WO2024092076A1

WO2024092076A1 - Constructive and/or destructive evoked resonant neural activity (erna) for providing deep brain stimulation (dbs) therapy

Info

Publication number: WO2024092076A1
Application number: PCT/US2023/077829
Authority: WO
Inventors: Kristin Nicole HAGEMAN; Rene A. MOLINA; Erik J. Peterson; Scott R. Stanslaski; Paul H. Stypulkowski
Original assignee: Medtronic Inc
Priority date: 2022-10-28
Filing date: 2023-10-26
Publication date: 2024-05-02

Abstract

A system is provided for providing deep brain stimulation (DBS) therapy based on constructive and destructive resonance concepts. For example, the system may measure a first response after applying a pulse of an electrical stimulation signal and may measure a second response after applying a plurality of pulses of the electrical stimulation signal. Subsequently, the system may determine a constructive resonance state and/or a destructive resonance state for applying the electrical stimulation signal to the anatomical element based on the first response and the second response and may apply the electrical stimulation signal using a plurality of stimulation parameters determined based on maintaining, changing, or switching the constructive resonance state and/or the destructive resonance state.

Description

CONSTRUCTIVE AND/OR DESTRUCTIVE EVOKED RESONANT NEURAL ACTIVITY (ERNA) FOR PROVIDING DEEP BRAIN STIMULATION (DBS) THERAPY

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/420,261, filed on October 28, 2022, which application is incorporated herein by reference in its entirety.

BACKGROUND

[0002] The present disclosure is generally directed to electrical stimulation therapy and, in particular, relates to deep brain stimulation (DBS) therapy.

[0003] Medical devices may be external or implanted, and may be used to deliver electrical stimulation therapy to various tissue sites of a patient to treat a variety of symptoms or conditions such as chronic pain, tremor, Parkinson’s disease, other movement disorders, epilepsy, urinary or fecal incontinence, sexual dysfunction, obesity, or gastroparesis. A medical device delivers electrical stimulation therapy via one or more leads that include electrodes located proximate to target locations associated with the brain, the spinal cord, pelvic nerves, peripheral nerves, or the gastrointestinal tract of a patient. Electrical stimulation is used in different therapeutic applications, such as DBS, spinal cord stimulation (SCS), pelvic stimulation, gastric stimulation, or peripheral nerve field stimulation (PNFS).

BRIEF SUMMARY

[0004] Example aspects of the present disclosure include:

[0005] A system for providing DBS therapy, comprising: a signal generator configured to generate an electrical stimulation signal; one or more leads coupled to the signal generator, the one or more leads configured to carry the generated electrical stimulation signal to an anatomical element of a patient; a respective plurality of electrodes disposed at distal portions of the one or more leads, the respective plurality of electrodes configured to be implanted in the anatomical element and to apply the generated electrical stimulation signal to the anatomical element based at least in part on being implanted in the anatomical element; a processor; and a memory storing data for processing by the processor. In some embodiments, the data, when processed, may cause the processor to: measure, via one or more electrodes of the respective plurality of electrodes, a first response after applying a pulse of the generated electrical stimulation signal to the anatomical element; measure, via one or more electrodes of the respective plurality of electrodes, a second response after applying a plurality of pulses of the generated electrical stimulation signal to the anatomical element; determine a constructive resonance state and/or a destructive resonance state for applying the generated electrical stimulation signal to the anatomical element based at least in part on the first response and the second response; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes based at least in part on one or more stimulation parameters determined based at least in part on the constructive resonance state and/or the destructive resonance state. [0006] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: extract a first set of timings corresponding to a peak and a trough for the first response; and extract a second set of timings corresponding to peaks and troughs for the second response, wherein the constructive resonance state and/or the destructive resonance state are determined based at least in part on the first set of timings and the second set of timings.

[0007] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: calculate a steady state behavior for the second response based at least in part on the constructive resonance state and/or the destructive resonance state.

[0008] Any of the aspects herein, wherein the one or more stimulation parameters are determined based at least in part on an alignment of a peak and/or trough for the first response from the first set of timings and the steady state behavior for the second response.

[0009] Any of the aspects herein, wherein: the constructive resonance state comprises a state where a peak corresponding to the first response would align with a first portion and/or a peak of an underlying resonance response corresponding to the second response; and the destructive resonance state comprises a state where the peak corresponding to the first response would align with a second portion and/or a trough of the underlying resonance response corresponding to the second response.

[0010] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes according to a first resonant state, wherein the first resonant state comprises a degree of the constructive resonance state and/or the destructive resonance state; monitor for changes in a peak-to-trough amplitude between each pulse of the generated electrical stimulation signal; determine a shift in phase alignment between an underlying resonance response corresponding to the second response and the first response, the shift in phase alignment determined based at least in part on detecting a change in the peak-to-trough amplitude; and adjust one or more parameters of the generated electrical stimulation signal to align a peak corresponding to the first response with the underlying resonance response to maintain the first resonant state based at least in part on determining the shift in phase alignment.

[0011] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: inhibit application of the generated electrical stimulation signal for one or more pulses; and determine the underlying resonance response for confirming the shift in phase alignment based at least in part on inhibiting application of the generated electrical stimulation signal for the one or more pulses.

[0012] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes according to a first resonant state, wherein the first resonant state comprises a degree of the constructive resonance state and/or the destructive resonance state; monitor for side effects caused by applying the generated electrical stimulation signal according to the first resonant state; adjust a resonant state of the generated electrical stimulation signal based at least in part on detecting the side effects; and adjust one or more parameters of the generated electrical stimulation signal to align a peak corresponding to the first response with an underlying resonance response corresponding to the second response to provide the generated electrical stimulation signal according to the adjusted resonant state.

[0013] Any of the aspects herein, wherein the data stored in the memory that, when processed causes the processor to adjust the resonant state of the electrical stimulation signal causes the system to: adjust the first resonant state to have a different degree of the constructive resonance state and/or the destructive resonance state, shift an alignment of the peak and/or trough corresponding to the first response off a peak of the underlying resonance response, switch from the first resonant state to a second resonant state, adjust a pulse timing for the electrical stimulation signal, or a combination thereof. [0014] Any of the aspects herein, wherein the side effects comprise a change in the second response, a local field potential signal side effect, a change in accelerometer sensing, or a combination thereof.

[0015] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: assign the constructive resonance state and/or the destructive resonance state to each of a plurality of neural states; detect a neural state of the plurality of neural states; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes according to the assigned constructive resonance state and/or destructive resonance state for the detected neural state.

[0016] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: monitor for a change from the detected neural state to a second neural state of the plurality of neural states, the second neural state corresponding to a different assigned resonant state of the detected neural state; switch a resonant state for providing the generated electrical stimulation signal based at least in part on detecting the change from the detected neural state to the second neural state; adjust one or more parameters of the generated electrical stimulation signal to align a peak corresponding to the first response with an underlying resonance response corresponding to the second response to provide the generated electrical stimulation signal according to the switched resonant state; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes using the adjusted one or more parameters.

[0017] Any of the aspects herein, wherein the one or more stimulation parameters comprises a frequency, an amplitude, a pulse width, a number of pulses, additional parameters, or a combination thereof for the electrical stimulation signal.

[0018] Any of the aspects herein, wherein the first response comprises an evoked potential (EP) response, and the second response comprises an evoked resonant neural activity (ERNA) response.

[0019] Any of the aspects herein, wherein the anatomical element comprises a brain of the patient.

[0020] Any of the aspects herein, wherein the signal generator is a part of an implantable medical device, a programmer, or both [0021] A system for providing DBS therapy, comprising: a processor and a memory storing data for processing by the processor, the data, when processed, causes the processor to: measure a first response of applying a pulse of an electrical stimulation signal to an anatomical element of a patient; measure a second response of applying a plurality of pulses of the electrical stimulation signal to the anatomical element; determine a constructive resonance state and/or a destructive resonance state for applying the generated electrical stimulation signal to the anatomical element based at least in part on the first response and the second response; and transmit instructions to provide the electrical stimulation signal to the anatomical element using one or more stimulation parameters determined based at least in part on the constructive resonance state and/or the destructive resonance state.

[0022] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: extract a first set of timings corresponding to a peak and trough for the first response; and extract a second set of timings corresponding to peaks and troughs for the second response, wherein the constructive resonance state and/or the destructive resonance state are determined based at least in part on the first set of timings and the second set of timings.

[0023] Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: calculate a steady state behavior for the second response based at least in part on the constructive resonance state and the destructive resonance state.

[0024] A system for providing DBS therapy, comprising: a signal generator configured to generate an electrical stimulation signal; one or more leads coupled to the signal generator, the one or more leads configured to carry the generated electrical stimulation signal to an anatomical element of a patient; and a respective plurality of electrodes disposed at distal portions of the one or more leads, the respective plurality of electrodes configured to be implanted in the anatomical element and to apply the generated electrical stimulation signal to the anatomical element based at least in part on being implanted in the anatomical element, wherein the signal generator is configured to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes based at least in part on one or more stimulation parameters determined based at least in part on a constructive resonance state and/or a destructive resonance state. [0025] Any of the aspects herein, wherein: the constructive resonance state comprises a state where a peak corresponding to a first response would align with a first portion and/or a peak of an underlying resonance response; and the destructive resonance state comprises a state where the peak corresponding to the first response would align with a second portion and/or a trough of the underlying resonance response, wherein the first response is acquired based at least in part on applying a pulse of the generated electrical stimulation signal and the underlying resonance response is acquired based at least in part on applying a plurality of pulses of the generated electrical stimulation signal.

[0026] Any aspect in combination with any one or more other aspects.

[0027] Any one or more of the features disclosed herein.

[0028] Any one or more of the features as substantially disclosed herein.

[0029] Any one or more of the features as substantially disclosed herein in combination with any one or more other features as substantially disclosed herein.

[0030] Any one of the aspects/features/embodiments in combination with any one or more other aspects/features/embodiments.

[0031] Use of any one or more of the aspects or features as disclosed herein.

[0032] It is to be appreciated that any feature described herein can be claimed in combination with any other feature(s) as described herein, regardless of whether the features come from the same described embodiment.

[0033] The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims.

[0034] The phrases “at least one”, “one or more”, and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions “at least one of A, B and C”, “at least one of A, B, or C”, “one or more of A, B, and C”, “one or more of A, B, or C” and “A, B, and/or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together. When each one of A, B, and C in the above expressions refers to an element, such as X, Y, and Z, or class of elements, such as Xl-Xn, Yl-Ym, and Zl-Zo, the phrase is intended to refer to a single element selected from X, Y, and Z, a combination of elements selected from the same class (e.g., XI and X2) as well as a combination of elements selected from two or more classes (e.g., Y1 and Zo). [0035] The term “a” or “an” entity refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. It is also to be noted that the terms “comprising”, “including”, and “having” can be used interchangeably.

[0036] The preceding is a simplified summary of the disclosure to provide an understanding of some aspects of the disclosure. This summary is neither an extensive nor exhaustive overview of the disclosure and its various aspects, embodiments, and configurations. It is intended neither to identify key or critical elements of the disclosure nor to delineate the scope of the disclosure but to present selected concepts of the disclosure in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other aspects, embodiments, and configurations of the disclosure are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.

[0037] Numerous additional features and advantages of the present disclosure will become apparent to those skilled in the art upon consideration of the embodiment descriptions provided hereinbelow.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS [0038] The accompanying drawings are incorporated into and form a part of the specification to illustrate several examples of the present disclosure. These drawings, together with the description, explain the principles of the disclosure. The drawings simply illustrate preferred and alternative examples of how the disclosure can be made and used and are not to be construed as limiting the disclosure to only the illustrated and described examples. Further features and advantages will become apparent from the following, more detailed, description of the various aspects, embodiments, and configurations of the disclosure, as illustrated by the drawings referenced below.

[0039] Fig. l is a diagram of a system according to at least one embodiment of the present disclosure;

[0040] Fig. 2 is a block diagram of an example implantable medical device (IMD) according to at least one embodiment of the present disclosure;

[0041] Fig. 3 is a block diagram of a programmer according to at least one embodiment of the present disclosure;

[0042] Fig. 4 is an example stimulation response according to at least one embodiment of the present disclosure; [0043] Fig. 5 is an example set of stimulation responses with differing number of stimulation pulses according to at least one embodiment of the present disclosure;

[0044] Fig. 6A is an example set of stimulation responses at different frequencies according to at least one embodiment of the present disclosure;

[0045] Fig. 6B is a set of measurements corresponding to the example set of stimulation responses at different frequencies of Fig. 6A according to at least one embodiment of the present disclosure;

[0046] Fig. 7 is an example curve for constructive/destructive concepts according to at least one embodiment of the present disclosure;

[0047] Figs. 8A-8F are examples of constructive and destructive concepts according to at least one embodiment of the present disclosure;

[0048] Figs. 9A and 9B are example stimulation responses according to at least one embodiment of the present disclosure;

[0049] Fig. 10 is a set of example stimulation responses that exhibit constructive and destructive concepts according to at least one embodiment of the present disclosure;

[0050] Figs. 11 A and 1 IB are example results of applying a stimulation according to at least one embodiment of the present disclosure;

[0051] Fig. 12 is a set of example stimulation responses for determining steady state behavior according to at least one embodiment of the present disclosure;

[0052] Fig. 13 is a flowchart according to at least one embodiment of the present disclosure;

[0053] Fig. 14 is a flowchart according to at least one embodiment of the present disclosure;

[0054] Fig. 15 is a flowchart according to at least one embodiment of the present disclosure; and

[0055] Fig. 16 is a flowchart according to at least one embodiment of the present disclosure.

DETAILED DESCRIPTION

[0056] It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example or embodiment, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, and/or may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the disclosed techniques according to different embodiments of the present disclosure). In addition, while certain aspects of this disclosure are described as being performed by a single module or unit for purposes of clarity, it should be understood that the techniques of this disclosure may be performed by a combination of units or modules associated with, for example, a computing device and/or a medical device.

[0057] In one or more examples, the described methods, processes, and techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Alternatively or additionally, functions may be implemented using machine learning models, neural networks, artificial neural networks, or combinations thereof (alone or in combination with instructions). Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e.g., random-access memory (RAM), read-only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

[0058] Instructions may be executed by one or more processors, such as one or more digital signal processors (DSPs), general purpose microprocessors (e.g., Intel Core i3, i5, i7, or i9 processors; Intel Celeron processors; Intel Xeon processors; Intel Pentium processors; AMD Ryzen processors; AMD Athlon processors; AMD Phenom processors; Apple A10 or 10X Fusion processors; Apple Al l, A12, A12X, A12Z, or A13 Bionic processors; or any other general purpose microprocessors), graphics processing units (e.g., Nvidia GeForce RTX 2000-series processors, Nvidia GeForce RTX 3000-series processors, AMD Radeon RX 5000-series processors, AMD Radeon RX 6000-series processors, or any other graphics processing units), application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor” as used herein may refer to any of the foregoing structure or any other physical structure suitable for implementation of the described techniques. Also, the techniques could be fully implemented in one or more circuits or logic elements. The processors listed herein are not intended to be an exhaustive list of all possible processors that can be used for implementation of the described techniques, and any future iterations of such chips, technologies, or processors may be used to implement the techniques and embodiments of the present disclosure as described herein.

[0059] Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Further, the present disclosure may use examples to illustrate one or more aspects thereof. Unless explicitly stated otherwise, the use or listing of one or more examples (which may be denoted by “for example,” “by way of example,” “e.g.,” “such as,” or similar language) is not intended to and does not limit the scope of the present disclosure.

[0060] The terms proximal and distal are used in this disclosure with their conventional medical meanings, proximal being closer to the operator, user, or device of a system, and further from the region of medical interest in or on the patient, and distal being closer to the region of medical interest in or on the patient, and further from the operator, user, or device of the system.

[0061] This disclosure describes example techniques to optimize stimulation parameters for a therapeutic electrical stimulation signal to promote and influence either constructive or destructive resonance of an evoked resonant neural activity (ERNA) signal. The example techniques are described with respect to DBS, but the example techniques are not so limited and may be applied to other types of therapies and/or other anatomical locations. DBS may provide relief for many different patient conditions such as essential tremors (ETs), Parkinson’s, obsessive compulsive disorder (OCD), depression, and others. For DBS, a surgeon implants one or more leads within the brain of the patient for outputting therapeutic electrical stimulation signals at depth within the brain. The one or more leads are coupled to an implantable medical device (IMD) that generates the therapeutic electrical stimulation signals for delivery through the one or more leads.

[0062] A common target for DBS (e.g., to treat Parkinson’s Disease or another condition) is the subthalamic nucleus (STN) (e.g., within the patient’s brain). In some examples, DBS therapy may incorporate sensing of local field potentials (LFPs) which are spontaneous activity representing background activity of the neural network. For example, an LFP may be an intrinsic signal within the brain of the patient. In some cases, the LFP is intrinsically generated by a signal source within the brain of the patient. The signal characteristics of the LFP may be indicative of a patient condition (e.g., brain state).

[0063] Additionally or alternatively, another potential signal of interest for DBS therapy may include evoked activity. A single stimulation pulse of the therapeutic electrical stimulation signals may elicit an evoked potential (EP) response due to activation of the local neural circuitry. However, due to the complex interconnected neural network within the brain (e.g., of the basal ganglia), stimulation of the STN may activate the complex interconnected neural network such that sensing EPs in the STN will show the response to that pulse in addition to any additional feedback or underlying activity from connected structures in the brain network (e.g., in the basal ganglia network) that are also activated. When multiple stimulation pulses are delivered for the therapeutic electrical stimulation signals, the EP elicited from each pulse can add to the underlying activity from the feedback from the complex neural network activated by previous pulses.

[0064] With consecutive stimulation pulses, a sensed signal from the DBS therapy (e.g., which equals the EP from each pulse plus underlying ongoing activity from previous pulses) may show a resonant behavior, referred to as ERNA. For example, an ERNA signal is distinguishable from an intrinsic signal in that an ERNA signal is a signal within the brain of a patient that is evoked due to, or responsive to, a stimulation signal delivered to the brain. The stimulation signal delivered to the brain that evokes the ERNA signal need not necessarily provide any therapeutic benefit, although it is possible for the stimulation signal that evokes the ERNA signal to provide therapeutic benefit.

[0065] As additional stimulation pulses are delivered to the brain, the properties of the sensed signal (e.g., peak-trough amplitude, peak latencies, number of resonant peaks, etc.) can change. For example, multiple stimulation pulses can elicit activity that is additive to the underlying activity. If a second stimulation pulse is applied after a first stimulation pulse, an evoked response from the second stimulation pulse would add to any underlying activity due to feedback from the previous pulse, and a sensed signal from the DBS therapy would represent that overall signal. That is, after two (2) consecutive stimulation pulses, a second peak after an EP may be larger than a second peak elicited from a single pulse. If a third consecutive stimulation pulse were to be delivered, the evoked response would add to any underlying activity that is ongoing from the previous two pulses. For example, a response sensed after three (3) consecutive pulses may include a larger initial peak-to-trough amplitude and more prominent resonant activity compared to similar activity elicited after a single pulse or two pulses. In general, as more pulses of therapeutic electrical stimulation signals for DBS therapy are delivered, the EP from each individual pulse adds or compliments to any underlying activity, thus changing properties of a resonance (e.g., ERNA response) seen after the burst of stimulation pulses.

[0066] Additionally, properties of the ERNA response (e.g., initial peak-to-trough amplitude, resonant frequency, damping of peaks, shifts in peak/trough latencies, etc.) may be different for different stimulation frequencies. For example, a variability may exist in the peak-to-trough amplitudes, the number of resonant peaks, the latency of the peaks, etc., across different stimulation frequencies. Accordingly, the properties of the ERNA response may vary based on a relationship between the timing of the evoked response from a stimulation pulse and the timing of the underlying activity.

[0067] As described herein, an alignment of an EP elicited by the stimulation pulse with the underlying activity may correspond to properties of the ERNA response. That is, an inherent EP latency plays a role in determining properties of the ERNA response, not just the timing of the stimulus pulse. The timing of EP latency may vary patient-to-patient (e.g., based on anatomy, disease state, neural state, etc.). Therefore, the change in ERNA properties due to different stimulation frequencies may be attributed to differences in phase alignment of an immediate EP (e.g., after a single pulse is applied of the therapeutic electrical stimulation signals) with the underlying activity, where the sensed ERNA signal then exhibits signs of constructive or destructive resonance.

[0068] Constructive resonance may result in an ERNA signal or response with larger peak-to-trough amplitudes, more resonant peaks, shorter latencies between peaks, or a combination thereof. Additionally or alternatively, destructive resonance may result in an ERNA signal or response with smaller peak-to-trough amplitudes, less resonant peaks, longer latencies between peaks, or a combination thereof. The constructive resonance may occur when a peak of an EP response would be aligned with a peak or first portion (e.g., “rising edge”) of an underlying ERNA response, and the destructive resonance may occur when the peak of the EP response would be aligned with a trough or second portion (e.g., “falling edge”) of the underlying ERNA response. Changes in the latency of the ERNA response can influence the alignment of the EP peak and the underlying resonance, causing changes in the constructive or destructive behavior. The changes in latency can be driven by constructive or destructive resonance from previous pulses or by a change in neural state (e.g., under anesthesia, asleep/awake, medication, disease progression, etc.). The changes in the ERNA response may also drive a need for changing in stimulation parameters to maintain a desired resonant state (e.g., constructive or destructive).

[0069] Accordingly, in some embodiments, controlling the ERNA signal to promote constructive or destructive resonance may be used to guide programing (e.g., in a clinic setting) to determine optimal stimulation parameters for DBS therapy (e.g., optimal stimulation frequency, amplitude, pulse width, etc.). Additionally, controlling the ERNA signal to promote constructive or destructive resonance may be used in a closed-loop fashion. For example, the ERNA signal may be monitored, and stimulation parameters can be adjusted to maintain a desired resonant state (constructive or destructive) or decide when the desired state should switch from constructive to destructive or vice versa.

Additionally, other input signals could inform a needed change in resonant state, such as detecting sleep, a certain LFP biomarker, accelerometer signals (e.g., sensing movement or non-movement in the patient), sensing posture of the patient, etc. In some embodiments, a placement of different components configured to deliver a DBS therapy (e.g., leads, electrodes, probes, etc.) may be determined based on controlling the ERNA signal to promote constructive or destructive resonance. For example, during surgery and/or implantation of the different components, a clinician or surgeon may use test electrical stimulation signals while controlling the ERNA signal to promote constructive or destructive resonance to determine whether the different components are correctly implanted within the patient.

[0070] In some examples, based in part on the techniques described herein, therapeutic electrical stimulation signals (e.g., for DBS therapy) may directly influence a resonance (e.g., ERNA signal) to a constructive or destructive state, and different parameters for delivering the therapeutic electrical stimulation signals can be adjusted directly to adjust or switch between the constructive or destructive state. Additionally or alternatively, changes in the resonance may be influenced by additional therapy delivery (e.g., perhaps at other sites in the patient) or may be an indication of some other change in the patient, and the different parameters for delivering the therapeutic electrical stimulation signals can be adjusted directly to adjust or switch between the constructive or destructive state based on the changes in the resonance.

[0071] Fig. 1 is a conceptual diagram illustrating an example system 100 that includes an implantable medical device (IMD) 106 configured to deliver a DBS therapy to a patient 112. In some examples, the DBS may be closed-loop in the sense that IMD 106, as one example, may adjust, increase, or decrease the magnitude of one or more parameters of the DBS in response to changes in patient activity or movement, a severity of one or more symptoms of a disease of the patient, a presence of one or more side effects due to the DBS, or one or more sensed signals of the patient.

[0072] For instance, one example of system 100 is a bi-directional DBS system with capabilities to both deliver stimulation, sense intrinsic neuronal signals, and sense neural signals that are evoked in response to delivery of stimulation. System 100 may be configured to treat a patient condition, such as a movement disorder (e.g., ET, Parkinson’s, etc.), neurodegenerative impairment, a mood disorder, or a seizure disorder of patient 112. Patient 112 ordinarily is a human patient. In some cases, however, therapy system 100 may be applied to other mammalian or non-mammalian, non-human patients. While movement disorders and neurodegenerative impairment are primarily referred to herein, in other examples, therapy system 100 may provide therapy to manage symptoms of other patient conditions, such as, but not limited to, seizure disorders (e.g., epilepsy) or mood (or psychological) disorders (e.g., major depressive disorder (MDD), bipolar disorder, anxiety disorders, post-traumatic stress disorder, dysthymic disorder, and obsessive- compulsive disorder (OCD)). At least some of these disorders may be manifested in one or more patient movement behaviors. As described herein, a movement disorder or other neurodegenerative impairment may include symptoms such as, for example, muscle control impairment, motion impairment or other movement problems, such as rigidity, spasticity, bradykinesia, rhythmic hyperkinesia, nonrhythmic hyperkinesia, and akinesia. In some cases, the movement disorder may be a symptom of Parkinson’s disease or ET. However, the movement disorder may be attributable to other patient conditions.

[0073] Example therapy system 100 includes medical device programmer 104, IMD 106, lead extension 110, and leads 114A and 114B with respective sets of electrodes 116, 118. In the example shown in FIG. 1, electrodes 116, 118 of leads 114 A, 114B are positioned to deliver electrical stimulation to a tissue site within brain 120, such as a deep brain site under the dura mater of brain 120 of patient 112. In some examples, delivery of stimulation to one or more regions of brain 120, such as the STN, globus pallidus or thalamus, ventralus intermediate (VIM), anterior nucleus (ANT), ventral internal capsule/ventral striatum (VCVS), cortico-basal ganglia-thalamocortical circuit, or anterior insular cortex (AIC), may be an effective treatment to manage disorders, such as Parkinson’s disease. Some or all of electrodes 116, 118 also may be positioned to sense neurological brain signals within brain 120 of patient 112. In some examples, some of electrodes 116, 118 may be configured to sense neurological brain signals and others of electrodes 116, 118 may be configured to deliver electrical stimulation to brain 120. In other examples, all of electrodes 116, 118 are configured to both sense neurological brain signals and deliver electrical stimulation to brain 120. In some examples, unipolar stimulation may be possible where one electrode is on the housing of IMD 106.

[0074] IMD 106 includes a therapy module (e.g., which may include processing circuitry or other electrical circuitry configured to perform the functions attributed to IMD 106) that includes stimulation generation circuitry configured to generate and deliver electrical stimulation therapy to patient 112 via a subset of electrodes 116, 118 of leads 114A and 114B, respectively. The subset of electrodes 116, 118 that are used to deliver electrical stimulation to patient 112, and, in some cases, the polarity of the subset of electrodes 116, 118, may be referred to as a stimulation electrode combination. As described in further detail below, the stimulation electrode combination can be selected for a particular patient 112 and target tissue site (e.g., selected based on the patient condition). The group of electrodes 116, 118 includes at least one electrode and can include a plurality of electrodes. In some examples, the plurality of electrodes 116 and/or 118 may have a complex electrode geometry such that two or more electrodes are located at different positions around the perimeter of the respective lead.

[0075] In some examples, the neurological signals sensed within brain 120 may reflect changes in electrical current produced by the sum of electrical potential differences across brain tissue. There may be various examples of neurological brain signals that electrodes 116, 118 may be configured to sense. One example of a neurological brain signal is an LFP. An LFP may be an intrinsic signal within brain 120 of patient 112 that is generated by a signal source within brain 120 of patient 112. Another example of a neurological brain signal is an ERNA signal. Delivery of electrical stimulation within brain 120 may evoke an ERNA signal, and the ERNA signal may be distinguishable from an intrinsic signal in that an ERNA signal is a signal within the brain of a patient that is evoked due to, or responsive to, a stimulation signal delivered to the brain. The electrical stimulation delivered within brain 120 to evoke the ERNA signal need not necessarily provide therapeutic benefit, but therapeutic benefit from the electrical stimulation used to evoke the ERNA signal is possible. Electroencephalogram (EEG) signal or an electrocorticogram (ECoG) signal are also examples of neurological signals. For example, neurons generate the neurological signals, and if measured at depth, it is LFP or ERNA (if evoked), if measured on the dura, it is ECoG, and if on scalp, it is EEG. [0076] In some examples, the delivery of therapeutic electrical stimulation signals may be based on a feature of interest (e.g., biomarker). One example of the feature of interest (e.g., biomarker) within the LFPs is synchronized beta frequency band (8-33Hz) LFP activity recorded within the sensorimotor region of the STN in Parkinson’s disease or ET patients. The source of the LFP activity can be considered as a signal source, within the brain of the patient, that outputs an oscillatory electrical voltage signal that is sensed by one or more of electrodes 116 and/or 118. The suppression of pathological beta activity (e.g., suppression or squelching of the signal component of the bioelectric signals generated from the LFP source that is within the beta frequency band) by both medication and DBS may correlate with improvements in the motor symptoms of patients who have Parkinson’s disease or essential tremor.

[0077] For example, one or more of electrodes 116 and/or 118 may sense the LFP activity. Accordingly, there may be a plurality of LFP measurements of an LFP, where each of the LFP measurements may be measured with different electrodes 116 and/or 118 on leads 114A, 114B or by the same electrodes 116 and/or 118 on leads 114A, 114B. As described, the LFP is intrinsically generated by a signal source (e.g., oscillatory electrical voltage source) within brain 120 of patient 122.

[0078] In some examples, the neurological brain signals that are used to select a stimulation electrode combination may be sensed within the same region of brain 120 as the target tissue site for the electrical stimulation. As previously indicated, the target tissue sites may include tissue sites within anatomical structures such as the thalamus, STN, or globus pallidus of brain 120, as well as other target tissue sites. The specific target tissue sites and/or regions within brain 120 may be selected based on the patient condition. Thus, in some examples, both a stimulation electrode combination and sense electrode combinations may be selected from the same set of electrodes 116, 118. In other examples, the electrodes used for delivering electrical stimulation may be different than the electrodes used for sensing neurological brain signals.

[0079] Therapeutic electrical stimulation generated by IMD 106 may be configured to manage a variety of disorders and conditions. In some examples, the stimulation generation circuitry of IMD 106 is configured to generate and deliver therapeutic electrical stimulation pulses to patient 112 via electrodes of a selected stimulation electrode combination. However, in other examples, the stimulation generation circuitry of IMD 106 may be configured to generate and deliver a continuous wave signal, e.g., a sine wave or triangle wave. In either case, stimulation generation circuitry within IMD 106 may generate the electrical stimulation therapy for DBS according to a selected therapy program. In examples in which IMD 106 delivers therapeutic electrical stimulation in the form of stimulation pulses, a therapy program may include a set of therapy parameter values (e.g., parameters), such as a stimulation electrode combination for delivering stimulation to patient 112, pulse frequency, pulse width, and a current or voltage amplitude of the pulses. As previously indicated, the electrode combination may indicate the specific electrodes 116, 118 that are selected to deliver therapeutic stimulation signals to tissue of patient 112 and the respective polarities of the selected electrodes.

[0080] In some examples, electrodes 116, 118 may be circumferentially-segmented DBS arrays of electrodes, and include some non-segmented electrodes as well, such as ring electrodes. Circumferentially-segmented DBS arrays refer to electrodes that are segmented circumferentially along the lead. As one example, leads 114A and 114B may include a first set of electrodes arranged circumferentially around leads 114A and 114B that are all at the same height level on leads 114A and 114B. Each of the electrodes in the first set of electrodes is a separate segmented electrode and form a level of circumferentially- segmented array of electrodes. Leads 114A and 114B may include a second set of electrodes arranged circumferentially around leads 114A and 114B that are all at the same height level on leads 114A and 114B. Each of the electrodes in the first set of electrodes is a separate segmented electrode and form a level of circumferentially-segmented array of electrodes. The electrodes may be beneficial by enabling directional stimulation and sensing.

[0081] With the electrodes, IMD 106 may be configured to perform both directional stimulation and sensing, thereby enhancing the ability to target the source of the LFP activities (also referred to as pathological neuronal activities). For example, IMD 106 may be configured to perform directional sensing to determine a direction and/or orientation of the LFP source (e.g., signal source that generates the LFP) having the signal component in the beta frequency band. IMD 106 may direct the electrical stimulation toward the signal source to suppress (e.g., squelch) the signal component produced by the signal source in the beta frequency band, as one example. This disclosure describes example techniques to utilize ERNA signals in relation to constructive and destructive resonance states to determine optimal parameters for the therapeutic electrical stimulation signals. The example techniques may be used generally for DBS, or other types of therapy where constructive and destructive resonance states and ERNA signals are used as part of closed- loop therapy. [0082] Further, the example techniques are not limited to examples where one or more of electrodes 116, 118 are circumferentially-segmented electrodes. The example of using circumferentially-segmented electrodes is described as a way of directional stimulation and sensing. However, the example techniques are also useable in examples where directional stimulation and sensing are not available or are not used. Moreover, there may be other ways of performing directional stimulation and sensing that do not require the use of circumferentially-segmented electrodes.

[0083] In an example, for DBS, IMD 106 may be configured to deliver therapeutic electrical stimulation signals based on one or more parameters such as amplitude, pulse width, and frequency. In some examples, shortly after implantation or during the implantation surgery for IMD 106 and/or leads 114A, 114B, a clinician/ surgeon may determine initial parameters (e.g., a first set of one or more parameters for a first set of one or more therapeutic electrical stimulation signals). As described herein, constructive and destructive resonance states may be used, in part, to guide programming of the parameters for the therapeutic electrical stimulation signals. For example, the clinician/surgeon may use the timing of a peak of an EP compared to underlying resonance to determine optimal stimulation frequency for constructive or destructive based on a desired resonant state.

Additionally, the clinician/surgeon may use the ERNA from a short burst of pulses to infer the steady state resonant behavior to optimize stimulation for steady state. By being able to infer steady state from a short burst of pulses, the programming process can be shorter in time. Additionally, the steady state resonant behavior may be based on an alignment of the peak of the EP and underlying resonance or based on other properties of the ERNA signal itself (e.g., shape, symmetry of peak and trough, damping rate of response, etc.).

[0084] However, the effectiveness of the first set of one or more therapeutic electrical stimulation signals may change overtime. For instance, due to lead migration, accommodation of the neural substrate to stimulation, or worsening of patient condition, the first set of one or more therapeutic electrical stimulation signals may be insufficient to provide effective therapy. Conversely, if patient condition improves, the intensity of the first set of one or more therapeutic electrical stimulation signals may be greater than needed to provide effective therapy.

[0085] Accordingly, there may be benefit in periodically, or possibly continuously, updating the first set of one or more parameters to a second set of one or more parameters for a second set of one or more therapeutic electrical stimulation signals. In the above examples, there may be benefit in updating the initial parameters. However, in some cases, after the initial parameters are updated, there may be benefit in periodically, or possibly continuously, determining whether to update the parameters for therapeutic electrical stimulation signals.

[0086] One way to update the parameters for therapeutic electrical stimulation signals may be for patient 112 to periodically schedule an appointment with a clinician to update the parameters. Another way to update the parameters for therapeutic electrical stimulation signals may be for patient 112 to manually adjust the parameters himself/herself. In both such examples, there may be burden on patient 112 to have to schedule appointments for parameter adjustment or self-titrate the parameters, which may also lead to delay in updates to parameters.

[0087] This disclosure describes example techniques for closed-loop parameter adjustment. For example, the processing circuitry of IMD 106 may be configured to perform closed-loop adjustments to parameters of the therapeutic electrical stimulation signals to maintain an optimal resonance selection. In some embodiments, medicine washin and medicine wash-out (e.g., or other neural states of patient 112) may cause slight changes in the underlying resonance, such that the processing circuitry of IMD 106 may adjust one or more parameters of the therapeutic electrical stimulation signals to better maintain a desired resonance state based on detecting the changes. Additionally or alternatively, certain activities or movements may cause a change in the underlying resonance, and processing circuitry of IMD 106 may adjust one or more parameters of the therapeutic electrical stimulation signals to better maintain a desired resonance state based on detecting the change.

[0088] In some embodiments, the processing circuitry of IMD 106 may be configured to perform closed-loop adjustments to switch resonant state based on a change in neural state for patient 112 or based on a presence of side effect(s). As an example, when patient 112 is awake, the processing circuitry of IMD 106 may promote constructive resonance, and when patient 112 is asleep, the processing circuitry of IMD 106 may switch to promoting destructive resonance. Additionally or alternatively, if the processing circuitry of IMD 106 senses a presence of side effect(s) (e.g., a change in the ERNA signal, an LFP signal side effect, a change in accelerometer sensing, etc.), the processing circuitry of IMD 106 may switch from a constructive resonance state to a destructive resonance state (e.g., or vice versa) and adjust one or more parameters of the therapeutic electrical stimulation signals accordingly to support the switch or may add some jitter into pulse timing to disrupt resonant behavior. [0089] The following describes one example way in which to determine parameters for the therapeutic electrical stimulation signal based on ERNA signals. However, the example techniques are not so limited. For instance, for initial parameters, a clinician may manually titrate parameters until the right parameters are identified for the initial therapeutic electrical stimulation signal.

[0090] For determining parameters based on ERNA signals, the processing circuitry of IMD 106 may cause the stimulation generation circuitry of IMD 106 to deliver a plurality of electrical stimulation signals via the one or more electrodes 116. In one or more examples, the plurality of electrical stimulation signals each include at least one different therapy parameter. For each of the plurality of electrical stimulation signals, the processing circuitry of IMD 106 may determine respective ERNA signals, where the respective ERNA signals are evoked by delivery of the respective plurality of electrical stimulation signals. The processing circuitry may determine parameters for the therapeutic electrical stimulation signal based on the respective ERNA signals.

[0091] In this disclosure, the phrase “therapeutic electrical stimulation signal” is used to refer to electrical stimulation signal that is delivered for providing therapy. Delivery of the therapeutic electrical stimulation signal may evoke an ERNA signal, but the techniques do not require the therapeutic electrical stimulation signal to evoke an ERNA signal. The phrase “electrical stimulation signal” is used to refer to electrical stimulation signal that is delivered for evoking an ERNA signal. Delivery of an electrical stimulation signal for evoking an ERNA signal may provide therapeutic effect, but the techniques do not require the electrical stimulation signal used for evoking an ERNA signal to provide therapeutic effect.

[0092] As described above, the processing circuitry may cause stimulation generation circuitry to deliver a plurality of electrical stimulation signals via the determined one or more electrodes, where the plurality of electrical stimulation signals each include at least one different therapy parameter. For instance, the processing circuitry may cause the stimulation generation circuitry to sweep across a range of frequencies such that frequency of each of the electrical stimulation signals is different. That is, the processing circuitry may be configured to cause the stimulation generation circuitry to deliver the plurality of electrical stimulation signals via the determined one or more electrodes, where a frequency for each of the plurality of electrical stimulation signals is within a range of frequencies (e.g., 5 Hz to 220 Hz). As another example, the processing circuitry may cause the stimulation generation circuitry to sweep across a range of amplitudes and/or pulse widths such that the amplitude and/or pulse width of each of the electrical stimulation signals is different. That is, the processing circuitry may be configured to cause the stimulation generation circuitry to deliver the plurality of electrical stimulation signals via the determined one or more electrodes, where an amplitude and/or pulse width for each of the plurality of electrical stimulation signals is within a range of amplitudes and/or pulse widths.

[0093] The processing circuitry may evaluate the respective ERNA signals for determining the parameters for the therapeutic electrical stimulation signal. For instance, the processing circuitry may determine characteristics of the respective ERNA signals such as resonant activity. Examples of resonant activity include one or more of peak-to- trough amplitude, time between peak-to-peak, decay time constant, change in peak amplitudes (e.g., damping), amount of oscillations (e.g., number of peaks), rise or fall times, and frequency shift from early resonance to late resonance of the respective ERNA signals.

[0094] Based on the determined resonant activity, the processing circuitry may select one of the ERNA signals. As an example, the processing circuitry may select the ERNA signal of the respective ERNA signals having the highest peak-to-trough amplitude (e.g., constructive resonant state). As another example, the processing circuitry may select the ERNA signal of the respective ERNA signals having the most of amount of oscillations (e.g., the most number of peaks before the ERNA signals dampens to noise level). As another example, the processing circuitry may select the ERNA signal of the respective ERNA signals having the fastest reduction in peak amplitudes (e.g., fastest damping). The above provide a few non-limiting examples resonant activity that the processing circuitry may evaluate to select an ERNA signal, and other examples of resonant activity are possible. Also, the processing circuitry may select an ERNA signal based on a combination of the resonant activity (e.g., a weighting of two or more examples the resonant activity).

[0095] The processing circuitry may determine the respective electrical stimulation signal of the selected ERNA signal, and may determine the parameters of the determined respective electrical stimulation signal. The processing circuitry may determine the parameters for the therapeutic electrical stimulation signal based on the determined parameters. In this way, the processing circuitry may determine parameters for the therapeutic electrical stimulation signal based on the respective ERNA signals. [0096] IMD 106 may be implanted within a subcutaneous pocket above the clavicle, or, alternatively, on or within cranium 122 or at any other suitable site within patient 112. Generally, IMD 106 is constructed of a biocompatible material that resists corrosion and degradation from bodily fluids. IMD 106 may comprise a hermetic housing to substantially enclose components, such as a processor, therapy module, and memory. [0097] As shown in FIG. 1, implanted lead extension 110 is coupled to IMD 106 via connector 108 (also referred to as a connector block or a header of IMD 106). In the example of FIG. 1, lead extension 110 traverses from the implant site of IMD 106 and along the neck of patient 112 to cranium 122 of patient 112 to access brain 120. In the example shown in FIG. 1, leads 114A and 114B (collectively “leads 114”) are implanted within the right and left hemispheres (or in just one hemisphere in some examples), respectively, of patient 112 in order to deliver electrical stimulation to one or more regions of brain 120, which may be selected based on the patient condition or disorder controlled by therapy system 100. The specific target tissue site and the stimulation electrodes used to deliver stimulation to the target tissue site, however, may be selected, e.g., according to the identified patient behaviors and/or other sensed patient parameters. Other lead 114 and IMD 106 implant sites are contemplated. For example, IMD 106 may be implanted on or within cranium 122, in some examples. Leads 114A and 114B may be implanted within the same hemisphere or IMD 106 may be coupled to a single lead implanted in a single hemisphere, in some examples.

[0098] Existing lead sets include axial leads carrying ring electrodes disposed at different axial positions and so-called "paddle" leads carrying planar arrays of electrodes. In some examples, more complex lead array geometries may be used.

[0099] Although leads 114 are shown in FIG. 1 as being coupled to a common lead extension 110, in other examples, leads 114 may be coupled to IMD 106 via separate lead extensions or directly to connector 108. Leads 114 may be positioned to deliver electrical stimulation to one or more target tissue sites within brain 120 to manage patient symptoms associated with a movement disorder of patient 112. Leads 114 may be implanted to position electrodes 116, 118 at desired locations of brain 120 through respective holes in cranium 122. Leads 114 may be placed at any location within brain 120 such that electrodes 116, 118 are capable of providing electrical stimulation to target tissue sites within brain 120 during treatment. For example, electrodes 116, 118 may be surgically implanted under the dura mater of brain 120 or within the cerebral cortex of brain 120 via a burr hole in cranium 122 of patient 112, and electrically coupled to IMD 106 via one or more leads 114.

[0100] In the example shown in FIG. 1, electrodes 116, 118 of leads 114 are shown as ring electrodes. Ring electrodes may be used in DBS applications because ring electrodes are relatively simple to program and are capable of delivering an electrical field to any tissue adjacent to electrodes 116, 118. In other examples, electrodes 116, 118 may have different configurations. For example, at least some of the electrodes 116, 118 of leads 114 may have a complex electrode array geometry that is capable of producing shaped electrical fields. The complex electrode array geometry may include multiple electrodes (e.g., partial ring or segmented electrodes) around the outer perimeter of each lead 114, rather than one ring electrode. In this manner, electrical stimulation may be directed in a specific direction from leads 114 to enhance therapy efficacy and reduce possible adverse side effects from stimulating a large volume of tissue. For example, one or more electrodes 116, 118 may be circumferentially-segmented DBS arrays of electrodes, and one or more electrodes 116, 118 may be non-segmented electrodes such as ring electrodes, as described above. In some examples, electrodes 116, 118 may only be circumferentially- segmented DBS arrays of electrodes, and in some examples, electrodes 116, 118 may only be non-segmented electrodes, such as ring electrodes.

[0101] In some examples, a housing of IMD 106 may include one or more stimulation and/or sensing electrodes. In some examples, leads 114 may have shapes other than elongated cylinders as shown in FIG. 1. For example, leads 114 may be paddle leads, spherical leads, bendable leads, or any other type of shape effective in treating patient 112 and/or minimizing invasiveness of leads 114.

[0102] IMD 106 includes a memory to store a plurality of therapy programs that each define a set of therapy parameter values. In some examples, IMD 106 may select a therapy program from the memory based on various parameters, such as sensed patient parameters and the identified patient behaviors. For example, as described above, the processing circuitry of IMD 106 may determine updates to parameters for the therapeutic electrical stimulation signal based on the respective LFP measurements and ERNA signals. In some examples, IMD 106 may output information indicative of the determined updated parameters for clinician approval. After approval, the processing circuitry of IMD 106 may store in a therapy program the determined parameter and may be configured to cause stimulation generation circuitry of IMD 106 to deliver the therapeutic electrical stimulation signal based on the determined parameters (e.g., by the processing circuitry selecting the therapy program that includes the determined parameters).

[0103] That is, the stimulation generation circuitry of IMD 106 may deliver a first set of one or more therapeutic electrical stimulation signals according to a first set of one or more parameters. Then, the processing circuitry may determine a second set of one or more parameters for a second set of one or more therapeutic electrical stimulation signals based on the one or more ERNA signals and constructive and destructive resonance states, and cause the stimulation generation circuitry to deliver the second set of the one or more therapeutic electrical stimulation signals. The second set of one or more parameters may be updates to the first set of one or more parameters.

[0104] The delivery of the first set of one or more therapeutic electrical stimulation signals may not be necessary in all cases. For instance, memory of IMD 106 or some other memory may store the first set of one or more parameters for the first set of one or more therapeutic electrical stimulations signals. The processing circuitry may periodically update the first set of one or more parameters to the second set of one or more parameters based on ERNA signals and constructive and destructive resonance states, as described in this disclosure.

[0105] In some examples, clinician approval may not be necessary, such as in examples where the determined parameters for the therapeutic electrical stimulation signal are within a “safe-range” as assigned by the surgeon/clinician. In such examples, the processing circuitry of IMD 106 may output information indicative of the determined parameters for storage as a therapy program, and the stimulation generation circuitry may deliver the therapeutic electrical stimulation signal based on the determined parameters (e.g., by processing circuitry selecting the therapy program that includes the determined parameters). In this way, IMD 106 may generate therapeutic electrical stimulation based on the parameters of the selected therapy program to manage the patient symptoms associated with the patient disorder.

[0106] Rather than or in addition to using therapy programs, in some examples, it may be possible for the processing circuitry to directly output the information indicative of the determined parameters to the stimulation generation circuitry. Accordingly, there may be various way in which the processing circuitry may output information indicative of the determined parameters, such as to an external device like external programmer 104, described, below, to a therapy program, or to the stimulation generation circuitry. [0107] External programmer 104 wirelessly communicates with IMD 106 as needed to provide or retrieve therapy information. Programmer 104 is an external computing device that the user, e.g., a clinician and/or patient 112, may use to communicate with IMD 106. For example, programmer 104 may be a clinician programmer that the clinician uses to communicate with IMD 106 and program one or more therapy programs for IMD 106. Alternatively, programmer 104 may be a patient programmer that allows patient 112 to select programs and/or view and modify therapy parameters. The clinician programmer may include more programming features than the patient programmer. In other words, more complex or sensitive tasks may only be allowed by the clinician programmer to prevent an untrained patient from making undesirable changes to IMD 106.

[0108] When programmer 104 is configured for use by the clinician, programmer 104 may be used to transmit initial programming information to IMD 106. This initial information may include hardware information, such as the type of leads 114 and the electrode arrangement, the position of leads 114 within brain 120, the configuration of electrode array 116, 118, initial programs defining therapy parameter values, and any other information the clinician desires to program into IMD 106. Programmer 104 may also be capable of completing functional tests (e.g., measuring the impedance of electrodes 116, 118 of leads 114).

[0109] The clinician may also store therapy programs within IMD 106 with the aid of programmer 104. During a programming session, the clinician may determine one or more therapy programs that may provide efficacious therapy to patient 112 to address symptoms associated with the patient condition, and, in some cases, specific to one or more different patient states, such as a sleep state, movement state or rest state. For example, the clinician may select one or more stimulation electrode combinations with which stimulation is delivered to brain 120. During the programming session, the clinician may evaluate the efficacy of the specific program being evaluated based on feedback provided by patient 112 or based on one or more physiological parameters of patient 112 (e.g., muscle activity, muscle tone, rigidity, tremor, etc.). In some examples, ERNA signals may be used to evaluate the efficacy of the specific program being evaluated (e.g., certain resonant activity in the ERNA signal may be indicative of efficacious therapy). Alternatively, identified patient behavior from video information may be used as feedback during the initial and subsequent programming sessions. Programmer 104 may assist the clinician in the creation/identification of therapy programs by providing a methodical system for identifying potentially beneficial therapy parameter values. [0110] Programmer 104 may also be configured for use by patient 112. When configured as a patient programmer, programmer 104 may have limited functionality (compared to a clinician programmer) in order to prevent patient 112 from altering critical functions of IMD 106 or applications that may be detrimental to patient 112. In this manner, programmer 104 may only allow patient 112 to adjust values for certain therapy parameters or set an available range of values for a particular therapy parameter.

[0111] Programmer 104 may also provide an indication to patient 112 when therapy is being delivered, when patient input has triggered a change in therapy or when the power source within programmer 104 or IMD 106 needs to be replaced or recharged. For example, programmer 104 may include an alert LED, may flash a message to patient 112 via a programmer display, generate an audible sound or somatosensory cue to confirm patient input was received, e.g., to indicate a patient state or to manually modify a therapy parameter.

[0112] Moreover, in some examples, the example techniques may be performed in the “cloud.” For example, IMD 106 and/or programmer 104 may upload the ERNA signals to one or more servers that form a cloud computing environment. Processing circuitry of the cloud computing environment may perform the example techniques described in this disclosure. Accordingly, in this disclosure, the processing circuitry that is configured to perform the example techniques may be any one or combination of the processing circuitry of IMD 106, the processing circuitry of programmer 104, and/or processing circuitry of a cloud computing environment.

[0113] Therapy system 100 may be implemented to provide chronic stimulation therapy to patient 112 over the course of several months or years. However, system 100 may also be employed on a trial basis to evaluate therapy before committing to full implantation. If implemented temporarily, some components of system 100 may not be implanted within patient 112. For example, patient 112 may be fitted with an external medical device, such as a trial stimulator, rather than IMD 106. The external medical device may be coupled to percutaneous leads or to implanted leads via a percutaneous extension. If the trial stimulator indicates DBS system 100 provides effective treatment to patient 112, the clinician may implant a chronic stimulator within patient 112 for relatively long-term treatment.

[0114] Although IMD 106 is described as delivering electrical stimulation therapy to brain 120, IMD 106 may be configured to direct electrical stimulation to other anatomical regions of patient 112. Further, an IMD may provide other electrical stimulation such as spinal cord stimulation to treat a movement disorder.

[0115] Fig. 2 is a block diagram of the example IMD 106 of Fig. 1 for delivering DBS therapy. In the example shown in Fig. 2, IMD 106 includes processing circuitry 210, memory 212, stimulation generation circuitry 202, sensing circuitry 204, telemetry circuitry 208, and power source 220. Each of these circuits may be or include electrical circuitry configured to perform the functions attributed to each respective circuit. Memory 212 may include any volatile or non-volatile media, such as a random-access memory (RAM), read only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, and the like. Memory 212 may store computer-readable instructions that, when executed by processing circuitry 210, cause IMD 106 to perform various functions. Memory 212 may be a storage device or other non- transitory medium. In some examples, IMD 106 may include or may be referred to as a signal generator.

[0116] In the example shown in Fig. 2, memory 212 stores EP measurements 214 and ERNA signals 216. EP measurements 214 may represent a first response measured by the IMD 106 after applying a pulse (e.g., a single pulse, a first pulse, etc.) of a generated electrical stimulation signal. ERNA signals 216 may be information indicative of a second response that is evoked by delivery of a respective plurality of pulses of the generated electrical stimulation signals that IMD 106 delivers for evoking the respective ERNA signals.

[0117] In one or more examples, processing circuitry 210 may utilize both EP measurements 214 and ERNA signals 216 to determine a constructive resonance state and a destructive resonance state for applying the generated electrical stimulation signal to an anatomical element as part of the DBS therapy. For example, memory 212 may store data for performing a resonant state determination 218. As part of resonant state determination 218, processing circuitry 210 may extract a first set of timings corresponding to a peak and a trough for the EP measurements 214 and may extract a second set of timings corresponding to peaks and troughs for the ERNA signals 216. Subsequently, the constructive resonance state may comprise a state where the peak for the EP measurements 214 would align with a first portion (e.g., “rising edge”) or peak of the ERNA signals 216 (e.g., an underlying resonance response), and the destructive resonance state may comprise a state where the peak for the EP measurements 214 would align with a second portion (e.g., “falling edge”) or trough of the ERNA signals 216. Additionally or alternatively, processing circuitry 210 may utilize both EP measurements 214 and ERNA signals 216 to determine a degree of the constructive resonance state and/or the destructive resonance state for applying the generated electrical stimulation signal to an anatomical element as part of the DBS therapy. For example, the degree of the constructive resonance state and/or the destructive resonance state may comprise a resonance state that is not fully constructive, not fully destructive, neither constructive nor destructive, or a combination of constructive and destructive.

[0118] In some embodiments, as part of resonant state determination 218, processing circuitry 210 may calculate a steady state ERNA behavior based on constructive and destructive concepts (e.g., the constructive resonance state and the destructive resonance state). Subsequently, stimulation parameters for applying the generated stimulation signal may be determined based on an alignment of an EP peak (e.g., from the first set of timings for EP measurements 214) and the steady state ERNA behavior.

[0119] Stimulation generation circuitry 202, under the control of processing circuitry 210, generates stimulation signals (e.g., electrical stimulation signals for evoking ERNA signals and/or therapeutic electrical stimulation signals for delivering therapy) for delivery to patient 112 via electrodes 116, 118. An example range of electrical parameters believed to be effective in DBS to manage a movement disorder of patient include: a. Pulse Rate, i.e., Frequency: between approximately 5 Hertz (Hz) and approximately 500Hz, such as between approximately 5 to 220Hz or such as approximately 130Hz. b. In the case of a voltage controlled system, Voltage Amplitude: between approximately 0.1 volts (V) and approximately 50V, such as between approximately 2V and approximately 3 V. c. In the case of a current controlled system, Current Amplitude: between approximately 0.1 milliamps (mA) to approximately 3.5mA, such as between approximately 1.0mA and approximately 1.75mA. d. Pulse Width: between approximately 20 microseconds (ps) and approximately 500ps, such as between approximately 50ps and approximately 200ps.

[0120] Accordingly, in some examples, stimulation generation circuitry 202 generates therapeutic electrical stimulation signals in accordance with the electrical parameters noted above. For example, processing circuitry 210 may utilize the example techniques described in this disclosure to determine the parameters for the therapeutic electrical stimulation signals (e.g., based on evaluation of EP measurements 214 and ERNA signals 216 and determining the constructive and destructive resonance states), and stimulation generation circuitry 202 may deliver the therapeutic electrical stimulation signals. Other ranges of therapy parameter values may also be useful, and may depend on the target stimulation site within patient 112. While stimulation pulses are described, stimulation signals may be of any form, such as continuous-time signals (e.g., sine waves) or the like. [0121] In addition to delivering therapeutic electrical stimulation signals, stimulation generation circuitry 202 may be configured to deliver electrical stimulation signals for evoking ERNA signals (e.g., where information indicative of the ERNA signals are stored as ERNA signals 216). Example parameters of the electrical stimulation signals for evoking ERNA signals include amplitude within range of 0 to 7.5 mA, such as 0 to 5 mA, frequency within range of 5 Hz to 250 Hz, such as 80 to 220 Hz, and pulse width in range of 20 to 450 microseconds, such as 60 to 120 microseconds.

[0122] Processing circuitry 210 may include fixed function processing circuitry and/or programmable processing circuitry, and may comprise, for example, any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), discrete logic circuitry, or any other processing circuitry configured to provide the functions attributed to processing circuitry 210 herein may be embodied as firmware, hardware, software or any combination thereof. Processing circuitry 210 may control stimulation generation circuitry 202 according to therapy programs stored in memory 212 to apply particular parameter values specified by one or more of programs, such as voltage amplitude or current amplitude, pulse width, and/or pulse rate.

[0123] In some embodiments, memory 212 may store further data for performing a stimulation adjustment 220 for adjusting one or more parameters of the electrical stimulation signals generated by stimulation generation circuitry 202. For example, stimulation adjustment 220 may be performed to maintain or switch a desired resonant state (e.g., constructive or destructive resonant state or a degree of constructive or destructive resonant state). In one example, as part of stimulation adjustment 220, processing circuitry 210 may apply the electrical stimulation signal generated by stimulation generation circuitry 202 to the anatomical element according to a first resonant state, where the first resonant state comprises at least a degree of the constructive resonance state or the destructive resonance state (e.g., fully constructive, fully destructive, neither constructive nor destructive, partially constructive, partially destructive, a combination of constructive and destructive, etc.). Subsequently, processing circuitry 210 may monitor for changes in a peak-to-trough amplitude between each pulse (e.g., from EP measurements 214) of the generated electrical stimulation signal and determine a shift in phase alignment between ERNA signals 216 (e.g., underlying resonance response) and EP measurements 214 based on detecting a change in the peak- to-trough amplitude. Accordingly, processing circuitry 210 may adjust one or more parameters for applying the electrical stimulation signal generated by stimulation generation circuitry 202 to align an EP peak (e.g., determined from EP measurements 214) with ERNA signals 216 to maintain the first resonant state based on determining the shift in phase alignment. In some examples, as part of stimulation adjustment 220, processing circuitry 210 may inhibit (e.g., pause) application of the generated electrical stimulation signal for one or more pulses (e.g., skip or drop one or more pulses when applying the generated electrical stimulation signal) to view ERNA signals 216 for confirming the shift in phase alignment.

[0124] Additionally or alternatively, as part of stimulation adjustment 220, processing circuitry 210 may apply the electrical stimulation signal generated by stimulation generation circuitry 202 to the anatomical element according to a first resonant state (e.g., the constructive resonance state or the destructive resonance state or a degree of the constructive resonance state and/or the destructive resonance state) and may monitor for side effects caused by applying the electrical stimulation signal according to the first resonant state. In some examples, the side effects may include a change in ERNA signals 216, an LFP signal side effect, a change in accelerometer signal(s) (e.g., indicating movement or no movement of the patient, indicating a posture of the patient, etc.), or a combination thereof. Subsequently, based on detecting a side effect, processing circuitry 210 may adjust a resonant state of the generated electrical stimulation signal and may adjust one or more parameters for the generated electrical stimulation signal to align an EP peak (e.g., determined from the EP measurements 214) with ERNA signals 216 to apply the generated electrical stimulation signal according to the adjusted resonant state. In some examples, adjusting the resonant state may include adjusting the first resonant state to have less constructive resonance (e.g., adjust a degree of the constructive resonance state), shift an alignment of the EP peak off a peak of ERNA signals 216, switch from the first resonant state to a second resonant state (e.g., an opposite of the constructive resonance state or the destructive resonance state configured for the first resonant state), adjust a pulse timing for the generated electrical stimulation signal, or a combination thereof. [0125] Additionally or alternatively, as part of resonant state determination 218, processing circuitry 210 may first assign the constructive resonance state or the destructive resonance state to each of a plurality of neural states, such that when a neural state is detected, processing circuitry 210 may apply the generated electrical stimulation signal to the anatomical element according to the assigned constructive resonance state or destructive resonance state for the detected neural state. For example, the plurality of neural states may include, but is not limited to, an awake state, an asleep state, an on- medication state, an off-medication state, a depth of anesthesia state, a disease progression state, a medication wash-in state, a medication wash-out state, a movement state (e.g., whether the patient is moving or not, such as indicated by an accelerometer), a posture of the patient (e.g., upright, laying down, etc.), or a different neural state. Subsequently, as part of stimulation adjustment 220, processing circuitry 210 may monitor for a change from the detected neural state to a second neural state of the plurality of neural states (e.g., the second neural state corresponding to a different assigned resonant state of the detected neural state), switch a resonant state for applying the generated electrical stimulation signal based on detecting the change from the detected neural state to the second neural state, and adjust one or more parameters for the generated electrical stimulation signal to align an EP peak (e.g., determined from EP measurements 214) with ERNA signals 216 to apply the generated electrical stimulation signal according to the switched resonant state. [0126] Sensing circuitry 204 is configured to monitor signals from any combination of electrodes 116, 118. Although sensing circuitry 204 is incorporated into a common housing with stimulation generation circuitry 202 and processing circuitry 210 in Fig. 2, in other examples, sensing circuitry 204 may be in a separate housing from IMD 106 and may communicate with processing circuitry 210 via wired or wireless communication techniques.

[0127] In some examples, sensing circuitry 204 includes one or more amplifiers, filters, and analog-to-digital converters. Sensing circuitry 204 may be used to sense physiological signals, such as EP measurements for storage as EP measurements 214 and ERNA signals for storage as ERNA signals 216. In some examples, sensing circuitry 204 measures EP and ERNA signals from a particular combination of electrodes 116, 118. In some cases, the particular combination of electrodes for sensing includes different electrodes than a set of electrodes 116, 118 used to deliver electrical stimulation signals (e.g., therapeutic electrical stimulation signals or electrical stimulation signals for evoking ERNA signals). Alternatively, in other cases, the particular combination of electrodes used for sensing includes at least one of the same electrodes as a set of electrodes used to deliver stimulation signals to patient 120. Sensing circuitry 204 may provide signals to an analog- to-digital converter, for conversion into a digital signal for processing, analysis, storage, or output by processing circuitry 210.

[0128] Electrodes 116, 118 on respective leads 114 may be constructed of a variety of different designs. For example, one or both of leads 114 may include two or more electrodes at each longitudinal location along the length of the lead, such as multiple electrodes, e.g., arranged as segments, at different perimeter locations around the perimeter of the lead at each of the locations.

[0129] As an example, one or both of leads 114 may include circumferentially- segmented DBS arrays of electrodes and non-segmented electrodes (e.g., ring electrodes). As one example, there may be a first ring electrode of electrodes 116 around the perimeter of lead 114A at a first longitudinal location on lead 114A (e.g., location A). Below the first ring electrode, there may be three segmented electrodes of electrodes 116 around the perimeter of lead 114A at a second longitudinal location on lead 114A (e.g., location B). Below the three segmented electrodes, there may be another set of three segmented electrodes of electrodes 116 around the perimeter of lead 114A at a third longitudinal location of lead 114A (e.g., location C). Below the three segmented electrodes, there may be a second ring electrode of electrodes 116 around the perimeter of lead 114A (e.g., location D). Electrodes 118 may be similarly positioned along lead 114B.

[0130] The above is one example of the array of electrodes, and the example techniques should not be considered limited to such an example. There may be other configurations of electrodes for DBS. Moreover, the example techniques are not limited to DBS, and other electrode configurations are possible.

[0131] In one example, the electrodes 116, 118 may be electrically coupled to stimulation generation circuitry 202 and sensing circuitry 204 via respective wires that are straight or coiled within the housing of the lead and run to a connector at the proximal end of the lead. In another example, each of the electrodes 116, 118 of the leads 114 may be electrodes deposited on a thin film. The thin film may include an electrically conductive trace for each electrode that runs the length of the thin film to a proximal end connector. The thin film may then be wrapped (e.g., a helical wrap) around an internal member to form the leads 114. These and other constructions may be used to create a lead with a complex electrode geometry. [0132] Telemetry circuitry 208 supports wireless communication between IMD 106 and an external programmer 104 or another computing device under the control of processing circuitry 210. Processing circuitry 210 of IMD 106 may receive, as updates to programs, values for various parameters such as magnitude and electrode combination, from programmer 104 via telemetry circuitry 208. Telemetry circuitry 208 in IMD 106, as well as telemetry modules in other devices and systems described herein, such as programmer 104, may accomplish communication by radiofrequency (RF) communication techniques. In addition, telemetry circuitry 208 may communicate with external medical device programmer 104 via proximal inductive interaction of IMD 106 with programmer 104. Accordingly, telemetry circuitry 208 may send information to external programmer 104 on a continuous basis, at periodic intervals, or upon request from IMD 106 or programmer 104.

[0133] Power source 220 delivers operating power to various components of IMD 106. Power source 220 may include a small rechargeable or non-rechargeable battery and a power generation circuit to produce the operating power. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within IMD 104. In some examples, power requirements may be small enough to allow IMD 104 to utilize patient motion and implement a kinetic energyscavenging device to trickle charge a rechargeable battery. In other examples, traditional batteries may be used for a limited period of time.

[0134] The DBS therapy is defined by one or more therapy programs having one or more parameters stored within memory 212. For example, the one or more parameters include a current amplitude (for a current-controlled system) or a voltage amplitude (for a voltage-controlled system), a pulse rate or frequency, and a pulse width, or a number of pulses per cycle. In examples where the electrical stimulation is delivered according to a “burst” of pulses, or a series of electrical pulses defined by an “on-time” and an “off- time,” the one or more parameters may further define one or more of a number of pulses per burst, an on-time, and an off-time. Processing circuitry 210, via electrodes 116, 118, delivers DBS to patient 120 and may adjust one or more parameters defining the electrical stimulation based on corresponding parameters of the sensed one or more signals of brain 120.

[0135] Fig. 3 is a block diagram of the external programmer 104 of Fig. 1. Although programmer 104 may generally be described as a hand-held device, programmer 104 may be a larger portable device or a more stationary device. In addition, in other examples, programmer 104 may be included as part of an external charging device or include the functionality of an external charging device. As illustrated in Fig. 3, programmer 104 may include processing circuitry 310, memory 312, user interface 302, telemetry circuitry 308, power source 320, resonance state assignment 306, and stimulation adjustment 304. Memory 312 may store instructions that, when executed by processing circuitry 310, cause processing circuitry 310 and external programmer 104 to provide the functionality ascribed to external programmer 104 throughout this disclosure. Each of these components, or modules, may include electrical circuitry that is configured to perform some or all of the functionality described herein. For example, processing circuitry 310 may include processing circuitry configured to perform the processes discussed with respect to processing circuitry 210 of the IMD 106 as described with reference to Fig. 2. In some examples, programmer 104 may include or may be referred to as a signal generator (e.g., in combination with or separate from IMD 106).

[0136] In general, programmer 104 comprises any suitable arrangement of hardware, alone or in combination with software and/or firmware, to perform the techniques attributed to programmer 104, and processing circuitry 310, user interface 302, and telemetry circuitry 308 of programmer 104. In various examples, programmer 104 may include one or more processors, which may include fixed function processing circuitry and/or programmable processing circuitry, as formed by, for example, one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. Programmer 104 also, in various examples, may include a memory 312, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, a CD-ROM, comprising executable instructions for causing the one or more processors to perform the actions attributed to them. Moreover, although processing circuitry 310 and telemetry circuitry 308 are described as separate modules, in some examples, processing circuitry 310 and telemetry circuitry 308 may be functionally integrated with one another. In some examples, processing circuitry 310 and telemetry circuitry 308 correspond to individual hardware units, such as ASICs, DSPs, FPGAs, or other hardware units.

[0137] Memory 312 (e.g., a storage device) may store instructions or data that, when executed by processing circuitry 310, cause processing circuitry 310 and programmer 104 to provide the functionality ascribed to programmer 104 throughout this disclosure. For example, memory 312 may include instructions that cause processing circuitry 310 to obtain a parameter set from memory or receive a user input and send a corresponding command to IMD 106, or instructions for any other functionality. In addition, memory 312 may include a plurality of programs, where each program includes a parameter set that defines stimulation therapy.

[0138] User interface 302 may include a button or keypad, lights, a speaker for voice commands, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or organic light-emitting diode (OLED). In some examples the display may be a touch screen. User interface 302 may be configured to display any information related to the delivery of stimulation therapy, identified patient behaviors, sensed patient parameter values, patient behavior criteria, or any other such information. User interface 302 may also receive user input via user interface 302. The input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen.

[0139] Telemetry circuitry 308 may support wireless communication between IMD 106 and programmer 104 under the control of processing circuitry 310. Telemetry circuitry 308 may also be configured to communicate with another computing device via wireless communication techniques, or direct communication through a wired connection. In some examples, telemetry circuitry 308 provides wireless communication via an RF or proximal inductive medium. In some examples, telemetry circuitry 308 includes an antenna, which may take on a variety of forms, such as an internal or external antenna.

[0140] Examples of local wireless communication techniques that may be employed to facilitate communication between programmer 104 and IMD 106 include RF communication according to the 802.11 or Bluetooth specification sets or other standard or proprietary telemetry protocols. In this manner, other external devices may be capable of communicating with programmer 104 without needing to establish a secure wireless connection.

[0141] In some examples, processing circuitry 310 of external programmer 104 defines the parameters of electrical stimulation therapy, stored in memory 312, for delivering DBS to patient 120. In one example, processing circuitry 310 of external programmer 104, via telemetry circuitry 308, issues commands to IMD 106 causing IMD 106 to deliver electrical stimulation therapy via electrodes 116, 118 via leads 114.

[0142] In one or more examples, programmer 104 may be configured to perform one or more of the example techniques described in this disclosure. For instance, processing circuitry 310 may be configured to perform one or more of the example operations described above with respect to processing circuitry 210. [0143] For example, processing circuitry 310 may be configured to cause stimulation generation circuitry 202 to deliver a first set of one or more therapeutic electrical stimulation signals according to a first set of one or more parameters. For instance, processing circuitry 310 may output the first set of one or more parameters to IMD 106 for storage, which stimulation generation circuitry 202 uses for delivery of the first set of one or more therapeutic electrical stimulation signals.

[0144] Additionally, processing circuitry 310 may be configured to perform resonance state assignment 306. Resonance state assignment 306 may include processing circuitry 310 assigning a constructive resonance state or a destructive resonance state to each of a plurality of neural states. In some examples, resonance state assignment 306 may be indicated or executed based on inputs from a clinician assigning a respective resonance state to each neural state. Accordingly, when a neural state is detected, a plurality of parameters for the therapeutic electrical stimulation signals may be determined by processing circuitry 310 according to the resonance state assigned to the detected neural state.

[0145] It will be appreciated that in some embodiments, resonance statement assignment 306 may be applied bilaterally in which two different neural states are assigned. In such instances, each of the two different neural states are independently tracked and a plurality of parameters for the therapeutic electrical stimulation signals may be determined for each of the two different neural states. Further, the plurality of parameters for the therapeutic electrical stimulation signals for each of the two different neural states may be independently adjusted or updated. Additionally, in some instances, deep brain stimulation can be applied to the subthalamic nucleus in each hemisphere of a patient’s brain. In such instances, the stimulation may or may not result in oscillation independently. Such oscillations may also be dependent on each other, which can be used to correlate or link the simulation timing for the two different neural states.

[0146] As an example, resonance state assignment 306 may be initially performed in a clinic, where the physician or clinician may set a neural state to include a constructive resonance state. Subsequently, the physician or clinician may observe how the constructive resonance state is treating symptoms for the patient (e.g., is the constructive resonance state comfortable for the patient). In some examples, the patient may toggle between the constructive resonance state and the destructive resonance state for the neural state or for different neural states. Accordingly, in some embodiments, programmer 104 may determine or learn trends for the patient (e.g., every time the patient is moving, the patient turns off the constructive resonant state) for resonance state assignment 306. Subsequently, programmer 104 may actively change resonance state assignment 306 so that processing circuitry 310 adjusts parameters of the generated electrical stimulation signal to use the destructive resonance state when the patient is moving. That is, programmer 104 (e.g., and/or IMD 106) may employ a deep learning model (e.g., an artificial intelligence (Al)-type algorithm) to learn how the patient is adjusting or switching between resonance states and then automatically build the learning into assigning resonance states or adjusting parameters in a closed-loop system.

[0147] In some embodiments, programmer 104 may be configured to perform functionality attributed to IMD 106 as described with reference to Fig. 2. For example, programmer 104 may be configured to perform stimulation adjustment 304 for adjusting one or more parameters of the therapeutic electrical stimulation signals (e.g., generated by stimulation generation circuitry 202) to maintain a desired resonant state or to switch resonant states, where stimulation adjustment 304 may be performed similar to the techniques for stimulation adjustment 220 performed by IMD 106 as described with reference to Fig. 2.

[0148] As an example, programmer 104 may use processing circuitry 310 to maintain a resonant state for the patient based on stimulation adjustment 304, resonance state assignment 306, or both. For example, programmer 104 (e.g., and/or IMD 106) may realize the patient has optimal symptom relief when a constructive resonance state is maintained while the patient is awake, but the patient sleeps when a destructive resonance state is maintained. Accordingly, a physician or clinician may program programmer 104 to modulate stimulation (e.g., adjust magnitude, amplitude, frequency, etc.) in a closed loop fashion to maintain the constructive resonance state while the patient is in an awake state. Additionally or alternatively, while maintaining the constructive resonance state, the processing circuitry 310 (e.g., and/or processing circuitry 210) begin to see a side effect show up. Accordingly, processing circuitry 310 may perform stimulation adjustment 304 so that the stimulation parameters for applying the therapeutic electrical stimulation signals correspond to a slightly less constructive resonance state (e.g., not a full destructive resonance state) to shift an EP peak off from a peak of the ERNA signal a little bit (e.g., adjusting the magnitude of the resonant state).

[0149] Additionally or alternatively, as part of stimulation adjustment 304, processing circuitry 310 (e.g., and/or processing circuitry 210) may change resonant state (e.g., from constructive to destructive or vice versa) based on a neural state of the patient (e.g., asleep versus awake). As a non-limiting example, an asleep state for the patient may be assigned a destructive resonance state, but when the patient is awake, the constructive resonance state is assigned and maintained for the patient. Additionally or alternatively, when the patient is moving and active (e.g., as indicated by an accelerometer), programmer 104 and processing circuitry 310 (e.g., and/or IMD 106 and processing circuitry 210) may maintain the constructive resonance state, but when the patient is not moving and/or sitting still in a chair (e.g., as indicated by the accelerometer), programmer 104 and processing circuitry 310 (e.g., and/or IMD 106 and processing circuitry 210) may maintain the destructive resonance state. Additional components not expressly listed herein may be used to determine a time to change to a desired resonant state. In some embodiments, the additional components (e.g., such as the accelerometer) may be housed or be part of the components described previously that are used for the DBS therapy (e.g., IMD 106) or may be separate components.

[0150] Fig. 4 is an example stimulation response 400 according to at least one embodiment of the present disclosure. The example stimulation response 400 may implement aspects of or may be implemented by aspects of Figs. 1-3. For example, the example stimulation response 400 may represent a neural response of applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-3, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.

[0151] The example stimulation response 400 may represent applying the electrical stimulation signal using a plurality of stimulation pulses 402A-402J (e.g., a burst comprising the plurality of stimulation pulses 402). Each single stimulation pulse 402 may elicit an EP response 404 due to activation of local neural circuitry when the electrical stimulation signal is applied to the anatomical element of the patient. Stimulation of the anatomical element may activate the local neural circuitry such that sensing Eps in the anatomical element (e.g., via the electrodes 116, 118) will show the response to a given stimulation pulse 402 in addition to any additional feedback or underlying activity from connected structures near the anatomical element that are also activated. When multiple stimulation pulses 402 are delivered, the EP response 404 elicited from each stimulation pulse 402 can add to the underlying activity from the feedback from the complex neural network near the anatomical element. [0152] With consecutive stimulation pulses 402, a sensed signal from the DBS therapy (e.g., which equals the EP response 404 from each stimulation pulse 402 plus underlying ongoing activity from previous pulses) may show a resonant behavior, referred to as ERNA 406. For example, the ERNA 406 (e.g., ERNA signal) is not an intrinsic signal within the anatomical element of the patient, but is evoked due to the electrical stimulation signal being delivered to the anatomical element. The stimulation signal delivered to the brain that evokes the ERNA 406 need not necessarily provide any therapeutic benefit, although it is possible for the stimulation signal that evokes the ERNA 406 to provide therapeutic benefit.

[0153] In some embodiments, the ERNA 406 may be generated based on applying the electrical stimulation signal to the anatomical element using a burst of the plurality of stimulation pulses 402 and then pausing application of the electrical stimulation signal after the burst of the plurality of stimulation pulses for a time duration (e.g., 30 ms or a different time duration). Subsequently, a neural response captured during the time duration may represent the ERNA 406. As shown in the example stimulation response 400 of Fig. 4, a time instance 408 may represent a time when a next occurring stimulation pulse 402 would have occurred after the stimulation pulse 402J, but did not occur based on pausing and/or inhibiting application of the electrical stimulation signal (e.g., time gap) to enable capturing of the ERNA 406. If a stimulation pulse were to be delivered at the time instance 408, the evoked response (e.g., the EP response 404) would add to any underlying activity (e.g., the ERNA 406) that is ongoing from the previous stimulation pulses 402.

[0154] While 10 stimulation pulses 402 are shown in the example stimulation response 400, a different number of stimulation pulses 402 may be used to generate the ERNA 406. As additional stimulation pulses 402 are added, properties of the ERNA 406 (e.g., sensed signal, underlying resonance, underlying resonant signal, underlying activity, etc.) can change. For example, a peak-trough amplitude 410, peak latencies (e.g., timing between peaks), a number of resonant peaks, etc., may depend on how many stimulation pulses 402 are used when applying the electrical stimulation signal. That is, multiple stimulation pulses 402 can elicit activity that is additive to the underlying activity (e.g., the ERNA 404). For example, as more consecutive stimulation pulses 402 are used for applying the electrical stimulation signal to the anatomical element, a peak of the EP response 404 following each stimulation pulse 402 may be larger than a peak of the EP response 404 for fewer stimulation pulses, a larger peak-to-trough amplitude 410 may be present after each stimulation pulse 402 (e.g., compared to applying the electrical stimulation signal using fewer stimulation pulses 402), shorter latencies may be present between each peak of the ERNA 406, a greater number of resonant peaks may be present in the ERNA 406 (e.g., more prominent resonant activity), or a combination thereof. In general, as more stimulation pulses 402 of the electrical stimulation signal for DBS therapy are delivered, the EP response 404 from each individual stimulation pulse 402 adds to any underlying activity, thus changing properties of a resonance (e.g., the ERNA 404) seen after the burst of stimulation pulses 402.

[0155] Fig. 5 is an example set of stimulation responses 500 with differing number of stimulation pulses according to at least one embodiment of the present disclosure. The example set of stimulation responses 500 may implement aspects of or may be implemented by aspects of Figs. 1-4. For example, the example set of stimulation responses 500 may represent different neural responses from applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-4, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.

[0156] As described previously, as additional stimulation pulses are added or used when applying the electrical stimulation signal to the anatomical element, properties of a sensed signal (e.g., peak-to-trough amplitude, peak latencies, number of resonant peaks, etc.) can change. For example, the example set of stimulation responses 500 may include a first stimulation response 502A that includes one (1) stimulation pulse, a second stimulation response 502B that includes two (2) stimulation pulses, a third stimulation response 502C that includes three (3) stimulation pulses, a fourth stimulation response 502D that includes four (4) stimulation pulses, a fifth stimulation response 502E that includes five (5) stimulation pulses, a sixth stimulation response 502F that includes six (6) stimulation pulses, a seventh stimulation response 502G that includes seven (7) stimulation pulses, an eight stimulation response 502H that includes eight (8) stimulation pulses, a ninth stimulation response 5021 that includes nine (9) stimulation pulses, and a tenth stimulation response 502J that includes 10 stimulation pulses.

[0157] As more stimulation pulses of the electrical stimulation signal for DBS therapy are delivered, an EP response 504 from each individual stimulation pulse adds to any underlying activity, thus changing properties of a resonance (e.g., a corresponding ERNA 506 for each stimulation response) seen after the burst of stimulation pulses. For example, each corresponding ERNA response 506 for each stimulation response 502 may include different properties from the other ERNA responses 506. The ERNA responses 506 may represent example ERNA sensed after varying number of consecutive stimulation pulses delivered at a same frequency (e.g., 110Hz in the example of Fig. 5, but not limited to such frequency). As the number of stimulation pulses increase, the resonant activity in the corresponding ERNA responses 506 becomes more prominent. For example, a peak value for the EP response 504 following each stimulation pulse increases as the number of stimulation pulses increase (e.g., the peak-to-trough value of the EP response 504 for the ERNA response 506J appears to be greater than the preceding ERNA responses 506), a peak-to-trough amplitude for the EP response 504 increases as the number of stimulation pulses increase (e.g., up to a point, such that the peak-to-trough amplitude does not continue to increase as more and more pulses are added), different latencies (e.g., shorter or longer) are present between each peak of the ERNA responses 506 as the number of stimulation pulses increase, a greater number of resonant peaks may be present in the ERNA responses 506 as the number of stimulation pulses increase, or a combination thereof.

[0158] Fig. 6A is an example set of stimulation responses 600 at different frequencies according to at least one embodiment of the present disclosure. The example set of stimulation responses 600 may implement aspects of or may be implemented by aspects of Figs. 1-5. For example, the example set of stimulation responses 600 may represent different neural responses from applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-5, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.

[0159] As shown in the example of Fig. 6A, the set of stimulation responses 600 include different stimulation responses for different stimulation frequencies (e.g., different indicated frequencies between 80Hz and 180 Hz). The properties of an ERNA response (e.g., initial peak-to-trough amplitude, resonant frequency, damping of peaks, shifts in peak/trough latencies, etc.) may be different for different stimulation frequencies. Each stimulation response in the set of stimulation responses 600 may represent example ERNA responses after a burst of 10 stimulation pulses are delivered for the electrical stimulation signal at the specified frequencies. As illustrated by the set of stimulation responses 600, a variability in the peak-to-trough amplitudes, the number of resonant peaks, and the latency of the peaks may exist between the different frequencies. [0160] Unlike the example illustrated in Fig. 5, where the properties of ERNA responses generally improved or increased as the number of stimulation pulses increased, the increase in frequency does not necessarily correspond to improved or increased properties. Some of the lower frequencies include a higher peak value for an EP response and a larger peak-to-trough amplitude than frequencies towards the middle of the shown range of frequencies.

[0161] Fig. 6B is a set of measurements 602 corresponding to the example set of stimulation responses 600 at different frequencies of Fig. 6A according to at least one embodiment of the present disclosure. A first measurement 604 may represent the first peak-to-trough amplitude for each stimulation frequency from the example set of stimulation responses 600 following the burst of stimulation pulses, a second measurement 606 may represent a first peak latency for each stimulation frequency from the example set of stimulation responses 600 following the burst of stimulation pulses (e.g., how long after the burst of stimulation pulses that a first peak occurs), a third measurement 608 may represent a second peak latency for each stimulation frequency from the example set of stimulation responses 600 following the burst of stimulation pulses (e.g., how long after the burst of stimulation pulses that a second peak occurs), and a fourth measurement 610 may represent a third peak latency for each stimulation frequency from the example set of stimulation responses 600 following the burst of stimulation pulses (e.g., how long after the burst of stimulation pulses that a third peak occurs). There is no strong correlation between the set of measurements 602 and increasing the stimulation frequency for applying the electrical stimulation signal to the anatomical element.

[0162] As described herein, the properties of the ERNA response (e.g., peak-to-trough amplitude, peak latencies, number of resonant peaks, etc.) may vary based on a relationship between a timing of the evoked response from a stimulation pulse (e.g., the EP response following each individual stimulation pulse) and the timing of the underlying activity (e.g., the ERNA following a burst of plurality of stimulation pulses). That is, an alignment of the EP response elicited by the stimulation pulse with the underlying activity may determine or correspond to certain properties of the ERNA response. Therefore, the inherent EP latency plays a role, not just the timing of the stimulus pulse. In some examples, the timing of EP latency can vary patient-to-patient (e.g., based on anatomy, disease state, neural state, etc.). Accordingly, the variability in ERNA properties due to different stimulation frequencies as seen in the example of Fig. 6B is due to differences in phase alignment of the immediate EP with the underlying activity, where the sensed ERNA signal then exhibits signs of constructive or destructive resonance as described herein.

[0163] Fig. 7 is an example curve 700 for constructive/destructive concepts according to at least one embodiment of the present disclosure. For example, the example curve 700 may include a sine wave 702. The sine wave 702 is split into six (6) different zones of underlying resonance that illustrate how the location of an EP peak following a stimulation pulse of an electrical stimulation signal can influence subsequent resonant activity. A first zone 704 may represent a trough of the sine wave 702, where destructive resonance would be present between the EP peak and the underlying resonant activity from previous stimulation pulses (e.g., ERNA). A second zone 706 may represent another area of the sine wave 702 with destructive resonance that would be present between the EP peak and the underlying resonant activity from previous stimulation pulses (e.g., ERNA). A third zone 708 may represent an area of the sine wave 702 with constructive resonance that would be present between the EP peak and the underlying resonant activity from previous stimulation pulses (e.g., ERNA). A fourth zone 710 may represent a peak of the sine wave 702, where constructive resonance would be present between the EP peak and the underlying resonant activity from previous stimulation pulses (e.g., ERNA). A fifth zone 712 may represent another area of the sine wave 702 with constructive resonance that would be present between the EP peak and the underlying resonant activity from previous stimulation pulses (e.g., ERNA). A sixth zone 714 may represent another area of the sine wave 702 with destructive resonance that would be present between the EP peak and the underlying resonant activity from previous stimulation pulses (e.g., ERNA).

[0164] As used and described herein, the third zone 708, the fourth zone 710, and the fifth zone 712 (e.g., “positive halves” of the sine wave 702) may be referred to as a first portion or first portions of the sine wave 702, such that the EP peak falling within similarly behaving portions of an ERNA response as the first portion(s) may correspond to different degrees of constructive resonance for a stimulation signal and DBS therapy. Additionally or alternatively, the first zone 704, the second zone 706, and the sixth zone 714 (e.g., “negative halves” of the sine wave 702) may be referred to as a second portion or second portions of the sine wave 702, such that the EP peak falling within similarly behaving portions of an ERNA response as the second portion(s) may correspond to different degrees of destructive resonance for a stimulation signal and DBS therapy. In some examples, “rising edge” may be used herein to describe or refer to the first portion(s), and “falling edge” may be used herein to describe or refer to the second portion(s).

[0165] Figs. 8A-8F are examples of constructive and destructive concepts 800 according to at least one embodiment of the present disclosure. The constructive and destructive concepts 800 may implement aspects of or may be implemented by aspects of Figs. 1-7. For example, the constructive and destructive concepts 800 may represent how a phase alignment 802 between underlying activity 804 (e.g., ERNA) from previous stimulation pulses of an electrical stimulation signal and an EP response 806 can influence an amplitude and latency of a summation 808 of the two signals according to the constructive and destructive concepts illustrated in Fig. 7.

[0166] Fig. 8A may correspond to the first zone 704 as described with reference to Fig. 7. Accordingly, based on the phase alignment 802 illustrating an alignment between a trough of the underlying activity 804 and a peak of the EP response 806, a degree of destructive resonance (e.g., full destructive resonance) occurs to result in the summation 808 having a smaller amplitude than the EP response 806. Fig. 8B may correspond to the second zone 706 as described with reference to Fig. 7. Accordingly, based on the phase alignment 802 illustrating an alignment between a lower portion of the underlying activity 804 and the peak of the EP response 806, a degree of destructive resonance (e.g., partial destructive resonance) occurs to result in the summation 808 having a smaller amplitude than the EP response 806 and shifting a peak of the underlying activity 804 to the left. Fig. 8C may correspond to the third zone 708 as described with reference to Fig. 7.

Accordingly, based on the phase alignment 802 illustrating an alignment between an upper portion of the underlying activity 804 and the peak of the EP response 806, a degree of constructive resonance (e.g., partial constructive resonance) occurs to result in the summation 808 having a larger amplitude than the EP response 806 and shifting a peak of the underlying activity 804 to the left.

[0167] Fig. 8D may correspond to the fourth zone 710 as described with reference to Fig. 7. Accordingly, based on the phase alignment 802 illustrating an alignment between a peak of the underlying activity 804 and a peak of the EP response 806, a degree of constructive resonance (e.g., full constructive resonance) occurs to result in the summation 808 having a larger amplitude than the EP response 806. Fig. 8E may correspond to the fifth zone 712 as described with reference to Fig. 7. Accordingly, based on the phase alignment 802 illustrating an alignment between an upper portion of the underlying activity 804 and the peak of the EP response 806, a degree of constructive resonance (e.g., partial constructive resonance) occurs to result in the summation 808 having a larger amplitude than the EP response 806 and shifting a peak of the underlying activity 804 to the right. Fig. 8F may correspond to the sixth zone 714 as described with reference to Fig. 7. Accordingly, based on the phase alignment 802 illustrating an alignment between a lower portion of the underlying activity 804 and the peak of the EP response 806, a degree of destructive resonance (e.g., partial destructive resonance) occurs to result in the summation 808 having a smaller amplitude than the EP response 806 and shifting a peak of the underlying activity 804 to the right.

[0168] While this simplified example illustrates the general concept of constructive and destructive resonances based on the alignment of the peaks, the EP response 806 and underlying activity 804 may not always be the same frequency or symmetric in shape. Accordingly, in some cases, the trough may have a bigger “pull” on influencing the latency of resonant activity than the peak.

[0169] Figs. 9A and 9B are example stimulation responses 900 and 902, respectively, according to at least one embodiment of the present disclosure. The example stimulation responses 900 and 902 may implement aspects of or may be implemented by aspects of Figs. 1-8F. For example, the example stimulation responses 900 and 902 may represent different neural responses from applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-8F, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc. Additionally, the example stimulation responses 900 and 902 may illustrate how the constructive resonance and destructive resonance concepts as described with reference to Figs. 7-8F impact properties of an ERNA response as described herein. The example stimulation response 900 may represent a burst of stimulation pulses at a first frequency (e.g., 110 Hz), and the example stimulation response 902 may represent a burst of stimulation pulses at a second frequency (e.g., 130 Hz).

[0170] As described herein, properties of an ERNA response are not completely governed by a timing of a stimulation pulse itself but rather by a timing of a response from the stimulation pulse. This distinction is especially important since the timing of the response (e.g., evoked response, such as an EP response) can vary patient-to-patient based on anatomy, neural-state, medication, etc., whereas the stimulation pulse timing would not vary from patient-to-patient. The example stimulation responses 900 and 902 include a first time instance 904 and a second time instance 906. The first time instance 904 may represent a time instance where a next stimulation pulse would have occurred, and the second time instance 906 may represent a time instance when an EP response corresponding to the next stimulation pulse would have occurred. That is, if another stimulation pulse were to be delivered at the respective frequencies at the first time instance 904, the timing of a peak of the EP response from that stimulation pulse would occur at the second time instance 906.

[0171] As shown in the example of Fig. 9A, the EP response of the example stimulation response 900 at the second time instance 906 aligns with a first portion (e.g., “rising edge” as described with reference to Fig. 7) of the underlying resonance activity (e.g., ERNA) following the burst of stimulation responses. As shown in the example of Fig. 9B, the EP response of the example stimulation response 902 at the second time instance 906 aligns with a second portion (e.g., “falling edge” as described with reference to Fig. 7) of the underlying resonance activity (e.g., ERNA) following the burst of stimulation responses. [0172] Based on the EP response of the example stimulation response 900 aligning with a first portion of the underlying resonance activity (e.g., indicating at least a degree of constructive resonance), the example stimulation response 900 comprises a higher first peak-to-trough amplitude than the example stimulation response 902 with the corresponding EP response aligning with a second portion of the underlying response (e.g., indicating at least a degree of destructive resonance). That is, an amplitude between a first peak 908 A and a first trough 910 after the burst of stimulation pulses of the example stimulation response 900 is larger than an amplitude between a first peak 912A and a first trough 914 after the burst of stimulation pulses of the example stimulation response 902. Additionally, the example stimulation response 900 includes a higher number of resonant peaks (e.g., six (6) peaks 908) than the number of resonant peaks in the example stimulation response 902 (e.g., five (5) peaks 912).

[0173] For the example stimulation response 900, the peak of the EP response is aligned with a first portion of the underlying ERNA (e.g., underlying behavior) which would promote constructive resonance behavior, explaining the larger peak-to-trough amplitude and higher number of resonant peaks. For the example stimulation response 902, the peak of the EP response is aligned with the trough and/or a second portion of the underlying ERNA, exhibiting destructive resonance behavior.

[0174] Accordingly, using Eps from DBS can help inform how to optimize stimulation based on the underlying neural activity. With certain stimulation settings, ERNA (e.g., the underlying neural activity) is present and can be used to optimize stimulation by maintaining a specified phase alignment of the peaks of the EP responses with different portions of the underlying neural activity or ERNA. As described herein, concepts are provided for optimizing stimulation parameters to promote and influence either constructive or destructive resonance of the ERNA signal.

[0175] Fig. 10 is a set of example stimulation responses 1000 that exhibit constructive and destructive concepts according to at least one embodiment of the present disclosure. The set of example stimulation responses 1000 may implement aspects of or may be implemented by aspects of Figs. 1-9B. For example, the set of example stimulation responses 1000 may represent different neural responses (e.g., measured in uV on the y- axis of each of the set of example stimulation responses 1000) from applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-9B, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc. Additionally, the set of example stimulation responses 1000 may illustrate how the constructive resonance and destructive resonance concepts as described with reference to Figs. 7-9B impact properties of an ERNA response as described herein.

[0176] The set of example stimulation responses 1000 may include a first stimulation response 1002 (e.g., delivered at a first frequency, such as 110Hz), a second stimulation response 1004 (e.g., delivered at a second frequency, such as 130Hz), a third stimulation response 1006 (e.g., delivered at a third frequency, such as 140Hz), a fourth stimulation response 1008 (e.g., delivered at a fourth frequency, such as 150Hz), and a fifth stimulation response 1010 (e.g., delivered at a fifth frequency, such as 160Hz). Each of the stimulation responses may include a first time instance 1014 and a second time instance 1016. The first time instance 1014 may represent a time instance where a next stimulation pulse would have occurred, and the second time instance 1016 may represent a time instance when an EP response corresponding to the next stimulation pulse would have occurred. That is, if another stimulation pulse were to be delivered at the respective frequencies at the first time instance 1014, the timing of a peak of the EP response from that stimulation pulse would occur at the second time instance 1016.

[0177] As described herein, set of example stimulation responses 1000 may illustrate constructive resonance or destructive resonance based on where the peak of the EP response (e.g., evoked response) aligns with the ERNA (e.g., underlying activity). For example, the first stimulation response 1002 and the fifth stimulation response 1010 may illustrate constructive resonance based on the peak of the EP response aligning with a first portion (e.g., “rising edge”) or peak of the ERNA. Additionally or alternatively, the second stimulation response 1004 and the third stimulation response 1006 may illustrate destructive resonance based on the peak of the EP response aligning with a second portion (e.g., “falling edge”) or trough of the ERNA. In some examples, the fourth stimulation response 1008 may illustrate constructive resonance based on the peak of the EP response aligning with a peak of the ERNA. However, the peak of the EP response in the fourth stimulation response 1008 also falls close to the beginning of a second portion (e.g., “falling edge”) of the ERNA, leading to a smaller peak-to-trough amplitude than the first stimulation 1002 and the fifth stimulation response 1010, but the fourth stimulation response 1008 may still represent a more constructive resonance than the second stimulation response 1004 and the third stimulation response 1006. Accordingly, based on having the constructive resonance, the first stimulation response 1002, the fourth stimulation response 1008, and the fifth stimulation response 1010 may have a larger amplitude of a first peak-to-trough after the burst of stimulation pulses applied as opposed to the amplitude of the first peak-to-trough for the second stimulation response 1004 and the third stimulation response 1006and their corresponding destructive resonance. In some embodiments, if the initial trough of the ERNA becomes larger in amplitude or wider, the trough can become the more influential part of the waveform of the ERNA and may dictate subsequent latency shifts.

[0178] In some examples, changes in the latency of the ERNA response can influence the alignment of the EP peak and the underlying resonance, causing changes in the constructive or destructive behavior. The changes in latency can be driven by constructive or destructive resonance from previous pulses, by a change in neural state (e.g., under anesthesia, asleep/awake, medication, disease progression, etc.), or a combination thereof. The changes in the ERNA response can then drive the need for changing in stimulation parameters to maintain the desired resonant state (constructive or destructive). In some embodiments, an optimal frequency may be determined to maintain constructive resonance or destructive resonance for the ERNA response. For example, the optimal frequency may be selected from a range of approximately 5Hz and approximately 500Hz. Additionally or alternatively, the constructive resonance or destructive resonance can be maintained or produced for the ERNA response by adjusting other parameters of the electrical stimulation signal. For example, the amplitude can be dynamically changed to control the resonance (e.g., adjusted between a range of approximately 0.1mA and 10mA), and/or the pulse width can be dynamically changed to control the resonance (e.g., adjusted between a range of approximately 20ps and approximately 500ps).

[0179] Subsequently, controlling the ERNA signal to promote constructive or destructive resonance could be used to guide programing in clinic to determine optimal stimulation parameters (e.g., stimulation frequency, amplitude, pulse width, etc.) to achieve a desired resonance state optimal or most satisfactory for the patient (e.g., reduces pain or symptoms of a corresponding condition of the patient without causing discomfort). Additionally, the concepts could be used in a closed-loop fashion that includes monitoring ERNA and adjusting stimulation parameters to maintain the desired resonant state (e.g., constructive or destructive) or decide when the desired state should switch from constructive to destructive or vice versa. Additionally, other input signals could inform a needed change in resonant state, such as detecting a specific neural state of the patient (e.g., sleep, awake, on medication, off medication, etc.) or detecting a certain LFP biomarker.

[0180] Figs. 11 A and 1 IB are example results 1100 and 1102, respectively, of applying a stimulation according to at least one embodiment of the present disclosure. The example results 1100 and 1102 may implement aspects of or may be implemented by aspects of Figs. 1-10. For example, the example results 1100 and 1102 may represent data collected after applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-10, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.

[0181] The example results 1100 and 1102 may represent data collected from a constant stimulation (e.g., applied at 130Hz) with a pulse (e.g., single pulse) skipped or dropped once each second (e.g., the constant stimulation is paused or inhibited for a single pulse or multiple pulses) to enable viewing underlying resonant activity (e.g., ERNA). The example results 1100 may represent an amplitude (e.g., in microvolts (uV)) of the sensed signal. The y-axis represents each consecutive data clip (e.g., one clip per second), and the x-axis represents time within each clip of data (e.g., where a stimulation pulse is delivered at 0ms and 15.4ms). A first time instance 1104 may represent where and when a stimulation pulse would have landed if the pulse(s) had not been skipped or dropped (e.g., at 7.7ms). A second time instance 1106 may represents where and when a peak of an evoked response (e.g., EP response) would have landed from the skipped or dropped stimulation pulse.

[0182] The example results 1102 may represent a waveform for the ERNA of the electrical stimulation signal captured at different points in time after stimulation was enabled. For example, the example results 1102 may include a first waveform 1108 A of the ERNA captured at a first time after the stimulation was enabled (e.g., 10s), a second waveform 1108B of the ERNA captured at a second time after the stimulation was enabled (e.g., 35s), a third waveform 1108C of the ERNA captured at a third time after the stimulation was enabled (e.g., 60s), a fourth waveform 1108D of the ERNA captured at a fourth time after the stimulation was enabled (e.g., 85s), a fifth waveform 1108E of the ERNA captured at a fifth time after the stimulation was enabled (e.g., 110s), a sixth waveform 1108F of the ERNA captured at a sixth time after the stimulation was enabled (e.g., 135s), a seventh waveform 1108G of the ERNA captured at a seventh time after the stimulation was enabled (e.g., 160s), and an eighth waveform 1108H of the ERNA captured at an eighth time after the stimulation was enabled (e.g., 185s). The example results 1102 also illustrate the first time instance 1104 and the second time instance 1106 to indicate where a peak of the EP response would have landed on the ERNA waveform. [0183] At around y=43s of the example results 1100, the stimulation was enabled, and initially, the alignment of the peak of the EP response (e.g., at the second time instance 1106) falls on a falling edge of the ERNA (e.g., underlying activity) as can be seen with the first waveform 1108 A of the example results 1102. Based on the constructive and destructive concepts described herein, the alignment of the peak of the EP response on the falling edge of the ERNA may slowly shift the underlying resonance to the right, as illustrated in the example results 1100 for the y-axis time = 45-110s and the movement of a third peak 1112 of the ERNA in the example results 1102 (e.g., the third peak 1112A of the first waveform 1108 A shifts to the right as can be seen with the third peak 1112H of the eighth waveform 1108H). Eventually, the ERNA (e.g., underlying resonance) has shifted such that the peak of the EP response (e.g., represented by the second time instance 1106) aligns with a peak of the underlying resonance (e.g., as illustrated with the fifth waveform 1108E, the sixth waveform 1108F, the seventh waveform 1108G, and the eighth waveform 1108H), thereby causing constructive resonance, which is illustrated by an increase in amplitude of a first peak 1114 for the waveforms as time elapses after the stimulation was enabled and seen by a color/shading transition 1116 around y-axis=130- 250s in the example results 1100. [0184] Because latency shifts can occur based on these concepts of constructive and destructive resonance as illustrated in the example of Figs. 11 A and 1 IB, an optimal stimulation frequency to maximize a peak-to-trough amplitude might appear differently from a burst of 10 pulses compared to constant stimulation (e.g., steady state).

[0185] Fig. 12 is a set of example stimulation responses 1200 for determining steady state behavior according to at least one embodiment of the present disclosure. The set of example stimulation responses 1200 may implement aspects of or may be implemented by aspects of Figs. 1-11. For example, the set of example stimulation responses 1200 may represent different neural responses from applying an electrical stimulation signal (e.g., therapeutic electrical stimulation signal) at different frequencies to an anatomical element (e.g., brain, STN, other area of the brain, the spine, etc.) of a patient as part of a DBS therapy (e.g., or other type of therapy) as described with reference to Figs. 1-11, such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.

[0186] The set of example stimulation responses 1200 may illustrate that change in peak-to-trough amplitude after constant frequency stimulation is enabled. Some stimulation frequencies may quickly show changes (e.g., 160Hz), while other stimulation frequencies can take 100s or more to start to show changes (e.g., 130Hz). Therefore, being able to infer the steady state behavior based on the initial characteristics from a short burst of stimulation can be advantageous to speed up a programming process for programming parameters of the electrical stimulation signal.

[0187] Because constant stimulation can cause shifts in the latencies of the underlying resonance (e.g., ERNA), the peak-to-trough amplitude can change as the system reaches a steady state at different stimulation frequencies. Stimulation was enabled for each of the stimulation frequencies in the set of example stimulation responses 1200 at around ~45s and kept at a constant stimulation amplitude of 0.7mA throughout. In some examples, the continuous stimulation may result in a slow stabilization time constant. The constant stimulation was applied at each frequency for one (1) second, then a pulse (e.g., or multiple pulses) was skipped or dropped (e.g., application of the constant stimulation was paused or inhibited for one or more pulses) after each second to sense the underlying resonance. In some embodiments, skipping or dropping one (1) pulse should not have a therapeutic impact on the patient based on beta bursts that are less than 500ms are not symptomatic.

[0188] Fig. 13 depicts a flowchart of a method 1300 that may be used, for example, for guided programming of stimulation parameters for applying an electrical stimulation signal to an anatomical element of a patient. For example, the method 1300 may use a timing of initial peak of an EP response compared to an ERNA signal (e.g., underlying resonance) to determine optimal settings based on patient specific response.

[0189] The method 1300 (and/or one or more steps thereof) may be carried out or otherwise performed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor(s) of a device as described herein. The at least one processor may be part of a programmer 104 and/or IMD 106 as described with reference to Figs. 1-3 (e.g., the processing circuitry 210 and/or the processing circuitry 310) and/or may be part of a control unit (e.g., computing device) in communication with the programmer 104 and/or IMD 106. A processor other than any processor described herein may also be used to execute the method 1300. The at least one processor may perform the method 1300 by executing elements stored in a memory (such as a memory in the programmer 104 and/or IMD 106 as described herein or a control unit, computing device, etc.). The elements stored in the memory and executed by the processor may cause the processor to execute one or more steps of a function as shown in method 1300. One or more portions of a method 1300 may be performed by the processor executing any of the contents of memory, such as capturing EP measurements, recording ERNA signals, determine a resonant state, adjusting stimulation parameters, and/or any associated operations as described herein.

[0190] The method 1300 comprises measuring a first response after applying a pulse of a generated electrical stimulation signal (e.g., via a signal generator, such as the programmer 104, the IMD 106, the stimulation generation circuitry 202, the processing circuitry 210, and/or the processing circuitry 310) to an anatomical element (e.g., brain, STN, etc.) of a patient (step 1302). For example, the first response may comprise a capture EP measurement that results from applying the pulse of the generated electrical stimulation signal.

[0191] The method 1300 also comprises measuring a second response after applying a plurality of pulses (e.g., a bust of pulses, a burst of a plurality of pulses, etc.) of the generated electrical stimulation signal to the anatomical element (step 1304). For example, the second response may comprise a captured ERNA signal that results from applying the plurality of pulses of the generated electrical stimulation signal.

[0192] The method 1300 also comprises extracting a first set of timings corresponding to a peak and a trough for the first response (step 1306). For example, the first set of timings may include a timing of a peak of the EP measurement and a timing of a trough of the EP measurement.

[0193] The method 1300 also comprises extracting a second set of timings corresponding to peaks and troughs for the second response (step 1308). For example, the second set of timings may include extracted timings of ERNA peaks and troughs.

[0194] The method 1300 also comprises calculating steady state ERNA behavior based on constructive and destructive concepts (step 1310). For example, a constructive resonance state and a destructive resonance state for applying the generated electrical stimulation signal to the anatomical element may be determined based on the first response and the second response. In some examples, the constructive resonance state may comprise a state where a peak corresponding to the first response (e.g., EP response peak) would align with a first portion (e.g., “rising edge” as described with reference to Fig. 7) or peak of an underlying resonance response corresponding to the second response (e.g., ERNA rising edge or peak). Additionally or alternatively, the destructive resonance state may comprise a state where the peak corresponding to the first response (e.g., EP response peak) would align with a second portion (e.g., “falling edge” as described with reference to Fig. 7) or trough of the underlying resonance response corresponding to the second response (e.g., ERNA falling edge or trough). In some examples, a degree of the constructive resonance state and/or the destructive resonance state may be determined for applying the generated electrical stimulation signal to the anatomical element. For example, the degree of the constructive resonance state and/or the destructive resonance state may comprise a resonance state that is not fully constructive, not fully destructive, neither constructive nor destructive, or a combination of constructive and destructive.

[0195] In some examples, the method 1300 also comprises using alignment of the peak and/or trough of the first response (e.g., EP response peak) and steady state ERNA behavior to determine stimulation parameters (e.g., amplitude, pulse width, frequency, etc.) for the generated electrical stimulation signal to maintain constructive resonance (step 1312). That is, the stimulation parameters may be determined based on producing an alignment of the peak and/or trough for the first response from the first set of timings and the steady state behavior for the second response (e.g., aligning the EP response peak with a first portion or peak of the steady state ERNA behavior).

[0196] Additionally or alternatively, the method 1300 comprises using alignment of the peak and/or trough of the first response (e.g., EP response peak) and steady state ERNA behavior to determine stimulation parameters (e.g., amplitude, pulse width, frequency, etc.) for the generated electrical stimulation signal to maintain destructive resonance (step 1314). That is, the stimulation parameters may be determined based on producing an alignment of the peak and/or trough for the first response from the first set of timings and the steady state behavior for the second response (e.g., aligning the EP response peak with a second portion or trough of the steady state ERNA behavior).

[0197] The present disclosure encompasses embodiments of the method 1300 that comprise more or fewer steps than those described above, and/or one or more steps that are different than the steps described above.

[0198] Fig. 14 depicts a flowchart of a method 1400 that may be used, for example, for closed-loop adjustments of stimulation parameters to maintain a resonant state.

[0199] The method 1400 (and/or one or more steps thereof) may be carried out or otherwise performed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor(s) of a device as described herein. The at least one processor may be part of a programmer 104 and/or IMD 106 as described with reference to Figs. 1-3 (e.g., the processing circuitry 210 and/or the processing circuitry 310) and/or may be part of a control unit (e.g., computing device) in communication with the programmer 104 and/or IMD 106. A processor other than any processor described herein may also be used to execute the method 1400. The at least one processor may perform the method 1400 by executing elements stored in a memory (such as a memory in the programmer 104 and/or IMD 106 as described herein or a control unit, computing device, etc.). The elements stored in the memory and executed by the processor may cause the processor to execute one or more steps of a function as shown in method 1400. One or more portions of a method 1400 may be performed by the processor executing any of the contents of memory, such as capturing EP measurements, recording ERNA signals, determine a resonant state, adjusting stimulation parameters, and/or any associated operations as described herein.

[0200] The method 1400 comprises choosing a desired resonant state for a patient (step 1402). For example, the desired resonant state may be a constructive resonant state or a destructive resonant state as described herein. In some examples, the desired resonant state for the patient may be set by a clinician based on inputs from the patient (e.g., level of satisfaction or comfort with a given resonant state, an efficacy of a resonant state to treat conditions for the patient, etc.). Accordingly, the electrical stimulation signal may be applied to the anatomical element according to the desired resonant state. For example, the electrical stimulation signal may be applied using a plurality of parameters configured to generate the desired resonant state.

[0201] The method 1400 also comprises monitoring for changes in a first peak-to-trough amplitude (e.g., or another stimulation parameter) between each pulse of the generated electrical stimulation signal (step 1404).

[0202] The method 1400 also comprises determining a shift in phase alignment between an underlying resonance response corresponding to the second response and the first response, the shift in phase alignment determined based on detecting a change in the peak- to-trough amplitude (step 1406). For example, a shift in phase alignment of the underlying resonance (e.g., ERNA) with a peak of the first response (e.g., EP peak response) may be inferred based on constructive/destructive concepts.

[0203] The method 1400 also comprises pausing application of the generated electrical stimulation signal for one or more pulses to view the underlying resonance response for confirming the shift in phase alignment (step 1408).

[0204] The method 1400 also comprises adjusting one or more parameters of the plurality of stimulation parameters to align a peak corresponding to the first response with the underlying resonance response to maintain the first resonant state based on determining the shift in phase alignment (step 1410). For example, a stimulation frequency may be adjusted to align a peak or trough of the first response (e.g., EP response) with a corresponding portion of the underlying resonance (e.g., ERNA) to maintain the desired resonant state. Additionally or alternatively, other parameters may be adjusted to maintain the desired resonant state, such as an amplitude and/or pulse width.

[0205] The present disclosure encompasses embodiments of the method 1400 that comprise more or fewer steps than those described above, and/or one or more steps that are different than the steps described above.

[0206] Fig. 15 depicts a flowchart of a method 1500 that may be used, for example, for closed-loop adjustments of stimulation parameters to adjust a magnitude of a resonant state.

[0207] The method 1500 (and/or one or more steps thereof) may be carried out or otherwise performed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor(s) of a device as described herein. The at least one processor may be part of a programmer 104 and/or IMD 106 as described with reference to Figs. 1-3 (e.g., the processing circuitry 210 and/or the processing circuitry 310) and/or may be part of a control unit (e.g., computing device) in communication with the programmer 104 and/or IMD 106. A processor other than any processor described herein may also be used to execute the method 1500. The at least one processor may perform the method 1500 by executing elements stored in a memory (such as a memory in the programmer 104 and/or IMD 106 as described herein or a control unit, computing device, etc.). The elements stored in the memory and executed by the processor may cause the processor to execute one or more steps of a function as shown in method 1500. One or more portions of a method 1500 may be performed by the processor executing any of the contents of memory, such as capturing EP measurements, recording ERNA signals, determine a resonant state, adjusting stimulation parameters, and/or any associated operations as described herein.

[0208] The method 1500 comprises choosing a desired resonant state for a patient (step 1502). For example, the desired resonant state may be a constructive resonant state or a destructive resonant state as described herein. In some examples, the desired resonant state for the patient may be set by a clinician based on inputs from the patient (e.g., level of satisfaction or comfort with a given resonant state, an efficacy of a resonant state to treat conditions for the patient, etc.). Accordingly, the electrical stimulation signal may be applied to the anatomical element according to the desired resonant state. For example, the electrical stimulation signal may be applied using a plurality of parameters configured to generate the desired resonant state.

[0209] The method 1500 also comprises monitoring for side effects caused by applying the electrical stimulation signal according to the desired resonant state (step 1504). For example, the side effects may comprise a change in the second response (e.g., change in ERNA signal), an LFP signal side effect, a change in accelerometer settings and/or accelerometer signal(s) (e.g., indicating the patient is moving or not moving, indicating a posture of the patient, etc.), or a combination thereof.

[0210] The method 1500 also comprises adjusting a resonant state of the electrical stimulation signal based at least in part on detecting the side effects (step 1506). For example, adjusting the resonant state may include adjusting the first resonant state to have less constructive resonance, shift an alignment of the peak corresponding to the first response off a peak of the underlying resonance response, switch from the first resonant state to a second resonant state (e.g., an opposite of the constructive resonance state or the destructive resonance state configured for the first resonant state), adjust a pulse timing for the electrical stimulation signal, or a combination thereof. [0211] The method 1500 also comprises adjusting one or more parameters of the plurality of stimulation parameters to align a peak corresponding to the first response with an underlying resonance response corresponding to the second response to apply the electrical stimulation signal according to the adjusted resonant state (step 1508). For example, a stimulation frequency may be adjusted to align a peak or trough of the first response (e.g., EP response) with a corresponding portion of the underlying resonance (e.g., ERNA) based on the adjusted resonant state. Additionally or alternatively, other parameters may be adjusted to produce the adjusted resonant state, such as an amplitude and/or pulse width.

[0212] The present disclosure encompasses embodiments of the method 1500 that comprise more or fewer steps than those described above, and/or one or more steps that are different than the steps described above.

[0213] Fig. 16 depicts a flowchart of a method 1600 that may be used, for example, for closed-loop adjustments of stimulation parameters to change a resonant state. In some embodiments, the method 1600 may be used for changing resonant states based on changes in a neural state of a patient (e.g., the resonant state is changed in response to a change in neural state). Additionally or alternatively, a resonant state of the patient may be changed in anticipation of changes in a neural state of the patient. For example, properties of different signal measurements associated with a DBS therapy (e.g., properties of an ERNA signal, EP measurement, etc.) may indicate that a neural state of the patient is about to change, and the techniques described herein may be used to change a resonant state of the patient prior to the neural state changing for the patient.

[0214] The method 1600 (and/or one or more steps thereof) may be carried out or otherwise performed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor(s) of a device as described herein. The at least one processor may be part of a programmer 104 and/or IMD 106 as described with reference to Figs. 1-3 (e.g., the processing circuitry 210 and/or the processing circuitry 310) and/or may be part of a control unit (e.g., computing device) in communication with the programmer 104 and/or IMD 106. A processor other than any processor described herein may also be used to execute the method 1600. The at least one processor may perform the method 1600 by executing elements stored in a memory (such as a memory in the programmer 104 and/or IMD 106 as described herein or a control unit, computing device, etc.). The elements stored in the memory and executed by the processor may cause the processor to execute one or more steps of a function as shown in method 1600. One or more portions of a method 1600 may be performed by the processor executing any of the contents of memory, such as capturing EP measurements, recording ERNA signals, determine resonant states, assign resonant states, adjusting stimulation parameters, and/or any associated operations as described herein.

[0215] The method 1600 comprises assigning a constructive resonance state or a destructive resonance state to each of a plurality of neural states (step 1602). As a nonlimiting example, the constructive resonance state may be assigned to an awake state for a patient, and a destructive resonance state may be assigned to a sleep state for the patient. In some examples, the plurality of neural states may include, but is not limited to, the awake state, the asleep state, an on-medication state, an off-medication state, a depth of anesthesia state, a disease progression state, a medication wash-in state, a medication wash-out state, a movement state (e.g., whether the patient is moving or not, such as indicated by an accelerometer), a posture of the patient (e.g., upright, laying down, etc.), or a different neural state. Accordingly, upon detecting a neural state of the plurality of neural states, an electrical stimulation signal may be applied to an anatomical element of the patient according to the assigned constructive resonance state or destructive resonance state for the detected neural state.

[0216] The method 1600 also comprises monitoring for a change from the detected neural state to a second neural state of the plurality of neural states, the second neural state corresponding to a different assigned resonant state of the detected neural state (step 1604). In some examples, the change in neural state may be detected based on one or more measurements (e.g., ERNA, LFP, resonant frequency, etc.) that indicate whether the patient is asleep or awake, if a medication is washing in or out for the patient, etc.

[0217] The method 1600 also comprises switching a resonant state for applying the electrical stimulation signal based on detecting the change from the detected neural state to the second neural state (step 1606). In some examples, a desired resonant state for the patient may be switched from the detected neural state to the second neural state based on a programmed setting (e.g., the assigned resonance states for each neural state).

[0218] The method 1600 also comprises adjusting one or more parameters of the plurality of stimulation parameters to align a peak corresponding to the first response with an underlying resonance response corresponding to the second response to apply the electrical stimulation signal according to the switched resonant state (step 1608). For example, a stimulation frequency may be adjusted to align a peak or trough of the first response (e.g., EP response) with a corresponding portion of the underlying resonance (e.g., ERNA) based on the new desired resonant state (e.g., second resonant state). Additionally or alternatively, other parameters may be adjusted to produce the new desired resonant state, such as an amplitude and/or pulse width. Subsequently, the electrical stimulation signal may be applied to the anatomical element using the adjusted one or more parameters.

[0219] It will be appreciated that in some embodiments, resonance statement assignment may be applied bilaterally in which two different neural states are assigned. In such instances, each of the two different neural states are independently monitored and a plurality of parameters for the therapeutic electrical stimulation signals may be determined for each of the two different neural states. Further, the plurality of parameters for the therapeutic electrical stimulation signals for each of the two different neural states may be independently adjusted or updated.

[0220] The present disclosure encompasses embodiments of the method 1600 that comprise more or fewer steps than those described above, and/or one or more steps that are different than the steps described above.

[0221] As noted above, the present disclosure encompasses methods with fewer than all of the steps identified in Figs. 13, 14, 15, and 16 (and the corresponding descriptions of the methods 1300, 1400, 1500, and 1600), as well as methods that include additional steps beyond those identified in Figs. 13, 14, 15, and 16 (and the corresponding descriptions of the methods 1300, 1400, 1500, and 1600). The present disclosure also encompasses methods that comprise one or more steps from one method described herein, and one or more steps from another method described herein. Any correlation described herein may be or comprise a registration or any other correlation.

[0222] The foregoing is not intended to limit the disclosure to the form or forms disclosed herein. In the foregoing Detailed Description, for example, various features of the disclosure are grouped together in one or more aspects, embodiments, and/or configurations for the purpose of streamlining the disclosure. The features of the aspects, embodiments, and/or configurations of the disclosure may be combined in alternate aspects, embodiments, and/or configurations other than those discussed above. This method of disclosure is not to be interpreted as reflecting an intention that the claims require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed aspect, embodiment, and/or configuration. Thus, the following claims are hereby incorporated into this Detailed Description, with each claim standing on its own as a separate preferred embodiment of the disclosure.

[0223] Moreover, though the foregoing has included description of one or more aspects, embodiments, and/or configurations and certain variations and modifications, other variations, combinations, and modifications are within the scope of the disclosure, e.g., as may be within the skill and knowledge of those in the art, after understanding the present disclosure. It is intended to obtain rights which include alternative aspects, embodiments, and/or configurations to the extent permitted, including alternate, interchangeable and/or equivalent structures, functions, ranges or steps to those claimed, whether or not such alternate, interchangeable and/or equivalent structures, functions, ranges or steps are disclosed herein, and without intending to publicly dedicate any patentable subject matter.

Claims

CLAIMS What is claimed is:

1. A system for providing deep brain stimulation (DBS) therapy, comprising: a signal generator configured to generate an electrical stimulation signal; one or more leads coupled to the signal generator, the one or more leads configured to carry the generated electrical stimulation signal to an anatomical element of a patient; a respective plurality of electrodes disposed at distal portions of the one or more leads, the respective plurality of electrodes configured to be implanted in the anatomical element and to apply the generated electrical stimulation signal to the anatomical element based at least in part on being implanted in the anatomical element; a processor; and a memory storing data for processing by the processor, the data, when processed, causes the processor to: measure, via one or more electrodes of the respective plurality of electrodes, a first response after applying a pulse of the generated electrical stimulation signal to the anatomical element; measure, via one or more electrodes of the respective plurality of electrodes, a second response after applying a plurality of pulses of the generated electrical stimulation signal to the anatomical element; determine a constructive resonance state and/or a destructive resonance state for applying the generated electrical stimulation signal to the anatomical element based at least in part on the first response and the second response; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes based at least in part on one or more stimulation parameters determined based at least in part on the constructive resonance state and/or the destructive resonance state.

2. The system of claim 1, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: extract a first set of timings corresponding to a peak and a trough for the first response; and extract a second set of timings corresponding to peaks and troughs for the second response, wherein the constructive resonance state and/or the destructive resonance state are determined based at least in part on the first set of timings and the second set of timings.

3. The system of claim 2, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: calculate a steady state behavior for the second response based at least in part on the constructive resonance state and/or the destructive resonance state.

4. The system of claim 3, wherein the one or more stimulation parameters are determined based at least in part on an alignment of a peak and/or trough for the first response from the first set of timings and the steady state behavior for the second response.

5. The system of claim 1, wherein: the constructive resonance state comprises a state where a peak corresponding to the first response would align with a first portion and/or a peak of an underlying resonance response corresponding to the second response; and the destructive resonance state comprises a state where the peak corresponding to the first response would align with a second portion and/or a trough of the underlying resonance response corresponding to the second response.

6. The system of claim 1, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes according to a first resonant state, wherein the first resonant state comprises a degree of the constructive resonance state and/or the destructive resonance state; monitor for changes in a peak-to-trough amplitude between each pulse of the generated electrical stimulation signal; determine a shift in phase alignment between an underlying resonance response corresponding to the second response and the first response, the shift in phase alignment determined based at least in part on detecting a change in the peak-to-trough amplitude; and adjust one or more parameters of the generated electrical stimulation signal to align a peak corresponding to the first response with the underlying resonance response to maintain the first resonant state based at least in part on determining the shift in phase alignment.

7. The system of claim 6, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: inhibit application of the generated electrical stimulation signal for one or more pulses; and determine the underlying resonance response for confirming the shift in phase alignment based at least in part on inhibiting application of the generated electrical stimulation signal for the one or more pulses.

8. The system of claim 1, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes according to a first resonant state, wherein the first resonant state comprises a degree of the constructive resonance state and/or the destructive resonance state; monitor for side effects caused by applying the generated electrical stimulation signal according to the first resonant state; adjust a resonant state of the generated electrical stimulation signal based at least in part on detecting the side effects; and adjust one or more parameters of the generated electrical stimulation signal to align a peak corresponding to the first response with an underlying resonance response corresponding to the second response to provide the generated electrical stimulation signal according to the adjusted resonant state.

9. The system of claim 8, wherein the data stored in the memory that, when processed causes the processor to adjust the resonant state of the electrical stimulation signal causes the system to: adjust the first resonant state to have a different degree of the constructive resonance state and/or the destructive resonance state, shift an alignment of the peak and/or trough corresponding to the first response off a peak of the underlying resonance response, switch from the first resonant state to a second resonant state, adjust a pulse timing for the electrical stimulation signal, or a combination thereof.

10. The system of claim 8, wherein the side effects comprise a change in the second response, a local field potential signal side effect, a change in accelerometer sensing, or a combination thereof.

11. The system of claim 1, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: assign the constructive resonance state and/or the destructive resonance state to each of a plurality of neural states; detect a neural state of the plurality of neural states; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes according to the assigned constructive resonance state and/or destructive resonance state for the detected neural state.

12. The system of claim 11, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: monitor for a change from the detected neural state to a second neural state of the plurality of neural states, the second neural state corresponding to a different assigned resonant state of the detected neural state; switch a resonant state for providing the generated electrical stimulation signal based at least in part on detecting the change from the detected neural state to the second neural state; adjust one or more parameters of the generated electrical stimulation signal to align a peak corresponding to the first response with an underlying resonance response corresponding to the second response to provide the generated electrical stimulation signal according to the switched resonant state; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes using the adjusted one or more parameters.

13. The system of claim 1, wherein the one or more stimulation parameters comprises a frequency, an amplitude, a pulse width, a number of pulses, additional parameters, or a combination thereof for the electrical stimulation signal.

14. The system of claim 1, wherein the first response comprises an evoked potential response, and the second response comprises an evoked resonant neural activity response.

15. The system of claim 1, wherein the anatomical element comprises a brain of the patient.

16. The system of claim 1, wherein the signal generator is a part of an implantable medical device, a programmer, or both.

17. A system for providing deep brain stimulation (DBS) therapy, comprising: a processor; and a memory storing data for processing by the processor, the data, when processed, causes the processor to: measure a first response of applying a pulse of an electrical stimulation signal to an anatomical element of a patient; measure a second response of applying a plurality of pulses of the electrical stimulation signal to the anatomical element; determine a constructive resonance state and/or a destructive resonance state for applying the generated electrical stimulation signal to the anatomical element based at least in part on the first response and the second response; and transmit instructions to provide the electrical stimulation signal to the anatomical element using one or more stimulation parameters determined based at least in part on the constructive resonance state and/or the destructive resonance state.

18. The system of claim 17, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: extract a first set of timings corresponding to a peak and trough for the first response; and extract a second set of timings corresponding to peaks and troughs for the second response, wherein the constructive resonance state and/or the destructive resonance state are determined based at least in part on the first set of timings and the second set of timings.

19. A system for providing deep brain stimulation (DBS) therapy, comprising: a signal generator configured to generate an electrical stimulation signal; one or more leads coupled to the signal generator, the one or more leads configured to carry the generated electrical stimulation signal to an anatomical element of a patient; and a respective plurality of electrodes disposed at distal portions of the one or more leads, the respective plurality of electrodes configured to be implanted in the anatomical element and to apply the generated electrical stimulation signal to the anatomical element based at least in part on being implanted in the anatomical element, wherein the signal generator is configured to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the respective plurality of electrodes based at least in part on one or more stimulation parameters determined based at least in part on a constructive resonance state and/or a destructive resonance state.

20. The system of claim 19, wherein: the constructive resonance state comprises a state where a peak corresponding to a first response would align with a first portion and/or a peak of an underlying resonance response; and the destructive resonance state comprises a state where the peak corresponding to the first response would align with a second portion and/or a trough of the underlying resonance response, wherein the first response is acquired based at least in part on applying a pulse of the generated electrical stimulation signal and the underlying resonance response is acquired based at least in part on applying a plurality of pulses of the generated electrical stimulation signal.