Improved feedback control of neural stimulation therapy

Abstract

Disclosed is a method of controllably delivering neural stimuli to a neural pathway of a patient. The method comprises: providing interleaved neural stimuli to the neural pathway according to each of a plurality of stimulation sets; measuring an intensity of an evoked neural response subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determining, based on the measured intensity of the evoked neural response and a stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and controlling a stimulus intensity parameter of the second stimulation set according to the determined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

Description

IMPROVED FEEDBACK CONTROL OF NEURAL STIMULATION THERAPY TECHNICAL FIELD

[0001] The present invention relates to neural stimulation therapy and in particular to improved methods for feedback control of neural stimulation therapy with multiple stimulation sets. BACKGROUND OF THE INVENTION

[0002] 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, Parkinson’s disease, and migraine. 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 effect. 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.

[0003] 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 orthodromic (in afferent fibres this means towards the head, or rostral) and antidromic (in afferent fibres this means towards the cauda, or caudal) directions. Action potentials propagating along A ^ (A-beta) fibres being stimulated in this way 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 frequency in the range of 30 Hz - 100 Hz.

[0004] 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 almost all neuromodulationapplications, 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 A ^ (A-beta) fibres. When recruitment is too large, A ^ fibres produce uncomfortable sensations. Stimulation at high intensity may even recruit Aδ (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.

[0005] The task of maintaining appropriate neural recruitment is made more difficult by electrode migration (change in position over time) and / 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. There is room in the epidural space for the electrode array to move, and such array movement from migration or posture change alters the electrode-to-cord distance and thus the recruitment efficacy of a given stimulus. Moreover, the spinal cord itself can move within the cerebrospinal fluid (CSF) with respect to the dura. During postural changes, the amount of CSF and / 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.

[0006] 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. Feedback control seeks to compensate for relative nerve / electrode movement by controlling the intensity of the delivered stimuli so as 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 the feedback variable. Based on the response intensity, the intensity of the applied stimulus may be adjusted to bring the response intensity closer to the target value.

[0007] 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 fibreaction potentials. The ECAP generated from the depolarisation of a group of similar fibres may be measured at 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.

[0008] 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.

[0009] For some patients, it is beneficial for a neural stimulation therapy program to comprise multiple stimulation sets. A stimulation set (“stimset”) is a set of stimulus electrodes along with the stimulus parameters that govern the stimulation pulses delivered via those stimulus electrodes. Each stimset may be independently programmed to target a different painful area, though all stimsets may have the same stimulus frequency. In a multi-stimset program, the stimuli from the multiple stimsets are delivered interleaved in time. However, the resources may only be available to analyse the evoked responses from one of the interleaved stimsets, referred to as the applied stimset. In such implementations, the adjustable parameters of the other, non-applied stimsets may be adjusted based on the evoked responses to the applied stimset. However, it is not immediately apparent how the parameters of the non-applied stimsets should be adjusted based on the evoked responses in order to maintain their respective therapeutic effects as they were at the time of programming the non-applied stimsets.

[0010] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. 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 invention as it existed before the priority date of each claim of this application.

[0011] Throughout this specification 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.

[0012] In this specification, a statement that an element may be “at least one 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. SUMMARY OF THE INVENTION

[0013] Disclosed herein are systems, devices and methods for feedback control of a multiple- stimulation-set neural stimulation system, in which measurements of neural response intensity may only be made for one stimset (the applied stimset) among the multiple stimsets. According to aspects of the present technology, measurements of neural response from the applied stimset may be used to determine the relationship between stimulus intensity and therapeutic effect in a non-applied stimset. The determined relationship may in turn be used to compute a stimulus intensity that would evoke a neural response whose therapeutic effect approximates the target effect for the non-applied stimset. Alternatively, the adjustment to the stimulus intensity of the non-applied stimset may be computed from the adjustment to the stimulus intensity of the applied stimset, in a manner that depends on posture.

[0014] According to a first aspect, there is provided an implantable device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to: control the stimulus source to provide interleaved neural stimuli according to each of a plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and control the stimulus intensity parameter of the second stimulation set according to the determined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

[0015] The relationship may be a relationship between intensities of neural responses evoked by neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set. The control unit may be configured to control the stimulus intensity parameter of the second stimulation set by: applying the determined parameter to a target value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set.

[0016] Alternatively, the relationship may be a relationship between neural recruitment of neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set. The parameter may be an ECAP threshold of the second stimulation set. The control unit may be configured to control the stimulus intensity parameter of the second stimulation set by: applying the determined parameter to a target recruitment value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set. The control unit may be configured to apply the determined parameter by multiplying the target recruitment value by the ECAP threshold of the second stimulation set.

[0017] The control unit may be further configured to control the stimulus intensity parameter of the first stimulation set to maintain the therapeutic effect of the neural stimuli provided according to the first stimulation set at a target value of the first stimulation set.

[0018] The control unit may be configured to determine the parameter of the relationship by: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing; and determining the parameter of the relationship based on the selected one activation plot for the first stimulation set.

[0019] In a second aspect, there is provided an automated method of controllably delivering neural stimuli to a neural pathway of a patient, the method comprising: providing interleaved neural stimuli to the neural pathway according to each of a plurality of stimulation sets; measuring an intensity of an evoked neural response subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determining, based on the measured intensity of the evoked neural response and a stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and controlling a stimulus intensity parameter of the second stimulation set according to thedetermined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

[0020] The relationship is a relationship between intensities of neural responses evoked by neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set. Controlling the stimulus intensity parameter of the second stimulation set may comprise: applying the determined parameter to a target value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set.

[0021] Alternatively, the relationship is a relationship between neural recruitment of neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set. The parameter may be an ECAP threshold of the second stimulation set. Controlling the stimulus intensity parameter of the second stimulation set may comprise: applying the determined parameter to a target recruitment value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set. Applying may comprise multiplying the target recruitment value by the ECAP threshold of the second stimulation set.

[0022] The method may further comprise controlling the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a target value of the first stimulation set.

[0023] Determining the parameter of the relationship may comprise: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing; and determining the parameter of the relationship based on the selected one activation plot for the first stimulation set.

[0024] In a third aspect, there is provided a neural stimulation system comprising: an implantable neuromodulation device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neuralstimuli; and a control unit configured to control the stimulus source to provide neural stimuli according to a plurality of stimulation sets; a processor configured to: instruct the control unit to control the stimulus source to provide interleaved neural stimuli according to each of the plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a provided neural stimulus corresponding to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and control the stimulus intensity parameter of the second stimulation set according to the determined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

[0025] The neural stimulation system of claim 19, wherein the processor is further configured to control a stimulus intensity parameter of the first stimulation set to maintain therapeutic effect of the neural stimuli provided according to the first stimulation set at a target value of the first stimulation set.

[0026] The neural stimulation system may further comprise an external computing device with which the implantable neuromodulation device is in communication. Alternatively, the processor may form part of the external computing device. Even further alternatively, the processor may form part of the implantable neuromodulation device.

[0027] According to a fourth aspect, there is provided an implantable device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to: control the stimulus source to provide interleaved neural stimuli according to each of a plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a posture of the patient; determine a first adjustment to the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of theevoked neural response at a first target value; and determine a second adjustment to a stimulus intensity parameter of a second stimulation set of the plurality of stimulation sets based on the first adjustment and according to the determined posture.

[0028] The control unit may be configured to determine the second adjustment to the stimulus intensity parameter of the second stimulation set according to the determined posture to maintain an intensity of neural responses evoked by neural stimuli provided according to the second stimulation set at a second target value.

[0029] The control unit may be configured to determine the second adjustment to the stimulus intensity parameter of the second stimulation set by: determining a scalar using the determined posture of the patient; and multiplying the first adjustment to the stimulation intensity parameter of the first stimulation set by the scalar. The control unit may be configured to determine the scalar by dividing the stimulus intensity parameter of the second stimulation set by the stimulus intensity parameter of the first stimulation set. The control unit may be configured to determine the scalar by dividing a derivative parameter of the first stimulation set in the determined posture by a derivative parameter of the second stimulation set in the determined posture. The control unit may be configured to determine the scalar from a ratio of: a derivative of the derivative parameter of the second stimulation set with respect to posture in the determined posture; and a derivative of the derivative parameter of the first stimulation set with respect to posture in the determined posture. The derivative parameter may be a patient sensitivity. The derivative parameter may be a reciprocal of an ECAP threshold.

[0030] The control unit may be configured to determine the posture by: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; and selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing, the one activation plot corresponding to the determined posture.

[0031] According to a fifth aspect, there is provided an automated method of controllably delivering neural stimuli to a neural pathway of a patient, the method comprising: providing interleaved neural stimuli to the neural pathway according to each of a plurality of stimulation sets; measuring an intensity of an evoked neural response subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determining, based on the measured intensity of the evoked neural response and a stimulus intensity parameter of the first stimulation set, a postureof the patient; determining a first adjustment to the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a first target value; and determining a second adjustment to a stimulus intensity parameter of a second stimulation set of the plurality of stimulation sets based on the first adjustment and according to the determined posture.

[0032] Determining the second adjustment to the stimulus intensity parameter of the second stimulation set according to the determined posture may maintain an intensity of neural responses evoked by neural stimuli provided according to the second stimulation set at a second target value.

[0033] Determining the second adjustment to the stimulus intensity parameter of the second stimulation set may comprise: determining a scalar using the determined posture of the patient; and multiplying the first adjustment to the stimulation intensity parameter of the first stimulation set by the scalar. Determine the scalar may comprise dividing the stimulus intensity parameter of the second stimulation set by the stimulus intensity parameter of the first stimulation set. Determining the scalar may comprise dividing a derivative parameter of the first stimulation set in the determined posture by a derivative parameter of the second stimulation set in the determined posture. The scalar comprises a ratio of: a derivative of the derivative parameter of the second stimulation set with respect to posture in the determined posture; and a derivative of the derivative parameter of the first stimulation set with respect to posture in the determined posture. The derivative parameter may be a patient sensitivity. Alternatively, the derivative parameter is a reciprocal of an ECAP threshold.

[0034] Determining the posture may comprise: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; and selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing, the one activation plot corresponding to the determined posture.

[0035] According to a sixth aspect, there is provided a neural stimulation system comprising: an implantable neuromodulation device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to control the stimulus sourceto provide neural stimuli according to a plurality of stimulation sets; a processor configured to: instruct the control unit to control the stimulus source to provide interleaved neural stimuli according to each of the plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a provided neural stimulus corresponding to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a posture of the patient; determine a first adjustment to the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a first target value; and determine a second adjustment to a stimulus intensity parameter of a second stimulation set of the plurality of stimulation sets based on the first adjustment and according to the determined posture.

[0036] The neural stimulation system may further comprise an external computing device with which the implantable neuromodulation device is in communication. The processor may form part of the external computing device. Alternatively, the processor may form part of the implantable neuromodulation device.

[0037] References herein to estimation, determination, comparison and the like are to be understood as referring to an automated process carried out on data by a processor operating to execute a predefined procedure suitable to effect the described estimation, determination and / or comparison step(s). The technology disclosed herein may be implemented in hardware (e.g., using digital signal processors, application specific integrated circuits (ASICs) or field programmable gate arrays (FPGAs)), or in software (e.g., using instructions tangibly stored on non-transitory computer-readable media for causing a data processing system to perform the steps described herein), or in a combination of hardware and software. The disclosed technology can also be embodied 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 and / or executed in a distributed fashion. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] One or more implementations of the invention will now be described with reference to the accompanying drawings, in which:

[0039] Fig. 1 schematically illustrates an implanted spinal cord stimulator, according to one implementation of the present technology;

[0040] Fig.2 is a block diagram of the stimulator of Fig.1;

[0041] Fig.3 is a schematic illustrating interaction of the implanted stimulator of Fig.1 with a nerve;

[0042] Fig.4a illustrates an idealised activation plot for one posture of a patient undergoing neural stimulation;

[0043] Fig.4b illustrates the variation in the activation plots with changing posture of the patient;

[0044] 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;

[0045] Fig.6 illustrates the typical form of an electrically evoked compound action potential (ECAP) of a healthy subject;

[0046] 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;

[0047] Fig.8 is an illustration of the stimulus pulses delivered by a multi-stimset stimulation program with four interleaved stimulation sets (stimsets);

[0048] Fig.9 is a schematic illustrating elements of a multi-stimset closed-loop neural stimulation system, according to aspects of the present technology.

[0049] Fig.10A is a graph containing two activation plots and for stimsets 1 (applied) and 2 (non- applied) respectively, in a first posture;

[0050] Fig.10B is a graph containing two activation plots and for stimsets 1 (applied) and 2 (non- applied) respectively, in a second posture;

[0051] Fig. 11 is a flow chart illustrating a method carried out by the multi-stimset feedback controller of Fig.9 according to one implementation of a first aspect of the present technology;

[0052] Fig. 12 is a flow chart illustrating a method carried out by the multi-stimset feedback controller of Fig.9 according to a second aspect of the present technology; and

[0053] Fig. 13 is a flow chart illustrating a method carried out by the multi-stimset feedback controller of Fig. 9 according to an alternative implementation of the first aspect of the present technology. DETAILED DESCRIPTION OF THE PRESENT TECHNOLOGY

[0054] 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. Stimulator 100 further comprises 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 the 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.

[0055] Numerous aspects of the operation of implanted stimulator 100 may be programmable by an external computing device 192, which may be operable by a user such as a clinician or the patient 108. Moreover, implanted stimulator 100 serves a data gathering role, with gathered data being communicated to external device 192 via a transcutaneous communications channel 190. Communications channel 190 may be active on a substantially continuous basis, at periodic intervals, at non-periodic intervals, or upon request from the external device 192. External device 192 may thus provide a clinical interface configured to program the implanted stimulator 100 and recover data stored on the implanted stimulator 100. This configuration is achieved by program instructions collectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the clinical interface.

[0056] 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), capacitiveand / or inductive transfer, may be used by telemetry module 114 to transfer power and / or data to and from the electronics module 110 via communications channel 190. Module controller 116 has an associated memory 118 storing one or more of clinical data 120, clinical settings 121, control programs 122, and the like. Controller 116 is configured by control programs 122, sometimes referred to as firmware, to control a pulse generator 124 to generate stimuli, such as in the form of electrical pulses, in accordance with the clinical settings 121. Electrode selection module 126 switches the generated pulses to the selected electrode(s) of electrode array 150, for delivery of the pulses to the tissue surrounding the selected electrode(s). Measurement circuitry 128, which may comprise an amplifier and / or an analog-to-digital converter (ADC), is configured to process signals comprising neural responses sensed at measurement electrode(s) of the electrode array 150 as selected by electrode selection module 126.

[0057] Fig.3 is a schematic illustrating interaction of the implanted stimulator 100 with a nerve 180 in the patient 108. In the implementation illustrated in Fig.3 the nerve 180 may be located in the spinal cord, however in alternative implementations the stimulator 100 may be positioned adjacent any desired neural tissue including a peripheral nerve, visceral 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 tissue including nerve 180. A pulse may comprise one or more phases, e.g. a monophasic pulse comprises one phase, 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 embodiments may apply other forms of bipolar stimulation, or may use a greater number of stimulus and / 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 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.

[0058] Delivery of an appropriate stimulus via electrodes 2 and 4 to the nerve 180 evokes a neural response 170 comprising an evoked compound action potential (ECAP) which will propagate alongthe nerve 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 to create paraesthesia at a desired location. To this end, the electrodes 2 and 4 are used to deliver stimuli periodically at any therapeutically suitable 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 is experienced by the user as paraesthesia. When a stimulus electrode configuration is found which evokes paraesthesia 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 stimulator 100 as the clinical settings 121.

[0059] Fig.6 illustrates the typical form of an ECAP 600 of a healthy subject, as recorded at a single measurement electrode referenced to the system ground 130. 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 P1, then a negative peak N1, 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.

[0060] 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 N1 and N2, and one positive peak P1. Alternatively, depending on the distance between the two measurement electrodes, a differential ECAP may resemble the time derivative of the ECAP 600, or more generally the difference between the ECAP 600 and a time-delayed copy thereof.

[0061] The ECAP 600 may be characterised by any suitable characteristic(s) of which some are indicated in Fig.6. The amplitude of the positive peak P1 is Ap1and occurs at time Tp1. The amplitude of the positive peak P2 is Ap2and occurs at time Tp2. The amplitude of the negative peak P1 is An1and occurs at time Tn1. The peak-to-peak amplitude is Ap1 + An1. 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.

[0062] The stimulator 100 is further configured to measure the intensity of ECAPs 170 propagating along nerve 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 selectively connects the chosen electrodes to the inputs of the measurement circuitry 128. Thus, signals sensed by the measurement electrodes 6 and 8 subsequent to the respective stimuli are passed to the measurement circuitry 128, which may comprise a differential amplifier and an analog-to-digital converter (ADC), as illustrated in Fig.3. The recording electrode and the reference electrode are referred to as the measurement electrode configuration. The measurement circuitry 128 for example may operate in accordance with the teachings of the above- mentioned International Patent Publication No. WO2012 / 155183.

[0063] 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 nerve 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 (µV). For example, the sensed signals may be processed by the ECAP detector to determine the peak-to-peak ECAP amplitude in accordance with the teachings of International Patent Publication No. WO2015 / 074121, the contents of which are incorporated herein by reference. Alternative implementations of the ECAP detector may measure and store an alternative characteristic from the neural response, or may measure and store two or more characteristics from the neural response.

[0064] Stimulator 100 applies stimuli over a potentially long period such as days, weeks, or months and during this time may store characteristics of neural responses, clinical settings, paraesthesia target level, and other operational parameters in memory 118. To effect suitable SCS therapy, stimulator 100 may deliver tens, hundreds or even thousands of stimuli per second, for many hours each day. Each neural response or group of responses generates one or more characteristics such as a measure of the intensity of the neural response. Stimulator 100 thus may produce such data at a rate of tens or hundreds of Hz, or even kHz, and over the course of hours or days this process results in largeamounts of clinical data 120 which may be stored in the memory 118. Memory 118 is however necessarily of limited capacity and care is thus required to select compact data forms for storage into the memory 118, to ensure that the memory 118 is not exhausted before such time that the data is expected to be retrieved wirelessly by external device 192, which may occur only once or twice a day, or less.

[0065] An activation plot, or growth curve, is an approximation to the relationship between stimulus intensity (e.g. an amplitude of the current pulse 160) and intensity of neural response 170 evoked by the stimulus (e.g. an ECAP amplitude). Fig.4a illustrates an idealised activation plot 402 for one posture of the patient 108. The activation plot 402 shows a linearly increasing ECAP amplitude for stimulus intensity values above a threshold 404 referred to as the ECAP threshold. The ECAP threshold exists because of the binary nature of fibre recruitment; if the field strength is too low, no fibres will be recruited. However, once the field strength exceeds a threshold, fibres begin to be recruited, and their individual evoked action potentials are independent of the strength of the field. The ECAP threshold 404 therefore reflects the field strength at which significant numbers of fibres begin to be recruited, and the increase in response intensity with stimulus intensity above the ECAP threshold reflects increasing numbers of fibres being recruited. Below the ECAP threshold 404, the ECAP amplitude may be taken to be zero. Above the ECAP threshold 404, the activation plot 402 has a positive, approximately constant slope indicating a linear relationship between stimulus intensity and the ECAP amplitude. Such a relationship may be modelled as:(1)

[0066] where s is the stimulus intensity, d is the ECAP amplitude, T is the ECAP threshold and P is the slope of the activation plot (referred to herein as the patient sensitivity). The sensitivity P and the ECAP threshold T are the key parameters of the activation plot 402.

[0067] Fig.4a also illustrates a discomfort threshold 408, which is a stimulus intensity above which the patient 108 experiences uncomfortable or painful stimulation. Fig.4a also illustrates a perception threshold 410. The perception threshold 410 corresponds to an ECAP amplitude that is barely perceptible by the patient. There are a number of factors which can influence the position of the perception threshold 410, including the posture of the patient. Perception threshold 410 may correspond to a stimulus intensity that is greater than the ECAP threshold 404, as illustrated in Fig. 4a, if patient 108 does not perceive low levels of neural activation. Conversely, the perceptionthreshold 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.

[0068] For effective and comfortable operation of an implantable neuromodulation device such as the stimulator 100, it is desirable to maintain stimulus intensity within a therapeutic range. A stimulus intensity within a therapeutic range 412 is above the ECAP threshold 404 and below the discomfort threshold 408. In principle, it would be straightforward to measure these limits and ensure that stimulus intensity, which may be closely controlled, always falls within the therapeutic range 412. However, the activation plot, and therefore the therapeutic range 412, varies with the posture of the patient 108.

[0069] Fig.4b illustrates the variation in the activation plots with changing posture of the patient. A change in posture of the patient may cause a change in impedance of the electrode-tissue interface or a change in the distance between electrodes and the spinal cord. Electrode-to-cord distance is therefore loosely referred to throughout the present disclosure as posture though the two terms are not strictly synonymous. While the activation plots for only three postures, 502, 504 and 506, are shown in Fig.4b, the activation plot for any given posture can lie between or outside the activation plots shown, on a continuously varying basis depending on posture. Consequently, as the patient’s posture changes, the ECAP threshold changes, as indicated by the ECAP thresholds 508, 510, and 512 for the respective activation plots 502, 504, and 506. Additionally, as the patient’s posture changes, the patient sensitivity also changes, as indicated by the varying slopes of activation plots 502, 504, and 506. In general, as the distance between the stimulus electrodes and the spinal cord increases, the ECAP threshold increases and the sensitivity decreases. The activation plots 502, 504, and 506 therefore correspond to increasing distance between stimulus electrodes and spinal cord, and decreasing patient sensitivity.

[0070] To keep the applied stimulus intensity within the therapeutic range as patient posture varies, in some implementations an implantable neuromodulation device such as the stimulator 100 may adjust the applied stimulus intensity based on a feedback variable that is determined from one or more measured ECAP characteristics. In one implementation, the device may adjust the stimulus intensity to maintain the measured ECAP amplitude at 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 reduce the error as much as possible, such as by adding the scaled error to the current stimulus intensity. A neuromodulation device that operates by adjusting theapplied stimulus intensity based on a measured ECAP characteristic 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 an appropriate target response intensity, such as a target ECAP amplitude 520 illustrated in Fig.4b, a CLNS device will generally keep the stimulus intensity within the therapeutic range as patient posture varies.

[0071] A CLNS device comprises a stimulator that takes a stimulus intensity value and converts it into a neural stimulus 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 feedback loop.

[0072] In an example CLNS system, a user (e.g. the patient or a clinician) sets a target response intensity, and the CLNS device performs proportional-integral-differential (PID) control. In some implementations, the differential contribution is disregarded and the CLNS device uses a first order integrating feedback loop. The stimulator produces 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.

[0073] 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 the target intensity. If the target intensity is properly chosen, the patient receives consistently comfortable and therapeutic stimulation through posture changes and other perturbations to the stimulus / response behaviour.

[0074] 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.

[0075] 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 n, as well as the artefact a, may add to the evoked response y 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.

[0076] 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.

[0077] Measurement circuitry 318, which may be identified with measurement circuitry 128, amplifies the sensed signal r (including evoked neural response, artefact, and measurement noise), and samples the amplified sensed signal r to capture a “signal window” 319 comprising a predetermined number of samples of the amplified sensed signal r. The ECAP detector 320 processes the signal window 319 and outputs a measured neural response intensity d. In one implementation, the neural response intensity comprises a peak-to-peak ECAP amplitude. The measured response intensity d (an example of a feedback variable) is input into the feedback controller 310. The feedback controller 310 comprises a comparator 324 that compares the measured response intensity d to 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.

[0078] 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 s to minimise the error value, e. In one implementation, the controller 310 utilises a first order integrating function, using a gainelement 336 and an integrator 338, in order to provide suitable adjustment to the stimulus intensity parameter s. According to such an implementation, the current stimulus intensity parameter s may be determined by the feedback controller 310 as ^^ =∫^^ ^^ ^^ ^^ (2)

[0079] where K is the gain of the gain element 336 (the controller gain). This relation may also be represented as ^^ ^^ = ^^ ^^ (3)

[0080] where ^s is an adjustment to the current stimulus intensity parameter s.

[0081] A target ECAP amplitude is input to the feedback controller 310 via the target ECAP controller 304. In one embodiment, the target ECAP controller 304 provides an indication of a specific target ECAP amplitude. In another embodiment, 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.

[0082] A clinical settings controller 302 provides clinical settings to the system 300, including the feedback controller 310 and the stimulus parameters for the stimulator 312 that are not under the 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.

[0083] 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, thestimulator 312 outputs a stimulus in accordance with the adjusted stimulus intensity s. Accordingly, there is a delay of one stimulus clock cycle before the stimulus intensity is updated in light of the error value e.

[0084] 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.

[0085] 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.

[0086] 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.

[0087] The CI 740 may be implemented as the external computing device 192 of Fig.1. The CI 740 is configured to program the neuromodulation device 710 and recover data stored on the neuromodulation device 710. This configuration is achieved by program instructions collectively referred to as the Clinical Programming Application (CPA) and stored in an instruction memory of the CI 740. Multiple stimulation set neural stimulation therapy

[0088] As mentioned above, for some patients, it is beneficial for a neural stimulation therapy program to comprise multiple interleaved stimulation sets. A stimulation set (“stimset”) is a set ofstimulus and return electrodes, or more precisely a stimulus electrode configuration (SEC), along with the stimulus parameters that govern the stimulation pulses delivered via that SEC.

[0089] Fig.8 is an illustration 800 of the stimulus pulses delivered by a stimulation program with four stimsets according to one implementation of the present technology. The stimulus pulse train delivered according to each stimset is illustrated on a separate, but vertically aligned, horizontal axis representing time. All the stimulus pulse trains are delivered at the same stimulus frequency. (It is not a requirement that all the stimulus pulse trains for the respective stimsets are delivered at the same stimulus frequency; however it is so represented in Fig.8 for ease of illustration). The first stimulus pulse 810, delivered according to the first stimset, is illustrated as a biphasic, anodic-first stimulus pulse, though many other stimulus pulse types are contemplated for the pulses of a multi-stimset program. The second, third, and fourth stimulus pulses 820, 830, and 840, delivered according to the second, third, and fourth stimsets in the program respectively, are also biphasic, anodic-first stimulus pulses with different pulse widths and different amplitudes. Each stimulus pulse is illustrated as delayed in time by a constant amount (the inter-stimulus interval, or ISI, 815) from the stimulus pulse delivered according to the preceding stimset. However, this is not to be interpreted as limiting, since the intervals between the pulses in the various stimsets may be different. Because all the stimulus pulse trains in Fig.8 are delivered at the same stimulus frequency, the four stimulus pulses 810, 820, 830, 840 form a cycle that repeats indefinitely without any change to the relative timing of the pulses from the different stimsets. The fifth stimulus pulse 850 is a subsequent pulse in the pulse train delivered according to the first SEC and is therefore illustrated on the same time axis as the first stimulus pulse 810, and the cycle repeats thereafter.

[0090] Also illustrated is an evoked neural response in the form of an evoked compound action potential (ECAP) 860 as sensed via a predetermined measurement electrode configuration (MEC) on a common time axis with the stimulus pulses. The illustrated ECAP 860 is evoked by the fourth stimulus pulse 840. If the ISI 815 is short, ECAPs evoked by the first three stimulus pulses 810, 820, and 830 are potentially obscured by stimulus crosstalk and / or artefact from the stimulus pulses 820, 830, and 840. Therefore, if the ISI 815 is short, only the final stimset in the cycle may provide a measurable ECAP. If the ISI 815 is greater than the refractory period and is sufficiently long that ECAPs evoked by the earlier stimsets are not obscured by stimulus crosstalk and artefact from other stimulus pulses in the cycle, any of the stimsets in the cycle may provide a measurable ECAP. In this latter case, each stimset may be feedback controlled independently by its own ECAP, so that the multi-stimset program effectively comprises multiple independent stimulation programs operating simultaneously.

[0091] However, for present purposes, it may be assumed that either the ISI is so short that only the final stimset in the cycle may provide a measurable ECAP, or there are insufficient processing resources to measure the characteristics of more than one ECAP in the cycle. Alternatively, only one ECAP may be measured per cycle as a means of saving power. In such cases, closed-loop adjustments to the stimulus parameters of each stimset may be based on measurements of the ECAP 860 from a single stimset, referred to as the applied stimset. In Fig.8, the final stimset in the cycle is the applied stimset. The other stimsets are referred to as the non-applied stimsets. In International Patent Application no. PCT / AU2023 / 050786, the contents of which are incorporated here by reference, methods are disclosed for selecting which stimset in a multi-stimset CLNS system is the most suitable to be used as the applied stimset.

[0092] If the stimulus frequencies for at least two of the stimsets are different, the stimulus pulses no longer form a repeating cycle as described above in relation to Fig.8. In such implementations, potentially any ECAP from the applied stimset may be obscured by stimulus crosstalk and / or artefact from a near-simultaneous stimulus pulse delivered according to a stimset with a different stimulus frequency. However, at least some ECAPs from the applied stimset will be unobscured and therefore measurable, and it is possible to predict which stimulus pulses will result in such measurable ECAPs. Therefore, for any non-applied stimset, there will always be a most recent valid ECAP characteristic measurement on which to base adjustment of the next stimulus pulse for the non-applied stimset.

[0093] Fig.9 is a schematic illustrating elements of a multi-stimset CLNS system 900, according to aspects of the present technology. The multi-stimset CLNS system 900 is the similar to the single- stimset CLNS system 300 of Fig.5, with like numbers indicating like elements, except that certain elements have been replaced, and new elements have been added. The stimulator 312 has been replaced by m stimulators 312-1, ..., 312-m, configured to deliver stimuli according to respective stimulus intensity parameters s1, ..., sm, via respective SECs. In other words, the m stimulators 312-1, ..., 312-m deliver stimulation according to the respective stimsets of a multi-stimset program as illustrated in Fig.8 (which shows m = 4). The applied stimset pulses are delivered by stimulator 312- 1 according to the stimulus intensity parameter s1. The feedback controller 310 has been replaced by a multi-stimset feedback controller 910. The multi-stimset feedback controller 910 receives and analyses the neural response intensity d1 of the applied stimset from the ECAP detector 320 to generate the stimulus intensity parameters s1, sm. The stimulators 312-2, ..., 312-m deliver the non- applied stimset pulses according to the stimulus intensity parameters s2, ..., smrespectively. Theclinical settings controller 302 provides the stimulus parameters to the stimulators 312-1, ..., 312-m that are not under the control of the multi-stimset feedback controller 910.

[0094] In some implementations, the multi-stimset feedback controller 910 adjusts the applied stimset intensity s1 in the same way as the feedback controller 310, that is, according to Equation (2) or Equation (3).

[0095] In one implementation, the multi-stimset feedback controller 910 adjusts the non-applied stimset intensities s2, ..., sm in fixed proportion with the applied stimset intensity s1. That is, the applied stimulus intensity s1is scaled by ratios R2, ...., Rmto obtain the stimulus intensities s2, ..., smfor stimsets 2 to m respectively. The ratios R2, ...., Rm are fixed at the ratios of the stimulus intensities at which the respective non-applied stimsets were originally programmed, to the originally programmed stimulus intensity of the applied stimset. In such an implementation, referred to herein as ratiometric control, the stimulus intensities s2, ..., smalways remain in fixed ratio with the applied stimulus intensity s1 and with each other. So for example, if the originally programmed stimulus intensities are 1 mA, 2 mA, 4 mA, and 6 mA for four stimsets respectively, the ratios R2, R3, and R4 are fixed at programming time at 2, 4, and 6 respectively. The ratios R2, R3, and R4form part of the clinical settings 121 of the multi-stimset program. If during therapy the multi-stimset feedback controller 910 adjusts the applied stimset intensity s1 to 1.1 mA, the stimulus intensities s2, s3, and s4 of the non- applied stimsets are adjusted by the multi-stimset feedback controller 910 to 2.2 mA, 4.4 mA, and 6.6 mA respectively.

[0096] Note that even though the stimulus intensity parameters s1, ..., sm are dynamically variable under the control of the multi-stimset feedback controller 910, they are still regarded as part of the respective stimsets. Such an implementation is effective to maintain each stimset at a constant neural response intensity on the condition that when the patient moves to a new posture, the threshold and slope of all activation plots, both for applied and non-applied stimsets, move in a proportional manner. (See Fig.4b for examples of activation plots for a given stimset in different postures.)

[0097] More explicitly, if we assume the relationship between stimulus intensity s and response intensity d for any stimset follows Equation (1) (the linear activation plot model), then for stimsets 1 and 2 in their linear regions,(4)and ^^ଶ( ^^ଶ) = ^^ଶ( ^^ଶ− ^^ଶ) (5)

[0098] where Piis the sensitivity (slope) and Tiis the threshold (intercept) of the respective activation plots. Pi and Ti both in general vary with the electrode-cord distance x which, as mentioned above, is related to posture.

[0099] Now let x change to x’ as the patient moves to a second posture. If P2 varies with x in the same proportion as P1, and T1 and T2 vary with x in inverse proportion to the variation in P1, i.e. (6)

[0100] then it may be shown that keeping s2 in any fixed ratio with s1 as x varies keeps d2 constant as long as d1 is kept constant. In other words, a feedback controller that varies s1 to keep d1 constant as posture varies (like the multi-stimset feedback controller 910), and varies s2 in any fixed ratio with s1, will also keep d2 constant as posture varies. Because neural response intensity is thought to be a measurable proxy for the therapeutic effect of a stimset, a ratiometric implementation of the multi- stimset feedback controller 910 will therefore maintain the therapeutic effect of all stimsets, as long as they all stay within the linear regions of their respective activation plots.

[0101] Note the proportionality condition of activation plots (Equation (6)) holds if: ^ P2varies with x in the same proportion as P1, i.e.^ (௫)^మ(௫)^భభ(௫ᇱ)=^మ(௫ᇱ), and ^ P and T for each stimset are in inverse proportion to each other regardless of posture, i.e.(7)

[0102] where ki is a constant for each stimset i. Equation (7) is equivalent to the condition that all activation plots across postures for stimset i intersect on the d-axis at the same point (0,-ki).

[0103] If the proportionality condition of activation plots (Equation (6)) does not hold, then in the second posture, varying s2 in fixed ratio with s1 will not keep d2 constant even if d1 is kept constant.This means a ratiometric implementation of the multi-stimset feedback controller 910 will fail to maintain the therapeutic effect of all stimsets.

[0104] This is illustrated in Figs.10A and 10B. Fig.10A is a graph 1000 containing two activation plots 1010 and 1015 for stimsets 1 (applied) and 2 (non-applied) respectively, in a first posture. The multi-stimset feedback controller 910 maintains the stimulus intensity s1at or near the value 1020 in order to maintain the response intensity d1 at or near the target intensity 1025 for stimset 1. The multi- stimset feedback controller 910 also maintains the stimulus intensity s2 at a fixed ratio of approximately 1.28 times the stimulus intensity s1, i.e. at or near the value 1030, with the result that the response intensity d2 stays at or near the target intensity 1035 for stimset 2.

[0105] Fig.10B illustrates the result of the patient moving to a second posture. Fig.10B is a graph 1050 containing two activation plots 1055 and 1060 for stimsets 1 and 2 respectively, in the new posture. The activation plots 1055 and 1060 for the second posture do not satisfy the proportionality condition of Equation (6) in relation to the activation plots 1010 and 1015 for the first posture.

[0106] The multi-stimset feedback controller 910 maintains the stimulus intensity s1 at or near the value 1065, lower than the previous value 1020, in order to maintain the response intensity d1at or near the target intensity 1025 for stimset 1. The multi-stimset feedback controller 910 also maintains the stimulus intensity s2 at a fixed ratio of approximately 1.28 times the stimulus intensity s1, i.e. at or near the value 1070, with the result that the response intensity d2stays at or near a value 1075 that is lower than the target intensity 1035 for stimset 2. The therapeutic effect of the second stimset under ratiometric adjustment is therefore different between the first and second postures, which is undesirable.

[0107] Implementations of the multi-stimset feedback controller 910 according to aspects of the present technology attempt to adjust the stimulus intensity s2 of a non-applied stimset based on the response intensity d1 of an applied stimset so as to maintain the therapeutic effect of the second stimset as posture changes without relying on the proportionality condition of activation plots.

[0108] Fig.11 is a flow chart illustrating a method 1100 carried out by the multi-stimset feedback controller 910 according to a first aspect of the present technology. The method 1100 makes use of a database 1190 that has been previously populated during programming of the multi-stimset CLNS system 900 and stored in the clinical settings 121 along with other therapy parameters. The database 1190 contains data representing a set of activation plots, i.e. relationships di(si) of response intensityto stimulus intensity, for each stimset i across multiple postures. Each activation plot for each stimset corresponds to a single posture that is the same across all stimsets. An activation plot for a given posture may be represented in the database by a vector pi(I) of parameters, where I is an index of the given posture and the subscript i corresponds to stimset i. The activation plot for stimset i in posture I may be reconstructed from the parameter vector pi(I) as follows:(8)

[0109] where f is an activation plot model with argument s and parameters pi(I).

[0110] Table 1 illustrates example contents of the database 1190 over three postures in an example multi-stimset CLNS system containing three stimsets, of which stimset 1 is the applied stimset.Table 1: Example database 1190 contents.

[0111] The parameter vector pi(I) may be a vector of parameters that allows the activation plot for stimset i in posture I to be reconstructed, either approximately or exactly. In one example, suitable for a linear model of activation plot as in Equation (1), each vector pi(I) of parameters comprises a sensitivity Pi(I) and a threshold Ti(I) for stimset i in posture I.

[0112] In another example, each vector pi(I) of parameters comprises multiple pairs {(sij, dij(I))} where the dij(I) are measured values of response intensity at stimset i at various values sij (indexed by j) of stimulus intensity in the posture indexed by I. The activation plot for stimset i in posture I may be reconstructed from the set of pairs {(sij, dij(I))} by interpolation of a value di(I) for any stimulus intensity si.

[0113] The database 1190 may be populated by applying conventional methods of activation plot measurement to each stimset separately from the other stimsets in each posture, under the assumption that as long as stimulation is delivered according to each stimset separately, the corresponding neural responses may be measured without interference from the other stimsets. It may be further assumed that when stimulation is delivered according to the full multi-stimset program, the activation plots for each stimset retain their measured parameters despite the interleaving with other stimsets.

[0114] Alternatively, the database 1190 may be populated according to the methods described in International Patent Publication no. WO2023 / 141677, the contents of which are herein incorporated by reference, according to which disclosure multiple activation plots corresponding to multiple stimsets may be constructed and measured simultaneously by interleaving the stimuli from the respective stimsets. Such an implementation is suitable for the case in which any of the stimsets in the program may provide a measurable ECAP.

[0115] The method 1100 starts at step 1110, which uses the most recent valid (stimulus intensity, response intensity) pair (s1, d1) from the applied stimset (before adjustment) to determine the index Iminof the closest posture to the current posture from among the postures Ijin the database 1190. In one implementation, step 1110 traverses the parameter vectors p1(Ij) in the first column of the database 1190 for the applied stimset in different postures Ij. For each parameter vector p1(Ij), step 1110 reconstructs the activation plot of the applied stimset in the posture Ijusing the parameter vector p1(Ij), and determines a distance Dj between the pair (s1, d1) and the reconstructed activation plot. For example, in the linear model case in which each vector p1(Ij) of parameters comprises a sensitivity P and a threshold T, step 1110 determines a distance Dj (e.g. a perpendicular distance) between the pair (s1, d1) and the line of slope P and intercept T. At the end of the traversal, step 1110 chooses the posture index Imin as the index of the reconstructed activation plot corresponding to the smallest distance value Dmin.

[0116] An alternative implementation of step 1110 is suitable for the case when Equation (7) (the inverse proportionality of sensitivity and threshold across postures under a linear model of the activation plot) holds for the applied stimset. Step 1110 determines posture by first solving Equation (7) simultaneously with the activation plot Equation (1) and the (stimulus intensity, response intensity) pair (s1, d1) to determine the slope P and intercept T for the applied stimset in the current posture:(9)

[0117] Step 1110 then traverses the parameter vectors p1(Ij) in the first column of the database 1190 for the applied stimset in different postures Ij to find the index Imin of the pair (P1(Ij), T1(Ij)) that most closely matches the determined slope P and intercept T for the applied stimset. For example, the closest match may be the pair (P1(Ij), T1(Ij)) with the smallest Euclidean distance from the determined pair (P, T).

[0118] Step 1110 then extracts from the database 1190 the parameter vector pi(Imin) corresponding to the posture index Imindetermined at step 1110, where i is the index of the non-applied stimset. Step 1120 thereby determines the activation plot (relationship) di(si) for the non-applied stimset i in the posture indexed by Imin using the parameter vector pi(Imin) and Equation (8).

[0119] Step 1120 then determines the stimulus intensity si’ that is mapped by the activation plot di(si) to the target response intensity ti for the non-applied stimset. Step 1120 essentially inverts the relationship di(si) to find the value of stimulus intensity si’ that produces a response intensity di that equals the target response intensity ti.

[0120] In an example of step 1120 in which the activation plot di(si) for the non-applied stimset i is linear (as in Equation (1)) and the parameter vector pi(Imin) comprises a sensitivity Pi and a threshold Ti, step 1120 determines the stimulus intensity si’ as

[0121] In one implementation, in which the target response intensity tifor the non-applied stimset is static and not adjustable by the patient, the target response intensity ti for the non-applied stimset may have been stored during programming among the therapy parameters in the clinical settings 121.

[0122] In other implementations, the target response intensity tifor the non-applied stimset is dynamically adjustable based on adjustments to the target response intensity t1 for the applied stimset. In such implementations, the target response intensity ti for the non-applied stimset is a function gi(t1) of the target response intensity t1for the applied stimset. In one such implementation, the targetresponse intensity ti for the non-applied stimset is a fixed multiple ai of the target response intensity t1for the applied stimset, so that as the target response intensity t1for the applied stimset is adjusted, e.g. by the patient using the remote controller 720, the target response intensity ti for the non-applied stimset is adjusted by the target ECAP controller 304 according to the multiple ai of the target response intensity t1. The multiples aifor one or more non-applied stimsets may have been stored during programming among the therapy parameters in the clinical settings 121. Functions gi(t1) other than a fixed multiplication are contemplated for deriving the target response intensity ti for the non- applied stimset from the target response intensity t1for the applied stimset. (Note that such lock-step adjustment of other target response intensities in response to manual adjustment of a single target intensity may be part of an implementation in which multiple feedback loops otherwise operate independently.)

[0123] The method 1100 may be carried out once before each stimulus pulse for each non-applied stimset, either before or after the multi-stimset feedback controller 910 updates the stimulus intensity of the applied stimset. Alternatively, the method 1100 may be carried out less frequently, for example once every ten stimulus pulses. In such implementations, all valid measurement pairs (s1, d1) from the applied stimset since the last iteration may be used in step 1110 to determine the current posture. In one such implementation, a representative distance ^ഥ^ఫ(such as a mean or median) from all valid measurement pairs (s1, d1) to each reconstructed activation plot may be determined and minimised. Such a determination is potentially more accurate, being based on more data, but comes at the cost of slower response by the multi-stimset feedback controller 910 to changes in posture.

[0124] The method 1100 is a method of operation of the multi-stimset feedback controller 910 that is based on the neural response intensity d as a proxy for the therapeutic effect of each stimset, and the activation plots that relate neural response intensity d to stimulus intensity s. Alternative implementations of the multi-stimset feedback controller 910 according to the first aspect are based on other methods of estimating the therapeutic effect of a stimset.

[0125] One such alternative method of operation of the multi-stimset feedback controller 910 is based on neural recruitment as a proxy for therapeutic effect. Neural recruitment Ri for a stimset in any posture may be estimated as the ratio of stimulus intensity si to the threshold Ti in that posture: ^^ ^ ^ =^்^(12)

[0126] One alternative method of operation based on neural recruitment is similar to the method 1100 in that the alternative method makes use of the database 1190. However, instead of extracting the complete parameter vector pi(Imin) at step 1110 so as to determine a relationship di(si) for the non- applied stimset i in the posture indexed by Imin, the alternative method extracts only the parameter pi of the parameter vector pi(Imin) that is needed to estimate recruitment for the non-applied stimset according to Equation (12). The alternative method then uses the extracted parameter pi to determine the adjusted stimulus intensity si’. In one example of such an alternative implementation, in which the activation plot di(si) for the non-applied stimset i is linear (as in Equation (1)) and the parameter vector pi(Imin) comprises a sensitivity Pi and a threshold Ti, the alternative method extracts the threshold Ti from the parameter vector pi(Imin). The alternative method then uses the threshold Ti and Equation (12) to determine the adjusted stimulus intensity si’, for example by multiplying the threshold Ti by a target^^^^for the non-applied stimset. As for the first-mentioned implementation, the target recruitment ^^^^may be stored during programming among the therapy parameters in the clinical settings 121, or dynamically adjustable based on manual adjustments to the target response intensity ^^^^for the applied stimset.

[0127] Alternatively, the database 1190 may contain only the parameters pi(I) that are needed to estimate recruitment for the non-applied stimset i in each posture I according to Equation (12), rather than the activation plot parameter vector pi(I) for each posture.

[0128] Fig.13 is a flow chart illustrating a method 1300 carried out by the multi-stimset feedback controller 910 according to such an alternative implementation of the first aspect of the present technology. The optional step 1305 delivers a stimulus according to the applied stimset and a first stimulus intensity parameter value s1, and measures an intensity d1of the neural response evoked by the delivered stimulus. Step 1310 determines a parameter of a relationship between stimulus intensity and therapeutic effect for the non-applied stimset i in the current posture from the measured response intensity d1and the and the stimulus intensity parameter value s1of the applied stimulation set. Step 1320 then uses the determined parameter to determine the adjusted stimulus intensity parameter si’ of the non-applied stimset that will maintain the therapeutic effect of the non-applied stimset.

[0129] Implementations of the multi-stimset feedback controller 910 according to a second aspect of the present technology adjust the non-applied stimset intensity by an amount ^si that is a scalar multiple of the adjustment ^s1 to the applied stimset intensity, where the scalar mi for each non- applied stimset varies according to the determined posture and / or the current stimulus intensities.(A straight ratiometric adjustment as described above is equivalent to this, except that the scalar mi for each non-applied stimset is invariant to posture and stimulus intensity.)

[0130] Implementations according to the second aspect assume the therapeutic effect is an approximately linear function of stimulus intensity, at least within the therapeutic range of stimulus intensity values. The key parameter according to the second aspect for each stimset i and posture I is the derivative di(I) of therapeutic effect with respect to stimulus intensity. For example, in the case where neural response intensity is a proxy for the therapeutic effect, the derivative parameter di(I) is the sensitivity Pi(I). In the case where neural recruitment R is a proxy for the therapeutic effect according to Equation (12), the derivative parameter d ^ i(I) is the reciprocal்^(ூ)of the ECAP threshold Ti(I). The derivative d’i(I) of this derivative parameter with respect to posture is a further parameter used by the methods according to the second aspect.

[0131] Fig.12 is a flow chart illustrating a method 1200 that may be carried out by the multi-stimset feedback controller 910 according to one implementation of the second aspect of the present technology. The database 1290 used by the method 1200 is similar in structure to the database 1190, but its contents are different. Table 2 illustrates the contents of the database 1290 over three postures in an example multi-stimset CLNS system containing three stimsets, of which stimset 1 is the applied stimset, according to one implementation.Table 2: Example database 1290 contents

[0132] The first column of the database 1290 contains the parameter vectors p1(Ij) (as in Table 1). In addition, the first column of the database 1290 contains the derivatives d1(Ij). The second andsubsequent columns contain the derivative , and derivative ratios d’i(Ij) / d’1(Ij). The derivative ratio d’i(Ij) / d’1(Ij) is the ratio of the derivative d’i(Ij) of the derivative parameter di(Ij) with respect to posture for the non-applied stimset i in posture Ij to the derivative d’1(Ij) of the derivative parameter d1(Ij) with respect to posture for the applied stimset 1 in posture Ij.

[0133] The method 1200 starts at step 1210, which determines the current posture in the same manner as in step 1110, using the parameter vectors p1(Ij) from the first column of the database 1290. Step 1220 then extracts from the database 1290 the derivative parameter d1(Imin) for the applied stimset, the derivative parameter di(Imin), and the derivative ratio d’i(Imin) / d’1(Imin) for the non-applied stimset i, corresponding to the determined posture index Imin. Step 1220 then determines the scalar mi(Imin) for the non-applied stimset i corresponding to the determined posture index Imin from the derivative parameters d1(Imin) and di(Imin), the derivative ratio d’i(Imin) / d’1(Imin), the current (pre-adjustment) stimulus intensity s1for the applied stimset, and the current stimulus intensity sifor the non-applied stimset i.

[0134] In one implementation of step 1220, the multi-stimset feedback controller 910 computes the scalar mi(Imin) using the following equation:

[0135] In an alternative implementation, step 1220 may use the respective target response intensities for the applied and non-applied stimsets, t1 and ti, in place of the stimulus intensities s1 and si respectively in Equation (13). The target response intensities are more stable variables than the stimulus intensities, which in principle may be updated before every stimulus pulse, so the control of the non-applied stimset may be smoother under this alternative implementation.

[0136] Step 1230 then adjusts the stimulus intensity si for the non-applied stimset by an adjustment ^si. The adjustment ^sifor the non-applied stimset may be determined by multiplying the most recent adjustment ^ ^s1 to the applied stimset intensity (previously determined by the multi-stimset feedback controller 910) by the scalar mi(Imin) from step 1220:

[0137] It may be shown that adjustment according to Equation (14) maintains the neural response intensity di of the non-applied stimset (a proxy for therapeutic effect) at a constant value as posturechanges, on the assumption the most recent adjustment ^ ^s1 to the applied stimset intensity maintains the neural response intensity d1 of the applied stimset at a constant value.

[0138] The method 1200 may be carried out before each stimulus pulse for each non-applied stimset. Alternatively, the method 1200 may be carried out less frequently, for example once every ten stimulus pulses. In such implementations, all valid measurement pairs (s1, d1) from the applied stimset since the last iteration may be used in step 1210, for example as described above in relation to step 1110, to determine the current posture. Such a determination is potentially more accurate, being based on more data, but comes at the cost of slower response by the multi-stimset feedback controller 910 to changes in posture.

[0139] Implementations of the multi-stimset feedback controller 910 according to yet another aspect of the present technology adjust the non-applied stimset intensity according to an affine function of the applied stimset intensity. In such implementations, posture is not determined. Instead, the multi- stimset feedback controller 910 adjusts the non-applied stimset intensity siusing the applied stimset intensity s1 according to the following equation: ^^^= ^^^^^^+ ^^^(15)

[0140] where ^i^i are constants for the non-applied stimset i. Affine adjustment according to Equation (15) differs from ratiometric control due to the presence of the (non-zero) offset ^i.

[0141] It may be shown that affine adjustment according to Equation (15) with properly calibrated constants ^i ^i maintains approximately constant neural recruitment (a proxy for therapeutic effect) in the non-applied stimset under the assumptions that: ^ neural recruitment of any stimset is, beyond some constant threshold T, proportional to the stimulus intensity times the electrode-to-cord distance xi of stimset i’s SEC raised to a negative exponent -n (where n > 0): ^^^∝ ^^^^^^ି^− ^^^ the electrode-to-cord distance xi of stimset i’s SEC is a constant offset Di from the electrode- to-cord distance of the applied stimset’s SEC:^^^

[0142] The constants ^i and ^i may be calibrated during programming by: finding the therapeutically effective values of applied and non-applied stimset intensities s1 and si in at least two different postures; and fitting a straight line to the pairs (s1, si). The constants ^i and ^i may be set to the slope and intercept of the fitted line. The constants ^i and ^i may then be stored as part of the clinical settings 121 for each non-applied stimset.

[0143] In the special case in which the exponent n is equal to one, i.e. recruitment is inversely proportional to electrode-to-cord distance x, and all stimsets start with equal recruitment, it may be shown that the constant ^i may be set to one. The non-applied stimset intensity may therefore be maintained at a constant offset from the applied stimset intensity to maintain its therapeutic effect.

[0144] It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not limiting or restrictive. LABEL LIST stimulator 100 nerve 180 patient 108 communications channel 190 electronics module 110 external computing device 192 battery 112 system 300 telemetry module 114 clinical settings controller 302 controller 116 target ECAP controller 304 memory 118 box 308 clinical data 120 box 309 clinical settings 121 feedback controller 310 control programs 122 box 311 pulse generator 124 stimulator 312 electrode selection module 126 stimulator 312-1 measurement circuitry 128 stimulator 312-2 system ground 130 stimulator 312-m electrode array 150 element 313 biphasic stimulus pulse 160 measurement circuitry 318 ECAP 170 ECAP detector 320comparator 324 multi - stimset CLNS system 900 gain element 336 multi - stimset feedback integrator 338 controller 910 activation plot 402 graph 1000 ECAP threshold 404 activation plot 1010 discomfort threshold 408 activation plot 1015 perception threshold 410 value 1020 therapeutic range 412 target intensity 1025 activation plot 502 value 1030 activation plot 504 target intensity 1035 activation plot 506 graph 1050 ECAP threshold 508 activation plot 1055 ECAP threshold 510 activation plot 1060 ECAP threshold 512 value 1065 target ECAP amplitude 520 value 1070 ECAP 600 value 1075 neuromodulation system 700 method 1100 neuromodulation device 710 step 1110 remote controller 720 step 1120 CST 730 database 1190 CI 740 method 1200 charger 750 step 1210 illustration 800 step 1220 stimulus pulse 810 step 1230 ISI 815 database 1290 stimulus pulse 820 method 1300 stimulus pulse 830 step 1305 stimulus pulse 840 step 1310 stimulus pulse 850 step 1320 ECAP 860

Claims

CLAIMS:

1. An implantable device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to: control the stimulus source to provide interleaved neural stimuli according to each of a plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and control the stimulus intensity parameter of the second stimulation set according to the determined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

2. The device of claim 1, wherein the relationship is a relationship between intensities of neural responses evoked by neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set.

3. The device of claim 2, wherein the control unit is configured to control the stimulus intensity parameter of the second stimulation set by: applying the determined parameter to a target value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set.

4. The device of claim 1, wherein the relationship is a relationship between neural recruitment of neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set.

5. The device of claim 4, wherein the parameter is an ECAP threshold of the second stimulation set.

6. The device of claim 5, wherein the control unit is configured to control the stimulus intensity parameter of the second stimulation set by: applying the determined parameter to a target recruitment value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set.

7. The device of claim 6, wherein the control unit is configured to apply the determined parameter by multiplying the target recruitment value by the ECAP threshold of the second stimulation set.

8. The device of any of claims 1 to 7, wherein the control unit is further configured to control the stimulus intensity parameter of the first stimulation set to maintain the therapeutic effect of the neural stimuli provided according to the first stimulation set at a target value of the first stimulation set.

9. The device of any of claims 1 to 8, wherein the control unit is configured to determine the parameter of the relationship by: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing; and determining the parameter of the relationship based on the selected one activation plot for the first stimulation set.

10. An automated method of controllably delivering neural stimuli to a neural pathway of a patient, the method comprising: providing interleaved neural stimuli to the neural pathway according to each of a plurality of stimulation sets;measuring an intensity of an evoked neural response subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determining, based on the measured intensity of the evoked neural response and a stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and controlling a stimulus intensity parameter of the second stimulation set according to the determined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

11. The method of claim 10, wherein the relationship is a relationship between intensities of neural responses evoked by neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set.

12. The method of claim 11, wherein controlling the stimulus intensity parameter of the second stimulation set comprises: applying the determined parameter to a target value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set.

13. The method of claim 10, wherein the relationship is a relationship between neural recruitment of neural stimuli provided according to the second stimulation set, and the stimulus intensity parameter of the second stimulation set.

14. The method of claim 13, wherein the parameter is an ECAP threshold of the second stimulation set.

15. The method of claim 14, wherein controlling the stimulus intensity parameter of the second stimulation set comprises: applying the determined parameter to a target recruitment value of the second stimulation set to obtain the stimulus intensity parameter of the second stimulation set.

16. The method of claim 15, wherein the applying comprises multiplying the target recruitment value by the ECAP threshold of the second stimulation set.

17. The method of any of claims 10 to 16, further comprising controlling the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a target value of the first stimulation set.

18. The method of any of claims 10 to 17, wherein determining the parameter of the relationship comprises: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing; and determining the parameter of the relationship based on the selected one activation plot for the first stimulation set.

19. A neural stimulation system comprising: an implantable neuromodulation device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to control the stimulus source to provide neural stimuli according to a plurality of stimulation sets; a processor configured to: instruct the control unit to control the stimulus source to provide interleaved neural stimuli according to each of the plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a provided neural stimulus corresponding to a first stimulation set of the plurality of stimulation sets;determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a parameter of a relationship between a therapeutic effect of neural stimuli provided according to a second stimulation set of the plurality of stimulation sets and a stimulus intensity parameter of the second stimulation set; and control the stimulus intensity parameter of the second stimulation set according to the determined parameter to maintain a therapeutic effect of the neural stimuli provided according to the second stimulation set.

20. The neural stimulation system of claim 19, wherein the processor is further configured to control a stimulus intensity parameter of the first stimulation set to maintain therapeutic effect of the neural stimuli provided according to the first stimulation set at a target value of the first stimulation set.

21. The neural stimulation system of claim 19, further comprising an external computing device with which the implantable neuromodulation device is in communication.

22. The neural stimulation system of claim 21, wherein the processor forms part of the external computing device.

23. The neural stimulation system of claim 19, wherein the processor forms part of the implantable neuromodulation device.

24. An implantable device for controllably delivering neural stimuli, the device comprising: a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to: control the stimulus source to provide interleaved neural stimuli according to each of a plurality of stimulation sets;measure an intensity of an evoked neural response in the captured signal window subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a posture of the patient; determine a first adjustment to the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a first target value; and determine a second adjustment to a stimulus intensity parameter of a second stimulation set of the plurality of stimulation sets based on the first adjustment and according to the determined posture.

25. The device of claim 24, wherein the control unit is configured to determine the second adjustment to the stimulus intensity parameter of the second stimulation set according to the determined posture to maintain an intensity of neural responses evoked by neural stimuli provided according to the second stimulation set at a second target value.

26. The device of any of claims 24 to 25, wherein the control unit is configured to determine the second adjustment to the stimulus intensity parameter of the second stimulation set by: determining a scalar using the determined posture of the patient; and multiplying the first adjustment to the stimulation intensity parameter of the first stimulation set by the scalar.

27. The device of claim 26, wherein the control unit is configured to determine the scalar by dividing the stimulus intensity parameter of the second stimulation set by the stimulus intensity parameter of the first stimulation set.

28. The device of claim 27, wherein the control unit is configured to determine the scalar by dividing a derivative parameter of the first stimulation set in the determined posture by a derivative parameter of the second stimulation set in the determined posture.

29. The device of claim 28, wherein the control unit is configured to determine the scalar from a ratio of: a derivative of the derivative parameter of the second stimulation set with respect to posture in the determined posture; anda derivative of the derivative parameter of the first stimulation set with respect to posture in the determined posture.

30. The device of any of claims 28 to 29, wherein the derivative parameter is a patient sensitivity.

31. The device of any of claims 28 to 29, wherein the derivative parameter is a reciprocal of an ECAP threshold.

32. The device of any of claims 24 to 31, wherein the control unit is configured to determine the posture by: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; and selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing, the one activation plot corresponding to the determined posture.

33. An automated method of controllably delivering neural stimuli to a neural pathway of a patient, the method comprising: providing interleaved neural stimuli to the neural pathway according to each of a plurality of stimulation sets; measuring an intensity of an evoked neural response subsequent to a neural stimulus provided according to a first stimulation set of the plurality of stimulation sets; determining, based on the measured intensity of the evoked neural response and a stimulus intensity parameter of the first stimulation set, a posture of the patient; determining a first adjustment to the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a first target value; and determining a second adjustment to a stimulus intensity parameter of a second stimulation set of the plurality of stimulation sets based on the first adjustment and according to the determined posture.

34. The method of claim 33, wherein determining the second adjustment to the stimulus intensity parameter of the second stimulation set according to the determined posture maintains an intensity of neural responses evoked by neural stimuli provided according to the second stimulation set at a second target value.

35. The method of any of claims 33 to 34, wherein determining the second adjustment to the stimulus intensity parameter of the second stimulation set comprises: determining a scalar using the determined posture of the patient; and multiplying the first adjustment to the stimulation intensity parameter of the first stimulation set by the scalar.

36. The method of claim 35, wherein determine the scalar comprises dividing the stimulus intensity parameter of the second stimulation set by the stimulus intensity parameter of the first stimulation set.

37. The method of claim 36, wherein determining the scalar comprises dividing a derivative parameter of the first stimulation set in the determined posture by a derivative parameter of the second stimulation set in the determined posture.

38. The method of claim 37, wherein the scalar comprises a ratio of: a derivative of the derivative parameter of the second stimulation set with respect to posture in the determined posture; and a derivative of the derivative parameter of the first stimulation set with respect to posture in the determined posture.

39. The method of any of claims 37 to 38, wherein the derivative parameter is a patient sensitivity.

40. The method of any of claims 37 to 38, wherein the derivative parameter is a reciprocal of an ECAP threshold.

41. The method of any of claims 33 to 40, wherein determining the posture comprises: comparing the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set to a plurality of activation plots for the first stimulation set, where the activation plots correspond to postures; and selecting one activation plot of the plurality of activation plots for the first stimulation set based on the comparing, the one activation plot corresponding to the determined posture.

42. A neural stimulation system comprising: an implantable neuromodulation device for controllably delivering neural stimuli, the device comprising:a stimulus source configured to provide neural stimuli to be delivered according to a stimulation set to a neural pathway of a patient in order to evoke a neural response from the neural pathway, wherein a stimulation set comprises: a stimulus electrode configuration of one or more stimulus electrodes, and a set of stimulus parameters including a stimulus intensity parameter; measurement circuitry configured to capture signal windows sensed on the neural pathway subsequent to respective neural stimuli; and a control unit configured to control the stimulus source to provide neural stimuli according to a plurality of stimulation sets; a processor configured to: instruct the control unit to control the stimulus source to provide interleaved neural stimuli according to each of the plurality of stimulation sets; measure an intensity of an evoked neural response in the captured signal window subsequent to a provided neural stimulus corresponding to a first stimulation set of the plurality of stimulation sets; determine, based on the measured intensity of the evoked neural response and the stimulus intensity parameter of the first stimulation set, a posture of the patient; determine a first adjustment to the stimulus intensity parameter of the first stimulation set to maintain the measured intensity of the evoked neural response at a first target value; and determine a second adjustment to a stimulus intensity parameter of a second stimulation set of the plurality of stimulation sets based on the first adjustment and according to the determined posture.

43. The neural stimulation system of claim 42, further comprising an external computing device with which the implantable neuromodulation device is in communication.

44. The neural stimulation system of claim 43, wherein the processor forms part of the external computing device.

45. The neural stimulation system of claim 42, wherein the processor forms part of the implantable neuromodulation device.

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