Power spectral characteristics for adaptive neural modulation applications

Abstract

This article discusses a neurostimulation device for monitoring electrical neural activity when connected to an implantable electrode. The neurostimulation device includes sensing circuitry and signal processing circuitry. The sensing circuitry is configured to sense a patient's local field potential (LFP) signal when connected to the implantable electrode, and the signal processing circuitry is operatively coupled to the sensing circuitry. The signal processing circuitry is configured to calculate the power spectral density (PSD) of the sensed LFP signal, calculate the slope of the PSD of the sensed LFP signal, and use the calculated slope of the PSD of the sensed LFP signal to determine the patient's physiological state.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 546,067, filed October 27, 2023, which is incorporated herein by reference in its entirety. Technical Field

[0003] This invention relates generally to medical devices, and more specifically to systems for nerve stimulation. Background Technology

[0004] Neurostimulation, also known as neuromodulation, has been proposed as a therapy for several conditions. Examples of neurostimulation include spinal cord stimulation (SCS), deep brain stimulation (DBS), peripheral nerve stimulation (PNS), and functional electrical stimulation (FES). Implantable neurostimulation systems have been used to deliver this type of therapy. An implantable neurostimulation system may include an implantable neurostimulator, also known as an implantable pulse generator (IPG), and one or more implantable leads, each including one or more electrodes. The implantable neurostimulator delivers neurostimulation energy through one or more electrodes placed at or near a target site in the nervous system. External programming devices can be used to program the implantable neurostimulator using stimulation parameters that control the delivery of neurostimulation energy.

[0005] In one example, neural stimulation energy is delivered in the form of electrical neural stimulation pulses. Delivery is controlled using stimulation parameters that specify the spatial (where to stimulate), temporal (when to stimulate), and informational (the pulse pattern that guides the nervous system to respond on demand) aspects of the neural stimulation pulse pattern. The neural stimulation system can offer numerous programmable options for the neural stimulation parameters to tailor the neural stimulation therapy to a specific patient. For certain types of neural stimulation (e.g., DBS), the efficacy of neural stimulation for the patient can depend on the neural stimulation system executing adaptive or decision-making algorithms to optimize the neural stimulation therapy. Decision-making algorithms executed by the neural stimulation system can use biomarkers as indicators to make therapy decisions or other treatment-related decisions. The decision-making performance of the neural stimulation system can be composited by indications of treatment-independent biomarkers. Summary of the Invention

[0006] Neural stimulation, also known as neural modulation, can involve delivering electrical nerve stimulation energy in the form of electrical nerve stimulation pulses to treat a patient's neurological condition. Biomarkers of neural activity can be used as feedback for adaptive neural modulation methods. However, dependence on a single measure of neural activity can lead to poorly performing adaptive algorithms due to non-treatment-related events affecting the measurement.

[0007] Example 1 includes topics such as methods of operating a medical device, which include: using the medical device to sense a patient's local field potential (LFP) signal; determining the power spectral density (PSD) of the sensed LFP signal and the slope of the PSD of the sensed LFP signal by the medical device; and using the slope of the PSD of the sensed LFP signal to determine the patient's physiological state.

[0008] In Example 2, the subject matter of Example 1 may optionally include: delivering electroneurostimulation therapy to a patient using a medical device; detecting the patient's motion state using the slope of the PSD of the sensed LFP signal, wherein the motion state indicates the patient's tremor motion; and changing the parameters of the neurostimulation therapy based on the detected patient's motion state.

[0009] In Example 3, the subject matter of one or both of Examples 1 and 2 may optionally include: determining a patient’s medication status using the slope of the PSD of the sensed LFP signal; and generating medication-related prompts for the patient based on the determined patient’s medication status.

[0010] In Example 4, the subject matter of one or any combination of Examples 1-3 may optionally include: delivering electroneurostimulation therapy to a patient using a medical device; detecting the patient's sleep state using the slope of the PSD of the sensed LFP signal, wherein the sleep state indicates the patient's sleep depth; and changing the neurostimulation therapy parameters based on the detected patient's sleep state.

[0011] In Example 5, the subject matter of one or any combination of Examples 1-4 may optionally include: delivering electroneurostimulation therapy to a patient using a medical device; detecting changes in the patient's injury status using the slope of the PSD of the sensed LFP signal; and altering neurostimulation therapy parameters based on the detected changes in the patient's injury status.

[0012] In Example 6, the subject matter of one or any combination of Examples 1-5 may optionally include: sensing spinal cord LFP signals from the patient's spinal nerve tissue; determining the slope of the PSD of the sensed spinal cord LFP signals; and using the slope of the PSD of the sensed peripheral LFP signals to determine changes in the patient's pain state.

[0013] In Example 7, the subject matter of one or any combination of Examples 1-6 may optionally include: sensing peripheral LFP signals from the patient's vagus nerve tissue; determining the slope of the PSD of the sensed peripheral LFP signals sensed from the vagus nerve tissue; and using the slope of the PSD of the sensed peripheral LFP signals to determine the patient's vagus nerve tension.

[0014] In Example 8, the subject matter of one or any combination of Examples 1-7 may optionally include: determining the slope of the PSD of the gamma EEG band of the sensed LFP signal.

[0015] Example 9 includes a subject (such as a neurostimulation device) or may optionally be combined with one or any combination of Examples 1-8 to include such a subject, which includes sensing circuitry and signal processing circuitry. The sensing circuitry is configured to sense a patient's local field potential (LFP) signal when connected to an implantable electrode, and the signal processing circuitry is operatively coupled to the sensing circuitry. The signal processing circuitry is configured to calculate the power spectral density (PSD) of the sensed LFP signal, calculate the slope of the PSD of the sensed LFP signal, and use the calculated slope of the PSD of the sensed LFP signal to determine the patient's physiological state.

[0016] In Example 10, the subject matter of Example 9 may optionally include: signal processing circuitry configured to detect a motion state indicative of a patient’s tremor movement using the slope of the PSD of the sensed LFP signal; stimulation circuitry configured to deliver electroneurostimulation therapy to the patient when connected to an implantable electrode; and control circuitry operatively coupled to the stimulation circuitry and signal processing circuitry. The control circuitry is configured to change the neurostimulation therapy parameters based on the detected motion state of the patient.

[0017] In Example 11, the subject matter of one or both of Examples 9 and 10 may optionally include: signal processing circuitry configured to determine a patient’s medication status using the slope of the PSD of the sensed LFP signal, and to generate medication-related prompts for the patient based on the determined patient’s medication status.

[0018] In Example 12, the subject matter of Example 9 optionally includes: signal processing circuitry configured to detect a patient's sleep state using the slope of the PSD of the sensed LFP signal, wherein the sleep state indicates the patient's sleep depth; stimulation circuitry configured to deliver electroneurostimulation therapy to the patient when connected to an implantable electrode; and control circuitry operatively coupled to the stimulation circuitry and the signal processing circuitry. The control circuitry is configured to: control the delivery of neurostimulation therapy to the patient; and to change neurostimulation therapy parameters based on the detected sleep state of the patient.

[0019] In Example 13, the subject matter of Example 9 may optionally include: signal processing circuitry configured to detect changes in the patient's injury status using the slope of the PSD of the sensed LFP signal; stimulation circuitry configured to deliver electroneurostimulation therapy to the patient when connected to an implantable electrode; and control circuitry operatively coupled to the stimulation circuitry and the signal processing circuitry. The control circuitry is configured to: control the delivery of neurostimulation therapy to the patient; and to change the parameters of the neurostimulation therapy based on the detected changes in the patient's injury status.

[0020] In Example 14, the subject matter of one or any combination of Examples 9-13 may optionally include: a sensing circuit configured to sense a spinal cord LFP signal from the spinal nerve tissue of a patient; and a signal processing circuit configured to determine the slope of the PSD of the sensed spinal cord LFP signal.

[0021] In Example 15, the subject matter of one or any combination of Examples 9-14 may optionally include: a sensing circuit configured to sense a peripheral LFP signal from peripheral nerve tissue surrounding the spinal cord of a patient; and a signal processing circuit configured to determine the slope of the PSD of the sensed peripheral LFP signal.

[0022] In Example 16, the subject matter of one or any combination of Examples 9-15 may optionally include: a sensing circuit configured to sense a peripheral LFP signal from peripheral neural tissue surrounding the patient's brain; and a signal processing circuit configured to determine the slope of the PSD of the sensed peripheral LFP signal.

[0023] In Example 17, the subject matter of one or any combination of Examples 9-16 may optionally include signal processing circuitry configured to: calculate the slope of the PSD of the gamma EEG band of the sensed LFP signal; and use the calculated slope of the PSD of the gamma EEG band of the sensed LFP signal to determine the patient's physiological state.

[0024] Example 18 includes subjects (or may optionally be combined with one or any combination of Examples 1-17 to include such subjects), such as a computer-readable storage medium, which includes instructions that, when operated by a medical device, cause the medical device to perform actions, including: sensing a local field potential (LFP) signal of a patient using the medical device; calculating the power spectral density (PSD) of the sensed LFP signal and the slope of the PSD of the sensed LFP signal; and determining the patient's physiological state using the slope of the PSD of the sensed LFP signal.

[0025] In Example 19, the subject matter of Example 18 optionally includes a computer-readable storage medium comprising instructions that cause a medical device to perform actions, including: delivering an electroneurostimulation therapy to a patient; and altering at least one neurostimulation therapy parameter based on the patient's physiological state determined using the slope of the PSD of a sensed LFP signal.

[0026] In Example 20, the subject matter of Example 18 optionally includes a computer-readable storage medium comprising instructions that cause a medical device to perform actions, including: determining at least one of a patient’s sleep state, movement state, medication state, or disease / injury state using the slope of the PSD of a sensed LFP signal.

[0027] These non-limiting examples can be combined in any arrangement or combination. This summary is intended to provide an overview of the subject matter of this patent application. It is not intended to provide a unique or exhaustive interpretation of this disclosure. The detailed description is included to provide further information about this patent application. Other aspects of this disclosure will be apparent to those skilled in the art upon reading and understanding the following detailed description and viewing the accompanying drawings, which form a part of it, and each of the drawings should not be construed as limiting. Attached Figure Description

[0028] In accompanying drawings that are not necessarily drawn to scale, the same numbers may describe similar parts in different views. The same numbers with different letter suffixes may represent different instances of similar parts. The accompanying drawings illustrate various embodiments discussed in this document by way of example and not by way of limitation.

[0029] Figure 1 This is a partial illustration of an example of a neural stimulation system.

[0030] Figure 2 This is a partial illustration of another example of a neural stimulation system.

[0031] Figure 3 This is an illustration of an example of an implantable pulse generator (IPG) and an implantable lead system.

[0032] Figure 4 This is an illustration of another example of IPG and implantable lead systems.

[0033] Figure 5 This is a schematic side view of an example of an electrical stimulation lead.

[0034] Figures 6A-6H This is an illustration of an example of an electrode that stimulates the lead.

[0035] Figure 7 This is a block diagram of a portion of an example of a medical device.

[0036] Figure 8 This is a flowchart illustrating an example of a method for operating medical devices to monitor electrical nerve activity.

[0037] Figure 9 This is an example of a graph showing the power spectrum distribution of local field potentials sensed in the subthalamic nucleus of an anesthetized subject.

[0038] Figure 10 This is an example of a graph showing the power spectrum distribution of a local field potential sensed in the medial part of the globus pallidus of an anesthetized subject.

[0039] Figure 11 This is a diagram illustrating the operation of implantable pulse generators and personal patient devices. Detailed Implementation

[0040] In the following detailed description, reference is made to the accompanying drawings, which form part of this invention, and specific embodiments in which the invention can be practiced are illustrated by way of illustration. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it should be understood that these embodiments may be combined, or other embodiments may be utilized, and structural, logical, and electrical changes may be made without departing from the spirit and scope of the invention. References to “a,” “an,” or “various” embodiments in this disclosure are not necessarily references to the same embodiment, and such references contemplate more than one embodiment. The following detailed description provides examples, and the scope of the invention is defined by the appended claims and their legal equivalents.

[0041] This article discusses devices, systems, and methods for programming and delivering electrical neural stimulation to patients or subjects. Advances in neuroscience and neurostimulation research have led to a need for sophisticated neural stimulation energy patterns to provide various types of therapies. This system can be implemented using a combination of hardware and software designed to apply any neural stimulation (neuromodulation) therapy, including but not limited to DBS, SCS, PNS, FES, occipital nerve stimulation (ONS), sacral nerve stimulation (SNS), and vagus nerve stimulation (VNS) therapies.

[0042] Figure 1An example of a portion of a neurostimulation system 100 is shown. System 100 includes electrodes 106, a stimulation device 104, and a programming device 102. Electrodes 106 are configured to be placed on or near one or more neural targets in a patient. Stimulation device 104 is configured to be electrically connected to electrodes 106 and to deliver neurostimulation energy, such as in the form of electrical pulses, to one or more neural targets through electrodes 106. The delivery of neurostimulation is controlled using a plurality of stimulation parameters, such as stimulation parameters specifying the pattern of the electrical pulses and the selection of the electrodes through which each electrical pulse is delivered. In various embodiments, at least some of the stimulation parameters are programmable by a user (such as a physician or other caregiver using system 100 to treat a patient). Programming device 102 provides the user with access to user-programmable parameters. In various embodiments, programming device 102 is configured to be communicatively coupled to stimulation device 104 via a wired or wireless link.

[0043] In this document, "user" includes physicians or other clinicians or caregivers who use system 100 to treat patients; "patient" includes a person who receives or intends to receive neural stimulation delivered using system 100. In various embodiments, patients may be permitted to use system 100 to adjust their treatment to some extent, such as by adjusting certain therapeutic parameters and inputting feedback and clinical effect information.

[0044] In various embodiments, the programming device 102 may include a user interface 110 that allows a user to control the operation of the system 100 and monitor the performance of the system 100 and the patient's condition, including responses to delivered neural stimulation. The user can control the operation of the system 100 by setting and / or adjusting values ​​of user-programmable parameters.

[0045] In various embodiments, the user interface 110 may include a graphical user interface (GUI) that allows a user to set and / or adjust values ​​of user-programmable parameters by creating and / or editing graphical representations of various stimulation waveforms. Such waveforms may include, for example, waveforms representing patterns of neural stimulation pulses to be delivered to a patient, and individual waveforms serving as building blocks of the pattern of neural stimulation pulses, such as the waveform of each pulse in the pattern of neural stimulation pulses. The GUI may also allow a user to set and / or adjust multiple stimulation fields, each defined by a set of electrodes through which one or more neural stimulation pulses, represented by the waveforms, are delivered to the patient. The stimulation fields may be further defined by the distribution of current in each neural stimulation pulse within the waveform. In various embodiments, neural stimulation pulses for stimulation periods (such as the duration of a therapeutic session) may be delivered to multiple stimulation fields.

[0046] In various embodiments, system 100 may be configured for neurostimulation applications. User interface 110 may be configured to allow a user to control the operation of system 100 for neurostimulation. For example, system 100 and user interface 110 may be configured for DBS applications. DBS configuration includes various features that can simplify the user's programming of stimulation device 104 to deliver DBS to a patient, such as those discussed in this document.

[0047] Figure 2 This is a partial illustration of another example of a neurostimulation system 10 including one or more stimulation leads 12 and an implantable pulse generator (IPG) 14. System 10 may also include one or more of an external remote control (RC) 16, a clinician's programmer (CP) 18, an external trial stimulator (ETS) 20, or an external charger 22. The IPG 14 may optionally be physically connected to the stimulation leads 12 via one or more lead extensions 24. Each lead carries a plurality of electrodes 26 arranged in an array. The IPG 14 includes pulse generation circuitry that delivers electrical stimulation energy to the electrode array 26 in the form of, for example, pulsed electrical waveforms (i.e., a time sequence of electrical pulses) according to a set of stimulation parameters. The IPG 14 may be implanted in a patient, for example, below the patient's clavicle region or in the patient's hip or abdominal cavity. The implantable pulse generator may have multiple stimulation channels (e.g., 8 or 16), which may be independently programmable to control the magnitude of the electrical stimulation from each channel. IPG 14 may have one, two, three, four or more connector ports for receiving terminals of lead 12.

[0048] The ETS 20 can also optionally be physically connected to the stimulation lead 12 via the percutaneous lead extension 28 and the external cable 30. The ETS 20, which may have a pulse generation circuit similar to that of the IPG 14, can also deliver electrical stimulation energy to the electrode array 26 in the form of, for example, pulsed electrical waveforms, according to a set of stimulation parameters. One difference between the ETS 20 and the IPG 14 is that the ETS 20 is typically a non-implantable device used experimentally after the neural modulation lead 12 has been implanted and before the IPG 14 has been implanted to test the responsiveness to the stimulation to be delivered. Any functionality described herein with respect to the IPG 14 can also be performed with respect to the ETS 20.

[0049] RC 16 can be used to telemetry communicate with or control IPG 14 or ETS 20 via wireless communication link 32. Once IPG 14 and neurostimulation lead 12 are implanted, RC 16 can be used to telemetry communicate with or control IPG 14 via communication link 34. This communication or control allows IPG 14 to be turned on or off and programmed with different sets of stimulation parameters. IPG 14 can also be operated to modify the programmed stimulation parameters to actively control the characteristics of the electrical stimulation energy output by IPG 14. CP 18 allows users (such as clinicians) to program stimulation parameters for IPG 14 and ETS 20 in the operating room and in subsequent sessions. CP 18 can perform this function by indirectly communicating with IPG 14 or ETS 20 via wireless communication link 36 through RC 16. Alternatively, CP 18 can communicate directly with IPG 14 or ETS 20 via a wireless communication link (not shown). The stimulation parameters provided by CP 18 are also used to program RC 16 so that the stimulation parameters can be subsequently modified by operating RC 16 in stand-alone mode (i.e., without the assistance of CP 18).

[0050] Figure 3 It is IPG 14 (e.g.) Figure 2 IPG 14 in the middle) and including stimulation leads (e.g. Figure 2 An illustration of an example of an implantable lead system (stimulation lead 12). IPG 14 can be used as... Figure 1 Stimulation device 104 in the middle. For example... Figure 3 As shown, IPG 14 can be coupled to implantable leads 12A and 12B at the proximal end of each lead. The distal end of each lead includes an electrical contact or electrode 26 for contacting the tissue site targeted for electrical nerve stimulation. Figure 3 As shown, leads 12A and 12B each include eight electrodes 26 at their distal ends. Figure 2 and Figure 3 The number and arrangement of leads 12A and 12B and electrodes 26 shown are merely examples, and other numbers and arrangements are possible. In various examples, lead electrodes 26 are ring electrodes. In various examples, lead electrodes 26 include one or more segmented electrodes.

[0051] IPG 14 may include a hermetically sealed IPG housing 322 to house the electronic circuitry of IPG 14. IPG 14 may include electrodes 326 formed on the IPG housing 322. IPG 14 may include an IPG head 324 for coupling the proximal ends of leads 12A and 12B. IPG head 324 may optionally also include an electrode 328. One or both of electrodes 326 and 328 may be used as a reference electrode.

[0052] Implantable leads and electrodes can be configured in shape and size to deliver electrical neurostimulation energy to neuronal targets included in the brain of a subject. Neurostimulation energy can be delivered in a monopolar (also called unipolar) mode using electrode 326 or electrode 328 and one or more electrodes selected from electrode 26. Neurostimulation energy can be delivered in a bipolar mode using a pair of electrodes from the same lead (lead 12A or lead 12B). Neurostimulation energy can be delivered in an extended bipolar mode using one or more electrodes from one lead (e.g., one or more electrodes from lead 12A) and one or more electrodes from different leads (e.g., one or more electrodes from lead 12B).

[0053] Figure 4 Another example is shown of an IPG 404 and an implantable lead system 408 arranged to provide neurostimulation to a patient. Examples of the IPG 404 include... Figure 2 and Figure 3 IPG 14. Examples of lead system 408 include Figure 3 One or more of leads 12A and 12B. The distal end 406 of the lead includes multiple electrodes (e.g., Figure 3 Electrode 26). In the illustrated embodiment, the implantable lead system 408 is arranged to deliver deep brain stimulation (DBS) to a patient, wherein the stimulation target is neuronal tissue in a subdivision of the thalamus in the patient's brain. Other examples of DBS targets include neuronal tissue of the globus pallidus (GPi), subthalamic nucleus (STN), peduncular nucleus (PPN), substantia nigra reticularis (SNr), cortex, lateral globus pallidus (GPe), medial forebrain tract (MFB), periaqueductal gray matter (PAG), periventricular gray matter (PVG), habenular nucleus, subgenual cingulate gyrus, ventral intermediate nucleus (VIM), anterior nucleus (AN), other nuclei of the thalamus, zona indeterminate, ventral bursa, ventral striatum, nucleus accumbens, and any white matter fiber bundles connecting these structures and other structures.

[0054] After implantation, clinicians will program the neurostimulation device 400 using a CP 18, remote control, or other programming device. The programmed neurostimulation device 400 can be used to treat patients' neurological conditions such as Parkinson's disease, tremor, epilepsy, Alzheimer's disease, other dementias, stroke, multiple sclerosis, amyotrophic lateral sclerosis (ALS), autism, brain injury, brain tumors, migraines or other pain or headache conditions, and any homologous, degenerative, or acquired neurological syndromes.

[0055] Back Figure 3The electronic circuitry of IPG 14 may include stimulation control circuitry that controls the delivery of neural stimulation energy. Stimulation control circuitry may include a microprocessor, digital signal processor, application-specific integrated circuit (ASIC), or other type of processor that interprets or executes instructions included in software or firmware. Neural stimulation energy may be delivered according to specified (e.g., programmed) modulation parameters. Examples of setting modulation parameters, among other things, may include: selecting an electrode or electrode combination used in the stimulation; configuring one or more electrodes as the anode or cathode of the stimulation; specifying the percentage of neural stimulation provided by the electrode or electrode combination; and specifying stimulation pulse parameters. Examples of pulse parameters, among other things, include: the amplitude of the pulse (specified in current or voltage), the pulse duration (e.g., in microseconds), the pulse rate (e.g., in pulses per second), and parameters associated with the pulse train or pattern, such as burst rate (e.g., an "ON" modulation time followed by an "OFF" modulation time), the pulse amplitude in the pulse train, the polarity of the pulse, etc.

[0056] Figure 5 This is a schematic side view of an embodiment of the electrical stimulation lead. Figure 5 A stimulation lead 12 is shown, wherein electrodes 26 are arranged at least partially around the circumference of the lead 12 along the distal portion of the lead, and terminals 27 are arranged along the proximal portion of the lead. The lead 12 can be implanted near or within a desired portion of the body to be stimulated, such as the brain, spinal cord, or other body organs or tissues. In one example of deep brain stimulation surgery, access to a desired location in the brain can be achieved by drilling holes in the patient's skull or cranium with a skull drill (commonly referred to as a burr) and coagulating and cutting the dura mater or brain covering. The lead 12 can be inserted into the skull and brain tissue with the assistance of a core needle (not shown). The lead 12 can be guided to the target location in the brain using, for example, a stereotactic frame and a micro-drive motor system. In some embodiments, the micro-drive motor system can be fully automated or partially automated. The micro-drive motor system can be configured to perform one or more of the following actions (alone or in combination): inserting the lead 12, advancing the lead 12, retracting the lead 12, or rotating the lead 12.

[0057] In some embodiments, the measuring device, coupled to muscle or other tissue stimulated by target neurons, or the unit responsive to a patient or clinician, may be coupled to an implantable pulse generator or micro-drive motor system. The measuring device, user, or clinician may instruct the target muscle or other tissue to respond to stimulation or recording electrodes to further identify the target neurons and facilitate the localization of the stimulating electrodes. For example, if the target neurons are directed to a muscle experiencing tremors, the measuring device may be used to observe the muscle and indicate, for example, changes in the frequency or amplitude of tremors in response to stimulation of the neurons. Alternatively, the patient or clinician may observe the muscle and provide feedback.

[0058] The lead 12 for deep brain stimulation may include stimulating electrodes, recording electrodes, or both. In at least some embodiments, the lead 12 is rotatable, such that after neurons have been located using recording electrodes, the stimulating electrodes can be aligned with the target neurons. The stimulating electrodes may be positioned on the circumference of the lead 12 to stimulate the target neurons. The stimulating electrodes may be annular, such that current is projected equally from each electrode in every direction along the length of the lead 12 from the electrode's location. Figure 5 In this embodiment, two of the electrodes in electrode 520 are ring electrodes 520. Ring electrodes typically cannot enable the guidance of stimulation current from only a limited angular range around the lead. However, segmented electrodes 530 can be used to guide stimulation current to a selected angular range around the lead. When segmented electrodes 530 are used in conjunction with IPG 14, which delivers constant current stimulation, current redirection can be achieved to deliver stimulation more precisely to a location around the lead axis (e.g., radially around the lead axis). To achieve current redirection, segmented electrodes can be used in addition to, or as an alternative to, ring electrodes.

[0059] Lead 12 includes a lead body 510, terminals 27, and one or more annular electrodes 520 and one or more segmented electrodes 530 (or any other combination of electrodes). The lead body 510 may be formed of a biocompatible, non-conductive material, such as, for example, a polymeric material. Suitable polymeric materials include, but are not limited to, silicone, polyurethane, polyurea, polyurethane urea, polyethylene, or the like. Once implanted in the body, lead 12 can be in contact with body tissue for an extended period of time. In at least some embodiments, lead 12 has a cross-sectional diameter not exceeding 1.5 mm and may be in the range of 0.5 to 1.5 mm. In at least some embodiments, lead 12 has a length of at least 10 cm and the length of lead 12 may be in the range of 10 to 70 cm.

[0060] Electrode 26 may be made of metal, alloy, conductive oxide, or any other suitable conductive biocompatible material. Examples of suitable materials include, but are not limited to, platinum, platinum-iridium alloy, iridium, titanium, tungsten, palladium, palladium-rhodium, or the like. Preferably, the electrode is made of a biocompatible material that is substantially non-corrosive under the intended operating conditions in the operating environment during the intended duration of use. Each electrode may be used or not used (OFF). When an electrode is used, it may function as an anode or cathode and carry anodic or cathodic current. In some cases, the electrode may be an anode for a period of time and a cathode for a period of time.

[0061] Deep brain stimulation leads and other leads may include one or more segments of segmented electrodes. Segmented electrodes can provide better current redirection than loop electrodes because the target structures in deep brain stimulation or other stimuli are typically not axially symmetric about the distal electrode array. Instead, the target may lie on one side of a plane passing through the lead axis. By using a radially segmented electrode array (RSEA), current redirection can be performed not only along the length of the lead but also around its circumference. This provides precise three-dimensional targeting and delivery of current stimulation to the neural target tissue, while potentially avoiding stimulation of other tissues.

[0062] Any number of segmented electrodes 530 may be disposed on the lead body 510, including, for example, any number from one to sixteen or more segmented electrodes 530. It will be understood that any number of segmented electrodes 530 may be disposed along the length of the lead body 510. The segmented electrodes 530 typically extend only 75%, 67%, 60%, 50%, 40%, 33%, 25%, 20%, 17%, 15%, or less around the circumference of the lead.

[0063] The segmented electrodes 530 can be divided into multiple groups of segmented electrodes, each group being disposed around the circumference of the lead 12 at a specific longitudinal portion of the lead 12. In a given group of segmented electrodes, the lead 12 can have any number of segmented electrodes 530. In a given group, the lead 12 can have one, two, three, four, five, six, seven, eight, or more segmented electrodes 530. In at least some embodiments, each group of segmented electrodes 530 of the lead 12 contains the same number of segmented electrodes 530. The segmented electrodes 530 disposed on the lead 12 can include a different number of electrodes than at least another group of segmented electrodes 530 disposed on the lead 12. The segmented electrodes 530 can vary in size and shape. In some embodiments, all segmented electrodes 530 are of the same size, shape, diameter, width, or area, or any combination thereof. In some embodiments, the segmented electrodes 530 of each circumferential group (or even all segmented electrodes disposed on the lead 12) can be identical in size and shape.

[0064] Each group of segmented electrodes 530 may be arranged around the circumference of the lead body 510 to form a generally cylindrical shape around the lead body 510. The spacing between individual electrodes in a given group of segmented electrodes may be the same as or different from the spacing between individual electrodes in another group of segmented electrodes on the lead 12. In at least some embodiments, equal spaces, gaps, or cuts are provided between each segmented electrode 530 around the circumference of the lead body 510. In other embodiments, the spaces, gaps, or cuts between the segmented electrodes 530 may differ in size, or the cuts between the segmented electrodes 530 may be consistent for a particular group of segmented electrodes 530 or for all group of segmented electrodes 530. The multi-group segmented electrodes 530 may be positioned at irregular or regular intervals along the length of the lead body 510.

[0065] Conductive wires (not shown) attached to the ring electrode 520 or segmented electrode 530 extend along the lead body 510. These conductor wires may extend through the material of the lead 12 or along one or more cavities defined by the lead 12, or both. The conductor wires couple the electrodes 520, 530 to the terminal 27.

[0066] Figures 6A-6H This is an illustration of different embodiments of leads 12 having segmented electrodes 330, optional ring electrodes 320 or tip electrodes 320a, and lead bodies 310. Each group of multi-group segmented electrodes 330 includes two ( Figure 6B ), three ( Figures 6E-6H ) or four ( Figure 6A , Figure 6C and Figure 6D () or any other number of segmented electrodes, including, for example, three, five, six or more. The multi-group segmented electrodes 330 can be aligned with each other ( Figures 6A-6G ) or interlaced ( Figure 6H ).

[0067] When lead 12 includes both a ring electrode 320 and segmented electrodes 330, the ring electrode 320 and segmented electrodes 330 can be arranged in any suitable configuration. For example, when lead 12 includes two ring electrodes 320 and two sets of segmented electrodes 330, the ring electrode 120 can be located on the flanks of the two sets of segmented electrodes 330 (see example...). Figure 2 , Figure 5 , Figure 6A and 6E - Figure 6H (ring electrode 320 and segmented electrode 330). Alternatively, the two sets of ring electrodes 320 may be disposed near the two sets of segmented electrodes 330 (see, for example...). Figure 6C (ring electrode 320 and segmented electrode 330), or the two sets of ring electrodes 320 may be disposed on the distal side of the two sets of segmented electrodes 330 (see, for example) Figure 6D (Ring electrode 320 and segmented electrode 330). One of the ring electrodes can be a tip electrode (see, for example, the ring electrode 320 and the segmented electrode 330). Figure 6E and Figure 6G (The tip electrode 320a). It will be understood that other configurations are also possible (e.g., alternating ring electrodes and segmented electrodes, or the like).

[0068] By changing the position of the segmented electrode 330, different coverage areas of the target neuron can be selected. For example, if the physician expects the neural target to be closer to the distal tip of the lead body 310, then... Figure 6C Electrode placement may be useful, especially if the physician expects the neural target to be closer to the proximal end of the lead body 310. Figure 6D The electrode arrangement may be useful.

[0069] Any combination of the annular electrode 320 and the segmented electrodes 330 can be disposed on the lead 12. For example, the lead 12 may include a first annular electrode 320, two sets of segmented electrodes (each set consisting of four segmented electrodes 330), and a final annular electrode 320 at the end of the lead. This configuration can be simply referred to as a 1-4-4-1 configuration. Figure 6A and Figure 6E (320 ring electrode and 330 segmented electrode). Using this abbreviated notation to refer to electrodes can be useful. Therefore, Figure 6C The implementation example can be referred to as a 1-1-4-4 configuration, while Figure 6D An example of this configuration may be referred to as a 4-4-1-1 configuration. Figure 6F , Figure 6G and Figure 6HAn embodiment may be referred to as a 1-3-3-1 configuration. Other electrode configurations include, for example, a 2-2-2-2 configuration in which four groups of segmented electrodes are disposed on the lead, and a 4-4 configuration in which two groups of segmented electrodes (each group having four segmented electrodes 330) are disposed on the lead. Figure 6F , Figure 6G and Figure 6H The 1-3-3-1 electrode configuration has two groups of segmented electrodes, each group containing three electrodes arranged in a circle around the lead wire, with two annular electrodes on the flanks. Figure 6F and Figure 6H ) or a ring electrode and a tip electrode ( Figure 6G In some embodiments, the lead includes 16 electrodes. Possible configurations for the 16-electrode lead include, but are not limited to: 4-4-4-4; 8-8; 3-3-3-3-3-1 (and all rearrangements of this configuration); and 2-2-2-2-2-2-2-2.

[0070] Any other suitable arrangement of segmented electrodes and / or loop electrodes can be used. As an example, one arrangement is in which the segmented electrodes are arranged spirally relative to each other. One embodiment includes a double helix. One or more electrical stimulation leads can be implanted within the patient's body (e.g., in the patient's brain or spinal cord) and used to stimulate surrounding tissues. The leads are coupled to an implantable pulse generator (such as...) Figure 2 (IPG 14 in the text).

[0071] Figure 7 This is a block diagram of a portion of an embodiment of medical device 700. Medical device 700 may be a monitoring device for monitoring neural activity signals of a patient or subject, or medical device 700 may be a neurostimulation device for providing neural stimulation to a patient (e.g., Figure 2 (IPG 14). Medical device 700 includes control circuitry 744 and sensing circuitry 746. Sensing circuitry 746 may include one or more sensing amplifiers to sense internal neural signals of a patient. The sensing amplifiers may switch between recording electrodes. Control circuitry 744 may include processing circuitry, such as a microprocessor, digital signal processor, application-specific integrated circuit (ASIC), or other type of processor, which interprets or executes instructions in a software module or firmware module. Instructions may be stored in memory 750, which may be integrated with or separate from control circuitry 744. Control circuitry 744 may include other circuitry or sub-circuitry for performing the described functions. These circuitry may include software, hardware, firmware, or any combination thereof. Multiple functions may be performed in one or more of the circuitry or sub-circuitry as needed.

[0072] Medical device 700 may also include communication circuitry 754, which communicates with individual devices (e.g., Figure 2(CP 18) Wireless communication. If the medical device 700 is a neurostimulation device, then the medical device 700 includes stimulation circuitry 742. Stimulation circuitry 742 may be operatively coupled to stimulation electrodes, such as any of the electrodes and leads described herein, and stimulation circuitry 742 provides or delivers electrical stimulation energy to the electrodes. Control circuitry 744 may use stimulation circuitry 742 to control the delivery of electrical neurostimulation. The electrical neurostimulation may be delivered according to neurostimulation therapy parameters configured in control circuitry 744, e.g., by programming.

[0073] Medical device 700 includes signal processing circuitry 748, which may be separate from or integrated with control circuitry 744. Signal processing circuitry 748 may include one or more processes running on one or more processors (e.g., one or more microprocessors that may include control circuitry 744 or may be separate from control circuitry 744) to perform signal analysis or other signal processing on neural signals sensed using sensing circuitry 746. Medical device 700 may include analog-to-digital converter (ADC) circuitry 752 to digitize the sensed neural signals for signal processing.

[0074] The medical device 700 can sense electrical nerve signals when coupled to electrodes. The medical device 700 can be used to sense a patient's response to nerve stimulation. The sensed response can be used to adjust the nerve stimulation by automatically adjusting the parameters of the nerve stimulation therapy or by recommending parameter settings to the user.

[0075] Figure 8 Is operating medical devices (e.g.) Figure 7 The flowchart illustrates an example of a method 800 for monitoring the electrical neural activity of a patient or subject using a medical device 700. The medical device calculates and utilizes the low-frequency power (e.g., 1 / f power) of the sensed neural signals to detect the patient's physiological condition or physiological events relevant to neuromodulation therapy. If the medical device provides neural stimulation, the 1 / f power distribution can be utilized as part of an adaptive neuromodulation therapy provided by the medical device. The 1 / f power distribution can be characterized by its slope, and the slope of the 1 / f power can be a robust measure of the therapeutic relevance to the patient's physiological condition.

[0076] At box 805, a sensing circuit for a medical device (e.g.) is used. Figure 7The sensing circuit 746 in the device senses the patient's local field potential (LFP) signal. The medical device can be connected to DBS electrodes and can sense LFP signals from brain tissue. For example, LFP signals can be sensed using electrodes located on or near the patient's subthalamic nucleus (STN), medial pallidum (GPi), or motor cortex. In some examples, the LFP signal is an electroencephalogram (EEG) signal. The sensing circuit can sense LFP signals whose frequencies fall within one or more of the alpha, beta, gamma, or theta bands of the EEG frequency band.

[0077] In some examples, the medical device is connected to SCS electrodes and senses LFP signals from the patient's spinal nerve tissue. In some examples, the medical device is connected to PNS electrodes and senses LFP signals from neural tissue (such as the patient's vagus nerve). In some examples, the medical device senses LFP signals from around the patient's brain.

[0078] At box 810, the signal processing circuitry of the medical device (e.g., Figure 7 The signal processing circuit 748 calculates the power spectral density (PSD) of one or more sensed LFP signals. In some examples, the signal processing circuit calculates the Fast Fourier Transform (FFT) or Short-Time Fourier Transform (STFT) of the LFP signal to obtain the 1 / f power distribution of the LFP signal. In some examples, the signal processing circuit performs autocorrelation function (ACF) analysis or wavelet spectral analysis on the LFP signal. The signal processing circuit calculates the slope of the PSD determined from the LFP signal.

[0079] Medical devices can use other methods to calculate PSD. In some examples, the medical device uses Welch's method to calculate an estimate of the PSD and then calculates the slope of the estimated PSD. In some examples, the medical device implements a neural network or other machine learning algorithm. The neural network can be trained to output PSD or the slope of the PSD from one or more LFP signals. The neural network can determine the PSD for a frequency band or frequency range.

[0080] At box 815, the medical device uses the calculated slope of the PSD of the sensed LFP signal to determine the patient's physiological state. The quantified PSD slope is related to the degree of excitation / inhibition (E / I) balance present in the neural activity reflected in the LFP signal. Examples of physiological states that can be detected by the medical device from the slope of the PSD of the sensed LFP signal are the sleep states of patients in normal sleep or under anesthesia. The medical device can determine whether the patient is in deep sleep or light sleep from the slope of the PSD of the sensed LFP signal.

[0081] In another example, the medical device determines a patient's pain state. LFP signals can be sensed from the patient's spinal nerve tissue, and the medical device uses the calculated slope of the PSD of the sensed spinal cord LFP signals to determine changes in the patient's pain state. In a further example, the medical device senses LFP signals from nerve tissue surrounding the patient's spinal cord, and uses the slope of the PSD of the sensed peripheral LFP signals to determine the patient's physiological state. For example, LFP signals can be sensed from the patient's vagus nerve, and the calculated slope of the PSD of the LFP signals sensed from the vagus nerve can be used to determine the patient's vagal nerve tone.

[0082] Figure 9 Here are two examples of PSD distribution curves for LFP sensed in the STN of an anesthetized subject. Curve 905 shows the relationship between PSD in dB and frequency for a subject under mild anesthesia, and curve 910 shows the relationship between PSD in dB and frequency for a subject under deep anesthesia. The curves show that above approximately 45 Hz, the PSD slope 920 for deep anesthesia is steeper than the PSD slope 915 for mild anesthesia. Therefore, the steeper PSD slope reflects greater inhibition of neural activity. The signal processing circuitry can calculate the PSD slope as the ratio of power change to frequency change. In some examples, the signal processing circuitry estimates the PSD slope as the average power over a first frequency range (e.g., P in 70-90 Hz). AVE ) and the average power over the second frequency range (e.g., P at 50-70 Hz) AVE The ratio of ).

[0083] Figure 10Here are two examples of PSD distribution curves for LFP sensed in the GPi of an anesthetized subject. The curves show that above approximately 35 Hz, the PSD slope of curve 1010 for deeper anesthesia is steeper than the PSD slope of curve 1005 for milder anesthesia, and again, the steeper slope reflects greater inhibition of neural activity. The slope of the PSD, which can be sensed from other regions of interest (e.g., the motor cortex) and determined by the medical device, can be used to distinguish physiological states with varying degrees of neural activity activation or inhibition, such as distinguishing between deeper and lighter sleep states. If the medical device provides neurostimulation therapy, the control circuitry of the medical device (e.g., Figure 7 The control circuit 744 in the middle can make decisions (e.g., change therapy parameters) to optimize neurostimulation therapy.

[0084] Because medical devices can calculate the PSD of LFP signals and quantify the PSD slope, they can monitor the PSD slope in response to changes in a patient's disease or injury status. For example, a medical device can cyclically monitor the PSD slope and detect when a change in the PSD slope exceeds a predetermined amount. When a change in the PSD slope is detected, the medical device can send a notification to another device to alert the user to the change in the patient's injury. If the medical device provides neurostimulation therapy, its control circuitry can adjust the neurostimulation therapy parameters in response to detected changes in the PSD slope.

[0085] Medical devices can use the slope of the PSD distribution to distinguish other physiological states. For example, a patient may be taking medication. A steeper PSD slope detected by the medical device can indicate a higher level of inhibition of neural activity, suggesting that the patient has taken the medication and that it is working. A flatter slope detected by the medical device can indicate a lower level of inhibition of neural activity, suggesting that the patient has not taken the medication or that the patient should take another dose. The signal processing circuitry of the medical device can then generate medication-related prompts based on the detected patient medication status.

[0086] Figure 11 This is an illustration of the operation of IPG 1114 and a patient's personal device (such as smartphone 1160). Smartphone 1160 includes a companion app for IPG 1114. This app can be used to train a classifier or regression algorithm that can detect medication status and provide information about the patient's medication status.

[0087] The IPG 1114 collects PSD slope data according to a time schedule (e.g., 2-minute LFP signals sensed every 30 minutes) and calculates the PSD slope data from the sensed signals. A smartphone user (e.g., a patient or caregiver) records medication events (e.g., when the patient takes medication, when the patient skips medication, etc.). The IPG 1114 pairs with smartphone 1152 to transmit the PSD slope data to smartphone 1160. The app associates the PSD slope data from the IPG 1114 with the recorded medication events.

[0088] PSD slope data and medication events can be compiled over multiple cycles of drug absorption and drug dissipation. These data cycles can be used as training data to train a machine learning model 1162 (e.g., a linear regression model, a Bayesian model, a logistic regression model, etc.). The machine learning model 1162 can be deployed on a smartphone 1160. Based on subsequent PSD slope data, the machine learning model 1162 can provide informed medication reminders 1164 to the patient on the smartphone 1160.

[0089] In another example, machine learning model 1162 is deployed in IPG 1114. Recorded medication events are transmitted to IPG 1114, and medication cycle and PSD slope data are input into machine learning model 1162. The trained model can be deployed in IPG 1114 (e.g., in IPG firmware), and IPG 1114 can send medication reminders to smartphone 1160 based on subsequent PSD slope data collected by the IPG.

[0090] In some examples, sensors can be used to provide additional context to the PSD slope information obtained from the LFP signal. For instance, PSD slope information can be used to detect a patient's motion state, such as whether the patient is experiencing, for example, a tremor. A flatter PSD slope can indicate more motion compared to a steeper PSD slope, which indicates inhibition in the neural activity that caused the motion. Motion sensors such as accelerometers (wearable or integrated into medical devices) can be used to identify the type of motion associated with a patient's injury or disease and to confirm the motion state detected from the PSD slope information. If the medical device provides neurostimulation therapy, the device's control circuitry can adjust therapy parameters based on the detected patient motion state.

[0091] Other wearable or implantable sensors can provide information about changes in a patient's injury status, such as sensors that can provide information about changes in a patient's speech, for example, due to increased injury from the disease. Additional information from one or more additional sensors can lead to a more accurate device-based assessment of the patient's condition.

[0092] The systems and methods described herein include techniques for improving the performance of adaptive neuromodulation methods. A 1 / f power distribution can provide robust feedback for closed-loop neuromodulation therapy.

[0093] The detailed description above is intended to be illustrative and not restrictive. Therefore, the scope of this disclosure should be determined by reference to the appended claims and the full scope of their equivalents.

Claims

1. A neural stimulation device, comprising: sensing circuitry configured to sense a local field potential (LFP) signal of a patient when connected to an implantable electrode; and signal processing circuitry operably coupled to the sensing circuitry and configured to: calculate a power spectral density (PSD) of the sensed LFP signal; calculate a slope of the PSD of the sensed LFP signal; and determine a physiological state of the patient using the calculated slope of the PSD of the sensed LFP signal.

2. The neural stimulation device of claim 1, comprising: stimulation circuitry configured to deliver electrical neurostimulation therapy to the patient when connected to the implantable electrode; and control circuitry operably coupled to the stimulation circuitry and the signal processing circuitry and configured to control delivery of neurostimulation therapy to the patient; wherein the signal processing circuitry is configured to detect a motion state indicative of tremor motion of the patient using the slope of the PSD of the sensed LFP signal; and wherein the control circuitry is configured to change a neurostimulation therapy parameter based on the detected motion state of the patient.

3. The nerve stimulation device of claim 1 or claim 2, wherein, the signal processing circuitry is configured to: determine a medication state of the patient using the slope of the PSD of the sensed LFP signal; and generate a medication-related prompt to the patient based on the determined medication state of the patient.

4. The neural stimulation device of claim 1, comprising: stimulation circuitry configured to deliver electrical neurostimulation therapy to the patient when connected to the implantable electrode; and control circuitry operably coupled to the stimulation circuitry and the signal processing circuitry and configured to control delivery of neurostimulation therapy to the patient; wherein the signal processing circuitry is configured to detect a sleep state of the patient using the slope of the PSD of the sensed LFP signal, wherein the sleep state is indicative of a sleep depth of the patient; and wherein the control circuitry is configured to change a neurostimulation therapy parameter based on the detected sleep state of the patient.

5. The neural stimulation device of claim 1, comprising: stimulation circuitry configured to deliver electrical neurostimulation therapy to the patient when connected to the implantable electrode; and control circuitry operably coupled to the stimulation circuitry and the signal processing circuitry and configured to control delivery of neurostimulation therapy to the patient; wherein the signal processing circuitry is configured to detect a change in an impairment state of the patient using the slope of the PSD of the sensed LFP signal; and wherein the control circuitry is configured to change a neurostimulation therapy parameter based on the detected change in the impairment state of the patient.

6. The neural stimulation device of any of claims 1-5, the sensing circuitry is configured to sense a spinal cord LFP signal from a spinal nerve tissue of the patient; and wherein wherein the signal processing circuitry is configured to determine the slope of the PSD of the sensed spinal cord LFP signal. ​ ​ 7. The neurostimulation device of any one of claims 1-6, wherein, the sensing circuitry is configured to sense a peripheral LFP signal from peripheral nervous tissue surrounding the patient's spinal cord; and wherein the signal processing circuitry is configured to determine a slope of a PSD of the sensed peripheral LFP signal.

8. The neurostimulation device of any one of claims 1-7, wherein the sensing circuitry is configured to sense a peripheral LFP signal from peripheral nervous tissue surrounding the patient's brain; and wherein the signal processing circuitry is configured to determine a slope of a PSD of the sensed peripheral LFP signal.

9. The nerve stimulation device of any one of claims 1-8, wherein, the signal processing circuitry is configured to: calculate a slope of a PSD of a gamma electroencephalography band of the sensed LFP signal; and determine a physiological state of the patient using the calculated slope of the PSD of the gamma electroencephalography band of the sensed LFP signal.

10. A computer-implemented method of operating a medical device, the method comprising: sensing, using the medical device, a local field potential (LFP) signal of a patient; determining, by the medical device, a power spectral density (PSD) of the sensed LFP signal and a slope of the PSD of the sensed LFP signal; and determining a physiological state of the patient using the slope of the PSD of the sensed LFP signal.

11. The method of claim 10, comprising: delivering, using the medical device, an electrical neurostimulation therapy to the patient; detecting a motor state of the patient using the slope of the PSD of the sensed LFP signal, wherein the motor state is indicative of tremor movement of the patient; and changing a neurostimulation therapy parameter based on the detected motor state of the patient.

12. The method of claim 10 or claim 11, comprising: determining a medication state of the patient using the slope of the PSD of the sensed LFP signal; and generating a prompt related to medication of the patient based on the determined medication state of the patient.

13. The method of any one of claims 10-12, comprising: delivering, using the medical device, an electrical neurostimulation therapy to the patient; detecting a sleep state of the patient using the slope of the PSD of the sensed LFP signal, wherein the sleep state is indicative of a depth of sleep of the patient; and changing a neurostimulation therapy parameter based on the detected sleep state of the patient.

14. The method of any one of claims 10-13, comprising: delivering, using the medical device, an electrical neurostimulation therapy to the patient; detecting a change in an impairment state of the patient using the slope of the PSD of the sensed LFP signal; and changing a neurostimulation therapy parameter based on the detected change in the impairment state of the patient.

15. The method of any one of claims 10-14, wherein, sensing the LFP signal comprises sensing a spinal LFP signal from spinal nervous tissue of the patient; wherein determining the slope of the PSD comprises determining a slope of a PSD of the sensed spinal LFP signal; and determining a change in a pain state of the patient using the slope of the PSD of the sensed peripheral LFP signal.

Images