first return electrode 1352 and the second return electrode 1354 are common, or substantially common, such as when the first and second return electrodes 1352 and 1354 are themselves connected to a fixed and common potential, such as a ground potential as illustrated in Fig. 13c.

[0176] In the third example circuit 1300” of Fig. 13c, the one or more control elements 1301 further comprise: a third electrical switch 1302’ configured to electrically connect the first input node 1102 of the measurement amplifier 1101 to the first measurement electrode 6; and a fourth electrical switch 1304’ configured to electrically connect the second input node 1104 of the measurement amplifier 1101 to the second measurement electrode 8.

[0177] The control unit 116 operates the first and second electrical switches 1302 and 1304, and optionally the third and fourth switches 1302’ and 1304’, analogously to the example circuit 1300 of Fig. 13a to maintain a fixed and common, or substantially common, potential (i.e., the ground potential, as provided by the respective first and second return electrodes 1352 and 1354) at the first input node 1102 and the second input node 1104 during autozeroing of the measurement amplifier 1101.

[0178] Fig. 13d illustrates a fourth example circuit 1300’” of the model 1200 depicted in Fig. 12, in which a fixed and common potential is maintained at the first input node 1102 and the second input node 1104 of the measurement amplifier 1101. The fourth example circuit 1300’” is configured analogously to the third example circuit 1300” of Fig. 13c, but where the respective first and second return electrodes 1352 and 1354 of Fig. 13c are instead implemented as the same return electrode 1355, which in turn is connected to a fixed potential, such as a ground potential as illustrated in Fig.13d. This advantageously prevents an offset between the respective potentials provided to the first input node 1102 and the second input node 1104, since only one fixed potential is obtained from the return electrode 1355.

[0179] In some implementations, the one or more control elements 1301 comprise one or more multiposition electrical switches each configured to establish an electrical connection between an input node 1102 or 1104 of the measurement amplifier 1101 and a plurality of electrodes. For example, any of the example circuits 1300, 1300’, 1300” and 1300’” may be implemented with a first multiposition switch that combines the functionality of individual electrical switches 1302 and 1302’ to control the potential at the first input node 1102 of the measurement amplifier 1101.

[0180] The first multi-position switch may be a Single Pole Triple Throw (SP3T) switch configured to toggle the first input node 1102 of the measurement amplifier 1101 between: an electrical connection to a potential-defining element (e.g., a ground node or voltage supply rail) or to the first return electrode 1352; an electrical connection to the first measurement electrode 6; and an electrical disconnection to any electrode or potential-defining element (i.e., an open-circuit output). A second multi-position switch may be implemented that combines the functionality of individual electrical switches 1304 and 1304’ to control the potential at the second input node 1104 of the measurement amplifier 1101. In some implementations, a multiplexing circuit is used to toggle the connection of each of the first and second input nodes 1102 and 1104 between a respective potential-defining element, a respective return electrode, a respective measurement electrode, and electrical disconnection.

[0181] The use of one or more return electrodes 1352, 1354 to set and maintain a fixed and common, or substantially common, potential at each of the first and second input nodes 1102 and 1104 of the measurement amplifier 1101 is advantageous in that the neuromodulation device 100 does not need to provide extra connections between the amplifier input nodes and ground nodes or a supply rail, but instead may utilize existing connections between the amplifier input nodes and the electrode array 150. Further, connecting the first and second input nodes 1102 and 1104 of the measurement amplifier 1101 to the return electrodes 1352 and 1354, while the return electrodes 1352 and 1354 are themselves connected to a fixed potential, allows the autozeroing phase to capture an accurate representation of the tissue potential on the input capacitors 1103 and 1105 before the ECAP measurement. This may advantageously limit transients occurring when the amplifier input nodes 1102 and 1104 are later connected to the measurement electrodes 6 and 8 for the purpose of ECAP measurement.

[0182] Further, in some implementations the neural tissue 1120 is held at a non-ground potential during stimulus and measurement phases (as described below). Therefore, the connection of the input nodes 1102 and 1104 of the amplifier 1101 to the tissue potential (e.g., via the return electrodes 1352, 1354), rather than to a ground potential, during autozeroing minimises transients at the start of the measurement phase.Method of neural response measurement during wireless charging

[0183] Fig. 14a illustrates a method 1400 for measuring a characteristic of an evoked neural response according to the techniques proposed herein. Method 1400 may be performed by a neural stimulation system operating a neuromodulation device for the purpose of providing neuromodulation therapy, such as for example the neural stimulation system 700 and corresponding neuromodulation device 710 depicted in Fig. 7.

[0184] At step 1402, wireless charging of an energy storage device 104 of the neuromodulation device commences. For example, with reference to the example configurations of Figs. Ila and 1 lb, the charger 102 is be placed in proximity of the charging coil 140 of the device 100. While in proximity, the charger 102 is configured to emit the electromagnetic charging signal 106 to induce the charging coil 140 to achieve wireless charging of the neuromodulation device, and to sustain the wireless charging through other steps of the method 1400, including at least steps 1406 and 1408.

[0185] At step 1404, a neural stimulus is delivered to a neural pathway to evoke a neural response from the neural pathway. In some examples, the neural stimulation system or device controls a stimulus source to deliver the neural stimulus to neural tissue via one or more stimulation electrodes (e.g., stimulation electrodes 2 and 4 of electrode array 150, as depicted in Fig. 3), and according to a stimulus intensity parameter. In some examples, the stimulus intensity parameter is set by a control unit or processor of the neural stimulation system or device.

[0186] At step 1406, at least during an autozeroing phase, the first input node and the second input node of the measurement amplifier are each set to and maintained at a fixed potential, according to the techniques proposed herein, to mitigate a noise contribution of the wireless charging on the measurement of a characteristic of the evoked neural response.

[0187] At step 1408, a characteristic of the neural response evoked by the neural stimulus is measured such as for example to determine an intensity of the neural response (e.g., an ECAP value). The sensed signal is amplified using the measurement amplifier, and the neural response is subsequently measured from the amplified sensed signal. The neural stimulation system or device measures the evoked neural response from a signal provided between the first input node and the second input node of the measurement amplifier subsequent to the provision of the neural stimulus. For example, the signal may be sensed by a first measurement electrode and a second measurement electrode (e.g., electrodes 6 and 8 of the electrode array 150 depicted in Fig. 3), where the sensed signal comprises the neural response evoked from the stimulus.

[0188] In some examples, the measurement amplifier is an amplifier of measurement circuitry 128 and 318, as depicted in Figs. 3 and 5, being a differential amplifier connected to the first and second measurement electrodes at respective first and second input nodes.

[0189] In some examples, the neural stimulation system is a CLNS system (e.g., as depicted in Fig.5) that performs periodic adjustments to the stimulus intensity parameter to maintain the neural response at a target intensity. In such examples, at step 1410 a feedback variable is determined from the measurement of the neural response characteristic, and then, at step 1412, the feedback variable is used to control the value of the stimulus intensity parameter for the delivery of further neural stimuli to the tissue (e.g., by repeating step 1404 with an adjusted stimulus intensity parameter).

[0190] Fig. 14b illustrates an example timing graph 1450 of operational phases of the neuromodulation device used for the measurement of a characteristic of an evoked neural response via the method 1400. A stimulation phase 1452 comprises a period of time (i.e., the interval [t0, t^)) in which the neural stimulus is provided to the neural tissue (step 1404 of the method 1400). The stimulation phase 1452 precedes an autozeroing phase 1454 which comprises a period of time (i.e., the interval [t1(t2)) immediately preceding the measurement of a characteristic of the evoked neural response.

[0191] In the autozeroing phase 1454, the signal amplification capability of the measurement amplifier is adjusted, for example to minimize offset voltage and drift. In some examples, the measurement amplifier used to perform measurement of a characteristic of the evoked neural response has a plurality of stages. The autozeroing phase of the measurement amplifier persists while at least one of the plurality of stages is subject to autozeroing. According to the proposed techniques, at least during the autozeroing phase, the first input node and the second input node of the measurement amplifier are maintained at the fixed potentials(s) (i.e., as performed in step 1406 of method 1400).

[0192] As shown in Fig. 14b, the autozeroing phase 1454 terminates (i.e., at time t2) on or shortly before the commencement of the measurement phase 1456. The measurement phase comprises a period of time (i.e., the interval [t3, t4)) in which the evoked neural response is measured from the amplified sensed signal (i.e., as performed in step 1408 of method 1400). In some examples, a buffer period 1455 exists, comprising a time interval between the termination of the autozeroing phase (i.e., at t2) and the commencement of the measurement phase (i.e., at t3). The buffer period 1455 is typically of a relatively short duration compared to the duration of the autozeroing and measurement phases 1454 and 1456.

[0193] Fig. 15 illustrates an example method 1500 of operating a neuromodulation device to maintain a fixed potential at the input node(s) of a measurement amplifier according to step 1406 of the method1400. The neuromodulation device may be implemented according to any of the example circuits 1300, 1300’, 1300”, and 1300’”, comprising a measurement amplifier 1101, and a control unit configured to operate the one or more control elements 1301 to electrically connect and disconnect the input nodes of the measurement amplifier from various electrodes.

[0194] At step 1502, the control unit is configured to electrically disconnect first and second measurement electrodes 6 and 8 from the measurement amplifier 1101, for example from the respective first and second input nodes 1102 and 1104. With reference to timing graph 1450 of Fig.14b, the electrical disconnection of the measurement electrodes 6 and 8 occurs prior to the commencement of the autozeroing phase 1454. In some implementations, the electrical disconnection of the measurement electrodes 6 and 8 from the measurement amplifier 1101 occurs prior to or during the stimulation phase 1452 preceding the autozeroing phase 1454.

[0195] As shown in Fig. 15, at step 1504 the autozeroing phase commences for example at time t1depicted in the timing graph 1450 of Fig. 14b. The electrical disconnection of the measurement electrodes 6 and 8 from the measurement amplifier 1101 persists through at least the autozeroing phase 1454.

[0196] At step 1506, the control unit operates the one or more control elements to electrically connect each input node of the measurement amplifier 1101 to a potential-defining element such as to set and maintain the input node(s) of the measurement amplifier 1101 at a fixed potential. For example, each of first and second input nodes 1102 and 1104 of the measurement amplifier may be connected to one of: a ground or a voltage supply rail, such that the fixed potential is a reference potential, or to a return electrode, which is in turn connected to a fixed potential. The fixed potentials at a plurality of input nodes of the measurement amplifier may be common potentials according to the examples described herein. The electrical connection persists through at least the autozeroing phase 1454.

[0197] At step 1508, the autozeroing phase terminates, for example at time t2depicted in the timing graph 1450 of Fig. 14b.

[0198] At step 1510, the control unit operates the one or more control elements to electrically disconnect each input node 1102 and 1104 of the measurement amplifier 1101 from the respective potential-defining element used to set and maintain the input node at a fixed potential. The electrical disconnection of the input nodes 1102 and 1104 of the measurement amplifier 1101 occurs after the autozeroing phase 1454 terminates, for example at a time in the buffer period 1455 between time t2and time t3in the timing graph 1450 of Fig. 14b.

[0199] At step 1512, the control unit operates the one or more control elements to electrically reconnect first and second measurement electrodes 6 and 8 to the measurement amplifier 1101, forexample to the respective first and second input nodes 1102 and 1104. The electrical reconnection of the measurement electrodes 6 and 8 to the measurement amplifier 1101 occurs after the autozeroing phase 1454 terminates. In some implementations, the electrical reconnection of the measurement electrodes 6 and 8 to the measurement amplifier 1101 occurs after the expiry of the buffer period 1455, for example at time t3depicted in the timing graph 1450 of Fig. 14b. The buffer period 1455 mitigates any minor timing errors between connection of measurement electrodes 6 and 8 to the measurement amplifier 1101 and the disconnection of the potential-defining elements from the measurement amplifier 1101 (e.g., a charging related offset that may result if the connection of the measurement electrodes 6 and 8 to the measurement amplifier 1101 occurs before the disconnection of the potential-defining element(s) at the termination of the autozeroing phase).

[0200] Following step 1512, the control unit operates the measurement amplifier 1101 to measure a characteristic of the evoked neural response, for example by determining an ECAP value from the output of the measurement amplifier 1101 (i.e., at step 1408 of Fig. 14a). By performing the operations of method 1500, the measurements of the evoked neural response are free from random DC offset noise contributions of the wireless charging.

[0201] In some implementations, the implantable neuromodulation device has a measurement amplifier with a plurality of stages configured in a cascade. Figs. 16a to 16d illustrate configurations of an example circuit model 1600 of an implantable neuromodulation device with a measurement amplifier 1601 having three stages 1601a, 1601b, and 1601c, configured to measure a characteristic of an evoked neural response. The control unit is configured to operate control elements 1602, 1604, 1602’ and 1604’ to maintain a fixed and common, or substantially common, potential at the first and second input nodes 1102 and 1104 of the measurement amplifier 1601 (i.e., at the first stage 1601a) according to the techniques described herein. The fixed and common potential is a ground potential in the configurations depicted in Figs. 16a to 16d. However, it will be appreciated that another reference potential may be maintained at the first and second input nodes instead of a ground potential, in accordance with the techniques described herein.

[0202] First stage 1601a comprises first and second input terminals 1642a and 1644a that are respectively connected to the first and second input nodes 1102 and 1104 of the measurement amplifier 1601 via first stage input capacitors 1603a and 1605a. The first stage 1601a has feedback impedances 1622a and 1624a, and corresponding autozeroing switches (“AZ switches”) 1632a and 1634a, at first and second feedback paths. First and second outputs 1606a, 1608a of the first stage 1601a are connected to corresponding first and second input terminals 1642b and 1644b of the second stage 1601b via second stage input capacitors 1603b and 1605b. The second stage 1601b has feedbackimpedances 1622b and 1624b, and corresponding AZ switches 1632b and 1634b, at first and second feedback paths. First and second outputs 1606b, 1608b of the second stage 1601b are connected to corresponding first and second input terminals 1642c and 1644c of the third stage 1601c via third stage input capacitors 1603c and 1605c. The third stage 1601c has feedback impedances 1622c and 1624c, and corresponding AZ switches 1632c and 1634c, at first and second feedback paths. The input capacitors and feedback impedances of each amplifier stage 1601a, 1601b, and 1601c are modelled as capacitances Cl to C12 in the example circuit models shown in Figs. 16a to 16d.

[0203] Fig. 16a illustrates circuit model 1600 at a time prior to the end of the stimulation phase. First and second switches 1602 and 1604 are opened to disconnect the ground node from the first and second input nodes 1102 and 1104 connected to the first stage 1601a. Third and fourth switches 1602’ and 1604’ are also open-circuited to disconnect the first and second measurement electrodes 6 and 8 from the first stage 1601a. In this configuration, the AZ switches for each amplifier stage 1601a, 1601b and 1601c are closed while the amplifier 1601 is autozeroed.

[0204] Fig. 16b illustrates circuit model 1600 at the commencement of the autozeroing phase (e.g., occurring at the end of the stimulation phase). The first and second switches 1602 and 1604 are closed to connect the ground node to the first and second input nodes 1102 and 1104 of the first stage 1601a. The fixed and common potential (i.e., the ground potential in this example) is stored by the input capacitors 1603a and 1605a, as shown in Figs. 16a to 16d, of the measurement amplifier 1601 during autozeroing. The AZ switches for each amplifier stage 1601a, 1601b and 1601c remain closed while the amplifier 1601 is autozeroed. The autozeroing phase persists while at least one of the plurality of stages 1601a, 1601b, 1601c is subject to autozeroing.

[0205] In some implementations, the individual stages of the measurement amplifier 1601 are configured to complete stage-specific autozeroing operations during the autozeroing phase. Fig. 16c illustrates circuit model 1600 when the first stage 1601a of the measurement amplifier 1601 ceases autozeroing at an end of a first period of time of the autozeroing phase. The second and third stages 1601b, 1601c of the measurement amplifier 1601 are still subject to autozeroing at the end of the first period of time of the autozeroing phase. The AZ switches 1632a and 1634a of the first stage 1601a are opened when the first stage 1601a ceases autozeroing at the end of the first period of time, while the AZ switches 1632b, 1634b, 1632c and 1634c of the second and third stages 1601b and 1601c remain closed.

[0206] Fig. 16d illustrates circuit model 1600 after one or more subsequent periods of time following the first period when the remaining stages of the measurement amplifier 1601 cease autozeroing. The second and third stages 1601b, 1601c of the measurement amplifier 1601 complete autozeroing at theend of a second period of the autozeroing phase and a third period of the autozeroing phase respectively. At the end of the third period of the autozeroing phase, the AZ switches 1632b, 1634b, 1632c and 1634c of the second and third stages 1601b and 1601c are opened. The effect of sampling the fixed and common potential provided at the first and second input nodes 1102 and 1104 has therefore propagated through all stages of the measurement amplifier 1601 to complete the autozeroing. First and second switches 1602 and 1604 are subsequently opened to disconnect the ground node from the first and second input nodes 1102 and 1104 of the first stage 1601a. Third and fourth switches 1602’ and 1604’ are closed to connect the first and second measurement electrodes 6 and 8 to the respective input nodes of the first stage 1601a after the termination of the autozeroing phase.Experimental evaluation

[0207] An experimental evaluation was performed of the method 1400 for measuring a characteristic of an evoked neural response. In a first experiment, evoked neural responses were measured using a stimulator 100 configured according to the circuit model 1100 shown in Fig. 1 lb. Fig. 17a illustrates a graph 1700 of evoked neural responses 1702 at the output of the measurement amplifier 1101 in the absence of charging. Fig. 17b illustrates a graph 1750 of evoked neural responses 1752 at the output of the measurement amplifier 1101 during a charging operation. The difference in the neural responses measured during the charging operation relative to the neural responses obtained in the absence of charging apparent in Figs. 17a and 17b is a result of a noise contribution from induced noise signal Vnoise. The difference in neural responses in turn interferes with the evoked response intensity (feedback variable) measurement.

[0208] Fig. 18a illustrates a graph 1800 of a feedback variable histogram 1802 for performing CLNS therapy using the stimulator 100 configured according to the circuit model 1100 shown in Fig. 1 lb. The feedback variable values shown in histogram 1802 are derived from the evoked neural responses 1702 measured from the output of the measurement amplifier 1101 in the absence of charging.

[0209] Fig. 18b illustrates a graph 1850 of a feedback variable histogram 1852 on a similar horizontal scale to that of Fig. 18a, but where the feedback variable values are instead derived from the evoked neural responses 1752 at the output of the measurement amplifier 1101 during a charging operation. As can be observed from Fig. 18b, the variance (spread) of the feedback variable histogram 1852 is significantly larger during charging, compared to the feedback variable histogram 1802 in the absence of charging (as shown in Fig. 18a).

[0210] Fig. 19a illustrates a graph 1900 of a stimulation current histogram 1902 of stimulation currents provided by the stimulator 100 for CLNS therapy performed using a feedback variablederived from ECAP measurements in the absence of charging, as depicted in Fig. 18a. Fig. 19b illustrates a graph 1950 of a stimulation current histogram 1952, on a similar horizontal scale to that of Fig. 19a, provided by the stimulator 100 for CLNS therapy performed using a feedback variable derived from ECAP measurements during charging, as depicted in Fig. 18b. The distribution (spread) of the histogram 1952 of stimulation current values obtained when corresponding ECAP measurements are conducted during wireless charging is significantly wider than the distribution of the histogram 1902 of stimulation current values in the absence of the charging (as shown in Fig.19a).

[0211] As can be observed from comparing the feedback variable histograms of Figs. 18a and 18b, and the stimulation current histograms of Figs. 19a, and 19b, inaccuracies in the measurement of ECAP values due to wireless charging of the energy storage device cause a distortion of the feedback variable, and hence greater variation of the stimulation current delivered by the stimulator 100 when it is configured to perform CLNS therapy during the charging.

[0212] In a second experiment, evoked neural responses were measured using a stimulator 100 configured according to the proposed techniques. Example circuit 1300”’ depicted in Fig. 13d was used to configure the model 1200 shown in Fig. 12 to conduct the second experiment. Fig. 20a illustrates a graph 2000 of evoked neural responses 2002 at the output of the measurement amplifier 1101 in the absence of charging. Fig. 20b illustrates a graph 2050 of evoked neural responses 2052 at the output of the measurement amplifier 1101 during a charging operation. The effect of maintaining the input nodes 1102 and 1104 of the measurement amplifier 1101 at a fixed and common potential is observed in the greater similarity of the neural responses measured during the charging operation (graph 2052) to the neural responses that are obtained in the absence of charging (i.e., graph 2002) than is apparent between the responses in Figs. 17a (no charging) and 17b (charging).

[0213] Fig. 21a illustrates a graph 2100 of a feedback variable histogram 2102 for performing CLNS using the stimulator 100 configured according to the circuit model 1300’” shown in Fig. 13d. The feedback variable values in the histogram 2102 are derived from the evoked neural responses 2002 at the output of the measurement amplifier 1101 in the absence of charging.

[0214] Fig. 21b illustrates a graph 2150 of a feedback variable histogram 2152 on a similar horizontal scale to that of Fig. 21a, but where the feedback variable values are instead derived from the evoked neural responses 2052 at the output of the measurement amplifier 1101 during a charging operation.

[0215] As can be observed from comparing Figs. 21a and 21b, the feedback variable histograms 2102 and 2152 have a similar distribution (spread). The experimental evaluation confirms that a stimulator 100 configured according to the proposed techniques experiences mitigation of a noise contributionof the wireless charging, resulting in an improved ability of the stimulator 100 to sense evoked responses, and to generate corresponding feedback variable values, with accuracy during charging (i.e., compared to a stimulator 100 configured according to the conventional model).Interpretation

[0216] The technology disclosed herein may be implemented in hardware (e.g., using digital signal processors, application specific integrated circuits (ASICs) or field programmable gate arrays (FPGAs)), or in software (e.g., using instructions tangibly stored on non-transitory computer-readable media for causing a data processing system to perform the steps described herein), or in a combination of hardware and software. The disclosed technology can also be implemented as computer-readable code on a computer-readable medium. The computer-readable medium can include any data storage device that can store data which can thereafter be read by a computer system. Examples of the computer-readable medium include read-only memory ("ROM"), random-access memory ("RAM"), magnetic tape, optical data storage devices, flash storage devices, or any other suitable storage devices. The computer-readable medium can also be distributed over network-coupled computer systems so that the computer-readable code is stored or executed in a distributed fashion. The present technology is not limited to any particular programming language or operating system.Wireless

[0217] In the context of the present disclosure, the term “wireless” and its derivatives may be used to describe circuits, devices, systems, methods, techniques, communications channels, etc., that may communicate data through the use of modulated electromagnetic radiation through a non-solid medium. The term does not imply that the associated devices do not contain any wires, although in some embodiments they might not. In the context of the present disclosure, the term “wired” and its derivatives may be used to describe circuits, devices, systems, methods, techniques, communications channels, etc., that may communicate data through the use of modulated signals propagating through a conductive medium. The term does not imply that the associated devices are coupled by electrically conductive wires.

[0218] Wireless communication standards that can be accommodated include IEEE 802.11 wireless LANs and links, Bluetooth, and wireless Ethernet. The technology disclosed herein may be implemented using devices conforming to other network standards and for other applications, including, for example other WLAN standards and other wireless standards such as MICS.Processes

[0219] Unless specifically stated otherwise, as apparent from the following discussions, it is appreciated that throughout the specification discussions utilizing terms such as “processing”,“computing”, “comparing”, “estimating”, “calculating”, “determining”, “analysing” or the like, refer to the action or processes of a computer or computing system, or similar electronic computing device, that manipulate or transform data represented as physical, such as electronic, quantities into other data similarly represented as physical quantities, or to otherwise execute a predefined procedure suitable to effect the described actions.Processor

[0220] In a similar manner, the term “processor” may refer to any device or portion of a device that processes electronic data, e.g., from registers or memory, to transform that electronic data into other electronic data that, e.g., may be stored in registers or memory. A “computer” or a “computing device” or a “computing machine” or a “computing platform” may include one or more processors.

[0221] The methods described herein are, in one embodiment, performable by one or more processors that accept computer-readable (also called machine-readable) code containing a set of instructions that when executed by one or more of the processors cause the one or more processors to carry out at least one of the methods described herein. Any processor capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken are included within the meaning of the term “processor”. Thus, one example is a typical processing system that includes one or more processors. The processing system further may include a memory subsystem including main RAM or a static RAM, or ROM.Networked or Multiple Processors

[0222] In alternative embodiments, the one or more processors operate as respective standalone device(s) or may be connected, e.g., networked to other processor(s), in a networked deployment. The one or more processors may operate in the capacity of a server or a client machine in serverclient network environment, or as a peer machine in a peer-to-peer or distributed network environment. The one or more processors may form a web appliance, a network router, switch or bridge, or any machine capable of executing a set of instructions (sequential or otherwise) that specify actions to be taken by that machine.

[0223] Note that while some diagram(s) only show(s) a single processor and a single memory that carries the computer-readable code, those in the art will understand that many of the components described above are included, but not explicitly shown or described in order not to obscure the inventive aspect. For example, while only a single machine may be illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methods discussed herein.Additional Implementations

[0224] Thus, one implementation of each of the methods described herein is in the form of a computer-readable medium carrying a set of instructions, e.g., a computer program that are for execution on one or more processors. Thus, as will be appreciated by those skilled in the art, aspects of the present technology may be implemented as a method, an apparatus such as a special purpose apparatus, an apparatus such as a data processing system, or a computer-readable medium. The computer-readable medium carries computer-readable code including a set of instructions that when executed on one or more processors cause the processor or processors to implement a method. Accordingly, aspects of the present technology may take the form of a method, an entirely hardware implementation, an entirely software implementation or an implementation combining software and hardware aspects. Furthermore, the present technology may take the form of a carrier medium (e.g., a computer program product) carrying computer-readable program code embodied in the medium.Carrier Medium

[0225] The software may further be transmitted or received over a network via a network interface device. While the carrier medium is shown in an example embodiment to be a single medium, the term “carrier medium” should be taken to include a single medium or multiple media (e.g., a centralized or distributed database, or associated caches and servers) that store the one or more sets of instructions. A carrier medium may take many forms, including but not limited to, non-volatile media, volatile media, and transmission media.Means For Carrying out a Method or Function

[0226] Furthermore, some of the implementations are described herein as a method or combination of elements of a method that can be implemented by a processor of a processor device, computer system, or by other means of carrying out the function. Thus, a processor with the necessary instructions for carrying out such a method or element of a method forms a means for carrying out the method or element of a method. Furthermore, an element described herein of an apparatus is an example of a means for carrying out the function performed by the element.

[0227] Those of skill would further appreciate that the various illustrative logical blocks, modules, and algorithm steps described in connection with the implementations disclosed herein may be implemented as electronic hardware, computer software running on a special purpose machine that is programmed to carry out the operations described in the present disclosure, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. Skilled artisans mayimplement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the exemplary implementations.Implementations

[0228] Reference throughout the present disclosure to “one implementation” or “an implementation” means that a particular feature, structure or characteristic described in connection with the implementation is included in at least one implementation of the present technology. Thus, appearances of the phrases “in one implementation” or “in an implementation” in various places throughout the present disclosure are not necessarily all referring to the same implementation, but may refer to different implementations. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more implementations.

[0229] Similarly, it should be appreciated that in the above description of example implementations of the present technology, various features are sometimes grouped together in a single implementation, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects may lie in less than all features of a single foregoing disclosed implementation. Thus, the claims following the Detailed Description of the Present Technology are hereby expressly incorporated into this Detailed Description of the Present Technology, with each claim standing on its own as a separate implementation of the present technology.

[0230] Furthermore, while some implementations described herein include some, but not other features included in other implementations, combinations of features of different implementations are meant to be within the scope of the present technology, and form different implementations of the present technology, as would be understood by those in the art. For example, in the following claims, any of the claimed implementations can generally be used in any combination.

[0231] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word "about" or "approximately," even if the term does not expressly appear. The phrase "about" or "approximately" may be used when describing magnitude or position to indicate that the value or position described is within a reasonable expected range of values or positions. For example, a numeric value may have a value that is + / - 0.1% of the stated value (or range of values), + / - 1% of the stated value (or rangeof values), + / - 2% of the stated value (or range of values), + / - 5% of the stated value (or range of values), + / - 10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that each value between two particular values is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.Different Instances of Objects

[0232] As used herein, unless otherwise specified the use of the ordinal adjectives “first”, “second”, “third”, etc., to describe a common object, merely indicates that different instances of like objects are being referred to, and is not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking, or in any other manner.Specific Details

[0233] In the description provided herein, numerous specific details are set forth. However, it is understood that implementations of the present technology may be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of the present technology.Terminology

[0234] Throughout the present disclosure, the terms "a" and "an" mean "one or more", unless expressly specified otherwise.

[0235] Throughout the present disclosure, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer, or step, or group of elements, integers, or steps, but not the exclusion of any other element, integer, or step, or group of elements, integers, or steps.

[0236] Throughout the present disclosure, a statement that an element may be “at least one of’ or “one or more of’ a list of options is to be understood to mean that the element may be any one of the listed options, or may be any combination of two or more of the listed options.

[0237] Throughout the present disclosure, the word “or” is to be read inclusively rather than exclusively, except where otherwise indicated.

[0238] Neither the title nor any abstract of the present disclosure should be taken as limiting in any way the scope of the claimed invention.

[0239] Where the preamble of a claim recites a purpose, benefit or possible use of the claimed invention, it does not necessarily limit the claimed invention to having only that purpose, benefit or possible use.

[0240] In the present specification, terms such as "part", "component", "means", "section", or "segment" may refer to singular or plural items and are terms intended to refer to a set of properties, functions, or characteristics performed by one or more items having one or more parts. It is envisaged that where a "part", "component", "means", "section", "segment", or similar term is described as consisting of a single item, then a functionally equivalent object consisting of multiple items is considered to fall within the scope of the term; and similarly, where a "part", "component", "means", "section", "segment", or similar term is described as consisting of multiple items, a functionally equivalent object consisting of a single item is considered to fall within the scope of the term. The intended interpretation of such terms described in this paragraph should apply unless the contrary is expressly stated or the context requires otherwise.

[0241] The term "connected" or a similar term, should not be interpreted as being limited to direct connections only. Thus, the scope of the expression “an item A connected to an item B” should not be limited to items or systems wherein an output of item A is directly connected to an input of item B. It means that there exists a path between an output of A and an input of B which may be a path including other items or means. "Connected", or a similar term, may mean either that two or more elements are in direct physical or causal contact, or that two or more elements are not in direct contact with each other yet still co-operate or interact with each other.

[0242] It will be appreciated by persons skilled in the art that numerous variations or modifications may be made to the present technology as shown in the specific implementations without departing from the spirit or scope of the invention as broadly described. For example, any formulas given above are merely representative of procedures that may be used. Functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present technology. The disclosed implementations are, therefore, to be considered in all respects as illustrative and not limiting or restrictive.

[0243] The features described in relation to one or more aspects of the present technology are to be understood as applicable to other aspects of the present technology. More generally, combinations of the steps in the method(s) of the present technology or the features of the system(s) or device(s) of the present technology described elsewhere in the present disclosure, including in the claims, are to be understood as falling within the scope of the present disclosure.INDUSTRIAL APPLICABILITY

[0244] It is apparent from the above that the arrangements described are applicable to the health care industries.LABEL LISTDevice 100 signal window 319 Charger 102 ECAP detector 320 energy storage device 104 comparator 324 charging signal 106 gain element 336 Patient 108 integrator 338 electronics module 110 activation plot 402 Battery 112 ECAP threshold 404 telemetry module 114 discomfort threshold 408 control unit 116 perception threshold 410 Memory 118 therapeutic range 412 clinical data 120 activation plot 502 clinical settings 121 activation plot 504 control programs 122 activation plot 506 pulse generator 124 ECAP threshold 508 electrode selection module 126 ECAP threshold 510 measurement circuitry 128 ECAP threshold 512 Ground 130 target ECAP amplitude 520 charging coil 140 ECAP 600 rectifier circuit 142 neural stimulation system 700 Array 150 neuromodulation device 710 biphasic stimulus pulse 160 remote controller 720 ECAPs 170 CST 730 target fibres 180 CI 740 communications channel 190 Charger 750 external computing device 192 Illustration 800 CLNS system 300 Pulse 810 clinical settings controller 302 ISI 815 target ECAP controller 304 Pulse 820 Box 308 stimulus pulse 830 Box 309 stimulus pulse 840 controller 310 stimulus pulse 850 Box 311 ECAP 860 pul se generator 312 stimulus period 890 pul se generator 312 A multi - stimset CLNS system 900 pul se generator 312B data flow 1000 pul se generator 312C neuromodulation device 1004 pul se generator 312D CPA 1010 element 313 clinical data log file 1012 measurement circuitry 318 CDV 1014clinical Data Uploader 1016 return el ectrode 1352 database Loader 1022 return el ectrode 1354 Database 1024 return el ectrode 1355 data analysis web API 1026 method 1400 analysis module 1032 step 1402 circuit model 1100 step 1404 Amplifier 1101 step 1406 input nodes 1102 step 1408 input capacitor 1103 step 1410 input node 1104 step 1412 input capacitor 1105 graph 1450 first output line 1106 stimulation phase 1452 output line 1108 measurement phase 1454 neural tissue 1120 buffer period 1455 tissue region 1122 measurement phase 1456 tissue region 1124 Method 1500 charging circuitry 1140 Step 1502 input terminal 1142 Step 1504 input terminal 1144 Step 1506 circuit model 1200 Step 1508 control elements 1201 Step 1510 set 1202 Step 1512 set 1204 circuit model 1600 element 1212 Amplifier 1601 element 1214 amplifier stage 1601a circuit 1300 amplifier stage 1601b circuit 1300’ amplifier stage 1601c circuit 1300” control elements 1602 circuit model 1300’” control elements 1602’ switches 1302’ input capacitor 1603 a electrical switch 1304’ input capacitor 1603b control elements 1301 input capacitor 1603 c electrical switch 1302 control elements 1604 electrical switch 1304 control elements 1604’ potential-defining switch 1307 input capacitor 1605a electrical switch 1309 input capacitor 1605b element set 1310 input capacitor 1605c potential-defining elements 1311 Output 1606a ground node 1312 Output 1606b ground node 1313 Output 1608a voltage supply rail 1314 Output 1608b voltage supply rail 1315 feedback impedance 1622a feedback impedance 1322 feedback impedance 1622b feedback impedance 1324 feedback impedance 1622c switch 1332 feedback impedance 1624a switch 1334 feedback impedance 1624bfeedback impedance 1624c feedback variable histogram 1852 input terminal 1642a graph 1900 input terminal 1642b stimulation current histogram 1902 input terminal 1642c graph 1950 input terminal 1644a stimulation current histogram 1952 input terminal 1644b graph 2000 input terminal 1644c evoked neural responses 2002 graph 1700 graph 2050 evoked neural responses 1702 evoked neural responses 2052 graph 1750 graph 2100 evoked neural responses 1752 feedback variable histogram 2102 graph 1800 graph 2150 feedback variable histogram 1802 feedback variable histogram 2152 graph 1850

Claims

CLAIMS:

1. An implantable device comprising:a charging component configured to perform wireless charging of an energy storage device of the implantable device;a measurement amplifier configured to amplify a signal between a first input node and a second input node of the measurement amplifier subsequent to provision of a neural stimulus to evoke a neural response from a neural pathway, the signal comprising the evoked neural response;one or more control elements connected to the first input node and the second input node of the measurement amplifier; anda control unit configured to:measure a characteristic of the evoked neural response of the amplified signal; and operate the one or more control elements to maintain, during an autozeroing phase comprising a period of time immediately preceding the measurement of the characteristic of the evoked neural response from the amplified signal, a fixed potential at the first input node and a fixed potential at the second input node of the measurement amplifier.

2. The implantable device of claim 1, wherein each fixed potential is common to the first input node and the second input node of the measurement amplifier.

3. The implantable device of claim 2, wherein the fixed and common potential is one of: a ground potential of the implantable device; and a system potential of the implantable device.

4. The implantable device of any of claims 1 to 3, wherein the signal is provided to the first input node of the measurement amplifier by a first measurement electrode and to the second input node of the measurement amplifier by a second measurement electrode.

5. The implantable device of claim 4, wherein the control unit is further configured to operate the one or more control elements to electrically disconnect each of the first and second measurement electrodes from the respective first and second input nodes of the measurement amplifier during the autozeroing phase.

6. The implantable device of claim 5, wherein the control unit is further configured to operate the one or more control elements to electrically reconnect each of the first and second measurementelectrodes to the respective first and second input nodes of the measurement amplifier following a buffer period of time commencing at the termination of the autozeroing phase.

7. The implantable device of any of claims 5 to 6, wherein the control unit is further configured to operate the one or more control elements to electrically disconnect each of the first and second measurement electrodes from the respective first and second input nodes of the measurement amplifier during a stimulation phase preceding the autozeroing phase, the stimulation phase comprising a period of time in which the neural stimulus is provided.

8. The implantable device of any of claims 1 to 7, wherein the control unit is further configured to control a stimulus source, wherein the stimulus source is configured to deliver the neural stimulus to the neural pathway via one or more stimulation electrodes comprising at least one return electrode.

9. The implantable device of claim 8, wherein the control unit is configured to operate the one or more control elements to, at or immediately following commencement of the autozeroing phase, electrically connect the first input node and the second input node of the measurement amplifier to respective first and second return electrodes of the one or more stimulation electrodes, the first and second return electrodes being connected to a fixed and common potential.

10. The implantable device of claim 9, wherein the respective first and second return electrodes are the same return electrode.

11. The implantable device of any of claims 9 to 10, wherein the control unit is further configured to operate the one or more control elements to electrically disconnect the first input node and the second input node of the measurement amplifier from the respective first and second return electrodes, at or immediately following termination of the autozeroing phase.

12. The implantable device of any of claims 1 to 11, wherein the measurement amplifier comprises a plurality of stages, and wherein the autozeroing phase persists while at least one of the plurality of stages is subject to autozeroing.

13. The implantable device of claim 12, wherein a first stage of the measurement amplifier ceases autozeroing after a first period of time of the autozeroing phase, and wherein one or more other stages of the measurement amplifier are still subject to autozeroing at an end of the first period of time.

14. The implantable device of any of claims 1 to 13, wherein the control unit is configured to store the fixed potentials on respective input capacitors of the measurement amplifier during the autozeroing phase.

15. The implantable device of any of claims 1 to 14, wherein the one or more control elements comprise one or more electrical switches.

16. A method for measuring a characteristic of an evoked neural response by an implantable device, the method comprising:measuring a characteristic of an evoked neural response of a signal between a first input node and a second input node of a measurement amplifier of the implantable device subsequent to provision of a neural stimulus to evoke the neural response from a neural pathway; and maintaining, during an autozeroing phase comprising a period of time immediately preceding the measurement of the characteristic of the evoked neural response, a fixed potential at the first input node and a fixed potential at the second input node of the measurement amplifier.

17. The method of claim 16, wherein each fixed potential is common to the first input node and the second input node of the measurement amplifier.

18. The method of claim 17, wherein the fixed and common potential is one of: a ground potential of the implantable device; and a system potential of the implantable device.

19. The method of any of claims 16 to 18, wherein the signal is provided to the first input node of the measurement amplifier by a first measurement electrode and to the second input node of the measurement amplifier by a second measurement electrode, and wherein the method further comprises:electrically disconnecting each of the first and second measurement electrodes from the respective first and second input nodes of the measurement amplifier during at least the autozeroing phase.

20. The method of claim 19, further comprising electrically reconnecting each of the first and second measurement electrodes to the respective first and second input nodes of the measurement amplifier following a buffer period of time commencing at the termination of the autozeroing phase.

21. The method of any of claims 16 to 20, wherein the neural stimulus is delivered via one or more stimulation electrodes comprising at least one return electrode.

22. The method of claim 21, further comprising, at or immediately following commencement of the autozeroing phase, electrically connecting the first input node and the second input node of the measurement amplifier to respective first and second return electrodes of the one or more stimulation electrodes, the first and second return electrodes being connected to a fixed and common potential.

23. The method of claim 22, wherein the respective first and second return electrodes are the same return electrode.

24. The method of any of claims 22 to 23, further comprising electrically disconnecting the first input node of the measurement amplifier and the second input node of the measurement amplifier from the respective first and second return electrodes, at or immediately following termination of the autozeroing phase.

25. The method of any of claims 16 to 24, wherein the measurement amplifier comprises a plurality of stages, and wherein the autozeroing phase persists while at least one of the plurality of stages is subject to autozeroing.

26. The method of claim 25, wherein a first stage of the measurement amplifier ceases autozeroing after a first period of time of the autozeroing phase, and wherein one or more other stages of the measurement amplifier are still subject to autozeroing at an end of the first period of time.

27. The method of any of claims 16 to 26, further comprising storing the fixed potentials on respective input capacitors of the measurement amplifier during the autozeroing phase.

28. The method of any of claims 16 to 27, wherein the maintaining takes place during wireless charging of an energy storage device of the implantable device.

29. A neural stimulation device configured to measure a neural response evoked in a neural pathway in response to a neural stimulus, the neural stimulation device comprising a controller configured to:amplify, using a measurement amplifier, a signal at one or more input nodes of the measurement amplifier subsequent to provision of the neural stimulus, the signal comprising the evoked neural response; andoperate one or more control elements of the neural stimulation device to maintain, during autozeroing of the measurement amplifier, respective fixed potentials at the one or more input nodes of the measurement amplifier.

30. The neural stimulation device of claim 29, wherein the measurement amplifier has a first input node maintained at a first fixed potential and a second input node maintained at a second fixed potential.

31. The neural stimulation device of claim 30, wherein the first fixed potential and the second fixed potential are common or substantially common.

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