Selecting thresholds for closed-loop neuromodulation systems

Abstract

A system includes a memory; and processing circuitry coupled to the memory and configured to: control sensing circuitry to sense a bioelectric signal of a patient over an ambulatory period of time; determine, based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determine, based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; select, based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

Description

Docket No.: A0012611W001SELECTING THRESHOLDS FOR CLOSED-LOOP NEUROMODULATION SYSTEMSCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 726,092 filed November 27, 2024, which is incorporated herein by reference in its entiretyTECHNICAL FIELD

[0002] This disclosure generally relates to medical devices and, more particularly, electrical stimulation therapy.BACKGROUND

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

[0004] In general, the disclosure describes devices, systems, and techniques for setting thresholds for electrical stimulation therapy systems based on chronic, averaged, and filtered data. In some examples, the system senses a bioelectric signal, e.g., a local field potential (LFP) signal over an ambulatory period of a patient. The ambulatory period may be a period of time, e.g., hours, days or weeks, during which the patient was outside of a clinic. In some examples, the patient may perform activities of daily living during the ambulatory period. In some examples, the patient may take a medication and / or receive electrical stimulation therapy during the ambulatory period. In some examples, the patient may be off medication and / or electrical stimulation therapy during the ambulatory period, e.g., during a first ambulatory period.

[0005] Based on the bioelectric signal sensed over the ambulatory period, the system determines characteristic values, e.g., amplitude values, of the bioelectric signal over a recurring interval of the bioelectric signal. As an example, the recurring interval may be 1 day, and theDocket No.: A0012611W001 ambulatory period may be within a range of 1 day to 1 month. Based on the characteristic values, the system determines representative values, e.g., average values of the characteristic values, corresponding to respective times within the recurring interval. In some examples, the system may filter the representative values based on a patient schedule. As an example, the system may filter times during which the patient is sleeping or resting and may maintain active hours of the patient. In this manner, the filter may reduce the number of representative values used for further analysis. Based on the filtered representative values, the system can select one or more threshold values, the one or more threshold values forming a homeostatic window. In some examples, to select the one or threshold values, the system selects one or more of an upper threshold value or a lower threshold value. The system may set the upper threshold to a value within a range of the 65thto the 85thpercentile of the range of representative values and / or set the lower threshold to a value within a range of the 15thto the 35thpercentile of the range of representative values. The system can be configured to then sense subsequent bioelectric signals and controls electrical stimulation therapy according to the one or more thresholds and characteristic values corresponding to the subsequent bioelectric signals.

[0006] In some examples, the ambulatory period is a monitoring phase in which therapy is not delivered, and the system controls electrical stimulation therapy during a subsequent therapeutic phase based on the one or more thresholds and the characteristic values of the subsequent bioelectric signal determined during the monitoring phase. In some examples, the ambulatory period is a first ambulatory period. The system may determine to adjust the one or more thresholds during the therapeutic phase and / or during a second ambulatory period in response to a criterion being met, such as a threshold period of time elapsing, a change in patient state, and / or a change between the representative values of the bioelectric signal and the characteristic values of the subsequent bioelectric signal. In response to the criterion being met, the system may determine second representative values corresponding to respective times within a second recurring interval over the second ambulatory period. The second recurring interval and the second ambulatory period may have the same or different values from the recurring interval of the first ambulatory period.

[0007] If the second representative values meet one or more criteria, e.g., if a difference between the representative values corresponding to the first ambulatory period and the second representative values meets a difference threshold, the system may adjust the one or more threshold values. In some examples, the system may adjust the one or more threshold values to a limited extent. As an example, the system may adjust the one or more thresholds within a threshold percentage. In this manner, the system may iteratively update thresholds or other data over time.Docket No.: A0012611W001

[0008] In one example, a system includes: a memory; and processing circuitry coupled to the memory and configured to: control sensing circuitry to sense a bioelectric signal of a patient over an ambulatory period of time; determine, based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determine, based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; select, based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

[0009] In another example, a method includes: controlling, by processing circuitry of a system, sensing circuitry of the system to sense a bioelectric signal of a patient over an ambulatory period of time; determining, by the processing circuitry and based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determining, by the processing circuitry and based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; selecting, by the processing circuitry and based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and controlling, by the processing circuitry, adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

[0010] In another example, a non-transitory computer-readable medium stores instructions that when executed cause processing circuitry to: control sensing circuitry to sense a bioelectric signal of a patient over an ambulatory period of time; determine, based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determine, based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; select, based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.Docket No.: A0012611W001

[0011] The details of one or more examples of the techniques of this disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0012] FIG. l is a conceptual diagram illustrating an example system that includes an implantable medical device (IMD) configured to deliver DBS to a patient according to an example of the techniques of the disclosure.

[0013] FIG. 2 is a block diagram of the example IMD of FIG. 1 for delivering DBS therapy according to an example of the techniques of the disclosure.

[0014] FIG. 3 is a block diagram of the external programmer of FIG. 1 for controlling delivery of DBS therapy according to an example of the techniques of the disclosure.

[0015] FIG. 4 is a conceptual diagram illustrating an example home screen for navigating within a user interface according to an example of the techniques of the disclosure.

[0016] FIG. 5 is a conceptual diagram illustrating an example screen for displaying a selected sensing electrode combination and signal of interest for a lead according to an example of the techniques of the disclosure.

[0017] FIG. 6 is a conceptual diagram illustrating an example screen for selecting an adaptive therapy mode according to an example of the techniques of the disclosure.

[0018] FIG. 7 is a conceptual diagram illustrating an example screen for determining one or more thresholds according to an example of the techniques of the disclosure.

[0019] FIG. 8 is a conceptual diagram illustrating an example pop-up window for confirming one or more thresholds according to an example of the techniques of the disclosure.

[0020] FIG. 9 is a flowchart illustrating an example operation for selecting one or more thresholds and controlling adjustment of electrical stimulation based on the one or more thresholds according to an example of the techniques of the disclosure.

[0021] FIG. 10 is a flowchart illustrating an example operation for adjusting the one or more thresholds according to an example of the techniques of the disclosure.

[0022] FIG. 11 is a flowchart illustrating an example operation for determining whether representative values meet one or more criteria for adjusting one or more thresholds according to an example of the techniques of the disclosure.DETAILED DESCRIPTION

[0023] This disclosure describes example devices, systems, and techniques for setting one or more threshold values for electrical stimulation therapy. The electrical stimulation therapy mayDocket No.: A0012611W001 be adaptive electrical stimulation therapy in which a system can adjust one or more parameters of stimulation therapy, based on chronic, averaged, and, optionally, filtered data. The data may include characteristic values, e.g., amplitude values, of a bioelectric signal, such as a local field potential (LFP) signal, of a patient. A patient may suffer from one or more symptoms treatable by electrical stimulation therapy. For example, a patient may suffer from brain disorder such as Parkinson’s disease, Alzheimer’s disease, or another type of movement disorder. Deep brain stimulation (DBS) may be an effective treatment to reduce the symptoms associated with such disorders. Current methods of configuring DBS therapy, e.g., automated DBS (aDBS) therapy, for a patient can include setting one or more threshold values corresponding to a bioelectric signal, e.g., the LFP signal, and, in some examples, one or more threshold values corresponding to stimulation parameters. To select the one or more threshold values corresponding to the bioelectric signal, current methods often include selecting the one or more threshold values based on an acute bioelectric signal sensed in a clinic, such as during system calibration. In some examples, the acute bioelectric signal sensed in the clinic may not be representative of typical system performance. For example, the in-clinic time may be for a very short time (e.g., less than 30 minutes) and the patient may not conduct normal activities or experience normal medication changes that would occur during a typical day.

[0024] As described herein, various devices, systems, and techniques enable selecting thresholds based on chronic, averaged, and, optionally, filtered data corresponding to tan ambulatory period. For example, systems described herein may be configured to sense and record bioelectric signals (e.g., LFP signals, associated with brain disorders) and determine characteristic values (e.g., amplitude values) of the bioelectric signal over a recurring interval of time (e.g., one day) within the ambulatory period (e.g., 2 days, 10 days, or 2 months). Based on the characteristic values, the system can determine representative values of the bioelectric signal for respective times within the recurring interval. Based on the representative values, the system selects one or more threshold values. The system may control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals. In some examples, the system may adjust the one or more threshold values in response to a criterion being met. The system may determine representative values based on the characteristic values of the subsequently sensed bioelectric signal, and, based on the representative values meeting one or more criteria, adjust the one or more threshold values.

[0025] These various features of the systems and techniques described herein may provide advantages over other systems and improve system functionality and patient outcomes. For example, by controlling stimulation therapy according to the one or more selected thresholdDocket No.: A0012611W001 values, the techniques of this disclosure may result in the one or more threshold values being more representative of typical system operation and typical patient activity and condition. By selecting more representative thresholds, the techniques of this disclosure may improve an accuracy of patient therapy, which may help to prevent patient side effects and symptoms.

[0026] Additionally, the techniques of this disclosure may include monitoring for changes in the bioelectric signal over time. The techniques of this disclosure may enable the system to identify changes in the bioelectric signal, which may improve one or more patient outcomes. As an example, based on the changes in the bioelectric signal, the system may adjust the one or more threshold values, which may improve patient symptom control.

[0027] FIG. 1 is a conceptual diagram illustrating an example system 100 that includes an implantable medical device (IMD) 106 configured to deliver DBS to a patient 112 according to an example of the techniques of the disclosure, in accordance with one or more techniques of this disclosure. In some examples, DBS may be adaptive (aDBS) in the sense that IMD 106 may adjust, increase, or decrease the value of one or more stimulation parameters that define the DBS in response to changes in patient activity or movement, a severity of one or more symptoms of a disease of the patient, a presence of one or more side effects due to the DBS, or one or more sensed signals of the patient, etc. For example, system 100 may use a bioelectric signal, e.g., an LFP signal, of patient 112 as a control signal such that the IMD 106 adjusts the magnitude of the one or more parameters of the electrical stimulation in response to the magnitude or change in magnitude of characteristic values, e.g., an amplitude, of the bioelectric signal. This process enables system 100 to automatically adjust stimulation therapy in response to changes to the patient condition, such as changes to brain activity indicative of a level of therapy efficacy.

[0028] Example therapy system 100 includes medical device programmer 104, IMD 106, lead extension 110, and leads 114A and 114B with respective sets of electrodes 116, 118. In the example shown in FIG. 1, electrodes 116, 118 of leads 114 A, 114B are positioned to deliver electrical stimulation to a tissue site within brain 120, such as a deep brain site under the dura mater of brain 120 of patient 112. In some examples, delivery of stimulation to one or more regions of brain 120, such as the subthalamic nucleus, globus pallidus or thalamus, may be an effective treatment to manage movement disorders, such as Parkinson’s disease. Some or all of electrodes 116, 118 also may be positioned to sense the bioelectric signal within brain 120 of patient 112. In some examples, some of electrodes 116, 118 may be configured to sense the bioelectric signal and others of electrodes 116, 118 may be configured to deliver adaptive electrical stimulation to brain 120. In other examples, all of electrodes 116, 118 are configured to both sense the bioelectric signal and deliver adaptive electrical stimulation to brain 120.Docket No.: A0012611W001

[0029] IMD 106 includes a therapy module (e.g., which may include processing circuitry, signal generation circuitry or other electrical circuitry configured to perform the functions attributed to IMD 106) that includes a stimulation generator configured to generate and deliver electrical stimulation therapy to patient 112 via a subset of electrodes 116, 118 of leads 114A and 114B, respectively. The subset of electrodes 116, 118 that are used to deliver electrical stimulation to patient 112, and, in some cases, the polarity of the subset of electrodes 116, 118, may be referred to as a stimulation electrode combination. As described in further detail below, the stimulation electrode combination can be selected for a particular patient 112 and target tissue site (e.g., selected based on bioelectric signal information and the patient condition). The group of electrodes 116, 118 includes at least one electrode and can include a plurality of electrodes. In some examples, the plurality of electrodes 116 and / or 118 may have a complex electrode geometry such that two or more electrodes are located at different positions around the perimeter of the respective lead.

[0030] According to some techniques of the disclosure, system 100, via IMD 106, delivers electrical stimulation therapy defined by one or more parameters, such as voltage or current amplitude within a therapeutic window (e.g., a window defined by one or more limits for the voltage or current amplitude), adjusted based on the characteristic the bioelectric signal feature and the one or more threshold values. System 100 may continuously monitor the bioelectric signal feature.

[0031] In some examples, system 100 adjusts the parameter of the electrical stimulation therapy adjusted in response to the bioelectric signal falling outside the one or more threshold values. In some examples, the one or more threshold values include one or more of an upper threshold or a lower threshold that forms a homeostatic window. The homeostatic window may be used as part of an adaptive mode for adjusting stimulation therapy over time. In some examples, system 100 may change other parameters in response to sensed signals such as stimulation pulse frequency, pulse burst duration, pulse burst frequency, duty cycle, or electrode combination. Throughout this disclosure, the terms “limit,” “threshold,” and “bound” can refer to similar concepts, e.g., each defines a window or range of acceptable values associated with adaptive therapy. Although the homeostatic window may be described as including an upper and lower threshold, only a single threshold (e.g., upper threshold or lower threshold) may be used in other examples.

[0032] In some examples, patient 112 takes a medication. In some examples, the medication taken by patient 112 is a medication for controlling one or more symptoms of Parkinson’s disease, such as tremor or rigidity due to Parkinson’s disease. Such medications include extended release forms of dopamine agonists, regular forms of dopamine agonists, controlled release formsDocket No.: A0012611W001 of carbidopa / levodopa (CD / LD), regular forms of CD / LD, entacapone, rasagiline, selegiline, and amantadine. To set the upper threshold and / or lower threshold of the homeostatic window, the patient may or may not be off medication. The patient may be considered to be not taking the medication when the patient has not taken the medication for at least approximately 72 hours for extended release forms of dopamine agonists, the patient has not taken the medication for at least approximately 24 hours for regular forms of dopamine agonists and controlled release forms of CD / LD, and the patient has not taken the medication for at least approximately 12 hours for regular forms of CD / LD, entacapone, rasagiline, selegiline, and amantadine. If only stimulation is suppressing bioelectric signals (e.g., LFP signals), then system 100 can measure the bioelectric signal for various values of stimulation parameters without outside inputs. Once the upper threshold and lower threshold is established, system 100 can identify when medication wears off because the brain signals will cross the lower or upper threshold. In response to identifying the characteristic values of the bioelectric signal crossing a threshold, system 100 may turn on, or adjust the amplitude or intensity of, electrical stimulation to bring the bioelectric signal amplitude back between the lower threshold and the upper threshold to reduce symptoms once again. Programmer 104 or IMD 106 may initially set the lower threshold and the upper threshold based on representative values of the bioelectric signal for respective times within an ambulatory period. Programmer 104 or IMD 106 may make adjustments to one or both thresholds over time based on subsequent representative values. Programmer 104 or IMD 106 may also determine and display information regarding the amount of time stimulation amplitude is above, below, or between the thresholds.

[0033] As described herein, “reducing” or “suppressing” the symptoms of the patient refer to alleviating, in whole or in part, the severity of one or more symptoms of the patient. In one example, the clinician makes a determination of the severity of one or more symptoms of Parkinson’s disease of patient 112 with reference to the Unified Parkinson's Disease Rating Scale (UPDRS) or the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). A discussion of the application of the MDS-UPDRS is provided by Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results, C. Goetz et al, Movement Disorders, Vol. 23, No. 15, pp. 2129-2170 (2008).

[0034] As described herein, system 100 may be configured to determine the upper limit of a therapeutic window while the patient is or is not taking medication, and while, via IMD 106, electrical stimulation therapy is delivered to the brain 120 of patient 112. In one example, system 100 determines the point at which increasing the magnitude of one or more parameters defining the electrical stimulation therapy, such as voltage amplitude or current amplitude, begins to causeDocket No.: A0012611W001 one or more side effects for the patient 112. For example, system 100 may gradually increase the magnitude of one or more parameters, such as amplitude, defining the electrical stimulation therapy and determine the point at which further increase to the magnitude of one or more parameters defining the electrical stimulation therapy causes a perceptible side effect for patient 112. System 100 may additionally determine a signal of interest, e.g., a 5 Hertz (Hz) band of the LFP signal, for monitoring during an ambulatory period. System 100 determines characteristic values of the LFP signal over a recurring interval within the ambulatory period. Based on the characteristic values, system 100 determines representative values, e.g., average values, for respective times within the recurring interval. Based on the representative values, system 100 determines one or more threshold values, such as one or more of an upper threshold or a lower threshold of a homeostatic window.

[0035] As also described above, system 100 can also determine the lower limit of the therapeutic window while the patient is on or off medication and while, via IMD 106, electrical stimulation therapy is delivered to the brain 120 of patient 112. In one example, system 100 determines the point at which decreasing the magnitude of one or more parameters, such as amplitude, defining the electrical stimulation therapy causes break-through of one or more symptoms of the patient 112. This break-through of symptoms may refer to re-emergence of at least some symptoms that were substantially suppressed up to the point of re-emergence due to the decrease in magnitude of the one or more electrical stimulation therapy parameters. For example, system 100 may gradually decrease the magnitude of one or more parameters defining the electrical stimulation therapy and determine the point at which the symptoms of Parkinson’s disease in patient 112 emerge, as measured by sudden increase with respect to tremor or rigidity, in the score of patient 112 under the UPDRS or MDS-UPDRS. In another example, system 100 measures a bioelectric parameter of patient 112 correlated to one or more symptoms of the disease of patient 112 (e.g., wrist flexion of patient 112) and determines the point at which further decrease to the magnitude of one or more parameters defining the electrical stimulation therapy causes a sudden increase in the one or more symptoms of the disease of patient 112 (e.g., onset of lack of wrist flexion of patient 112).

[0036] In some examples, for Beta signals, system 100 may select an upper threshold of the homeostatic window to be a predetermined amount, e.g., 15% or 35%, lower than a maximum representative value of the ambulatory period or select the upper threshold to between the 65thand 85thpercentile of the representative values. In some examples, the upper threshold may be outside the example ranges provided herein, such as the 60thpercentile or the 90thpercentile. In some examples, system 100 can set a lower threshold. In some examples, system 100 may select a value for the lower threshold of the homeostatic window to be a predetermined amount, e.g.,Docket No.: A0012611W00115% or 35%, higher than a minimum representative value of the ambulatory period or select the lower threshold to be between the 15thand 35thpercentile of the representative values. In some examples, the upper threshold may be selected from different ranges, such as in a range from the 10thpercentile to the 40thpercentile. In one example, the upper threshold may be 25% below the maximum representative value and the lower threshold may be 25% higher than the minimum representative value. In some examples, system 100 filters the representative values of the ambulatory period to exclude times at which patient 112 is resting or sleeping. System 100 selects the one or more threshold values based on the filtered representative values. In some examples, system 100 selects the one or more threshold values based on, or according to, clinician input received via a user interface that is indicative of the one or more threshold values.

[0037] As described herein, system 100 can monitor one or more signals of patient 112 for selecting one or more parameters defining stimulation and / or adjusting stimulation in a closed- loop manner. In one example, the signal is a bioelectric signal of patient 112, such as an LFP signal with a frequency within a Beta frequency band and / or a Gamma frequency band of the brain of patient 112. For example, the monitored signal may be a power of the respective Beta frequency band and / or Gamma frequency band. In yet a further example, the signal can be a signal indicative of a bioelectric parameter of the patient, such as a severity of a symptom of the patient, a movement of the patient, a posture of the patient, a respiratory function of the patient, a heart rate, or an activity level of the patient. System 100 may use a single signal or combination of different signals for initially selecting and / or adjusting one or more parameters that define subsequent electrical stimulation therapy. System 100, via IMD 106, can be configured to deliver electrical stimulation to patient 112, wherein one or more parameters defining the electrical stimulation are related by a transfer function (which may or may not be proportional to the magnitude of the monitored signal or adjusted in response to a magnitude of the monitored signal exceeding one or more thresholds).

[0038] System 100 may be configured to treat one or more patient conditions, such as a movement disorder, neurodegenerative impairment, a mood disorder, or a seizure disorder of patient 112. Patient 112 ordinarily is a human patient. In some cases, however, therapy system 100 may be applied to other mammalian or non-mammalian, non-human patients. While movement disorders and neurodegenerative impairment are primarily referred to herein, in other examples, therapy system 100 may provide therapy to manage symptoms of other patient conditions, such as, but not limited to, seizure disorders (e.g., epilepsy) or mood (or psychological) disorders (e.g., major depressive disorder (MDD), bipolar disorder, anxiety disorders, post-traumatic stress disorder, dysthymic disorder, and obsessive-compulsive disorder (OCD)). At least some of these disorders may be manifested in one or more patient movementDocket No.: A0012611W001 behaviors. As described herein, a movement disorder or other neurodegenerative impairment may include symptoms such as, for example, muscle control impairment, motion impairment or other movement problems, such as rigidity, spasticity, bradykinesia, rhythmic hyperkinesia, nonrhythmic hyperkinesia, and akinesia. In some cases, the movement disorder may be a symptom of Parkinson’s disease. However, the movement disorder may be attributable to other patient conditions.

[0039] In some examples, the bioelectric signals sensed within brain 120 may reflect changes in electrical current produced by the sum of electrical potential differences across brain tissue, or any voltage potentials between electrodes. In some examples, the bioelectric signal that is used to select a stimulation electrode combination may be sensed within the same region of brain 120 as the target tissue site for the electrical stimulation. As previously indicated, these tissue sites may include tissue sites within anatomical structures such as the thalamus, subthalamic nucleus or globus pallidus of brain 120, as well as other target tissue sites. The specific target tissue sites and / or regions within brain 120 may be selected based on the patient condition. Thus, in some examples, the electrodes used for delivering electrical stimulation may be different than the electrodes used for sensing the bioelectric signal. In other examples, the same electrodes may be used to deliver electrical stimulation and sense brain signals. However, this configuration may require system 100 to switch between stimulation generation and sensing circuitry and may reduce the time system 100 can sense brain signals.

[0040] Electrical stimulation generated by IMD 106 may be configured to manage a variety of disorders and conditions. In some examples, the stimulation generator of IMD 106 is configured to generate and deliver electrical stimulation pulses to patient 112 via electrodes of a selected stimulation electrode combination. However, in other examples, the stimulation generator of IMD 106 may be configured to generate and deliver a continuous wave signal, e.g., a sine wave or triangle wave. In either case, a stimulation generator within IMD 106 may generate the electrical stimulation therapy for DBS according to a therapy program that is selected at that given time in therapy. In examples in which IMD 106 delivers electrical stimulation in the form of stimulation pulses, a therapy program may include a set of therapy parameter values (e.g., stimulation parameters), such as a stimulation electrode combination for delivering stimulation to patient 112, pulse frequency, pulse width, stimulation cycling, and a current or voltage amplitude of the pulses. As previously indicated, the electrode combination may indicate the specific electrodes 116, 118 that are selected to deliver stimulation signals to tissue of patient 112 and the respective polarities of the selected electrodes. In some examples, a clinician may set up a plurality of therapy programs that patient 112 can manually switch between and / or that IMD 106 can cycle through. Based on patient feedback and / or sensedDocket No.: A0012611W001 signals, the clinician, the patient, and / or IMD 106 may select a therapy program for subsequent use.

[0041] IMD 106 may be implanted within a subcutaneous pocket above the clavicle, or, alternatively, on or within cranium 122 or at any other suitable site within patient 112. Generally, IMD 106 is constructed of a biocompatible material that resists corrosion and degradation from bodily fluids. IMD 106 may comprise a hermetic housing to substantially enclose components, such as a processor, therapy module, and memory.

[0042] As shown in FIG. 1, implanted lead extension 110 is coupled to IMD 106 via connector 108 (also referred to as a connector block or a header of IMD 106). In the example of FIG. 1, lead extension 110 traverses from the implant site of IMD 106 and along the neck of patient 112 to cranium 122 of patient 112 to access brain 120. In the example shown in FIG. 1, leads 114A and 114B (collectively “leads 114”) are implanted within the right and left hemispheres, respectively, of patient 112 in order deliver electrical stimulation to one or more regions of brain 120, which may be selected based on the patient condition or disorder controlled by therapy system 100. In some examples, more than two leads may be used in total or in each hemisphere, e.g., two leads per hemisphere (4 leads total), or an uneven number of leads between the hemispheres. The specific target tissue site and the stimulation electrodes used to deliver stimulation to the target tissue site, however, may be selected, e.g., according to the identified patient behaviors and / or other sensed patient parameters. Other lead 114 and IMD 106 implant sites are contemplated. For example, IMD 106 may be implanted on or within cranium 122, in some examples. Or leads 114 may be implanted within the same hemisphere or IMD 106 may be coupled to a single lead implanted in a single hemisphere.

[0043] Existing lead sets include axial leads carrying ring electrodes disposed at different axial positions and so-called “paddle” leads carrying planar arrays of electrodes. Selection of electrode combinations within an axial lead, a paddle lead, or among two or more different leads presents a challenge to the clinician. In some examples, more complex lead array geometries may be used.

[0044] Although leads 114 are shown in FIG. 1 as being coupled to a common lead extension 110, in other examples, leads 114 may be coupled to IMD 106 via separate lead extensions or directly to connector 108. Leads 114 may be positioned to deliver electrical stimulation to one or more target tissue sites within brain 120 to manage patient symptoms associated with a movement disorder of patient 112. Leads 114 may be implanted to position electrodes 116, 118 at desired locations of brain 120 through respective holes in cranium 122. Leads 114 may be placed at any location within brain 120 such that electrodes 116, 118 are capable of providing electrical stimulation to target tissue sites within brain 120 during treatment. For example,Docket No.: A0012611W001 electrodes 116, 118 may be surgically implanted under the dura mater of brain 120 or within the cerebral cortex of brain 120 via a burr hole in cranium 122 of patient 112, and electrically coupled to IMD 106 via one or more leads 114.

[0045] In the example shown in FIG. 1, electrodes 116, 118 of leads 114 are shown as ring electrodes. Ring electrodes may be used in aDBS applications because they are relatively simple to program and are capable of delivering an electrical field to any tissue adjacent to electrodes 116, 118. In other examples, electrodes 116, 118 may have different configurations. For example, in some examples, at least some of the electrodes 116, 118 of leads 114 may have a complex electrode array geometry that is capable of producing shaped electrical fields. The complex electrode array geometry may include multiple electrodes (e.g., partial ring or segmented electrodes) around the outer perimeter of each lead 114, rather than one ring electrode. In this manner, electrical stimulation may be directed in a specific direction from leads 114 to enhance therapy efficacy and reduce possible adverse side effects from stimulating a large volume of tissue. In some examples, a housing of IMD 106 may include one or more stimulation and / or sensing electrodes. In alternative examples, leads 114 may have shapes other than elongated cylinders as shown in FIG. 1. For example, leads 114 may be paddle leads, spherical leads, bendable leads, or any other type of shape effective in treating patient 112 and / or minimizing invasiveness of leads 114.

[0046] In the example shown in FIG. 1, IMD 106 includes a memory to store a plurality of therapy programs that each define a set of therapy parameter values. In some examples, IMD 106 may select a therapy program from the memory based on various parameters, such as sensed patient parameters and the identified patient behaviors. IMD 106 may generate electrical stimulation based on the selected therapy program to manage the patient symptoms associated with a movement disorder.

[0047] External programmer 104 wirelessly communicates with IMD 106 as needed to provide or retrieve therapy information. Programmer 104 is an external computing device that a user, e.g., a clinician and / or patient 112, may use to communicate with IMD 106. For example, programmer 104 may be a clinician programmer that the clinician uses to communicate with IMD 106 and program one or more therapy programs for IMD 106. Alternatively, programmer 104 may be a patient programmer that allows patient 112 to select programs and / or view and modify therapy parameters. The clinician programmer may include more programming features than the patient programmer. In other words, more complex or sensitive tasks may only be allowed by the clinician programmer to prevent an untrained patient from making undesirable changes to IMD 106.Docket No.: A0012611W001

[0048] When programmer 104 is configured for use by the clinician, programmer 104 may be used to transmit initial programming information to IMD 106. This initial information may include hardware information, such as the type of leads 114 and the electrode arrangement, the position of leads 114 within brain 120, the configuration of electrode array 116, 118, initial programs defining therapy parameter values, and any other information the clinician desires to program into IMD 106. Programmer 104 may also be capable of completing functional tests (e.g., measuring the impedance of electrodes 116, 118 of leads 114). In addition, or as an alternative, to programmer 104, a different external computing device may perform any of the functionality of programmer 104. The external computing device may be a networked device and in communication with IMD 106 directly or via programmer 104.

[0049] The clinician may also store therapy programs within IMD 106 with the aid of programmer 104. During a programming session, system 100 may determine one or more therapy programs that may provide efficacious therapy to patient 112 to address symptoms associated with the patient condition, and, in some cases, specific to one or more different patient states, such as a sleep state, movement state or rest state. For example, system 100 may select one or more stimulation electrode combinations with which stimulation is delivered to brain 120. During the programming session, system 100 may evaluate the efficacy of the specific program being evaluated based on feedback provided by the clinician or patient 112 or based on one or more physiological parameters of patient 112 (e.g., muscle activity, muscle tone, rigidity, tremor, etc.). Alternatively, identified patient behavior from video information may be used as feedback during the initial and subsequent programming sessions.

[0050] Programmer 104 may also be configured for use by patient 112. When configured as a patient programmer, programmer 104 may have limited functionality (compared to a clinician programmer) in order to prevent patient 112 from altering critical functions of IMD 106 or applications that may be detrimental to patient 112. In this manner, programmer 104 may only allow patient 112 to mark events and to adjust values for certain therapy parameters or set an available range of values for a particular therapy parameter. When programmer 104 is configured for use by patient 112 (e.g., a patient programmer), programmer 104 may have a limited set of adjustments and / or data available to the user compared with a clinician programmer. In this manner, the patient programmer version may prevent the patient from causing detrimental changes to therapy but allow the patient to make some adjustments to therapy as desired.

[0051] Therapy system 100 may be implemented to provide chronic stimulation therapy to patient 112 over the course of several months or years. However, system 100 may also be employed on a trial basis to evaluate therapy before committing to full implantation. If implemented temporarily, some components of system 100 may not be implanted within patientDocket No.: A0012611W001112. For example, patient 112 may be fitted with an external medical device, such as a trial stimulator, rather than IMD 106. The external medical device may be coupled to percutaneous leads or to implanted leads via a percutaneous extension. If the trial stimulator indicates DBS system 100 provides effective treatment to patient 112, the clinician may implant a chronic stimulator within patient 112 for relatively long-term treatment.

[0052] Although IMD 104 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 in other examples. As examples, IMD 106 may be configured to sacral neuromodulation therapy or tibial neuromodulation therapy. In some examples, system 100 may include an implantable drug pump in addition to, or in place of, IMD 106. Further, an IMD may provide other electrical stimulation such as spinal cord stimulation to treat a movement disorder.

[0053] According to the techniques of the disclosure, system 100 can define a homeostatic window and / or a therapeutic window for delivering aDBS to patient 112. System 100 may adaptively deliver electrical stimulation and adjust one or more parameters defining the electrical stimulation within a parameter range defined by upper and lower limits of the therapeutic window based on the activity of the bioelectric signal, e.g., LFP signal, within the homeostatic window. For example, system 100 may adjust the one or more parameters defining the electrical stimulation in response to the sensed bioelectric signal falling below the lower threshold or exceeding the upper threshold of the homeostatic window but may not adjust the one or more parameters defining the electrical stimulation such that they fall below the lower limit or exceed the upper limit of the therapeutic window.

[0054] In one example, external programmer 104 issues commands to IMD 106, via instructions transmitted from external programmer 104 to IMD 106, causing IMD 106 to deliver electrical stimulation therapy via electrodes 116, 118 via leads 114. As described above, in one example, the therapeutic window can define an upper bound and / or a lower bound for one or more parameters defining the delivery of electrical stimulation therapy to patient 112. In other words, the one or more bounds for the therapeutic window may refer to the limits of values that the parameter defining stimulation can be adjusted. For example, the one or more parameters include a current amplitude (for a current-controlled system) or a voltage amplitude (for a voltage-controlled system), a pulse rate or frequency, and a pulse width. In examples where the electrical stimulation is delivered according to a “burst” of pulses, or a series of electrical pulses defined by an “on-time” and an “off-time,” the one or more parameters may further define one or more of a number of pulses per burst, an on-time, and an off-time. In one example, the therapeutic window defines an upper bound and a lower bound for one or more parameters, such as upper and lower threshold for a current amplitude of the electrical stimulation therapy (inDocket No.: A0012611W001 current-controlled systems) or upper and lower threshold of a voltage amplitude of the electrical stimulation therapy (in voltage-controlled systems). While the examples herein are typically given with respect to adjusting a voltage amplitude or a current amplitude, the techniques herein may equally be applied to a homeostatic window and a therapeutic window using other parameters, such as, e.g., pulse rate or pulse width.

[0055] In some examples, a patient may provide feedback, e.g., via programmer 104, to adjust one or both thresholds of the homeostatic window. For example, programmer 104 may provide an input mechanism where the patient can provide an input indicating when therapy is no longer effective or a side effect is felt by patient 112. Programmer 104 may then adjust a threshold of the homeostatic window and / or a bound of the therapeutic window to reduce the issue associated with the patient feedback. To adjust the threshold(s), programmer 104 may determine characteristic values of the bioelectric signal over a recurring interval within an ambulatory period, and based on the characteristic values, programmer 104 may determine representative values of the bioelectric signal for respective times within recurring interval. Based on the representative values, programmer 104 adjusts the threshold(s). As another example, in response to deviations in the signal of the patient outside of the homeostatic window, system 100 (e.g., IMD 106 or programmer 104) may determine to adjust the homeostatic window.

[0056] In some examples, system 100, via programmer 104 or IMD 106, may adjust one or more parameters of the electrical stimulation, such as voltage or current amplitude, within the therapeutic window based on patient input that adjusts the homeostatic window, or based on the bioelectric signal. In particular, system 100 may adjust a parameter of the electrical stimulation, automatically in response to the sensed signal satisfying the one or more thresholds of the homeostatic window and / or in response to patient input that adjusts the homeostatic window, provided the value of the electrical stimulation parameter is constrained to remain within a range specified by the upper and lower bound of the therapeutic window. This range may be considered to include the upper and lower bound themselves.

[0057] In some examples where system 100 adjusts multiple parameters of the electrical stimulation, system 100 may adjust at least one of a voltage amplitude or current amplitude, a stimulation frequency, a sensing frequency of interest, a pulse width, a stimulation cycling setting, a selection of electrodes, and the like. In such an example, system 100 may set an order or sequence for adjustment of the parameters (e.g., adjust voltage amplitude or current amplitude, then adjust stimulation frequency, and then adjust the selection of electrodes). In other examples, system 100 may randomly select a sequence of adjustments to the multiple parameters. In either example, system 100 may adjust a value of a first parameter of the parameters of the electricalDocket No.: A0012611W001 stimulation. If the signal does not exhibit a response to the adjustment of the first parameter, system 100 may adjust a value of a second parameter of the parameters of the electrical stimulation, and so on until the signal returns to within the homeostatic window.

[0058] To adaptively adjust a parameter that defines DBS based on the bioelectric signal, for example, two or more electrodes 116, 118 of IMD 106 may be configured to monitor the bioelectric signal of patient 112. In some examples, at least one of electrodes 116, 118 may be provided on a housing of IMD 106, providing a unipolar stimulation and / or sensing configuration. In one example, the bioelectric signal may be selected to be a signal within a Beta frequency band of brain 120 of patient 112. For example, bioelectric signals within the Beta frequency band of patient 112 may correlate to one or more symptoms of Parkinson’s disease in patient 112. Generally, bioelectric signals within the Beta frequency of patient 112 may be approximately proportional to the severity of the symptoms of patient 112. For example, as tremor induced by Parkinson’s disease increases, bioelectric signals within the Beta frequency of patient 112 increase (e.g., magnitude of the signal and / or spectral power). Moreover, bioelectric signals within the Beta frequency are considered proportional because system 100 may be configured such that an increase in signal magnitude may trigger system 100 to increase delivered stimulation therapy magnitude according to disclosed techniques. Similarly, as tremor induced by Parkinson’s disease decreases, bioelectric signals within the Beta frequency of patient 112 decrease (e.g., magnitude of the signal and / or spectral power), and the decrease may trigger system 100 to decrease the magnitude of delivered stimulation. However, in some examples, these relationships between signal changes and symptom changes may be inversed for some patients which require the system to react in an inverse manner.

[0059] In some examples, each of a sensor within IMD 106 is an accelerometer, a bonded piezoelectric crystal, a mercury switch, or a gyro. In some examples, these sensors may provide a signal that indicates a bioelectric parameter of the patient, which in turn varies as a function of patient activity. For example, the device may monitor a signal that indicates the heart rate, electrocardiogram (ECG) morphology, electroencephalogram (EEG) morphology, respiration rate, respiratory volume, core temperature, subcutaneous temperature, or muscular activity of the patient.

[0060] The architecture of system 100 illustrated in FIG. 1 is shown as an example. The techniques as set forth in this disclosure may be implemented in the example system 100 of FIG. 1, as well as other types of systems not described specifically herein. Nothing in this disclosure should be construed so as to limit the techniques of this disclosure to the example architecture illustrated by FIG. 1.Docket No.: A0012611W001

[0061] FIG. 2 is a block diagram of the example IMD 106 of FIG. 1 for delivering DBS therapy according to an example of the techniques of the disclosure, in accordance with one or more techniques of this disclosure. In the example shown in FIG. 2, IMD 106 includes processing circuitry 210, memory 211, stimulation generator 202, sensing module 204, switch module 206, telemetry module 208, sensor 212, and power source 220. Each of these modules may be or may include electrical circuitry configured to perform the functions attributed to each respective module. For example, processing circuitry 210 may include one or more processors as part of the processing circuitry, switch module 206 may include switch circuitry, sensing module 204 may include sensing circuitry, stimulation generator 202 may include stimulation generation circuitry, and telemetry module 208 may include telemetry circuitry. Switch module 204 may not be necessary for multiple current source and sink configurations in which each current source and sink are directly connected to each electrode but may be connected or disconnected via a respective switch. Memory 211 may include any volatile or non-volatile media, such as a random-access memory (RAM), read only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, and the like. Memory 211 may store computer-readable instructions that, when executed by processing circuitry 210, cause IMD 106 to perform various functions. Memory 211 may be a storage device or other non- transitory medium.

[0062] In the example shown in FIG. 2, memory 211 stores patient history 214 and sense electrode combinations and medication information 218 in separate memories within memory 211 or separate areas within memory 211. Patient history 214 includes historical information which may be indicative of one or more of patient state or therapy efficacy, e.g., stimulation therapy efficacy and / or medication efficacy.

[0063] Memory 211 may include sense and stimulation electrode combinations 218. Sense and stimulation electrode combinations 218 stores sense electrode combinations and associated stimulation electrode combinations. As described above, in some examples, the sense and stimulation electrode combinations may include the same subset of electrodes 116, 118, a housing of IMD 106 functioning as an electrode, or may include different subsets or combinations of such electrodes. Thus, memory 211 can store a plurality of sense electrode combinations and, for each sense electrode combination, store information identifying the stimulation electrode combination that is associated with the respective sense electrode combination. The associations between sense and stimulation electrode combinations can be determined, e.g., automatically by processing circuitry 210. In some examples, corresponding sense and stimulation electrode combinations may comprise some or all of the same electrodes. In other examples, however, some or all of the electrodes in corresponding sense and stimulationDocket No.: A0012611W001 electrode combinations may be different. For example, a stimulation electrode combination may include more electrodes than the corresponding sense electrode combination in order to increase the efficacy of the stimulation therapy. In some examples, as discussed above, stimulation may be delivered via a stimulation electrode combination to a tissue site that is different than the tissue site closest to the corresponding sense electrode combination but is within the same region, e.g., the thalamus, of brain 120 in order to mitigate any irregular oscillations or other irregular brain activity within the tissue site associated with the sense electrode combination.Alternatively, stimulation may be delivered via one of leads 114, and sensing may be performed via the other lead of leads 114.

[0064] Stimulation generator 202, under the control of processing circuitry 210, generates stimulation signals for delivery to patient 112 via selected combinations of electrodes 116, 118. An example range of electrical stimulation parameters believed to be effective in DBS to manage a movement disorder of patient include:

[0065] 1. Pulse Rate, i.e., Frequency: between approximately 40 Hertz and approximately500 Hertz, such as between approximately 1 to 185 Hertz or such as approximately 140 Hertz.

[0066] 2 In the case of a voltage controlled system, Voltage Amplitude: between approximately 0.1 volts and approximately 50 volts, such as between approximately 2 volts and approximately 3 volts.

[0067] 3. In the alternative case of a current controlled system, Current Amplitude: between approximately 0.2 milliamps to approximately 100 milliamps, such as between approximately 1.3 milliamps and approximately 2.0 milliamps.

[0068] 4. Pulse Width: between approximately 10 microseconds and approximately 5000 microseconds, such as between approximately 100 microseconds and approximately 1000 microseconds, or between approximately 180 microseconds and approximately 450 microseconds.

[0069] Accordingly, in some examples, stimulation generator 202 generates electrical stimulation signals in accordance with the electrical stimulation parameters noted above, subject to application of the upper and lower limit of a therapeutic window to one or more of the parameters, such that an applicable parameter resides within the range prescribed by the window. Other ranges of therapy parameter values may also be useful and may depend on the target stimulation site within patient 112. While stimulation pulses are described, stimulation signals may be of any form, such as continuous-time signals (e.g., sine waves) or the like.

[0070] Processing circuitry 210 may include fixed function processing circuitry and / or programmable processing circuitry, and may comprise, for example, any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integratedDocket No.: A0012611W001 circuit (ASIC), a field-programmable gate array (FPGA), discrete logic circuitry, or any other processing circuitry configured to provide the functions attributed to processing circuitry 210 herein may be embodied as firmware, hardware, software or any combination thereof. Processing circuitry 210 may control stimulation generator 202 according to therapy programs 214 stored in memory 211 to apply particular stimulation parameter values specified by one or more of programs, such as voltage amplitude or current amplitude, pulse width, or pulse rate.

[0071] In the example shown in FIG. 2, the set of electrodes 116 includes electrodes 116A, 116B, 116C, and 116D, and the set of electrodes 118 includes electrodes 118A, 118B, 118C, and 118D. Processing circuitry 210 also controls switch module 206 to apply the stimulation signals generated by stimulation generator 202 to selected combinations of electrodes 116, 118. In particular, switch module 204 may couple stimulation signals to selected conductors within leads 114, which, in turn, deliver the stimulation signals across selected electrodes 116, 118. Switch module 206 may be a switch array, switch matrix, multiplexer, or any other type of switching module configured to selectively couple stimulation energy to selected electrodes 116, 118 and to selectively sense the bioelectric signal with selected electrodes 116, 118. Hence, stimulation generator 202 is coupled to electrodes 116, 118 via switch module 206 and conductors within leads 114. In some examples, however, IMD 106 does not include switch module 206.

[0072] Stimulation generator 202 may be a single channel or multi-channel stimulation generator. In particular, stimulation generator 202 may be capable of delivering a single stimulation pulse, multiple stimulation pulses, or a continuous signal at a given time via a single electrode combination or multiple stimulation pulses at a given time via multiple electrode combinations. In some examples, however, stimulation generator 202 and switch module 206 may be configured to deliver multiple channels on a time-interleaved basis (e.g., pulses from one channel are at least partially alternating with at least some pulses from another channel). For example, switch module 206 may serve to time divide the output of stimulation generator 202 across different electrode combinations at different times to deliver multiple programs or channels of stimulation energy to patient 112. Alternatively, stimulation generator 202 may comprise multiple voltage or current sources and sinks that are coupled to respective electrodes to drive the electrodes as cathodes or anodes. In this example, IMD 106 may not require the functionality of switch module 206 for time-interleaved multiplexing of stimulation via different electrodes.

[0073] Electrodes 116, 118 on respective leads 114 may be constructed of a variety of different designs. For example, one or both of leads 114 may include two or more electrodes at each longitudinal location along the length of the lead, such as multiple electrodes at different perimeter locations around the perimeter of the lead at each of the locations A, B, C, and D. InDocket No.: A0012611W001 one example, the electrodes may be electrically coupled to switch module 206 via respective wires that are straight or coiled within the housing the lead and run to a connector at the proximal end of the lead. In another example, each of the electrodes of the lead may be electrodes deposited on a thin film. The thin film may include an electrically conductive trace for each electrode that runs the length of the thin film to a proximal end connector. The thin film may then be wrapped (e.g., a helical wrap) around an internal member to form the lead 114. These and other constructions may be used to create a lead with a complex electrode geometry.

[0074] Although sensing module 204 is incorporated into a common housing with stimulation generator 202 and processing circuitry 210 in FIG. 2, in other examples, sensing module 204 may be in a separate housing from IMD 106 and may communicate with processing circuitry 210 via wired or wireless communication techniques.

[0075] Sensor 212 may include one or more sensing elements that sense values of a respective patient parameter. For example, sensor 212 may include one or more accelerometers, optical sensors, chemical sensors, temperature sensors, pressure sensors, or any other types of sensors. Sensor 212 may output patient parameter values that may be used as feedback to control delivery of therapy. IMD 106 may include additional sensors within the housing of IMD 106 and / or coupled via one of leads 114 or other leads. In addition, IMD 106 may receive sensor signals wirelessly from remote sensors via telemetry module 208, for example. In some examples, one or more of these remote sensors may be external to patient (e.g., carried on the external surface of the skin, attached to clothing, or otherwise positioned external to the patient).

[0076] Telemetry module 208 supports wireless communication between IMD 106 and an external programmer 104 or another computing device under the control of processing circuitry 210. Processing circuitry 210 of IMD 106 may receive, as updates to programs, values for various stimulation parameters such as magnitude and electrode combination, from programmer 104 via telemetry module 208. The updates to the therapy programs may be stored within therapy programs 214 portion of memory 211. Telemetry module 208 in IMD 106, as well as telemetry modules in other devices and systems described herein, such as programmer 104, may accomplish communication by radiofrequency (RF) communication techniques. In addition, telemetry module 208 may communicate with external medical device programmer 104 via proximal inductive interaction of IMD 106 with programmer 104. Accordingly, telemetry module 208 may send information to external programmer 104 on a continuous basis, at periodic intervals, or upon request from IMD 106 or programmer 104.

[0077] Power source 220 delivers operating power to various components of IMD 106. Power source 220 may include a small rechargeable or non-rechargeable battery and a power generation circuit to produce the operating power. Recharging may be accomplished throughDocket No.: A0012611W001 proximal inductive interaction between an external charger and an inductive charging coil within IMD 220. In some examples, power requirements may be small enough to allow IMD 220 to utilize patient motion and implement a kinetic energy-scavenging device to trickle charge a rechargeable battery. In other examples, traditional batteries may be used for a limited period of time.

[0078] According to the techniques of the disclosure, processing circuitry 210 of IMD 106 controls stimulation generator 202 to deliver of electrical stimulation therapy to patient 112 via electrodes 116, 118 interposed along leads 114 (and optionally switch module 206). One or more parameters of the stimulation therapy may include a current amplitude (for a current-controlled system) or a voltage amplitude (for a voltage-controlled system), a pulse rate or frequency, and a pulse width, or quantity of pulses per cycle. The collection of one or more of these parameter values may define a parameter set that defines a therapy program. In examples where the electrical stimulation is delivered according to a “burst” of pulses, or a series of electrical pulses defined by an “on-time” and an “off-time,” the one or more parameters may further define one or more of a number of pulses per burst, an on-time, and an off-time. In one example, the therapeutic window defines an upper limit and / or a lower limit for a voltage amplitude of the electrical stimulation therapy. In another example, the therapeutic window defines an upper limit and / or a lower limit for a current amplitude of the electrical stimulation therapy. In particular, a parameter of the electrical stimulation therapy, such as voltage or current amplitude, is constrained to a therapeutic window having an upper limit and a lower limit, such that the voltage or current amplitude may be adjusted provided the amplitude remains greater than or equal to the lower limit and less than or equal to the upper limit. It is noted that a single limit may be used in some examples.

[0079] In one example, processing circuitry 210, via electrodes 116, 118 of IMD 106, monitors the behavior of a signal of patient 112 that correlates to one or more symptoms of a disease of patient 112 within a homeostatic window. Processing circuitry determines one or more threshold values associated with the homeostatic window based on a chronically sensed bioelectric signal, e.g., LFP signal. Processing circuitry 210, via electrodes 116, 118, delivers to patient 112 aDBS and may adjust one or more parameters defining the electrical stimulation within a parameter range defined by lower and upper limits of a therapeutic window based on the activity of the sensed signal within the homeostatic window.

[0080] In some examples, processing circuitry 210 continuously measures the signal in real time. In other examples, processing circuitry 210 periodically samples the signal according to a predetermined frequency or after a predetermined amount of time. In some examples, processingDocket No.: A0012611W001 circuitry 210 periodically samples the signal at a frequency selected from a range of appropriate frequencies, such as a frequency of approximately 150 Hertz.

[0081] Furthermore, processing circuitry 210 delivers electrical stimulation therapy that is constrained by an upper limit and a lower limit of a therapeutic window. In some examples, values defining the therapeutic window are stored within memory 211 of IMD 106. For example, in response to detecting that characteristic values, e.g., amplitude values, of the bioelectric signal have deviated from the homeostatic window, processing circuitry 210 of IMD 106 may adjust one or more parameters of the electrical stimulation therapy to provide responsive treatment to patient 112.

[0082] In response to detecting that the signal has exceeded an upper threshold of the homeostatic window and prior to delivering the electrical stimulation therapy, processing circuitry 210 increases an amplitude of stimulation (e.g., but not above the upper limit) in order to bring the signal back down below the upper threshold. For example, in a voltage-controlled system wherein the clinician has set the upper limit of the therapeutic window to be 3 Volts, processing circuitry 210 can increase the voltage amplitude to values no greater than 3 Volts in an attempt to decrease the brain signal below the upper threshold.

[0083] In another example, in response to detecting that the signal has fallen below a lower threshold of the homeostatic window and prior to delivering the electrical stimulation therapy, processing circuitry 210 decreases the voltage amplitude, for example, but not lower than the magnitude of the lower limit. For example, in the above voltage-controlled system wherein the clinician has set the lower bound of the therapeutic window to be 1.2 Volts, processing circuitry 210 can decrease the voltage amplitude down to no lower than 1.2 Volts in an attempt to raise the brain signal back above the lower threshold and into the homeostatic window. Thus, processing circuitry 210 of IMD 106 may deliver aDBS to patient 112 wherein the one or more parameters defining the aDBS is within the therapeutic window defined by a lower and upper limit for the parameter.

[0084] In the foregoing example, the limit of the therapeutic window is inclusive (i.e., the upper and lower limit are valid values for the one or more parameters). However, in other examples, the limit of the therapeutic window is exclusive (i.e., the upper and lower limits are not valid values for the one or more parameters). In such an example of an exclusive therapeutic window, processing circuitry 210 instead sets the adjustment to the one or more parameters to be the next highest valid value (in the case of an adjustment potentially exceeding the upper limit) or the next lowest valid value (in the case of an adjustment potentially exceeding the lower limit).

[0085] In another example, values defining the therapeutic window are stored within a memory 311 (FIG. 3) of external programmer 104. In this example, in response to detecting thatDocket No.: A0012611W001 the signal has deviated from the homeostatic window, processing circuitry 210 of IMD 106 transmits, via telemetry module 208, data representing the measurement of the signal to external programmer 104. In one example, in response to detecting that the signal has exceeded an upper threshold of the homeostatic window, processing circuitry 210 of IMD 106 transmits, via telemetry module 208, data representing the measurement of the signal to external programmer 104. External programmer 104 may determine to adjust a parameter value to reduce the signal below the upper threshold as long as the parameter value remains within the one or more limits to the parameter.

[0086] FIG. 3 is a block diagram of the external programmer of FIG. 1 for controlling delivery of DBS therapy according to an example of the techniques of the disclosure. FIG. 3 is a block diagram of the external programmer 104 of FIG. 1. Although programmer 104 may generally be described as a hand-held device, programmer 104 may be a larger portable device or a more stationary device. In some examples, programmer 104 may be referred to as a tablet computing device. In addition, in other examples, programmer 104 may be included as part of an external charging device or include the functionality of an external charging device. As illustrated in FIG. 3, programmer 104 may include processing circuitry 310, memory 311, user interface 302, telemetry module 308, and power source 320. Memory 311 may store instructions that, when executed by processing circuitry 310, cause processing circuitry 310 and external programmer 104 to provide the functionality ascribed to external programmer 104 throughout this disclosure. Each of these components, or modules, may include electrical circuitry that is configured to perform some or all of the functionality described herein. For example, processing circuitry 310 may include processing circuitry configured to perform the processes discussed with respect to processing circuitry 310.

[0087] In general, programmer 104 comprises any suitable arrangement of hardware, alone or in combination with software and / or firmware, to perform the techniques attributed to programmer 104, and processing circuitry 310, user interface 302, and telemetry module 308 of programmer 104. In various examples, programmer 104 may include one or more processors, which may include fixed function processing circuitry and / or programmable processing circuitry, as formed by, for example, one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. Programmer 104 also, in various examples, may include a memory 311, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, or an optical media (e.g., DVD or CD- ROM), comprising executable instructions for causing the one or more processors to perform the actions attributed to them. Moreover, although processing circuitry 310 and telemetry module 308 are described as separate modules, in some examples, processing circuitry 310 and telemetryDocket No.: A0012611W001 module 308 may be functionally integrated with one another. In some examples, processing circuitry 310 and telemetry module 308 correspond to individual hardware units, such as ASICs, DSPs, FPGAs, or other hardware units.

[0088] Memory 311 (e.g., a storage device) may store instructions that, when executed by processing circuitry 310, cause processing circuitry 310 and programmer 104 to provide the functionality ascribed to programmer 104 throughout this disclosure. For example, memory 311 may include instructions that cause processing circuitry 310 to select one or more parameters for electrical stimulation or adaptive stimulation according to sensed signals or receive user input and send a corresponding command to IMD 104, or instructions for any other functionality. In addition, memory 311 may include a plurality of programs, where each program includes a parameter set that defines stimulation therapy.

[0089] User interface 302 may include a button or keypad, lights, a speaker for voice commands, a display, such as a liquid crystal (LCD), light-emitting diode (LED), or organic light-emitting diode (OLED). In some examples the display may be a touch screen. User interface 302 may be configured to display any information related to the delivery of stimulation therapy, identified patient behaviors, sensed patient parameter values, automatically selected parameters, prompts for user input regarding stimulation parameters or adaptive stimulation parameters, patient behavior criteria, or any other such information. User interface 302 may also receive user input via user interface 302. The input may be, for example, in the form of pressing a button on a keypad or selecting an icon from a touch screen. User interface 302 may refer to hardware configured to present information to the user and / or receive input from the user. In some examples, processing circuitry 310 directly controls this hardware. In other examples, processing circuitry 310 may communicate with drive hardware that controls hardware of user interface 302. In some examples, user interface 302 may include display and / or interactive display configurations as described herein.

[0090] Telemetry module 308 may support wireless communication between IMD 106 and programmer 104 under the control of processing circuitry 310. Telemetry module 308 may also be configured to communicate with another computing device via wireless communication techniques, or direct communication through a wired connection. In some examples, telemetry module 308 provides wireless communication via an RF or proximal inductive medium. In some examples, telemetry module 308 includes an antenna, which may take on a variety of forms, such as an internal or external antenna. In some examples, telemetry modules 308 may support communications with intermediate devices between programmer 104 and IMD 106 or other external devices.Docket No.: A0012611W001

[0091] Examples of local wireless communication techniques that may be employed to facilitate communication between programmer 104 and IMD 106 include RF communication according to the 802.11 or Bluetooth specification sets or other standard, inductive telemetry, or any proprietary telemetry protocols. In this manner, other external devices may be capable of communicating with programmer 104 without needing to establish a secure wireless connection. As described herein, telemetry module 308 may be configured to transmit a spatial electrode movement pattern or other stimulation parameter values to IMD 106 for delivery of stimulation therapy.

[0092] According to the techniques of the disclosure, in some examples, processing circuitry 310 of external programmer 104 defines the parameters of a therapeutic window, stored in memory 311, for delivering DBS to patient 112. In one example, processor 311 of external programmer 104, via telemetry module 308, issues commands to IMD 106 causing IMD 106 to deliver electrical stimulation therapy via electrodes 116, 118.

[0093] The following examples illustrate various user interfaces and techniques for managing the sensing of bioelectric signals, programming adaptive stimulation therapy, and managing electrical stimulation as described herein. Programmer 104, or another external computing device, may output the user interfaces and screens described herein. The example user interface screens may be separately presented or selectable in any order, or programmer 106 (for example) may present each screen in order as part of a guided programming process to assist the user through the programming process and during follow-up visits. During programming, user input may be prompted at various times, either to select parameter values or to confirm automatically selected parameter values. In some examples, programmer 106 may perform each step automatically and present the user with fully automated and selected parameters at the end of the process. The user may confirm the parameter values or review one or more of the parameter values using each respective screen of the user interface as needed to customize the stimulation therapy, which may include adaptive stimulation therapy such as aDBS. During follow-up visits or at other times after programming, the user interface screens may present alerts and other information to the clinician.

[0094] FIG. 4 is a conceptual diagram illustrating an example home screen for navigating within a user interface according to an example of the techniques of the disclosure. User interface 400 may include several different screens as the user can navigate to different functions to view sensed information, view stored data, or adjust various stimulation parameter values. As shown in the example of FIG. 4, home screen 402 includes information associated with patient 112, such as patient specific information 406 such as name, patient ID, date of birth, and patient diagnosis. Other information may include device specific information such as model number, implant date,Docket No.: A0012611W001 battery level, and estimated batter life remaining. Information such as impedance status for the system and event summary may also be provided in the home screen 402. Screen 402 may also include stimulation toggle switch 404 that, when selected, toggles between turning stimulation on or turning stimulation off. Stimulation toggle switch 404 may be provided in some, most, or all of the different screens within user interface 400 to enable the user to turn stimulation on or off at any time. Alert button 410 shows “no alerts” because there are no alerts to be shown. However, if there are alerts for the user, alert button 410 may indicate that there are alerts, or the number of alerts, and alert button 410 may be selectable to cause user interface 400 to show a list of the alerts for the user.

[0095] The home screen 402 in FIG. 4 may also include a menu 408 that includes several selectable buttons that enable the user to navigate to other screen and functionality supported by user interface 400. These selectable buttons include “setup,” “stimulation,” “impedance,” “MRI eligibility,” “replacement,” “events,” and “end session.” Programmer 104 may switch to the appropriate screen in response to user selection of the respective selectable button.

[0096] As shown in the example of FIG. 4, in response to user selection, the setup button takes the user to screens associated with selecting electrode combinations for sensing and / or stimulation and / or frequency for sensing. In response to user selection, the stimulation button takes the user to screens associated with managing electrical stimulation therapy for the patient, such as selecting an adaptive stimulation mode, selecting thresholds for the adaptive mode, selecting parameters that define stimulation, bounds for stimulation parameters, or any other parameters related to stimulation therapy. In response to user selection, the impedance button takes the user to screens associated with viewing impedances of one or more electrode combinations and / or leads and running impedance testing for any electrical pathways.

[0097] In some examples, processing circuitry 310 senses the bioelectric signal over an ambulatory period to determine one or more threshold values, e.g., one or more LFP signal threshold values. Based on the bioelectric signal, processing circuitry 310 determines characteristic values, e.g., average values, of the bioelectric signal over a recurring interval within the ambulatory period. Based on the characteristic values, processing circuitry 310 determines representative values for respective times of the recurring interval. Processing circuitry 310 selects one or more thresholds for the adaptive mode based on the representative values. In some examples, processing circuitry 310 determines the one or more thresholds based on filtered representative values. As an example, processing circuitry 310 may filter the representative values according to a patient schedule, such as by excluding representative values corresponding to respective times within the recurring interval that patient 112 is typically resting or sleeping.Docket No.: A0012611W001

[0098] The MRI eligibility button takes the user to screens associated with checking MRI eligibility of any implanted device (e.g., IMD 106) and / or placing the implanted device into an MRI eligible mode. The replacement button causes user interface 400 to displace screens related to when the IMD 106 should be replaced (e.g., remaining operational life for a primary cell non- rechargeable power supply). The events button enables the user to navigate to various screens that display events and data associated with sensing and delivering electrical stimulation. The end session button enables the user to terminate the management session via user interface 400. In addition to the menu, user interface 400 may include a stimulation toggle switch that enables the user to request turning stimulation on or off. These different navigation categories in menu 408 are merely examples, and the functionality within each category may be separated into additional categories or combined into fewer categories in other examples.

[0099] User interface 400 may be configured for a clinician programmer that enables the clinician to oversee all aspects of stimulation therapy and / or sensing, both manual and / or automated. In some examples, user interface 400 may enable the language of the clinician programmer to be different from a patient programmer configured to enable the patient to control a subset of features related to IMD 106. For example, user interface 400 may enable the clinician to set up the patient programmer language in the setup button, where the patient programmer language is different from the language of user interface 400 presented by the clinician programmer. For example, user interface 400 may enable the clinician to set up therapy group names, device names, and patient events to appear in a patient’s local language irrespective of the primary or supported clinician language of user interface 400. In this manner, user interface 400 may enable the clinician (or a translator assisting the clinician) to program group names and patient events in the desired language for the patient even if it is not the primary language of the clinician.

[0100] FIG. 5 is a conceptual diagram illustrating an example screen for displaying a selected sensing electrode combination and signal of interest for a lead according to an example of the techniques of the disclosure. In some examples, electrode combinations 502 may be referred to as sense channels. In some examples, system 100 may automatically select an electrode combination based on a weighted summation of multiple sensing metrics (or other criteria). In some examples, the sensing metric information is collected when system 100 controls sensing circuitry to sense respective bioelectric signals from each of the plurality of electrode combinations 502. System 100 may perform this collection of the bioelectric signals upon navigation to screen 500 or prior to this step of the process. System 100 may in any example analyze the sensed signals and generate one or more recommended electrode combinations for sensing and / or a frequency for sensing signals during therapy, such as during adaptiveDocket No.: A0012611W001 stimulation (e.g., aDBS). In some examples, sensing metrics include bioelectric signal information, e.g., LFP signal information, whether the electrode combination supports already configured therapy electrodes, and the quantity of artifacts associated with each electrode combination.

[0101] Screen 500 may include information summarizing the metrics of selected electrode combination 504. Lead 516 shows the electrodes of the lead used for the selected electrode combination 504. Screen 500 may include a LFP power vs. frequency graph 512. Data line 510 corresponds to the powers for the combination “0 to 2” that is selected and shows the highest magnitude of power at the frequency of 22.48 Hz. This frequency may also be recommended for this reason. Processing circuitry, e.g., processing circuitry 210 and / or 310, may control sensing module 204 to sense and record the LFP signal within a 5 Hz band including the 22.48 Hz frequency. In some examples, the LFP signal within the 5 Hz band and / or the LFP signal at the 22.48 Hz frequency may be referred to as the signal of interest. Generally, the recommended electrode combinations are those with peaks present at a certain frequency as shown in the LFP power vs. frequency graph. Additionally, electrode combinations with relatively low artifact levels and already supported therapy electrodes are the best electrode combinations. In some examples, the weighting of each metric may be patient-dependent. In other examples, the metric weights are based on aggregate patient data.

[0102] If desired, the user may choose different electrode combinations and frequencies. For example, screen 500 may receive user selection of a different electrode combination of electrode combinations 504, which may cause screen 500 to update the corresponding selected data line in graph 512 and, if necessary, the frequency. The user may select a different frequency using slider 506 on graph 512 or another numerical input field in other examples. Selection of the close button 518 will accept the selected or recommended parameters shown in screen 500 for subsequent sensing, close screen 500, and may prompt system 100 to continue automated programming. In some examples, a different “save” or “confirm” button may be presented for the user to select when satisfied with the identified parameters in screen 500. The techniques described herein are not limited to LFP signals. Other bioelectric signals may be used in other examples. LFP signals serve merely as a non-limiting example.

[0103] In some examples, screen 500 may include auto selection button 508. The user may select auto selection button 508, and processing circuitry 310 may select an electrode combination and a signal of interest. Screen 500 may include a pop-up window (not depicted), confirming the selections. The user may either confirm the selections or adjust the selections.

[0104] During the automated selection process discussed herein, programmer 104 may initiate an automatic scan of brain signals from all or most electrode combinations available toDocket No.: A0012611W001 enable programmer 104 or the user to identify where signals might be located (which hemisphere, which region of a lead, which specific combinations of contacts) for the purpose of identifying such signals, the integrity or quality of the recording system, and then guiding sensing configuration and / or stimulation parameters values

[0105] In this manner, user interface 400 can provide a view of all signals in a hemisphere simultaneously and enable selection of one signal to be compared to the others. Programmer 104 may measure aspects of the signal (e.g., difference between maximum and / or minimum at a specific frequency of interest). Programmer 104 may enable IMD 106 to continuously record a subset of signals. In some examples, programmer 104 may perform statistical comparisons (e.g., an energy in a region of frequencies compared to the energy at a specific peak, the relative amplitude above 1 / frequency of the curve, the width of the peak, or simultaneous comparison or measurement of two or more peaks. In some examples, user interface 400 may provide additional views for leads having electrodes at different locations around a perimeter of a lead (e.g., segmented electrodes of directional leads). User interface 400 may also provide visualization of anatomic structures or other reference in combination with a signal location (e.g., whether or not a signal is in or out of target, or if a signal is medial or lateral from an anatomical structure).

[0106] FIG. 6 is a conceptual diagram illustrating an example screen 600 for selecting an adaptive therapy mode, e.g., an aDBS mode, from two or more different adaptive modes. As shown in the example of FIG. 6, user interface 400 may include a screen 600 that indicates the automated system selection of dual threshold mode 604, single threshold mode 606, or single threshold inverse mode 608. Dual threshold mode 604 is shown as selected. Dual threshold mode 604 enables the system to adjust stimulation amplitude based on upper and lower thresholds of the LFP signals. Single threshold mode 606 enables the system to increase stimulation when LFP signals are above the threshold, and single threshold inverse mode 608 enables the system to decrease stimulation when LFP signals are above the threshold.

[0107] This feature of user interface 400 for programming aDBS is intended to enable IMD 106 to automatically adjust, within system-defined limits and / or clinician-defined limits, one or more stimulation parameters based on changes in brain state. A patient’s brain state will be measured using a brain signal, such as LFPs, recorded concurrently from the implanted electrodes during therapy. The goal of the automatic adjustment of therapy may be to maintain the brain state (as defined by these signals) within a specified range (e.g., the range between an upper and lower threshold in the dual threshold mode example), understanding that clinical symptoms and side effects may be well correlated with these detected brain states. In this manner of managing brain states, the user may be able to manage clinical symptoms and side effects. This feature is referred to as closed loop DBS or aDBS.Docket No.: A0012611W001

[0108] In this manner, user interface 400 enables the user to monitor automated adaptive therapy configuration by confirming or modifying algorithm, thresholds, and / or stimulation settings for adaptive stimulation modes. Menu 602 allows the user to monitor the automated programming process and to switch between setup stages. Adaptive mode is the current setup stage in this example. The user may select previous button 610 to go back to a previous setup stage, e.g., BrainSense setup, or may select next button 612 to move on to a next setup stage, e.g., thresholds. In some examples, processing circuitry 310 controls stimulation generator 202 to generate electrical stimulation at a plurality of values of a stimulation parameter, e.g., current amplitude, that at least partially defines the electrical stimulation during a period of time. In some examples, user interface 400 presents screen 600 to the user after selecting an adaptive mode based on information representative of bioelectric signals sensed by sensing module 204.

[0109] In some examples, in addition to the information representative of the bioelectric signals, processing circuitry 310 determines which adaptive mode of the plurality of adaptive modes to select based on user input. For example, user input may comprise information regarding a condition of a patient, e.g., patient 112, which may be used to determine which aDBS mode to use for patient 112. Example conditions may include different symptoms or diseases, patient specific reactions to stimulation (e.g., dyskinesia at higher stimulation amplitudes), or unstable reactions to medication also consumed by the patient. For example, single threshold inverse mode may be selected for patients that have dyskinesia at higher stimulation amplitudes or if the patient responds in the Gamma band. In some examples, the system selects the single or dual threshold for Beta band sensing when the patient needs help controlling swings in symptoms from taking medication. Additionally, or alternatively, user interface 400 may enable the user to select a different aDBS mode, i.e., override the aDBS selection made by processing circuitry 310, by selecting a different adaptive mode in screen 600.

[0110] While the techniques are described using processing circuitry 310, other processing circuitry, such as processing circuitry 210 or a combination of processing circuitry 310 and processing circuitry 210, may also be used. Selection of next button 612 may save the selected adaptive mode and move to the next screen of user interface 400.[oni] FIG. 7 is a conceptual diagram illustrating an example screen 700 for determining one or more thresholds according to an example of the techniques of the disclosure. In some examples, screen 700 may include auto selection button 714. When the user selects auto selection button 714, processing circuitry 310 may select one or thresholds based on chronic, averaged, filtered bioelectric signal data. Example screen 700 may include LFP signal vs. time graph 716. In some examples, to select one or more threshold values corresponding to the adaptive mode, processing circuitry 310 determines representative values 708 corresponding to respective timesDocket No.: A0012611W001 of a recurring interval 718, e.g., a 1 day interval, within an ambulatory period, e.g., a multi-day period in which patient 112 is out of the clinic. In other examples, the recurring interval may be set to an interval that is less than 1 day, such as a desired period of time (e.g., specific time range, morning, evening, sleeping, awake, etc.), or more than 1 day (e.g., several days, 1 week, etc.).

[0112] Processing circuitry 310 may apply a filter to include representative values 708 within range 706 based on schedule of patient 112. As an example, processing circuitry 310 may filter the representative values to include times within range 706, which includes times during which patient 112 is active and / or awake and may exclude times during which patient 112 is inactive and / or asleep. Processing circuitry 310 may determine a range 704 of the filtered representative values and set the one or more thresholds to fall within the range of the filtered representative values. As an example, processing circuitry 310 may select an upper threshold 710 to be less than a maximum representative value and lower threshold 712 to be greater than a minimum representative value. Box 702 may be defined by range 704 and range 706. In one example, processing circuitry 310 may select an upper threshold 710 to be 15% to 35% lower than a maximum representative value and may select a lower threshold 712 to be 15% to 35% higher than a minimum representative value. As another example, processing circuitry 310 may select upper threshold 710 to be between a 65thand 85thpercentile of the range 704 of the filtered representative values, and processing circuitry 310 may select lower threshold 712 to be between a 15thand 35thpercentile of the range 704 of the filtered representative values. In some examples, processing circuitry 310 sets the one or more threshold values such that a corresponding homeostatic window has at least a threshold range of values, e.g., a range of at least 80 microvolts. In some examples, the user may adjust the one or more threshold values. As described herein, each threshold may be set to be within range 704 set by the maximum representative value and the minimum representative value. In some examples, the thresholds may be based on the range of values, the maximum and minimum values, or some combination thereof. For example, the percentage or absolute value from the maximum or minimum values may be calculated from the maximum or minimum values and / or based on the value of range 704 between the maximum and minimum values.

[0113] In some examples, the user may not select auto selection button 714. Instead of selecting auto selection button 714, the user may manually set one or more of the one or more of upper threshold 710 or lower threshold 712. In some examples, the user may set the threshold value(s) by moving sliders 720 and 722 of the user interface to the desired value. In other examples, user interface 700 may provide other input mechanisms, such as buttons to increase and decrease the values, numerical input boxes, etc. The system may limit the user definedDocket No.: A0012611W001 thresholds to be within range 704. However, in some examples, the system may enable the user to set a threshold value outside of range 704.

[0114] FIG. 8 is a conceptual diagram illustrating a pop-up window of example screen 700 for confirming one or more thresholds according to an example of the techniques of the disclosure. In some examples, pop-up window 802 appears when the user selects next button 812. In some examples, next button 812 replaced auto selection button 714 of FIG. 7 after user selection of auto selection button 714. Pop-up window 802 may provide an indication of one or more selected threshold values selected as described with respect to FIG. 7. If the user selects confirm button 804, processing circuitry 310 confirms the threshold value(s) and may control electrical stimulation therapy according to the selected threshold value(s) and a subsequently sensed LFP signal, e.g., characteristic values of the subsequently sensed LFP signal. If the user selects adjust button 806, the user may adjust the threshold value(s) using sliders 720 and 722. In other examples, screen 700 may present a field, arrows, or other input mechanism that is configured to accept user input that sets or changes any of the threshold values. In some examples, processing circuitry 310 may limit the adjustments to be within range 704, but in other examples the threshold values may be set to a value within different limits or to any unlimited value in other examples.

[0115] FIG. 9 is a flowchart illustrating an example operation for selecting one or more thresholds and controlling adjustment of electrical stimulation based on the one or more thresholds according to an example of the techniques of the disclosure. The example operation of FIG. 9 will be described with respect to processing circuitry 310 of programmer 104, but any processing circuitry of system 100 may additionally or alternatively perform the example operation, such as processing circuitry 210 of IMD 106 and / or other devices or systems may be used in other examples to select the one or more thresholds for controlling adjustment of electrical stimulation. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0116] As shown in the example of FIG. 9, processing circuitry 310 controls sensing module 204 to sense a bioelectric signal, e.g., an LFP signal, of a patient, e.g., patient 112, over an ambulatory period of time (902). In some examples, the ambulatory period comprises a chronic period of time, such as a multi-day or multi-week period, such as 3 days, 1 week, 4 weeks, etc. The ambulatory period may also be less than 1 day, such as 12 hours. The ambulatory period may be a period during which patient 112 is not in the clinic. For example, patient 112 may, after implantation and initial stimulation threshold setting, go home for the duration of the ambulatory period and may return to normal daily activities. Processing circuitry 310 determines, based on the bioelectric signal, characteristic values, e.g., amplitude values, of the bioelectric signal over aDocket No.: A0012611W001 recurring interval of time within the ambulatory period (904). The recurring interval may, as an example, be a one day interval. The recurring interval may alternatively be shorter or longer than one day, such as 4 hours, 8 hours, 12 hours, 36 hours, 48 hours, etc.

[0117] Based on the characteristic values, processing circuitry 310 determines representative values of the bioelectric signal for respective times within the recurring interval, e.g., times of day within the 1 day interval (906). In some examples, the representative values may be referred to as daily average values. The representative values may comprise average values of the characteristic values at each of the respective times. In some examples, the representative values may comprise maximum, minimum, or median values of the characteristic values at each of the respective times. Processing circuitry 310 selects one or more threshold values based on the representative values of the bioelectric signal (908). Processing circuitry 310 may filter the representative values based on a patient schedule. As an example, to select the one or more threshold values, e.g., an upper threshold and / or a lower threshold, processing circuitry 310 filters the representative values to include representative values corresponding to respective times at which patient 112 is generally awake and / or active. In some examples, the resulting subset of representative values for the respective times may be referred to as an average daily range (ADR). The times of day associated with the ADR may be patient specific. As an example, the ADR for a patient who generally wakes up at 7:00 AM and goes to sleep at 7:00 PM may include representative values corresponding to respective times between and including 7:00 AM and 7:00 PM. The ADR for a patient who generally wakes up at 10:00 AM and goes to sleep at 9:00 PM may include representative values corresponding to respective times between 10:00 AM and 9:00 PM. Based on the ADR, processing circuitry 310 selects the one or more thresholds. In some examples, processing circuitry 310 selects one or more thresholds that fall within the ADR.

[0118] In examples in which processing circuitry 310 selects a lower threshold, processing circuitry 310 may set the lower threshold to be a threshold percentage or amount higher than a minimum representative value within the ADR, such as 10% to 35% higher than the minimum representative value within the ADR. In examples in which processing circuitry 310 selects an upper threshold, processing circuitry 310 may set the upper threshold to be a threshold percentage or amount lower than a maximum representative value within the ADR, such as 10% to 35% lower than the maximum representative value within the ADR. Processing circuitry 310 may additionally or alternatively select either of the upper threshold or the lower threshold based on percentile values within the ADR, e.g., based on a 15thpercentile value, a 25thpercentile value, a 35thpercentile value, a 65thpercentile value, a 75thpercentile value, or an 85thpercentile value. In some examples, processing circuitry 310 may select the upper threshold and the lower threshold such that the upper threshold and the lower threshold define at least a thresholdDocket No.: A0012611W001 minimum range, e.g., a range of at least 80 microvolts. Thresholds may be set above or below these ranges in other examples.

[0119] Processing circuitry 310 controls simulation generator 202 to deliver subsequent electrical stimulation therapy according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals (910). As an example, processing circuitry 310 may control stimulation generator 202 to adjust, e.g., increase or decrease, a stimulation parameter, e.g., a voltage amplitude, when a characteristic value of the subsequently sensed bioelectric signal meets the upper threshold or the lower threshold.

[0120] In some examples, the example operation of FIG. 9 occurs during a monitoring phase, such as an initialization phase, to make initial threshold value selections. In some examples, the example operation of FIG. 9 occurs during a therapy phase, such as a period of time after initial threshold values were set. In examples in which the example operation of FIG. 9 occurs during a therapy phase, processing circuitry 310 may determine to adjust the one or more threshold values. Processing circuitry 310 may determine to maintain a minimum range when adjusting the one or more threshold values during the therapy phase. In some examples, when patient 112 receives electrical stimulation therapy, a range associated with patient 112’ s LFP values may change, e.g., become narrower. Processing circuitry 310 may determine to maintain a minimum range of LFP values to prevent any symptoms or side effects associated with a narrow homeostatic window. In some examples, processing circuitry 310 may adjust the one or more threshold values to a threshold extent relative to previously selected threshold values, such as within a threshold value, e.g., 80 microvolts, or within a threshold percentage, e.g., 5%.

[0121] In some examples, processing circuitry 310 may require clinician and / or patient confirmation of the one or more threshold values before selecting and / or adjusting the one or more threshold values. In other examples, processing circuitry 310 may select the one or more threshold values without clinician and / or patient confirmation.

[0122] FIG. 10 is a flowchart illustrating an example operation for adjusting the one or more thresholds according to an example of the techniques of the disclosure. The example operation of FIG. 10 will be described with respect to processing circuitry 210, but any processing circuitry of system 100 may additionally or alternatively perform the example operation, such as processing circuitry 310 of programmer 104 and / or other devices or systems may be used in other examples to select the one or more thresholds for controlling adjustment of electrical stimulation. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model.

[0123] In some examples, the example operation of FIG. 10 follows the example operation of FIG. 9. As shown in the example of FIG. 10, processing circuitry 210 controls stimulationDocket No.: A0012611W001 generator 202 to deliver electrical stimulation therapy according to one or more threshold values and characteristic values of a sensed bioelectric signal, e.g., the subsequently sensed bioelectric signal (1002).

[0124] Processing circuitry 210 determines whether one or more trigger criteria is / are met (1004). To determine the one or more trigger criteria is / are met, processing circuitry 210 may determine that a patient state has changed to a threshold extent. Processing circuitry 210 may determine that the patient state has changed based on the bioelectric signal, e.g., an LFP signal, one or more additional signals, and / or historical patient data. Additionally, or alternatively, processing circuitry 210 may determine that a patient activity level has changed to a threshold extent to determine the one or more trigger criteria is / are met based on an accelerometer signal. Processing circuitry 210 may additionally or alternatively determine the one or more trigger criteria is / are met based on, user input, e.g., patient or clinician input. As an example, patient input indicating that patient 112 is experiencing symptoms or side effects may be indicative of a need to consider adjusting the one or more threshold values.

[0125] Processing circuitry 210 may additionally or alternatively determine the one or more trigger criteria is / are met based on a determination that adjusting the electrical stimulation, e.g., subsequent electrical stimulation, according to the one or more threshold values has caused an electrical stimulation parameter value, e.g., a stimulation voltage amplitude and / or a stimulation current amplitude, to meet one or more electrical stimulation parameter value thresholds a threshold number of times over a period of time. As an example, if patient 112’ s characteristic values meet an upper threshold a threshold number of times within the period of time, e.g., a 12 hour period, a 24 hour period, a multi-day period, or a multi-week period, processing circuitry 210 may determine the one or more trigger criteria is / are met. In some examples, the period of time comprises an ambulatory period.

[0126] As another example, processing circuitry 210 may determine the one or more trigger criteria is / are met based on a determination that adjusting the subsequent electrical stimulation according to the one or more threshold values has caused the stimulation voltage amplitude to meet one or more electrical stimulation parameter value thresholds for a threshold amount of time. In some examples, the threshold amount of time may be a percentage of the period of time, e.g., the 12 hour period, the 24 hour period, the multi-day period, or the multi-week period. In some examples, processing circuitry 210 may determine the one or more trigger criteria is / are met based on the determination that the stimulation voltage amplitude has met the one or more electrical stimulation parameter value thresholds for the threshold amount of time based on electrical stimulation delivered during the day while patient 112 is awake. Processing circuitry 210 may or may not make the determination based on electrical stimulation delivered whileDocket No.: A0012611W001 patient 112 is sleeping. During sleep, stimulation voltage amplitudes generally remain low, such as near a lower threshold of the one or more electrical stimulation parameter value thresholds. In examples in which processing circuitry 210 makes the determination based on electrical stimulation delivered while patient 112 is sleeping, the threshold amount of time may be higher while patient 112 is sleeping than the threshold amount of time while patient 112 is awake.

[0127] Processing circuitry 210 may additionally or alternatively determine the one or more trigger criteria is / are met based on a determination that a period of time that a difference between the first representative values and the characteristic values, e.g., a trend in the characteristic values of the subsequent bioelectric signal, has met a change criterion meets a time threshold. As an example, if the characteristic values have different from representative values to a threshold extent for a threshold period of time, processing circuitry 210 may determine the one or more trigger criteria is / are met.

[0128] If the one or more trigger criteria is / are not met (“NO” branch of block 1004), processing circuitry 210 continues to control electrical stimulation according to the one or more threshold values and characteristic values of the sensed bioelectric signal (1002) and continues to check whether the one or more trigger criteria is / are met (1004). If the one or more trigger criteria is / are met (“YES” branch of block 1004), processing circuitry 210 controls sensing circuitry, e.g., sensing module 204, to sense a subsequent bioelectric signal over an ambulatory period, e.g., a 12 hour period, a 24 hour period, a multi-day period, or a multi-month period (1006). In some examples, the ambulatory period comprises a second ambulatory period following the ambulatory period described with respect to FIG. 9. In other examples, the ambulatory period comprises a first ambulatory period.

[0129] Processing circuitry 210 determines, based on the subsequent bioelectric signal, characteristic values, e.g., bioelectric signal amplitude values, of the subsequent bioelectric signal over a recurring interval of time, e.g., a 4 hour interval, a 12 hour interval, or a 24 hour interval, within the ambulatory period (1008). Processing circuitry 210 determines representative values, e.g., average values, of the subsequent bioelectric signal for respective times within the recurring interval based on the characteristic values (1010). Processing circuitry 210 adjusts the one or more threshold values based on the representative values (1012). In some examples, processing circuitry 210 adjusts the one or more threshold values to within a threshold extent, such as within a threshold absolute value or within a threshold percentage.

[0130] In some examples, the bioelectric signal may change temporarily due to temporary changes in patient posture, patient activity level, patient stress, and / or patient environment. Processing circuitry 210 may avoid adjusting the one or more threshold values due to temporary changes in the bioelectric signal. As an example, processing circuitry 210 may determine not toDocket No.: A0012611W001 adjust the one or more threshold values unless processing circuitry 210 determines the change in the bioelectric signal is associated with a change in patient state, e.g., disease state, or that the bioelectric signal has been changed relative to previous representative values for a threshold period of time meeting a time threshold, e.g., 48 hours.

[0131] In some examples, processing circuitry 210 may, in response to determining the bioelectric signal change is temporary, determine to temporarily adjust the one or more threshold values. Processing circuitry 210 may switch back to previous threshold values after a period of time associated with the temporary change in the bioelectric signal has passed.

[0132] FIG. 11 is a flowchart illustrating an example operation for determining whether representative values meet one or more criteria for adjusting one or more thresholds according to an example of the techniques of the disclosure. The example operation of FIG. 11 will be described with respect to processing circuitry 210, but any processing circuitry of system 100 may additionally or alternatively perform the example operation, such as processing circuitry 310 of programmer 104 and / or other devices or systems may be used in other examples to select the one or more thresholds for controlling adjustment of electrical stimulation. In some examples, processing circuitry of different devices may be used to collectively perform this technique in a distributed computing model. In some examples, the example operation of FIG. 11 occurs subsequent to either of FIG. 9 or FIG. 10.

[0133] As described in the example of FIG. 11, processing circuitry 210 determines second representative values of the subsequent bioelectric signal for respective times within a second recurring interval based on characteristic values of the subsequent bioelectric signal (1102). In some examples, the recurring interval of the example operation of FIG. 9 is a first recurring interval. In some examples, the second recurring interval is shorter or longer than the first recurring interval. Processing circuitry 210 may determine to determine the second representative values based on one or more trigger criteria being met, such as the one or more trigger criteria described with respect to FIG. 10.

[0134] Processing circuitry 210 determines whether the second representative values of the subsequent bioelectric signal meet one or more criteria (1104). To meet the one or more criteria, processing circuitry 210 may determine the second representative values are associated with a change in patient state, e.g., a change in disease state, such as worsening or improving disease state, and / or that a change between the first representative values and the second representative values has met a change criterion for a threshold period of time, e.g., 2 days. If the second representative values meet the one or more change criteria (“YES” branch of block 1104), processing circuitry 210 adjusts the one or more threshold values based on the second representative values (1106). In some examples, processing circuitry 210 adjusts the one or moreDocket No.: A0012611W001 threshold values to within a threshold extent, such as within a threshold absolute value or within a threshold percentage. If the second representative values do not meet the one or more change criteria (“NO” branch of block 1104), processing circuitry 210 does not adjust the one or more threshold values (1108).

[0135] In some examples, the bioelectric signal may change temporarily due to temporary changes in patient posture, patient activity level, patient stress, and / or patient environment. Processing circuitry 210 may avoid adjusting the one or more threshold values due to temporary changes in the bioelectric signal. As an example, processing circuitry 210 may determine not to adjust the one or more threshold values unless processing circuitry 210 determines the change in the bioelectric signal is associated with a change in patient state, e.g., disease state, or that the bioelectric signal has been changed relative to previous representative values for a threshold period of time meeting a time threshold, e.g., 48 hours.

[0136] The following examples are described herein.

[0137] Example 1. A system comprising: a memory; and processing circuitry coupled to the memory and configured to: control sensing circuitry to sense a bioelectric signal of a patient over an ambulatory period of time; determine, based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determine, based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; select, based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

[0138] Example 2. The system of example 1, wherein the ambulatory period of time includes delivery of electrical stimulation.

[0139] Example 3. The system of any of examples 1 or 2, wherein the ambulatory period of time comprises a monitoring period having a duration of at least 24 hours, and wherein the processing circuitry is configured to control the adjustment of the subsequent electrical stimulation according to the one or more threshold values and the characteristic values of the subsequently sensed bioelectric signal during a therapy period.

[0140] Example 4. The system of any of examples 1 through 3, wherein the ambulatory period of time comprises a first ambulatory period of time, the recurring interval comprises a first recurring interval, the representative values comprise first representative values, and wherein the processing circuitry is further configured to: determine, based on theDocket No.: A0012611W001 characteristic values of the subsequent bioelectric signal, the subsequent bioelectric signal corresponding to a second recurring interval of time within the second ambulatory period of time, second representative values of the subsequent bioelectric signal for respective times within the second recurring interval; and adjust, based on the second representative values of the subsequent bioelectric signal, the one or more threshold values.

[0141] Example 5. The system of example 4, wherein the processing circuitry is further configured to: determine the second representative values meet one or more criteria; and in response to the determination that the second representative values meet the one or more criteria, determine to adjust the one or more threshold values.

[0142] Example 6. The system of example 5, wherein the processing circuitry is configured to determine that the second representative values meet the one or more criteria by being configured to: determine a change between the first representative values and the second representative values meets a change criterion, wherein to meet the change criterion, the processing circuitry is configured to determine the change is one or more of: associated with a change in patient state; or associated with a period of time meeting a time threshold.

[0143] Example 7. The system of any of examples 5 or 6, wherein the processing circuitry is configured to adjust the one or more threshold values based on the second representative values of the subsequent bioelectric signal by being configured to: adjust the one or more threshold values one or more of: within a threshold absolute value; or within a threshold percentage.

[0144] Example 8. The system of any of examples 4 through 7, wherein the processing circuitry is configured to determine the second representative values of the subsequent bioelectric signal based on one or more of: a periodic schedule; a determination that a patient state has changed; a determination that a patient activity level has changed; user input; a determination that controlling adjustment of the subsequent electrical stimulation according to the one or more threshold values has caused an electrical stimulation parameter value to meet one or more electrical stimulation parameter value thresholds a threshold number of times over the second ambulatory period; or determining a period of time that a difference between the first representative values and the second representative values has met a change criterion meets a time threshold.

[0145] Example 9. The system of any of examples 1 through 8, wherein the processing circuitry is configured to select the one or more threshold values by being configured to: filter the representative values of the bioelectric signal for respective times within the recurring interval based on a patient schedule.Docket No.: A0012611W001

[0146] Example 10. The system of any of examples 1 through 9, wherein the recurring interval comprises a daily interval.

[0147] Example 11. The system of any of examples 1 through 10, wherein the one or more threshold values comprise one or more of an upper threshold or a lower threshold defining a homeostatic window, and wherein the processing circuitry is configured to select the one or more of the upper threshold or the lower threshold by being configured to: select the one or more of the upper threshold or the lower threshold based on a range of the representative values of the bioelectric signal.

[0148] Example 12. The system of example 11, wherein the processing circuitry is configured to select the one or more of the upper threshold or the lower threshold based on the range of the representative values of the bioelectric signal by being configured to one or more of: set the upper threshold to a value within a range of the 65thto the 85thpercentile of the range of representative values; or set the lower threshold to a value within a range of the 15thto the 35thpercentile of the range of representative values.

[0149] Example 13. The system of any of examples 1 through 12, the system further comprising an external programmer comprising the processing circuitry and the memory, wherein the external programmer further comprises a user interface, and wherein the processing circuitry is further configured to: control the user interface to output an indication of the selected one or more threshold values; and receive, via the user interface, user confirmation of the one or more threshold values.

[0150] Example 14. The system of any of examples 1 through 13, further comprising an implantable medical device configured to deliver the electrical stimulation according to the one or more threshold values.

[0151] Example 15. The system of any of examples 1 through 14, wherein the bioelectric signal comprises a local field potential, and wherein the electrical stimulation comprises deep brain stimulation.

[0152] Example 16. A method comprising: controlling, by processing circuitry of a system, sensing circuitry of the system to sense a bioelectric signal of a patient over an ambulatory period of time; determining, by the processing circuitry and based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determining, by the processing circuitry and based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; selecting, by the processing circuitry and based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least oneDocket No.: A0012611W001 parameter value that defines subsequent electrical stimulation; and controlling, by the processing circuitry, adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

[0153] Example 17. The method of example 16, wherein the ambulatory period of time includes delivery of electrical stimulation.

[0154] Example 18. The method of any of examples 16 or 17, wherein the ambulatory period of time comprises a monitoring period having a duration of at least 24 hours, and wherein controlling the adjustment of the subsequent electrical stimulation according to the one or more threshold values and the characteristic values of the subsequently sensed bioelectric signal comprises controlling the adjustment of the subsequent electrical stimulation according to the one or more threshold values and the characteristic values of the subsequently sensed bioelectric signal during a therapy period.

[0155] Example 19. The method of any of examples 16 through 18, wherein the ambulatory period of time comprises a first ambulatory period of time, wherein the recurring interval comprises a first recurring interval, wherein the representative values comprise first representative values, and wherein the method further comprises: determining, by the processing circuitry and based on the characteristic values of the subsequent bioelectric signal, the subsequent bioelectric signal corresponding to a second recurring interval of time within the second ambulatory period of time, second representative values of the subsequent bioelectric signal for respective times within the second recurring interval; and adjusting, by the processing circuitry and based on the second representative values of the subsequent bioelectric signal, the one or more threshold values.

[0156] Example 20. The method of example 19, further comprising: determining, by the processing circuitry, the second representative values meet one or more criteria; and determining, by the processing circuitry and in response to the determination that the second representative values meet the one or more criteria, to adjust the one or more threshold values.

[0157] Example 21. The method of example 20, wherein determining the second representative values meet the one or more criteria comprises: determining, by the processing circuitry, that a change between the first representative values and the second representative values meets a change criterion, wherein to meet the change criterion, the processing circuitry is configured to determine the change is one or more of: associated with a change in patient state; or associated with a period of time meeting a time threshold.

[0158] Example 22. The method of any of examples 20 or 21, wherein adjusting the one or more threshold values based on the second representative values of the subsequent bioelectricDocket No.: A0012611W001 signal comprises: adjusting, by the processing circuitry, the one or more threshold values one or more of: within a threshold absolute value; or within a threshold percentage.

[0159] Example 23. The method of any of examples 19 through 22, wherein determining the second representative values of the subsequent bioelectric signal comprises determining the second representative values based on one or more of: a periodic schedule; a determination that a patient state has changed; a determination that a patient activity level has changed; user input; a determination that controlling adjustment of the subsequent electrical stimulation according to the one or more threshold values has caused an electrical stimulation parameter value to meet one or more electrical stimulation parameter value thresholds a threshold number of times over the second ambulatory period; or determining a period of time that a difference between the first representative values and the second representative values has met a change criterion meets a time threshold.

[0160] Example 24. The method of any of examples 16 through 23, wherein selecting the one or more threshold values comprises: filtering, by the processing circuitry, the representative values of the bioelectric signal for respective times within the recurring interval based on a patient schedule; and selecting, by the processing circuitry, the one or more threshold valued based on the filtered representative values.

[0161] Example 25. The method of any of examples 16 through 24, wherein the recurring interval comprises a daily interval.

[0162] Example 26. The method of any of examples 16 through 25, wherein the one or more threshold values comprise one or more of an upper threshold or a lower threshold defining a homeostatic window, and wherein selecting the one or more of the upper threshold or the lower threshold comprises: selecting, by the processing circuitry, the one or more of the upper threshold or the lower threshold based on a range of the representative values of the bioelectric signal.

[0163] Example 27. The method of any of examples 16 through 26, wherein selecting the one or more threshold values comprises: generating for output by a user interface, a representation of a range of the representative values of the bioelectric signal; and receiving, by the user interface, user input indicative of one or more of an upper threshold value or a lower threshold value within the range of representative values of the bioelectric signal.

[0164] Example 28. The method of any of examples 16 through 27, wherein the system further comprises an external programmer comprising the processing circuitry and the memory, wherein the external programmer further comprises a user interface, and wherein the method further comprises: controlling, by the processing circuitry, the user interface to output an indication of the selected one or more threshold values; and receiving, via the user interface, user confirmation of the one or more threshold values.Docket No.: A0012611W001

[0165] Example 29. The method of any of examples 16 through 28, further comprising an implantable medical device configured to deliver the electrical stimulation according to the one or more threshold values.

[0166] Example 30. The method of any of examples 16 through 29, wherein the bioelectric signal comprises a local field potential, and wherein the electrical stimulation comprises deep brain stimulation.

[0167] Example 31. A non-transitory computer-readable medium storing instructions that when executed cause processing circuitry to: control sensing circuitry to sense a bioelectric signal of a patient over an ambulatory period of time; determine, based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determine, based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; select, based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

[0168] The techniques of this disclosure may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the described techniques may be implemented within one or more processors or processing circuitry, including one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry. A control unit including hardware may also perform one or more of the techniques of this disclosure.

[0169] Such hardware, software, and firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any of the described units, circuits or components may be implemented together or separately as discrete but interoperable logic devices. Depiction of different features as circuits or units is intended to highlight different functional aspects and does not necessarily imply that such circuits or units must be realized by separate hardware or software components. Rather, functionality associated with one or more circuits or units may be performed by separate hardware or software components or integrated within common or separate hardware or software components.Docket No.: A0012611W001

[0170] The techniques described in this disclosure may also be embodied or encoded in a computer-readable medium, such as a computer-readable storage medium, containing instructions that may be described as non-transitory media. Instructions embedded or encoded in a computer-readable storage medium may cause a programmable processor, or other processor, to perform the method, e.g., when the instructions are executed. Computer readable storage media may include random access memory (RAM), read only memory (ROM), programmable read only memory (PROM), erasable programmable read only memory (EPROM), electronically erasable programmable read only memory (EEPROM), flash memory, a hard disk, a CD-ROM, a floppy disk, a cassette, magnetic media, optical media, or other computer readable media.

[0171] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

Docket No.: A0012611W001WHAT IS CLAIMED IS:

1. A system comprising: a memory; and processing circuitry coupled to the memory and configured to: control sensing circuitry to sense a bioelectric signal of a patient over an ambulatory period of time; determine, based on the bioelectric signal sensed over the ambulatory period of time, characteristic values of the bioelectric signal over a recurring interval of time within the ambulatory period of time; determine, based on the characteristic values, representative values of the bioelectric signal for respective times within the recurring interval; select, based on the representative values of the bioelectric signal for respective times within the recurring interval, one or more threshold values as feedback for adjusting at least one parameter value that defines subsequent electrical stimulation; and control adjustment of the subsequent electrical stimulation according to the one or more threshold values and characteristic values of subsequently sensed bioelectric signals.

2. The system of claim 1, wherein the ambulatory period of time includes delivery of electrical stimulation.

3. The system of any of claims 1 or 2, wherein the ambulatory period of time comprises a monitoring period having a duration of at least 24 hours, and wherein the processing circuitry is configured to control the adjustment of the subsequent electrical stimulation according to the one or more threshold values and the characteristic values of the subsequently sensed bioelectric signal during a therapy period.

4. The system of any of claims 1 through 3, wherein the ambulatory period of time comprises a first ambulatory period of time, the recurring interval comprises a first recurring interval, the representative values comprise first representative values, and wherein the processing circuitry is further configured to: determine, based on the characteristic values of the subsequent bioelectric signal, the subsequent bioelectric signal corresponding to a second recurring interval of time within theDocket No.: A0012611W001 second ambulatory period of time, second representative values of the subsequent bioelectric signal for respective times within the second recurring interval; and adjust, based on the second representative values of the subsequent bioelectric signal, the one or more threshold values.

5. The system of claim 4, wherein the processing circuitry is further configured to: determine the second representative values meet one or more criteria; and in response to the determination that the second representative values meet the one or more criteria, determine to adjust the one or more threshold values.

6. The system of claim 5, wherein the processing circuitry is configured to determine that the second representative values meet the one or more criteria by being configured to: determine a change between the first representative values and the second representative values meets a change criterion, wherein to meet the change criterion, the processing circuitry is configured to determine the change is one or more of: associated with a change in patient state; or associated with a period of time meeting a time threshold.

7. The system of any of claims 5 or 6, wherein the processing circuitry is configured to adjust the one or more threshold values based on the second representative values of the subsequent bioelectric signal by being configured to: adjust the one or more threshold values one or more of: within a threshold absolute value; or within a threshold percentage.

8. The system of any of claims 4 through 7, wherein the processing circuitry is configured to determine the second representative values of the subsequent bioelectric signal based on one or more of: a periodic schedule; a determination that a patient state has changed; a determination that a patient activity level has changed; user input; a determination that controlling adjustment of the subsequent electrical stimulation according to the one or more threshold values has caused an electrical stimulation parameterDocket No.: A0012611W001 value to meet one or more electrical stimulation parameter value thresholds a threshold number of times over the second ambulatory period; or a determination that a period of time that a difference between the first representative values and the second representative values has met a change criterion meets a time threshold.

9. The system of any of claims 1 through 8, wherein the processing circuitry is configured to select the one or more threshold values by being configured to: filter the representative values of the bioelectric signal for respective times within the recurring interval based on a patient schedule.

10. The system of any of claims 1 through 9, wherein the recurring interval comprises a daily interval.

11. The system of any of claims 1 through 10, wherein the one or more threshold values comprise one or more of an upper threshold or a lower threshold defining a homeostatic window, and wherein the processing circuitry is configured to select the one or more of the upper threshold or the lower threshold by being configured to: select the one or more of the upper threshold or the lower threshold based on a range of the representative values of the bioelectric signal.

12. The system of claim 11, wherein the processing circuitry is configured to select the one or more of the upper threshold or the lower threshold based on the range of the representative values of the bioelectric signal by being configured to one or more of: set the upper threshold to a value within a range of the 65thto the 85thpercentile of the range of representative values; or set the lower threshold to a value within a range of the 15thto the 35thpercentile of the range of representative values.

13. The system of any of claims 1 through 12, the system further comprising an external programmer comprising the processing circuitry and the memory, wherein the external programmer further comprises a user interface, and wherein the processing circuitry is further configured to: control the user interface to output an indication of the selected one or more threshold values; and receive, via the user interface, user confirmation of the one or more threshold values.Docket No.: A0012611W00114. The system of any of claims 1 through 13, further comprising an implantable medical device configured to deliver the electrical stimulation according to the one or more threshold values.

15. The system of any of claims 1 through 14, wherein the bioelectric signal comprises a local field potential, and wherein the electrical stimulation comprises deep brain stimulation.

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