Constructive and / or destructive evoked resonance neural activity (ERNA) for providing deep brain stimulation (DBS) therapy

Abstract

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

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 420,261, filed on October 28, 2022, which is incorporated herein by reference in its entirety. Background Art

[0003] The present disclosure relates generally to electrical stimulation therapy, and particularly to deep brain stimulation (DBS) therapy.

[0004] The medical device 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 through one or more leads that include electrodes located near a target location associated with the patient's brain, spinal cord, pelvic nerves, peripheral nerves, or gastrointestinal tract. Electrical stimulation is used for different therapeutic applications, such as DBS, spinal cord stimulation (SCS), pelvic stimulation, gastric stimulation, or peripheral nerve field stimulation (PNFS). Summary of the invention

[0005] Example aspects of the present disclosure include:

[0006] A system for providing DBS therapy, the system 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 corresponding plurality of electrodes disposed at a distal portion of the one or more leads, the corresponding 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 a first response via one or more of the corresponding plurality of electrodes after applying a pulse of the generated electrical stimulation signal to the anatomical element; measure a second response via one or more of the corresponding plurality of electrodes after applying multiple 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 corresponding plurality of electrodes based at least in part on one or more stimulation parameters, the one or more stimulation parameters being determined at least in part based on the constructive resonance state and / or the destructive resonance state.

[0007] Any of the aspects herein, wherein the memory stores additional data for processing by the processor, which when processed causes the processor to: extract a first set of timings corresponding to peaks and valleys of the first response; and extract a second set of timings corresponding to peaks and valleys of the second response, wherein the constructive resonant state and / or the destructive resonant state is determined based at least in part on the first set of timings and the second set of timings.

[0008] Any of the aspects herein, wherein the memory stores further data for processing by the processor, the further data when processed causing the processor to: calculate a steady-state behavior of the second response based at least in part on the constructive resonant state and / or the destructive resonant state.

[0009] Any of the aspects herein, wherein the one or more stimulation parameters are determined based at least in part on a comparison of peaks and / or valleys of the first response from the first set of timings with the steady-state behavior of the second response.

[0010] Any of the aspects herein, wherein: the constructive resonance state includes a state in which a peak corresponding to the first response is aligned with a first portion and / or peak of a fundamental resonance response corresponding to the second response; and the destructive resonance state includes a state in which the peak corresponding to the first response is aligned with a second portion and / or valley of the fundamental resonance response corresponding to the second response.

[0011] Any of the aspects of the present invention, wherein the memory stores additional data for processing by the processor, which, 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 corresponding plurality of electrodes according to a first resonance state, wherein the first resonance state includes a certain degree of the constructive resonance state and / or the destructive resonance state; monitor the change in the peak-to-valley amplitude between each pulse of the generated electrical stimulation signal; determine a phase comparison shift between a base resonance response corresponding to the second response and the first response, the phase comparison shift being determined at least in part based on detecting the change in the peak-to-valley amplitude; and adjust one or more parameters of the generated electrical stimulation signal based at least in part on determining the phase comparison shift to align a peak corresponding to the first response with the base resonance response, thereby maintaining the first resonance state.

[0012] Any of the aspects herein, wherein the memory stores additional data for processing by the processor, which when processed causes the processor to: inhibit application of the electrical stimulation signal generated for one or more pulses; and determine the fundamental resonant response based at least in part on application of the electrical stimulation signal generated for the one or more pulses inhibiting to confirm the phase comparison shift.

[0013] Any of the aspects of the present invention, wherein the memory stores additional data for processing by the processor, which, 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 corresponding plurality of electrodes according to a first resonance state, wherein the first resonance state includes a certain degree of the constructive resonance state and / or the destructive resonance state; monitor side effects caused by applying the generated electrical stimulation signal according to the first resonance state; adjust the resonance state of the generated electrical stimulation signal based at least in part on the detection of the side effects; and adjust one or more parameters of the generated electrical stimulation signal according to the adjusted resonance state to compare the peak corresponding to the first response with the base resonance response corresponding to the second response, thereby providing the generated electrical stimulation signal.

[0014] In any of the aspects herein, 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 different degrees of the constructive resonant state and / or the destructive resonant state, shift the peaks and / or valleys corresponding to the first response away from the peaks of the base resonant response, switch from the first resonant state to a second resonant state, adjust the pulse timing of the electrical stimulation signal, or perform a combination of these operations.

[0015] Any of the aspects herein, wherein the side effect comprises a change in the second response, a local field potential signal side effect, a change in accelerometer sensing, or a combination thereof.

[0016] Any of the aspects of the present invention, wherein the memory stores additional data for processing by the processor, which, 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 among 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 corresponding plurality of electrodes based on the assigned constructive resonance state and / or destructive resonance state of the detected neural state.

[0017] Any of the aspects herein, wherein the memory stores additional data for processing by the processor, which, when processed, causes the processor to: monitor a change from the detected neural state to a second neural state among the plurality of neural states, the second neural state corresponding to a different assigned resonance state of the detected neural state; switch the resonance 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 based on the switched resonance state to compare a peak corresponding to the first response with a base resonance response corresponding to the second response, thereby providing the generated electrical stimulation signal; and cause the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the corresponding plurality of electrodes using the adjusted one or more parameters.

[0018] Any of the aspects herein, wherein the one or more stimulation parameters include frequency, amplitude, pulse width, number of pulses, additional parameters, or combinations thereof for the electrical stimulation signal.

[0019] 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.

[0020] Any of the aspects herein, wherein the anatomical element comprises the patient's brain.

[0021] Any of the aspects herein, wherein the signal generator is part of an implantable medical device, a programmer, or both.

[0022] A system for providing DBS therapy, the system comprising: a processor; and a memory storing data for processing by the processor, the data, when processed, causing the processor to: measure a first response to applying pulses of an electrical stimulation signal to an anatomical element of a patient; measure a second response to applying multiple 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 at least in part on the constructive resonance state and / or the destructive resonance state.

[0023] Any of the aspects herein, wherein the memory stores additional data for processing by the processor, which when processed causes the processor to: extract a first set of timings corresponding to peaks and valleys of the first response; and extract a second set of timings corresponding to peaks and valleys of the second response, wherein the constructive resonant state and / or the destructive resonant state is determined based at least in part on the first set of timings and the second set of timings.

[0024] Any of the aspects herein, wherein the memory stores further data for processing by the processor, the further data when processed causing the processor to: calculate a steady-state behavior of the second response based at least in part on the constructive resonant state and the destructive resonant state.

[0025] A system for providing DBS therapy, the system 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 corresponding plurality of electrodes disposed at a distal portion of the one or more leads, the corresponding 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 corresponding plurality of electrodes based at least in part on one or more stimulation parameters, the one or more stimulation parameters being determined at least in part based on a constructive resonance state and / or a destructive resonance state.

[0026] Any of the aspects herein, wherein: the constructive resonance state includes a state in which a peak corresponding to a first response is aligned with a first portion and / or a peak of a fundamental resonance response; and the destructive resonance state includes a state in which a peak corresponding to the first response is aligned with a second portion and / or a valley of the fundamental resonance response, wherein the first response is obtained at least in part based on applying a pulse of the generated electrical stimulation signal, and the fundamental resonance response is obtained at least in part based on applying multiple pulses of the generated electrical stimulation signal.

[0027] Any aspect may be combined with any one or more other aspects.

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

[0029] Any one or more of the features is generally disclosed herein.

[0030] Any one or more of the features generally disclosed herein may be combined with any one or more of the other features generally disclosed herein.

[0031] Any of the aspects / features / embodiments may be combined with any one or more of the other aspects / features / embodiments.

[0032] Use any one or more of the aspects or features disclosed herein.

[0033] It should be understood that any feature described herein may be claimed in combination with any other feature described herein, regardless of whether the features are from the same described embodiment.

[0034] The details of one or more aspects of the present disclosure are set forth in the following drawings and description. Other features, objectives, and advantages of the techniques described in the present disclosure will be apparent from the description and drawings, and from the claims.

[0035] The phrases "at least one", "one or more", and "and / or" are open expressions that have both connective and dissociative properties in operation. For example, 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" each mean only A, only B, only C, A and B together, A and C together, B and C together, or A, B, and C together. When each of A, B, and C in the above expressions refers to an element such as X, Y, and Z or a class of elements such as X1-Xn, Y1-Ym, and Z1-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., X1 and X2), and a combination of elements selected from two or more classes (e.g., Y1 and Zo).

[0036] The term "an" entity refers to one or more of that entity. Therefore, the terms "a", "one or more", and "at least one" can be used interchangeably herein. It should also be noted that the terms "including", "comprising", and "having" can be used interchangeably.

[0037] The foregoing is a simplified overview of the present disclosure to provide an understanding of some aspects of the present disclosure. The present disclosure is neither a broad overview nor an exhaustive overview of the present disclosure and its various aspects, embodiments, and configurations. It is neither intended to determine the key or important elements of the present disclosure nor to delimit the scope of the present disclosure, but rather to present the selected concepts of the present disclosure in a simplified form as an introduction to the more detailed description presented below. As should be understood, other aspects, embodiments, and configurations of the present disclosure may utilize one or more of the features set forth above or described in detail below, either individually or in combination.

[0038] Numerous additional features and advantages of the present disclosure will become apparent to those skilled in the art after considering the description of the embodiments provided below. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The accompanying drawings are incorporated into and form a part of this specification to illustrate several examples of the present disclosure. These drawings, together with the description, explain the principles of the present disclosure. The accompanying drawings illustrate only preferred and alternative examples of how to implement and use the present disclosure, and these examples should not be interpreted as limiting the present disclosure to only the illustrated and described examples. Additional features and advantages will become apparent from the following more detailed description of various aspects, embodiments and configurations of the present disclosure, as illustrated by the accompanying drawings referenced below.

[0040] Figure 1 is a diagram of a system according to at least one embodiment of the present disclosure;

[0041] Figure 2 is a block diagram of an example implantable medical device (IMD) according to at least one embodiment of the present disclosure;

[0042] Figure 3 is a block diagram of a programmer according to at least one embodiment of the present disclosure;

[0043] Figure 4 is an example stimulus response according to at least one embodiment of the present disclosure;

[0044] Figure 5 is a set of example stimulation responses having different numbers of stimulation pulses according to at least one embodiment of the present disclosure;

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

[0046] Figure 6B is a method according to at least one embodiment of the present disclosure corresponding to Fig. 6A A set of measurements of responses to a set of example stimuli at different frequencies;

[0047] Figure 7 is an example curve of a constructive / destructive concept according to at least one embodiment of the present disclosure;

[0048] FIG. 8A to FIG. 8F are examples of constructive and destructive concepts according to at least one embodiment of the present disclosure;

[0049] Fig. 9A and Fig. 9B is an example stimulus response according to at least one embodiment of the present disclosure;

[0050] Fig.10 is a set of example stimulus responses that exhibit constructive and destructive concepts in accordance with at least one embodiment of the present disclosure;

[0051] Fig.11A and Fig. 11B is an example result of applying stimulation according to at least one embodiment of the present disclosure;

[0052] Fig.12 is a set of example stimulus responses for determining steady-state behavior according to at least one embodiment of the present disclosure;

[0053] Fig.13 is a flow chart according to at least one embodiment of the present disclosure;

[0054] Fig.14 is a flow chart according to at least one embodiment of the present disclosure;

[0055] Fig.15 is a flow chart according to at least one embodiment of the present disclosure; and

[0056] Fig.16 is a flow chart according to at least one embodiment of the present disclosure. DETAILED DESCRIPTION

[0057] It should be understood that the various aspects disclosed herein may be combined in combinations different from those specifically presented in the specification and drawings. It should also be understood that, depending on the example or implementation, certain actions or events of any process or method described herein may be performed in a different order and / or may be added, combined, or omitted entirely (e.g., not all described actions or events may be required to practice the disclosed technology, according to different implementations of the present disclosure). In addition, although for clarity, certain aspects of the present disclosure are described as being performed by a single module or unit, it should be understood that the technology of the present disclosure may be performed by a combination of units or modules associated with, for example, a computing device and / or a medical device.

[0058] 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 codes on a computer-readable medium and executed by a hardware-based processing unit. Alternatively or in addition, the functions may be implemented using a machine learning model, a neural network, an artificial neural network, or a combination thereof (alone or in combination with instructions). A computer-readable medium may include a non-transitory computer-readable medium corresponding to a tangible medium, such as a data storage medium (e.g., a random access memory (RAM), a read-only memory (ROM), an electrically erasable programmable ROM (EEPROM), a flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and can be accessed by a computer).

[0059] 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 A11, A12, A12X, A12Z, or A13 Bionic processors; or any other general-purpose microprocessor), 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 unit), application-specific integrated circuits (ASICs), field-programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuits. Thus, the term "processor" as used herein may refer to any of the foregoing structures or any other physical structure suitable for implementing the described techniques. Additionally, these techniques may 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 to implement the described techniques, and any future iterations of such chips, techniques, or processors can be used to implement the techniques and embodiments of the present disclosure as described herein.

[0060] Before explaining any embodiment of the present disclosure in detail, it should be understood that the present disclosure is not limited to the construction details and component arrangements set forth in the following description or illustrated in the accompanying drawings in terms of its application. The present disclosure can have other embodiments and can be practiced or implemented in various ways. In addition, it should be understood that the wording and terminology used herein are for the purpose of description and should not be considered as restrictive. The use of "comprises", "including" or "having" and its variations herein is intended to cover the items listed thereafter and their equivalents, as well as additional items. In addition, the present disclosure can use examples to illustrate one or more aspects thereof. Unless otherwise expressly stated, the use or listing of one or more examples (which can be indicated by "for example", "by way of example", "such as" or similar language) is not intended to and does not limit the scope of the present disclosure.

[0061] The terms proximal and distal are used in this disclosure in their conventional medical sense, with proximal being closer to an operator, user, or device of the system and farther away from an area of ​​medical interest within or on the patient's body, and distal being closer to the area of ​​medical interest within or on the patient's body and farther away from an operator, user, or device of the system.

[0062] The present disclosure describes example techniques for optimizing stimulation parameters of therapeutic electrical stimulation signals to promote and influence constructive resonance or destructive resonance of evoked resonant neural activity (ERNA) signals. The example techniques are described with respect to DBS, but the example techniques are not limited thereto and may be applied to other types of treatments and / or other anatomical locations. DBS can provide relief for many different patient conditions, such as essential tremor (ET), Parkinson's disease, obsessive compulsive disorder (OCD), depression, etc. For DBS, a surgeon implants one or more leads in the patient's brain for outputting therapeutic electrical stimulation signals deep within the brain. The one or more leads are coupled to an implantable medical device (IMD) that generates therapeutic electrical stimulation signals for delivery through the one or more leads.

[0063] A common target for DBS (e.g., to treat Parkinson's disease or another condition) is the subthalamic nucleus (STN) (e.g., within a patient's brain). In some examples, DBS therapy can incorporate the sensing of local field potentials (LFPs), which are spontaneous activities that represent background activity of a neural network. For example, the LFPs can be intrinsic signals within the patient's brain. In some cases, the LFPs are intrinsically generated by a signal source within the patient's brain. The signal characteristics of the LFPs can indicate a patient condition (e.g., a brain state).

[0064] Additionally or alternatively, another potential signal of interest for DBS treatment may include evoked activity. Due to the activation of local neural circuits, a single stimulation pulse of a therapeutic electrical stimulation signal may trigger an evoked potential (EP) response. However, due to the complex interconnected neural network in the brain (e.g., basal ganglia), the stimulation of the STN may activate the complex interconnected neural network, so that in addition to any additional feedback or basal activity from the connection structure in the same activated brain network (e.g., basal ganglia network), the EP in the sensing STN will also show a response to the pulse. When multiple stimulation pulses are delivered for a therapeutic electrical stimulation signal, the EP triggered by each pulse may be added to the basal activity of feedback from the complex neural network activated by the previous pulse.

[0065] With continuous stimulation pulses, the sensed signal from DBS therapy (e.g., which is equal to the EP from each pulse plus the basal ongoing activity from the previous pulse) can exhibit resonant behavior, which is referred to as ERNA. For example, an ERNA signal can be distinguished from an intrinsic signal in that an ERNA signal is a signal within the patient's brain that is induced due to or in response to a stimulation signal delivered to the brain. A stimulation signal delivered to the brain that induces an ERNA signal does not necessarily provide any therapeutic benefit, although a stimulation signal that induces an ERNA signal has the potential to provide a therapeutic benefit.

[0066] When additional stimulation pulses are delivered to the brain, the properties of the sensed signal (e.g., peak-to-trough amplitude, peak latency, number of resonance peaks, etc.) can change. For example, multiple stimulation pulses can induce activity that is additive to the basal activity. If a second stimulation pulse is applied after the first stimulation pulse, the evoked response from the second stimulation pulse will be added to any basal activity due to feedback from the previous pulse, and the sensed signal from the DBS treatment will represent this overall signal. That is, after two (2) consecutive stimulation pulses, the second peak after the EP can be larger than the second peak evoked from a single pulse. If a third consecutive stimulation pulse is to be delivered, the evoked response will be added to any basal activity 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 than similar activity evoked after a single pulse or two pulses. In general, when more pulses of a therapeutic electrical stimulation signal for DBS treatment are delivered, the EP from each individual pulse will add to or supplement any basal activity, thereby changing the properties of the resonance (e.g., ERNA response) seen after the burst of stimulation pulses.

[0067] Additionally, the properties of the ERNA response (e.g., initial peak-to-trough amplitude, resonant frequency, damping of peaks, shifts in peak / trough latencies, etc.) can be different for different stimulation frequencies. For example, there can be variability in peak-to-trough amplitude, number of resonant peaks, latency of peaks, etc. across different stimulation frequencies. Thus, the properties of the ERNA response can vary based on the relationship between the timing of the evoked response from the stimulation pulse and the timing of the underlying activity.

[0068] As described herein, the comparison of the EP induced by the stimulation pulse to the basal activity can correspond to the nature of the ERNA response. That is, the intrinsic EP latency plays a role in determining the nature of the ERNA response, not just the timing of the stimulation pulse. The timing of the EP latency may vary from patient to patient (e.g., based on anatomy, disease state, neural state, etc.). Therefore, changes in the properties of the ERNA due to different stimulation frequencies can be attributed to differences in the phase comparison of the immediate EP (e.g., after a single pulse of the therapeutic electrical stimulation signal is applied) to the basal activity, where the sensed ERNA signal then exhibits signs of constructive resonance or destructive resonance.

[0069] Constructive resonance can result in an ERNA signal or response with a larger peak-to-valley amplitude, more resonance peaks, shorter inter-peak latency, or a combination thereof. Additionally or alternatively, destructive resonance can result in an ERNA signal or response with a smaller peak-to-valley amplitude, fewer resonance peaks, longer inter-peak latency, or a combination thereof. Constructive resonance can occur when the peak of the EP response is aligned with the peak or first portion (e.g., "rising edge") of the basal ERNA response, and destructive resonance can occur when the peak of the EP response is aligned with the valley or second portion (e.g., "falling edge") of the basal ERNA response. Changes in the latency of the ERNA response can affect the alignment of the EP peak with the basal resonance, thereby causing changes in constructive or destructive behavior. Changes in latency can be driven by constructive or destructive resonance from previous pulses or by changes in neural state (e.g., under anesthesia, sleep / wakefulness, medication, disease progression, etc.). Changes in ERNA responses may also drive the need to change stimulation parameters to maintain a desired resonant state (e.g., a constructive resonant state or a destructive resonant state).

[0070] Thus, in some embodiments, controlling the ERNA signal to promote constructive resonance or destructive resonance can be used (e.g., in a clinical setting) to guide programming to determine optimal stimulation parameters (e.g., optimal stimulation frequency, amplitude, pulse width, etc.) for DBS therapy. Additionally, controlling the ERNA signal to promote constructive resonance or destructive resonance can be used in a closed-loop manner. For example, the ERNA signal can be monitored, and the stimulation parameters can be adjusted to maintain a desired resonant state (a constructive resonant state or a destructive resonant state) or to determine when the desired state should switch from constructive to destructive or vice versa. Additionally, other input signals can inform changes in the desired resonant state, such as detecting sleep, a certain LFP biomarker, an accelerometer signal (e.g., sensing a patient's movement or inactivity), sensing a patient's posture, etc. In some embodiments, the placement of different components (e.g., leads, electrodes, probes, etc.) configured to deliver DBS therapy can be determined based on controlling the ERNA signal to promote constructive resonance or destructive resonance. For example, during surgery and / or implantation of various components, a clinician or surgeon may use test electrical stimulation signals while controlling the ERNA signals to promote constructive resonance or destructive resonance to determine whether the various components are properly implanted in the patient.

[0071] In some examples, based in part on the techniques described herein, a therapeutic electrical stimulation signal (e.g., for DBS therapy) can directly affect the resonance (e.g., ERNA signal) of a constructive state or a destructive state, and different parameters used to deliver the therapeutic electrical stimulation signal can be directly adjusted to adjust or switch between the constructive state or the destructive state. Additionally or alternatively, the change in resonance can be affected by the delivery of additional therapy (e.g., possibly at other sites in the patient's body) or can be an indication of some other change in the patient's body, and different parameters used to deliver the therapeutic electrical stimulation signal can be directly adjusted to adjust or switch between the constructive state or the destructive state based on the change in resonance.

[0072] Figure 1 is a conceptual diagram illustrating an example system 100 that includes an implantable medical device (IMD) 106 configured to deliver DBS therapy to a patient 112. In some examples, the DBS can be closed-loop, i.e., the IMD 106, as an example, can adjust, increase, or decrease the magnitude of one or more parameters of the DBS in response to changes in patient activity or movement, severity of one or more symptoms of the patient's disease, presence of one or more side effects due to the DBS, or one or more sensed signals from the patient.

[0073] For example, an example of system 100 is a bidirectional DBS system, which has the ability of delivering stimulation, sensing intrinsic neuron signals and sensing the neural signals induced in response to the delivery of stimulation.System 100 can be configured to treat patient conditions, such as movement disorders (e.g., ET, Parkinson's disease, etc.), neurodegenerative damage, mood disorders or epilepsy of patient 112.Patient 112 is usually a human patient.However, in some cases, treatment system 100 can be applied to other mammals or non-mammals, non-human patients.Although movement disorders and neurodegenerative damage are mainly mentioned herein, in other examples, treatment system 100 can provide treatment to manage the symptoms of other patient conditions, such as but not limited to epilepsy (e.g., epilepsy) or mood (or psychological) disorders (e.g., major depressive disorder (MDD), bipolar disorder, anxiety disorder, post-traumatic stress disorder, dysthymia and obsessive-compulsive disorder (OCD)).At least some of these obstacles can be manifested as one or more patient motor behaviors. As described herein, movement disorders or other neurodegenerative injuries can include symptoms such as muscle control impairment, motor impairment or other movement problems such as stiffness, spasticity, bradykinesia, rhythmic hyperkinesia, non-rhythmic hyperkinesia and akinesia. In some cases, movement disorders may be a symptom of Parkinson's disease or ET. However, movement disorders may be attributed to other patient conditions.

[0074] Example treatment system 100 includes medical device programmer 104, IMD 106, lead extension 110, and leads 114A and 114B with corresponding electrode sets 116, 118. Figure 1 In the example shown, the electrodes 116, 118 of the leads 114A, 114B are positioned to deliver electrical stimulation to a tissue site within the brain 120, such as a deep brain site beneath the dura mater of the brain 120 of the patient 112. In some examples, delivering stimulation to one or more regions of the brain 120, such as the STN, globus pallidus or thalamus, ventral media (VIM), anterior nucleus (ANT), ventral internal capsule / ventral striatum (VCVS), cortico-basal ganglia-thalamocortical loop, or anterior insular cortex (AIC) can be an effective treatment for managing disorders such as Parkinson's disease. Some or all of the electrodes 116, 118 may also be positioned to sense neural brain signals within the brain 120 of the patient 112. In some examples, some of the electrodes 116, 118 may be configured to sense neural brain signals, and other electrodes of the electrodes 116, 118 may be configured to deliver electrical stimulation to the brain 120. In other examples, all of electrodes 116, 118 are configured to sense neural brain signals and deliver electrical stimulation to brain 120. In some examples, with one electrode located on the housing of IMD 106, monopolar stimulation is possible.

[0075] IMD 106 includes a therapy module (e.g., which may include processing circuitry or other circuitry configured to perform functions attributed to IMD 106) that includes a stimulation generation circuit 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 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, a stimulation electrode combination may be selected (e.g., based on the patient's condition) for a particular patient 112 and target tissue site. Electrode groups 116, 118 include at least one electrode and may 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 locations around the perimeter of the respective leads.

[0076] In some examples, the neural signal sensed in the brain 120 may reflect the current change generated by the sum of the potential difference of the entire brain tissue. There may be various examples of neural brain signals that the electrodes 116 and 118 may be configured to sense. One example of a neural brain signal is LFP. LFP may be an intrinsic signal in the brain 120 of the patient 112, which is generated by a signal source in the brain 120 of the patient 112. Another example of a neural brain signal is an ERNA signal. The delivery of electrical stimulation in the brain 120 may induce an ERNA signal, and the difference between the ERNA signal and the intrinsic signal may be that the ERNA signal is a signal in the patient's brain induced due to or in response to the stimulation signal delivered to the brain. Electrical stimulation delivered in the brain 120 to induce an ERNA signal does not necessarily provide a therapeutic benefit, but a therapeutic benefit from the electrical stimulation for inducing an ERNA signal is possible. Electroencephalogram (EEG) signals or electrocorticogram (ECoG) signals are also examples of neural signals. For example, neurons generate a neural signal and if measured deep, the neural signal is LFP or ERNA (if evoked), if measured on the dura, the neural signal is ECoG, and if measured on the scalp, the neural signal is EEG.

[0077] In some examples, delivery of therapeutic electrical stimulation signals can be based on a feature of interest (e.g., a biomarker). An example of a feature of interest (e.g., a biomarker) within an LFP is synchronized beta band (8 Hz-33 Hz) LFP activity recorded within the sensorimotor region of the STN of a patient with Parkinson's disease or ET. The source of the LFP activity can be considered to be a signal source within the patient's brain that outputs an oscillating voltage signal sensed by one or more of electrodes 116 and / or 118. Inhibition of pathological beta activity by both drugs and DBS (e.g., inhibiting or clearing a signal component of a bioelectric signal generated by an LFP source in the beta band) can be associated with improvement in motor symptoms in patients with Parkinson's disease or essential tremor.

[0078] For example, one or more of the electrodes 116 and / or 118 may sense LFP activity. Thus, there may be multiple LFP measurements of the LFP, where each of the LFP measurements may be measured with a different electrode 116 and / or 118 on the leads 114A, 114B, or by the same electrode 116 and / or 118 on the leads 114A, 114B. As described, the LFP is inherently generated by a signal source (e.g., an oscillating voltage source) within the brain 120 of the patient 122.

[0079] In some examples, the neural brain signals used to select the stimulation electrode combination may be sensed in the same area of ​​the brain 120 as the target tissue site for electrical stimulation. As previously indicated, the target tissue site may include tissue sites within the anatomical structure (such as, the thalamus, STN, or globus pallidus of the brain 120) as well as other target tissue sites. Specific target tissue sites and / or regions within the brain 120 may be selected based on the patient's condition. Therefore, in some examples, both the stimulation electrode combination and the sensing electrode combination may be selected from the same set of electrodes 116, 118. In other examples, the electrodes used to deliver electrical stimulation may be different from the electrodes used to sense the neural brain signals.

[0080] The therapeutic electrical stimulation generated by the IMD 106 can be configured to manage various disorders and conditions. In some examples, the stimulation generation circuit of the IMD 106 is configured to generate therapeutic electrical stimulation pulses via electrodes of a selected stimulation electrode combination and deliver the therapeutic electrical stimulation pulses to the patient 112. However, in other examples, the stimulation generation circuit of the IMD 106 can be configured to generate and deliver a continuous wave signal, such as a sine wave or a triangle wave. In either case, the stimulation generation circuit within the IMD 106 can generate electrical stimulation therapy for DBS according to the selected treatment program. In an example in which the IMD 106 delivers therapeutic electrical stimulation in the form of stimulation pulses, the treatment program may include a set of treatment parameter values ​​(e.g., parameters), such as the stimulation electrode combination, pulse frequency, pulse width, and current or voltage amplitude of the pulse for delivering the stimulation to the patient 112. As previously noted, the electrode combination may indicate the specific electrodes 116, 118 selected for delivering the therapeutic stimulation signal to the tissue of the patient 112, and the corresponding polarity of the selected electrodes.

[0081] In some examples, electrodes 116, 118 may be a circumferentially segmented DBS electrode array and also include some non-segmented electrodes, such as ring electrodes. A circumferentially segmented DBS array refers to electrodes that are segmented circumferentially along the lead. As an example, leads 114A and 114B may include a first set of electrodes arranged circumferentially around leads 114A and 114B, which are all at the same height level on leads 114A and 114B. Each electrode in the first set of electrodes is a separate segmented electrode and forms a layer of a circumferentially segmented electrode array. Leads 114A and 114B may include a second set of electrodes arranged circumferentially around leads 114A and 114B, which are all at the same height level on leads 114A and 114B. Each electrode in the first set of electrodes is a separate segmented electrode and forms a layer of a circumferentially segmented electrode array. These electrodes may be beneficial by enabling directional stimulation and sensing.

[0082] Utilizing these electrodes, the IMD 106 may be configured to perform both directional stimulation and sensing, thereby enhancing the ability to target sources of LFP activity (also referred to as pathological neuronal activity). For example, the IMD 106 may be configured to perform directional sensing to determine the direction and / or orientation of an LFP source (e.g., a signal source that generates the LFP) that has a signal component in the beta band. As an example, the IMD 106 may direct electrical stimulation toward the signal source to suppress (e.g., eliminate) the signal component generated by the signal source in the beta band. The present disclosure describes example techniques for determining optimal parameters for therapeutic electrical stimulation signals using ERNA signals associated with constructive resonance states and destructive resonance states. The example techniques may be generally useful for DBS or other types of therapy in which constructive resonance states and destructive resonance states and ERNA signals are used as part of a closed-loop therapy.

[0083] In addition, the example techniques are not limited to examples in which one or more of electrodes 116, 118 are circumferentially segmented electrodes. Examples using circumferentially segmented electrodes are described as ways of directional stimulation and sensing. However, the example techniques may also be used in examples in which directional stimulation and sensing are not available or are not used. In addition, there may be other ways of performing directional stimulation and sensing that do not require the use of circumferentially segmented electrodes.

[0084] In one example, for DBS, the IMD 106 can 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 of the IMD 106 and / or leads 114A, 114B, the clinician / surgeon can determine initial parameters (e.g., a first set of one or more parameters of a first set of one or more therapeutic electrical stimulation signals). As described herein, constructive resonance states and destructive resonance states can be used in part to guide the programming of parameters of therapeutic electrical stimulation signals. For example, a clinician / surgeon can use the timing of the EP peak compared to the base resonance to determine the optimal stimulation frequency for constructive or destructive based on the desired resonance state. In addition, the clinician / surgeon can use the ERNA from a short burst of pulses to infer steady-state resonance behavior to optimize steady-state stimulation. By being able to infer steady-state from a short burst of pulses, the programming process can be shorter in time. Additionally, steady-state resonant behavior can be based on the alignment of the EP peak and basal resonance or based on other properties of the ERNA signal itself (e.g., shape, symmetry of peaks and valleys, damping rate of the response, etc.).

[0085] However, the effectiveness of the first set of one or more therapeutic electrical stimulation signals may change over time. For example, due to lead migration, adaptation of the neural substrate to stimulation, or worsening of the patient's condition, the first set of one or more therapeutic electrical stimulation signals may be insufficient to provide effective treatment. Conversely, if the patient's condition improves, the intensity of the first set of one or more therapeutic electrical stimulation signals may be greater than the intensity required to provide effective treatment.

[0086] Therefore, it may be beneficial to periodically or possibly continuously update the first set of one or more parameters to a second set of one or more parameters of the second set of one or more therapeutic electrical stimulation signals. In the above example, updating the initial parameters may be beneficial. However, in some cases, after updating the initial parameters, it may be beneficial to periodically or possibly continuously determine whether to update the parameters of the therapeutic electrical stimulation signals.

[0087] One way to update the parameters of the therapeutic electrical stimulation signal may be for the patient 112 to periodically schedule an appointment with the clinician to update the parameters. Another way to update the parameters of the therapeutic electrical stimulation signal may be for the patient 112 to manually adjust the parameters themselves. In both examples, the patient 112 may be burdened by the need to schedule an appointment for parameter adjustment or to titrate the parameters themselves, which may also result in delays in parameter updates.

[0088] The present 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 the parameters of the therapeutic electrical stimulation signal to maintain optimal resonance selection. In some embodiments, drug wash-in and drug wash-out (e.g., or other neurological states of patient 112) may cause slight changes in the base resonance, such that the processing circuitry of IMD 106 may adjust one or more parameters of the therapeutic electrical stimulation signal based on detecting the change to better maintain the desired resonant state. Additionally or alternatively, certain activities or movements may cause changes in the base resonance, and the processing circuitry of IMD 106 may adjust one or more parameters of the therapeutic electrical stimulation signal based on detecting the change to better maintain the desired resonant state.

[0089] In some embodiments, the processing circuitry of IMD 106 may be configured to perform closed-loop adjustments to switch resonant states based on changes in the neural state of patient 112 or based on the presence of a side effect. For 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 promote destructive resonance. Additionally or alternatively, if the processing circuitry of IMD 106 senses the presence of a side effect (e.g., a change in the ERNA signal, a side effect of the LFP signal, a change in accelerometer sensing, etc.), the processing circuitry of IMD 106 may switch from a constructive resonant state to a destructive resonant state (e.g., or vice versa) and adjust one or more parameters of the therapeutic electrical stimulation signal accordingly to support the switch or may add some jitter to the pulse timing to disrupt the resonant behavior.

[0090] An example method for determining parameters of a therapeutic electrical stimulation signal based on an ERNA signal is described below. However, the example technology is not limited thereto. For example, for initial parameters, a clinician can manually titrate the parameters until the correct parameters are identified for the initial therapeutic electrical stimulation signal.

[0091] For determining parameters based on the 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 one or more electrodes 116. In one or more examples, the plurality of electrical stimulation signals each include at least one different therapeutic parameter. For each of the plurality of electrical stimulation signals, the processing circuitry of IMD 106 may determine a corresponding ERNA signal, wherein the corresponding ERNA signal is induced by the delivery of the corresponding plurality of electrical stimulation signals. The processing circuitry may determine parameters of the therapeutic electrical stimulation signal based on the corresponding ERNA signal.

[0092] In the present disclosure, the phrase "therapeutic electrical stimulation signal" is used to refer to an electrical stimulation signal that is delivered for providing therapy. The delivery of a therapeutic electrical stimulation signal can induce an ERNA signal, but the technology does not require a therapeutic electrical stimulation signal to induce an ERNA signal. The phrase "electrical stimulation signal" is used to refer to an electrical stimulation signal that is delivered for inducing an ERNA signal. The delivery of an electrical stimulation signal for inducing an ERNA signal can provide a therapeutic effect, but the technology does not require an electrical stimulation signal for inducing an ERNA signal to provide a therapeutic effect.

[0093] As described above, the processing circuit may cause the stimulation generation circuit to deliver multiple electrical stimulation signals via the determined one or more electrodes, wherein the multiple electrical stimulation signals each include at least one different treatment parameter. For example, the processing circuit may cause the stimulation generation circuit to scan across a frequency range so that the frequency of each of the electrical stimulation signals is different. That is, the processing circuit may be configured to cause the stimulation generation circuit to deliver multiple electrical stimulation signals via the determined one or more electrodes, wherein the frequency of each of the multiple electrical stimulation signals is within a frequency range (e.g., 5 Hz to 220 Hz). As another example, the processing circuit may cause the stimulation generation circuit to scan across an amplitude and / or pulse width range so that the amplitude and / or pulse width of each of the electrical stimulation signals is different. That is, the processing circuit may be configured to cause the stimulation generation circuit to deliver multiple electrical stimulation signals via the determined one or more electrodes, wherein the amplitude and / or pulse width of each of the multiple electrical stimulation signals is within an amplitude and / or pulse width range.

[0094] The processing circuitry may evaluate the corresponding ERNA signal for determining parameters of the therapeutic electrical stimulation signal. For example, the processing circuitry may determine characteristics of the corresponding ERNA signal, such as resonant activity. Examples of resonant activity include one or more of peak-to-trough amplitude, peak-to-peak time, decay time constant, peak amplitude variation (e.g., damping), oscillation amount (e.g., number of peaks), rise or fall time, and frequency shift from early resonance to late resonance of the corresponding ERNA signal.

[0095] Based on the determined resonance activity, the processing circuit may select one of the ERNA signals. As an example, the processing circuit may select the ERNA signal with the highest peak-to-valley amplitude (e.g., constructive resonance state) of the corresponding ERNA signals. As another example, the processing circuit may select the ERNA signal with the most oscillations (e.g., the most number of peaks before the ERNA signal decays to the noise level) of the corresponding ERNA signals. As another example, the processing circuit may select the ERNA signal with the fastest peak amplitude reduction (e.g., the fastest damping) of the corresponding ERNA signals. Several non-limiting examples of resonance activity that the processing circuit may evaluate to select the ERNA signal are provided above, and other examples of resonance activity are also possible. Moreover, the processing circuit may select the ERNA signal based on a combination of resonance activities (e.g., a weighting of two or more examples of resonance activity).

[0096] The processing circuit may determine a corresponding electrical stimulation signal for the selected ERNA signal, and may determine parameters of the determined corresponding electrical stimulation signal. The processing circuit may determine parameters of the therapeutic electrical stimulation signal based on the determined parameters. In this manner, the processing circuit may determine parameters of the therapeutic electrical stimulation signal based on the corresponding ERNA signal.

[0097] IMD 106 may be implanted in a subcutaneous pocket above the clavicle, or alternatively, on or in skull 122, or at any other suitable site in patient 112. Generally, IMD 106 is constructed of biocompatible materials that resist corrosion and degradation by body fluids. IMD 106 may include a hermetic housing to substantially enclose components, such as a processor, a therapy module, and a memory.

[0098] like Figure 1 As shown, implant lead extension 110 is coupled to IMD 106 via connector 108 (also referred to as a connector block or connector of IMD 106). Figure 1 In the example of FIG. 1 , lead extension 110 is passed from the implantation site of IMD 106 and along the neck of patient 112 to skull 122 of patient 112 to enter brain 120. Figure 1 In the example shown, leads 114A and 114B (collectively referred to as "leads 114") are implanted in the right and left hemispheres of patient 112, respectively (or in some examples, only one hemisphere) to deliver electrical stimulation to one or more regions of brain 120, which may be selected based on a patient condition or disorder controlled by treatment system 100. However, a particular target tissue site and a stimulation electrode for delivering stimulation to the target tissue site may be selected, for example, based on identified patient behavior and / or other sensed patient parameters. Other lead 114 and IMD 106 implantation sites are contemplated. For example, in some examples, IMD 106 may be implanted on or in skull 122. In some examples, leads 114A and 114B may be implanted in the same hemisphere, or IMD 106 may be coupled to a single lead implanted in a single hemisphere.

[0099] Existing lead sets include axial leads carrying annular electrodes disposed at different axial positions and so-called "paddle" leads carrying planar electrode arrays. In some examples, more complex lead array geometries may be used.

[0100] Although lead 114 is Figure 1108. The leads 114 are shown as being coupled to a common lead extension 110, but in other examples, the leads 114 may be coupled to the IMD 106 via separate lead extensions or directly to the connector 108. The leads 114 may be positioned to deliver electrical stimulation to one or more target tissue sites within the brain 120 to manage patient symptoms associated with a movement disorder of the patient 112. The leads 114 may be implanted to position the electrodes 116, 118 at desired locations of the brain 120 through corresponding holes in the skull 122. The leads 114 may be placed at any location within the brain 120 so that the electrodes 116, 118 are able to provide electrical stimulation to target tissue sites within the brain 120 during treatment. For example, the electrodes 116, 118 may be surgically implanted beneath the dura mater of the brain 120 or within the cerebral cortex of the brain 120 via a burr hole in the skull 122 of the patient 112 and electrically coupled to the IMD 106 via one or more leads 114.

[0101] exist Figure 1 In the example shown, the electrodes 116, 118 of the lead 114 are shown as ring electrodes. Ring electrodes can be used in DBS applications because they are relatively easy to program and can deliver electric fields to any tissue adjacent to the electrodes 116, 118. In other examples, the electrodes 116, 118 may have different configurations. For example, at least some of the electrodes 116, 118 of the lead 114 may have a complex electrode array geometry that can generate a shaped electric field. The complex electrode array geometry may include multiple electrodes (e.g., partial rings or segmented electrodes) around the outer periphery of each lead 114, rather than one ring electrode. In this way, electrical stimulation can be guided from the lead 114 in a specific direction to enhance the therapeutic efficacy and reduce possible adverse side effects caused by stimulating a large amount of tissue. For example, one or more electrodes 116, 118 may be a circumferentially segmented DBS electrode array, and one or more electrodes 116, 118 may be non-segmented electrodes, such as ring electrodes, as described above. In some examples, the electrodes 116, 118 may be only circumferentially segmented DBS electrode arrays, and in some examples, the electrodes 116, 118 may be only non-segmented electrodes, such as ring electrodes.

[0102] In some examples, the housing of IMD 106 may include one or more stimulation and / or sensing electrodes. In some examples, lead 114 may have a plurality of electrodes other than Figure 1 For example, lead 114 may be a paddle lead, a ball lead, a bendable lead, or any other type of shape that is effective in treating patient 112 and / or minimizing the invasiveness of lead 114.

[0103] IMD 106 includes a memory for storing a plurality of treatment programs, each treatment program defining a set of treatment parameter values. In some examples, IMD 106 may select a treatment program from the memory based on various parameters (such as sensed patient parameters and identified patient behaviors). For example, as described above, the processing circuitry of IMD 106 may determine an update to the parameters of the therapeutic electrical stimulation signal based on the corresponding LFP measurement results and the ERNA signal. In some examples, IMD 106 may output information indicating the determined updated parameters for approval by a clinician. After approval, the processing circuitry of IMD 106 may store the determined parameters in the treatment program, and may be configured to cause the stimulation generation circuitry of IMD 106 to deliver the therapeutic electrical stimulation signal based on the determined parameters (e.g., by selecting a treatment program including the determined parameters by the processing circuitry).

[0104] That is, the stimulation generation circuit of IMD 106 can deliver a first set of one or more therapeutic electrical stimulation signals based on the first set of one or more parameters. Then, the processing circuit can 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 the constructive resonance state and the destructive resonance state, and cause the stimulation generation circuit to deliver the second set of one or more therapeutic electrical stimulation signals. The second set of one or more parameters can be an update to the first set of one or more parameters.

[0105] Delivery of the first set of one or more therapeutic electrical stimulation signals is not necessary in all cases. For example, a memory of IMD 106 or some other memory may store a first set of one or more parameters for the first set of one or more therapeutic electrical stimulation signals. The processing circuit may periodically update the first set of one or more parameters to a second set of one or more parameters based on the ERNA signal and the constructive resonance state and the destructive resonance state, as described in the present disclosure.

[0106] In some examples, clinician approval may not be necessary, such as in examples where the parameters of the determined therapeutic electrical stimulation signal are within a "safe range" specified 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 treatment program, and the stimulation generation circuitry may deliver the therapeutic electrical stimulation signal based on the determined parameters (e.g., by the processing circuitry selecting a treatment program that includes the determined parameters). In this manner, IMD 106 may generate therapeutic electrical stimulation based on the parameters of the selected treatment program to manage patient symptoms associated with the patient's disorder.

[0107] As an alternative or in addition to using a therapy program, in some examples, the processing circuitry may output information indicative of the determined parameters directly to the stimulation generation circuitry. Thus, there may be a variety of ways in which the processing circuitry may output information indicative of the determined parameters, such as to an external device (such as external programmer 104 as described below), a therapy program, or a stimulation generation circuitry.

[0108] The external programmer 104 wirelessly communicates with the IMD 106 as needed to provide or retrieve treatment information. The programmer 104 is an external computing device that a user (e.g., a clinician and / or a patient 112) can use to communicate with the IMD 106. For example, the programmer 104 may be a clinician programmer, which the clinician uses to communicate with the IMD 106 and program one or more treatment programs for the IMD 106. Alternatively, the programmer 104 may be a patient programmer that allows the patient 112 to select a program and / or view and modify treatment parameters. The clinician programmer may include more programming features than the patient programmer. In other words, only the clinician programmer may allow more complex or sensitive tasks to prevent untrained patients from making undesirable changes to the IMD 106.

[0109] When programmer 104 is configured for use by a 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 and electrode arrangement of leads 114, the location of leads 114 within brain 120, the configuration of electrode arrays 116, 118, an initial program defining therapy parameter values, and any other information that the clinician wishes to program into IMD 106. Programmer 104 may also be able to perform functional testing (e.g., measuring the impedance of electrodes 116, 118 of leads 114).

[0110] The clinician may also store treatment programs in the IMD 106 with the aid of the programmer 104. During a programming session, the clinician may determine one or more treatment programs that may provide effective treatment to the patient 112 to address symptoms associated with the patient's condition, and in some cases, symptoms specific to one or more different patient states (such as a sleeping state, a moving state, or a resting state). For example, the clinician may select one or more stimulation electrode combinations with which stimulation is delivered to the brain 120. During a programming session, the clinician may evaluate the efficacy of a particular program based on feedback provided by the patient 112 or based on one or more physiological parameters of the patient 112 (e.g., muscle activity, muscle tension, stiffness, tremor, etc.). In some examples, the ERNA signal may be used to evaluate the efficacy of the particular program being evaluated (e.g., a particular resonant activity in the ERNA signal may indicate an effective treatment). Alternatively, the identified patient behavior based on the video information may be used as feedback during the initial programming session and subsequent programming sessions. The programmer 104 may assist the clinician in creating / identifying treatment programs by providing a structured system for identifying potentially beneficial treatment parameter values.

[0111] 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) to prevent patient 112 from altering critical functions of IMD 106 or applications that may be harmful to patient 112. Thus, programmer 104 may only allow patient 112 to adjust values ​​of certain therapy parameters or set an available range of values ​​for a particular therapy parameter.

[0112] Programmer 104 may also provide indications to patient 112 when therapy is being delivered, when patient input has triggered a therapy change, or when a power source within programmer 104 or IMD 106 needs to be replaced or recharged. For example, programmer 104 may include an alert LED, may send messages to patient 112 via a programmer display, generate audible sounds, or physical cues to confirm receipt of patient input, such as to indicate patient status or to manually modify therapy parameters.

[0113] Furthermore, in some examples, the example techniques may be performed in the "cloud". For example, IMD 106 and / or programmer 104 may upload the ERNA signal 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 the present disclosure. Thus, in the present disclosure, the processing circuitry configured to perform the example techniques may be any one or a combination of the processing circuitry of IMD 106, the processing circuitry of programmer 104, and / or the processing circuitry of the cloud computing environment.

[0114] Therapeutic system 100 may be implemented to provide chronic stimulation therapy to patient 112 over the course of months or years. However, system 100 may also be used to evaluate therapy on a trial basis prior to full implantation. If implemented temporarily, certain components of system 100 may not be implanted in patient 112. For example, patient 112 may be fitted with an external medical device, such as a trial stimulator, instead of IMD 106. The external medical device may be coupled to a percutaneous lead or implanted lead via a percutaneous extension. If the trial stimulator indicates that DBS system 100 provides effective therapy to patient 112, the clinician may implant a chronic stimulator in patient 112 for relatively long-term therapy.

[0115] 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. Additionally, an IMD may provide other electrical stimulation, such as spinal cord stimulation, to treat movement disorders.

[0116] Figure 2 is used to deliver DBS therapy Figure 1 A block diagram of an example IMD 106 is shown. Figure 2 In the example shown, IMD 106 includes processing circuit 210, memory 212, stimulation generation circuit 202, sensing circuit 204, telemetry circuit 208, and power supply 220. Each of these circuits may be or include circuits configured to perform the functions attributed to each respective circuit. Memory 212 may include any volatile or non-volatile media, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, etc. Memory 212 may store computer-readable instructions that, when executed by processing circuit 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.

[0117] exist Figure 2 In the example shown, memory 212 stores EP measurements 214 and ERNA signals 216. EP measurements 214 may represent a first response measured by IMD 106 after applying a pulse (e.g., a single pulse, a first pulse, etc.) of a generated electrical stimulation signal. ERNA signal 216 may be information indicative of a second response induced by delivering a corresponding plurality of pulses of the generated electrical stimulation signal that IMD 106 delivers to induce a corresponding ERNA signal.

[0118] In one or more examples, the processing circuit 210 can utilize both the EP measurement 214 and the ERNA signal 216 to determine a constructive resonance state and a destructive resonance state to apply the generated electrical stimulation signal to the anatomical element as part of DBS therapy. For example, the memory 212 can store data for performing the resonance state determination 218. As part of the resonance state determination 218, the processing circuit 210 can extract a first set of timings corresponding to the peaks and valleys of the EP measurement 214, and can extract a second set of timings corresponding to the peaks and valleys of the ERNA signal 216. Subsequently, the constructive resonance state can include a state in which the peak of the EP measurement 214 will be aligned with a first portion (e.g., a "rising edge") or peak of the ERNA signal 216 (e.g., a base resonance response), and the destructive resonance state can include a state in which the peak of the EP measurement 214 will be aligned with a second portion (e.g., a "falling edge") or valley of the ERNA signal 216. Additionally or alternatively, the processing circuit 210 may utilize both the EP measurement results 214 and the ERNA signal 216 to determine a degree of constructive resonance state and / or destructive resonance state to apply the generated electrical stimulation signal to the anatomical element as part of DBS treatment. For example, the degree of constructive resonance state and / or destructive resonance state may include a resonance state that is not completely constructive, not completely destructive, neither constructive nor destructive, or a combination of constructive and destructive.

[0119] In some embodiments, the processing circuit 210 can calculate steady-state ERNA behavior based on constructive concepts and destructive concepts (e.g., constructive resonant state and destructive resonant state) as part of the resonance state determination 218. Subsequently, stimulation parameters for applying the generated stimulation signal can be determined based on a comparison of the EP peak (e.g., the first set of timings from the EP measurements 214) and the steady-state ERNA behavior.

[0120] Stimulation generation circuit 202 generates stimulation signals (e.g., electrical stimulation signals for inducing ERNA signals and / or therapeutic electrical stimulation signals for delivering therapy) under the control of processing circuit 210 for delivery to patient 112 via electrodes 116, 118. Example ranges of electrical parameters that are believed to be effective in DBS for managing movement disorders in patients include:

[0121] a. Pulse rate (ie, frequency): between about 5 Hertz (Hz) and about 500 Hz, such as between about 5 Hz and 220 Hz, or such as about 130 Hz.

[0122] b. In case of a voltage controlled system, voltage amplitude: between about 0.1 volts (V) and about 50V, such as between about 2V and about 3V.

[0123] c. In the case of a current control system, current amplitude: between about 0.1 milliamperes (mA) to about 3.5 mA, such as between about 1.0 mA and about 1.75 mA.

[0124] d. Pulse width: between about 20 microseconds (μs) and about 500 μs, such as between about 50 μs and about 200 μs.

[0125] Thus, in some examples, the stimulation generation circuit 202 generates a therapeutic electrical stimulation signal based on the electrical parameters described above. For example, the processing circuit 210 may determine the parameters of the therapeutic electrical stimulation signal using the example techniques described in the present disclosure (e.g., based on the evaluation of the EP measurement results 214 and the ERNA signal 216 and determining the constructive resonance state and the destructive resonance state), and the stimulation generation circuit 202 may deliver the therapeutic electrical stimulation signal. Other ranges of therapeutic parameter values ​​may also be useful and may depend on the target stimulation site in the patient 112. Although stimulation pulses are described, the stimulation signal may have any form, such as a continuous time signal (e.g., a sine wave), etc.

[0126] In addition to delivering therapeutic electrical stimulation signals, the stimulation generation circuit 202 may also be configured to deliver electrical stimulation signals for inducing ERNA signals (e.g., where information indicating the ERNA signals is stored as the ERNA signals 216). Example parameters of the electrical stimulation signals for inducing ERNA signals include an amplitude in the range of 0 mA to 7.5 mA (such as 0 mA to 5 mA), a frequency in the range of 5 Hz to 250 Hz (such as 80 Hz to 220 Hz), and a pulse width in the range of 20 microseconds to 450 microseconds (such as 60 microseconds to 120 microseconds).

[0127] Processing circuitry 210 may include fixed function processing circuitry and / or programmable processing circuitry, and may include, for example, one or more of the following: 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 functionality attributed to processing circuitry 210, which may be embodied herein as firmware, hardware, software, or any combination thereof. Processing circuitry 210 may control stimulation generation circuitry 202 according to a therapy program stored in memory 212 to apply specific parameter values, such as voltage or current amplitude, pulse width, and / or pulse frequency, specified by one or more of the programs.

[0128] In some embodiments, the memory 212 can store additional data for performing stimulation adjustment 220 for adjusting one or more parameters of the electrical stimulation signal generated by the stimulation generation circuit 202. For example, the stimulation adjustment 220 can be performed to maintain or switch a desired resonance state (e.g., a constructive resonance state or a destructive resonance state or a degree of constructive resonance state or a destructive resonance state). In one example, as part of the stimulation adjustment 220, the processing circuit 210 can apply the electrical stimulation signal generated by the stimulation generation circuit 202 to the anatomical element according to a first resonance state, wherein the first resonance state includes at least a degree of constructive resonance state or 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, the processing circuit 210 can monitor the change in peak-to-valley amplitude between each pulse of the generated electrical stimulation signal (e.g., from the EP measurement result 214), and determine the phase comparison shift between the ERNA signal 216 (e.g., the basic resonance response) and the EP measurement result 214 based on the detected change in the peak-to-valley amplitude. Thus, processing circuitry 210 may adjust one or more parameters for applying the electrical stimulation signal generated by stimulation generation circuitry 202 based on determining the phase alignment shift to align the EP peak (e.g., determined from EP measurement results 214) with ERNA signal 216 to maintain the first resonant state. In some examples, as part of stimulation adjustment 220, processing circuitry 210 may review ERNA signal 216 to confirm the phase alignment shift by inhibiting (e.g., pausing) application of the generated electrical stimulation signal for one or more pulses (e.g., skipping or discarding one or more pulses when applying the generated electrical stimulation signal).

[0129] Additionally or alternatively, as part of stimulation adjustment 220, processing circuit 210 may apply an electrical stimulation signal generated by stimulation generation circuit 202 to an anatomical element according to a first resonance state (e.g., a constructive resonance state or a destructive resonance state or a degree of constructive resonance state and / or destructive resonance state), and may monitor side effects caused by applying the electrical stimulation signal according to the first resonance state. In some examples, the side effects may include changes in ERNA signal 216, LFP signal side effects, changes in accelerometer signals (e.g., indicating movement or inactivity of a patient, indicating a patient's posture, etc.), or a combination thereof. Subsequently, based on detecting the side effects, processing circuit 210 may adjust the resonance state of the generated electrical stimulation signal, and may adjust one or more parameters of the generated electrical stimulation signal according to the adjusted resonance state to align an EP peak (e.g., determined from EP measurement results 214) with ERNA signal 216, thereby applying the generated electrical stimulation signal. In some examples, adjusting the resonance state can include adjusting the first resonance state to have less constructive resonance (e.g., adjusting the degree of the constructive resonance state), shifting the EP peak away from the peak of the ERNA signal 216, switching from the first resonance state to a second resonance state (e.g., an opposite state of the constructive resonance state or the destructive resonance state configured for the first resonance state), adjusting the pulse timing of the generated electrical stimulation signal, or a combination thereof.

[0130] Additionally or alternatively, as part of the resonance state determination 218, the processing circuit 210 may first assign a constructive resonance state or a destructive resonance state to each of the plurality of neural states, such that when a neural state is detected, the processing circuit 210 may apply the generated electrical stimulation signal to the anatomical element according to the assigned constructive resonance state or destructive resonance state of the detected neural state. For example, the plurality of neural states may include, but are not limited to, an awake state, a sleeping state, a medication state, a drug withdrawal state, an anesthesia depth state, a disease progression state, a drug wash-in state, a drug wash-out state, a motion state (e.g., whether the patient is moving, such as indicated by an accelerometer), a patient's posture (e.g., upright, lying down, etc.), or different neural states. Subsequently, as part of stimulation adjustment 220, processing circuit 210 may monitor a change from the detected neural state to a second neural state among a plurality of neural states (e.g., a second neural state corresponding to a different assigned resonance state of the detected neural state), switch the resonance 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 of the generated electrical stimulation signal according to the switched resonance state to align the EP peak (e.g., determined from EP measurement results 214) with the ERNA signal 216, thereby applying the generated electrical stimulation signal.

[0131] The sensing circuit 204 is configured to monitor signals from any combination of electrodes 116, 118. Figure 2 Although incorporated into a common housing with stimulation generation circuitry 202 and processing circuitry 210 in the IMD 106, in other examples, sensing circuitry 204 may be located in a housing separate from IMD 106 and may communicate with processing circuitry 210 via wired or wireless communication techniques.

[0132] In some examples, the sensing circuit 204 includes one or more amplifiers, filters, and analog-to-digital converters. The sensing circuit 204 can 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, the sensing circuit 204 measures EP and ERNA signals from a specific combination of electrodes 116, 118. In some cases, the specific combination of electrodes used for sensing includes electrodes different from a set of electrodes 116, 118 used to deliver electrical stimulation signals (e.g., therapeutic electrical stimulation signals or electrical stimulation signals for inducing ERNA signals). Alternatively, in other cases, the specific combination of electrodes used for sensing includes at least one electrode in the same set of electrodes as a set of electrodes used to deliver stimulation signals to the patient 120. The sensing circuit 204 can provide a signal to the analog-to-digital converter for conversion into a digital signal for processing, analysis, storage, or output by the processing circuit 210.

[0133] The electrodes 116, 118 on the respective leads 114 may be constructed of a variety of different designs. For example, one or both of the leads 114 may include two or more electrodes (such as a plurality of electrodes) at each longitudinal position along the length of the lead, e.g., the electrodes are arranged in segments at different peripheral positions around the perimeter of the lead at each of the positions.

[0134] As an example, one or both of leads 114 may include circumferentially segmented DBS electrode arrays and non-segmented electrodes (e.g., ring electrodes). As an example, at a first longitudinal position (e.g., position A) on lead 114A, there may be a first ring electrode of electrode 116 around the periphery of lead 114A. Below the first ring electrode, at a second longitudinal position (e.g., position B) on lead 114A, there may be three segmented electrodes of electrode 116 around the periphery of lead 114A. Below these three segmented electrodes, there may be another set of three segmented electrodes of electrode 116 around the periphery of lead 114A at a third longitudinal position (e.g., position C) of lead 114A. Below these three segmented electrodes, there may be a second ring electrode of electrode 116 around the periphery of lead 114A (e.g., position D). Electrode 118 may be similarly positioned along lead 114B.

[0135] The above is one example of an electrode array, and the example technology should not be considered limited to such examples. There may be other electrode configurations for DBS. Furthermore, the example technology is not limited to DBS, and other electrode configurations are also possible.

[0136] In one example, the electrodes 116, 118 can be electrically coupled to the stimulation generation circuit 202 and the sensing circuit 204 via respective wires that are straight or coiled within the housing of the lead and extend to a connector at the proximal end of the lead. In another example, each of the electrodes 116, 118 of the lead 114 can be an electrode deposited on a film. The film may include a conductive trace for each electrode that extends along the length of the film to the proximal connector. The film can then be wrapped (e.g., spirally wrapped) around the internal member to form the lead 114. These and other configurations can be used to form leads with complex electrode geometries.

[0137] Telemetry circuitry 208 supports wireless communication between IMD 106 and external programmer 104 or another computing device under the control of processing circuitry 210. Processing circuitry 210 of IMD 106 may receive values ​​of various parameters (such as magnitudes and electrode combinations) from programmer 104 via telemetry circuitry 208 as updates to the program. Telemetry circuitry 208 in IMD 106 and telemetry modules (such as programmer 104) in other devices and systems described herein may communicate via radio frequency (RF) communication techniques. In addition, telemetry circuitry 208 may communicate with external medical device programmer 104 via proximal sensing interaction of IMD 106 with programmer 104. Thus, 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.

[0138] Power supply 220 delivers operating power to various components of IMD 106. Power supply 220 may include a small rechargeable or non-rechargeable battery and a power generation circuit to generate 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, the power requirements may be small enough to allow IMD 104 to utilize patient motion and implement a kinetic energy scavenging device to trickle charge the rechargeable battery. In other examples, conventional batteries may be used for a limited time.

[0139] The DBS treatment is defined by one or more treatment programs having one or more parameters stored in the memory 212. For example, the one or more parameters include current amplitude (for a current control system) or voltage amplitude (for a voltage control system), pulse frequency or frequency, and pulse width, or the number of pulses per cycle. In examples where 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 also define one or more of the number of pulses per burst, the on time, and the off time. The processing circuit 210 delivers DBS to the patient 120 via the electrodes 116, 118, and may adjust the one or more parameters defining the electrical stimulation based on corresponding parameters of one or more signals of the sensed brain 120.

[0140] Figure 3 yes Figure 1 1 is a block diagram of an external programmer 104. Although programmer 104 may be generally described as a handheld device, programmer 104 may be a larger portable device or a more fixed device. Furthermore, in other examples, programmer 104 may be included as part of an external charging device or include the functionality of an external charging device. Figure 3 As illustrated, programmer 104 may include processing circuitry 310, memory 312, user interface 302, telemetry circuitry 308, power supply 320, resonance state assignment 306, and stimulation adjustment 304. Throughout the present disclosure, memory 312 may store instructions that, when executed by processing circuitry 310, cause processing circuitry 310 and external programmer 104 to provide the functionality attributed to external programmer 104. Each of these components or modules may include circuitry configured to perform some or all of the functionality described herein. For example, processing circuitry 310 may include circuitry configured to perform the functions described in reference to Figure 2 Processing circuitry for the processes discussed herein is described with respect to processing circuitry 210 of IMD 106. In some examples, programmer 104 may include or may be referred to as a signal generator (eg, combined with or separate from IMD 106).

[0141] In general, programmer 104 includes any suitable hardware arrangement, 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, such as formed by, for example, one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, and any combination of such components. In various examples, programmer 104 may also include memory 312 (such as, RAM, ROM, PROM, EPROM, EEPROM, flash memory, hard disk, CD-ROM) that includes executable instructions for causing one or more processors to perform actions attributed to them. In addition, 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 each other. In some examples, processing circuit 310 and telemetry circuit 308 correspond to respective hardware units, such as an ASIC, DSP, FPGA, or other hardware units.

[0142] Throughout the present disclosure, memory 312 (e.g., a storage device) may store instructions or data that, when executed by processing circuit 310, cause processing circuit 310 and programmer 104 to provide functionality attributed to programmer 104. For example, memory 312 may include instructions that cause processing circuit 310 to obtain a parameter set from memory or receive user input and send a corresponding command to IMD 106, or instructions for any other functionality. Furthermore, memory 312 may include a plurality of programs, where each program includes a parameter set that defines a stimulation therapy.

[0143] The user interface 302 may include buttons or a keypad, lights, a speaker for voice commands, a display such as a liquid crystal (LCD), a light emitting diode (LED), or an organic light emitting diode (OLED). In some examples, the display may be a touch screen. The user interface 302 may be configured to display any information related to the delivery of the stimulation therapy, the identified patient behavior, the sensed patient parameter values, the patient behavior criteria, or any other such information. The user interface 302 may also receive user input via the user interface 302. The input may be in the form of, for example, pressing a button on a keypad or selecting an icon from a touch screen.

[0144] 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 directly with another computing device via a wired connection. In some examples, telemetry circuitry 308 provides wireless communication via RF or a proximal inductive medium. In some examples, telemetry circuitry 308 includes an antenna, which may take a variety of forms, such as an internal antenna or an external antenna.

[0145] Examples of local wireless communication technologies that can be used to facilitate communication between programmer 104 and IMD 106 include RF communication according to the 802.11 or Bluetooth specification set or other standard or proprietary telemetry protocols. In this way, other external devices may be able to communicate with programmer 104 without establishing a secure wireless connection.

[0146] In some examples, processing circuitry 310 of external programmer 104 defines parameters of the electrical stimulation therapy stored in memory 312 to deliver DBS to patient 120. In one example, processing circuitry 310 of external programmer 104 issues commands to IMD 106 via telemetry circuitry 308, causing IMD 106 to deliver the electrical stimulation therapy via electrodes 116, 118 via leads 114.

[0147] In one or more examples, programmer 104 can be configured to perform one or more of the example techniques described in this disclosure. For example, processing circuit 310 can be configured to perform one or more of the example operations described above with respect to processing circuit 210.

[0148] For example, processing circuit 310 may be configured to cause stimulation generation circuit 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 example, processing circuit 310 may output the first set of one or more parameters to IMD 106 for storage, and stimulation generation circuit 202 may use the first set of one or more parameters to deliver the first set of one or more therapeutic electrical stimulation signals.

[0149] In addition, processing circuit 310 can be configured to perform resonance state assignment 306. Resonance state assignment 306 can include processing circuit 310 that assigns a constructive resonance state or a destructive resonance state to each of a plurality of neural states. In some examples, resonance state assignment 306 can be indicated or performed based on input from a clinician to assign a corresponding resonance state to each neural state. Thus, when a neural state is detected, a plurality of parameters of the therapeutic electrical stimulation signal can be determined by processing circuit 310 based on the resonance state assigned to the detected neural state.

[0150] It should be understood that in some embodiments, the resonance statement distribution 306 can be applied bidirectionally, wherein two different neural states are distributed. In such instances, each of the two different neural states is tracked independently, and multiple parameters of the therapeutic electrical stimulation signal can be determined for each of the two different neural states. In addition, multiple parameters of the therapeutic electrical stimulation signal for each neural state in the two different neural states can be adjusted or updated independently. In addition, in some instances, deep brain stimulation can be applied to the subthalamic nucleus in each hemisphere of the patient's brain. In such instances, the stimulation may or may not independently cause oscillations. Such oscillations can also be dependent on each other, which can be used to associate or connect the simulated timing of two different neural states.

[0151] As an example, the resonance state assignment 306 may be initially performed in the clinic, where a physician or clinician may set the neural state to include a constructive resonance state. Subsequently, the physician or clinician may observe how the constructive resonance state treats the patient's symptoms (e.g., whether the constructive resonance state makes the patient feel comfortable). In some examples, the patient may switch between a constructive resonance state and a destructive resonance state for a neural state or for different neural states. Therefore, in some embodiments, the programmer 104 may determine or learn the patient's tendency for the resonance state assignment 306 (e.g., whenever the patient moves, the patient turns off the constructive resonance state). Subsequently, the programmer 104 may actively change the resonance state assignment 306 so that the processing circuit 310 adjusts the parameters of the generated electrical stimulation signal to use the destructive resonance state when the patient moves. That is, the programmer 104 (e.g., and / or the IMD 106) may employ a deep learning model (e.g., an artificial intelligence (AI) type algorithm) to learn how the patient adjusts or switches between resonance states, and then automatically builds the learning into assigning resonance states or adjusting parameters in a closed-loop system.

[0152] In some embodiments, programmer 104 may be configured to perform the Figure 2 For example, programmer 104 can be configured to perform stimulation adjustment 304 for adjusting one or more parameters of a therapeutic electrical stimulation signal (e.g., generated by stimulation generation circuit 202) to maintain a desired resonant state or to switch resonant states, wherein stimulation adjustment 304 can be similar to that described by reference 104. Figure 2 1. The techniques for stimulation adjustment 220 performed by IMD 106 are described herein.

[0153] As an example, programmer 104 may use processing circuitry 310 to maintain a resonant state of the patient based on stimulation adjustment 304, resonant state assignment 306, or both. For example, programmer 104 (e.g., and / or IMD 106) may realize that maintaining a constructive resonant state while the patient is awake provides the patient with the best symptom relief, but maintaining a destructive resonant state while the patient is asleep provides the patient with the best symptom relief. Thus, the physician or clinician may program programmer 104 to modulate stimulation (e.g., adjust magnitude, amplitude, frequency, etc.) in a closed-loop manner while the patient is awake to maintain a constructive resonant state. Additionally or alternatively, while maintaining a constructive resonant state, processing circuitry 310 (e.g., and / or processing circuitry 210) begins to see side effects manifest. Thus, processing circuit 310 may perform stimulation adjustment 304 such that stimulation parameters used to apply the therapeutic electrical stimulation signal correspond to a slightly less constructive resonance state (e.g., not a completely destructive resonance state) to slightly shift the EP peak away from the peak of the ERNA signal (e.g., adjust the magnitude of the resonance state).

[0154] Additionally or alternatively, as part of stimulation adjustment 304, processing circuitry 310 (e.g., and / or processing circuitry 210) may change the resonant state (e.g., from constructive to destructive or vice versa) based on the patient's neural state (e.g., sleeping and awake). As a non-limiting example, a destructive resonant state may be assigned to a patient's sleeping state, but a constructive resonant state may be assigned and maintained for the patient when the patient is awake. Additionally or alternatively, programmer 104 and processing circuitry 310 (e.g., and / or IMD 106 and processing circuitry 210) may maintain a constructive resonant state when the patient is moving and active (e.g., as indicated by an accelerometer), but a destructive resonant state may be maintained when the patient is not moving and / or sitting still in a chair (e.g., as indicated by an accelerometer). Additional components not explicitly listed herein may be used to determine when to change to a desired resonant state. In some embodiments, additional components (eg, such as accelerometers) may be housed or part of the components previously described for DBS therapy (eg, IMD 106), or may be separate components.

[0155] Figure 4 is an example stimulus response 400 according to at least one embodiment of the present disclosure. The example stimulus response 400 may be implemented Figures 1 to 3 For example, the example stimulation response 400 may represent applying an electrical stimulation signal (e.g., a therapeutic electrical stimulation signal) to an anatomical element of a patient (e.g., the brain, STN, other regions of the brain, spine, etc.) as a reference. Figures 1 to 3 A neural response as a portion of DBS therapy (eg, or other types of therapy) is described (such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.).

[0156] The example stimulation response 400 may represent the application of an electrical stimulation signal using multiple stimulation pulses 402A-402J (e.g., a burst including multiple stimulation pulses 402). When the electrical stimulation signal is applied to an anatomical element of the patient, each single stimulation pulse 402 may elicit an EP response 404 due to activation of a local neural circuit. Stimulation of the anatomical element may activate a local neural circuit such that the Ep in the sensing anatomical element (e.g., via electrodes 116, 118) will also exhibit a response to a given stimulation pulse 402, in addition to any additional feedback or basal activity from similarly activated connected structures near the anatomical element. When multiple stimulation pulses 402 are delivered, the EP response 404 elicited from each stimulation pulse 402 may be added to the basal activity of feedback from a complex neural network near the anatomical element.

[0157] With continuous stimulation pulses 402, the sensed signal from DBS therapy (e.g., which is equal to the EP response 404 from each stimulation pulse 402 plus the basal ongoing activity from the previous pulse) can exhibit resonant behavior, which is referred to as ERNA 406. For example, ERNA 406 (e.g., ERNA signal) is not an intrinsic signal within the patient's anatomical element, but is induced as a result of the electrical stimulation signal being delivered to the anatomical element. The stimulation signal delivered to the brain that induces ERNA 406 does not necessarily provide any therapeutic benefit, but the stimulation signal that induces ERNA 406 has the potential to provide a therapeutic benefit.

[0158] In some embodiments, ERNA 406 can be generated based on applying an electrical stimulation signal to an anatomical element using a burst of multiple stimulation pulses 402 and then pausing the application of the electrical stimulation signal for a certain period of time (e.g., 30 ms or a different period of time) after the burst of multiple stimulation pulses. Subsequently, the neural response captured during this period of time can represent ERNA 406. Figure 4 As shown in the example stimulation response 400 of FIG. 4 , time instance 408 may represent a time at which the next occurring stimulation pulse 402 should have occurred after stimulation pulse 402J but did not occur based on pausing and / or inhibiting the application of the electrical stimulation signal (e.g., a time gap) to enable capture of ERNA 406. If a stimulation pulse is delivered at time instance 408, the evoked response (e.g., EP response 404) will be added to any underlying activity (e.g., ERNA 406) from the previous stimulation pulse 402.

[0159] Although ten 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. Properties of the ERNA 406 (e.g., sensed signal, base resonance, base resonance signal, base activity, etc.) may change when additional stimulation pulses 402 are added. For example, the peak-to-trough amplitude 410, peak latency (e.g., inter-peak timing), number of resonance peaks, etc. may depend on how many stimulation pulses 402 are used when applying the electrical stimulation signal. That is, multiple stimulation pulses 402 may induce activity that is additive to the base activity (e.g., ERNA 404). For example, when more consecutive stimulation pulses 402 are used to apply the electrical stimulation signal to the anatomical element, the peak of the EP response 404 after each stimulation pulse 402 can be greater than the peak of the EP response 404 for fewer stimulation pulses, there can be a larger peak-to-trough amplitude 410 after each stimulation pulse 402 (e.g., compared to applying the electrical stimulation signal using fewer stimulation pulses 402), there can be a shorter latency between each peak of the ERNA 406, there can be a greater number of resonance peaks (e.g., more prominent resonance activity) in the ERNA 406, or a combination thereof. In general, when more stimulation pulses 402 of an electrical stimulation signal for DBS therapy are delivered, the EP response 404 from each individual stimulation pulse 402 adds to any basal activity, thereby changing the nature of the resonance (e.g., ERNA 404) seen after the burst of stimulation pulses 402.

[0160] Figure 5 is a set of example stimulation responses 500 with different numbers of stimulation pulses according to at least one embodiment of the present disclosure. The set of example stimulation responses 500 may implement Figures 1 to 4 For example, the set of example stimulation responses 500 may represent the results of applying an electrical stimulation signal (e.g., a therapeutic electrical stimulation signal) to an anatomical element of a patient (e.g., the brain, STN, other regions of the brain, spine, etc.) as a reference. Figures 1 to 4 Different neural responses as part of a DBS therapy (eg, or other type of therapy) are described (such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.).

[0161] As previously described, when additional stimulation pulses are added or used when applying an electrical stimulation signal to an anatomical element, the properties of the sensed signal (e.g., peak-to-trough amplitude, peak latency, number of resonance peaks, etc.) may change. For example, the set of example stimulation responses 500 may include: a first stimulation response 502A including one (1) stimulation pulse, a second stimulation response 502B including two (2) stimulation pulses, a third stimulation response 502C including three (3) stimulation pulses, a fourth stimulation response 502D including four (4) stimulation pulses, a fifth stimulation response 502E including five (5) stimulation pulses, a sixth stimulation response 502F including six (6) stimulation pulses, a seventh stimulation response 502G including seven (7) stimulation pulses, an eighth stimulation response 502H including eight (8) stimulation pulses, a ninth stimulation response 502I including nine (9) stimulation pulses, and a tenth stimulation response 502J including ten stimulation pulses.

[0162] As more stimulation pulses of the electrical stimulation signal for DBS therapy are delivered, the EP response 504 from each individual stimulation pulse adds to any underlying activity, thereby changing the properties of the resonance (e.g., the corresponding ERNA 506 of each stimulation response) seen after the burst of stimulation pulses. For example, each corresponding ERNA response 506 of each stimulation response 502 may include properties that are different from the other ERNA responses 506. The ERNA responses 506 may represent the resonance of the same frequency (e.g., Figure 5 110 Hz in the example, but not limited to such frequencies). As the number of stimulation pulses increases, the resonant activity in the corresponding ERNA response 506 becomes more prominent. For example, the peak value of the EP response 504 after each stimulation pulse increases as the number of stimulation pulses increases (e.g., the peak-to-trough values ​​of the EP response 504 of the ERNA response 506J appear to be larger than the previous ERNA response 506), the peak-to-trough amplitude of the EP response 504 increases as the number of stimulation pulses increases (e.g., increases to a point where the peak-to-trough amplitude does not continue to increase as more and more pulses are added), there is a different latency (e.g., shorter or longer) between each peak of the ERNA response 506 as the number of stimulation pulses increases, there may be a greater number of resonant peaks in the ERNA response 506 as the number of stimulation pulses increases, or a combination thereof.

[0163] Fig. 6A is a set of example stimulus responses 600 at different frequencies according to at least one embodiment of the present disclosure. The set of example stimulus responses 600 may be implemented Figures 1 to 5For example, the set of example stimulation responses 600 may represent the results of applying an electrical stimulation signal (e.g., a therapeutic electrical stimulation signal) to an anatomical element of a patient (e.g., the brain, STN, other regions of the brain, spine, etc.) as a reference. Figures 1 to 5 Different neural responses as part of a DBS therapy (eg, or other type of therapy) are described (such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.).

[0164] like Fig. 6A As shown in the example of, the set of stimulation responses 600 includes different stimulation responses for different stimulation frequencies (e.g., different indicated frequencies between 80 Hz and 180 Hz). The properties of the ERNA response (e.g., initial peak-to-valley amplitude, resonant frequency, damping of the peak, shift of the peak / valley latency, etc.) can be different for different stimulation frequencies. Each stimulation response in the set of stimulation responses 600 can represent an example ERNA response after a burst of 10 stimulation pulses is delivered to the electrical stimulation signal at a specified frequency. As illustrated in the set of stimulation responses 600, there may be variability in the peak-to-valley amplitude, the number of resonance peaks, and the latency of the peaks between different frequencies.

[0165] exist Figure 5 Unlike the illustrated example, in which the properties of the ERNA response generally improve or increase with increasing number of stimulation pulses, an increase in frequency does not necessarily correspond to an improvement or increase in properties. Some of the lower frequencies include higher peaks and larger peak-to-trough amplitudes of the EP response than frequencies in the middle of the frequency range shown.

[0166] Figure 6B is a method according to at least one embodiment of the present disclosure corresponding to Fig. 6A A set of measurements 602 of a set of example stimulation responses 600 at different frequencies of the set of example stimulation responses 600. A first measurement 604 may represent a first peak-to-trough amplitude for each stimulation frequency from the set of example stimulation responses 600 after a burst of stimulation pulses, a second measurement 606 may represent a first peak latency for each stimulation frequency from the set of example stimulation responses 600 after a burst of stimulation pulses (e.g., how long after the burst of stimulation pulses the first peak occurs), a third measurement 608 may represent a second peak latency for each stimulation frequency from the set of example stimulation responses 600 after a burst of stimulation pulses (e.g., how long after the burst of stimulation pulses the second peak occurs), and a fourth measurement 610 may represent a third peak latency for each stimulation frequency from the set of example stimulation responses 600 after a burst of stimulation pulses (e.g., how long after the burst of stimulation pulses the third peak occurs). There is no strong correlation between the set of measurements 602 and increasing stimulation frequencies for applying electrical stimulation signals to anatomical elements.

[0167] As described herein, the properties of the ERNA response (e.g., peak-to-trough amplitude, peak latency, number of resonance peaks, etc.) can vary based on the relationship between the timing of the evoked response from the 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 multiple stimulation pulses). That is, a comparison of the EP response elicited by the stimulation pulse to the underlying activity can determine or correspond to certain properties of the ERNA response. Thus, intrinsic EP latency plays a role, not just the timing of the stimulation pulse. In some examples, the timing of the EP latency may vary from patient to patient (e.g., based on anatomy, disease state, neural state, etc.). Thus, as in Figure 6B The variability in ERNA properties due to different stimulation frequencies seen in the examples of is due to differences in the phase alignment of the immediate EP with the basal activity, where the sensed ERNA signal then exhibits signs of constructive or destructive resonance as described herein.

[0168] Figure 7 700 is an example graph of a constructive / destructive concept in accordance with at least one embodiment of the present disclosure. For example, the example graph 700 may include a sine wave 702. The sine wave 702 is divided into six (6) different fundamental resonance zones, which illustrate how the location of the EP peak after a stimulation pulse of an electrical stimulation signal can affect subsequent resonance activity. A first zone 704 may represent a valley of the sine wave 702 where a destructive resonance will exist between the EP peak and the fundamental resonance activity (e.g., ERNA) from a previous stimulation pulse. A second zone 706 may represent another region of the sine wave 702 with a destructive resonance that will exist between the EP peak and the fundamental resonance activity (e.g., ERNA) from a previous stimulation pulse. A third zone 708 may represent a region of the sine wave 702 with a constructive resonance that will exist between the EP peak and the fundamental resonance activity (e.g., ERNA) from a previous stimulation pulse. The fourth zone 710 may represent a peak of the sine wave 702 where a constructive resonance will exist between the EP peak and the underlying resonant activity (e.g., ERNA) from the previous stimulation pulse. The fifth zone 712 may represent another region of the sine wave 702 having a constructive resonance that will exist between the EP peak and the underlying resonant activity (e.g., ERNA) from the previous stimulation pulse. The sixth zone 714 may represent another region of the sine wave 702 having a destructive resonance that will exist between the EP peak and the underlying resonant activity (e.g., ERNA) from the previous stimulation pulse.

[0169] As used and described herein, the third zone 708, the fourth zone 710, and the fifth zone 712 (e.g., the "positive half" of the sine wave 702) may be referred to as a first portion or multiple first portions of the sine wave 702, such that EP peaks falling within portions of the ERNA response that behave similarly to the first portion may correspond to different degrees of constructive resonance for the stimulation signal and DBS treatment. Additionally or alternatively, the first zone 704, the second zone 706, and the sixth zone 714 (e.g., the "negative half" of the sine wave 702) may be referred to as a second portion or multiple second portions of the sine wave 702, such that EP peaks falling within portions of the ERNA response that behave similarly to the second portion may correspond to different degrees of destructive resonance for the stimulation signal and DBS treatment. In some examples, "rising edge" may be used herein to describe or refer to the first portion, and "falling edge" may be used herein to describe or refer to the second portion.

[0170] FIG. 8A to FIG. 8F is an example of a constructive and destructive concept 800 according to at least one embodiment of the present disclosure. The constructive and destructive concept 800 may be implemented Figures 1 to 7 For example, constructive and destructive concepts 800 may represent how a phase comparison 802 between a basal activity 804 (e.g., ERNA) from a previous stimulation pulse of an electrical stimulation signal and an EP response 806 may be based on Figure 7 The constructive and destructive concepts illustrated in FIG. 8 are used to influence the amplitude and latency of the sum 808 of the two signals.

[0171] Fig. 8A Can correspond to the reference Figure 7 The first zone 704 is depicted. Thus, based on the phase comparison 802 illustrating the comparison between the valleys of the basal activity 804 and the peaks of the EP response 806, a degree of destructive resonance (eg, a complete destructive resonance) occurs to cause the sum 808 to have a smaller amplitude than the EP response 806. Figure 8B Can correspond to the reference Figure 7 The depicted second zone 706. Thus, based on the phase comparison 802 illustrating the comparison between the lower portion of the basal activity 804 and the peak of the EP response 806, a certain degree of destructive resonance (e.g., partial destructive resonance) occurs to cause the sum 808 to have a smaller amplitude than the EP response 806 and to shift the peak of the basal activity 804 to the left. Figure 8C Can correspond to see Figure 7The third region 708 is depicted. Thus, based on the phase comparison 802 illustrating the comparison between the upper portion of the basal activity 804 and the peak of the EP response 806, a degree of constructive resonance (e.g., partial constructive resonance) occurs to cause the sum 808 to have a larger amplitude than the EP response 806 and to shift the peak of the basal activity 804 to the left.

[0172] Fig.8D Can correspond to the reference Figure 7 Depicted fourth zone 710. Thus, based on phase alignment 802 illustrating alignment between peaks of basal activity 804 and peaks of EP response 806, a degree of constructive resonance (eg, full constructive resonance) occurs to cause sum 808 to have a greater amplitude than EP response 806. Fig. 8E Can correspond to the reference Figure 7 The fifth zone 712 is depicted. Thus, based on the phase comparison 802 illustrating the comparison between the upper portion of the base activity 804 and the peak of the EP response 806, a certain degree of constructive resonance (e.g., partial constructive resonance) occurs to cause the sum 808 to have a larger amplitude than the EP response 806 and to shift the peak of the base activity 804 to the right. Figure 8F Can correspond to the reference Figure 7 Depicted sixth zone 714. Thus, based on phase comparison 802 illustrating the comparison between the lower portion of base activity 804 and the peak of EP response 806, a degree of destructive resonance (e.g., partial destructive resonance) occurs to cause sum 808 to have a smaller amplitude than EP response 806 and to shift the peak of base activity 804 to the right.

[0173] While this simplified example illustrates the general concept of constructive and destructive resonances based on peak alignment, the EP response 806 and the underlying activity 804 may not always be of the same frequency or symmetrical in shape. Thus, in some cases, the valleys may have a greater "pull" than the peaks in affecting the latency of the resonant activity.

[0174] Fig. 9A and Fig. 9B 900 and 902, respectively, are example stimulus responses according to at least one embodiment of the present disclosure. Example stimulus responses 900 and 902 may be implemented Figures 1 to 8F For example, example stimulation responses 900 and 902 may represent electrical stimulation signals (e.g., therapeutic electrical stimulation signals) applied to an anatomical element of a patient (e.g., the brain, STN, other regions of the brain, spine, etc.) as a reference. Figures 1 to 8FDifferent neural responses as a portion of a DBS therapy (e.g., or other type of therapy) described herein (such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.). Additionally, example stimulation responses 900 and 902 may be illustrated as in reference Figures 7 to 8F Described are how the constructive resonance concepts and destructive resonance concepts affect the properties of ERNA responses as described herein.Example stimulation response 900 may represent a burst of stimulation pulses at a first frequency (e.g., 110 Hz), and example stimulation response 902 may represent a burst of stimulation pulses at a second frequency (e.g., 130 Hz).

[0175] As described herein, the nature of the ERNA response is not entirely controlled by the timing of the stimulation pulse itself, but rather by the timing of the response from the stimulation pulse. This distinction is particularly important because the timing of a response (e.g., an induced response, such as an EP response) may vary from patient to patient based on anatomical structure, neural state, medication, etc., while the stimulation pulse timing will not vary from patient to patient. Example stimulation responses 900 and 902 include a first time instance 904 and a second time instance 906. The first time instance 904 can represent a time instance at which the next stimulation pulse should have occurred, and the second time instance 906 can represent a time instance at which the EP response corresponding to the next stimulation pulse should have occurred. That is, if another stimulation pulse is delivered at the first time instance 904 at a corresponding frequency, the timing of the peak of the EP response from the stimulation pulse will occur at the second time instance 906.

[0176] like Fig. 9A As shown in the example of , the EP response of the example stimulus response 900 at the second time instance 906 is consistent with the first part of the underlying resonant activity (e.g., ERNA) after the burst of the stimulus response (e.g., as shown in reference Figure 7 The "rising edge" described in the previous section is compared. Fig. 9B As shown in the example of , the EP response of the example stimulus response 902 at the second time instance 906 is related to the second part of the underlying resonant activity (e.g., ERNA) after the burst of the stimulus response (e.g., as shown in reference Figure 7 The “falling edge” described in the previous section is compared.

[0177] Based on the EP response of example stimulation response 900 aligned with the first portion of the underlying resonant activity (e.g., indicating at least some degree of constructive resonance), example stimulation response 900 includes a higher first peak-to-trough amplitude than example stimulation response 902, where the corresponding EP response is aligned with the second portion of the underlying response (e.g., indicating at least some degree of destructive resonance). That is, the amplitude between the first peak 908A and the first valley 910 after the stimulation pulse burst of example stimulation response 900 is greater than the amplitude between the first peak 912A and the first valley 914 after the stimulation pulse burst of example stimulation response 902. In addition, example stimulation response 900 includes a higher number of resonance peaks (e.g., six (6) peaks 908) than the number of resonance peaks in example stimulation response 902 (e.g., five (5) peaks 912).

[0178] For example stimulus response 900, the peaks of the EP response align with the first portion of the underlying ERNA (e.g., the underlying behavior), which promotes constructive resonant behavior, thereby explaining the larger peak-to-trough amplitudes and the higher number of resonant peaks. For example stimulus response 902, the peaks of the EP response align with the valleys and / or the second portion of the underlying ERNA, thereby exhibiting destructive resonant behavior.

[0179] Therefore, using Ep from DBS can help inform how to optimize stimulation based on underlying neural activity. Under certain stimulation settings, ERNA (e.g., underlying neural activity) is present and can be used to optimize stimulation by maintaining a specified phase alignment of the peak of the EP response with different parts of the underlying neural activity or ERNA. As described herein, concepts for optimizing stimulation parameters to promote and influence constructive resonance or destructive resonance of ERNA signals are provided.

[0180] Fig.10 is a set of example stimulus responses 1000 that demonstrate constructive and destructive concepts according to at least one embodiment of the present disclosure. The set of example stimulus responses 1000 may implement Figures 1 to 9B For example, the set of example stimulation responses 1000 may represent the effects of applying an electrical stimulation signal (e.g., a therapeutic electrical stimulation signal) to an anatomical element of a patient (e.g., a brain, STN, other regions of the brain, spine, etc.) as described in reference to FIG. Figures 1 to 9B Different neural responses (e.g., measured in uV on the y-axis of each stimulation response in the set of example stimulation responses 1000) of a portion of a DBS treatment (e.g., or other type of therapy) described herein (such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.). Additionally, the set of example stimulation responses 1000 may be exemplified as in reference Figures 7 to 9BDescribed are how the concepts of constructive resonance and destructive resonance affect the nature of the ERNA response as described herein.

[0181] The set of example stimulation responses 1000 may include a first stimulation response 1002 (e.g., delivered at a first frequency such as 110 Hz), a second stimulation response 1004 (e.g., delivered at a second frequency such as 130 Hz), a third stimulation response 1006 (e.g., delivered at a third frequency such as 140 Hz), a fourth stimulation response 1008 (e.g., delivered at a fourth frequency such as 150 Hz), and a fifth stimulation response 1010 (e.g., delivered at a fifth frequency such as 160 Hz). 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 at which the next stimulation pulse should have occurred, and the second time instance 1016 may represent a time instance at which the EP response corresponding to the next stimulation pulse should have occurred. That is, if another stimulation pulse is delivered at the corresponding frequency at the first time instance 1014, the timing of the peak of the EP response from the stimulation pulse will occur at the second time instance 1016.

[0182] As described herein, the set of example stimulus responses 1000 can exemplify constructive resonance or destructive resonance based on the position of the peak of the EP response (e.g., evoked response) aligned with the ERNA (e.g., basal activity). For example, the first stimulus response 1002 and the fifth stimulus response 1010 can exemplify constructive resonance based on the peak of the EP response aligned with the first portion (e.g., "rising edge") or peak of the ERNA. Additionally or alternatively, the second stimulus response 1004 and the third stimulus response 1006 can exemplify destructive resonance based on the peak of the EP response aligned with the second portion (e.g., "falling edge") or valley of the ERNA. In some examples, the fourth stimulus response 1008 can exemplify constructive resonance based on the peak of the EP response aligned with the peak of the ERNA. However, the peak of the EP response in the fourth stimulation response 1008 also drops close to the beginning of the second portion (e.g., the "falling edge") of the ERNA, resulting in a smaller peak-to-valley amplitude than the first stimulation 1002 and the fifth stimulation response 1010, but the fourth stimulation response 1008 may still represent a more constructively higher resonance than the second stimulation response 1004 and the third stimulation response 1006. Therefore, based on having a constructive resonance, the first stimulation response 1002, the fourth stimulation response 1008, and the fifth stimulation response 1010 may have a larger first peak-to-valley amplitude after applying a burst of stimulation pulses, while the second stimulation response 1004 and the third stimulation response 1006 and their corresponding destructive resonances have smaller first peak-to-valley amplitudes. In some embodiments, if the amplitude of the initial valley of the ERNA becomes larger or wider, the valley may become a more influential part of the waveform of the ERNA and may indicate a subsequent latency shift.

[0183] In some examples, the change in the latency of the ERNA response can affect the comparison of the EP peak and the basic resonance, thereby causing a change in constructive behavior or destructive behavior. The change in latency can be driven by the constructive resonance or destructive resonance from the previous pulse, the change in the neural state (e.g., under anesthesia, sleep / wakefulness, drug treatment, disease progression, etc.), or a combination thereof. Then, the change in the ERNA response can drive the need to change the stimulation parameters to maintain the desired resonance state (e.g., constructive resonance state or destructive resonance state). In some embodiments, the optimal frequency can be determined to maintain the constructive resonance or destructive resonance of the ERNA response. For example, the optimal frequency can be selected from the range of about 5Hz and about 500Hz. Additionally or alternatively, constructive resonance or destructive resonance can be maintained or generated 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 the range of about 0.1mA and 10mA), and / or the pulse width can be dynamically changed to control the resonance (e.g., adjusted between the range of about 20μs and about 500μs).

[0184] Subsequently, controlling the ERNA signal to promote constructive resonance or destructive resonance can be used to guide programming in the clinic to determine the optimal stimulation parameters (e.g., stimulation frequency, amplitude, pulse width, etc.) to achieve the desired resonance state that is best or most satisfactory for the patient (e.g., reducing the pain or symptoms of the patient's corresponding condition without causing discomfort). In addition, these concepts can be used in a closed-loop manner that includes monitoring the ERNA and adjusting the stimulation parameters to maintain the desired resonance state (e.g., a constructive resonance state or a destructive resonance state) or to determine when the desired state should be switched from constructive to destructive or vice versa. In addition, other input signals can notify changes in the desired resonance state, such as detecting a specific neural state of the patient (e.g., sleeping, awake, taking medication, stopping medication, etc.) or detecting a certain LFP biomarker.

[0185] Fig.11A and Fig. 11B 1100 and 1102 are example results of applying stimulation according to at least one embodiment of the present disclosure. Example results 1100 and 1102 can achieve Figures 1 to 10 For example, example results 1100 and 1102 may represent the effects of applying an electrical stimulation signal (e.g., a therapeutic electrical stimulation signal) to an anatomical element of a patient (e.g., a brain, STN, other regions of the brain, spine, etc.) as a reference. Figures 1 to 10Data collected after a portion of a described DBS therapy (eg, or other type of therapy), such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.

[0186] Example results 1100 and 1102 may represent data collected from a constant stimulation (e.g., applied at 130 Hz) where a pulse (e.g., a single pulse) is skipped or abandoned once per second (e.g., the constant stimulation is paused or inhibited for a single pulse or multiple pulses) to enable viewing of underlying resonant activity (e.g., ERNA). Example result 1100 may represent the amplitude of the sensed signal (e.g., in microvolts (uV)). The y-axis represents each continuous data segment (e.g., one segment per second), and the x-axis represents the time within each data segment (e.g., where stimulation pulses are delivered at 0 ms and 15.4 ms). The first time instance 1104 may represent the location and time where the stimulation pulse would have landed if the pulse had not been skipped or abandoned (e.g., at 7.7 ms). The second time instance 1106 may represent the location and time where the peak of the evoked response (e.g., EP response) would have landed from the skipped or abandoned stimulation pulse.

[0187] Example results 1102 may represent waveforms of ERNA of an electrical stimulation signal captured at different time points after stimulation is enabled. For example, the example results 1102 may include a first waveform 1108A of ERNA captured at a first time after stimulation is enabled (e.g., 10 s), a second waveform 1108B of ERNA captured at a second time after stimulation is enabled (e.g., 35 s), a third waveform 1108C of ERNA captured at a third time after stimulation is enabled (e.g., 60 s), a fourth waveform 1108D of ERNA captured at a fourth time after stimulation is enabled (e.g., 85 s), a fifth waveform 1108E of ERNA captured at a fifth time after stimulation is enabled (e.g., 110 s), a sixth waveform 1108F of ERNA captured at a sixth time after stimulation is enabled (e.g., 135 s), a seventh waveform 1108G of ERNA captured at a seventh time after stimulation is enabled (e.g., 160 s), and an eighth waveform 1108H of ERNA captured at an eighth time after stimulation is enabled (e.g., 185 s). The example results 1102 also show a first time instance 1104 and a second time instance 1106 to indicate where the peak of the EP response should have landed on the ERNA waveform.

[0188] At approximately y=43s of the example result 1100, stimulation is enabled, and initially, the alignment of the peak of the EP response (e.g., at the second time instance 1106) falls on the falling edge of the ERNA (e.g., basal activity), as can be seen by the first waveform 1108A of the example result 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 can slowly shift the basal resonance to the right, as illustrated in the example result 1100 at y-axis time=45-110s and the movement of the third peak 1112 of the ERNA in the example result 1102 (e.g., the third peak 1112A of the first waveform 1108A shifts to the right, as can be seen by the third peak 1112H of the eighth waveform 1108H). Ultimately, the ERNA (e.g., the fundamental resonance) has shifted such that the peak of the EP response (e.g., represented by the second time instance 1106) aligns with the peak of the fundamental resonance (e.g., as illustrated by 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 the increase in amplitude of the first peak 1114 of the waveform over time after stimulation is enabled and is seen by the color / shading transition 1116 at approximately y-axis = 130-250s in the example results 1100.

[0189] Because based on Fig.11A and Fig. 11B These concepts of constructive and destructive resonance illustrated in the example of may occur with latency shifts, so the optimal stimulation frequency that maximizes the peak-to-trough amplitude may occur differently than a burst of 10 pulses compared to a constant stimulation (e.g., steady state).

[0190] Fig.12 is a set of example stimulus responses 1200 for determining steady-state behavior according to at least one embodiment of the present disclosure. The set of example stimulus responses 1200 may implement Figure 1 to Figure 1 1 or may be implemented by the various aspects of 1. For example, the set of example stimulation responses 1200 may represent electrical stimulation signals (e.g., therapeutic electrical stimulation signals) applied to anatomical elements of a patient (e.g., brain, STN, other regions of the brain, spine, etc.) at different frequencies as a reference. Figure 1 to Figure 1 1 (eg, or other types of therapy) as a portion of the DBS therapy described above (such as by using IMD 106, leads 114A and 114B, electrodes 116 and 118, etc.).

[0191] The set of example stimulation responses 1200 can illustrate changes in peak-to-trough amplitudes after constant frequency stimulation is enabled. Some stimulation frequencies can exhibit changes quickly (e.g., 160 Hz), while other stimulation frequencies can take 100s or longer to begin to exhibit changes (e.g., 130 Hz). Therefore, being able to infer steady-state behavior based on initial characteristics from short bursts of stimulation can be beneficial in accelerating the programming process for programming parameters of electrical stimulation signals.

[0192] Because constant stimulation can cause a shift in the latency of the base resonance (e.g., ERNA), the peak-to-valley amplitude can change as the system reaches a steady state at different stimulation frequencies. Stimulation is enabled for each of the stimulation frequencies in the set of example stimulation responses 1200 at approximately 45s, and the stimulation is always maintained at a constant stimulation amplitude of 0.7mA. In some examples, continuous stimulation can result in a slow stabilization time constant. Constant stimulation is applied for one (1) second at each frequency, and then a pulse (e.g., or multiple pulses) is skipped or abandoned after each second (e.g., for one or more pulses, the application of constant stimulation is suspended or suppressed) to sense the base resonance. In some embodiments, based on beta bursts, skipping or abandoning one (1) pulse will not have a therapeutic effect on the patient, and these beta bursts are less than 500ms and will not produce symptoms.

[0193] Fig.13 A flow chart of a method 1300 is depicted that can be used, for example, to guide programming of stimulation parameters for applying an electrical stimulation signal to an anatomical element of a patient. For example, the method 1300 can use the timing of the initial peak of the EP response compared to the ERNA signal (e.g., the fundamental resonance) to determine the optimal settings based on the patient-specific response.

[0194] The method 1300 (and / or one or more steps thereof) may be performed or otherwise executed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor of the apparatus described herein. The at least one processor may be as described in reference Figures 1 to 3Method 1300 may be performed by a processor other than any processor described herein (e.g., processing circuit 210 and / or processing circuit 310) of programmer 104 and / or IMD 106 as described herein and / or may be a part of a control unit (e.g., a computing device) in communication with programmer 104 and / or IMD 106. Method 1300 may also be performed using a processor other than any processor described herein. At least one processor may perform method 1300 by executing elements stored in a memory (such as a memory or a control unit, computing device, etc. in programmer 104 and / or IMD 106 as described herein). The elements stored in the memory and executed by the processor may cause the processor to perform one or more steps of the functions shown in method 1300. One or more portions of method 1300 may be performed by a processor executing any of the contents of the memory, such as capturing EP measurements, recording ERNA signals, determining resonance states, adjusting stimulation parameters, and / or any associated operations as described herein.

[0195] Method 1300 includes measuring a first response after applying pulses of a generated electrical stimulation signal (e.g., via a signal generator, such as programmer 104, IMD 106, stimulation generation circuit 202, processing circuit 210, and / or processing circuit 310) to an anatomical element (e.g., brain, STN, etc.) of a patient (step 1302). For example, the first response may include captured EP measurements resulting from applying the pulses of the generated electrical stimulation signal.

[0196] The method 1300 also includes measuring a second response after applying a plurality of pulses (e.g., a burst of pulses, a burst of multiple pulses, etc.) of the generated electrical stimulation signal to the anatomical element (step 1304). For example, the second response may include a captured ERNA signal generated by applying the plurality of pulses of the generated electrical stimulation signal.

[0197] Method 1300 also includes extracting a first set of timings corresponding to peaks and valleys of the first response (step 1306). For example, the first set of timings may include timings of peaks of the EP measurement and timings of valleys of the EP measurement.

[0198] Method 1300 also includes extracting a second set of timings corresponding to peaks and valleys of the second response (step 1308). For example, the second set of timings may include extracted timings of ERNA peaks and valleys.

[0199] The method 1300 also includes calculating steady-state ERNA behavior based on the constructive concept and the destructive concept (step 1310). For example, a constructive resonant state and a destructive resonant state for applying the generated electrical stimulation signal to the anatomical element can be determined based on the first response and the second response. In some examples, the constructive resonant state can include a peak corresponding to the first response (e.g., an EP response peak) being aligned with a first portion of a base resonant response corresponding to the second response (e.g., as shown in reference Figure 7 Additionally or alternatively, the destructive resonance state may include a peak corresponding to the first response (e.g., an EP response peak) being aligned with a second portion of the base resonance response corresponding to the second response (e.g., as described in reference Figure 7 In some examples, a certain degree of constructive resonance state and / or destructive resonance state can be determined to apply the generated electrical stimulation signal to the anatomical element. For example, the degree of constructive resonance state and / or destructive resonance state can include a resonance state that is not completely constructive, not completely destructive, neither constructive nor destructive, or a combination of constructive and destructive.

[0200] In some examples, method 1300 also includes determining stimulation parameters (e.g., amplitude, pulse width, frequency, etc.) of the generated electrical stimulation signal to maintain constructive resonance using a comparison of peaks and / or valleys of the first response (e.g., EP response peaks) and the steady-state ERNA behavior (step 1312). That is, the stimulation parameters can be determined based on a comparison of peaks and / or valleys of the first response generated from the first set of timings and the steady-state behavior of the second response (e.g., comparing the EP response peaks to the first portion or peak of the steady-state ERNA behavior).

[0201] Additionally or alternatively, method 1300 includes determining stimulation parameters (e.g., amplitude, pulse width, frequency, etc.) of the generated electrical stimulation signal to maintain destructive resonance using a comparison of peaks and / or valleys of the first response (e.g., EP response peaks) and the steady-state ERNA behavior (step 1314). That is, the stimulation parameters may be determined based on a comparison of peaks and / or valleys of the first response generated from the first set of timings and the steady-state behavior of the second response (e.g., comparing the EP response peaks to a second portion or valley of the steady-state ERNA behavior).

[0202] The present disclosure encompasses embodiments of method 1300 that include more or fewer steps than those described above and / or one or more steps that are different than those described above.

[0203] Fig.14Depicted is a flow chart of a method 1400 that may be used, for example, to make closed-loop adjustments to stimulation parameters to maintain a resonant state.

[0204] The method 1400 (and / or one or more steps thereof) may be performed or otherwise executed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor of the apparatus described herein. The at least one processor may be as described in reference Figures 1 to 3 104 and / or IMD 106 as described herein (e.g., processing circuit 210 and / or processing circuit 310) and / or may be part of a control unit (e.g., a computing device) in communication with programmer 104 and / or IMD 106. Method 1400 may also be performed using a processor other than any processor described herein. At least one processor may perform method 1400 by executing elements stored in a memory (such as a memory or a control unit, computing device, etc. in programmer 104 and / or IMD 106 as described herein). The elements stored in the memory and executed by the processor may cause the processor to perform one or more steps of the functions shown in method 1400. One or more portions of method 1400 may be performed by a processor executing any of the contents of the memory, such as capturing EP measurements, recording ERNA signals, determining resonance states, adjusting stimulation parameters, and / or any associated operations as described herein.

[0205] Method 1400 includes selecting a desired resonance state for a patient (step 1402). For example, the desired resonance state can be a constructive resonance state or a destructive resonance state as described herein. In some examples, the patient's desired resonance state can be set by a clinician based on input from the patient (e.g., a satisfaction or comfort level of a given resonance state, the efficacy of the resonance state in treating the patient's condition, etc.). Thus, an electrical stimulation signal can be applied to the anatomical element according to the desired resonance state. For example, the electrical stimulation signal can be applied using multiple parameters configured to generate a desired resonance state.

[0206] Method 1400 also includes monitoring changes in a first peak-to-trough amplitude (eg, or another stimulation parameter) between each pulse of the generated electrical stimulation signal (step 1404).

[0207] The method 1400 also includes determining a phase shift between a fundamental resonance response corresponding to the second response and the first response, the phase shift being determined based on detecting a change in peak-to-valley amplitude (step 1406). For example, a phase shift between a fundamental resonance (e.g., ERNA) and a peak of the first response (e.g., EP peak response) can be inferred based on a constructive / destructive concept.

[0208] The method 1400 also includes reviewing the fundamental resonant response for application of the electrical stimulation signal generated by the one or more pulse pauses to confirm phase comparison shifts (step 1408).

[0209] The method 1400 also includes adjusting one or more of the plurality of stimulation parameters based on the determined phase alignment shift to align a peak corresponding to the first response with the base resonance response, thereby maintaining the first resonance state (step 1410). For example, the stimulation frequency can be adjusted to align a peak or a valley of the first response (e.g., an EP response) with a corresponding portion of the base resonance (e.g., ERNA), thereby maintaining the desired resonance state. Additionally or alternatively, other parameters can be adjusted to maintain the desired resonance state, such as amplitude and / or pulse width.

[0210] The present disclosure encompasses embodiments of method 1400 that include more or fewer steps than those described above and / or one or more steps that are different than those described above.

[0211] Fig.15 Depicted is a flow chart of a method 1500 that may be used, for example, to make closed-loop adjustments to stimulation parameters to adjust the magnitude of a resonant state.

[0212] The method 1500 (and / or one or more steps thereof) may be performed or otherwise executed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor of the apparatus described herein. The at least one processor may be as described in reference Figures 1 to 3 Method 1500 may be performed by a processor other than any processor described herein (e.g., processing circuit 210 and / or processing circuit 310) of programmer 104 and / or IMD 106 as described herein and / or may be a part of a control unit (e.g., a computing device) in communication with programmer 104 and / or IMD 106. Method 1500 may also be performed using a processor other than any processor described herein. At least one processor may perform method 1500 by executing elements stored in a memory (such as a memory or a control unit, computing device, etc. in programmer 104 and / or IMD 106 as described herein). The elements stored in the memory and executed by the processor may cause the processor to perform one or more steps of the functions shown in method 1500. One or more portions of method 1500 may be performed by a processor executing any of the contents of the memory, such as capturing EP measurements, recording ERNA signals, determining resonance states, adjusting stimulation parameters, and / or any associated operations as described herein.

[0213] Method 1500 includes selecting a desired resonance state for a patient (step 1502). For example, the desired resonance state can be a constructive resonance state or a destructive resonance state as described herein. In some examples, the patient's desired resonance state can be set by a clinician based on input from the patient (e.g., a satisfaction or comfort level of a given resonance state, the efficacy of the resonance state in treating the patient's condition, etc.). Thus, an electrical stimulation signal can be applied to the anatomical element according to the desired resonance state. For example, the electrical stimulation signal can be applied using multiple parameters configured to generate a desired resonance state.

[0214] The method 1500 also includes monitoring side effects caused by applying the electrical stimulation signal according to the desired resonance state (step 1504). For example, the side effects can include changes in the second response (e.g., changes in the ERNA signal), LFP signal side effects, changes in accelerometer settings and / or accelerometer signals (e.g., indicating that the patient is moving or not moving, indicating the patient's posture, etc.), or a combination thereof.

[0215] The method 1500 also includes adjusting a resonant state of the electrical stimulation signal based at least in part on detecting the side effect (step 1506). For example, adjusting the resonant state can include adjusting the first resonant state to have less constructive resonance, shifting a peak corresponding to the first response away from a peak of the base resonant response, switching from the first resonant state to a second resonant state (e.g., an opposite state of a constructive resonant state or a destructive resonant state configured for the first resonant state), adjusting pulse timing of the electrical stimulation signal, or a combination thereof.

[0216] The method 1500 also includes adjusting one or more of the plurality of stimulation parameters to align a peak corresponding to the first response with a base resonance response corresponding to the second response based on the adjusted resonance state, thereby applying an electrical stimulation signal (step 1508). For example, the stimulation frequency can be adjusted based on the adjusted resonance state to align a peak or a valley of the first response (e.g., an EP response) with a corresponding portion of the base resonance (e.g., an ERNA). Additionally or alternatively, other parameters can be adjusted to produce the adjusted resonance state, such as amplitude and / or pulse width.

[0217] The present disclosure encompasses embodiments of method 1500 that include more or fewer steps than those described above and / or one or more steps that are different than those described above.

[0218] Fig.16A flow chart of method 1600 is depicted, which can be used, for example, to make closed-loop adjustments to stimulation parameters to change the resonant state. In some embodiments, method 1600 can be used to change the resonant state based on a change in the patient's neural state (e.g., the resonant state changes in response to the change in the neural state). Additionally or alternatively, the patient's resonant state can change in anticipation of a change in the patient's neural state. For example, properties of different signal measurements associated with DBS therapy (e.g., properties of ERNA signals, EP measurements, etc.) can indicate that the patient's neural state is about to change, and the techniques described herein can be used to change the patient's resonant state before the patient's neural state changes.

[0219] The method 1600 (and / or one or more steps thereof) may be performed or otherwise executed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor of the apparatus described herein. The at least one processor may be as described in reference Figures 1 to 3 104 and / or IMD 106 as described herein (e.g., processing circuit 210 and / or processing circuit 310) and / or may be part of a control unit (e.g., a computing device) in communication with programmer 104 and / or IMD 106. Method 1600 may also be performed using a processor other than any processor described herein. At least one processor may perform method 1600 by executing elements stored in a memory (such as a memory or a control unit, computing device, etc. in programmer 104 and / or IMD 106 as described herein). The elements stored in the memory and executed by the processor may cause the processor to perform one or more steps of the functions shown in method 1600. One or more portions of method 1600 may be performed by a processor executing any of the contents of the memory, such as capturing EP measurements, recording ERNA signals, determining resonance states, assigning resonance states, adjusting stimulation parameters, and / or any associated operations as described herein.

[0220] Method 1600 includes assigning a constructive resonance state or a destructive resonance state to each neural state in a plurality of neural states (step 1602). As a non-limiting example, a constructive resonance state may be assigned to a patient's awake state, and a destructive resonance state may be assigned to a patient's sleeping state. In some examples, the plurality of neural states may include, but are not limited to, awake states, sleeping states, medication states, discontinuation states, depth of anesthesia states, disease progression states, drug wash-in states, drug wash-out states, motion states (e.g., whether the patient is moving, such as indicated by an accelerometer), a patient's posture (e.g., upright, lying down, etc.), or different neural states. Thus, when one of the plurality of neural states is detected, 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 of the detected neural state.

[0221] Method 1600 also includes monitoring a change from the detected neural state to a second neural state in the plurality of neural states, the second neural state corresponding to a different assigned resonance state of the detected neural state (step 1604). In some examples, the change in neural state can be detected based on one or more measurements (e.g., ERNA, LFP, resonance frequency, etc.) that indicate whether the patient is asleep or awake, whether a medication is being washed in or out of the patient, etc.

[0222] Method 1600 also includes switching the resonance state for applying the generated electrical stimulation signal based on detecting a change from the detected neural state to a second neural state (step 1606). In some examples, the patient's desired resonance state can be switched from the detected neural state to the second neural state based on a programmed setting (e.g., a resonance state assigned to each neural state).

[0223] The method 1600 also includes adjusting one or more of the plurality of stimulation parameters to align a peak corresponding to the first response with a base resonance response corresponding to the second response based on the switched resonance state, thereby applying an electrical stimulation signal (step 1608). For example, the stimulation frequency can be adjusted based on the new desired resonance state (e.g., the second resonance state) to align a peak or a valley of the first response (e.g., the EP response) with a corresponding portion of the base resonance (e.g., the ERNA). Additionally or alternatively, other parameters can be adjusted to produce the new desired resonance state, such as amplitude and / or pulse width. Subsequently, the electrical stimulation signal can be applied to the anatomical element using the adjusted one or more parameters.

[0224] It should be understood that in some embodiments, the resonance statement distribution can be applied bidirectionally, wherein two different neural states are distributed. In such examples, each of the two different neural states is monitored independently, and multiple parameters of the therapeutic electrical stimulation signal can be determined for each of the two different neural states. In addition, multiple parameters of the therapeutic electrical stimulation signal for each of the two different neural states can be independently adjusted or updated.

[0225] The present disclosure encompasses embodiments of method 1600 that include more or fewer steps than those described above and / or one or more steps that are different than those described above.

[0226] As mentioned above, the present disclosure covers Fig.13 , Fig.14 , Fig.15 and Fig.16 A method comprising fewer than all of the steps identified in (and the corresponding descriptions of methods 1300, 1400, 1500, and 1600) and including more than Fig.13 , Fig.14 , Fig.15 and Fig.16 The present disclosure also encompasses methods comprising 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 include registration or any other correlation.

[0227] The foregoing is not intended to limit the present disclosure to one or more forms disclosed herein. In the aforementioned specific embodiments, for example, for the purpose of simplifying the present disclosure, the various features of the present disclosure are grouped together in one or more aspects, embodiments and / or configurations. The features of the aspects, embodiments and / or configurations of the present disclosure may be combined in alternative aspects, embodiments and / or configurations other than those discussed above. The method of the present disclosure should not be interpreted as reflecting the following intention: the claims require more features than the features explicitly stated in each claim. On the contrary, as reflected in the following claims, aspects of the present invention are less than all the features of a single aforementioned disclosed aspect, embodiment and / or configuration. Therefore, the following claims are hereby incorporated into this specific embodiment, wherein each claim exists independently as a separate preferred embodiment of the present disclosure.

[0228] In addition, although the foregoing has included descriptions 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 present disclosure, for example, within the skill and knowledge of those skilled in the art after understanding the present disclosure. It is intended to obtain rights to include alternative aspects, embodiments and / or configurations, including alternative, interchangeable and / or equivalent structures, functions, ranges or steps of those claimed, regardless of whether such alternative, interchangeable and / or equivalent structures, functions, ranges or steps are disclosed herein, and are not intended to be disclosed for any patentable subject matter.

Claims

1. A system for providing deep brain stimulation (DBS) therapy, the system include: 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 signals to an anatomical element of a patient; a respective plurality of electrodes disposed at a distal portion 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; processor; as well as a memory storing data for processing by the processor, the data, when processed, causing the processor to: measuring a first response via one or more of the corresponding plurality of electrodes after applying a pulse of the generated electrical stimulation signal to the anatomical element; measuring a second response via one or more of the corresponding plurality of electrodes after applying the plurality of pulses of the generated electrical stimulation signal to the anatomical element; determining a constructive resonance state and / or a destructive resonance state for applying a generated electrical stimulation signal to the anatomical element based at least in part on the first response and the second response; as well as The signal generator is caused to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the corresponding plurality of electrodes based at least in part on one or more stimulation parameters, wherein the one or more stimulation parameters are determined at least in part based 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, the further data when processed causing the processor to: extracting a first set of timings corresponding to peaks and valleys of the first response; and A second set of timings corresponding to peaks and valleys of the second response is extracted, wherein the constructive resonant state and / or the destructive resonant state is 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, the further data when processed causing the processor to: A steady-state behavior of the second response is calculated based at least in part on the constructive resonant state and / or the destructive resonant state.

4. The system of claim 3, wherein the one or more stimulation parameters are determined based at least in part on a comparison of peaks and / or valleys of the first response from the first set of timings with the steady-state behavior of the second response.

5. The system according to claim 1, in: The constructive resonance state includes a state in which a peak corresponding to the first response is aligned with a first portion and / or peak of a fundamental resonance response corresponding to the second response; and The destructive resonance state includes a state where the peak corresponding to the first response will align with a second portion and / or valley of the fundamental resonance response corresponding to the second response.

6. The system of claim 1 , wherein the memory stores additional data for processing by the processor, the additional data when processed causing the processor to: causing the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the corresponding plurality of electrodes according to a first resonance state, wherein the first resonance state includes a certain degree of the constructive resonance state and / or the destructive resonance state; monitoring changes in peak-to-trough amplitude between each pulse of the generated electrical stimulation signal; determining a phase comparison shift between a fundamental resonant response corresponding to the second response and the first response, the phase comparison shift being determined based at least in part on detecting a change in the peak-to-valley amplitude; as well as One or more parameters of the generated electrical stimulation signal are adjusted based at least in part on determining the phase alignment shift to align a peak corresponding to the first response with the base resonant response to maintain the first resonant state.

7. A system according to claim 6, wherein the memory stores further data for processing by the processor, the further data when processed causing the processor to: inhibiting application of the generated electrical stimulation signal for one or more pulses; and The fundamental resonant response is determined based at least in part on inhibiting application of the generated electrical stimulation signal for the one or more pulses to confirm the phase comparison shift.

8. The system of claim 1 , wherein the memory stores additional data for processing by the processor, the additional data when processed causing the processor to: causing the signal generator to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the corresponding plurality of electrodes according to a first resonance state, wherein the first resonance state includes a certain degree of the constructive resonance state and / or the destructive resonance state; monitoring side effects caused by applying the generated electrical stimulation signal according to the first resonance state; adjusting a resonant state of the generated electrical stimulation signal based at least in part on detecting the side effect; as well as One or more parameters of the generated electrical stimulation signal are adjusted according to the adjusted resonance state to align a peak corresponding to the first response with a base resonance response corresponding to the second response to provide the generated electrical stimulation signal.

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: Adjusting the first resonant state to have different degrees of the constructive resonant state and / or the destructive resonant state, shifting the peaks and / or valleys corresponding to the first response away from the peaks of the base resonant response, switching from the first resonant state to a second resonant state, adjusting the pulse timing of the electrical stimulation signal, or performing a combination of these operations.

10. The system of claim 8, wherein the side effect comprises 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 additional data for processing by the processor, the additional data when processed causing the processor to: assigning the constructive resonance state and / or the destructive resonance state to each neural state of a plurality of neural states; detecting a neural state of the plurality of neural states; and The signal generator is caused to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the corresponding plurality of electrodes in accordance with the assigned constructive resonance state and / or destructive resonance state of the detected neural state.

12. The system of claim 11, wherein the memory stores further data for processing by the processor, the further data when processed causing the processor to: monitoring 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 resonance state of the detected neural state; switching a resonance 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; adjusting one or more parameters of the generated electrical stimulation signal according to the switched resonance state to align a peak corresponding to the first response with a base resonance response corresponding to the second response to provide the generated electrical stimulation signal; as well as The signal generator is caused to provide the generated electrical stimulation signal to the anatomical element via the one or more leads and the corresponding plurality of electrodes using the adjusted one or more parameters.

13. The system of claim 1, wherein the one or more stimulation parameters include frequency, amplitude, pulse width, number of pulses, additional parameters, or combinations 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 part of an implantable medical device, a programmer, or both.

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

18. A system according to claim 17, wherein the memory stores further data for processing by the processor, the further data when processed causing the processor to: extracting a first set of timings corresponding to peaks and valleys of the first response; and A second set of timings corresponding to peaks and valleys of the second response is extracted, wherein the constructive resonant state and / or the destructive resonant state is 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, the system include: 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 signals to an anatomical element of a patient; as well as a corresponding plurality of electrodes disposed at a distal portion of the one or more leads, the corresponding plurality of electrodes being 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 corresponding plurality of electrodes based at least in part on one or more stimulation parameters, the one or more stimulation parameters being determined at least in part based on a constructive resonance state and / or a destructive resonance state.

20. The system according to claim 19, in: The constructive resonant state includes a state in which a peak corresponding to the first response is aligned with a first portion and / or peak of the fundamental resonant response; and The destructive resonant state comprises a state in which the peak corresponding to the first response is aligned with a second portion and / or a valley of the fundamental resonant response, wherein the first response is obtained at least in part based on applying a pulse of the generated electrical stimulation signal, and the fundamental resonant response is obtained at least in part based on applying multiple pulses of the generated electrical stimulation signal.

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