Improved measurement of evoked responses to neural stimulation

Abstract

Disclosed is an implantable device for controllably delivering neural stimuli. The device comprises a pulse generator configured to deliver neural stimuli via one or more stimulation electrodes to a neural pathway of a patient. The device comprises measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signal windows. The device is configured to control the pulse generator to deliver a neural stimulus according to one or more stimulus parameters, measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus, determine a feedback variable from the measured characteristic of the evoked neural response and adjust the one or more stimulus parameters so as to maintain the feedback variable at or near a target value.

Description

IMPROVED MEASUREMENT OF EVOKED RESPONSES TO NEURAL STIMULATION

[0001] The present application claims priority from Australian Provisional Patent Application No. 2024903835 filed on 21 November 2024, the contents of which are incorporated herein by reference in their entirety.TECHNICAL FIELD

[0002] The present invention relates to implantable neural stimulation therapy and in particular to measurement of evoked responses to neural stimulation for control of the neural stimulation therapy.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 neuropathic 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 being stimulated 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 amount of CSF or 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 of neural 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 thefeedback 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 the stimulus 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 times a second), then care must be taken that the detector should consume only a small fraction of the power budget.

[0015] 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

[0016] The present invention seeks to provide evoked response measurement circuitry which will overcome or substantially ameliorate at least some of the deficiencies of the prior art, or at least provide an alternative.

[0017] According to a first aspect of the present technology, there is provided an implantable device for controllably delivering neural stimuli. The device comprises a pulse generator configured to deliver neural stimuli via one or more stimulation electrodes to a neural pathway of a patient, the neural stimuli being configured to evoke neural responses from the neural pathway. The device further comprises measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signal windows. The device further comprises a control unit configured to control the pulse generator to deliver a neural stimulus according to one or more stimulus parameters, and measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus. The control unit is further configured to determine a feedback variable from the measured characteristic of the evoked neural response, and adjust, using a feedback controller, the one or more stimulus parameters so as to maintain the feedback variable at or near a target value.

[0018] According to a second aspect of the present technology, there is provided a neural stimulation system comprising an implantable device for controllably delivering neural stimuli. The device comprises a pulse generator configured to deliver neural stimuli via one or more stimulation electrodes to a neural pathway of a patient, the neural stimuli being configured to evoke neural responses from the neural pathway. The device further comprises measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signal windows. The device further comprises a control unit configured to control the pulse generator to deliver a neural stimulus according to one or more stimulus parameters, measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus, The control unit is further configured to determine a feedback variable from the measured characteristic of the evoked neural response, and adjust, using a feedback controller, the one or more stimulus parameters so as to maintain the feedback variable at or near a target value. The device further comprises a processor configured to instruct the control unit to control the pulse generator to deliver a neural stimulus, and instruct the control unit to measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus. The processor is further configured to determine one or more patient characteristics from the measured characteristic, and configure the configurable compound amplifier based on the one or more patient characteristics.

[0019] According to a third aspect of the present technology, there is provided a method of programming a closed-loop neural stimulation device comprising a configurable compound amplifier. The method comprises delivering one or more neural stimuli to a neural pathway of a patient, and measuring one or more characteristics of an evoked response to each delivered neural stimulus. The method further comprises determining one or more patient characteristics from the one or more measured characteristics, and configuring the configurable compound amplifier based on the one or more patient characteristics.

[0020] According to a fourth aspect of the present technology, there is provided a closed-loop neural stimulation device for controllably delivering neural stimuli. The device comprises a pulse generator configured to deliver neural stimuli via one or more stimulus electrodes to a neural pathway of a patient, the neural stimuli being configured to evoke neural responses from the neural pathway. The device further comprises measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signalwindows. The device further comprises a control unit configured to adjust, using a feedback controller, one or more stimulus parameters of the neural stimuli so as to maintain a characteristic of the evoked neural responses measured from the amplified captured signal windows at or near a target value.

[0021] 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 for treatment 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

[0022] 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:Fig. 1 schematically illustrates an implanted spinal cord stimulator, according to one implementation of the present technology;Fig. 2 is a block diagram of the stimulator of Fig. 1;Fig. 3 is a schematic illustrating interaction of the implanted stimulator of Fig. 1 with a bundle of target nerve fibres;Fig. 4 illustrates an idealised activation plot for one posture of a patient undergoing neural stimulation;Fig. 5 is a schematic illustrating elements and inputs of a closed-loop neural stimulation (CLNS) system, according to one implementation of the present technology;Fig. 6 illustrates the typical form of an electrically evoked compound action potential (ECAP) of a healthy subject;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 present technology;Fig. 8 contains a graph that indicates the general shape of the power spectral density (PSD) of the input measurement noise (on log-log axes);Fig. 9a is a schematic illustration of one implementation of a configurable compound amplifier (CCA), according to an aspect of the present technology;Fig. 9b is a schematic illustration of the CCA of Fig. 9a;Fig. 10 is a flowchart illustrating a method of configuring the CCA of Fig. 9a, according to one aspect of the present technology;Fig. 1 la is a graph containing a PSD that is the same as the PSD in Fig. 8;Fig. 11b is a graph showing the PSD of Fig. I la after the bias current has been adjusted, according to an aspect of the present technology; andFig. 11c is a graph showing the PSD of Fig. 1 lb after the number of connected amplifiers has been adjusted, according to an aspect of the present technology.DETAILED DESCRIPTION OF THE PRESENT TECHNOLOGY

[0023] 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.

[0024] 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 instructionscollectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the clinical interface.

[0025] 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. A pulse generator comprises a stimulus source, configured 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 140 followed by an analog-to-digital converter (ADC) 142, 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.

[0026] 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.

[0027] Delivery of an appropriate stimulus via 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, for example 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.

[0028] 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.

[0029] 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 twomeasurement 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.

[0030] The ECAP 600 may be characterised by any suitable character! stic(s) of which some are indicated in Fig. 6. The amplitude of the positive peak Pl isApi and occurs at time Tp . The amplitude of the positive peak P2 is Api and occurs at time Tpi. The amplitude of the negative peak N1 is Am and occurs at time Tm. The peak-to-peak amplitude is Ap\ + Am. 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 or more 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.

[0031] 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 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 comprises switches that selectively connect 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 140 followed by an analog-to-digital converter (ADC) 142, 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.

[0032] 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. W02015 / 074121, the contents of which are incorporated herein by reference. Alternative implementations of the ECAP detectormay measure and store an alternative characteristic from the neural response, or may measure and store two or more characteristics from the neural response.

[0033] 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. 4 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: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.

[0034] Fig. 4 also illustrates a discomfort threshold 408, which is a stimulus intensity above which the patient 108 experiences uncomfortable or painful stimulation. Fig. 4 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. 4, 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.

[0035] 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 stimulusintensity 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.

[0036] 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. For example, the measured ECAP characteristic may be a peak-to- peak amplitude, and the feedback variable may simply be the measured ECAP characteristic. 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, a CLNS device will generally keep the stimulus intensity within the therapeutic range as patient posture varies.

[0037] 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 varied in proportion to the received stimulus intensity value.

[0038] 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 integratingfeedback loop. The pulse generator generates a 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.

[0039] 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.

[0040] Fig. 5 is a schematic illustrating elements and inputs of a closed-loop neural stimulation (CLNS) system 300, according to one implementation of the present technology. The system 300 comprises a stimulator 312 which converts a stimulus intensity parameter (for example a stimulus current amplitude) s, in concert with a set of predefined stimulus parameters, to a neural stimulus comprising a sequence of electrical pulses on the stimulus 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, and the stimulus rate or frequency.

[0041] 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 is dependent 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.

[0042] 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.

[0043] 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 determines a measured neural response intensity d. In one implementation, the neural response intensity comprises a peak-to-peak ECAP amplitude. The feedback variable, determined as the measured response intensity d, 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.

[0044] 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 as s = f Kedt (2) where K is the gain of the gain element 336 (the controller gain). This relation may also be represented as8s = Ke (3) where 6 is an adjustment to the current stimulus intensity parameter .s.

[0045] 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.

[0046] A clinical settings controller 302 provides clinical settings to the system 300, including the feedback controller 310 and the stimulus parameters for the pulse generator 312 that are not underthe control of the feedback controller 310. 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.

[0047] 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.

[0048] 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 of stimulus intensity or target response intensity; and selection of a stimulation control program from the control programs stored on the neuromodulation device 710.

[0049] 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.

[0050] 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.

[0051] 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 theneuromodulation 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.Design considerations for evoked response measurement amplifier

[0052] The measurement noise n in Fig. 5 is mostly a mix of white (or thermal) noise (constant power spectral density across frequencies) and pink (i.e. 1 / f or shot) noise. Thermal noise is primarily generated by resistive elements in the measurement chain, which includes the measurement electrode configuration, the electrode selection module 126, the measurement circuitry 128, and the ECAP detector 320. As resistance increases, so does the thermal noise. Resistive elements include the electrode / tissue interface (roughly 500 Q per electrode), and the switches in the electrode selection module 126 (roughly 700 Q per switch). Thermal noise comes from active elements (transistors) as well, and the noise power is proportional to the inverse of transistor transconductance. Therefore, thermal noise power in transistors is inversely proportional to bias current. Pink noise is primarily generated by MOSFET transistors in the measurement chain (as gate capacitance increases, pink noise goes down). However, pink noise is unaffected by bias current. There are multiple sources of pink noise having different comer frequencies. Fig. 8 contains a graph 800 that indicates the general shape of the power spectral density (PSD) of the input measurement noise (on log-log axes). The PSD trace 810 contains a flat portion 820 representing thermal noise and a down-trending linear portion 830 representing pink noise. The portions 820 and 830 intersect at the corner frequency f co er.

[0053] The PSD of the measurement noise at the output of the ECAP detector is the product of the input measurement noise PSD and the transfer functions of each of the components of the measurement chain up to and including the ECAP detector (which is digitally implemented by the controller 116 as described above). Since the transfer function of the ECAP detector is relatively narrow band (typically one octave centred on the ECAP frequency fscAp) compared to the other components of the measurement chain, the ECAP detector is the dominant component of the measurement chain in terms of noise filtering. A reasonable approximation to the output measurement noise power Pn(which is the denominator of the measurement signal-to-noise ratio (SNR)) may therefore be taken as the input measurement noise PSD at the ECAP frequency fscAP, a value labelled as 850 in Fig. 8, multiplied by the bandwidth of the ECAP detector (a predetermined value, typically a few hundred Hz).

[0054] Another component of the sensed signal is artefact. Artefact is primarily caused by current flowing through the measurement electrode-tissue interface of the recording electrodes as a result of stimulus or shorting pulses. This current results in a voltage transient as the resulting charge isredistributed along the conductive surface of the electrode. The amount of this transient at each measurement electrode depends on many factors such as the impedance (mostly capacitive) of the corresponding input of the amplifier 140, the proximity of the measurement electrodes to the stimulus electrode, and the geometry of the measurement electrodes, which govern the impedance of the electrode-tissue interface. Because the measurement chain is differential, the amount of transient that appears as artefact is further dependent on the mismatch of the impedance of the electrode-tissue interfaces at the two measurement electrodes as a proportion of each input impedance of the amplifier.

[0055] The measurement circuitry 128 is often implemented as part of an application-specific integrated circuit (ASIC). On such an ASIC, area is a valuable commodity and is therefore part of the design considerations for the amplifier 140. There is a tradeoff between the amount of measurement noise generated by the measurement chain, the amount of artefact generated thereby (through the amplifier input capacitance), the bias current drawn by the amplifier (which determines the power consumed by the amplifier), and the ASIC area occupied by the amplifier.

[0056] The tradeoff is governed by the “Amplifier noise principle”: If two identical amplifiers are connected in parallel in the measurement chain and their outputs combined by averaging before passing to an ADC, the bias current drawn and ASIC area double, and the measurement noise power halves, compared to a measurement chain containing a single amplifier. This occurs because the signals presented to the two amplifiers are correlated but their measurement noise is uncorrelated.

[0057] It follows that doubling the ASIC area occupied by the amplifier 140 halves the pink noise power and the thermal noise power. Moreover, doubling the bias current halves the thermal noise power but has no effect on the pink noise power.

[0058] These relations are captured by the following equation for measurement noise power Pn, in which the two terms relate to pink noise and thermal noise respectively:where N is the number of amplifiers connected in parallel, Ibias is the bias current for each amplifier, and KA and KB are constants relating to pink noise and thermal noise respectively.

[0059] Another design consideration is that input capacitance of the amplifier (assuming some amount of electrode-tissue interface mismatch between measurement electrodes) contributes to artefact; the greater the input capacitance, the greater the artefact. The input capacitance is proportional to the number N of amplifiers connected in parallel. It may be seen from equation (4) that increasing N to reduce the noise power Pn, and hence increase the SNR of the measurement chain, is in tension with the resulting increase in artefact, which will reduce the signal-to-artefact ratio (SAR) Increasing N also increases the ASIC area.

[0060] Finally, the power consumed is generally proportional to the number TV of connected parallel amplifiers times the bias current Ibias, ignoring fixed overheads.

[0061] A single choice of measurement chain parameters such as ASIC area and bias current is unlikely to be optimal for all circumstances. For example, different patients have widely differing ECAP amplitudes. To maintain a desired SNR, the acceptable measurement noise for a patient with a small ECAP is lower than for one with a large ECAP. Also, different measurement electrode configurations lead to widely differing amounts of artefact.

[0062] There is therefore a need for a dynamically configurable amplifier whose area and bias current can be configured to give the best possible tradeoff between SNR, SAR, and power consumed in any circumstances.Configurable compound amplifier

[0063] According to an aspect of the present technology, the amplifier 140 is a configurable compound amplifier (CCA). Fig. 9a is a schematic illustration of one implementation of a CCA 910 according to an aspect of the present technology, as part of a measurement chain 900. Signal paths are not shown in Fig. 9a, only control paths, but signal flow is from bottom to top.

[0064] At the bottom (start of the measurement chain 900) are two measurement electrode configurations, the primary MEC 955 and the secondary MEC 960, that sense primary and secondary (differential) signals, respectively. The CCA 910 is configurable, under the control of the controller 920, which may be implemented as the controller 116, to amplify both the primary and secondary signals in parallel, or only the primary signal. For example, the two signals (primary and secondary) may be used to derive two separate feedback variables to control two separate feedback loops, or a single feedback loop, both of which options are described in International Patent Publication no. W02024 / 036380 by the present applicant.

[0065] In the former case of parallel amplification of both the primary and secondary signals, the input demultiplexer (DMUX) 950 is configured by the controller 920 to direct the primary signal to the primary DMUX 945 and the secondary signal to the secondary DMUX 940. In the latter case of primary signal amplification only, the input DMUX 950 is configured by the controller 920 to direct the primary signal to both the primary DMUX 945 and the secondary DMUX 940.

[0066] The CCA 910 comprises a bank 930 of Nmax amplifiers 935-1 to 935-Nmax, partitioned into a primary portion 932 and a secondary portion 937 comprising Nmax_p and Nmax_s of the amplifiers 935- 1 to 935-Nmax respectively. In Fig. 9a, Nmax is shown as eight for the CCA 910, but another implementation of the CCC may comprise another number of amplifiers. In Fig. 9a, the primary portion 932 and secondary portion 937 of the bank 930 are shown with Nmax_p and Nmax _sboth equalto four, but other values for Nmax_p and Nmax-s(such as five and three) are contemplated for the CCA 910 so long as Nmax_p plus Nmax_s equals Nmax. In some implementations, Nmax_p may not equal Nmax_s. The primary portion 932 of the bank 930 is connected to the primary DMUX 945 and the primary multiplexer (MUX) 975. The secondary portion 937 of the bank 930 is connected to the secondary DMUX 940 and the secondary MUX 970.

[0067] Fig. 9b is a schematic illustration of the implementation of the CCA 910 from Fig. 9a, with like labels indicating like elements, not showing the control paths but instead showing the primary signal chain 965 (solid arrows) and the secondary signal chain 966 (dashed arrows) in the case of parallel amplification of two signals.

[0068] Any or all of the amplifiers in the bank 930 are connectable in parallel into the primary signal chain 965 or the secondary signal chain 966 in the measurement chain 900 under the control of the controller 920. In the case of primary signal amplification only, the controller 920 connects N amplifiers from both the primary and secondary portions of the bank 930 into the primary signal chain965 by appropriately configuring the primary DMUX 945, the secondary DMUX 940, the primary MUX 975, and the secondary MUX 970. The number N of amplifiers connected into the primary signal chain 965 is configurable from one to Nmax. In the case of parallel amplification of two signals, the controller 920 connects N amplifiers from the primary portion 932 of the bank 930 into the primary signal chain 965 by appropriately configuring the primary DMUX 945 and the primary MUX 975. The number A of amplifiers connected into the primary signal chain 965 is configurable from one to Nmax_p. The controller 920 also connects Nsamplifiers from the secondary portion 937 of the bank 930 into the secondary signal chain 966 by appropriately configuring the secondary DMUX 940 and the secondary MUX 970. The number A of amplifiers connected into the secondary signal chain966 is configurable from one to Nmax_s.

[0069] In the case of primary signal amplification only, the primary DMUX 945 and the secondary DMUX 940 are configured to connect the primary signal to a total of N amplifiers in the bank 930, made up of one or more amplifiers in the primary portion 932 of the bank 930 via the primary DMUX 945, and zero or more amplifiers in the secondary portion 937 of the bank 930 via the secondary DMUX 940.

[0070] In the case of parallel amplification of two signals, the primary MUX 975 is configured to combine (e.g. add) the amplified primary signals from each of the N connected amplifiers in the primary portion 932 of the bank 930 into a combined primary amplified signal, and the secondary MUX 970 is configured to combine the amplified secondary signals from each of the Nsconnected amplifiers in the secondary portion 937 of the bank 930 into a combined secondary amplified signal.In the case of primary signal amplification only, the primary MUX 975 is configured to combine the amplified primary signals from each of the connected amplifiers in the primary portion 932 of the bank 930 into a combined primary amplified signal, and the secondary MUX 970 is configured to combine the amplified primary signals from each of the connected amplifiers in the secondary portion 937 of the bank 930 into a further combined primary amplified signal.

[0071] In the case of parallel amplification of two signals, the output MUX 980 is configured to connect the combined primary amplified signal from the primary MUX 975 to a primary ADC 995 and the combined secondary amplified signal from the secondary MUX 970 to a secondary ADC 990. In the case of primary signal amplification only, the output MUX 980 is configured to combine (e.g. add) the combined primary amplified signals from the primary MUX 975 and the secondary MUX 970 before forwarding the output combined primary amplified signal to the primary ADC 995.

[0072] The chain 900 also contains a variable bias current source 925 under the control of the controller 920. The variable bias current source 925 is configured to supply a common bias current to each amplifier. Each connected amplifier in the CCA 910 is configured to draw a common bias current Ibias. The controller 920 achieves this by configuring the bias current source 925 to supply the common bias current Ibias to each of the connected amplifiers. The total bias current for the primary signal chain 965 through the CCA 910 is therefore equal to N times Ibias. This quantity may be taken as a proxy for the power consumed by the primary signal chain 965 through the CCA 910.

[0073] In some implementations of the CCA 910, the Nmaxamplifiers 935-1 to 935-Nmaxin the bank 930 are all substantially identical, that is, they are the same in terms of one or more of: area; gain; noise performance; bandwidth; input and output impedance; and other relevant performance characteristics. The configuration methods described below are suitable for such implementations. However, in other implementations, the Nmaxamplifiers 935-1 to 935-Nmaxin the bank 930 may be different from one another in terms of ASIC area occupied or noise characteristics. In such implementations, the measurement noise power equation (4) involving only N and Ibias no longer holds, but a more sophisticated expression will exist for measurement noise power depending not only on the total number of amplifiers, but on which amplifiers are connected into the primary signal chain 965. Such an expression may be used to formulate alternative configuration methods to those described below that optimise the tradeoff between power consumed by the CCA 910 and measurement noise power for such non-identical amplifier implementations. Likewise, in further implementations, the Nmaxamplifiers 935-1 to 935-Nmaxin the bank 930 may be all identical but with different bias currents. Alternative configuration methods to those described below that optimise thetradeoff between power consumed by the CCA 910 and measurement noise power may also be formulated for such non-identical bias current implementations.Configuration of the configurable compound amplifier

[0074] According to a further aspect of the present technology, the CCA 910 may be configured based on the characteristics of the patient and the therapy parameters. The first programming decision is whether the CCA 910 is to be configured in the two-parallel-signal mode or the primary-signal- only mode. In some circumstances, it may be beneficial to sense signals at two different MECs and process them jointly, compared to sensing a signal at only one MEC. In such circumstances the CCA 910 may be configured in the two-parallel-signal mode.

[0075] Fig. 10 is a flowchart illustrating a method 1000 of configuring the CCA 910 for the primary signal chain 965 according to one aspect of the present technology, suitable for implementations of the CCA 910 in which all the amplifiers 935-1 to 935-Nmax in the bank 930 are identical with a common bias current Ibias. The method 1000 presumes that certain therapy parameters such as the stimulus electrode configuration and the measurement electrode configuration to be used by the therapy program have been determined. The method 1000 may be carried out by an external processing device 192 such as the clinical interface 740, configured by the program instructions making up the CPA as described above, in concert with the controller 116 of the electronics module 110 within the stimulator 100.

[0076] The method 1000 starts at step 1010, which delivers one or more neural stimuli and measures a characteristic of each evoked neural response.

[0077] Step 1020 then determines one or more patient characteristics from the one or more measured characteristics. The term “patient characteristics” may be interpreted broadly in this context to mean characteristics of the interaction between the patient and the stimulator 100 according to the predetermined therapy parameters. One example of a patient characteristic is the growth curve quality index (GCQI), which is indicative of the signal-to-noise ratio of the primary signal chain 965 including the primary measurement electrode configuration. The determination of the GCQI for a given SEC / MEC combination is described in International Patent Publication no. WO2023 / 115132 by the present applicant, the contents of which are herein incorporated by reference in their entirety. As disclosed in WO2023 / 115132, the GCQI may be determined by fitting a set of (stimulus intensity, response intensity) value pairs to an activation plot model such as the piecewise linear model of equation (1). The GCQI may be determined by dividing the full vertical extent of the fitted activation plot model by the standard deviation of the residuals of the fitted activation plot model.

[0078] Other examples of patient characteristics include signal power, noise power spectral density, artefact power, signal-to-artefact ratio, and the complex impedance of the electrode-to-tissue interface at each measurement electrode of the primary measurement electrode configuration, which is closely related to artefact.

[0079] The method 1000 then proceeds to step 1030, which configures the CCA 910 based on the one or more patient characteristics determined at step 1020, and optionally also on one or more predetermined performance criteria. Step 1030 selects the number N of amplifiers connected into the primary signal chain 965 to amplify the primary signal, and the bias current bias to be applied to each of the connected amplifiers.

[0080] In some implementations of the method 1000, the values of N and bias are chosen to jointly optimise both the power consumed by, and the SNR of, the primary signal chain 965. In such implementations, step 1010 and step 1020 may be carried out for each candidate value of N (in the case of primary-signal-only mode, from 1 to Nmax) and for multiple candidate values of bias spanning the full range of possible values for bias. In one such implementation, step 1020 determines the SNR of the primary signal chain 965 for each candidate pair of values (N, bias). In one such implementation, the SNR may be determined as the measured GCQI value for the candidate pair of values (A, bias). In another implementation, the SNR may be determined by dividing an estimate of the neural response signal power Psby the measurement noise power Pnat the output of the primary signal chain 965 (i.e. the noise power output by the ECAP detector in the absence of any stimulation). One estimate of the neural response signal power Psis the square of a representative neural response intensity value d measured at a stimulus intensity 5 in the middle of the therapeutic range.

[0081] The result of such implementations of step 1020 is an SNR value for each candidate pair of values (A, bias).

[0082] In an alternative implementation, instead of traversing each candidate pair of values (A, bias), the SNR is determined for only one candidate value of A, say Ao, for each candidate value of bias. The SNR for the other candidate values of A at that candidate value of is bias is determined by scaling the SNR determined at (Ao, bias) by A / Ao. This alternative is based on the inverse relationship in Equation (4) between the measurement noise power Pn(the denominator of the SNR) and the number A of connected primary amplifiers.

[0083] Such implementations of step 1020 of the method 1000 also estimate the power (A, bias) consumed by the CCA 910 when configured with each candidate pair of values (A, bias) as the product of A and bias. Step 1030 then chooses the candidate pair of values (A, bias) which minimises an overall figure of merit that balances the SNR and the consumed power P(N, bias). (Recall that while the SNRgenerally increases with N and bias, the consumed power P increases proportionally to both parameters.) One example of such a figure of merit F iswhere X is a predetermined balancing parameter.

[0084] In other implementations of the method 1000, a predetermined performance criterion is used by step 1030 to configure the CCA 910. In some such implementations, the predetermined performance criterion is a desired measurement SNR. In one such implementation, step 1020 determines the neural response signal power Psas the square of a representative neural response intensity value d measured at a stimulus intensity 5 in the middle of the therapeutic range. This value Psof neural response signal power is independent of N and bias and may therefore be measured at any values of those parameters within their respective ranges. However, for the purposes of such implementations it is convenient for both N and bias to be set at candidate values in the middle of their respective ranges when measuring Ps. Step 1020 also measures the PSD of the measurement noise at the intermediate values of N and bias.

[0085] Also at step 1020, the neural response signal power Psmay be divided by the desired measurement SNR to obtain the desired measurement noise power Pn. The desired measurement noise power Pnin turn may be converted at step 1020 to a desired PSD value PSDdesired at the ECAP frequency ECAP by dividing the desired measurement noise power Pnby the bandwidth of the ECAP detector.

[0086] Step 1030 then adjusts the values of N and bias so that:• the PSD of the measurement noise has a value of PSDdesired at the ECAP frequency fscAP, and• the PSD of the measurement noise has a corner frequency fcomer equal O ECAF.

[0087] By adjusting the values of N and bias to meet these two criteria, the primary signal chain will meet the desired performance criterion with the smallest possible values of N and bias, thereby minimising the power consumed by the primary signal chain (which is proportional to both N and bias).

[0088] Figs. 1 la to 11c are graphs illustrating how step 1030 may be implemented to adjust the values of N and bias to meet the two criteria listed above. Fig. 1 la is a graph illustrating a PSD trace 1110, measured at the intermediate values of N and bias, that has the same form as the PSD 810 in Fig. 8, containing a portion 1120 representing thermal noise and a portion 1130 representing pink noise. The PSD trace 1110 has the value 1140 at the ECAP frequency fscAP, which is not equal to the desired value PSDdesired fECAP, marked with a black dot 1125 below the pink noise portion 1130 of the PSD trace 1110. The corner frequency fcomer in the PSD trace 1110 is also not equal O ECAF.

[0089] Fig. 1 lb is a graph showing a PSD trace 1150 comprising the PSD trace 1110 after i s has been adjusted so that the new PSD trace 1150 has a corner frequency fcomer equal tofscAP, according to an aspect of the present technology. The adjustment of Ibias affects only the thermal noise portion 1120 of the original PSD trace 1110 (shown dashed in Fig. 1 lb), pushing it up to the thermal noise portion 1160 while keeping the pink noise portion 1130 unchanged. This has the effect of shifting the comer frequency fcomer to ECAP. However, the new PSD trace 1150 still has the value 1140 at the ECAP frequency fscAP, which is not equal to the desired value PSDdesired atfscAP.

[0090] Fig. 11c is a graph showing a PSD trace 1170 comprising the PSD trace 1150 after Ahas been adjusted so that the new PSD trace 1170 has a value of PSDdesired at the ECAP frequency fpc p, according to an aspect of the present technology. The adjustment of N affects the entire PSD trace 1150 (shown dashed in Fig. 11c), pushing the pink noise portion 1130 and the thermal noise portion 1160 by equal amounts down to the down to the pink noise portion 1190 and the thermal noise portion 1180 respectively of the final PSD trace 1170.

[0091] As mentioned above, increasing the input capacitance (by increasing the number N of connected amplifiers) increases the artefact, all other things being equal. This could offset the improvement in SNR by decreasing the SAR. To counteract this effect, a stimulus scheme referred to as “disconnect during stimulus” (DDS) may be employed. This scheme involves disconnecting the measurement electrodes of the primary MEC 955 from the primary signal chain (e.g. at the primary DMUX 945) during, and for a short delay after, each stimulus pulse. Such a “disconnect during stimulus” scheme is disclosed in the above-mentioned International Patent Publication no. WO2012 / 155183 by the present applicant. The disconnect during stimulus scheme prevents the flow of current through the measurement electrode-tissue interface into the amplifier input capacitance during the stimulus pulse. When the interfaces are mismatched, this flow of current is a principal source of artefact. The increased artefact that would otherwise result from the increased input capacitance contingent on the increase in N is thereby mitigated.

[0092] The external processing device 192 may therefore implement further optional steps at the end of the method 1000. In a first optional step, the external processing device 192 may estimate the SAR by dividing the previously-estimated neural response signal power Psby the artefact power. The artefact power may be estimated by scaling the output of the ECAP detector 320 at sub-threshold stimulus intensities when no neural response is present by the ratio of the supra-threshold stimulus intensity 5 used to estimate the neural response signal power Psto the sub-threshold stimulus intensity and squaring the result. In a further processing step, the external processing device 192 compares the estimated SAR with a threshold level of acceptable SAR. If the SAR does not exceed the threshold,the external processing device 192 configures the stimulator 100 to implement the DDS scheme to mitigate the artefact.

[0093] In the case that the CCA 910 is to be configured in the primary-signal-only mode, the method 1000 as described above may be implemented to configure the CCA 910 for the primary signal chain.

[0094] In the case that the CCA 910 is to be configured in the two-parallel-signal mode, the method 1000 as described above may be implemented to configure the CCA 910 for the primary signal chain, except that the upper limit on the number N of amplifiers connectable into the primary signal chain is Nmax_p rather than Nmax. After the method 1000 has been utilised to configure the CCA 910 for the primary signal chain by selecting N and the bias current Ibias, the CCA 910 may be configured for the secondary signal chain by selecting the number of amplifiers in the secondary portion 937 of the bank 930 to be connected into the secondary signal chain (the bias current Ibias has already been configured by the method 1000).

[0095] In one implementation, the number Nsof amplifiers may be selected according to a predetermined performance criterion of the secondary signal chain. Similar implementations to those of the method 1000 described above that use a predetermined performance criterion (e.g. a desired secondary measurement SNR) to configure the CCA 910 for the primary signal chain may be used for this purpose, with the exception that Ibias is fixed at its previously selected value, rather than variable. In other words, step 1030 attempts to select a value of Nssuch that the PSD of the secondary measurement noise has a value as close as possible to PSDdesired at the ECAP frequency ECAP.

[0096] It will be appreciated that most amplifiers have multiple cascaded stages, with different noise contributions from each stage. Most are also designed so the dominant noise source comes from the front-end stage. Therefore, it may only be the front-end stage that has variable bias current control, and subsequent stages may have a fixed bias current. The fixed bias current of the subsequent stages does not affect the configuration of the CCA 910 as described above.

[0097] For the same reason, in some implementations the CCA 910 has a single instance of each subsequent stage, while replicating only the front-end stage in the bank 930. In other words, in some implementations of the CCA 910, the Nmax identical elements 935-n in the bank 930 are not complete amplifiers, but front-end stages fed by a common bias current Ibias. The subsequent stages with their respective fixed bias currents follow the MUX 980 in the signal chain. The term “amplifier” in the foregoing may therefore be interpreted as “amplifier front-end stage”.

[0098] 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-readablemedia 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

[0099] 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.

[0100] 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

[0101] 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

[0102] 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.

[0103] 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

[0104] 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.

[0105] 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

[0106] 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 whenexecuted 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

[0107] 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

[0108] 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.

[0109] 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 may implement 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

[0110] Reference throughout the present disclosure to “one implementation” or “an implementation” means that a particular feature, structure or characteristic described in connection with theimplementation 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.

[0111] 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.

[0112] 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.

[0113] 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 range of 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 alsounderstood 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

[0114] 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

[0115] 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

[0116] Throughout the present disclosure, the terms "a" and "an" mean "one or more", unless expressly specified otherwise.

[0117] 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.

[0118] 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.

[0119] Throughout the present disclosure, the word “or” is to be read inclusively rather than exclusively, except where otherwise indicated.

[0120] Neither the title nor any abstract of the present disclosure should be taken as limiting in any way the scope of the claimed invention.

[0121] 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.

[0122] 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 asconsisting 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.

[0123] 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.

[0124] 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.

[0125] 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 disclosure of the present disclosure.INDUSTRIAL APPLICABILITY

[0126] It is apparent from the above that the arrangements described are applicable to the health care industries.LABEL LIST stimulator 100 battery 112 patient 108 telemetry module 114 electronics module 110 controller 116memory 118 CI 740 clinical data 120 charger 750 clinical settings 121 graph 800 control programs 122 power spectral density 810 pulse generator 124 thermal noise portion 820 electrode selection module 126 pink noise portion 830 measurement circuitry 128 ECAP frequency 850 ground 130 measurement chain 900 amplifier 140 configurable compound digital converter 142 amplifier 910 electrode array 150 controller 920 biphasic stimulus pulse 160 bias current source 925ECAP 170 bank 930 target fibres 180 amplifier 935-1 communications channel 190 Amplifier 935 -Nmaxexternal computing device 192 secondary DMUX 940CLNS system 300 primary DMUX 945 clinical settings controller 302 input DMUX 950 target ECAP controller 304 primary MEC 955 box 308 secondary MEC 960 box 309 primary signal chain 965 controller 310 secondary signal chain 966 box 311 secondary MUX 970 pul se generator 312 primary MUX 975 element 313 output MUX 980 measurement circuitry 318 secondary ADC 990 signal window 319 primary ADC 995ECAP detector 320 method 1000 comparator 324 step 1010 gain element 336 step 1020 integrator 338 step 1030 activation plot 402 power spectral density 1110ECAP threshold 404 thermal noise portion 1120 discomfort threshold 408 pink noise portion 1130 perception threshold 410 value 1140 therapeuti c range 412 power spectral density 1150ECAP 600 thermal noise portion 1160 neural stimulation system 700 power spectral density 1170 neuromodulation device 710 thermal noise portion 1180 remote controller 720 pink noise portion 1190CST 730

Claims

CLAIMS:

1. An implantable device for controllably delivering neural stimuli, the device comprising: a pulse generator configured to deliver neural stimuli via one or more stimulation electrodes to a neural pathway of a patient, the neural stimuli being configured to evoke neural responses from the neural pathway; measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signal windows; and a control unit configured to: control the pulse generator to deliver a neural stimulus according to one or more stimulus parameters; measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus; determine a feedback variable from the measured characteristic of the evoked neural response; and adjust, using a feedback controller, the one or more stimulus parameters so as to maintain the feedback variable at or near a target value.

2. The device of claim 1, wherein the configurable compound amplifier comprises a bank of parallel amplifiers, each amplifier being connectable into a primary signal chain from a primary pair of the one or more measurement electrodes to a primary analog-to-digital converter.

3. The device of claim 2, wherein the amplifiers are substantially identical.

4. The device of claim 3, wherein the bank of parallel amplifiers comprises a primary portion comprising a predetermined number of the amplifiers and a secondary portion comprising the remaining amplifiers in the bank.

5. The device of claim 4, wherein each amplifier in the secondary portion is connectable into a secondary signal chain from a secondary pair of the one or more measurement electrodes to a secondary analog-to-digital converter.

6. The device of any one of claims 3 to 5, wherein each amplifier is configured to draw a common bias current.

7. The device of claim 6, further comprising a variable bias current source configured to supply the common bias current to each amplifier.

8. The device of claim 7, wherein the control unit is configured to control the variable bias current source.

9. A closed-loop neural stimulation device for controllably delivering neural stimuli, the device comprising: a pulse generator configured to deliver neural stimuli via one or more stimulus electrodes to a neural pathway of a patient, the neural stimuli being configured to evoke neural responses from the neural pathway; measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signal windows; and a control unit configured to adjust, using a feedback controller, one or more stimulus parameters of the neural stimuli so as to maintain a characteristic of the evoked neural responses measured from the amplified captured signal windows at or near a target value.

10. A neural stimulation system comprising: an implantable device for controllably delivering neural stimuli, the device comprising: a pulse generator configured to deliver neural stimuli via one or more stimulation electrodes to a neural pathway of a patient, the neural stimuli being configured to evoke neural responses from the neural pathway; measurement circuitry configured to capture signal windows from signals sensed on the neural pathway by one or more measurement electrodes, wherein the measurement circuitry comprises a configurable compound amplifier configured to amplify the captured signal windows; and a control unit configured to:control the pulse generator to deliver a neural stimulus according to one or more stimulus parameters; measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus; determine a feedback variable from the measured characteristic of the evoked neural response; and adjust, using a feedback controller, the one or more stimulus parameters so as to maintain the feedback variable at or near a target value; and a processor configured to: instruct the control unit to control the pulse generator to deliver a neural stimulus; instruct the control unit to measure a characteristic of an evoked neural response in an amplified captured signal window subsequent to the delivery of the neural stimulus; determine one or more patient characteristics from the measured characteristic; and configure the configurable compound amplifier based on the one or more patient characteristics.

11. The system of claim 10, wherein the configurable compound amplifier comprises a bank of parallel amplifiers, each amplifier being connectable into a primary signal chain from a primary pair of the one or more measurement electrodes to a primary analog-to-digital converter.

12. The system of claim 11, wherein the amplifiers are substantially identical.

13. The system of claim 12, wherein each amplifier is configured to draw a common bias current.

14. The system of claim 13, wherein the processor is configured to configure the configurable compound amplifier by selecting a number of amplifiers connected into the primary signal chain based on the one or more patient characteristics.

15. The system of claim 14, wherein the processor is configured to configure the configurable compound amplifier by selecting the common bias current.

16. The system of claim 15, wherein the one or more patient characteristics comprise a signal - to-noise ratio of the primary signal chain at each of one or more candidate values of the common bias current.

17. The system of claim 15, wherein the one or more patient characteristics comprise a signal power of the evoked neural response and a power spectral density of measurement noise at candidate values of the number of amplifiers and the common bias current.

18. The system of claim 17, wherein the processor is configured to select the number of amplifiers and the common bias current such that the power spectral density of the measurement noise has a desired value at a predetermined frequency.

19. The system of any one of claims 10 to 18, further comprising an external device configured to be in communication with the implantable device.

20. The system of claim 19, wherein the processor forms part of the external device.

21. The system of any one of claims 10 to 18, wherein the processor forms part of the implantable device.

22. A method of programming a closed-loop neural stimulation device comprising a configurable compound amplifier, the method comprising: delivering one or more neural stimuli to a neural pathway of a patient; measuring one or more characteristics of an evoked response to each delivered neural stimulus; determining one or more patient characteristics from the one or more measured characteristics; and configuring the configurable compound amplifier based on the one or more patient characteristics.

23. The method of claim 22, wherein the configurable compound amplifier comprises a bank of parallel amplifiers, each amplifier being connectable into a primary signal chain from a primary pair of measurement electrodes to a primary analog-to-digital converter.

24. The method of claim 23, wherein the amplifiers are substantially identical.

25. The method of claim 24, wherein each amplifier is configured to draw a common bias current.

26. The method of claim 25, wherein configuring the configurable compound amplifier comprises selecting a number of amplifiers connected into the primary signal chain based on the one or more patient characteristics.

27. The method of claim 26, wherein configuring the configurable compound amplifier comprises selecting the common bias current.

28. The method of claim 27, wherein the one or more patient characteristics comprise a signal- to-noise ratio of the primary signal chain at each of one or more candidate values of the common bias current.

29. The method of claim 27, wherein the one or more patient characteristics comprise a signal power of the evoked neural response and a power spectral density of measurement noise at candidate values of the number of amplifiers and the common bias current.

30. The method of claim 29, wherein the number of amplifiers and the common bias current are selected such that the power spectral density of the measurement noise has a desired value at a predetermined frequency.

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