Coordinated neurostimulation for epilepsy and depression treatment

Abstract

Coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device can include determining a total therapy dosage based on epilepsy therapy parameters and depression therapy parameters. In response to determining the total therapy dosage is within a specified therapy limit, a signal generator circuit in the implantable device can provide epilepsy and depression therapy signals to therapy delivery electrodes according to the epilepsy and depression therapy parameters, respectively. If a total therapy dosage exceeds a specified maximum therapy dosage limit, then the signal generator circuit can be inhibited from providing at least one of the therapies using the epilepsy and depression therapy parameters, respectively. If a total therapy dosage is less than a specified minimum therapy dosage limit, the signal generator circuit can be configured to automatically update parameters for one or more therapies to achieve at least the specified minimum dosage.

Description

COORDINATED NEUROSTIMULATION FOR EPILEPSY ANDDEPRESSION TREATMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is related to and claims priority to United States Provisional Application No. 63 / 605,030, filed on December 1, 2023, and entitled “COORDINATED NEUROSTIMULATION FOR EPILEPSY AND DEPRESSION TREATMENT,” the entirety of which is incorporated herein by reference.BACKGROUND

[0002] Epilepsy is a disorder in which nerve cell activity in the brain is disturbed, causing seizures. During a seizure, a person can experience abnormal behavior, symptoms, and sensations, sometimes including loss of consciousness. Epilepsy is usually treated by medications and in some cases by surgery, devices, or dietary changes. Though some seizures can be controlled with medication, if medication becomes ineffective, other forms of treatment may be considered, including neurostimulation therapy.

[0003] Clinical depression is a mood disorder characterized by persistent feelings of sadness, hopelessness, and loss of interest that can disrupt daily functioning. Depression is typically treated first with antidepressant medications and psychotherapy. If medications are not effective, then other options may be explored such as nerve or brain stimulation therapy. Stimulation therapies for depression include electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). ECT involves sending electric currents through the brain to trigger a brief seizure, under anesthesia. It can be effective for severe depression not responsive to medications. VNS uses an implanted device to send electric signals to the brain via the vagus nerve. TMS is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain. DBS uses surgically implanted electrodes that provide electric currents to target areas involved in mood regulation. Whenantidepressant medications and psychotherapy do not sufficiently improve depressive symptoms, neurostimulation therapies may be considered.SUMMARY

[0004] Systems and methods are provided for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device. In an example, an implantable neurostimulation system includes at least one electrode pair for delivering epilepsy and depression therapies to portions of a vagus nerve. A neurostimulation signal generator circuit provides therapy signals based on respective epilepsy and depression therapy parameters. A control circuit can manage therapy delivery based on a total therapy dosage. For example, when the dosage is below or within a specified maximum therapy limit, both therapies are provided according to their parameters; when the specified maximum therapy limit is exceeded, at least one therapy is inhibited or its intensity is reduced.

[0005] Methods include determining a total therapy dosage based on therapy parameters, controlling signal delivery within specified limits, and inhibiting signals when limits are exceeded. The methods can include providing depression therapy, detecting seizure events, and managing therapy delivery based on dosage limits. User interface methods enable displaying therapy parameters, receiving parameter modifications, and recording changes in patient logs.

[0006] The system and methods discussed herein thus enable coordinated delivery of multiple neurostimulation therapies while managing total dosage to avoid overstimulation, improve therapy effectiveness, and extend device longevity. The therapies can be delivered concurrently or separately using shared or independent electrodes, with parameters adjusted based on patient needs and therapy priorities.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0007] To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the figure number in which that element is first introduced. The drawings are not drawn to scale.

[0008] FIG. 1 illustrates generally an example of a neurostimulation system.

[0009] FIG. 2 illustrates generally an example of a tripolar lead assembly.

[0010] FIG. 3 illustrates generally a pictorial representation of physiological parameters and therapy parameters.

[0011] FIG. 4 illustrates generally an example of a first method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device.

[0012] FIG. 5 illustrates generally an example of a second method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device.

[0013] FIG. 6 illustrates generally an example of an external interface device.

[0014] FIG. 7 illustrates generally an example of a third method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device.

[0015] FIG. 8 illustrates generally an example of a fourth method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device.

[0016] FIG. 9 illustrates generally an example of a fifth method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device.

[0017] FIG. 10 illustrates generally an example of a machine in the form of a computer system within which a set of instructions may be executed for causing the machine to perform any one or more of the methodologies discussed herein, according to an example embodiment.DETAILED DESCRIPTION

[0018] Patients suffering from epilepsy may also suffer from clinical depression. The two conditions may co-occur because the chronic nature of epilepsy and dealing with uncontrolled seizures can lead to feelings of hopelessness, frustration, and mood changes that may trigger depression.Additionally, some of the same neurotransmitters and neural circuits are implicated in both epilepsy and depression. Abnormalities in serotonin, gamma-aminobutyric acid (GABA), and glutamate function may contribute to both conditions. Furthermore, structural changes in the brain due to recurrent seizures may play a role in depression risk. Some patients dealing with epilepsy and clinical depression report symptoms of fatigue, insomnia, and cognitive dysfunction, which may have a compounding effect.

[0019] The present inventors have recognized that a neurostimulation device may be configured to treat epilepsy and depression in a coordinated manner. For example, the present inventors have recognized that effective therapies for epilepsy and depression can include or use vagus nerve stimulation, such as can be provided by an implantable device. The present inventors have further recognized that a neurostimulation therapy that is effective for treatment of epilepsy may be different than a neurostimulation therapy that is effective for treatment of depression. Therefore, the inventors have recognized the importance of balancing the potentially competing demands of epilepsy and depression therapies to ensure long term therapy effectiveness and avoid overstimulation.

[0020] The inventors have recognized that concurrently delivering and adapting two distinct neurostimulation therapies requires timing, control, and monitoring mechanisms that go beyond adapting existing single-purpose systems for sequential delivery. Providing coordinated epilepsy and depression treatment enables real-time therapy adjustments tailored to a patient's needs at a given time (e.g., prioritizing seizure prevention or mood, depending on sensed or patient-reported physiological status). Furthermore, monitoring and responding to a total therapy dosage enables optimization of treatment levels for multimodal therapies without exceeding safe limits, and helps reduce habituation effects while improving device longevity. By optimizing therapy for multiple conditions in coordination, side effects can be minimized while efficacy is maximized.

[0021] Neurostimulation therapy for treatment of epilepsy and / or depression may become ineffective over time, for example due to patient habituation to therapy. Habituation can manifest as a patient adapting oracclimating to ongoing treatment, in some cases reducing an effectiveness of a therapy or requiring a more intense therapy to achieve the same therapeutic result that was previously achieved using a lower intensity therapy. Methods and devices for displaying data from, or for programming, a treatment system can be provided to assist in improving therapy effectiveness and titrating an amount of neurostimulation therapy, or therapy intensity, received by a patient to reduce habituation.

[0022] In an example, a method can include providing an epilepsy therapy and providing a depression therapy using an implantable neurostimulation device. The therapies can be provided separately, concurrently, or at least partially overlapping in time. The therapies can include neurostimulation that is provided via the same or different electrodes, for example, to one or more areas of a vagus nerve. For example, the therapies can be provided using the same electrodes at different scheduled time intervals, such as at alternating or interleaved times. This interleaved delivery allows multiple therapeutic protocols to be administered through shared electrodes by temporally separating their activation periods. The therapies can be delivered at one or more specified therapeutic intensities, which can be determined by adjusting one or more electrostimulation parameters including: electrostimulation magnitude, pulse width, duty cycle, pulse morphology, or pulse frequency, among other parameters. These parameters can be modulated individually or in combination to achieve the desired therapeutic intensity level.

[0023] In an example, a coordinated therapy method can include determining a total therapy dosage based on epilepsy therapy parameters and depression therapy parameters. In response to determining the total therapy dosage is within a specified maximum therapy limit, the method can include controlling a signal generator circuit in the implantable device to provide epilepsy and depression therapy signals to therapy delivery electrodes according to the epilepsy and depression therapy parameters, respectively. In response to determining the total therapy dosage exceeds the specified maximum therapy limit, the method can include inhibiting the signal generator circuit from providing at least one of the epilepsy and depressiontherapy signals using the epilepsy and depression therapy parameters, respectively. If the therapy dosage exceeds the maximum therapy limit, then one or more parameters can be updated before therapy resumes.

[0024] In an example, a coordinated therapy method can include monitoring for therapy delivery that falls below a minimum therapy limit or baseline. The minimum therapy limit can help ensure therapeutic efficacy is maintained for one or both of epilepsy and depression conditions. In response to determining a total therapy dosage has fallen below a specified minimum therapy limit, the method can include automatically increasing the intensity of at least one of the epilepsy therapy or depression therapy to a specified minimum therapy dosage. For example, if depression therapy intensity has been reduced to accommodate increased epilepsy therapy (e.g., coinciding with a predicted or actual seizure event), the method can include gradually increasing the depression therapy back to a minimum therapeutic level, for example, after a seizure event has passed or when a risk of seizure is reduced. This helps prevent either therapy from becoming ineffective due to extended periods of reduced intensity while still respecting maximum dosage limits. Exceptions to the minimum therapy limit or baseline can be provided to help ensure patient safety, comfort, and device longevity.

[0025] In an example, a processor circuit (e.g., comprising a portion of an implantable device or an external device or system) is configured to execute a multiple-therapy optimization algorithm that coordinates delivery of epilepsy and depression therapies. The algorithm can modulate stimulation intensity for epilepsy therapy, which may require higher intensity stimulation during seizure events, while maintaining depression therapy at a constant reduced intensity level. This approach enables the system to provide therapeutic benefit for both conditions while keeping the total therapy dosage within specified minimum and maximum therapy dosage limits. For example, when a seizure event is detected, the processor circuit can temporarily increase the epilepsy therapy intensity while automatically reducing or holding constant the depression therapy intensity. The algorithm continuously monitors and titrates the combined therapy dosage to remain within specified safety and efficacy thresholds. By maintaining thedepression therapy dosage at a lower but consistent intensity during periods of increased epilepsy therapy, the system can preserve some therapeutic benefit for depression while prioritizing seizure treatment. The processor circuit can gradually adjust therapy parameters after the seizure event to return both therapies to optimal therapeutic levels while ensuring the total dosage remains within limits.

[0026] In an example, an interface device can be provided for interacting with or controlling the implantable neurostimulation device. The interface device can include a display comprising neurostimulation parameter information about the neurostimulation therapies provided to the patient. The neurostimulation parameter information can include an indication of an intensity of the neurostimulation therapy. In some examples, the neurostimulation parameter information can include information about a programmed neurostimulation signal magnitude, frequency, pulse width, pulse morphology, duty cycle, or therapy duration. The interface device can comprise neurostimulation therapy effectiveness information about a patient response to the neurostimulation therapy. In an example, the interface device can be configured to display information about a single patient or about a population of multiple patients. In an example, the interface device can be configured to provide information about the epilepsy therapy alongside information about the depression therapy such that the therapies can be updated together. In an example, the interface device can be configured to recognize conflicts between the therapy parameters for the different therapies, or to recognize when a total therapy dosage will be or may be exceeded, and can notify a patient or clinician.

[0027] An illustrative (but non-restrictive) example, as shown in FIG. 1, includes a system for providing neurostimulation to a vagus nerve 102, or vagus nerve stimulation (VNS). In an example, the system can be configured to sense nerve activity or other electrical activity or motion. In an example, the system includes an implantable device 116 such as can comprise a processor circuit 118 and a signal generator 120. The processor circuit 118, or control circuit, can control operation of the signal generator 120 according to various therapy delivery algorithms or therapy signal-definingparameters. The signal generator 120 can be configured to generate neurostimulation signals or pulses according to parameters or instructions from the control circuit. In an example, the signal generator 120 includes independent current sources and controllers to enable independent and simultaneous output of multiple respective therapy signals. In an example, the implantable device 116 and the processor circuit 118 are configured to execute a multiple-therapy optimization algorithm that modulates stimulation intensity for a higher priority therapy while holding a lower priority therapy at a constant reduced intensity. The algorithm helps titrate overall dosage below specified limits while maintaining some therapeutic benefit for multiple conditions.

[0028] In an example, the implantable device 116 comprises or is coupled to one or more physiological status sensors that are configured to sense information about a patient. For example, the system can include a sensor 122. The sensor 122 can comprise a portion of the implantable device 116 or can be coupled to a lead that is coupled to the implantable device 116. In an example, the physiological status sensor can include an electrocardiogram sensor, a heart rate sensor, a blood pressure sensor, a respiratory rate sensor, a blood oxygen saturation sensor, a sleep sensor, a blood glucose sensor, an accelerometer, or a combination thereof. Other sensors can additionally or alternatively be used.

[0029] In an example, the system includes an external interface device 124 that can communicate with the implantable device 116. The external interface device 124 can include a patient device or clinician device that is configured to receive information from, or provide information to, the implantable device 116. For example, the external interface device 124 can be used to set one or more neurostimulation parameters for a neurostimulation therapy that is provided to the patient by the implantable device 116. In an example, the external interface device 124 can be used to monitor, display, initiate, modify, or control one or more therapies provided by the implantable device 116. The external interface device 124 can receive physiological sensor data or therapy delivery parameters, display real-time and historical patient status information, initiate new or modify existingtherapeutic protocols, or otherwise control ongoing treatment and device settings.

[0030] In an example, seizure detection and VNS can include or use one or more vagus nerve sensing electrodes (e.g., “recording cuff’ or helical electrodes) coupled to one or more implantable leads. The electrodes can be located in different longitudinal positions along the cervical vagus region, relative to a stimulation site. Separate stimulating electrodes (e.g., an anode and a cathode) can be positioned to provide VNS. In the example of FIG. 1, the system includes a first electrode 108, a separate second electrode 110, a separate third electrode 112, and a separate nth electrode 114 positioned at or near the vagus nerve 102. The various electrodes can be used in various combinations to provide a neurostimulation therapy, such as an epilepsy therapy, a depression therapy, or both epilepsy and depression therapies.

[0031] The count and position of electrodes in the example of FIG. 1 is merely illustrative. For example, an implantable device can include circuitry for sensing (e.g., recording) neural activity (e.g., an action potential or compound action potential), along with circuitry for generating VNS. In such an example, a machine-learning approach, such as an instance of a machine learning -based model (e.g., such as can be referred to as an artificial intelligence or “AI”-based technique) can be instantiated by the implant circuitry or the processor circuit 118. Such a machine-learning - based model can be used for detection of a seizure, or for therapy control in response thereto, or both.

[0032] In an example, the sensing electrodes and related circuitry can be separate from the stimulating electrodes and the sensing electrodes can be monitored by a separate unit (e.g., an external assembly) that can be used in an acute or temporary manner, such as supporting an implantation procedure or implantable device configuration. For example, in the case that the sensing and stimulating electrodes are separate, the sensing electrode may be explanted acutely as a portion of a first procedure or soon after the first procedure. In yet another example, there can be three or more electrodes that are respectively configurable as either a stimulating electrode or a sensing electrode at any time. For example, two electrodes closest to a brain of apatient could be assigned as an anode and a cathode, respectively, and another electrode that is located more distally could be assigned as a sensing electrode to detect efferent nerve activation. As another illustration, two electrodes most distal to the brain could be assigned as an anode and a cathode, respectively, and an electrode more or most proximal to the brain could be assigned as a sensing electrode to detect afferent activity.

[0033] In an example, a lead can comprise one or more electrodes and can optionally comprise a retention or affixation feature. The affixation feature can be provided at a proximal or distal end of the lead, or can be provided at an intermediate location along the length of the lead. The affixation feature can be electrically functional (e.g., comprising one or more electrodes for sensing or delivery of electrical neurostimulation) or electrically nonfunctional (e.g., without conductive materials or without electrodes). In some examples, an electrode can be coupled to, or integrated with, a retention feature. In some examples, the electrodes can be made of biocompatible conductive materials, such as, platinum, platinum-iridium alloy, medical-grade stainless steel, gold, silver, titanium, titanium alloys, or a combination thereof. In some examples, insulating or coating materials of the leads can be made of biocompatible materials, such as, silicone rubber, polyurethane, ploytetrafluoroethylene (PTFE), medical-grade silicone, biocompatible polymers, or combinations thereof.

[0034] FIG. 2 illustrates generally an example of a first tripolar lead assembly 200 with a first retention feature 218. The first tripolar lead assembly 200 can be coupled to a stimulator circuit (e.g., in an implantable housing) and can be configured for implantation at a neural target, such as at the vagus nerve 202. The first tripolar lead assembly 200 can comprise a lead body 204 and one or more distal electrodes, anchors, or affixation features. In an example, the first tripolar lead assembly 200 comprises the first electrode 108, the second electrode 110, and the third electrode 112 from the example of FIG. 1.

[0035] The first tripolar lead assembly 200 includes multiple helical anchors, and each of the anchors comprises a separately addressable electrode. For example, the first tripolar lead assembly 200 includes a firsthelical anchor 206 with a first electrode 208 (e.g., comprising an example of the first electrode 108), a second helical anchor 210 with a second electrode 212 (e.g., comprising an example of the second electrode 110), and a third helical anchor 214 with a third electrode 216 (e.g., comprising an example of the third electrode 112). Any one or more of the anchors can optionally comprise an array of multiple, separately-addressable electrodes. Each of the helical anchors can be configured to receive a respective portion of the vagus nerve 202 (or other nerve) and can be adjustable in size to accommodate variations in width of the vagus nerve 202 and other tissue. For ease of reference herein, the first electrode 208 can be referred to as “electrode A” or “A,” the second electrode 212 can be referred to as “electrode B” or “B,” and the third electrode 216 can be referred to as “electrode C” or “C.” Combinations or pairs of the electrodes used for electrostimulation can be referred to by letters, for example, electrode pair A-B can refer to one of the first electrode 208 and the second electrode 212 configured as an anode and the other of the electrodes configured as a cathode for use in an electrostimulation vector. In other examples, two or more of the electrodes can be electrically coupled to provide an anode or cathode for another electrostimulation vector. For example, the first electrode 208 and the second electrode 212 can be electrically coupled to provide an anode and the third electrode 216 can be used as a cathode. Other combinations can similarly be used to provide other electrostimulation vectors for neurostimulation therapy delivery or sensing. The various combinations can be used for respective different therapies or can be used together for one or multiple therapies.

[0036] In the example of FIG. 2, the electrodes are illustrated schematically as having discrete locations, however, other locations in, on, or around the helical anchors can be used. In an example, one or more of the electrodes can comprise a ring electrode or conductive ribbon that extends partially or entirely around a revolution of its respective helical anchor, such as to encircle the target tissue (e.g., the vagus nerve 202). Other configurations can similarly be used.

[0037] In an example, the first retention feature 218 comprises a mesh or other structure. In the example of FIG. 2, the mesh structure can be coupled to a distal portion of the lead body 204 and configured to grow into tissue at, near, adjacent to, or around the vagus nerve 202 or other nerve tissue. In an example, additionally or alternatively to providing the first retention feature 218 at the distal portion of the lead body 204, one or more other instances of the first retention feature 218 can be coupled to a proximal or intermediate portion of the lead body 204.

[0038] FIG. 3 illustrates generally an example of an interface device 302, such as can comprise an example of the external interface device 124. The interface device 302 can be configured to provide, among other things, pictorial representations of therapy intensity and therapy efficacy over time. An intensity index 324 displayed on the interface device 302 represents a relative or absolute magnitude of an intensity of a neurostimulation therapy provided by a neurostimulation device to a patient. The intensity index can be a numerical value that is determined as a function of one or more neurostimulation parameters such as neurostimulation magnitude, frequency, pulse width, pulse morphology, duty cycle, therapy duration, or other parameter. For example, the intensity index can be a number between 0 and 100. In the example of FIG. 3, the intensity index 324 is displayed as “97.” Representations of therapy intensity other than numerical values can be similarly used, for example, colors or other icons can be used.

[0039] An efficacy index 326 displayed on the interface device 302 represents a metric that describes a patient response to the neurostimulation therapy. The efficacy index 326 can be a numerical value that is determined as a function of one or more patient response indicators, such as can include information about a seizure type, seizure frequency, or seizure intensity, or a presence or absence of side effect. In the example of FIG. 3, the efficacy index 326 is displayed as “84.” Representations of therapy efficacy other than numerical values can be similarly used, for example, colors or other icons can be used.

[0040] The intensity index 324 and the efficacy index 326 can be represented over time such that therapy information (e.g., from the intensityindex) is shown in visual or pictorial correspondence with information about an effect of therapy (e.g., using the efficacy index). In a particular nonlimiting example, the intensity index can be a function of a magnitude of a neurostimulation pulse signal (e.g., expressed in mA), a frequency of the pulse signal (e.g., expressed in Hertz), a pulse width of the pulse signal (e.g., expressed in microseconds), and a duty cycle of the pulse signal (e.g., expressed as a percentage). For example,

[0041] Intensity index = 100 * (magnitude) * (frequency) * (pulse width) * (duty cycle) I (magnitudemax) * (frequencymax) * (pulse widthmax) * (duty cyclemax)

[0042] where magnitudeniaxis a maximum available magnitude of the pulse signal, frequencymaxis a maximum available frequency of the pulse signal, pulse widthmax is a maximum available pulse width of the pulse signal, and duty cyclemaxis a maximum available duty cycle of the pulse signal.

[0043] In a particular non-limiting example, the efficacy index can be a function of one or more parameters that indicate an effect of the therapy (e.g., at a particular therapy intensity) on a patient.

[0044] In the example of FIG. 3, the interface device 302 shows an example interface 304. The example interface 304 includes a graphical representation of time-varying physiological signal information sensed from a patient, stimulation parameters for a therapy (or combination of therapies) delivered to the patient using an implanted neurostimulation device, and information about a composite index or therapy intensity for the therapy delivered to the patient. FIG. 3 can represent an example of a clinician or patient device display with information for monitoring therapy effectiveness relative to therapy parameters.

[0045] The display or graphical representation in the example of FIG. 3 can include a first display portion showing physiological parameters 312 over time and a second display portion showing intensity and effectiveness metrics 314 over time. The first display portion can include parameters such as heart rate 306 and heart rate variability 308, and can include information about seizure detection 310 or patient-reported depression episodes or severity. In an example, the first display portion can include informationabout physiological parameters, such as heart rate, blood pressure, respiratory rate, blood oxygen saturation, blood glucose, sleep quality, or a combination thereof. The first display portion can thus show graphically relationships between seizure activity and one or more physiological status indicators for the patient. The second display portion can include information about an intensity index 316 of a therapy (or therapies) provided to a patient over time. In an example, the second display portion can include a therapy effectiveness index 322, a depression index 320, and information about one or more therapy parameters, such as therapy pulse frequency 318 information. The second display portion can thus show graphically relationships between therapy intensity, therapy effectiveness, and one or more therapy parameters. The time scales for the first and second display portions can be the same or different. In some examples, the interface device can include information about a current therapy intensity index 324 and current therapy efficacy index 326.

[0046] In an example, events derived from the physiological parameter information (or reported by the patient or clinician) can be represented on the example interface 304. In an example, changes in programming of the neurostimulation device can be represented on the example interface 304, such as to help identify a patient physiological response to changes in therapy parameters.

[0047] In an example, the display can include at least one neurostimulation parameter change indication that is provided or displayed in visual correspondence with one or more of the intensity and effectiveness metrics 314 and the physiological parameter information (e.g., physiological parameters 312). For example, therapy parameter change events can be indicated together with the seizure detection 310 information.

[0048] In an example, the first display portion can include seizure detection 310 information. For example, the seizure detection 310 portion of the display can include a seizure event-indicating signal 328. The seizure eventindicating signal 328 can represent a determined likelihood of a seizure event based on a detected or reported physiological status of the patient. The likelihood determination can be based on, among other things, physiologicalinformation received from a physiological status sensor or other information reported by the patient. In an example, the seizure event-indicating signal 328 can be determined using a machine learning approach that receives various physiological status information about the patient, time of day information, environmental information, or other inputs, and identifies correlations with actual seizure events.

[0049] The seizure detection 310 portion of the display can include information about confirmed seizure events, such as at a first seizure event 330, a second seizure event 332, a third seizure event 334, and so on. The confirmed seizure events can be indicated by the patient or clinician at particular times. For example, the system can record a time of a received magnet swipe from the patient to indicate occurrence of a seizure event, such as the first seizure event 330 at a first time. The first display portion can then display the physiological parameters 312 and intensity and effectiveness metrics 314 in visual correspondence with an indication of the first seizure event 330, to help enable better patient or clinician analysis of the patient's physiological status leading up to, during, or following the first seizure event 330. In an example, the interface device 302 provides the indication of the first seizure event 330 in visual correspondence with information about the therapy used to address the first seizure event 330.

[0050] In an example, the interface device 302 can show or include neurostimulation parameter information about a neurostimulation therapy provided to a patient during a first time interval. The neurostimulation parameter information can include an indication of an intensity of the neurostimulation therapy. The interface device can include, or can be communicatively coupled to, a processor circuit (e.g., the processor circuit 118) configured to determine the indication of the intensity of the neurostimulation therapy based on, for example, two or more of an amplitude, frequency, pulse width, duty cycle, and duration of the neurostimulation therapy, among other factors. The processor circuit can be configured to determine the neurostimulation therapy effectiveness based on a seizure event rate at or following the first time interval. The processor circuit 118 can be configured to quantify or determine the neurostimulationtherapy effectiveness based on a seizure event type or seizure event severity at or following the first time interval.

[0051] In FIG. 3, therapy parameter changes can be visually indicated in coordination with the seizure detection 310 information and the seizure event-indicating signal 328. A first therapy parameter change event 336 is shown in correspondence with an increasing risk of seizure as-indicated by the rising trend of the seizure event-indicating signal 328 preceding the first therapy parameter change event 336. The example of FIG. 3 includes a second therapy parameter change event 338 in coordination with a later peak of the seizure event-indicating signal 328. Other therapy parameter change event indicators are also shown. The therapy parameter change event indicators can help a patient or clinician to readily identify correlations between therapy adjustments and their physiological effects (e.g., including seizure events experienced by the patient). In an example, upon seizure detection, the processor circuit 118 can be configured to automatically initiate or adjust a neurostimulation therapy to treat the seizure.

[0052] In an example, the system can detect depression using information reported from the patient or using one or more sensed physiological parameters 312. For example, depression in a patient can be deduced from reduced heart rate variability patterns, irregular heart rhythm variations, elevated resting heart rate, disrupted sleep patterns, changes in rapid eye movement (REM) sleep cycles, altered sleep-wake rhythms, total sleep duration, blood pressure variations, breathing pattern irregularities, shallow breathing, respiratory changes linked to anxiety symptoms, oxygen level fluctuations, metabolic changes associated with depression, or the like. These physiological parameters, among others, can be sensed and tracked to determine the depression index 320. For example, one or more sensors such as an electrocardiogram sensor, a heart rate sensor, a blood pressure sensor, a respiratory rate sensor, a blood oxygen saturation sensor, a sleep sensor, a blood glucose sensor, or a combination thereof can be used. In an example, depression experienced by the patient can be manually logged into a depression log in the system through manual patient input, manual clinician input, or a combination thereof. Upon detection of depression either throughphysiological parameters 312, patient input, clinician input, or a combination thereof, the processor circuit can be configured to automatically initiate or adjust a neurostimulation therapy to treat the depression event.

[0053] The graphical interface and / or the information displayed therein can be augmented in various ways. For example, the interface can be configured to allow customization or configuration of the visualization (e.g., of therapy effectiveness, side effects, therapy intensity, or other patient or therapy- related parameters) by clinicians, such as selecting specific parameters to display, adjusting or scaling of axes, or overlaying information about patient events (e.g., patient-reported or automatically detected or sensed events).

[0054] In another example, the interface can include or use predictive analytics or machine learning to forecast future therapy effectiveness (e.g., based on tried or projected therapy intensity) or can make automated recommendations for neurostimulation parameter changes.

[0055] In another example, the interface can be configured to allow interaction with the visualization to simulate potential therapy changes and view projected outcomes. This interactive component can enable more informed decisions about therapy parameter changes.

[0056] In another example, the interface can be configured to incorporate multi-modal patient data like audio, video (e.g., such as can be sensed using an external device or one or more other sensors configured to receive information about the patient), or textual patient reports. Integrating and displaying correlations with this data can further improve understanding of therapy efficacy, incidence of side effects, and more.

[0057] In another example, the user interface or interface device 302 can be configured to provide additional statistical views or analyses, such as correlating effectiveness with patient demographics or other conditions or events. In another example, the user interface can be configured to enable access to the visualization remotely from multiple devices, or to share visualizations across clinicians.

[0058] FIG. 4 illustrates generally an example of a first method 400 that can include determining whether a therapy dosage limit is met or exceeded.In an example, a therapy dosage limit is based on a quantity of a neurostimulation therapy that is provided to a patient during a specified unit of time. In an example, the therapy dosage limit or specified therapy limit can be based on a therapy intensity or an average intensity over time. In an example, the limit can be determined by calculating the integrated area under a curve of a therapy intensity versus time graph. For example, the area under the curve measurement can provide a metric that represents a cumulative total energy delivered during the therapeutic session, accounting for both the magnitude and duration of the stimulation. Generally, it can be advantageous to provide therapy at a minimum intensity that elicits a therapeutic effect to avoid habituation and preserve battery life of an implanted neurostimulation device. Implementation of therapy dosage limits or a specified therapy limit can improve multiple aspects of the treatment, such as improving patient safety, improving patient comfort, extending device longevity, or reducing battery drain.

[0059] At operation 402, the first method 400 includes receiving therapy parameters that define one or more neurostimulation therapies provided by an implantable neurostimulation device. For example, operation 402 can include receiving information about epilepsy therapy parameters and receiving information about depression therapy parameters. The parameters can indicate aspects of an epilepsy therapy and a depression therapy, respectively. For example, the parameters can indicate a neurostimulation signal magnitude, frequency, pulse width, duty cycle, pulse morphology, therapy duration or timing, or other aspect of a therapy. A therapy intensity or dosage can be calculated based on the parameters and duration of actual or expected therapy delivery.

[0060] At decision operation 404, the first method 400 includes determining whether a therapy dosage is within a specified therapy dosage limit. For example, decision operation 404 can include determining whether the therapy dosage is below a specified maximum therapy limit. The therapy dosage can be based on, for example, the therapy or therapies defined by the therapy parameters. For example, all other parameters being equal, a therapy that uses a greater magnitude neurostimulation signal will correspond to ahigher therapy dosage than a therapy that uses a lower magnitude neurostimulation signal for the same duration of time. In an example, the determination at decision operation 404 can be performed by the processor circuit 118 of the implantable device 116, or can be performed by an external device or processor.

[0061] If, at decision operation 404, the therapy dosage based on the therapy parameters received at operation 402 is within (e.g., does not exceed) the specified maximum therapy limit, then the first method 400 can proceed to operation 410. At operation 410, the therapy or therapies can be provided to the patient based on the therapy parameters received at operation 402. For example, operation 410 can include providing epilepsy and / or depression therapies in accordance with respective epilepsy therapy parameters and depression therapy parameters. In an example, therapies can be provided in accordance with the same respective therapy parameters unless or until updated parameters are received, such as at operation 412.

[0062] If, at decision operation 404, a therapy dosage based on the therapy parameters received at operation 402 is not within (e.g., exceeds) the specified maximum therapy limit, then the first method 400 can proceed to operation 406. At operation 406, the therapy or therapies defined by the parameters received at operation 402 can be withheld or inhibited. In response to identifying the therapy dosage is outside of the specified limit, the first method 400 can continue at operation 408 with notifying a patient or clinician. For example, operation 408 can include using the interface device 302 to provide a notification and request a change to one or more of the therapy parameters. In an example, the system can be configured to suggest a particular parameter that can be changed to adjust the therapy dosage to within the specified limit. At operation 412, the first method 400 can include receiving updated therapy parameters, such as via the interface device 302. For example, operation 412 can include receiving updated or changed parameters for one or both of an epilepsy therapy or a depression therapy.

[0063] In some examples, the specified limit can be associated with a tolerance. For example, the therapy or therapies can be permitted to exceedthe limit by a specified amount for a specified duration of time before the therapy is withheld at operation 406.

[0064] In an example, the control circuit can be configured to control the therapy parameters in response to a patient input and without regard for the therapy dosage and specified therapy limit. This patient input can comprise a magnetic signal received at the implantable neurostimulation device.

[0065] In an example, operation 406 can include withholding one therapy without withholding another. For example, a lower-intensity depression therapy can be allowed to continue while a higher-intensity epilepsy therapy is withheld, or a higher-intensity but shorter-duration therapy can be allowed to continue while a lower-intensity but longer-duration therapy can be withheld. That is, at least one of the therapies can be prioritized such that it is provided without interruption. For example, when total dosage limits are reached, a therapy control circuit can perform an automated prioritization algorithm that temporarily reduces parameters for one therapy (e.g., the depression therapy) while maintaining a second therapy (e.g., the epilepsy therapy) at therapeutic levels. In some examples, a therapy priority indication can be input into the therapy controller (e.g., the processor circuit 118), to configure the control circuit to prioritize the therapies based on the therapy priority indication.

[0066] In an example, operation 412 can include automatically updating or adjusting a therapy parameter to a default value if a new therapy parameter value is not received from the patient or clinician, for example, within a specified amount of time after notifying the patient or clinician at operation 408. In an example, the notification can prompt the patient or clinician to change at least one of the epilepsy therapy parameter or depression therapy parameter.

[0067] In an example, the neurostimulation system can use a closed-loop algorithm to automatically adjust stimulation therapy parameters in real-time to keep overall therapy dosages within or below specified limits. As a calculated therapy dosage approaches a defined limit based on the specified parameters, the stimulation intensity or duty cycle can be progressively lowered by small increments. For example, if a maximum allowed amplitudefor a depression therapy is 1.0 mA, the system could start stimulation at 0.75 mA. If the stimulation signal amplitude is increased (e.g., automatically or in response to a patient or clinician command), a cumulative dosage limit can be reached. In response, the stimulation signal amplitude can be gradually stepped down (e.g., in 0.1 mA increments) to a specified baseline (e.g., half of the limit amount, or 0.50 mA in this example) rather than abruptly disabled. Accordingly, some therapeutic effect can continue to be realized while respecting dosage constraints.

[0068] In an example, the system can be configured to monitor a dosage over time and use machine learning to optimize when and how to taper stimulation, for example, in a manner that is personalized to the patient's usage patterns or therapy demands. For example, tapering of the stimulation can follow a linear, step-wise, exponential, or other tapering trend or algorithm. As limits are approached, patients can be notified that one or more parameters will be automatically adjusted for safety and / or device longevity reasons unless changes are manually entered. Such automated, progressive titration can help maximize therapy availability within predefined boundaries.

[0069] In an example, the system can be configured to provide only an epilepsy therapy or a depression therapy at one time. In the event where a seizure event occurs during a depression therapy session, the system can prioritize the epilepsy therapy by pausing the depression therapy to administer the epilepsy therapy. After the epilepsy therapy concludes, the depression therapy can be reinstated, for example, after a pre-determined amount of time.

[0070] FIG. 5 illustrates generally an example of a second method 500 that can include determining whether a therapy dosage meets a specified lower limit or minimum therapy limit. In an example, automatically providing at least a baseline level of therapy can help ensure that therapeutic goals are met.

[0071] At operation 502, the second method 500 includes receiving therapy parameters that define one or more neurostimulation therapies provided by an implantable neurostimulation device. At decision operation 504, thesecond method 500 includes determining whether a therapy dosage is above a specified lower therapy limit. The therapy dosage can be based on, for example, the therapy or therapies defined by the therapy parameters. In an example, the determination at decision operation 504 can be performed by the processor circuit 118 of the implantable device 116, or can be performed by an external device or processor.

[0072] If, at decision operation 504, the therapy dosage based on the therapy parameters received at operation 502 exceeds the specified minimum or lower dosage limit, then the second method 500 can proceed to operation 508. At operation 508, the therapy or therapies can be provided to the patient based on the therapy parameters received at operation 502. For example, operation 508 can include providing epilepsy and / or depression therapies in accordance with respective epilepsy therapy parameters and depression therapy parameters. In an example, therapies can be provided in accordance with the same respective therapy parameters unless or until updated parameters are received, such as at operation 510.

[0073] If, at decision operation 504, a therapy dosage based on the therapy parameters received at operation 502 is less than the specified minimum or lower dosage limit, then the second method 500 can optionally proceed to operation 506. At operation 506, the second method 500 can include using the interface device 302 to provide a notification to a patient or clinician about the therapy dosage status. In an example, the notification can include a request or recommendation to change one or more of the therapy parameters. In an example, the system can be configured to suggest a particular parameter that can be changed to adjust the therapy dosage to within the specified limit. At operation 510, the second method 500 can include receiving updated therapy parameters, such as via the interface device 302. For example, operation 510 can include receiving updated or changed parameters for one or both of an epilepsy therapy or a depression therapy.

[0074] In some examples, the specified limit can be associated with a tolerance. For example, the therapy or therapies can be permitted to exceed the lower limit by a specified amount for a specified duration of time before the therapy is automatically updated to use one or more baseline parameters.

[0075] In an example, the control circuit can be configured to control the therapy parameters in response to a patient input and without regard for the therapy dosage and specified therapy limit. This patient input can comprise a magnetic signal received at the implantable neurostimulation device.

[0076] In an example, operation 510 can include automatically updating or adjusting a therapy parameter to a default value if a new therapy parameter value is not received from the patient or clinician, for example, within a specified amount of time after notifying the patient or clinician at operation 506. In an example, the notification can prompt the patient or clinician to change at least one of the epilepsy therapy parameter or depression therapy parameter. In an example, the neurostimulation system can use a closed-loop algorithm to automatically adjust stimulation therapy parameters in real-time to maintain overall therapy dosages at a specified lower therapy limit to thereby provide a baseline therapy.

[0077] In an example, the first method 400 and the second method 500 can be combined to provide monitoring and adjustment of therapy parameters to optimize treatment while preventing both over-stimulation and understimulation. The system can use a closed-loop algorithm to automatically adjust stimulation therapy parameters in real-time to keep overall therapy dosages within specified limits. As a calculated or actual therapy dosage approaches a defined maximum limit based on the specified parameters, one or more therapy parameters (e.g., stimulation intensity or duty cycle) can be progressively lowered by small increments. If the stimulation signal amplitude is increased, a cumulative dosage limit can be reached. In response, the stimulation signal amplitude can be gradually stepped down (e.g., in 0.1 mA increments) to a specified baseline rather than abruptly disabled. Accordingly, some therapeutic effect can continue to be realized while respecting dosage constraints.

[0078] The system can be configured to monitor for therapy delivery that falls below minimum therapy dosage limits or baselines. When a therapy dosage drops (i.e., a therapy-specific dosage, or a cumulative total therapy dosage) below a specified minimum therapy limit, the system can automatically increase the intensity of at least one therapy to maintaintherapeutic efficacy. For example, if depression therapy intensity has been reduced to accommodate increased epilepsy therapy during a seizure event, the system can gradually increase the depression therapy back to its minimum therapeutic level after the seizure event has passed.

[0079] In an example, the system can use machine learning to optimize when and how to taper stimulation in a manner that is personalized to the patient's usage patterns and therapy demands. The tapering of stimulation can follow linear, step-wise, exponential or other trends based on the optimization algorithm. As therapy limits are approached, patients can be notified through the interface device that parameters will be automatically adjusted unless manual changes are entered. This automated, progressive titration helps maximize therapy availability within predefined boundaries while maintaining therapeutic benefit for both conditions.

[0080] FIG. 6 illustrates generally an example of an external interface device 602 that is configured to display therapy parameters and is configured to receive information from a patient or clinician. The external interface device 602 can comprise an example of the external interface device 124.

[0081] In an example, the external interface device 602 includes a first interface area 616 with output or input information associated with a first therapy (e.g., an epilepsy therapy) and the external interface device 602 includes a second interface area 618 with output or input information associated with a different second therapy (e.g., a depression therapy). The external interface device 602 can thus provide information to, or receive information from, a patient or clinician about multiple therapies in an efficient, side-by-side manner that helps the user visually receive, compare and interpret the information about the multiple therapies. In some examples, the different interface areas can be visually distinct, such as using respective different colors or patterns to differentiate the displayed information.

[0082] In the example of FIG. 6, the external interface device 602 shows first therapy parameters 604, second therapy parameters 606, a first input 608 configured to adjust one or more of the first therapy parameters 604, a second input 610 configured to adjust one or more of the second therapy parameters 606, a first log 612 associated with the first therapy, and a secondlog 614 associated with the second therapy. The first log 612 and the second log 614 can be configured to receive patient-reported or clinician-reported information that is specific to the first and second therapies, respectively. In an example, the one or more first therapy parameters 604 and the one or more second therapy parameters 606 can be selected from pre-set therapy profiles that include pre-determined first therapy parameters 604 such as amplitude, frequency, pulse width, pulse morphology, duty cycle, therapy duration, or a combination thereof.

[0083] In an example, the external interface device 602 is configured to allow clinicians to set predefined limits on therapy parameters such as amplitude, frequency, pulse width, and on / off times, among others. Patients can then adjust parameters like amplitude within these constraints using simple controls. For example, the clinician may set the maximum amplitude limit to 3.5 mA for the first therapy (e.g., an epilepsy therapy). The patient can then adjust the therapy amplitude between 0.0 mA (e.g., off or no therapy) and 3.5 mA (e.g., maximum permitted therapy) using a dial (e.g., using the first input 608), while not exceeding safety and efficacy thresholds.

[0084] The external interface device 602 communicates wirelessly with the implanted neurostimulation device (e.g., the implantable device 116) so that current therapy settings can be read from the neurostimulation device and displayed using the external interface device 602. Any parameter adjustments entered via the interface can be wirelessly transmitted to the neurostimulation device for implementation. This allows patients and clinicians to easily view and modify therapy settings as needed.

[0085] In an example, the external interface device 602 is configured to display graphs and usage logs, such as can be used to illustrate the cumulative therapy dosage over time based on the selected parameters. Dosage limits can be displayed concurrently. The dosage history can help inform manual therapy adjustments to avoid exceeding defined limits. For instance, usage graphs can help a user select appropriate on / off times and stimulation intensities to maintain a cumulative dosage within specified limits.

[0086] The interface provides structured inputs like sliding scales and multiple choice buttons to tailor aspects of therapy delivery to patient needs, side effects, seizure control, depression control, or a combination thereof. For example, patients can complete electronic questionnaires about mood or side effects, log seizure occurrences, or provide therapy efficacy ratings to guide appropriate parameter adjustments, optionally using clinician review and recommendations.

[0087] In an example, the external interface device 602 is configured to receive therapy priority information. The therapy priority information can be used by the implantable device 116 to automatically determine which of multiple available therapies to prioritize when a therapy dosage limit is reached or is approached.

[0088] The external interface device 602 can automatically upload reports, usage data, physiological data, and activity logs from the neurostimulation device to provider systems. Analysis of this data further aids in optimizing therapy parameters for safety and efficacy on an ongoing basis. Alerts about unsafe dosage accumulation or patient or device status requiring clinician input can be requested or displayed automatically.

[0089] In an example, the external interface device 602 is configured to receive or display patient logs in the form of a first log 612 and second log 614. The first log 612 and second log 614 can include a information about usage of the neurostimulation system, a physiological parameter 312, a stimulation parameter, a selected epilepsy therapy profile, a selected depression therapy profile, an adjustment to an intensity and effectiveness metrics 314, an intensity index 324, an efficacy index 326, a note from a clinician, a note from a patient, or a combination thereof. The data for these logs can be collected continuously in real-time, gathered in periodic intervals, or recorded at pre-determined time intervals as specified by the clinician or device settings. The collection frequency and timing can be adjusted based on therapeutic needs and monitoring requirements.

[0090] In an example, the patient log can include recording information about a modification of an epilepsy therapy parameter. The information can include a time the modification to the epilepsy therapy parameter was made,a type of modification to the epilepsy therapy parameter, a value of modification to the epilepsy therapy parameter, information about a user who made the modification to the epilepsy therapy parameter, or a combination thereof.

[0091] The patient logs can include, among other things, system usage records including information about timing of therapy sessions, duration of therapy sessions, location of therapy, system errors, or malfunctions. The patient logs can include, for example, information about a type of therapy used (e.g., epilepsy therapy, depression therapy, or both), an epilepsy therapy parameter setting, a depression therapy parameter setting, an adjustment to the epilepsy therapy parameter setting, an adjustment to the depression therapy parameter setting, an intensity index, an efficacy index, a seizure event, a seizure severity, a titration or tapering profile used, or a preset therapy profile used. The patient logs can include clinical documentation, such as clinician notes and observations, patient feedback and reported symptoms, patient medical history, or patient medication history. The patient logs can include data analytics and trends, such as therapy response patterns, long-term efficacy tracking, or predictive analytics of future therapy treatment.

[0092] The patient logs can include an epilepsy log and a depression log. The epilepsy log can track the severity and frequency of seizure events. The depression log can track the severity and frequency of depression events at regular intervals (e.g., daily, weekly, or monthly), or when depression events occur.

[0093] FIG. 7 illustrates an example of a third method 700 for delivering epilepsy and depression neurostimulation therapies from an implantable device. Although the example of the third method 700 depicts a particular sequence of operations, the sequence may be altered without departing from the scope of the present disclosure. For example, some of the operations depicted may be performed in parallel or in a different sequence that does not materially affect the function or outcome of the third method 700. In other examples, different components of an example device or system thatimplements the third method 700 may perform functions at substantially the same time or in a specific sequence.

[0094] At operation 702, the third method 700 can include determining a total therapy dosage based on epilepsy therapy parameters and depression therapy parameters. The determination of the total therapy dosage can be performed at the implantable device 116 or at an external device, such as the external interface device 124 or elsewhere. In an example, operation 702 can be performed automatically, such as on an ongoing or substantially continuous basis, or can be performed intermittently or periodically (e.g., hourly, daily, etc.). In an example, operation 702 can be performed prior to delivery of an epilepsy therapy or depression therapy.

[0095] At operation 704, the third method 700 can include, in response to determining the total therapy dosage is within a specified therapy limit, controlling a signal generator circuit in the implantable device (e.g., the signal generator 120 in the implantable device 116) to provide epilepsy and depression therapy signals to therapy delivery electrodes according to the epilepsy and depression therapy parameters, respectively.

[0096] In an example, operation 704 can include providing first neurostimulation signals to a first portion of a vagus nerve using a first electrode pair based on the epilepsy therapy parameters, and providing second neurostimulation signals to a second portion of the vagus nerve using a second electrode pair based on the depression therapy parameters. In an example, one or more electrodes can be shared between the first and second electrode pairs.

[0097] At operation 706, the third method 700 can include, in response to determining the total therapy dosage exceeds the specified therapy limit, inhibiting the signal generator circuit from providing at least one of the epilepsy and depression therapy signals using the epilepsy and depression therapy parameters, respectively. The operation 706 can further include, in response to determining the total therapy dosage exceeds the specified therapy limit, changing at least one of the epilepsy and depression therapy parameters to reduce the total therapy dosage, and controlling the signalgenerator circuit to provide epilepsy and depression therapy signals using the changed therapy parameters.

[0098] In an example, the third method 700 can include using an external interface device to provide information about the epilepsy therapy parameters in visual correspondence with the depression therapy parameters. The third method 700 can further include using the external interface device to provide information about a longevity or expected battery life of the implantable device, wherein the longevity or expected battery life information is based on current or proposed epilepsy therapy parameters and the depression therapy parameters. In an example, the third method 700 can further include using the external interface device to receive respective patient logs for epilepsy-related events and depression-related events.

[0099] FIG. 8 illustrates an example of a fourth method 800 for delivering epilepsy and depression neurostimulation therapies from an implantable device. Although the example of the fourth method 800 depicts a particular sequence of operations, the sequence may be altered without departing from the scope of the present disclosure. For example, some of the operations depicted may be performed in parallel or in a different sequence that does not materially affect the function of the fourth method 800. In other examples, different components of an example device or system that implements the fourth method 800 may perform functions at substantially the same time or in a specific sequence.

[0100] At operation 802, the fourth method 800 can include providing a depression therapy signal to a patient using a signal generator circuit in the implantable device. For example, operation 802 can include using the signal generator 120 of the implantable device 116 to provide an ongoing depression therapy signal to a patient using one or more electrodes. In an example, providing the depression therapy at operation 802 can include providing the depression therapy with or without providing an epilepsy therapy.

[0101] At operation 804, the fourth method 800 can include detecting a seizure event. Detecting the seizure event at operation 804 can include detecting the seizure event automatically, such as using sensed physiologicalparameters of the patient, or can include receiving information about a manually reported seizure event.

[0102] At operation 806, the fourth method 800 can include providing an epilepsy therapy signal to the patient to address the detected seizure event. In an example, operation 806 can include using the same implantable device that was used to provide the depression therapy signal at operation 802. In an example, one or more conditions can be imposed by the implantable device before responding to the detected seizure event. For example, a severity of the detected seizure event can be determined and used to determine when or whether to provide the epilepsy therapy signal to the patient. In another example, when or whether to respond to the seizure event can be based on a total therapy dosage already received by the patient.

[0103] For example, at operation 808, the fourth method 800 can include determining a total therapy dosage provided to the patient by the implantable device. In an example, the total therapy dosage provided can be based on depression therapy parameters of the depression therapy signal and further based on therapy parameters of one or more other therapies received by or provided to the patient, such as an epilepsy therapy. In some examples, the one or more other therapies can be provided by the same implantable device or by another device.

[0104] At operation 810, the fourth method 800 can include determining if a specified total therapy dosage limit for a patient is exceeded by the total therapy dosage determined at operation 806. In response to determining the total therapy dosage exceeds the specified therapy limit, the operation 808 can include inhibiting the signal generator circuit from providing a further therapy (e.g., the depression therapy signal). In an example, the particular therapy to inhibit can be based on information about a therapy priority received from a patient or clinician. Alternatively to inhibiting the further therapy, the further therapy can be provided at a relatively lower intensity, such as to allow some therapeutic effect to be realized while minimizing overexposure of the patient to therapy signals.

[0105] FIG. 9 illustrates generally an example of a fifth method 900 for delivering epilepsy and depression neurostimulation therapies from animplantable device, such as the implantable device 116. Although the example of the fifth method 900 depicts a particular sequence of operations, the sequence may be altered without departing from the scope of the present disclosure. For example, some of the operations depicted may be performed in parallel or in a different sequence that does not materially affect the function of the fifth method 900. In other examples, different components of an example device or system that implements the fifth method 900 may perform functions at substantially the same time or in a specific sequence.

[0106] At operation 902, the fifth method 900 can include providing an epilepsy therapy signal and a depression therapy signal. The therapy signals can be provided concurrently, in an overlapping manner, or can be provided separately, such as at different respective times or according to different therapy delivery schedules.

[0107] At operation 904, the fifth method 900 can include displaying, on a display device, a user interface including information about an epilepsy therapy parameter of the epilepsy therapy signal and a depression therapy parameter of the depression therapy signal. In an example, operation 904 includes using the external interface device 124 to display the user interface.

[0108] At operation 906, the fifth method 900 can include receiving, using the user interface, a user input indicating a modification to the epilepsy therapy parameter or the depression therapy parameter. The implantable device 116 can optionally implement the therapy parameter change automatically or, in some examples, can provide information about a likely effect of the parameter change. The information about the likely effect can include, for example, information about a change in device battery life, information about an expected change in therapy intensity, or information about an expected change in therapy effectiveness, among other information.

[0109] At operation 908, the fifth method 900 can include recording information about the parameter modification in a patient log or clinician log. The recorded information can include information about, for example, a time the modification was made, a type of the modification, a value of the modification, a user who made the modification, or a combination thereof.

[0110] In an example, operation 908 includes displaying information about the parameter modification in visual correspondence with a therapy effectiveness metric. For example, substantially in real-time with the parameter change, the user interface can be configured to display for the patient or clinician an actual or expected change in the therapy effectiveness in response to the parameter change. The effectiveness information can be useful to the patient or clinician to see an actual or prospective effect of the parameter change, to help balance device longevity, patient comfort, and therapeutic benefit.

[0111] In an example, the implantable device 116 or an external device can be configured to optimize a patient experience by periodically testing the effect of one or more therapy parameter changes, and then suggesting to the patient or clinician one or more therapy parameter changes that are predicted to lead to better outcomes or improved device longevity. In an example, the external interface device is configured to display a predicted future therapy effectiveness and a recommendation for a change in at least one of an epilepsy therapy parameter and a depression therapy parameter to achieve the predicted future therapy effectiveness.

[0112] FIG. 10 illustrates generally an example of a machine in the form of a computer system within which a set of instructions may be executed for causing the machine to perform any one or more of the methodologies discussed herein, according to an example embodiment. FIG. 10 is a diagrammatic representation of a machine 1000 within which instructions 1008 (e.g., software, a program, an application, an applet, an app, or other executable code) for causing the machine 1000 to perform any one or more of the methodologies discussed herein may be executed. In various examples, the machine 1000 is a representative example of the implantable device 116 or one or more of the external devices (e.g., user interface devices) discussed herein.

[0113] In an example, the instructions 1008 may cause the machine 1000 to execute any one or more of the methods, controls, therapy algorithms, signal generation routines, or other processes described herein. The instructions1008 transform the general, non-programmed machine 1000 into a particularmachine 1000 programmed to carry out the described and illustrated functions in the manner described. The machine 1000 may operate as a standalone device or may be coupled (e.g., networked) to other machines. In a networked deployment, the machine 1000 may operate in the capacity of a server machine or a client machine in a server-client network environment, or as a peer machine in a peer-to-peer (or distributed) network environment. The machine 1000 can comprise, but is not limited to, various systems or devices that can communicate with the implantable device 116 or one or more of the external devices discussed herein, and can include a server computer, a client computer, a personal computer (PC), a tablet computer, a laptop computer, a netbook, a set-top box (STB), a PDA, an entertainment media system, a cellular telephone, a smart phone, a mobile device, a wearable device (e.g., a smart watch), a smart home device (e.g., a smart appliance), other smart devices, a web appliance, a network router, a network switch, a network bridge, or any machine capable of executing the instructions 1008, sequentially or otherwise, that specify actions to be taken by the machine 1000. Further, while only a single machine 1000 is illustrated, the term “machine” shall also be taken to include a collection of machines that individually or jointly execute the instructions 1008 to perform any one or more of the methodologies discussed herein.

[0114] The machine 1000 may include processors 1002, memory 1004, and I / O components 1042, which may be configured to communicate with each other via a bus 1044. In an example embodiment, the processors 1002 (e.g., a Central Processing Unit (CPU), a Reduced Instruction Set Computing (RISC) processor, a Complex Instruction Set Computing (CISC) processor, a Graphics Processing Unit (GPU), a Digital Signal Processor (DSP), an ASIC, a Radio-Frequency Integrated Circuit (RFIC), another processor, or any suitable combination thereof) may include, for example, a processor 1006 and a processor 1010 that execute the instructions 1008. The term “processor” is intended to optionally include multi-core processors that may comprise two or more independent processors (sometimes referred to as “cores”) that may execute instructions contemporaneously. Although FIG. 10 shows multiple processors 1002, the machine 1000 may include a singleprocessor with a single core, a single processor with multiple cores (e.g., a multi-core processor), multiple processors with a single core, multiple processors with multiples cores, or any combination thereof.

[0115] The memory 1004 includes a main memory 1012, a static memory 1014, and a storage unit 1016, both accessible to the processors 1002 via the bus 1044. The main memory 1004, the static memory 1014, and storage unit 1016 store the instructions 1008 embodying any one or more of the methodologies or functions described herein. The instructions 1008 may also reside, completely or partially, within the main memory 1012, within the static memory 1014, within a machine-readable medium 1018 within the storage unit 1016, within at least one of the processors 1002 (e.g., within the processor’s cache memory), or any suitable combination thereof, during execution thereof by the machine 1000.

[0116] The I / O components 1042 may include a variety of components to receive input, provide output, produce output, transmit information, exchange information, capture measurements, and so on. The specific I / O components 1042 that are included in a particular machine will depend on the type of machine. For example, portable machines such as device programmers or mobile phones may include a touch input device or other such input mechanisms, while a headless server machine will likely not include such a touch input device. It will be appreciated that the I / O components 1042 may include other components that are not shown in FIG. 10. In various example embodiments, the I / O components 1042 may include output components 1028 and input components 1030. The output components 1028 may include pictorial, graphical, or visual components (e.g., a display such as a plasma display panel (PDP), a light emitting diode (LED) display, a liquid crystal display (LCD), a projector, or a cathode ray tube (CRT)) such as can be used to provide an interface device (e.g., the external interface device 124) or other interfaces that can be configured to display therapy parameter, intensity or effectiveness metrics, among other information. The output components 1028 can include acoustic components (e.g., speakers), haptic components (e.g., a vibratory motor, resistance mechanisms), other signal generators, and so forth. The input components1030 may include alphanumeric input components (e.g., a keyboard, a touch screen configured to receive alphanumeric input, a photo-optical keyboard, or other alphanumeric input components), point-based input components (e.g., a mouse, a touchpad, a trackball, a joystick, a motion sensor, or another pointing instrument), tactile input components (e.g., a physical button, a touch screen that provides location and / or force of touches or touch gestures, or other tactile input components), audio input components (e.g., a microphone), physiological sensor components, and the like.

[0117] In further example embodiments, the I / O components 1042 may include biometric components 1032, motion components 1034, environmental components 1036, or position components 1038, among others. For example, the biometric components 1032 can include components to detect expressions (e.g., hand expressions, facial expressions, vocal expressions, body gestures, or eye tracking), measure biosignals (e.g., blood pressure, heart rate, body temperature, perspiration, or brain waves), identify a person (e.g., voice identification, retinal identification, facial identification, fingerprint identification, or electroencephalogram-based identification), and the like. The motion components 1034 can include an acceleration sensor (e.g., an accelerometer), gravitation sensor components, rotation sensor components (e.g., a gyroscope), or similar. The environmental components 1036 can include, for example, illumination sensor components (e.g., photometer), temperature sensor components (e.g., one or more thermometers that detect ambient temperature), humidity sensor components, pressure sensor components (e.g., barometer), acoustic sensor components (e.g., one or more microphones that detect background noise), proximity sensor components (e.g., infrared sensors that detect nearby objects), gas sensors (e.g., gas detection sensors to detection concentrations of hazardous gases for safety or to measure pollutants in the atmosphere), or other components that may provide indications, measurements, or signals corresponding to a surrounding physical environment, such as may contribute to the onset of seizures. The position components 1038 can include location sensor components (e.g., a GPS receiver component), altitude sensor components (e.g., altimeters or barometers that detect airpressure from which altitude may be derived), orientation sensor components (e.g., magnetometers), and the like.

[0118] Communication may be implemented using a wide variety of technologies. The I / O components 1042 further include communication components 1040 operable to couple the machine 1000 to a network 1020 or other devices 1022 via a coupling 1024 and a coupling 1026, respectively. For example, the communication components 1040 may include a network interface component or another suitable device to interface with the network 1020. In further examples, the communication components 1040 may include wired communication components, wireless communication components, cellular communication components, Near Field Communication (NFC) components, Bluetooth components, or Wi-Fi components, among others. The devices 1022 may be another machine or any of a wide variety of peripheral devices such as can include other implantable or external devices.

[0119] The various memories (e.g., memory 1004, main memory 1012, static memory 1014, and / or memory of the processors 1002) and / or storage unit 1016 can store one or more sets of instructions and data structures (e.g., software) embodying or used by any one or more of the methodologies or functions described herein. These instructions (e.g., the instructions 1008), when executed by processors 1002, cause various operations to implement the disclosed embodiments, including various neuromodulation or neurostimulation therapies or functions supportive thereof.

[0120] The following Examples provide a non-limiting overview of, among other things, the therapy coordination, therapy parameter visualization, and therapy optimization techniques discussed herein.

[0121] Example 1 is a system comprising: an implantable neurostimulation device configured to deliver an epilepsy therapy and a depression therapy to a patient, the implantable neurostimulation device comprising: a first electrode pair configured to provide the epilepsy therapy to a first portion of a vagus nerve; a second electrode pair configured to provide the depression therapy to a second portion of the vagus nerve; a neurostimulation signal generator circuit configured to provide first neurostimulation signals for theepilepsy therapy based on epilepsy therapy parameters, and configured to provide second neurostimulation signals for the depression therapy based on depression therapy parameters; and a control circuit configured to control the neurostimulation signal generator circuit to provide the epilepsy and depression therapies, wherein: when a total therapy dosage is less than a specified maximum therapy limit, the control circuit controls the signal generator circuit to provide the epilepsy and depression therapies according to the epilepsy and depression therapy parameters, respectively, wherein the total therapy dosage is based on the epilepsy therapy parameters and the depression therapy parameters; and when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit inhibits the signal generator circuit from providing at least one of the epilepsy and depression therapies.

[0122] In Example 2, the subject matter of Example 1 optionally includes the control circuit is configured to: determine the total therapy dosage is below a specified minimum therapy limit; and in response to determining the total therapy dosage is below the specified minimum therapy limit, automatically increase an intensity of at least one of the epilepsy therapy or the depression therapy to achieve a specified minimum therapy dosage.

[0123] In Example 3, the subject matter of any one or more of Examples 1-2 optionally includes the first electrode pair comprises a first electrode and a separate second electrode, and the second electrode pair comprises the first electrode and the separate second electrode.

[0124] In Example 4, the subject matter of any one or more of Examples 1-3 optionally includes the first electrode pair comprises a first electrode and a separate second electrode, and the second electrode pair comprises the first electrode and a separate third electrode.

[0125] In Example 5, the subject matter of any one or more of Examples 1-4 optionally includes the first and second electrode pairs comprise electrodes coupled to a first implantable lead, and one or more of the electrodes is configured to be disposed at or around a portion of a vagus nerve of a patient.

[0126] In Example 6, the subject matter of any one or more of Examples 1-5 optionally includes the total therapy dosage is based on one or more of a therapy intensity, an average therapy intensity, or an integrated area under a curve of a therapy intensity curve, for one or more therapies provided to the patient.

[0127] In Example 7, the subject matter of any one or more of Examples 1-6 optionally includes when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit is configured to control the signal generator circuit to prioritize a specified one of the epilepsy and depression therapies.

[0128] In Example 8, the subject matter of Example 7 optionally includes the control circuit is configured to receive a therapy priority indication, and the control circuit is configured to prioritize the therapies based on the therapy priority indication.

[0129] In Example 9, the subject matter of any one or more of Examples 1- 8 optionally includes when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit is configured to change at least one of the epilepsy therapy parameters and the depression therapy parameters to thereby reduce the total therapy dosage.

[0130] In Example 10, the subject matter of any one or more of Examples 1-9 optionally includes when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit is configured to taper an intensity of the first neurostimulation signals or the second neurostimulation signals.

[0131] In Example 11, the subject matter of any one or more of Examples 1-10 optionally includes each of the epilepsy therapy parameters and the depression therapy parameters comprise respective parameters defining a neurostimulation signal magnitude, frequency, pulse width, pulse morphology, duty cycle, and therapy duration.

[0132] In Example 12, the subject matter of any one or more of Examples 1-11 optionally includes when the total therapy dosage is less than the specified maximum therapy limit, the control circuit is configured to update the epilepsy therapy parameters, the depression therapy parameters, or boththe epilepsy therapy parameters and the depression therapy parameters, based on a therapy control input.

[0133] In Example 13, the subject matter of Example 12 optionally includes the control circuit is configured to receive the therapy control input from a patient or clinician, and the therapy control input indicates a relative patient need for the epilepsy therapy or the depression therapy.

[0134] In Example 14, the subject matter of any one or more of Examples 12-13 optionally includes the control circuit is configured to receive the therapy control input from a physiological sensor, and the physiological sensor indicates a patient response to the epilepsy therapy or the depression therapy.

[0135] In Example 15, the subject matter of any one or more of Examples 1-14 optionally includes the depression therapy has a lower intensity than the epilepsy therapy, and the intensity of a therapy is based on a magnitude or duration of the neurostimulation signals that comprise the therapy.

[0136] In Example 16, the subject matter of any one or more of Examples 1-15 optionally includes the control circuit is configured to control the neurostimulation signal generator circuit to provide the epilepsy therapy in response to a patient input and without regard for the therapy dosage and specified maximum therapy limit.

[0137] In Example 17, the subject matter of Example 16 optionally includes the patient input comprises a magnetic signal received at the implantable neurostimulation device.

[0138] In Example 18, the subject matter of any one or more of Examples 1-17 optionally includes the control circuit is configured to control the neurostimulation signal generator circuit to provide one or more of the epilepsy therapy and the depression therapy in response to respective patient inputs, wherein the patient inputs comprise respective magnetic signals received at the implantable neurostimulation device.

[0139] In Example 19, the subject matter of any one or more of Examples 1-18 includes a physiological status sensor configured to sense physiological status information about the patient, and the control circuit isconfigured to control the neurostimulation signal generator circuit to provide the epilepsy and depression therapies in response to information from the physiological status sensor about a physiological status of the patient.

[0140] In Example 20, the subject matter of Example 19 optionally includes the physiological status sensor includes one of an electrocardiogram sensor, a heart rate sensor, a blood pressure sensor, a respiratory rate sensor, a blood oxygen saturation sensor, a sleep sensor, a blood glucose sensor, or an accelerometer.

[0141] In Example 21, the subject matter of any one or more of Examples 1-20 optionally includes the control circuit is configured to control the neurostimulation signal generator circuit to provide the epilepsy and depression therapies concurrently.

[0142] In Example 22, the subject matter of any one or more of Examples 1-21 includes an external interface device configured to communicate with the implantable neurostimulation device, wherein the external interface device comprises a user interface that is configured to receive information about the epilepsy therapy parameters and the depression therapy parameters.

[0143] In Example 23, the subject matter of Example 22 optionally includes the external interface device is configured to display a physiological parameter about the patient, a stimulation parameter, a stimulation intensity index, and a stimulation efficacy index.

[0144] In Example 24, the subject matter of any one or more of Examples 22-23 optionally includes the external interface device is configured to display a predicted future therapy effectiveness and a recommendation for a change in at least one of the epilepsy therapy parameter and the depression therapy parameter to achieve the predicted future therapy effectiveness.

[0145] In Example 25, the subject matter of any one or more of Examples 22-24 includes the external interface device is configured to display seizure event information.

[0146] In Example 26, the subject matter of any one or more of Examples 22-25 optionally includes when the total therapy dosage exceeds thespecified maximum therapy limit, the external interface device is configured to prompt a patient or clinician to change at least one of the epilepsy therapy parameters or depression therapy parameters.

[0147] In Example 27, the subject matter of any one or more of Examples 22-26 optionally includes the external interface device comprises a display configured to provide, to a user, side-by-side controls for the epilepsy therapy parameters and the depression therapy parameters.

[0148] In Example 28, the subject matter of any one or more of Examples 22-27 optionally includes the external interface device is configured to receive respective patient logs for epilepsy-related events and depression- related events.

[0149] In Example 29, the subject matter of Example 28 optionally includes the patient logs include one or more of a record of usage of the neurostimulation system, a physiological parameter, a stimulation parameter, a selected epilepsy therapy profile, a selected depression therapy profile, an adjustment to a stimulation parameter, an intensity index, an efficacy index, a note from a clinician, or a note from a patient.

[0150] Example 30 is a method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device, the method comprising: determining a total therapy dosage based on epilepsy therapy parameters and depression therapy parameters; in response to determining the total therapy dosage is less than a specified maximum therapy limit, controlling a signal generator circuit in the implantable device to provide epilepsy and depression therapy signals to therapy delivery electrodes according to the epilepsy and depression therapy parameters, respectively; and in response to determining the total therapy dosage exceeds the specified maximum therapy limit, inhibiting the signal generator circuit from providing at least one of the epilepsy and depression therapy signals using the epilepsy and depression therapy parameters, respectively.

[0151] In Example 31, the subject matter of Example 30 optionally includes controlling the signal generator circuit to provide the epilepsy and depression therapy signal includes providing first neurostimulation signals to a first portion of a vagus nerve using a first electrode pair based on theepilepsy therapy parameters, and providing second neurostimulation signals to a second portion of the vagus nerve using a second electrode pair based on the depression therapy parameters.

[0152] In Example 32, the subject matter of Example 31 optionally includes providing the first neurostimulation signals using the first electrode pair includes using first and second electrodes, and providing the second neurostimulation signals to the second electrode pair includes using the first electrode and a third electrode.

[0153] In Example 33, the subject matter of any one or more of Examples 30-32 includes, in response to determining the total therapy dosage exceeds the specified maximum therapy limit, changing at least one of the epilepsy and depression therapy parameters to reduce the total therapy dosage, and controlling the signal generator circuit to provide epilepsy and depression therapy signals using the changed therapy parameters.

[0154] In Example 34, the subject matter of any one or more of Examples 30-33 includes using an external interface device, providing information about the epilepsy therapy parameters in visual correspondence with the depression therapy parameters.

[0155] In Example 35, the subject matter of Example 34 includes using the external interface device to provide information about a longevity or expected battery life of the implantable device, wherein the longevity or expected battery life information is based on the epilepsy therapy parameters and the depression therapy parameters.

[0156] In Example 36, the subject matter of any one or more of Examples 34-35 includes using the external interface device to receive respective patient logs for epilepsy-related events and depression-related events.

[0157] Example 37 is a method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device, the method comprising: providing a depression therapy signal to a patient using a signal generator circuit in the implantable device; detecting a seizure event; determining a total therapy dosage provided to the patient based on epilepsy therapy parameters of an epilepsy therapy signal and depressiontherapy parameters of the depression therapy signal; in response to determining the total therapy dosage exceeds a specified maximum therapy limit, inhibiting the signal generator circuit from providing the depression therapy signal; and providing the epilepsy therapy signal to the patient using the signal generator circuit.

[0158] In Example 38, the subject matter of Example 37 includes receiving physiological status information about the patient from an implantable sensor, and detecting the seizure event includes using the received physiological status information from the sensor.

[0159] In Example 39, the subject matter of Example 38 optionally includes detecting the seizure event using a machine learning-based model to analyze physiological status information from the sensor.

[0160] In Example 40, the subject matter of any one or more of Examples 37-39 optionally includes detecting the seizure event by receiving a seizure event indication from the patient.

[0161] In Example 41, the subject matter of any one or more of Examples 37-40 optionally includes determining the total therapy dosage by calculating an integrated area under a curve of a therapy intensity versus time graph, and the therapy intensity is based on one or more of: neurostimulation signal magnitude, frequency, pulse width, duty cycle, or therapy duration.

[0162] In Example 42, the subject matter of any one or more of Examples 37-41 includes receiving a therapy priority indication indicating the epilepsy therapy is prioritized over the depression therapy; and prioritizing delivery of the epilepsy therapy signal over the depression therapy signal based on the therapy priority indication when the total therapy dosage exceeds the specified maximum therapy limit.

[0163] In Example 43, the subject matter of any one or more of Examples 37-42 optionally includes inhibiting the signal generator circuit from providing the depression therapy signal includes providing a lower-intensity depression therapy signal in coordination with the epilepsy therapy signal.

[0164] Example 44 is a method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device, the method comprising: providing an epilepsy therapy signal and a depression therapy signal; displaying, on a display device, a user interface including information about an epilepsy therapy parameter of the epilepsy therapy signal and a depression therapy parameter of the depression therapy signal; receiving, using the user interface, a user input indicating a modification to the epilepsy therapy parameter or the depression therapy parameter; and recording information about the modification in a patient log.

[0165] In Example 45, the subject matter of Example 44 optionally includes the information about the modification includes one or more of a time the modification was made, a type of the modification, a value of the modification, a user who made the modification, or a combination thereof.

[0166] In Example 46, the subject matter of any one or more of Examples 44-45 optionally includes displaying the user interface includes displaying information about a therapy effectiveness metric in visual correspondence with the epilepsy therapy parameter or depression therapy parameter.

[0167] In Example 47, the subject matter of any one or more of Examples 44-46 optionally includes the user interface comprises side-by-side controls for the epilepsy therapy parameters and the depression therapy parameters.

[0168] In Example 48, the subject matter of any one or more of Examples 44-47 optionally includes displaying the user interface includes displaying a predicted future therapy effectiveness and a recommendation for a change in at least one of the epilepsy therapy parameter and the depression therapy parameter to achieve the predicted future therapy effectiveness.

[0169] Example 49 is a system for coordinated neurostimulation therapy, the system comprising: an implantable neurostimulation device configured to deliver epilepsy and depression therapies to a vagus nerve of a patient; a physiological status sensor configured to sense physiological status information about the patient; an external interface device configured to display therapy parameters and receive user inputs; and a control circuit configured to: determine a seizure event based on the sensed physiological status information; in response to the determined seizure event, temporarilysuspend an ongoing depression therapy and initiate an epilepsy therapy; monitor a total therapy dosage based on parameters of both the epilepsy and depression therapies; and automatically adjust therapy parameters to maintain the total therapy dosage within a specified therapy limit while prioritizing the epilepsy therapy during detected seizure events.

[0170] In Example 50, the subject matter of Example 49 optionally includes the control circuit is configured to: detect a rising trend in a seizure event-indicating signal based on the sensed physiological status information; automatically increase an intensity of the epilepsy therapy in response to the detected rising trend; and display the increased intensity in visual correspondence with the seizure event-indicating signal on the external interface device.

[0171] In Example 51, the subject matter of any one or more of Examples 49-50 optionally includes the control circuit is configured to: execute a multiple-therapy optimization algorithm that modulates stimulation intensity for the epilepsy therapy while holding the depression therapy at a constant reduced intensity; and titrate the total therapy dosage below the specified therapy limit while maintaining therapeutic benefit for both epilepsy and depression conditions.

[0172] Example 52 is at least one machine-readable medium including instructions that, when executed by processing circuitry, cause the processing circuitry to perform operations to implement of any of Examples 1-51.

[0173] Example 53 is an apparatus comprising means to implement of any of Examples 1-51.

[0174] Example 54 is a system to implement of any of Examples 30-48.

[0175] Each of these non-limiting examples or embodiments can stand on its own or can be combined in various permutations or combinations with one or more of the other examples or embodiments discussed herein.

[0176] This detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can bepracticed. These embodiments are also referred to herein as“examples.” Such examples can include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. The present inventors contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0177] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.”

[0178] In the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

[0179] Method examples described herein can be machine or computer- implemented at least in part. Some examples can include a computer- readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods can include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code can include computer readable instructions for performing various methods. The code may form portions of computer program products. Such instructions can be read and executed by one or more processors to enable performance of operations comprising a method,for example. The instructions are in any suitable form, such as but not limited to source code, compiled code, interpreted code, executable code, static code, dynamic code, and the like.

[0180] Further, in an example, the code can be tangibly stored on one or more volatile, non-transitory, or non-volatile tangible computer-readable media, such as during execution or at other times. Examples of these tangible computer-readable media can include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like.

[0181] The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment.

Claims

CLAIMSWhat is claimed is:

1. A system comprising: an implantable neurostimulation device configured to deliver an epilepsy therapy and a depression therapy to a patient, the implantable neurostimulation device comprising: a first electrode pair configured to provide the epilepsy therapy to a first portion of a vagus nerve; a second electrode pair configured to provide the depression therapy to a second portion of the vagus nerve; a neurostimulation signal generator circuit configured to provide first neurostimulation signals for the epilepsy therapy based on epilepsy therapy parameters, and configured to provide second neurostimulation signals for the depression therapy based on depression therapy parameters; and a control circuit configured to control the neurostimulation signal generator circuit to provide the epilepsy and depression therapies, wherein: when a total therapy dosage is less than a specified maximum therapy limit, the control circuit controls the signal generator circuit to provide the epilepsy and depression therapies according to the epilepsy and depression therapy parameters, respectively, wherein the total therapy dosage is based on the epilepsy therapy parameters and the depression therapy parameters; and when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit inhibits the signal generator circuit from providing at least one of the epilepsy and depression therapies.

2. The system of claim 1, wherein the control circuit is configured to: determine the total therapy dosage is below a specified minimum therapy limit; and in response to determining the total therapy dosage is below the specified minimum therapy limit, automatically increase an intensity of at least one of the epilepsy therapy or the depression therapy to achieve a specified minimum therapy dosage.

3. The system of claim 1, wherein the first electrode pair comprises a first electrode and a separate second electrode, and wherein the second electrode pair comprises the first electrode and the separate second electrode.

4. The system of claim 1, wherein the first electrode pair comprises a first electrode and a separate second electrode, and wherein the second electrode pair comprises the first electrode and a separate third electrode.

5. The system of claim 1, wherein the first and second electrode pairs comprise electrodes coupled to a first implantable lead, and wherein one or more of the electrodes is configured to be disposed at or around a portion of a vagus nerve of a patient.

6. The system of claim 1, wherein the total therapy dosage is based on one or more of a therapy intensity, an average therapy intensity, or an integrated area under a curve of a therapy intensity curve, for one or more therapies provided to the patient.

7. The system of claim 1, wherein when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit is configured to control the signal generator circuit to prioritize a specified one of the epilepsy and depression therapies.

8. The system of claim 7, wherein the control circuit is configured to receive a therapy priority indication, and wherein the control circuit is configured to prioritize the therapies based on the therapy priority indication.

9. The system of claim 1, wherein when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit is configured to change at least one of the epilepsy therapy parameters and the depression therapy parameters to thereby reduce the total therapy dosage.

10. The system of claim 1, wherein when the total therapy dosage exceeds the specified maximum therapy limit, the control circuit is configured to taper an intensity of the first neurostimulation signals or the second neurostimulation signals.

11. The system of claim 1, wherein each of the epilepsy therapy parameters and the depression therapy parameters comprise respective parameters defining a neurostimulation signal magnitude, frequency, pulse width, pulse morphology, duty cycle, and therapy duration.

12. The system of claim 1, wherein when the total therapy dosage is less than the specified maximum therapy limit, the control circuit is configured to update the epilepsy therapy parameters, the depression therapy parameters, or both the epilepsy therapy parameters and the depression therapy parameters, based on a therapy control input.

13. The system of claim 12, wherein the control circuit is configured to receive the therapy control input from a patient or clinician, and wherein the therapy control input indicates a relative patient need for the epilepsy therapy or the depression therapy.

14. The system of claim 12, wherein the control circuit is configured to receive the therapy control input from a physiological sensor, and wherein the physiological sensor indicates a patient response to the epilepsy therapy or the depression therapy.

15. The system of claim 1, wherein the depression therapy has a lower intensity than the epilepsy therapy, and wherein the intensity of a therapy is based on a magnitude or duration of the neurostimulation signals that comprise the therapy.

16. The system of claim 1, wherein the control circuit is configured to control the neurostimulation signal generator circuit to provide the epilepsy therapy in response to a patient input and without regard for the therapy dosage and specified maximum therapy limit.

17. The system of claim 16, wherein the patient input comprises a magnetic signal received at the implantable neurostimulation device.

18. The system of claim 1, wherein the control circuit is configured to control the neurostimulation signal generator circuit to provide one or more of the epilepsy therapy and the depression therapy in response to respective patient inputs, wherein the patient inputs comprise respective magnetic signals received at the implantable neurostimulation device.

19. The system of claim 1, comprising a physiological status sensor configured to sense physiological status information about the patient, and wherein the control circuit is configured to control the neurostimulation signal generator circuit to provide the epilepsy and depression therapies in response to information from the physiological status sensor about a physiological status of the patient.

20. The system of claim 19, wherein the physiological status sensor includes one of an electrocardiogram sensor, a heart rate sensor, a blood pressure sensor, a respiratory rate sensor, a blood oxygen saturation sensor, a sleep sensor, a blood glucose sensor, or an accelerometer.

21. The system of claim 1, wherein the control circuit is configured to control the neurostimulation signal generator circuit to provide the epilepsy and depression therapies concurrently.

22. The system of claim 1, comprising an external interface device configured to communicate with the implantable neurostimulation device, wherein the external interface device comprises a user interface that is configured to receive information about the epilepsy therapy parameters and the depression therapy parameters.

23. The system of claim 22, wherein the external interface device is configured to display a physiological parameter about the patient, a stimulation parameter, a stimulation intensity index, and a stimulation efficacy index.

24. The system of claim 22, wherein the external interface device is configured to display a predicted future therapy effectiveness and a recommendation for a change in at least one of the epilepsy therapy parameter and the depression therapy parameter to achieve the predicted future therapy effectiveness.

25. The system of claim 22, wherein the external interface device is configured to display seizure event information.

26. The system of claim 22, wherein when the total therapy dosage exceeds the specified maximum therapy limit, the external interface device is configured to prompt a patient or clinician to change at least one of the epilepsy therapy parameters or depression therapy parameters.

27. The system of claim 22, wherein the external interface device comprises a display configured to provide, to a user, side-by-side controls for the epilepsy therapy parameters and the depression therapy parameters.

28. The system of claim 22, wherein the external interface device is configured to receive respective patient logs for epilepsy-related events and depression-related events.

29. The system of claim 28, wherein the patient logs include one or more of a record of usage of the neurostimulation system, a physiological parameter, a stimulation parameter, a selected epilepsy therapy profile, a selected depression therapy profile, an adjustment to a stimulation parameter, an intensity index, an efficacy index, a note from a clinician, or a note from a patient.

30. A method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device, the method comprising: determining a total therapy dosage based on epilepsy therapy parameters and depression therapy parameters; in response to determining the total therapy dosage is less than a specified maximum therapy limit, controlling a signal generator circuit in theimplantable device to provide epilepsy and depression therapy signals to therapy delivery electrodes according to the epilepsy and depression therapy parameters, respectively; and in response to determining the total therapy dosage exceeds the specified maximum therapy limit, inhibiting the signal generator circuit from providing at least one of the epilepsy and depression therapy signals using the epilepsy and depression therapy parameters, respectively.

31. The method of claim 30, wherein controlling the signal generator circuit to provide the epilepsy and depression therapy signal includes providing first neurostimulation signals to a first portion of a vagus nerve using a first electrode pair based on the epilepsy therapy parameters, and providing second neurostimulation signals to a second portion of the vagus nerve using a second electrode pair based on the depression therapy parameters.

32. The method of claim 31, wherein providing the first neurostimulation signals using the first electrode pair includes using first and second electrodes, and providing the second neurostimulation signals to the second electrode pair includes using the first electrode and a third electrode.

33. The method of claim 30, comprising: in response to determining the total therapy dosage exceeds the specified maximum therapy limit, changing at least one of the epilepsy and depression therapy parameters to reduce the total therapy dosage, and controlling the signal generator circuit to provide epilepsy and depression therapy signals using the changed therapy parameters.

34. The method of claim 30, comprising: using an external interface device, providing information about the epilepsy therapy parameters in visual correspondence with the depression therapy parameters.

35. The method of claim 34, comprising using the external interface device to provide information about a longevity or expected battery life of the implantable device, wherein the longevity or expected battery life information is based on the epilepsy therapy parameters and the depression therapy parameters.

36. The method of claim 34, comprising using the external interface device to receive respective patient logs for epilepsy-related events and depression- related events.

37. A method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device, the method comprising: providing a depression therapy signal to a patient using a signal generator circuit in the implantable device; detecting a seizure event; determining a total therapy dosage provided to the patient based on epilepsy therapy parameters of an epilepsy therapy signal and depression therapy parameters of the depression therapy signal; in response to determining the total therapy dosage exceeds a specified maximum therapy limit, inhibiting the signal generator circuit from providing the depression therapy signal; and providing the epilepsy therapy signal to the patient using the signal generator circuit.

38. The method of claim 37, comprising receiving physiological status information about the patient from an implantable sensor, and wherein detecting the seizure event includes using the received physiological status information from the sensor.

39. The method of claim 38, wherein detecting the seizure event comprises using a machine learning-based model to analyze physiological status information from the sensor.

40. The method of claim 37, wherein detecting the seizure event includes receiving a seizure event indication from the patient.

41. The method of claim 37, wherein determining the total therapy dosage comprises calculating an integrated area under a curve of a therapy intensity versus time graph, and wherein the therapy intensity is based on one or more of: neurostimulation signal magnitude, frequency, pulse width, duty cycle, or therapy duration.

42. The method of claim 37, further comprising: receiving a therapy priority indication indicating the epilepsy therapy is prioritized over the depression therapy; and prioritizing delivery of the epilepsy therapy signal over the depression therapy signal based on the therapy priority indication when the total therapy dosage exceeds the specified maximum therapy limit.

43. The method of claim 37, wherein inhibiting the signal generator circuit from providing the depression therapy signal includes providing a lower- intensity depression therapy signal in coordination with the epilepsy therapy signal.

44. A method for coordinating delivery of epilepsy and depression neurostimulation therapies from an implantable device, the method comprising: providing an epilepsy therapy signal and a depression therapy signal; displaying, on a display device, a user interface including information about an epilepsy therapy parameter of the epilepsy therapy signal and a depression therapy parameter of the depression therapy signal; receiving, using the user interface, a user input indicating a modification to the epilepsy therapy parameter or the depression therapy parameter; and recording information about the modification in a patient log.

45. The method of claim 44, wherein the information about the modification includes one or more of a time the modification was made, a type of the modification, a value of the modification, a user who made the modification, or a combination thereof.

46. The method of claim 44, wherein displaying the user interface includes displaying information about a therapy effectiveness metric in visual correspondence with the epilepsy therapy parameter or depression therapy parameter.

47. The method of claim 44, wherein the user interface comprises side-by- side controls for the epilepsy therapy parameters and the depression therapy parameters.

48. The method of claim 44, wherein displaying the user interface includes displaying a predicted future therapy effectiveness and a recommendation for a change in at least one of the epilepsy therapy parameter and the depression therapy parameter to achieve the predicted future therapy effectiveness.

49. A system for coordinated neurostimulation therapy, the system comprising: an implantable neurostimulation device configured to deliver epilepsy and depression therapies to a vagus nerve of a patient; a physiological status sensor configured to sense physiological status information about the patient; an external interface device configured to display therapy parameters and receive user inputs; and a control circuit configured to: determine a seizure event based on the sensed physiological status information; in response to the determined seizure event, temporarily suspend an ongoing depression therapy and initiate an epilepsymonitor a total therapy dosage based on parameters of both the epilepsy and depression therapies; and automatically adjust therapy parameters to maintain the total therapy dosage within a specified therapy limit while prioritizing the epilepsy therapy during detected seizure events.

50. The system of claim 49, wherein the control circuit is configured to: detect a rising trend in a seizure event-indicating signal based on the sensed physiological status information; automatically increase an intensity of the epilepsy therapy in response to the detected rising trend; and display the increased intensity in visual correspondence with the seizure event-indicating signal on the external interface device.

51. The system of claim 49, wherein the control circuit is configured to: execute a multiple-therapy optimization algorithm that modulates stimulation intensity for the epilepsy therapy while holding the depression therapy at a constant reduced intensity; and titrate the total therapy dosage below the specified therapy limit while maintaining therapeutic benefit for both epilepsy and depression conditions.

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