Time-dependent adaptive neuromodulation system

Abstract

A neuromodulation system disclosed herein provides adaptive stimulation such as time-dependent adaptive stimulation, personalized therapy, and improves battery management while maintaining desired therapeutic effect. Mixed urinary incontinence and other conditions are treated using electrical stimulation, according to several implementations.

Description

TIME-DEPENDENT ADAPTIVE NEUROMODULATION SYSTEMINCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 710,245, filed October 22, 2024, and U.S. Provisional Application No. 63 / 771,855, filed March 14, 2025, the entire disclosures of which are hereby incorporated by reference in their entirety.BACKGROUNDField

[0002] The present disclosure generally relates to systems and methods for providing neuromodulation to treat mixed urinary incontinence and other disorders. For example, adaptive and / or customized stimulation is provided, including electrical neurostimulation that is configurable to personalized needs and unique patient signatures, thereby capable of providing improved therapeutic effect and patient comfort.Description of the Related Art

[0003] Electrodes may be implanted in a pelvic region of a patient to provide electrical stimulation as clinical treatment and / or condition management. For example, a neuromodulation device, which may include an implantable pulse generator (IPG) coupled with an electrode lead, can electrically stimulate the sacral nerve, which may improve neural communication between the brain and the bladder or the bowel. Once the neuromodulation device is implanted, a physician may program the device to stimulate the pelvic nerve.SUMMARY

[0004] Several embodiments described herein advantageously provide neurostimulation configurable to an individual's specific needs and / or based on the individual's circadian rhythm. Several embodiments described herein advantageously provide neurostimulation based on a combination of different sensor inputs to improve therapy while prolonging battery life.

[0005] Incontinence, including a lack of control over micturition or bowel movements, has many causes but may involve injury or weakness of the pelvic floor muscles and the nerves that innervate these muscles and involved organs. Several embodiments described herein provide systems and methods for providing time-dependent adaptive neurostimulation to treat various conditions, such as urinary incontinence, fecal incontinence, pain, sexual dysfunction, or any combination thereof medical condition and / or diseases within the pelvic region. In some embodiments, the pelvic condition includes urinary incontinence, fecal incontinence, pain, sexual dysfunction, or any combination thereof. Although several embodiments are described herein with respect to the pelvic region to treat and / or manage pelvic conditions, they may also be used in other regions of the body or to treat other conditions as described elsewhere herein. With respect to urinary incontinence, several embodiments are particularly beneficial because they address more than one type of incontinence. For example, both urge and stress incontinence can be treated with several of the systems described herein. Many patients have mixed urinary incontinence (MUI), which involves features of both stress and urge incontinence. The combination of an automated background level and one or more patient-activated higher levels benefits a UUI patient, an SUI patient, and / or a MUI patient, according to several embodiments.

[0006] In several embodiments, severe refractory urge incontinence is treated. For example, the technology described herein may be particularly useful for patients (e.g., patients with urge incontinence) who do not respond to other types of therapy, including for example, botulinum toxin therapy and sacral neuromodulation.

[0007] In several embodiments, the neuromodulation systems described herein, and uses thereof, have at least one or more of the following features or advantages:• provide time-dependent configurability of stimulation programs depending on the patient's circadian rhythm and other rhythms;• provide adaptive stimulation with flexible sensor input selections and / or combinations of sensor inputs; • use personalized breakthrough signature detection and / or tiered levels of stimulation; and• implement additional safety and / or comfort features such as timing interlock, disable function, and / or fallback modes.

[0008] The neuromodulation system disclosed herein may include time-dependent configurations. Sleep and circadian rhythm may be relevant to neuromodulation therapy. In some instances, patient needs, biomarkers, and symptoms can show predictable diurnal patterns. For example, urinary or fecal incontinence can demonstrate time-dependent symptoms, such as, but not limited to, higher rate of incidence during daytime versus nighttime for an individual with a diurnal rhythm. The kidneys and bladder may allow more storage of urine at nighttime. The bowel activity may also have a circadian rhythm with increased propulsive activity occurring on waking and ambulation. The different stimulation programs disclosed herein may include one pattern designed with daytime activity in mind and another pattern designed with the nighttime needs in mind. In some embodiments, a user (for example, a clinician) may create and assign different stimulation programs to different times of the day, days of the week and / or month. Different parameters can be used based on time-dependency, which can include but are not limited to physiological rhythms. Non-limiting examples of physiological rhythms can include circadian, ultradian, and / or infradian rhythms. In some embodiments, different parameters can be used depending on the time of the day and / or the patient's circadian rhythm. In some embodiments, one or more stimulation programs may include diurnal stimulation parameters. In some instances, the stimulation programs for daytime may include background stimulation at a higher level than background stimulation for nighttime. At night, the sphincter closing effect and / or the inhibition function of the stimulation may be less needed. In some embodiments, the stimulation program at night can provide more regenerative function at night and / or reduce likelihood of fatigue. The system disclosed herein can allow multiple stimulation programs to be saved to the implantable pulse generator. For example, the system disclosed herein may allow for up to 8 different stimulation programs, although embodiments are not so limited. Each stimulation program may have different electrode configurations and / or stimulation patterns. Within each stimulation program, the stimulation parameters, including, but not limited to, amplitude, frequency, and / or pulse width, can be adjusted.

[0009] In some implementations, the circadian-based programming can be optimized for patients who are more nocturnal (due to habit and / or scheduling needs). For example, the timing of the daytime stimulation programs and the night stimulation programs may be shifted according to a more nocturnal individual's schedule. The parameters and / or settings of the stimulation programs may include nocturnal parameters.

[0010] In addition to daily (circadian / diurnal) activities, in some embodiments, the time-dependency configurations may include other physiological rhythms. Non-limiting examples of physiological rhythms include ultradian or faster than daily (sub-day, e.g., after each meal or other fluctuations in daytime that may depend onvariables like sleep pressure, feeding, and / or exercise) rhythms, and / or infradian or slower than daily (e.g., menstrual cycles, cycles spanning multiple days, weeks, and / or months) rhythms.

[0011] The neuromodulation system disclosed herein may include time-dependent nerve stimulation (for example, pudendal nerve stimulation) in response to or being adaptive to one or more stimuli (which may also be referred to as "adaptive” stimulation in the present disclosure). The processor of the implantable pulse generator, upon determining a breakthrough signature, can provide one or more higher levels of stimulation than immediately prior to the breakthrough signature. The breakthrough signature may include detection of a change in motion and / or posture detected by a motion or posture sensor (for example, a three-axis accelerometer), a change in biopotential measured by a bioelectrical sensor, a user notification, a use location change, ambulation detection of the user, or any combinations thereof. Each of the different types of sensor input may be saved as an adaptive sensing profile. Any or all of the sensors disclosed herein may provide more than one adaptive sensing profile. Embodiments disclosed herein may use the appropriate sensor input or combination of sensor inputs based on the time of the day to provide higher stimulation level when it is most needed. In some instances, peak incontinence rates may occur in the morning. One reason may be that the bladder activity and / or the bowel activity may be more suppressed at night, and may be stimulated by waking, moving, and / or eating. Upon standing up, gravity may also influence risk of more urinary and / or fecal incontinence. Embodiments disclosed herein may activate a posture sensor and / or a bioelectrical sensor in the morning. The bioelectrical sensor may be more accurate than a motion or posture sensor in predicting the need for higher level stimulation. Embodiments disclosed herein may also activate only the posture sensor at night. Limiting the use of the bioelectrical sensor to daytime and / or when there is higher incidence of incontinence may ensure accuracy in adaptive stimulation, and at the same time prolong battery life.

[0012] In some implementations, the posture determination from the posture sensor may be used to differentiate different muscle contractions measured by the bioelectrical sensor. In some implementations, the posture determination from the posture sensor may be used to overwrite a triggering to a different stimulation level based on data from the bioelectrical sensor.

[0013] Several embodiments disclosed herein may advantageously provide a patient-specific or personalized sensor threshold. The threshold may involve readings of the respective sensor may result in an interrupt command being sent to the IPG processor to trigger the higher level stimulation (e.g., greater frequency, greater pulse width, etc.). The readings, when exceeding the threshold, may be indicative of a breakthrough signature from the patient. In some embodiments, the patient-specific threshold may be calibrated and / or determined with data collected from the patient, such as by asking the individual implanted with the implantable pulse generator to perform various breakthrough signature activities. In some implementations, the breakthrough signature may include a tap or double tap on the location of the implantable pulse generator, the individual getting out of bed to use the bathroom at night, or the individual squeezing the pelvic floor or other parts of the body due to an event that would likely cause a leak (e.g., heavy coughing, laughing, heavy movement, etc.) or due the patient getting an urge that a leak is about to occur, a posture change of the patient, and / or a combination of any of the above (that is, combining input from more than one sensor to detect a breakthrough signature). Detecting when the sensor reading exceeds a threshold may allow the disturbances (e.g., imminent incontinence events) to be provided via feedforward pathways to the processor of the implantable pulse generator. In some instances, the patient-specific threshold may be a geographical location (suchas the front door of the patient's home), with the breakthrough signature being the patient arriving at the front door of the patient's home as measured by a GPS signal. The patient-specific threshold rather than "one size fit all” threshold for all patients may improve accuracy in the detection to start the more enhanced stimulation current (e.g., higher intensity) and / or reduce false positives.

[0014] Some embodiments disclosed herein may advantageously provide a patient-specific or personalized stimulation program or level based on the personalized sensor threshold. The stimulation program may include two, or more than two (e.g., 3, 4, 5, 6 or more) stimulation levels in response to different strengths in the sensor input and / or the different types of sensor input, including but not limited to the patient's level of activity, sensitivity, etc. In some embodiments, the stimulation levels are tiered. For example, a first parameter of a sensor may trigger a first stimulation level different from a background stimulation level; a second parameter of the sensor and / or a parameter of a different sensor may trigger a second stimulation level different from the background stimulation level and the first stimulation level, and so on. In other embodiments, the stimulation levels include increases in stimulation parameters on a continuum. For example, the system disclosed herein may use an equation, matrix, or any mathematical model to generate a stimulation level different from a ground stimulation level based on one or more sensor parameters. As a result, the stimulation level may vary along a sliding scale.

[0015] In several embodiments, the system disclosed herein may include a time interlock after detection of each trigger to prevent or reduce over-triggering and / or false positives (e.g., due to stim artifacts), and / or improve patient comfort. In some instances, the patient may override the interlock. In other instances, the patient may not override the interlock. In some implementations, the stimulation programs may include a disable function to turn off stimulation (e.g., by ramping down or in a step function). In some instances, the stimulation programs may include a fallback mode, which may provide a lower frequency background stimulation that may be more comfortable and / or less disruptive for the individual. In some embodiments, when the fallback mode is activated, the higher levels of stimulation cannot be triggered until the patient switches off the fallback mode or switches back to full function (including the background stimulation and the triggered higher levels of stimulation). The fallback mode may improve patient comfort when the stimulation level provided to the patient is causing adverse effects, including but not limited to discomfort. The fallback mode may additionally or alternatively improve patient experience when the patient is engaging in activities such as driving, business meeting, or any activity that requires focus, as a sudden increase in the stimulation level may distract or disrupt the patient's performance. In some cases, the fallback mode provides a compromise between full functions (including the background stimulation and the triggered higher levels of stimulation) and no electrical stimulation so that the patient still receives a certain amount of stimulation to help reduce incontinence events without having to be distracted by the sudden trigger of higher levels of stimulation. The disable and / or fallback mode may be activated via a patient controller and / or a trigger from the patient (e.g., double tap or the like).

[0016] In several embodiments, the system disclosed herein may monitor the patient and / or usage data over days, weeks, months, and / or years. The patient and / or usage data may be aggregated. For example, data aggregation may occur at a centralized location that is remote to the individual using the system. The aggregated longterm data may further improve personalized therapy for the individual. In some instances, the data transfer may occur during charging of the implantable pulse generator. In some cases, frequency of re-visits to the clinician for data collection and / or reconfiguration of the stimulation programs may be reduced.

[0017] In several embodiments, artificial intelligence and / or machine learning are used. For example, one or more classifiers for detecting a breakthrough signature may include machine learning models. These models may be trained with sensor data collected from the patient when the patient is performing various triggering activities to improve accuracy in detecting the breakthrough signature.

[0018] Disclosed herein, as well as in PCT Application No. PCT / EP2025 / 080505 titled "ADAPTIVE NEUROMODULATION SYSTEM,” filed on the same day as the present application, which is hereby incorporated by reference in its entirety, are embodiments of devices, systems and methods for neurostimulation. For example, through patient engagement, feedback, neural retraining, or tissue strengthening, or combinations thereof, an incontinence episode or other clinical conditions can be treated or otherwise ameliorated through prevention of one or more actual episode. As another example, the systems and methods disclosed herein may provide stimulation using bilateral leads and / or stimulation based on artificial intelligence ("Al”) trained classifiers, which, alone or combined, improves accuracies in the stimulation generated to provide more personalized treatment. In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application No. PCT / EP2025 / 080505 can be used with any one or more of the time-dependent programming, adaptive stimulation with flexible sensor input(s) selections for determining breakthrough signatures, personalized thresholds, additional patient safety and / or comfort features, or combinations thereof disclosed herein.

[0019] In some embodiments, a system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition (including but not limited to incontinence, pain, etc.) is provided. The system may include an implantable pulse generator comprising an actuator and a processor. The processor may be configured to control the actuator to generate an electrical stimulation of at least first, second, and third levels. The system may further include one or more electrode leads(e.g., two four, six, eight, or other numbers) in electrical communication with the processor. The one or more electrode leads can include at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient (e.g., pudendal nerve). The processor can be configured to: generate a background level of electrical stimulation, wherein the background level can be the first level or the second level based on time-dependency (e.g., a time of a day, a month, etc.), determine a breakthrough signature, and in response to determination of the breakthrough signature, generate the third level of electrical stimulation. The third level can be higher than the second level and the second level can be higher than the first level.

[0020] In several embodiments, the system disclosed herein are configured to such that the first background level can be run at nighttime and the second background level can be run at daytime. In some embodiments, the breakthrough signature can be configured to be activated based on a time of the day. In some embodiments, the breakthrough signature can be configured to be activated based on the patient's physiological rhythm (e.g., circadian rhythm, ultradian rhythm, infradian rhythm, etc.).

[0021] In several embodiments, the system disclosed herein are configured to such that the breakthrough signature can be determined by artificial intelligence and / or machine learning.

[0022] In several embodiments, the system disclosed herein are configured to such that delivering the third level of electrical stimulation in response to determination of the breakthrough signature can be configured to reduce or prevent habituation.

[0023] In several embodiments, the system disclosed herein are configured to such that the breakthrough signature can include a tap on the location of the implantable pulse generator. The implantable pulse generator may include a motion / posture sensor (e.g., an accelerometer, a gyroscope, or an inertial measurement unit (I MU)) configured to detect the tap (or a sequence of tap) on the implantable pulse generator. The tap can be detected in response to a reading of the motion / posture sensor exceeding a personalized sensor threshold. The personalized sensor threshold can include patient-specific tap sensitivity. In some embodiments, the breakthrough signature can further include a postural change in response to a reading of the motion / posture sensor exceeding a personalized sensor threshold.

[0024] In several embodiments, the system disclosed herein are configured to such that the breakthrough signature can further include a muscle (e.g., pelvic muscles, gluteal muscle, leg muscles, etc.) contraction in response to a reading of a bioelectrical sensor exceeding a personalized sensor threshold, the bioelectrical sensor located on the one or more electrode leads.

[0025] In several embodiments, the system disclosed herein are configured to such that the personalized sensor threshold can be determined based at least in part on patient-specific data using artificial intelligence or machine learning.

[0026] In several embodiments, the system disclosed herein are configured to such that determination of a different breakthrough signature can be configured to trigger a fourth level (and / or more levels) of electrical stimulation different from the first, second, and third levels.

[0027] In several embodiments, the system disclosed herein are configured to such that the stimulation can work synergistically with and / or reduce one or more side effects of a pharmaceutical therapy.

[0028] In some embodiments, a system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition (including but not limited to incontinence, pain, etc.) is provided. The system may include an implantable pulse generator comprising at least one processor. The at least one processor may be configured to control the actuator to generate an electrical stimulation of at least first, second, and third levels. The system may further include one or more electrode leads (e.g., two four, six, eight, or other numbers) in electrical communication with the processor. The one or more electrode leads can include at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient (e.g., pudendal nerve). The processor can be configured to: generate the first level or the second level based on timedependency (e.g., a time of a day, a month, etc.), determine a breakthrough signature, and in response to determination of the breakthrough signature, generate the third level of electrical stimulation. The third level can be different than the first level and the second level of stimulation.

[0029] In several embodiments, the system disclosed herein are configured to such that the breakthrough signature can be determined in response to a personalized sensor threshold being met. The personalized sensor threshold can be determined based at least in part on patient-specific data associated with thebreakthrough signature collected from the patient. In some embodiments, the breakthrough signature can be determined by artificial intelligence and / or machine learning.

[0030] In several embodiments, the system disclosed herein are configured to such that the first background level can be run at nighttime and the second background level can be run at daytime. In some embodiments, the breakthrough signature can be configured to be activated based on a time of the day. In some embodiments, the breakthrough signature can be configured to be activated based on the patient's physiological rhythm (e.g., circadian rhythm, ultradian rhythm, infradian rhythm, etc.).

[0031] In several embodiments, the system disclosed herein are configured to such that delivering the third level of electrical stimulation in response to determination of the breakthrough signature can be configured to reduce or prevent habituation.

[0032] In several embodiments, the system disclosed herein are configured to such that the breakthrough signature can include a tap on the implantable pulse generator be detected in response to a reading of a motion / posture sensor (e.g., an accelerometer, a gyroscope, or an inertial measurement unit (IMU)) exceeding a personalized sensor threshold. The motion sensor can be located on the implantable pulse generator. The personalized sensor threshold can include patient-specific tap sensitivity. In some embodiments, the breakthrough signature can further include a postural change in response to a reading of the motion / posture sensor exceeding a personalized sensor threshold.

[0033] In several embodiments, the system disclosed herein are configured to such that the breakthrough signature can further include a muscle (e.g., pelvic muscles, gluteal muscle, leg muscles, etc.) contraction in response to a reading of a bioelectrical sensor exceeding a personalized sensor threshold, the bioelectrical sensor located on the one or more electrode leads.

[0034] In several embodiments, the system disclosed herein are configured to such that the personalized sensor threshold can be determined based on incontinence triggering events specific to the patient.

[0035] In several embodiments, the system disclosed herein are configured to such that determination of a different breakthrough signature can be configured to trigger a fourth level (and / or more levels) of electrical stimulation different from the first, second, and third levels.

[0036] In several embodiments, the system disclosed herein are configured to such that the stimulation can work synergistically with a pharmaceutical therapy. In several embodiments, the system disclosed herein are configured to such that the stimulation can reduce one or more side effects of a pharmaceutical therapy.

[0037] In several embodiments, the system disclosed herein are configured to such that the personalized neuromodulation can be configured to preemptively stop an incontinence event. The personalized neuromodulation can be configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event. In some embodiments, the personalized neuromodulation is configured to preemptively stop a fecal incontinence event. In some embodiments, the personalized neuromodulation is configured to train pain.

[0038] In some embodiments, a method for delivering personalized neuromodulation using breakthrough signatures (such as to treat a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The method may include determining a first, second, third, (and optionally more) breakthrough signatures of a patient. The first breakthrough signature may include a postural or motion change of the patient. The secondbreakthrough signature may include a muscle contraction of the patient. The third breakthrough signature may include patient notification. The method may further include providing at least three levels of stimulation. A first level may be a first background level. A second level may be a second background level. At least a third level may be triggered by at least one of the first, second, or third (or other(s)) breakthrough signatures. The at least third level may be higher than the second level and the second level may be higher than the first level. The method may further include outputting stimulation at the first or second background level (for example, based on a time of a day, user setting, etc.) unless the third level is triggered.

[0039] In some embodiments, a neuromodulation system configured to deliver personalized neuromodulation using breakthrough signatures (such as to treat a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The system may include an implantable pulse generator including a processor. The processor may be configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of at least first, second, and third levels. The system may further include one or more electrode leads in electrical communication with the processor. The one or more electrode leads may include at least one stimulation electrode configured to deliver the electrical stimulation (e.g., to a target nerve or tissue adjacent to the target nerve of a patient). The system (e.g., the processor) may be further configured to determine a first, second, and / or third (or other(s)) breakthrough signature of a patient. The system (e.g., the processor) may be further configured to output stimulation at the first or second background level (for example, based on a time of day, user setting, etc.) unless the third level is triggered. The first breakthrough signature may include a postural or motion change of the patient. The second breakthrough signature may include a muscle contraction of the patient. The third breakthrough signature may include patient notification. The system (e.g., the processor) may be further configured to provide the three (or more) levels of stimulation. A first level may be a first background level. A second level may be a second background level. At least a third level may be triggered by at least one of the (e.g., first, second, or third, or more) breakthrough signatures. The third level may be higher than the second level and the second level may be higher than the first level.

[0040] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured to run the first background level at nighttime and run the second background level at daytime.

[0041] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured such that the postural or motion change may be determined by a posture or motion sensor located on the implantable pulse generator or a global positioning system (GPS) sensor. In some embodiments, the muscle contraction may be determined by a bioelectrical sensor. The bioelectrical sensor may be located on the electrode lead(s) implanted in the patient's body. In some embodiments, the patient notification may include a tap on the implantable pulse generator or an input on an external device (e.g., via a remote controller). The tap may be detected by a motion sensor (e.g., accelerometer, gyroscope, inertial measurement unit (IMU), etc.), e.g., located on the implantable pulse generator, or by a pressure sensor.

[0042] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured such that the three (or more) levels of stimulation may be configured to preemptively stop an incontinence event, such as a urinary incontinence event or a fecal incontinence event. The three (or more) levels of stimulation may be configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event.The three (or more) levels of stimulation may be delivered to a pudendal nerve or tissue near the pudendal nerve of the patient, and / or a sacral nerve or tissue near the sacral nerve of the patient.

[0043] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured to use a machine learning classifier model to determine the first, second, and / or third breakthrough signatures. In some embodiments, the system (e.g., processor) or method disclosed herein may be configured to determine the first, second, and / or third breakthrough signatures in response to, for example, a sensor reading exceeding (or falling below) a predetermined threshold. The third level of stimulation triggered by the first breakthrough signature may include different parameters from the third level of stimulation triggered by the second or third breakthrough signature. In some embodiments, the third level may be configured to be triggered by the first breakthrough signature, for example, in a time of the day when the patient is sleeping, and / or configured to be triggered by the second breakthrough signature, for example, in a time of the day when the patient is awake, or vice versa.

[0044] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured such that the at least third level includes at least two triggered stimulation levels different from the first background level and the second background level. The at least two triggered stimulation levels may be tiered based at least in part on strength and / or type of sensor input. The at least two triggered stimulation levels may vary along a sliding scale based at least in part on strength and / or type of sensor input.

[0045] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured to further include a fallback mode in which a stimulation level lower than the first and second background levels is provided and the at least third level is deactivated. The fallback mode may be patient activated.

[0046] In some embodiments, a system configured to deliver personalized neuromodulation (such as to treat a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The system may include a memory device configured to store instructions and a hardware processor. The hardware processor may be configured to execute the instructions to output a graphical user interface including a programs element, a breakthrough signature settings element, and a program assignment element. The programs element may include a library of stimulation programs (e.g., user-configured programs). The program assignment element may include a plurality of time windows. The hardware processor may be further configured to create user-configured stimulation instructions. The instructions may be created by the hardware processor receiving a first user input (e.g., on a graphical user interface or otherwise) to assign a first background program of the library of stimulation programs to a first time window of the program assignment element. The instructions may be created by the hardware processor further receiving a second user input (e.g., on a graphical user interface or otherwise) to assign a second background program of the library of stimulation programs to a second time window of the program assignment element. The instructions may be created by the hardware processor further receiving a third user input (e.g., on a graphical user interface or otherwise) to assign a first breakthrough signature to the first time window, and receiving a fourth user input (e.g., on a graphical user interface or otherwise) to assign a second breakthrough signature to the second time window. The hardware processor may be further configured to transmit the user-configured stimulation instructions to an implantable pulse generator implanted in a patient's body, e.g., upon establishing connection with the implantable pulse generator. As such, in the first time window, the implantable pulse generator may be configured to implement the first background program until a third program from the library of stimulation programs is triggered by determination of the first breakthrough signature. Andas such, in the second time window, the implantable pulse generator may be configured to implement the second background program until the third program is triggered by determination of the second breakthrough signature. The second background program may include a higher stimulation level than the first background program, and the third program may include a higher stimulation level than the second background program.

[0047] In some embodiments, a method for delivering personalized neuromodulation (such as to treat a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The method may include outputting a graphical user interface including a programs element, a breakthrough signature settings element, and a program assignment element. The programs element may include a library of stimulation programs (e.g., user-configured programs). The program assignment element may include a plurality of time windows. The method may further include creating user-configured stimulation instructions, which may be by the steps of receiving first, second, third and fourth user inputs. The first user input (e.g., via a graphical user interface or otherwise) may assign a first background program of the library of stimulation programs to a first time window of the program assignment element. The second user input (e.g., via a graphical user interface or otherwise) to assign a second background program of the library of stimulation programs to a second time window of the program assignment element. The third user input (e.g., via a graphical user interface or otherwise) may assign a first breakthrough signature to the first time window. The fourth user input (e.g., via a graphical user interface or otherwise) may assign a second breakthrough signature to the second time window. The method may further include transmitting the user-configured stimulation instructions to an implantable pulse generator implanted in a patient's body, e.g., upon establishing connection with the implantable pulse generator. As such, in the first time window, the implantable pulse generator may be configured to implement the first background program until a third program from the library of stimulation programs is triggered by determination of the first breakthrough signature. And as such, in the second time window, the implantable pulse generator may be configured to implement the second background program until the third program is triggered by determination of the second breakthrough signature. The second background program may include a higher stimulation level than the first background program, and the third program may include a higher stimulation level than the second background program.

[0048] In some embodiments, the implantable pulse generator may be configured to determine the first breakthrough signature based in part on input from a motion or posture sensor or another sensor (e.g., pressure sensor), which may be located on the implantable pulse generator. In some embodiments, the implantable pulse generator or method disclosed herein may be configured to determine the second breakthrough signature is determined based in part on input from a bioelectrical sensor, e.g., located on one or more electrode leads configured to be implanted in the patient's body.

[0049] In some embodiments, the system or method disclosed herein may be configured such that creating the stimulation instructions may further include the processor receiving a fifth user input (e.g., on the graphical user interface or otherwise) to assign a third breakthrough signature to the second time window.

[0050] In some embodiments, in the second time window, the implantable pulse generator may be configured to implement the second background program until the third program is triggered by the second breakthrough signature or the third breakthrough signature (or another breakthrough signature).

[0051] In some embodiments, the implantable pulse generator may determine the third breakthrough signature based in part on input from the motion or posture sensor or another sensor. The first breakthrough signature may be a postural change, and the third breakthrough signature may be a patient notification causing a motion detected by the motion or posture sensor or another sensor. Alternatively, the implantable pulse generator may determine the third breakthrough signature based in part on input from the patient via a remote controller.

[0052] In some embodiments, the system or method disclosed herein may be configured such that the first or second time window may be a 30-minute window or of a different duration, or variable durations. The program assignment element may include a plurality of time windows, which optionally may total a 24-hour period or any other time period. The program assignment element may be (for example, automatically) adjusted for change in time or time zone.

[0053] In some embodiments, the system or method disclosed herein may be configured such that the library of stimulation programs include, but are not limited to, any combination of: a daytime program, a sleep program, an evening program, a wakeup program or a fallback program. The library of stimulation programs may include the fallback program, and when the fallback program is activated by the patient, a stimulation level lower than the first and second background programs may be provided and the third program may be deactivated.

[0054] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured such that the third program includes at least two triggered stimulation levels different from the first background level and the second background level. The at least two triggered stimulation levels may be tiered based at least in part on strength and / or type of sensor input. The at least two triggered stimulation levels may vary along a sliding scale based at least in part on strength and / or type of sensor input.

[0055] In some embodiments, a system configured to deliver personalized neuromodulation using breakthrough signatures to treat a medical condition (e.g., a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The system may include an implantable pulse generator including a processor. The system may include an implantable pulse generator including a processor. The processor may be configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of at least first, second, and third (or more) levels. The system may further include one or more electrode leads in electrical communication with the processor. The one or more electrode leads may include at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient. The system (e.g., the processor) may be configured to deliver a background level of electrical stimulation, which may be the first level or the second level (e.g., based on a time of a day and / or other user settings). The system (e.g., the processor) may be further configured to determine a breakthrough signature by assessing a personalized sensor threshold of the patient. In response to determination of the breakthrough signature, the system (e.g., the processor) may deliver the third level of electrical stimulation. The third level may be higher than the second level and the second level may be higher than the first level. The personalized sensor threshold may be determined based at least in part on patient-specific data associated with the breakthrough signature (which may be, for example, collected from the patient).

[0056] In some embodiments, a method for delivering personalized neuromodulation using breakthrough signatures to treat a medical condition (e.g., a pelvic condition including but not limited to incontinence,pain, etc.) is provided. The method may include providing electrical stimulation of at last first, second, and third (or more) levels. The method may further include delivering a background level of electrical stimulation. The background level may be the first level or the second level (e.g., based on a time of day and / or other user settings). The method may further include determining a breakthrough signature by assessing a personalized sensor threshold of the patient. In response to determination of the breakthrough signature, the method may further include delivering the third level of electrical stimulation. The third level may be higher than the second level and the second level may be higher than the first level. The personalized sensor threshold may be determined based at least in part on patient-specific data associated with the breakthrough signature (which may be, for example, collected from the patient).

[0057] In some embodiments, the system or method disclosed herein may be configured such that the three (or more) levels of stimulation may be configured to preemptively stop an incontinence event, such as a urinary incontinence event or a fecal incontinence event. The three (or more) levels of stimulation may be configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event. The three (or more) levels of stimulation may be delivered to a pudendal nerve or tissue near the pudendal nerve of the patient, and / or a sacral nerve or tissue near the sacral nerve of the patient.

[0058] In some embodiments, the system or method disclosed herein may be configured such that the breakthrough signature may include a postural change in response to a reading of a posture sensor exceeding the personalized sensor threshold. The posture sensor may be located on the implantable pulse generator or elsewhere (e.g., on the electrode lead).

[0059] In some embodiments, the system or method disclosed herein may be configured such that the breakthrough signature may include a muscle contraction in response to a reading of a bioelectrical sensor exceeding the personalized sensor threshold. In one embodiment, the bioelectrical sensor is located on the one or more electrode leads.

[0060] In some embodiments, the system or method disclosed herein may be configured such that the breakthrough signature may include patient notification. The patient notification may include a tap on the implantable pulse generator detected in response to a reading of a motion sensor (or another sensor such as a pressure sensor) exceeding the personalized sensor threshold. In one embodiment, the motion sensor (or another sensor) may be located on the implantable pulse generator or elsewhere (e.g., on the electrode lead). In some embodiments, the personalized threshold may include patient-specific tap sensitivity.

[0061] In some embodiments, the system or method disclosed herein may be configured such that the breakthrough signature that is activated in the system may vary based on a time of the day and / or other user settings.

[0062] In some embodiments, the system or method disclosed herein may be configured such that the personalized sensor threshold may be determined based at least in part on the patient-specific data using a machine learning model. In some embodiments, the personalized sensor threshold may be further determined based on incontinence triggering events specific to the patient. In some embodiments, the personalized sensor threshold may be further configured to be updated based on an updated physical condition of the patient.

[0063] In some embodiments, the system or method disclosed herein may be configured such that the personalized sensor threshold may be configured to be updated via a software program by a user. The software program may be configured to be run on a device in communication directly or indirectly with the system, e.g., with theprocessor of the implantable pulse generator. The software program may be further configured such that the user can assign the breakthrough signature to a time window of the day.

[0064] In some embodiments, the system (e.g., processor) or method disclosed herein may be configured such that determination of a different breakthrough signature is configured to trigger a fourth level of electrical stimulation or at least a fourth level of electrical stimulation different from the first, second, and third levels.

[0065] In some embodiments, a system configured to deliver personalized neuromodulation using breakthrough signatures (e.g., to treat a medical condition such as a pelvic condition (including but not limited to incontinence, pain, etc.) is provided. The system may include an implantable pulse generator including a processor. The system may include an implantable pulse generator including a processor. The processor may be configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of different levels. The system may further include one or more electrode leads in electrical communication with the processor. The one or more electrode leads may include at least one (or more) stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient. The system (e.g., the processor) may be configured to be triggered from a background level of electrical stimulation to a higher level of electrical stimulation (e.g., for a first duration) in response to determining a first instance of a breakthrough signature. The system (e.g., the processor), such as after the first duration, may be configured to resume the background level for at least a second duration. The system (e.g., the processor) may be configured to ignore determination of a second instance of the breakthrough signature in the second duration.

[0066] In some embodiments, a method for delivering personalized neuromodulation using breakthrough signatures (e.g., to treat a medical condition such as a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The method may include outputting a background level of electrical stimulation and determining a first instance of a breakthrough signature. In response to determining the first instance, the method may further include triggering from the background level of electrical stimulation to a higher level of electrical stimulation (e.g., for a first duration). Upon resuming the background level of electrical stimulation (e.g., after the first duration), the method may further include ignoring determination of a second instance of the breakthrough signature in the second duration.

[0067] In some embodiments, the system or method disclosed herein may be configured such that the personalized neuromodulation may be configured to preemptively stop an incontinence event, such as a urinary incontinence event or a fecal incontinence event. The personalized neuromodulation may be configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event. The personalized neuromodulation may be delivered to a pudendal nerve or tissue near the pudendal nerve of the patient, and / or a sacral nerve or tissue near the sacral nerve of the patient.

[0068] In some embodiments, the system or method disclosed herein may further include one or more sensors. The system or method may be configured to determine the breakthrough signature in response to a reading of the one or more sensors exceeding (or falling below) a threshold (e.g., a patient-specific threshold). In some embodiments, the one or more sensors may include a motion or posture sensor or other sensors (e.g., a pressure sensor). The patient-specific threshold may be indicative of a patient input on the implantable pulse generator or apostural change. The one or more sensors may include a bioelectrical sensor. The patient-specific threshold may be indicative of a muscle contraction.

[0069] In some embodiments, the system or method disclosed herein may be configured such that the first duration and / or the second duration may be user-adjustable. The first duration may be at least as long as the second duration. The second duration may be between 0 seconds and about 90 seconds (or any other suitable duration disclosed herein).

[0070] In some embodiments, (e.g., in the first duration or otherwise), the system or method disclosed herein may be configured to enter a fallback mode from the higher level to a lower level of stimulation. In some embodiments, the system (e.g., processor) or the method may be configured to disable stimulation based on a user input, e.g., in the first or second duration, or at any other time.

[0071] In some embodiments, a system configured to deliver personalized neuromodulation using breakthrough signatures to treat a medical condition (e.g., a pelvic condition including but not limited to incontinence, pain, etc.). The system may include an implantable pulse generator including a processor and a motion sensor (or any other suitable sensor, such as a pressure sensor). The system may include an implantable pulse generator including a processor. The processor may be configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of different levels. The system may further include one or more electrode leads in electrical communication with the processor. The one or more electrode leads may include at least one (or more) stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient. The one or more electrode leads may further include a biopotential sensor. The system (e.g., the processor) may be configured to output a background level of electrical stimulation. In response to determining (e.g., only) a first breakthrough signature of the patient based on readings of the motion sensor, the system (e.g., the processor) may be configured to increase the electrical stimulation from the background level to a higher level. In response to determining (e.g., only) a second breakthrough signature of the patient based on readings of the biopotential sensor, the system (e.g., the processor) may be configured to increase the electrical stimulation from the background level to the higher level. In response to determining both the first breakthrough signature and the second breakthrough signature (e.g., simultaneously or in an overlapped time period), the system (e.g., the processor) may be configured to only respond to the second breakthrough signature.

[0072] In some embodiments, a method for delivering personalized neuromodulation using breakthrough signatures to treat a medical condition (e.g., a pelvic condition including but not limited to incontinence, pain, etc.). The method may include outputting a background level of electrical stimulation. In response to determining (e.g., only) a first breakthrough signature of the patient based on readings of a motion sensor, the method may include increasing the electrical stimulation from the background level to a higher level. In response to determining (e.g., only) a second breakthrough signature of the patient based on readings of a biopotential sensor, the method may include increasing the electrical stimulation from the background level to the higher level. In response to determining both the first breakthrough signature and the second breakthrough signature (e.g., simultaneously or in an overlapped time period), the method may include only responding to the second breakthrough signature.

[0073] In some embodiments, the system or method disclosed herein may be configured such that the first breakthrough signature includes a postural change. The first breakthrough signature may include a patient inputon the implantable pulse generator (or on the electrode lead) or on an external device (e.g., an external patient controller disclosed herein).

[0074] In some embodiments, the system or method disclosed herein may be configured such that the first breakthrough signature may be configured to be activated based on a time of the day (and / or other user settings). In some embodiments, the second breakthrough signature may be activated throughout (or substantially throughout) the day. In some embodiments, the second breakthrough signature may be configured to be activated based on a time of the day (and / or other user settings). In one embodiment, the second breakthrough signature may be activated only for certain hours of the day. In one embodiment, the second breakthrough signature may be activated for the hours when the patient is awake.

[0075] In some embodiments, the background level stimulation may be turned off for certain hours of the day (and / or based on other user settings), for example, when the user is sleeping.

[0076] In some embodiments, a method of differentiating muscle contractions based on a patient's posture for delivering personalized neuromodulation using breakthrough signatures (e.g., to treat a medical condition such as a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The method may include providing a first biopotential breakthrough signature and a second biopotential breakthrough signature. The first biopotential breakthrough signature may include a first muscle contraction and the second biopotential breakthrough signature may include a second muscle contraction. The first muscle contraction and the second muscle contraction may be detected using a biopotential sensor (e.g., located on one or more electrode leads implanted in the patient's body). The method may further include determining the patient's posture using a posture sensor (e.g., an accelerometer, gyroscope, or I MU), which may be located on an implantable pulse generator (or the electrode lead) implanted in the patient's body. Based on the patient's posture, the method may include activating one of the first or second biopotential breakthrough signature. The patient's posture may include but are not limited to (e.g., at least two of) a supine position, a prone position, a left lateral recumbent position, a right lateral recumbent position, standing, or sitting. In response to the first or second biopotential breakthrough signature, the method may further include delivering an electrical stimulation to the patient. The electrical stimulation may be configured to increase from a background level to a higher level.

[0077] In some embodiments, a neuromodulation system configured to differentiate muscle contractions based on a patient's posture for delivering personalized neuromodulation using breakthrough signatures (e.g., to treat a medical condition such as a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The system may include an implantable pulse generator including a posture sensor and a processor. The processor may be configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of different levels. One or more electrode leads may be in electrical communication with the processor. The one or more electrode leads may include at least one (or more) stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient. The electrode lead(s) may further include a biopotential sensor. The system (e.g., the processor) may be configured to provide a first biopotential breakthrough signature and a second biopotential breakthrough signature. The first biopotential breakthrough signature may include a first muscle contraction and the second biopotential breakthrough signature may include a second muscle contraction. The first muscle contraction and the second muscle contractionmay be detected using the biopotential sensor. The system (e.g., the processor) may be further configured to determine the patient's posture using the posture sensor. Based on the patient's posture, the system (e.g., the processor) may be configured to activate one of the first or second biopotential breakthrough signature. The patient's posture may include but are not limited to (e.g., at least two of) a supine position, a prone position, a left lateral recumbent position, a right lateral recumbent position, standing, or sitting. In response to the first or second biopotential breakthrough signature, the system (e.g., the processor) may be configured to increase the electrical stimulation from a background level to a higher level.

[0078] In some embodiments, the system or method disclosed herein may be configured such that the personalized neuromodulation may be configured to preemptively stop an incontinence event, such as a urinary incontinence event or a fecal incontinence event. The personalized neuromodulation may be configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event. The personalized neuromodulation may be delivered to a pudendal nerve or tissue near the pudendal nerve of the patient, and / or a sacral nerve or tissue near the sacral nerve of the patient.

[0079] In some embodiments, the system or method disclosed herein may be configured such that activating one of the first or second biopotential breakthrough signature may include assigning the first or second biopotential breakthrough signature to a time period of the day.

[0080] In some embodiments, a generator for generating an electrical stimulation (such as to treat a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The generator may include a memory device and a processor to execute instructions stored on a non -transitory computer readable storage medium to generate the electrical stimulation of at least first, second, and third (or more) levels. A first level may be a first background level. A second level may be a second background level. The third level may be higher than the second level and the second level may be higher than the first level. The generator may be in electrical communication with one or more electrode leads. The one or more electrode leads may include at least one (or more) stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient. The generator (e.g., the processor) may be further configured to determine a first, second, and / or third (or more) breakthrough signature of a patient. The generator (e.g., the processor) may be further configured to generate electrical stimulation at the first or second background level (e.g., based at least in part on a time of the day, user settings, etc.) unless the third level is triggered. The first breakthrough signature may include a postural change of the patient. The second breakthrough signature may include a muscle contraction of the patient. The third breakthrough signature may include patient notification. The generator (e.g., the processor) may be further configured to provide at least three (or more) levels of stimulation. The third level may be triggered by at least one of the first, second, or third (or more) breakthrough signatures.

[0081] In some embodiments, a method for generating electrical stimulation for neuromodulation (such as to treat a pelvic condition including but not limited to incontinence, pain, etc.) is provided. The method may include determining a first, second, and third (or more) breakthrough signature of a patient. The first breakthrough signature may include a postural change of the patient. The second breakthrough signature may include a muscle contraction of the patient. The third breakthrough signature may include patient notification. The method may further include generating the electrical stimulation at a first or second background level (based at least in part on a time of a day,user settings, etc.) unless a third level is triggered. The third level may be higher than the second level and the second level may be higher than the first level. The third level may be triggered by at least one of the first, second, or third breakthrough signatures.

[0082] In some embodiments, the generator or method disclosed herein may be configured to run the first background level at nighttime and run the second background level at daytime.

[0083] In some embodiments, the generator or method disclosed herein may be configured such that the postural change may be determined by a posture sensor located on the generator. In some embodiments, the muscle contraction may be determined by a bioelectrical sensor. The bioelectrical sensor may be located on the electrode lead(s) implanted in the patient's body. In some embodiments, the patient notification may include a tap on the generator or an input on an external device (e.g., via a remote controller). The tap may be detected by a motion sensor (e.g., accelerometer, gyroscope, inertial measurement unit (I M U), etc.) located on the generator or by a different sensor such as a pressure sensor.

[0084] In some embodiments, the generator or method disclosed herein may be configured such that the three (or more) levels of stimulation may be configured to preemptively stop an incontinence event, such as a urinary incontinence event or a fecal incontinence event. The three (or more) levels of stimulation may be configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event. The three (or more) levels of stimulation may be delivered to a pudendal nerve or tissue near the pudendal nerve of the patient, and / or a sacral nerve or tissue near the sacral nerve of the patient.

[0085] In some embodiments, the generator or method disclosed herein may be configured to use a machine learning classifier model to determine the first, second, and / or third breakthrough signatures. In some embodiments, the generator or method disclosed herein may determine the first, second, and / or third breakthrough signatures in response to, for example, a sensor reading exceeding (or falling below) a predetermined threshold. The third level of stimulation triggered by the first breakthrough signature may include different parameters from the third level of stimulation triggered by the second or third breakthrough signature. In some embodiments, the third level may be configured to be triggered by the first breakthrough signature, for example, in a time of the day when the patient is sleeping, and / or configured to be triggered by the second breakthrough signature, for example, in a time of the day when the patient is awake, or vice versa.

[0086] In some embodiments, the generator or method of generating electrical stimulation for neuromodulation disclosed herein may be configured to further include a fallback mode in which a stimulation level lower than the first and second background levels is generated and the at least third level may be deactivated. The fallback mode may be patient activated.

[0087] In some embodiments, the system and method disclosed herein can be configured for the treatment of pain, e.g., pelvic pain. In some embodiments, the system and method disclosed herein can be configured for the treatment of sexual dysfunction.BRIEF DESCRIPTION OF THE DRAWINGS

[0088] Several features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of various embodiments can be obtained by reference to the following detailed description that sets forth illustrative non-limiting embodiments, in which the principles of the disclosure areutilized, and the accompanying drawings described below. Features from one figure may be combined with features of other figures.

[0089] Figure 1A illustrates a block diagram of an example neuromodulation system of the present disclosure.

[0090] Figure 1 B illustrates an example implantable pulse generator of the neuromodulation system.

[0091] Figure 1C illustrates an example controller of the neuromodulation system.

[0092] Figure 1 D illustrates an example electrode lead of the neuromodulation system.

[0093] Figure 1E illustrates an example second electrode lead of two-lead neuromodulation system embodiments disclosed herein.

[0094] Figure 1F illustrates schematically communications among the neuromodulation system disclosed herein and with another device.

[0095] Figure 2A illustrates a first example sagittal plane schematic of the anatomy and unilateral implanted leads and IPG in an individual.

[0096] Figure 2B illustrates a second example sagittal plane schematic of the anatomy and implanted leads and IPG in an individual.

[0097] Figure 2C illustrates an example frontal plane schematic of the anatomy and implanted IPG in an individual.

[0098] Figure 2D illustrates an example frontal plane schematic of the anatomy and implanted leads and IPG in an individual, showing a bilateral lead placement at the pudendal nerve.

[0099] Figure 3 illustrates schematically certain input and output of the implantable pulse generator of the neuromodulation system disclosed herein.

[0100] Figure 4 illustrates schematically assignment of different adaptive profiles to a program assignment element according to one embodiment.

[0101] Figure 5A illustrates schematically assignments of background model and adaptive profiles to different times of the day for a first patient according to one embodiment.

[0102] Figure 5B illustrates schematically assignments of background model and adaptive profiles to different times of the day for a second patient according to one embodiment.

[0103] Figure 5C illustrates schematically assignments of background model and adaptive profiles to different times of the day for a third patient according to one embodiment.

[0104] Figure 6 illustrates a block diagram of motion adaptive profile embodiments and other control policies of the neuromodulation system disclosed herein.

[0105] Figure 7A illustrates a block diagram of sense adaptive profile embodiments and other control policies of the neuromodulation system disclosed herein.

[0106] Figure 7B illustrates a block diagram of a biopotential classifier according to one embodiment.

[0107] Figure 7C illustrates an example graph illustrating an above-threshold interrupt and the below-threshold interrupt according to one embodiment.

[0108] Figure 8 is a flowchart illustrating an interrupt priority rule of the implantable pulse generator according to one embodiment.

[0109] Figure 9 is a flowchart illustrating a time interlock according to one embodiment.

[0110] Figures 10A and 10B illustrate example displays of a patient controller of the neuromodulation system disclosed herein.

[0111] Figure 11 illustrates an example patient tab user interface of a software program configured to be in communication with the implantable pulse generator.

[0112] Figure 12A illustrates an example device tab user interface of a software program configured to be in communication with the implantable pulse generator.

[0113] Figure 12B illustrates an example usage report pop-up window of the software program according to one embodiment.

[0114] Figures 12C illustrates an example patient settings window of the software program according to one embodiment.

[0115] Figure 12D illustrates an example impedance measurement window of the software program according to one embodiment.

[0116] Figures 13A and 13B illustrate example stimulation tab user interfaces of a software program configured to be in communication with the implantable pulse generator.

[0117] Figure 13C illustrates an example advanced stimulation programming pop-up window of the software program according to one embodiment.

[0118] Figures 14A illustrates an example adaptive tab user interface of a software program configured to be in communication with the implantable pulse generator.

[0119] Figures 14B and 14C illustrate example portions of an adaptive user interface of the software program for configuring movement adaptive profiles according to one embodiment.

[0120] Figure 14D illustrates an example portion of an adaptive user interface of the software program for configuring sense adaptive profiles according to one embodiment.

[0121] Figures 15A and 15B illustrate example monitor tab user interface of a software program configured to be in communication with the implantable pulse generator.

[0122] Figures 16A and 16B illustrate example portions of a user interface showing usage data of different patients according to one embodiment.

[0123] Figure 17 is a block diagram illustrating an embodiment of the neuromodulation system.DETAILED DESCRIPTION

[0124] Electrical stimulation has clinical application in providing treatment and / or management of a variety of clinical conditions, for example within the pelvic region. For example, electrical stimulation may be used to treat urinary incontinence, fecal incontinence, pain, sexual dysfunction, or any combination thereof medical condition and / or diseases within the pelvic region. In one embodiment, pelvic organ prolapse is treated. In one embodiment, restless leg syndrome and / or restless genital syndrome are treated separately or when there is co-morbidity with overactive bladder. In some embodiments, symptoms or episodes are prevented through use of the technology described herein. For example, through time-dependent (e.g., circadian based) programming, adaptive (that is, adapting to or responsive to one or more stimuli, as disclosed herein elsewhere) stimulation with flexible sensor input(s) selections for determining breakthrough signatures, personalized thresholds, additional patient safety and / or comfortfeatures, or combinations thereof, an incontinence episode can be treated or otherwise ameliorated through prevention of one or more actual episode. In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application No. PCT / EP2025 / 080505 titled "ADAPTIVE NEUROMODULATION SYSTEM,” filed on the same day as the present application, which is hereby incorporated in its entirety, can be used with any one or more of time-dependent programming, adaptive stimulation with flexible sensor input(s) selections for determining breakthrough signatures, personalized thresholds, additional patient safety and / or comfort features, or combinations thereof disclosed herein.

[0125] Although certain devices, systems, and methods are described herein with respect to the pelvic region to prevent, treat and / or manage pelvic conditions, the devices, systems, and methods can be used in other regions of the body or to treat other conditions. The implantable devices may be implanted in other regions of the body and / or to treat other conditions. In some embodiments, electrode lead(s) of the implantable devices may be implanted in the spinal region, for example to treat chronic or incidental pain. The electrode lead(s) may be implanted in or near the spine to treat, for example, pain (e.g., the spinal cord region caudal of the occiput or other spinal regions). In other embodiments, the electrode lead(s) may be implanted near peripheral or cranial nerves, and / or may monitor and / or sense brain activity. For example, lead(s) may be implanted near the vagus nerve (e.g., in the facial / cranial region) for treatment of several disorders, including but not limited to balance issues, headache, migraines, etc. In several embodiments, restless leg is treated.Embodiments of Neuromodulation Systems

[0126] Provided herein are methods, devices, and systems for aiding an incontinence patient, for example, in improving personalization of therapy, patient comfort, patient safety, and / or other advantages including but not limited to advantages disclosed herein. Figure 1A illustrate an example neuromodulation system 10. The system 10 may include devices that may be implanted in the body 2 of an individual, comprising or consisting essentially of at least one electrode lead 102 (for example, two electrode leads or more, such as three, four, etc.) and an implantable pulse generator (IPG) 108. In some embodiments, the pulse generator may be external to the body. The pulse generator may be coupled to the at least one electrode lead 102, which may have at least a portion thereof implanted inside the body. In some embodiments, the pulse generator may be placed in or on the body but at a location further away from the pelvic floor than the examples shown in Figures 2A-2D, for example, the pulse generator may be placed under the skin or transcutaneously. In other embodiments, the pulse generator may be remote to the individual and may be wirelessly coupled to the at least one lead. The at least one electrode lead 102 may be coupled to the IPG 108, for example, via wire(s). Figure 1B illustrates a non-limiting example of the IPG 108. The IPG 108 may be implanted anywhere in the body 2 of the individual in or near the pelvic region. For example, the IPG 108 may be implanted in buttock fat, a leg, the abdomen, etc. Figure 1D illustrates a non-limiting example of an electrode lead 102. Figure 1E illustrates a non-limiting example of a second electrode lead 104 for embodiments including a two-lead configuration. The neuromodulation system 10 may further include a controller 110 that may be external to the body 2 of the individual. The controller 110 may be used by the patient or another user. The controller 110 and the IPG 108 may be in wireless communication via wireless communication hardware.

[0127] The communication hardware may implement any suitable wireless communication protocols, including but not limited to those disclosed herein. Non-limiting examples of wireless communication protocol may include Wireless Fidelity (WIFI), Bluetooth, Zigbee, Near Field Communication (NFC), Z-wave, Long Range (LoRa), Cellular Networks (e.g., 4G LTE, 5G, etc.). In some implementations, the wireless communication between the controller 110 and the IPG 108 is via a Medical Implant Communication System (MICS). The wireless communication between the controller 110 and the IPG 108 may be in a frequency band between about 300 MHz to about 500 MHz, or about 400 MHz to about 499 MHz, or about 401 MHz to about 406 MHz, or about 402 MHz to about 405 MHz, or about 413 MHz to about 419 MHz, or about 426 MHz to about 432 MHz, or about 438 MHz to about 444 MHz, or about 451 MHz to about 457 MHz, or a smaller range within any of the defined ranges, or another range defined by any of the values between 300 MHz to 500 MHz. The frequency band between about 300 MHz and about 500 MHz may improve device security and reliability when data is transmitted to support diagnostic or therapeutic functions associated with medical implant devices. In some implementations, the maximum distance between the controller 110 and the IPG 108 for wireless communication may be less than about 4.0 m, or about 3.8 m, or about 3.6 m, or about 3.4 m, or about 3.2 m, or about 3.0 m, or about 2.8 m, or about 2.6 m, or about 2.4 m, or about 2.2 m, or about 2 m, or a distance within a range defined by any of these values.

[0128] The IPG 108 may include a processor 122, which may execute software or instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation pattern according to a stimulation program (also referred to as a "mode”). In some embodiments, the processor 122 may be a microprocessor. In some implementations, the processor 122 may include a clock and a memory device for recording and storing data. The processor 122 may further include hardware and / or software modules for controlling the electrical stimulation generated by an actuator of the IPG 108. The processor 122 may further include hardware and / or software modules for analyzing signals from one or more sensors 124 and / or sensing electrodes, and / or other sensors described elsewhere in the present disclosure.

[0129] The IPG 108 may include a power source 126. The power source 126 may be a battery, which may be a lithium polymer ion battery, lithium iodine, lithium manganese dioxide, lithium carbon monofluoride, or any combination thereof. The battery may be rechargeable. In some implementations, recharging can be via a wireless charger, including but not limited to an inductive charger. The wireless charger may be placed on the torso of the individual over the location of the IPG 108 to perform wireless charging. In some implementations, the wireless charger may be secured to a recharge belt and holster to hold the wireless charger in the correct position. The wireless charger, when connected to the controller 110 (wirelessly or in a wired connection), may connect to the IPG 108 to charge the battery in the IPG 108. In some implementations, the maximum distance between the wireless charger and the IPG 108 during charging may be less than about 3.0 cm, or about 2.8 cm, or about 2.6 cm, or about 2.4 cm, or about 2.2 cm, or about 2.0 cm, or about 1.8 cm, or about 1.6 cm, or about 1.4 cm, or about 1.2 cm, or about 1.0 cm, or a distance within a range defined by any of these values. Alternatively, the battery power source may be a single use.

[0130] In some embodiments, the battery may last at least about 24 hour, about 48 hours, about 72 hours, about 96 hours, about 120 hours, or longer after each charge, or a duration within a range defined by any of these values. As described elsewhere in the present disclosure, the battery life may be improved so that the patient needs not charge the IPG 108 after several hours of use or daily, which may be inconvenient. As also describedelsewhere in the present disclosure, the battery saving features do not sacrifice accuracy in adaptive stimulation in some embodiments. In some implementations, the system may include a cost function including power requirements and may optimize the stimulation algorithm for the total cost function inclusive of maximizing symptom management, while minimizing power usage and side-effects. In some implementations, the system may use artificial intelligence to optimize the stimulation based on any of the inputs described herein, e.g., power requirements, battery level, etc.

[0131] In some embodiments, during recharging, the programs on the neuromodulation system disclosed herein may still be activated but restricted to more robust signals that may still be valid during battery recharging. For example, the biopotential signals might be corrupted by induction and the bioelectrical sensing may be disabled during recharge. However, the other sensors disclosed herein, such as the motion or posture sensor, remain activated. In one example, the motion or posture sensor may be used for automated environmental detection and safety features.

[0132] The electrical stimulation current generated by the IPG 108 may be delivered to one or more electrodes at or near a distal end of the electrode lead 102 and / or a distal end of the electrode 104 (if present). In some embodiments, the electrodes 102, 104 may be coupled to an actuator circuitry of the IPG 108. As shown in Figures 1A, 1D, and 1E, each electrode lead (e.g., the electrode lead 102, the second electrode lead 104, etc.) may be a quadripolar lead. The electrode lead 102 may include four electrodes 132, 134, 136, 138 along a distal end of the lead 102. In some implementations, each lead may include more than four electrodes (for example, five, six, seven, eight, nine, ten, eleven, twelve, or more) or fewer than four electrodes (for example, one, two, or three).

[0133] The remainder of the electrode lead 102, 104 other than at the electrodes may be insulated. A proximal end of the electrode lead 102 may be connected to the IPG 108 via a wire (also referred to as a "lead body”). In the illustrated example as shown in Figures 1D and 1E, the electrodes may be numbered and may be coupled to the respective connection point in the IPG 108 having the same number (see Figure 1 B). The IPG 108 as shown in Figure 1B may couple to two electrode leads, which may include the electrode lead 102 and second electrode lead 104 as shown in Figures 1D and 1 E respectively. In some implementations, the electrodes 132, 134, 136, 138 on the electrode lead 102 may be labeled as Nos. 1, 2, 3, and 4; and the electrodes 131, 133, 135, 137 on the second electrode lead 104 may be labeled as Nos. 5, 6, 7, and 8. Similar numberings of the electrodes may be used in a software used to program or configure the system, which is described elsewhere in the present disclosure.

[0134] The stimulation programs may be set by a healthcare provider on an external device. Turning to Figure 1F, the external device 20 is in communication with the controller 110 or directly with the IPG 108. The external device 20 may include a desktop, a laptop, a tablet, a smartphone, a wearable device, and / or the like. The programs may be transmitted (e.g., wirelessly or optionally via a wired connection) to the IPG 108 from the external device 20. A user (including but not limited to a clinician or a patient) may modify or set electrical stimulation parameters via the external device 20 via a wireless communication between the external device 20 and the IPG 108. Alternatively, the user may modify or set electrical stimulation parameters via the user interface 114 of the controller 110. The electrical stimulation parameters that may be adjusted may include frequency, amplitude, pulse width, or any combinations thereof. In some implementations, the system may use artificial intelligence to automatically determine and / or set stimulation programs and / or parameters based on any of the inputs described herein, e.g., sensor data. The usage data may be stored on the IPG 108. Alternatively or additionally, the usage data may be transmitted from theIPG 108 to the controller 110, the external device 20, and / or a remote server (e.g., a data repository, a cloud, etc.). In some implementations, the usage data may be transmitted from the IPG 108 to the controller 110 and / or the external device 20 during charging of the power source on the IPG 108. The data received by the external device 20 and / or the remote server may be accessible by the clinician. In some cases, the data transmission during recharging may reduce the patient's frequency of re-visits to the clinician's office.

[0135] The electrical stimulation may be delivered to the nerve (for example, the pudendal nerve and / or the sacral nerve) or tissue adjacent to the nerve via one or more of the electrodes 132, 134, 136, 138 of the electrode lead 102 and / or the electrodes 131, 133, 135, 137 of the second electrode lead 104 functioning as stimulating electrodes. In some implementations, the system 10 may include two electrode leads 102, 104 for stimulating a nerve at two sites or stimulating nerves on two sides of the body. Depending on the indication, the length of the wire or lead body may vary. In some cases, bilateral leads may have different lengths for the lead body. The length of the lead contralateral to the IPG may be greater than the length of the lead ipsilateral to the IPG. In some cases, having a bilateral approach, the difference between the length of a first lead body and a second lead body may be between about 100 mm and 200 mm. In some cases, the difference between the length of two bilateral lead bodies may be about 100 mm, about 110 mm, about 120 mm, about 130 mm, about 140 mm, about 150 mm, about 160 mm, about 170 mm, about 180 mm, about 190 mm, about 200 mm, or a length in a range defined by any of these values.

[0136] One or more of the electrodes 132, 134, 136, 138 in the lead 102 and / or the electrodes 131, 133, 135, 137 in the lead 104 may function as stimulating electrodes to deliver various amounts of voltage, current, and / or power. The electrodes may be designed to deliver a voltage of about 10V per electrode. The electrodes may be designed to deliver a voltage of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 V per electrode. In some embodiments, the electrodes may be designed to deliver a voltage of at most about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 V per electrode. The electrodes may be designed to deliver a voltage of about 1 to about 50 V per electrode, about 1 to about 40 V per electrode, about 1 to about 30 V per electrode, or about 1 to about 20 V per electrode. The electrodes may be designed to deliver a current of about 10mA per electrode. In some embodiments, the electrodes may be designed to deliver a current of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mA per electrode. The electrodes may be designed to deliver a current of at most about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mA per electrode. The electrodes may be designed to deliver a current of about 1 to about 50 mA per electrode, about 1 to about 40 mA per electrode, about 1 to about 30 mA per electrode, or about 1 to about 20 mA per electrode. The electrodes may be designed to deliver a power (VA) of about 0.1 W per electrode. In some embodiments, the electrodes may be designed to deliver a power (VA) of at least about 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, or 5 W per electrode. In some embodiments, the electrodes may be designed to deliver a power (VA) of at most about 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 W per electrode. The electrodes may be designed to deliver a power (VA) of about 0.01 to about 10W per electrode, about 0.01 to about 5W per electrode, or about 0.01 to about 1 W per electrode. The electrodes may be designed to deliver stimulation with a pulse width of about 1 pis to about 1000 pis. In some embodiments, the electrodes may be designed to deliver stimulation with a pulse width of at least about 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 pis, or any value in a range defined by these values.

[0137] Another one or more of the electrodes 132, 134, 136, 138 in the lead 102 and / or the electrodes 131, 133, 135, 137 in the lead 104 may function as sensing electrodes. In some implementations, the sensing electrodes may include bioelectrical sensing electrodes. In some implementations, a biopotential across two sensing electrodes may be measured. In some implementations, the sensing electrodes may sense an Electromyography (EMG) signal. The EMG signal may be analyzed to determine whether a contraction (or relaxation, or any other muscle activity) of at least one pelvic muscle, a sphincter muscle, an abdominal muscle, or another muscle (e.g., leg muscle, glute muscle, etc.) has occurred. In some implementations, the strength of the EMG signal may indicate that a contraction of a muscle has occurred. The data collected by the sensing electrodes may be stored on a memory device of the IPG 108. The memory device may be part of the processor 122. In some implementations, the processor 122 may process the data to determine whether a contraction of a certain muscle has occurred. In some embodiments, the data collected by the sensing electrodes may be fed into a biopotential classifier of the IPG processor 122 (described elsewhere herein) for determining whether a different stimulation program needs to be activated. In some implementations, the IPG 108 may include amplifier circuitry to amplify the signal from the sensing electrodes prior to feeding into the classifier. In some implementations, the processor 122 may transmit the data collected by the sensing electrodes to the controller 110 and / or to the external device 20 (e.g., a laptop, a desktop, a tablet, a smartphone, watch or other wearable, etc.). In some implementations, the controller 110 or the other device that receives the data may process the data to determine whether a contraction of a certain muscle has occurred.

[0138] In some implementations, the IPG 108 may activate sensing only when the IPG is not running any stimulation program. In those embodiments, during a stimulation program, the user input in the form of a tap on the location of the IPG 108 detected by a motion or posture sensor (which is described in greater details elsewhere in the present disclosure) may trigger a different stimulation program. As referred to herein, a "tap” (or "taps” or "tapping”) may refer to tap(s) on the portion of patient's body overlying the IPG (e.g., a tap on the skin of the abdomen if the IPG is implanted in the abdomen), rather than a tap directly onto the IPG case. In some implementations, the IPG 108 may only trigger a different stimulation program based on a user input detected by the motion or posture sensor, such as a tap, a double tap, or another tap sequence on the IPG. In some implementations, the IPG 108 may alternate between a sensing program and a stimulation program. In some implementations, the IPG 108 may run a stimulation program to generate stimulation while receiving data at the sensing electrodes during the stimulation program. In some embodiments, concurrent stimulation and sensing during a stimulation program may include stop sensing when a pulse of the electrical stimulation is generated, and enable sensing in between the pulses. Concurrent stimulation and sensing may improve the accuracy in detecting a breakthrough signature (described elsewhere in the present disclosure) from the patient to change the stimulation program or mode. Additionally or alternatively, one or more sensors may be positioned on one or more leads 102, 104, including but not limited to a motion / posture sensor, a pressure sensor, a global positioning system (GPS), etc. In one embodiment, one or more leads 102, 104 do not include sensors other than the sensing electrodes disclosed herein. In one embodiment, only motion, posture, or motion and posture sensor(s) are included.

[0139] As shown in Figure 1A, the IPG 108 can include one or more sensors 124, including but not limited to a motion / posture sensor, a pressure sensor, a global positioning system (GPS), a temperature sensor (e.g., a thermistor), etc. e.g., 1, 2, 3, 4 or more sensors, which may be on one lead, more than one leads, and / or on locationsothers than a lead). The motion / posture sensor can detect the individual's movement and / or posture. The motion / posture sensor may include an accelerometer, a gyroscope, and / or a magnetometer. In some implementations, the motion / posture sensor may include a three-axis accelerometer. Data from the one or more sensors 124 (including but not limited to a motion or posture sensor, or a combined motion / posture sensor) may be used by the processor 122 of the IPG 108 (or another controller) to control switching between different stimulation programs, as described in greater detail elsewhere in the present disclosure. In some implementations, data from the one or more sensors 124 on the IPG 108, the sensing electrodes and / or one or more sensors in the one or more leads 102, or any combinations thereof may be used for determining whether the IPG 108 should switch to a different stimulation program. In some implementations, data from the one or more sensors 124 on the IPG 108, the sensing electrodes, and / or one or more sensors in the one or more leads 102, or any combinations thereof may be used for determining whether the IPG 108 should disable certain sensors and / or switch to a different adaptive mode, as described in greater detail elsewhere in the present disclosure. In some implementations, a sensor of a first input mode may cooperate with one or more other sensors of another input mode to provide multimodal sensing with improved specificity when performing any of the functions described herein with respect to sensing. In some implementations, data from the one or more sensors may be used to determine a patient-specific circadian profile, e.g., the patient's circadian patterns, for adjusting a stimulation program schedule, as described in greater detail elsewhere in the present disclosure. For example, the temperature sensor, and optionally one or more other sensors described herein, e.g., a motion sensor, may be used to determine a patient-specific circadian profile, as body temperature fluctuation may be indicative of a circadian rhythm.

[0140] The controller 110 may include a user interface 114, for example, buttons, switches, graphic user interface on a touch screen, etc. The controller 110 may optionally include a display screen. Figure 1D illustrates a non-limiting example of the controller 110. The controller 110 may optionally be in communication with an external device (e.g., not necessarily part of the neuromodulation system 10) (see Figure 1F), for example, a computer, a tablet, a smartphone, watch or other wearable, and the like. The external device may run software as described elsewhere in the present disclosure that can be used to program the IPG 108. The communication between the controller 110 and the external device may be via a wired or wireless connection. When connected, the controller 110 may transmit data to the other / external device and / or receive data from the other / external device. Alternatively, the IPG 108 may establish wireless communication with the external device other than the controller 110 to allow transmission and receiving of data between the IPG 108 and the external device.

[0141] In several embodiments, one or more stimulation parameters (e.g., frequency, amplitude, pulse width, duration, timing etc.) or locations of stimulation are varied automatically (e.g., using machine learning and / or artificial intelligence) to reduce or prevent habituation and / or to facilitate patient tolerance (if for example, the patient feels any discomfort from stimulation). In some embodiments, stimulation parameters or locations are controlled by the patient to reduce or prevent habituation and / or to facilitate patient tolerance. Varying stimulation includes, for example, reducing stimulation by 25%-95% or stopping stimulation for a time period. As described elsewhere in the present disclosure, several embodiments may include other safety and / or comfort features in addition to varying stimulation.

[0142] In several embodiments, the system 10 may support monophasic and / or biphasic stimulation pulses. Monophasic stimulation may use passive recharge. Biphasic stimulation may use active recharge.Monophasic stimulation may deliver a pulse in only one direction leading to charge accumulation at the electrodetissue interface. Monophasic stimulation may rely on passive recharge, which may include a waiting period allowing the accumulated charge to dissipate before delivering the next pulse. Biphasic stimulation may deliver a pulse in one direction followed by one or more reverse pulses in an opposite direction, e.g., up to 1, 2, 3, or more reverse pulses. The one or more reverse pulses serve as an active recharge to balance the charge. The contact output for each electrode may be independently controllable and can receive a portion of the set total charge, as disclosed elsewhere herein. The system 10 may use time-division multiplexing to divide the stimulation waveform into a series of interlaced high-speed pulses. The current may be distributed across multiple electrodes using time-division multiplexing, e.g., by splitting delivered charge between contacts based on a time sequence. The system 10 may be capable of pulse width modulation, allowing for adjustability of the percentage of the total charge delivered by each electrode. These features may allow for shaping of the electric field and improving stimulation precision, which may enhance therapy personalization and reduce unwanted side effects.Lead Placements

[0143] In some implementations, at least one electrode lead can be implanted on a nerve or tissue adjacent to the nerve that serve one or more muscles used for treating urinary or fecal incontinence. The lead may be placed to target the pudendal nerve and / or the sacral nerve. The pudendal nerve stimulation may inhibit the bladder at three levels, S2, S3, and S4. Thus, the pudendal nerve stimulation may have a stronger inhibition than other target nerves, for example sacral nerve stimulation, because the pudendal nerve may have three different levels (S2, S3, and / or S4) that can be stimulated, whereas the sacral nerve may have a single level for stimulation, as described in greater detail elsewhere in the present disclosure. In some embodiments, the pudendal nerve is stimulated at 2, 3 or more places, but stimulation at a single level of the pudendal nerve is also contemplated.

[0144] In one embodiment, the lead is placed to only target the pudendal nerve, not other nerves. In one embodiment, only the pudendal nerve, but not other nerves, is stimulated. In another embodiment, a combination of only two nerves are stimulated (e.g., the pudendal nerve and the sacral nerve).

[0145] Figures 2A-2D illustrate the anatomical path desired for lead placements in some implementations. Figure 2A shows a schematic of the anatomy and the disposition of leads and IPG in an individual. Figure 2A shows iliac crest 222 of the ileum, gluteus minimus 224, piriformis 206, sacrotuberous ligament 228, pudendal nerve 210, and sciatic nerve 211. The leads 202, 204 may be placed on one or more locations along the length of the pudendal nerve 210. The wires 203 of the leads 202, 204 may be connected to the IPG 208. The placement of the leads 202, 204 on the pudendal nerve may be verified and fixed before their wires 203 are connected to the IPG 208. Figure 2B shows two leads 202, 204, each lead with four electrodes (shown as dark circles), placed on two sections of the pudendal nerve 214. The wires 203 of the leads 202 and 204 may be connected to the IPG 208. Shown in Figure 2B are the inferior gluteal nerve 234, pudendal nerve 210, obturator internus 216, sacrotuberous ligament 228, posterior femoral cutaneous nerve 220, gluteus medius 232, gluteus minimus 224, piriformis 206, quadratus femoris 244, gluteus maximus 230, and sciatic nerve 211. Figure 2C shows the IPG 208 placed in a pocket in the buttock fat overlying the gluteal muscles. In other embodiments, the IPG 208 may be placed at or near the abdomen. Figure 2C show the iliac crest 222, intergluteal cleft 236, greater trochanter 238 of the femur, ischial tuberosity 240 of the pelvis, and gluteal fold 242.

[0146] In some cases, one electrode lead can be placed on each side of the body at a nerve that serves one or more muscles controlling or used for urination or bowel movement, resulting in a bilateral placement. The lead may be placed at any suitable locations on the nerve, such as a trunk lead, or a lead at another location on the nerve. In some instances, a trunk lead electrode stimulation may lead to higher external anal sphincter (EAS) EMG amplitudes compared to an anterior lead electrode stimulation, indicating better therapy efficacy being delivered to the patient. In some implementations, both leads may be trunk leads. For example, bilateral stimulation of the pudendal nerve may allow for better control and / or effectiveness in treating urinary or fecal incontinence than unilateral stimulation. Figure 2D shows a schematic of a bilateral lead placement at the pudendal nerve. A first lead 204 may be positioned in the right side of the body at the trunk (e.g., the Alcock's canal) of the right pudendal nerve. A second lead 202 may be positioned contralateral to the first lead 204, in the left side of the body at the trunk (e.g., the Alcock's canal) of the left pudendal nerve. Alternatively, one of the first lead 204 or the second lead 202 may be positioned at a distal end of the pudendal nerve. The first and second leads 204, 202 may be tunneled through the gluteal region to connect to a unilateral IPG 208. The length of the lead contralateral to the IPG may be greater than the length of the lead ipsilateral to the IPG. As illustrated by Figure 2D, the first lead 204 may be longer than the second lead 202. For example, the length of the first lead 204 may be about 550 mm and the length of the second lead 202 may be about 400 mm. The difference between the length of the first lead 204 and the second lead 202 may be between about 100 mm and 200 mm. For example, the difference between the length of two bilateral leads may be about 100 mm, about 110 mm, about 120 mm, about 130 mm, about 140 mm, about 150 mm, about 160 mm, about 170 mm, about 180 mm, about 190 mm, about 200 mm, or a length in a range defined by any of these values.Time-dependent Personalized Stimulation

[0147] Described herein are devices, systems, and methods that may, among other features, prevent an episode of incontinence in an individual by providing electrical nerve stimulation. The episode of incontinence may include urinary incontinence, fecal incontinence, or any combination thereof. The devices, systems and methods disclosed herein may treat one or more sub-types of incontinence. Common sub-type of incontinence may include urge incontinence, stress incontinence, overflow incontinence, or mixed incontinence, which are described in greater detail elsewhere in the present disclosure. One advantage of several embodiments is the ability to treat both urge and stress incontinence, and to personalize therapy depending on the patient's circadian rhythm and / or the patient's needs.

[0148] Several embodiments advantageously provide time-dependent personalized stimulation. Different parameters, a different background stimulation level, and / or different stimulation schedules can be used based on time-dependency, which can include but are not limited to physiological rhythms. Non-limiting examples of physiological rhythms can include circadian, ultradian, and / or infradian rhythms. In some embodiments, depending on the time of the day, the system disclosed herein may deliver a different background stimulation level. One example of time-dependency includes sleep schedule and circadian rhythms, which may be relevant to neuromodulation therapy. Patient needs, biomarkers, and symptoms can show predictable diurnal patterns. In some embodiments, a user (for example, a clinician) may assign different stimulation programs to be run at different times of the day. In some embodiments, one or more stimulation programs may include one or more time-dependent characteristics of the patient, including but not limited to diurnal parameters. The different stimulation programs may include at least one pattern designed with the daytime activity in mind and another pattern designed with the nighttime activity in mind. Insome instances, the stimulation programs for daytime may include background stimulation at a higher level (e.g., greater frequency, pulse width, etc.) than the background stimulation programs for nighttime. As used herein, "higher” may refer to the level of nerve activation by the stimulation. The stimulation program may include different parameters, variations in parameters, patterned parameters, burst and / or pulsed stimulation patterns etc. that overall result in higher (or increased) nerve activation without necessarily using higher frequency, amplitude, and the like. A first background level may be assigned to daytime and a second background level may be assigned to nighttime. In some embodiments, the first level may be higher than the second level. During nighttime, the sphincter closing effect and / or the inhibition function of the stimulation may be less needed. In some embodiments, the stimulation program during nighttime may provide more regenerative function. In some embodiments, the stimulation programs may be adjusted for a more nocturnal patient. For example, the timing of the daytime stimulation programs and the night stimulation programs may be shifted according to a more nocturnal individual's schedule. As another example, the stimulation programs include nocturnal parameters, such as by providing background stimulation at a higher level (e.g., greater frequency, greater pulse width, etc.) at nighttime than the background stimulation during early morning hours (e.g., 3 am, 4 am or later).

[0149] In some embodiments, the time-dependency may include more than the circadian rhythm, for example, the patient's routine daily schedule, commute schedule, workout schedule, and the like. These schedules may include but are not limited to wakeup time, sleep time, evening winddown time, commute schedule, workout schedule, etc., which may not necessarily coincide with the patient's circadian rhythm and / or which may be driven by work, school, family, medical, and / or travel needs. For example, the patient may experience more stress events during workout time, as the patient engages in strenuous physical activity like jumping, weightlifting, etc. As another example, the patient may more likely experience an urge event as the patient arrives home after work. In some instances, the time-dependency may include the patient's medical conditions, e.g., different stages of pregnancy, postpartum, postsurgery, etc. For example, the patient may experience higher rate of incontinence after childbirth. Non-limiting examples of other time-dependency may include physiological rhythms other than or in addition to circadian / diurnal rhythms. Such rhythms may include ultradian or faster than daily (sub-day, e.g., after each meal or other fluctuations in daytime that may depend on variables like sleep pressure, feeding, and / or exercise) rhythms. Such rhythms may include infradian or slower than daily (e.g., menstrual cycles, cycles spanning multiple days, weeks, and / or months) rhythms.

[0150] Several embodiments disclosed herein advantageously allow multiple background stimulation levels to be saved in a library of stimulation programs for any of the different needs of the patient. Any of the background stimulation levels may be assigned to be running based on any of the time-dependencies disclosed herein, such as at a certain time of the day, a certain day of the week or month, etc. In some embodiments, the assigned background level can be run until a breakthrough signature of the patient is determined (as described elsewhere in the present disclosure). In some embodiments, the entire program of the neuromodulation system disclosed herein can be varied based on the time-dependency disclosed herein, including but not limited to the sensors used, how the sensor signals are classified, and what stimulation programs are activated based on the classifier output (including the fallback modes as well as for safety and / or comfort).

[0151] Different stimulation programs may be used throughout the 24-hour day, throughout a week, throughout a month, etc. Alternatively, intermittent stimulation may be used (in one block of time or multiple blocks oftime) when the patient is most likely to experience incontinence or other medical conditions disclosed herein. In some embodiments, background stimulation may be turned off for certain periods of time. In one example, the background stimulation program may be stopped when the patient is sleeping. In some implementations, the stimulation program may only include adaptive stimulation for turning on stimulation upon determining one or more breakthrough signatures (described elsewhere in the present disclosure). The intermittent stimulation may reduce habituation, improve patient comfort, and / or improve battery life of the system. In some implementations, the system may use machine learning and / or artificial intelligence, and using any of the inputs described herein, e.g., sensor data, to automatically determine and / or set the stimulation program that should be used at a given time period.

[0152] The neuromodulation system disclosed herein may include a clock and program assignment features (for example, a 24-hour program assignment feature, assignment features based on a weekly and / or monthly calendar). In some embodiments, the clock may be automatically time-zone adjusted. As shown in Figure 3, the IPG may include a clock 302, which may be embedded on the processor 300. Alternatively, the processor 300 may receive time information from another clock. The IPG processor 300 may receive a program assignment input 304. The program assignment input 304 may include information such as what background stimulation program is assigned to run in a certain time or time period of the day (or day of the week, day of the month, etc.) and / or whether an adaptive profile is activated for that time or time period. The stimulation programs assigned to that time or time period may include parameters biased towards the patient's circadian rhythm and / or activity level at that time or time period of the day, as described elsewhere in the present disclosure. In some implementations, data from the one or more sensors may be used to determine a patient-specific circadian profile, e.g., the patient's circadian patterns, for adjusting a stimulation program schedule, as described in greater detail elsewhere in the present disclosure. For example, the temperature sensor, and optionally one or more other sensors described herein, e.g., a motion sensor, may be used to determine a patient-specific circadian profile, as body temperature fluctuation may be indicative of a circadian rhythm. In some cases, the sensor-based circadian profile may be used for program assignment rather than the clock. In some implementations, the system may use machine learning and / or artificial intelligence to evaluate the data from the one or more sensors, or any other inputs described herein, to determine a patient-specific circadian profile.

[0153] In some embodiments, the program assignment input 304 can include a background stimulation program mapped to a particular time window. The background program may run continuously as the selected stimulation program 312 during its assigned time window (which may not necessarily require that the "on time” of the simulation is as long as the duration of the time window, as described elsewhere in the present disclosure) when an adaptive profile is off, when no adaptive profile has been assigned to the window, and / or when the adaptive profile has not triggered any change of the stimulation program during the assigned time window. In some cases, when a particular time window begins, the background stimulation program mapped to that particular time window is triggered, even if a higher level of stimulation had been triggered right at the end of the previous time window.

[0154] In some implementations, the program assignment feature may be used to configure a clinician-specified profile to drive a desired physiological profile for therapy (e.g., to reinforce a certain sleep-wake pattern).

[0155] When adaptive stimulation is activated, the program assignment input 304 may include an adaptive profile assigned to be activated in a certain time or time period of the day disclosed herein. A background stimulation level may be run continuously in an assigned time period until a breakthrough signature is determined viaan assigned adaptive profile. The adaptive profile assigned to that time or time period may incorporate a timedependent character of the patient, e.g., being biased towards the patient's circadian rhythm, other rhythms disclosed herein, and / or activity level at that time or time period of the day, as described elsewhere in the present disclosure.

[0156] The IPG processor 300 may receive a first breakthrough signature input 306, a second breakthrough signature input 308, and / or a third breakthrough signature input 310 for adaptive stimulation. In some embodiments, the first breakthrough signature input 306 may include detection of a postural change of the patient. In some embodiments, the second breakthrough signature input 308 may include detection of a muscle contraction. In some embodiments, the third breakthrough signature input 310 may include detection of a patient notification. In some embodiments, the breakthrough signature inputs may be determined using any of the sensors disclosed herein, and / or via the controller (see, e.g., controller 110) or an external device disclosed herein. In some implementations, the system may use machine learning and / or artificial intelligence along with the sensors, or any other inputs described herein, to determine breakthrough signature inputs. For example, a motion or posture sensor disclosed herein may facilitate providing the first or third breakthrough signature input 306, 310. As another example, a bioelectrical sensor may facilitate providing the second breakthrough signature input 308. In some implementation, one of the breakthrough signatures may include a geographical location change, a pressure change, etc. In some embodiments, the breakthrough signature may be based on a combination of sensor inputs, for example, the motion or posture sensor input and the bioelectrical sensor input. In one example, the motion or posture sensor input may indicate that the patient is sleeping, but the bioelectrical sensor input indicates increased activity, which may indicate a muscle contraction. In that case, the system disclosed herein may interpret that the patient is likely waking up and walking to the bathroom, which may trigger a different stimulation program than the background stimulation at nighttime. As another example, the breakthrough signature indicating a stress urinary incontinence event may include a combination of a motion sensor input (e.g., indicating a motion shock) and a bioelectrical sensor input (e.g., indicating a muscle contraction). In another example, even though the bioelectrical sensor input may trigger a higher level of stimulation, data from the motion sensor may overwrite the triggering. Depending on the adaptive profile(s) assigned to be activated, the IPG processor 300 may operate to automatically switch from an assigned background program to a different stimulation program 312 upon receiving one or more of the breakthrough signature inputs disclosed herein. In other words, the sensors disclosed herein can provide multiple independent actions in detecting one or more breakthrough signatures, and / or be merged, which may be for greater specificity in detecting other breakthrough signatures and / or for reduction stimulation artifact and / or lock up of the stimulation programs.

[0157] The system disclosed herein can allow multiple stimulation programs to be saved to the IPG processor 300. In some instances, the predefined thresholds, which may include specific biomarkers, may be defined by a clinician using a software program on the external device disclosed herein. The predefined thresholds may be adjusted when the patient revisits the clinician and / or when the external device running the software program establishes communication with the IPG. In some cases, other stimulation parameters (e.g., frequency, amplitude, pulse width, duration, safety / comfort features, etc.) may be defined by a clinician using the software program. The parameters may be adjusted by the clinician when the patient revisits the clinic and / or when the external device disclosed herein running the software program establishes communication with the IPG. In some instances, certain parameters may be adjusted by the patient using the controller and / or an external device disclosed herein. In someimplementations, the system may use machine learning and / or artificial intelligence, and using any of the inputs described herein, to automatically determine and / or set stimulation parameters (e.g., frequency, amplitude, pulse width, duration, safety / comfort features, or combinations thereof) for any of the stimulation programs described herein.

[0158] Additional details of the time-dependent adaptive stimulation will now be described. The adaptive stimulation can be effective in improving reduction of both urge incontinence events and stress incontinence events. Several embodiments disclosed herein may include adaptive nerve stimulation (for example, pudendal nerve stimulation) that may toggle between a first, background level and a second, higher level. The background level and the higher level may include different stimulation programs. In one example, the background level is a basal stimulation, and the higher level is a boost stimulation. The background and higher levels may differ in at least one stimulation parameter. Examples of such stimulation parameters may include but are not limited to frequency, pulse width, amplitude, or any combinations thereof. In some embodiments, the higher level may include a higher frequency in the stimulating electrical current than the background level. According to several embodiments, the higher level stimulation is higher in one, two or all of frequency, pulse width, and amplitude (as compared to any background level assigned to certain time).

[0159] In some implementations, the background or higher level includes a fixed pulse width and / or a fixed amplitude. In some implementations, the background or higher level may include variable pulse widths and / or variable amplitudes. In some embodiments, the higher level has a ramp up from the background level or another higher level and / or a ramp down from the background level or another higher level, so that one, two or all of frequency, pulse width, and amplitude increase and / or decrease gradually. The ramp may be about 0.01 to about 3 mA per pulse, or about 0.2 mA per pulse, about 0.4 mA per pulse, about 0.6 mA per pulse, about 0.8 mA per pulse, about 1 mA per pulse, about 1.2 mA per pulse, about 1.4 mA per pulse, about 1.6 mA per pulse, about 1.8 mA per pulse, about 2 mA per pulse, about 2.2 mA per pulse, about 2.4 mA per pulse, about 2.6 mA per pulse, about 2.8 mA per pulse, about 3 mA per pulse, or any value within a range defined by these values.

[0160] In one embodiment, tri-level stimulation is provided in adaptive stimulation, where a third stimulation program is provided with a third, highest level stimulation that is higher than the second level. The third stimulation level may be higher than the second stimulation level to address a patent's needs and / or to reduce habituation, with additional details described elsewhere herein. The third stimulation level may be constant or varied. In some implementations, the second stimulation level may be triggered by determining a breakthrough signature from the bioelectric sensor (e.g., when the patient squeezes a muscle), and the third stimulation level may be triggered when the readings from the motion or posture sensor indicate that the event is a sever event, such as a severe refractory urge incontinence. In some implementations, more than three levels of stimulation (e.g., an infinite number of levels of stimulation) may be provided in adaptive stimulation, with additional details described elsewhere herein. In some embodiments, the stimulation program may include two, or more than two (e.g., 3, 4, 5, 6 or more) stimulation levels in response to different strengths in the sensor input and / or the different types of sensor input, including but not limited to the patient's level of activity, sensitivity, etc. In some embodiments, the stimulation levels are tiered. For example, a first parameter of a sensor may trigger a first stimulation level different from a background stimulation level; a second parameter of the sensor and / or a parameter of a different sensor may trigger a second stimulation level different from the background stimulation level and the first stimulation level, and so on. In other embodiments, the stimulation levelsinclude increases in stimulation parameters on a continuum. For example, the system disclosed herein may use an equation, matrix, or any mathematical model to generate a stimulation level different from a ground stimulation level based on one or more sensor parameters. As a result, the stimulation level may vary along a sliding scale.

[0161] In some implementations, the first, background level may include a frequency of about 1 Hz to about 50 Hz, or a stimulating frequency of about 2 Hz, about 4 Hz, about 6 Hz, about 8 Hz, about 10 Hz, about 12 Hz, about 14 Hz, about 16 Hz, about 18 Hz, about 20 Hz, about 22 Hz, about 24 Hz, about 26 Hz, about 28 Hz, about 30 Hz, about 32 Hz, about 34 Hz, about 36 Hz, about 38 Hz, about 40 Hz, about 42 Hz, about 44 Hz, about 46 Hz, about 48 Hz, or about 50 Hz, or any frequency within a range defined by these values. In some implementations, the first mode may include a frequency of about 1 Hz to about 150 Hz, or a stimulating frequency of about 5 Hz, about 10 Hz, about 15 Hz, about 20 Hz, about 25 Hz, about 30 Hz, about 35 Hz, about 40 Hz, about 45 Hz, about 50 Hz, about 65 Hz, about 70 Hz, about 75 Hz, about 80 Hz, about 85 Hz, about 90 Hz, about 95 Hz, about 100 Hz, about 105 Hz, about 110 Hz, about 115 Hz, about 120 Hz, about 125 Hz, about 130 Hz, about 135 Hz, about 140 Hz, about 145 Hz, or about 150 Hz, or any frequency within a range defined by these values.

[0162] In some implementations, the second, higher level may include a frequency of about 50 Hz to about 1,000 Hz, or about 100 Hz to about 800 Hz, or about 200 Hz to about 500 Hz, or a stimulating frequency of about 50 Hz, about 60 Hz, about 70 Hz, about 80 Hz, about 90 Hz, about 100 Hz, about 110 Hz, about 120 Hz, about 130 Hz, about 140 Hz, about 150 Hz, about 160 Hz, about 170 Hz, about 180 Hz, about 190 Hz, about 200 Hz, about 210 Hz, about 220 Hz, about 230 Hz, about 240 Hz, or about 250 Hz, or any frequency within a range defined by those values. In some embodiments, the higher level(s) may include a frequency of about 50 Hz to about 1,000 Hz, or about 100 Hz to about 800 Hz, or about 200 Hz to about 500 Hz, or a stimulating frequency of about 50 Hz, about 60 Hz, about 70 Hz, about 80 Hz, about 90 Hz, about 100 Hz, about 110 Hz, about 120 Hz, about 130 Hz, about 140 Hz, about 150 Hz, about 160 Hz, about 170 Hz, about 180 Hz, about 190 Hz, about 200 Hz, about 210 Hz, about 220 Hz, about 230 Hz, about 240 Hz, or about 250 Hz, or any frequency within a range defined by those values. In some implementations, the second mode may include a frequency of about 1 Hz to 10 kHz, or a stimulating frequency of about 500 Hz, about 1,000 Hz, about 1,500 Hz, about 2,000 Hz, about 2,500 Hz, about 3,000 Hz, about 3,500 Hz, about 4,000 Hz, about 4,500 Hz, about 5,000 Hz, about 6,500 Hz, about 7,000 Hz, about 7,500 Hz, about 8,000 Hz, about 8,500 Hz, about 9,000 Hz, about 9,500 Hz, or about 10,000 Hz, or any frequency within a range defined by these values.

[0163] As disclosed herein with the breakthrough signatures, the second stimulation, or the higher level(s) of stimulation is(are) controlled by a breakthrough signature from the patient in some embodiments by, for example, a voluntary and / or involuntary patient movement (squeezing of muscles, engaging in certain physical activities including but not limited to heavy coughing, laughing, heavy movements, or tapping the device, or using an external device to control stimulation, such as a smartphone, wearable, or other device). The breakthrough signature may be detected by the motion or posture sensor, the bioelectrical sensor, or another sensor disclosed herein, or any combinations thereof. In some implementations, one sensor may detect the breakthrough signature using different adaptive profiles, which is described elsewhere in the present disclosure. In some embodiments, the second or higher levels of stimulation may be triggered based on a location of the patient, for example, by the patient arriving at home. The location of the patient may be determined by a GPS sensor, which may be embedded on the IPG or the one ormore leads, or a GPS signal from the patient's cellphone or wearable transmitted to the IPG. In some embodiments, ambulation of the patient may be detected, e.g., by the GPS and / or the motion or posture sensor. Ambulation detection may be helpful for determining periods of time when the patient is mostly stationary and periods of time when the patient is out and about. With the flexibility in the selection of sensor input, multiple levels of stimulation may be provided to a patient, for example, based on the patient's activity level, time of the day, sensitivity to stimulation, and the like.

[0164] In some instances, the processor of the IPG may implement the background level automatically based on the program assignment input in the absence of a breakthrough signature for increasing to the higher level(s) and / or in the presence of a breakthrough signature for returning the background level.

[0165] The higher level (s) may be run for only a few seconds, while the background level may be run for hours. In some embodiments, when triggered, the higher level is applied for about one second to about one minute, or about several seconds to about 30 seconds, or about 2-5 seconds, or about 30-60 seconds, or a duration within a range defined by any of these values. In some implementations, a duration of less than ten seconds may be effective for preemptively stopping a stress event. In some implementations, a duration of about 30 seconds may be effective for preemptively stopping an urge event (e.g., lasting for a duration long enough for a person to reach the toilet). In certain stimulation programs the higher stimulation level may be provided for a longer period of time than a few seconds so that the patient needs not activate the higher stimulation level as frequently for a period of time. For example, a wake up program may be personalized for a mother with birth trauma and is getting her children ready for school. As disclosed herein elsewhere, the wake-up hours may be high risk hours for incontinence events. Instead of repeatedly activating the higher stimulation levels during those hours with each higher stimulation level lasting a short duration (e.g., no more than 30 seconds), the wake up program may provide the higher stimulation level for a longer duration (e.g., for more than one minute) in those wake up hours. In some embodiments, the second or a higher level of stimulation is applied for a total of 30 seconds to 60 minutes per day. In some embodiments, the second or a higher level of stimulation may be triggered at least about 5 times to about 25 times per day, or at least about 10 times to about 20 times per day, or any number of times within a range defined by these values.

[0166] As shown in Figure 4, any number of the breakthrough signature(s) may be assigned according to the time of the day. A visual representation of a 24-hour based program assignment element according to one embodiment is shown in Figure 4. One or more adaptive profiles may be assigned to any of the time windows 400 in the program assignment element. In some embodiments, a time window may be a 30 minute interval. In other embodiments, another suitable duration may be used for a time window, such as about 10 minutes, 20 minutes, 1 hour, 2 hours, 3 hours, 4 hours, or any duration within a range defined by those values. In some implementations, the 24 hours may be evenly divided among the time windows. In some implementations, the time windows may have varying sizes. For example, during nighttime when the patient is sleeping, the time window may include a 2 hour, 3 hour, 4 hour, 5 hour, 6 hour, or longer interval. In some embodiments, the systems and methods disclosed herein automatically adjusts the time-based program assignments to the time zone in which the system is located, which may be advantageous for traveling, or to time changes due to daylight savings, etc. In some embodiments, the automatic adjustment to the clock by the systems and methods disclosed herein may include gradual adjustments to the timebased program assignments to make the changes less abrupt for the patient. For example, when the patient travelsfrom Pacific Time to Eastern Time, the clock and / or the time-based program assignments may be shifted by a duration that is less than the actual time difference (that is, three hours in this case) initially such that the clock and the timebased program assignments are fully adjusted to the new time or new time zone within a certain time (for example, within 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, etc. or any value within ranges defined by those durations) after arriving at the new time zone or after the time change.

[0167] Embodiments disclosed herein include more than one adaptive profile for one or more of the sensors disclosed herein. In the illustrated embodiment such as shown in Figure 4, the motion or posture sensor (M) may include two motion adaptive profiles, M1 and M2. Additionally, or alternatively, the bioelectrical sensor (S) may include two adaptive profiles, S1 and S2. In some implementations, M1 and M2 may differ in terms of whether the motion or posture sensor is in a motion detection mode or a posture detection mode. In some implementations, S1 and S2 may differ in terms of the different biomarkers (e.g., power in a frequency band, amplitude, etc.) monitored. In some embodiments, one or more sensors disclosed herein may include more than two adaptive profiles. In some embodiments, a breakthrough signature may include more than one adaptive profile as disclosed elsewhere herein.

[0168] The neuromodulation system disclosed herein may advantageously provide flexibility in the assignment of background models and adaptive profiles. The flexibility may allow the therapy to be more tailored to the patient's circadian rhythm and other needs. For ease of reference, an adaptive profile based on the biopotential signal may be referred to as a "sense adaptive profile” and an adaptive profile based on the signal from the motion or posture sensor may be referred to as a "motion adaptive profile.” The sense adaptive profile may be more accurate in predicting whether the higher level should be trigger than the motion adaptive profile. The motion adaptive profile may include more false positives and / or false negatives than the sense adaptive profile. However, the sense adaptive profile may consume more battery power than the motion adaptive profile. Other adaptive profiles based on other sensors disclosed herein may be included in some embodiments. For example, another sensor may monitor other bio-indicators and / or biomarkers for incontinence, e.g., a pressure sensor or catheter for measuring the bladder fullness (bladder filling cystometry). The flexibility in the assignment of the background programs and adaptive profiles may allow more optimal battery management while maintaining or improving therapeutic effect of the system. In some implementations, the system may use machine learning and / or artificial intelligence, and using any of the inputs described herein, to automatically determine and / or set the optimal adaptive profile(s) to be used in a given time period.

[0169] In some embodiments, one motion adaptive profile (e.g., M1) may use a motion based breakthrough signature (e.g., single tap or double tap on the IPG) to increase to the higher level. In some embodiments, another motion adaptive profile (e.g., M2) may use posture change to increase to the higher level. These different profiles can be mapped to different times of the day. In some embodiments, one motion adaptive profile may be assigned to daytime and another motion adaptive profile may be assigned to nighttime. In some embodiments, the higher level triggered by the different motion adaptive profiles needs not be the same stimulation program. In some embodiments, the system may only implement stimulation programs assigned based on time-dependency and motion adaptive profiles as disclosed herein. For example, the system may include different background stimulation levels based on different time of the day (such as daytime and nighttime, etc.) and may trigger a different stimulation level in response to user input detected by the motion or posture sensor, such as tap, double tap, or other tap sequences.

[0170] In some implementations, the sense adaptive profiles may be used during daytime or portions of the daytime, or the most active hours (which are patient specific and may not always be during the daytime). The sense adaptive profiles may be turned on concurrently with the motion adaptive profiles, for example, at high risk time periods. In some embodiments, the sense adaptive profiles may be turned off during non-active hours, for example, when the patient is sleeping. In some implementations, different sense adaptive profiles (for example, two or more) may be used depending on the time of the day. For example, a first sense adaptive profile may be used for the most active hours of the day and a second sense adaptive profile may be used during sleep. The different sense adaptive profiles may include different thresholds. In some embodiments, the higher level triggered by the different sense adaptive profiles needs not be the same stimulation program.

[0171] In some instances, the postural data may be used to differentiate muscle contractions. The first sense adaptive profile may be configured to determine a first biopotential breakthrough signature, which is a first muscle contraction. The second sense adaptive profile may be configured to determine a second biopotential breakthrough signature, which is a second muscle contraction. In some embodiments, the first and second muscle contractions may be contractions of different strength and / or duration of the same muscle due to the different postures of the patient. In some embodiments, the first and second muscle contractions may be contractions of different muscles due to the different postures of the patient. The system (e.g., the processor of the IPG or another processor) may determine the subject's posture using the motion or posture sensor disclosed herein. The posture may include two or more of a supine position, a prone position, a left lateral recumbent position, a right lateral recumbent position, standing, sitting, and the like. Based on the determined posture, the system may activate one of the first or second biopotential breakthrough signature. The system may be triggered from the background stimulation level to a higher level in response to either the first or second biopotential breakthrough signature.

[0172] In some cases, the postural data may be used to confirm whether the patient's circadian schedule has shifted from the previous schedule. For example, if a sleep mode is assigned as a background mode at a certain hour for a patient, but the postural data indicates that the patient is not lying down, the assignment of the background mode for that hour may need to be adjusted.

[0173] Figures 5A-5C illustrate non-limiting time-dependent adaptive stimulation use case examples for different patients. As shown in Figure 5A, the background modes may include a day background (from about 0800 hour to about 0000 hour) and a night background (from about 0000 hour to about 0800 hour the next day) for this patient with urinary incontinence. In some embodiments, depending on the patient, the daytime background stimulation program or mode may be different from the nighttime background program or mode in at least one of the parameters and / or settings. In some embodiments, depending on the patient, the daytime background stimulation program may have the same parameters and / or settings as the night background stimulation program. As also shown in Figure 5A, adaptive stimulation may be activated for the entire 24 hours of a day for this patient. The daytime adaptive profile may have different parameters and / or settings than the nighttime adaptive profile. Additionally, or alternatively, the daytime adaptive profile may be based on a biopotential signal (e.g., band power, amplitude, etc.) from the bioelectrical sensor. In contrast, the nighttime adaptive profile may be based on a signal from the motion or posture sensor (e.g., an accelerometer). In either adaptive profile, the signal from the respective sensor may be indicative of breakthrough signatures described elsewhere in the present disclosure. The breakthrough signatures during the daytime mayinclude a biomarker (e.g., band power, amplitude, etc.) exceeding a threshold due to the patient squeezing a muscle. The breakthrough signatures during the nighttime may include the patient getting up from a lying down position or the patient tapping on the IPG, each of which may be due to a need to use the bathroom.

[0174] For another patient such as shown in Figure 5B, the nighttime background mode 500 may be assigned between about the 2200 hour to about the 0200 hour. The duration of sleep for this patient is shorter than the first patient as shown in Figure 5A. The patient as shown in Figure 5B may go to bed earlier and wake up earlier than the patient as shown in Figure 5A. The daytime background mode 502 may be assigned to the hours outside the 2200 hour to 0200 hour range, except where a high risk mode 504 may be assigned to certain hours during the daytime. For example, in the illustrated example as shown in Figure 5B, the high risk mode 504 may be assigned between about the 0630 hour to about the 0830 hour (which may correspond to when the patient has just woken up and is going through morning routines) and between about the 1930 hour to about the 2030 hour (which may correspond to post dinner / evening activity time). This patient may have the highest incontinence rate during the wake-up routine hours and the post dinner hours. In the night background mode 500 for this patient, stimulation may be turned off or at a background level, and an adaptive profile based on the signal from the motion or posture sensor may be activated for the breakthrough signatures disclosed herein. This night background mode 500 may be effective for this patient with minimum battery usage from the motion or posture sensor. In the daytime background mode 502, a background stimulation program or background level may be activated (e.g., to reduce or avoid urge incontinence) and the adaptive profile based on the motion or posture sensor may be turned on for periodic stress issues. For this patient, the periodic stress issues may occur with low probability (e.g., less than once an hour, or once every two hours, or once every three hours, or once every four hours, etc.). In the high risk mode 504, the background stimulation program may include a higher stimulation level (e.g., higher frequency, amplitude, and / or pulse width), which may reduce or avoid urge incontinence more effectively, and the adaptive profile based on the bioelectrical sensor may be turned on to address the periodic stress issues. In the high risk mode 504, the threshold for breakthrough signatures (e.g., using a classifier and / or using input from the posture sensor, as described elsewhere in the present disclosure) may be adjusted to avoid false positives and / or excess battery use.

[0175] For yet another patient such as shown in Figure 5C, the nighttime background mode 510 may be assigned between about the 2000 hour to about the 0530 hour. The duration of sleep of this third patient is similar to the first patient as shown in Figure 5A but the sleep hours are shifted earlier by about two hours. The daytime background mode 512 may be assigned to the hours outside the 2000 hour to 0530 hour range, except where a high risk mode 514 may be assigned to certain hours of the day. The high risk mode 514 is assigned to a different time period for this patient than for the patient in Figure 5B. As shown in Figure 5C, the high risk mode 514 assignment has been tuned in a patient-specific manner based on a symptom time profile. For example, in the illustrated example as shown in Figure 5C, the high risk mode 514 may be assigned between about the 0830 hour to about the 1000 hour, which may correspond to the time period with the highest rate of incontinence for this patient. In the night background mode 510 for this patient, stimulation may be at a background level or turned off, and an adaptive profile based on the signal from the motion or posture sensor may be activated for the breakthrough events disclosed herein. This night background mode 510 may be effective for this patient with minimum battery usage from the motion or posture sensor. In the daytime background mode 512, a background stimulation program or background level may be activated (e.g.,to reduce or avoid urge incontinence) and the adaptive profile based on the motion or posture sensor may be turned on at least for periodic stress issues. For this patient, the periodic stress issues may occur with low probability (e.g., less than once an hour, or once every two hours, or once every three hours, or once every four hours, etc.). In the high risk mode 514, the background stimulation program may include a high stimulation level (e.g., higher frequency, amplitude, and / or pulse width), which may reduce or avoid urge incontinence more effectively, and the adaptive profile based on the bioelectrical sensor may be turned on address to the periodic stress issues. In the high risk mode 514, the threshold for breakthrough events (e.g., using a classifier or using input from the posture sensor, as described elsewhere in the present disclosure) may be adjusted to avoid false positives and / or excess energy use.

[0176] In some embodiments, the daytime background, nighttime background, and / or high risk modes for the patients in Figures 5A-5C may have different stimulation parameters and / or settings. In some embodiments, switching between the daytime background, nighttime background, high risk, and / or any other time-dependent modes disclosed herein, may have a ramp up and / or a ramp down depending on the stimulation parameters, so that one, two or all of frequency, pulse width, and amplitude increase and / or decrease gradually. For example, the ramp may be about 0.01 to about 3 mA per pulse, or about 0.2 mA per pulse, about 0.4 mA per pulse, about 0.6 mA per pulse, about 0.8 mA per pulse, about 1 mA per pulse, about 1.2 mA per pulse, about 1.4 mA per pulse, about 1.6 mA per pulse, about 1.8 mA per pulse, about 2 mA per pulse, about 2.2 mA per pulse, about 2.4 mA per pulse, about 2.6 mA per pulse, about 2.8 mA per pulse, about 3 mA per pulse, or any value within a range defined by these values.

[0177] In several embodiments, the system disclosed herein may use artificial intelligence and / or machine learning model(s) to predict when a patient gets up and thereby assign the higher background level stimulation to be run independent of and / or in addition to an adaptive profile. For example, if the patient typically gets up on Mondays between the 0645 hour and the 0715 hour, the system can automatically begin the higher level stimulation at the 0630 hour. As another example, if the patient typically gets up between the 0745 hour to the 0800 hour, the system can automatically begin the higher level stimulation at the 0730 hour. The patient may override the automatic higher level stimulation using any of the safety and / or comfort features described elsewhere in the present disclosure. In some implementations, the artificial intelligence and / or machine learning model(s) may be trained with postural data from the motion or posture sensor to learn about the wakeup time of the patient. Additionally or alternatively, the artificial intelligence and / or machine learning model(s) may be trained with patient responses to a questionnaire about the patient's daily schedule.

[0178] In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application PCT / EP2025 / 080505, which is hereby incorporated by reference in its entirety, can be used with the time-dependent programming disclosed herein.Personalized Thresholds for Breakthrough Signature

[0179] In some embodiments, the thresholds for entering the higher level stimulation from the background level may be patient specific or personalized. For example, one person's tapping may result in a different reading from the motion sensor than another person's tapping. As another example, the EMG signal from one person squeezing the pelvic floor or other muscles may be different from another person squeezing the same muscles.

[0180] In some implementations, the threshold for what is considered the patient movement and / or posture that may trigger the higher level may be determined by asking patient to perform the different types of breakthrough signatures described herein after the IPG and the lead(s) have been implanted in the patient. Patientspecific data including but not limited to readings from the sensors disclosed herein (including but not limited to the motion or posture sensor and the bioelectrical sensor) as the patient is performing those breakthrough signatures may be recorded. The appropriate threshold for a particular patient performing a particular breakthrough signature may be determined based on the readings collected. In some embodiments, the sensor readings may be analyzed in the time domain and / or the frequency domain to identify features in the sensor readings that may be indicative of the particular breakthrough signature performed by the patient. The features may include time-domain features, frequency domain features, statistical features, and any combinations thereof. In some instances, a classifier (see, e.g., Figures 6, 7A, and 17) may be trained with the collected readings to improve accuracy in detection of the breakthrough signature, as described elsewhere in the present disclosure. In some cases, the classifier may automatically output recommendations of an adaptive profile configuration based on the sensor data. In some embodiments, the classifiers can be optimized using a machine learning algorithm (e.g., using artificial intelligence or machine learning). In one example, the process implemented by the machine learning algorithm may include Bayesian Optimization to search the classifier space and look to optimize it against a cost function (e.g., F-1 score for classifier versus power required).

[0181] In some instances, the threshold for detecting a particular breakthrough signature may be such that an increasing sensor reading exceeding the threshold may result in an increase to the higher level and a decreasing sensor data falling below the threshold may result in returning to the background level. In other instances, the threshold may only trigger the higher level and the system may automatically fall back to the background level after a predetermined amount of time. The higher level may only last seconds, while the background level may be hours. In some embodiments, the higher stimulation is applied for 1 second, 2 second, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, 30 seconds, 1 minute, 5 minutes, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 60 minutes per day, or any duration within a range defined by those values. In other instances, the threshold for triggering the higher level may be a different value / sensor profile than the threshold for triggering a return to the background level. In other instances, any combinations of the thresholds disclosed herein may be applied and multiple higher levels of stimulation may be triggered by different types of thresholds disclosed herein. In some embodiments, the detection of a breakthrough signature may be based on more than one threshold and / or different criteria than a threshold, for example, using fuzzy logic and membership function. In some instances, a confidence value for the threshold-based determination may be calculated such that the breakthrough signature is detected only if the confidence value that a threshold has been exceeded is greater than a certain percentage.

[0182] Embodiments disclosed herein may include other patient-specific configurations, such as based on the patient's medical condition and / or changes in a person's physical conditions. For example, the type of patient movement that may precede an event (e.g., a urinary or fecal incontinence event), in other words, the incontinence triggering pattern may be different among patients. Therefore, the threshold for the higher level (motion or sense adaptive profile) may be set lower for a patient who experiences stress incontinence from daily movements (e.g., walking, carrying bags of groceries, squatting down, etc.), whereas the threshold for the higher level may be set higher for someone who has stress incontinence only in certain heavy movements (e.g., jumping, heavy sneezes, etc.). Asanother example, in the case of sense adaptive profile, if a patient has been strengthening the pelvic floor with physiotherapy, exercise, and / or surgery, the corresponding threshold may be updated. In one implementation, the threshold may be the amplitude of an electrophysiological signal, e.g., an EMG signal. With strengthened pelvic floor muscles, the amplitude threshold value may be reduced in some patients. In contrast, for another patient, after the pelvic floor has been strengthened, the patient's medical condition (e.g., a urinary or fecal incontinence event) may have lessened. For that patient, the "on time” of the higher level, when triggered, may be reduced, and / or the sense adaptive profile may be mapped to fewer time windows to further improve battery life of the IPG and patient comfort. As another example, the patient-specific thresholds may take into account whether the patient is nocturnal. As disclosed elsewhere in the present disclosure, micturition frequency may be decreased and the natural inhibitory mechanism may be active at nighttime. For nocturnal patients, the threshold for triggering a higher level of stimulation at night may be different from the threshold for triggering a higher level of stimulation in a patient with diurnal rhythms.

[0183] In some embodiments, the motion or posture sensor and / or the sensing electrode may be turned on all the time. In some implementations, activation of any of the adaptive profiles disclosed herein may not require assigning the profile to a particular time of the day. In some instances, the adaptive profile may be activated upon user command, for example, via the breakthrough signatures, when no adaptive profile is assigned to a time window.

[0184] In some embodiments, in addition to personalized thresholds, the systems and methods disclosed herein may include a patient-specific or personalized stimulation program or level based on the personalized sensor threshold. The stimulation program may include more than two stimulation levels in response to different strengths in the sensor input, the different types of sensor input, including but not limited to the patient's level of activity, sensitivity, etc. In some embodiments, the more than two stimulation levels may be tiered. For example, different levels of biopotential signals may trigger different stimulation levels or programs in different patients. As another example, there may be three or more different stimulation levels based on the strength of the biopotential signals and / or time-based rules. As yet another example, a trigger based on bioelectrical sensor data may provide a first higher level of stimulation and a trigger based on the motion or position sensor may provide a second higher level of stimulation, with the first level being lower than the second level. In other embodiments, the more than two stimulation levels may include increases in stimulation parameters on a continuum. For example, templates of different stimulation levels may be available for patients to choose from so as to customize to the patient's activity level, circadian rhythm, sensitivity to stimulation, and the like. In some embodiments, the template may be available at a doctor's office and / or stored on an electronic database that is accessible to patients. In several embodiments, the programming of the different stimulation levels may be tied to an electronic bladder diary. In some embodiments, the different stimulation levels or programs may differ in one or more stimulation parameters, including but not limited to amplitude, frequency, pulse width, and the like.

[0185] In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application PCT / EP2025 / 080505, which is hereby incorporated by reference in its entirety, can be used with any one or more of the personalized thresholds disclosed herein.

[0186] In several embodiments, adaptive nerve stimulation disclosed herein (e.g., pudendal nerve stimulation) may treat patients with unmet clinical needs, including patients with mixed urinary incontinence (MUI)failing first-line therapies (e.g., bladder training and / or pelvic floor muscle training) and / or patients with urge urinary incontinence (UUI) failing first and second line therapies (e.g., sacral neuromodulation with or without botulinum toxin injection). Patients with UUI failing second line therapies may be considered to have severe refractory UUI. In some cases, those patients may be implanted with the system disclosed herein, including the IPG and two quadripolar electrode leads. In some embodiments, the leads may be placed on the trunk (e.g., the Alcock's canal) and anterior pudendal nerve (e.g., a distal pudendal nerve) using radiological guidance and intraoperative electromyography (EMG) of the pelvic floor muscles (PFM) and external anal sphincter (EAS). Specific EMG findings associated with the adaptive stimulation disclosed herein may provide confirmation of correct placement during the implantation surgery.

[0187] In several embodiments, the stimulation may be monophasic (e.g., with a pulse width of about 200 pis) stimulation. A first stimulation level may include a frequency at about 15 Hz. A second stimulation level may include a frequency at about 40 Hz. A combination of the bioelectrical sensor and the motion or posture sensor (e.g., an accelerometer) disclosed herein may cause the stimulation to change from the first level to a second level. In other embodiments, the stimulation may be biphasic. In some implementations, the biphasic stimulation may require a lower motor threshold, that is, the minimum amount of electrical stimulation needed to cause a muscle to response, compared to the monophasic stimulation.

[0188] Some embodiments disclosed herein may include reviewing the patient outcomes at a desired time period post therapy (e.g., 1, 3, 6 months, 12 months, etc.) and adjusting therapy or recalibrating based on such reviewed outcomes. Such outcomes include but are not limited to: safety (primary outcome), surgical feasibility, physiological (e.g., urodynamic testing) and / or clinical efficacy (e.g., voiding diaries, questionnaires, etc.). In some instances, positive results from voiding diaries may be confirmed by quality of life questionnaires (e.g., dropping by one or more severity categories in the quality of life questionnaires such as the ICIQ GAB OoL and / or the ICIQ Ul SF). In some instances, pudendal nerve stimulation disclosed herein may lead to immediate and sustained (for example, up to about six months) effects on bladder and urethral physiology.

[0189] In some implementations, incontinence patients using the adaptive stimulation disclosed herein may regain complete continence. Some of those patients may previously experience from about 5.7 incontinence events / day, and may have no incontinence event throughout the day, or may have reduction in incontinence events by 95%, 96%, 97%, or more, or any values within the ranges defined by those values, by using the adaptive stimulation disclosed herein. In some implementations, patients may show improvement by at least about 90% after using the adaptive stimulation disclosed herein. In some implementations, patients may show improvement by reducing the number of incontinence events / day from about 3-9 to about 0-4.7, or from about 6 to about 1.8, after using the adaptive stimulation disclosed herein. In some embodiments, patients may show improvement by reducing the number of incontinence events / day by at least about 50%. In some embodiments, the improvements disclosed herein may last for at least about six months.

[0190] In some implementations, MUI patients using the adaptive stimulation disclosed herein may regain complete continence. Some of those MUI patients may previously experience from about 6.2 incontinence events / day, and may have no incontinence event throughout the day by using the adaptive stimulation disclosed herein. In some implementations, MUI patients may show improvement by about 90% after using the adaptive stimulation disclosed herein. In some implementations, MUI patients may show improvement by reducing the number ofincontinence events / day from about 6.2 to about 1.3, or about 1.5, or about 1.9, or about 2.1 (or any values within ranges defined by those values) after using the adaptive stimulation disclosed herein. In some implementations, MUI patients may show improvement by reducing the number of incontinence events / day by about 50%, or about 65%, or about 70%, or about 80%, or any values within ranges defined by those values. In some embodiments, the improvements disclosed herein may last for at least about six months.

[0191] In some implementations, a refractory urge urinary incontinence (rUUl) patient using the adaptive stimulation disclosed herein may regain complete continence. Some of those rUUl patients may previously experience from about 4.8 incontinence events / day, and may have no incontinence event throughout the day by using the adaptive stimulation disclosed herein. In some implementations, rUUl patients may show improvement by greater than about 90% after using the adaptive stimulation disclosed herein. In some implementations, rUUl patients may show improvement by reducing the number of incontinence events / day from about 4.8 to about 1.4, or about 1.6, or about 1.8 or any values within ranges defined by those values, after using the adaptive stimulation disclosed herein. In some implementations, rUUl patients may show improvement by reducing the number of incontinence events / day by about 50%, or about 65%, or about 70%, or about 80%, or any values within ranges defined by those values. In some embodiments, the improvements disclosed herein may last for at least about six months.

[0192] In addition to its effect on incontinence, the adaptive stimulation disclosed herein in several embodiments has an immediate and / or sustained positive effects on bladder capacity. In some embodiments, a patient who has used the adaptive stimulation disclosed herein for a period of time may show a significant increase in mean baseline MCC with a first level stimulation (as compared to their measured MCC before being stimulated with embodiments described herein). Additionally, the patient's MCC may show further increments with adaptive stimulation (such as a second or higher levels of stimulation). In some example, a patient may start with a baseline MCC of about 122 ml to about 346 ml. With the first level stimulation, the MCC may be increased to about 171 ml to about 439 ml, or about 173 ml to about 509 ml. With the second or higher levels of stimulation, the MCC may be increased to about 218 ml to about 498 ml, or about 203 ml to about 553 ml.

[0193] Using a first stimulation level (e.g., background level of stimulation) according to several embodiments described herein increases a patient's baseline MCC (as measured pre-stimulation) by 20-80% (e.g., 20-50%, 50-70%, 60-80%, and overlapping ranges therein). Using a second stimulation type (e.g., higher levels of stimulation) according to several embodiments described herein increases a patient's baseline MCC (as measured pre-stimulation) by 40-100% or more (e.g., 40-50%, 50-60%, 70-80%, 70-90%, 80-100%, and overlapping ranges therein). Using the higher levels of stimulation according to several embodiments described herein provides increases of 5-25% as compared to the first level stimulation (e.g., 5-10%, 5-15%, 10-25%, and overlapping ranges therein).

[0194] In some embodiments, provided herein are systems and methods to increase a baseline MCC by 25-70% after a background level of stimulation and by 50-100% after a higher level of stimulation. Such increased capacity may be temporary or sustained over a period of days, weeks, months and years. In one embodiment, the increase in MCC with the background level of stimulation is sustained over at least 6 months and the increase in MCC with the higher level of stimulation is temporary or more short-lived (e.g., days). In some embodiments, a patient who has used the adaptive stimulation disclosed herein may show increased baseline bladder capacity by about 25% to about 50% with the background level of stimulation (e.g., immediately post-operatively or soon after). In someembodiments, a patient who has used the adaptive stimulation disclosed herein may show increased baseline bladder capacity by about 50% to about 80% with the higher level of stimulation (e.g., immediately post-operatively or soon after). In some embodiments, a patient who has used the adaptive stimulation disclosed herein may show increased baseline bladder capacity by about 35% to about 70% with the background level of stimulation after usage for a period of time (e.g., about 4 months to about 8 months). In some embodiments, a patient who has used the adaptive stimulation disclosed herein may show increased baseline bladder capacity by about 50% to about 90% with the higher level of stimulation after usage for a period of time (e.g., about 4 months to about 8 months).

[0195] In some embodiments, provided herein are systems and methods to improve incontinence by 20-100% (e.g., 23-100%, 20-90%, and overlapping ranges therein). In some embodiments, the systems and methods disclosed herein reduce incontinence events by 20-100% (e.g., 23-100%, 20-90%, and overlapping ranges therein).

[0196] In some embodiments, provided herein are systems and methods to improve quality of life as evidenced in reduction in ICIQ-OAB-QoL and / or ICI Q-UI-SF scores, for example, a reduction of those scores by about 40% to about 60%, or about 50% to about 55 %, or any overlapping ranges.Motion and Sense Adaptive Profiles

[0197] Embodiments disclosed herein, such as shown in Figures 6 and 7A-7C, may include use of classifiers for detection of triggers for a particular stimulation program. Figure 6 illustrates example motion adaptive profile 600 based on an onboard 3-axis inertial sensor (e.g., accelerometer) 602 and its associated inertial (motion) classifier 604, although similar logic may be used for other types of motion or posture sensors (e.g., gyroscope, piezoelectric) or classifiers. The motion adaptive profile 600 may include inertial classifier parameters, trigger / time interlock parameters, and / or stimulation parameters. The inertial classifier 604 and the inertial sensor 602 may form an inertial processor 606. In some implementations, the inertial classifier 604 may be part of the IPG processor.

[0198] The inertial classifier 604 can detect various breakthrough signatures of a patient 608, such as single tap, double tap, activity, inactivity, free-fall, and orientation. In some embodiments, the inertial classifier 604 may detect breakthrough signatures for specific activities, e.g., running, jumping, etc. Activity / inactivity detection can be absolute (DC) or relative (AC). The inertial classifier 604 may include registers, e.g. types of breakthrough signature detection enabled, mapping breakthrough signature detection to interrupt, scaling parameters, axis involved in breakthrough signature detection, acceleration thresholds, timing, etc. The inertial processor 606 may detect an event by comparing the inertial classifier parameters from the motion adaptive profile 600 and the readings from the 3-axis inertial sensor 602. When the inertial processor 606 detects a breakthrough signature, the inertial processor 606 may communicate with the IPG processor disclosed herein via interrupt lines. In some embodiments, an interrupt may send a change-of-stimulation request to the IPG processor. In some implementations, the motion adaptive profile 600 may include two interrupts, although more interrupts are possible. In some implementations, the interrupts may correspond to movement in a specific axis, for example, different interrupts for tap (one particular axis), jumping (z axis), or walking (x or y axis). Each of these interrupts can be mapped to a stimulation program, for example, inertial-triggered stimulation program A and program B respectively. The stimulation parameters of the programs A and B may be determined by the stimulation parameters configuration of the motion adaptive profile 600. In an example, program A may be a background stimulation mode and program B may be a higher stimulation mode as disclosed herein. In the illustrated embodiment, the two interrupts may include an activity / orientation state estimate or a tap detection. If theinterrupt is acknowledged by the IPG processor (for example, if the motion adaptive profile has been assigned to the time window, and / or if a debounce period has expired as described elsewhere in the present disclosure), the interrupt may trigger the stimulation program mapped to the interrupt. For example, a tap detection may cause an interrupt which triggers program B stimulation, while a detection of inactivity may cause an interrupt which triggers program A stimulation. In another example, a tap detection may cause an interrupt which triggers program B stimulation, while a double tap detection may cause an interrupt which triggers program A stimulation.

[0199] To prevent multiple interrupts from the same classifier in a short time, a configurable time interlock may block the inertial-processor interrupts following a breakthrough inertial-processor interrupt. An additional interrupt may be assigned to a fallback stimulation program, which is described elsewhere in the present disclosure. Each of the parameters in Figure 6, except the fallback stimulation program parameters, may be specific to the motion adaptive profile 600.

[0200] Figure 7A illustrates an example sense adaptive profile 700 is based on the onboard biopotential sensor 702 and a biopotential classifier 704. The biopotential sensor 702 and the biopotential classifier 704 may form a biopotential processor 706. The biopotential sensor 702 may include an amplifier and an analog-to-digital (ADC) converter. In some embodiments, the biopotential amplifier input can be configured as a combination of cathode and anode electrodes from the lead(s). In some embodiments, the biopotential classifier 706 may be part of the IPG processor. The sense adaptive profile 700 may include acquisition parameters for the biopotential sensor 702, algorithm parameters for the biopotential classifier 704, trigger / time interlock parameters, and / or stimulation parameters.

[0201] In some implementations, the biopotential classifier 704 may include a version of the Oxford Thermostat Algorithm (see Figure 7B). As shown in Figure 7B, the biopotential classifier may estimates the power in a frequency band (referred to as a "biomarker”) of the biopotential signal at its input and compare the power in the frequency band to a threshold in a threshold module 716. The threshold may be a configurable parameter, as described elsewhere in the present disclosure. In some instances, as also shown in Figure 7B, the determination of the power in the frequency band may first include the biopotential signal being processed at a filtering stage 718 for biomarker frequency band selection. The filtering stage may include a high pass filter 720 and a band pass filter 722. The output of the filtering stage 718 may be fed into an envelope detection stage 724. The envelop detection stage 724 may include rectifier circuitry 726 and smoothing circuitry 728. The output of the threshold module 716 may include a classifier output to trigger a selection of a mapped stimulation program. The signal-block chain shown in Figure 7B illustrates a standard configuration of the Oxford Thermostat algorithm. Embodiments disclosed herein may advantageously allow for flexibility in the order and / or the type of the blocks. For instance, the envelope detection stage can be omitted for certain applications. The biopotential classifier configuration that can be made include configurations of the filter stages, the filter parameters, the threshold module, etc.

[0202] The classifier output may send an interrupt to the IPG processor to change the stimulation program when the level of the biomarker goes above the threshold. The classifier output can also interrupt to change the stimulation program when the output goes below the threshold. Figure 7C shows how the above-threshold interrupt and the below-threshold interrupt trigger the stimulation program mapped to the respective interrupt. As shown, an increasing biomarker (e.g., power in the frequency band) value exceeding the threshold may result in Trigger 2, whichmay trigger the higher level disclosed herein. A decreasing biomarker falling below the threshold may result in Trigger 1, which may trigger the background level disclosed herein.

[0203] To prevent multiple interrupts from the same classifier in a short time, a configurable time interlock may block the biopotential-processor interrupts following a breakthrough biopotential-processor interrupt. An additional interrupt may be assigned to a fallback stimulation program, which is described elsewhere in the present disclosure. Each of the parameters in Figure 7A, except the fallback stimulation program parameters, may be specific to the sense adaptive profile 700. The stimulation programs mapped to the breakthrough signatures of the sense adaptive profile 700 can be different to the ones mapped to the motion adaptive profile 600.

[0204] In some cases, the classifiers disclosed herein may include programmable classifiers, which may be trained with sensor data to improve accuracy. In some cases, the classifiers, such as the inertial classifier 604 and the biopotential classifier 704 may include classifiers based on mathematical models, calibration equations, and / or look-up tables.

[0205] In some cases, the classifiers, such as the inertial classifier 604 and the biopotential classifier 704, may include machine learning classifiers. One or more machine learning algorithms may be used to construct the machine learning and / or artificial intelligence model, such as support vector machines. For example, machine learning and / or artificial intelligence algorithms or other statistical algorithms may be used such as alternating decision trees (ADTree), decision stumps, functional trees (FT), logistic model trees (LMT), logistic regression, random forests (if), receiver operational characteristic curves (ROC), linear regression, extreme gradient boosting (xgb), classification and regression trees, support vector machines (SVM), generalized additive model using splines (e.g., gamSpline), glmnet, multivariate adaptive regression splint (earth), neural network, k-means clustering, or any other suitable machine learning algorithm or statistical algorithm. One or more algorithms may be used together to generate an ensemble method, wherein the ensemble method may be optimized using a machine learning ensemble metaalgorithm such as boosting (e.g., AdaBoost, LPBoost, TotalBoost, BrownBoost, MadaBoost, LogitBoost, etc.) to reduce bias and / or variance.

[0206] In some embodiments, the machine learning and / or artificial intelligence algorithm may include a constrained machine learning and / or artificial intelligence algorithm configured to run on microprocessors. In some cases, the machine learning and / or artificial intelligence algorithm may operate within a Tiny ML framework. In some instances, the machine learning and / or artificial intelligence algorithm may be trained offline. The offline training may be completed on a server, cloud, or other dedicated computing clusters. In some cases, the trained machine learning and / or artificial intelligence algorithm may then be downloaded, deployed, and / or imported into the IPG to iteratively improve upon the IPG and system performance, for example, in preventing incontinent events.

[0207] In some cases, the one or more machine learning and / or artificial intelligence models may be trained on raw and / or processed signals measured by the IPG, sensors, and systems disclosed herein. In some cases, the processed signals may include original raw signals that have been filtered to optimize the signal-to-noise ratio of the raw signal. In some cases, the filter may include a high-pass, low-pass, band-pass, notch, or any combination thereof filters. In some instances, the one or more machine learning and / or artificial intelligence models may alternatively, or in addition to, be trained on user feedback regarding whether or not the stimulation parameters prevented an incontinent event, and / or whether such parameters caused any discomfort. In some embodiments, thefilters may be adjusted to save power. In some embodiments, the classifiers may be adjusted to save power. In one example, the use of a simpler classifier structure may double the battery lifetime.

[0208] As also shown in Figures 6 and 7A, an interrupt from one of the adaptive profiles may enable the flow of therapy, e.g., programs A and B through the stimulation device 610 and a neural interface 612 to the patient 608. The stimulation device 610 may include the IPG processor and the stimulating electrode(s). The neural interface 612 may include a sensing electrode that captures the neural response of the subject and a processing module that can interpret the neural response.

[0209] Additionally or alternatively, the patient 608 may manually enable the delivery of electrical stimulation via a manual controller 610. In one implement, the manual controller 610 may include a user interface, such as a button, on the patient controller described elsewhere herein.

[0210] Figure 8 illustrates an example flowchart of interrupt priority or sensor input hierarchy at the IPG processor for a time window disclosed herein, when a background program and two types of adaptive profiles (e.g., motion and sense) have been assigned to the time window. At step 800, the IPG processor may check the background stimulation programs and / or adaptive profiles assigned to the time window. If the IPG processor is not already running on the background program disclosed herein, at step 802, the IPG processor may change to the background program mapped to the time window. At decision step 804, the IPG processor may determine if a motion or inertial interrupt has been received. If no motion or inertial interrupt is received, the IPG processor may return to step 802. If a motion or inertial interrupt is received, at step 808, the IPG processor may change from the background program to the stimulation program mapped to the motion or inertial interrupt. The IPG processor may run the assigned program for an assigned duration (described elsewhere in the present disclosure). After the assigned duration, the IPG processor may return to step 802. At decision step 806, the IPG processor may also determine if a sense or biopotential interrupt has been received. If no sense or biopotential interrupt is received or an interrupt that the biomarker falls below a threshold (Trigger 1) is received, the IPG processor may return to step 802. If an interrupt that the biomarker goes above a threshold (Trigger 2) is received, at step 810, the IPG processor may run the stimulation program mapped to the sense or biopotential interrupt. The IPG processor may run the assigned program for an assigned duration (described elsewhere in the present disclosure) or until Trigger 1 (below threshold trigger) is received. The process in Figure 8 may be repeated until the time window has expired.

[0211] The decision steps 804 and 806 may be run simultaneously or with the two steps immediately following each other. In an example, if both adaptive profiles received new interrupts, the sense interrupt may be the last interrupt to be attended by the IPG processor. In that example, the sense interrupt may be the active interrupt and a program mapped to the sense interrupt may be activated. In that example, the motion interrupt may be ignored. In another example, the sense interrupt may be ignored. At other times, when only one of the adaptive profiles receives an interrupt, the interrupt from either type of adaptive profiles may change the stimulation program mapped to the interrupt.

[0212] In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application PCT / EP2025 / 080505, which is hereby incorporated by referencein its entirety, can be used with the adaptive stimulation with flexible sensor input(s) selections for determining breakthrough signatures disclosed herein.Patient Safety and / or Comfort

[0213] As described elsewhere in the present disclosure, the adaptive profiles may include time interlock parameters. Time interlock may also be referred to as the "debounce” time. The time interlock may limit how fast the system can switch between the background level and the higher level. In some embodiments, the time interlock parameter may be set by a clinician. In some instances, the time interlock may be changed from 0 second to about 90 seconds, or about 1 second to about 60 seconds, or about 2 seconds to about 30 seconds, or about 3 seconds to about 20 seconds, or about 4 seconds to about 10 seconds, or about 5 seconds to about 8 seconds, or any duration within ranges defined by those values. The time interlock parameter may be set based on the patient's needs. In some cases, the time interlock parameter may be at least 5 seconds. In some implementations, the system may use machine learning and / or artificial intelligence, and using any of the inputs described herein, to automatically determine and / or set a time interlock for any given profile.

[0214] Figure 9 illustrates an example process of the time interlock preventing re-triggering in a short period of time. At step 902, the IPG processor may return from the higher level stimulation to the background level stimulation, after the IPG processor has responded to a prior interrupt for the higher level. At step 904, the IPG processor may receive a new instance of breakthrough signature for the higher level. At decision step 906, the IPG processor may determine whether the debounce period has expired. If the debounce period has not expired, at step 908, the IPG processor may ignore the new instance of breakthrough signature and maintain the background level stimulation. If the debounce period has expired, at step 910, the IPG processor may change to the higher level stimulation program assigned to the breakthrough signature.

[0215] In several embodiments, each adaptive profile may have its own timing interlock parameters (debounce period), which may operate independently of one another. Therefore, for example, if both motion and sense adaptive profiles are set for the same time window, a breakthrough signature from the sense adaptive profile may overwrite the previous breakthrough signature from the motion adaptive profile, even if the debounce period has not lapsed, and vice versa.

[0216] Embodiments including the time interlock may avoid the system being locked into continuously triggering of the higher level. While the higher level may provider greater immediate physiological effect, for example in reducing urge and / or stress incontinence events, than the background level, the patients may not need the neuromodulation system to be constantly in the higher level in order to be in control of their body. In some instances, over-triggering may be uncomfortable for certain patients. In some embodiments, the time interlock may also avoid false positive triggering, which may include triggering by artifact signals (also referred to as "stim artifact”).

[0217] In several embodiments, habituation is reduced by having one or more interlock durations. In one embodiment, a patient can override the interlock duration. In another embodiment, the patient is unable to override the interlock duration.

[0218] In some implementations, the time interlock may ensure that the higher level, once triggered, run for at least the duration of the time interlock before the IPG processor returns to the background level. The minimumruntime requirement may further prevent rapid changes in the stimulation therapy due to potential unstable conditions in the algorithm input (e.g., from the stim artifact).

[0219] In some embodiments, the stimulation programs mapped to the adaptive profiles may be preset by the clinician and tested for tolerance on the patient before enabling the adaptive algorithm. The testing may prevent unexpected adverse side-effects.

[0220] Embodiments disclosed herein may advantageously allow the patient to completely turn off stimulation, disable the higher level and return to the background level, and / or switch to a fallback mode, when the stimulation becomes uncomfortable to the patient and / or for any other reason (for example, to completely turn off stimulation in response to detecting voiding, such as by detecting relaxation of certain muscle(s)). In some cases, the fallback mode may include the same parameters as the background level. In other cases, the fallback mode may include stimulation with a lower level than the background level. To turn off stimulation, the patient may use the controller described elsewhere in the present disclosure. In some cases, the patient may provide a user input, e.g. a specific sequence of taps, to switch to the fallback mode. In some embodiments, when the fallback mode is activated, the higher levels of stimulation cannot be triggered until the patient switches off the fallback mode or switches back to full function (including the background stimulation and the triggered higher levels of stimulation). The fallback mode may improve patient comfort when the stimulation level provided to the patient is causing adverse effects, including but not limited to discomfort. The fallback mode may additionally or alternatively improve patient experience when the patient is engaging in activities such as driving, business meeting, or any activity that requires focus, as a sudden increase in the stimulation level may distract or disrupt the patient's performance. In some cases, the fallback mode provides a compromise between full functions (including the background stimulation and the triggered higher levels of stimulation) and no electrical stimulation so that the patient still receives a certain amount of stimulation to help reduce incontinence events without having to be distracted by the sudden trigger of higher levels of stimulation. To be able to switch back to the background level from the higher level, a disable function may be selected when configuring the adaptive profile so that the IPG processor can automatically return to the background level without the patient having to manually select a different stimulation program. In some embodiments, the disable function may be activated in response to a user input. The parameters and / or settings of the fallback mode may be pre-set by the clinician. In some implementations, the system may use machine learning and / or artificial intelligence, along with input from any of the sensors described herein, to automatically to determine if stimulation should be turned off or if the fallback mode should be activated.

[0221] In some embodiments, an additional safety and / or comfort feature may include the motion and / or posture sensor input forcing the IPG processor to return to the background level. This may happen when the bioelectrical sensor input keeps triggering the higher level, but the motion or posture sensor input indicates that the patient is not moving the body or any of the muscles of interest. In some embodiments, a patient may be able to provide a user input detectable by a sensor of the system, a motion / posture sensor and / or a bioelectrical sensor, in order to disable an adaptive profile for a certain period of time, or indefinitely. For example, the patient may be able to perform a tap, specific sequence of taps, a specific squeeze or sequence of squeezes, standing, sitting, or any other action, in order to enable and / or disable an adaptive profile corresponding to the specific user input.

[0222] In some implementations, the system disclosed herein may store a log of stimulation transitions, which is described elsewhere in the present disclosure. The log may facilitate assessing any fault modes in the algorithm.

[0223] In some embodiments such as shown in Figures 10A and 10B, the display of the patient controller disclosed herein may show the current stimulation status. Figure 10A illustrates the display showing the active stimulation program (and whether it is off or on). The green light bulb 1000 indicates that the stimulation is running, with the program name 1002 shown above (or alternatively below or elsewhere relative to) the green light bulb 1000. When the stimulation program is not running but the controller is coupled to the IPG, the green light bulb may turn to a red light bulb. The light bulb may be gray when the external device is in control of the IPG. The display in Figure 10A further shows a STOP icon 1004, which may be selected to turn off stimulation. The display may include an OHM icon (not shown), which may be used for measuring impedances, as described elsewhere herein. Figure 10B illustrates the display showing the current state of the adaptive algorithm, which is on. The display in Figure 10B further includes an icon 1006 for disabling the adaptive profile (for example, to return to the background level as described elsewhere in the present disclosure).

[0224] In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application PCT / EP2025 / 080505, which is hereby incorporated by reference in its entirety, can be used with the additional patient safety and / or comfort features disclosed herein.User Interfaces

[0225] In some implementations, a software program for configuring the neuromodulation system disclosed herein may run on an external device. When the external device is in communication with the IPG and / or the controller (see, e.g., Figures 1F and 16), a clinician may configure the various stimulation programs and adaptive profiles via the software program. The software program may include multiple tabs, including but not limited to a patient tab, a device tab, a monitoring tab, a stimulation tab, and an adaptive tab. Figures 11-15B illustrate various user interface or portions of the user interface of the software program.

[0226] As shown in Figure 11, the patient tab may include patient information. The patient tab may allow for managing of patient details, medical history, and generating reports. For example, the clinician may export patient data 1104 and generate report 1102. The patient tab may also show a log 1106 of history of visits and / or the type of visits. The clinician may add notes to the history at each patient visit.

[0227] As shown in Figure 12A, the device tab may show details 1202 of the connected IPG device, including but not limited to a battery level, serial number, signal strength, etc. The device tab may allow for viewing of system information, adjusting system settings, and for downloading error and usage logs. A user may select the "Usage Report” button 1200 to open up a new window as shown in Figure 12B. The usage report such as shown in Figure 12B may include records of how the implanted device is working, history of the adaptive profile, impedance measurement of the bioelectrical sensor prior to operating the device to provide therapy (e.g., to determine whether the bioelectrical sensor is functioning properly), and / or interactions between the patient and device. The usage report may provide insights on how the device has been operating between visits to the clinician. The device tab may be used to erase stimulation programs when a new schedule is required, e.g. based on revised diagnostics or aprogression of the patient's condition. The device tab may further be used to adjust patient settings, e.g., adjusting the maximum stimulation amplitude and / or choosing which features are blinded on the external controller. As shown in Figure. 12C, the patient settings tab may include a maximum current, a maximum pulse width, and a maximum frequency to which the patient can adjust their stimulation for a given program. The patient settings tab can also be used to blind the patient, e.g., on the patient controller, to settings such as stimulation settings, impedance checking, or adaptive settings. As shown in Figure 12D, the impedance measurement may be performed in a separate window displaying each electrode of the leads. The displayed electrodes may have a corresponding color based on the impedance, e.g., green for acceptable, red for unacceptable (too high or too low). For example, as shown in Figure 12D, the impedance measurement on electrode 6 is too high, while the impedance measurements for the other electrodes are acceptable. Electrodes with impedances that are too high or low may not be suitable for stimulation. In one example, a suitable impedance for stimulation may be between 200 and 4000 Ohm.

[0228] Figure 13A illustrates the stimulation tab, where the therapy and / or each stimulation program disclosed herein may be programmed. The "Programs” field 1300 may show previously saved programs and allow the user to switch between them by clicking on the name label. To create a new program, the user may begin by click on the "New Stimulation” edit icon 1302. The battery icon 1304 below the "Programs” field 1300 may give an indication of how long the battery will last in this program before requiring recharging. The estimated battery life may change depending on the settings of the program.

[0229] A clinician may select the best electrode (referred to as the "Stimpoints” 1306 in the stimulation tab) on each lead for stimulation to achieve the best therapeutic effect. In one example, CH1A and CH1B may correspond to the lead implanted close to the nerve trunk. In another example, CH2A and CH2B may correspond to implantation into the branching pudendal nerve and pelvic floor, or another location along the pudendal nerve or the sacral nerve. In some embodiments, the clinician may determine the best electrode based on electrode responses received during the implantation surgery, urodynamics study, and / or the clinic visits. The selected electrode 1312 may be shown on the lead 1308 displayed in the stimulation tab. The clinician may select a monopolar stimulation (using one electrode 1312 and the IPG 1314 as the cathode and anode), such as shown in Figure 13A, or bipolar stimulation (using two electrodes, which may be from the same lead or different leads), such as shown in Figure 13B. In some embodiments, the electrode for sensing and / or delivering stimulation may be automatically selected or recommended based on sensor data.

[0230] As shown, the parameters 1310 for each program may be adjustable or programmable. For example, the parameters 1310 may include, without limitation, pulse width, pulse rate, and / or amplitude. The user may perform an immediate stop or a ramped stop of the stimulation for a single lead using the double down arrows on the "Amplitude” slider. The user may choose to turn on or off "Sense / Stim Restriction” 1316. Setting the "Sense / Stim Restriction” button to "On” may only allow the selection of stimulation parameters that are compatible with sense adaptive profile. This may automatically limit which stimulation frequencies, maximum pulse width, maximum stimpoints, and / or reverse pulses can be selected.

[0231] Each selected electrode may have a different program and setting. For example, each electrode can have its own frequency setting. In the illustrated embodiment, pulse width, pulse rate, and amplitude may be adjusted using the arrow buttons on the sliding scales to the right side of the screen. The grey band may change to adifferent color (such as green in the illustrated embodiment) as the value is changed at the top of the scale. The patent default parameter may set the default values for patient's selection (e.g., via the controller disclosed herein). The patient max parameter may set the maximum value allowed in a patient's selection (e.g., via the controller disclosed herein). For example, the patient max may set the maximum amplitude that a patient may adjust the stimulation to have in a given stimulation program.

[0232] Figure 13B illustrates the stimulation tab in a show target mode. The electrodes viewed in the show target mode may help visualization of the target area 1318 of the stimulation. In some cases, it may be appropriate to shift the centre of the stimulation part way between the two electrodes, by delivering more charge via one electrode than the other. Control of the charge distribution between electrodes can be achieved either by individually setting the charge on each electrode, or by dragging, moving, or stretching the target to the desired position. The centre of the target 1308 may be the weighted centre of the selected electrodes. The show target mode can be used in the event of a damaged contact to create a virtual stimulation point between adjacent electrode contacts to improve the localization of therapy.

[0233] Figure 13C illustrates an advanced programming pop-up window by selecting the "Advanced” button 1320 in the stimulation tab as shown in Figures 13A and 13B. The advanced settings may include ramp, pulse cycling (pulse on and pulse off), reverse pulses, and the like. In some cases, the pulse cycling may allow for bursts (pulse on) and / or burst intervals (pulse off) of up to 50,000 pulses. When using constant stimulation, the pulse on and pulse off may both be set to OFF. In some implementations, reversing the direction of the pulse intermittently may improve electrode balancing. Setting the reverse pulses to 0 may set a monophasic waveform with a passive discharge. Setting a reverse pulse value of n, e.g., 1 or more, may result in a biphasic waveform with an active discharge. In some cases, the number of reverse pulses must be set to at least 1 when using concurrent sensing and stimulation.

[0234] When configuration is complete, the stimulation program may be saved to the IPG by selecting the "Save to IPG” button 1322 in the Stimulation tab.

[0235] Turning to Figure 14A, the adaptive tab may allow a user to create a stimulation plan that repeats every 24 hours (which can be any other duration of time) or stimulation instructions. In the illustrated embodiment, the user interface may include a program assignment element for creating the stimulation plan. The stimulation plan or instructions may be saved to the IPG, for example, by selecting the "Save to IPG” button. One or more stimulation programs, or no stimulation, can run for a pre-defined length of time each day. In other implementations, the adaptive tab may allow a user to create a stimulation plan that repeats every week, or every month, etc.

[0236] The "Programs” field 1400 may include a list or library of the non-limiting pre-configured and saved stimulation programs. Although Figure 14A shows three pre-configured programs, 1: program 1, 2: program 2, and 3: program 3, other programs may be saved, including but not limited to wake-up, evening, arriving home, exercise, fallback, etc. In some cases, the "program 1” program may provide stimulation of a first background level, the "program 3” program may provide stimulation of a second background level lower than the first background level, e.g., for nighttime, and the "program 2” program may provide boosted stimulation of a third level higher than the first background level. As disclosed herein, there may be different tiers of stimulation programs and / or stimulation programs with parameters varying on a continuum.

[0237] The "On Time” field 1402 shows the amount of active stimulation time for the program in each time window. The on time may be configured in the stimulation tab. The default on time may be the same duration as the length of the time window, which may be adjusted down by the user. Any of the programs in the library of programs may be assigned to any of the time windows 1404 in the program assignment element. In the illustrated embodiment, the time window 1404 has 30 minutes, which may be shorter or longer as described elsewhere in the present disclosure. In some embodiments, the background color of each time window 1404 may match the color of the background program assigned to the time window 1400 (e.g., green for program 3, blue for program 1, and red for program 2). The background programs may be annotated as P1 , P2, P3 based on their order in the library of programs. As disclosed herein, the time windows may be automatically adjusted to the time zone in which the IPG is located, providing convenience to the patients when travelling across different time zones, or to time changes (such as for daylight saving).

[0238] Adaptive stimulation may be turned on by selecting the "Adaptive” button in the "Dynamic Stim” field 1406, or be turned off by selecting the "Off' button in the same field. Other parameters that may be configured in the "Dynamic Stim” field may include the debounce or time interlock period, and mapping the breakthrough signatures to the stimulation programs. As shown in Figure 14A, for example, where the sense adaptive profile is being configured, the program 1 mode (e.g., a first background level) may be mapped to Trigger 1 and the "On Disable” function and the program 2 mode (e.g., a third level) may be mapped to Trigger 2. The mapping may be color coded to match the color assigned in the Programs field 1400. In some implementations, for example, when the motion adaptive profile is being configured, trigger 1 may be replaced by "Double Tap” and trigger 2 may be replaced by "Tap”, or otherwise. In some other implementations, for example, when the motion adaptive profile is being configured, trigger 1 may be replaced by "Inactivity” and trigger 2 may be replaced by "Tap”. As also shown in Figure 14A, one or more adaptive profiles may be assigned to each time window 1404 of the program assignment element. For example, some windows may include only a sense adaptive profile S2; some windows may include only a motion adaptive profile M2; and time windows may include both a sense profile S2 and a motion adaptive profile M2, or both a sense profile S1 and a motion adaptive profile M1, the advantages of which are described elsewhere in the present disclosure.

[0239] Figure 14B illustrates an exploded view of the Movement Preset field 1408 in the adaptive tab of Figure 14A, showing a classifier configuration table with a list of the movement registers. Upon selection of one of the thresholds, e.g., a tap threshold, a window such as shown in Figure 14C may pop up. In the pop-up window in Figure 14C, parameters of the tap threshold may be adjusted. For example, in the illustrated embodiment in Figure 14C, the Tap preset settings have a sliding bar for the tap sensitivity (THRESH_TAP register) and a second sliding bar for the double tap speed (LATENT register). In some cases, the detection of inactivity may be based on a time inactive parameter. The time inactive parameter may be an amount of time that sensed movement remains below a set threshold for the system to register inactivity. The time inactive parameter may be adjusted, e.g., by a slider.

[0240] Figure 14D illustrates an exploded view of the Sense Preset field showing a classifier configuration table with a list of the sense registers. When one of the registers in the list is selected, e.g., Function 4, a mathematical graph may be displayed so that the user may visualize the classifier transfer function. In some embodiments, the registers in the list can be changed manually. Figure 14D further illustrates two leads (for a two-lead configuration) showing the sensing dipole selection, which is electrodes 1 and 3 in the illustrated embodiment.The biopotential can be measured between any combination of two of the four electrodes on one lead, or two of eight electrodes in a two-lead configuration. In some implementations, electrodes 1 and 4, or electrodes 5 and 8, or two electrodes across the two leads (which may be implanted on the same side or different sides of the body) may be selected. For some patients, if stimulation is more effective using one of the electrodes selected for sensing, another electrode may be assigned for sensing.

[0241] The clinician may select the best electrodes for sensing. Turning to Figures 15A and 15B, the monitor tab may aid the user in selecting / assigning the sensing electrodes and / or collecting biopotential data from patient by providing the ability to visualize electrophysiological activity, e.g., EMG signals. For example, the clinician may first identify the optimal sensing electrodes by streaming raw data, asking the patient to perform a task such as a squeeze, and identifying a bipolar electrode pair with the greatest signal-to-noise ratio. Figure 15A illustrates the monitor tab with concurrent sense / stimulation (described elsewhere in the present disclosure) on and showing the biopotential data in a time domain. The "Sense / Stim” option in the monitor tab may allow streaming of data in the presence of stimulation. Figure 15B illustrates the monitor tab with concurrent sense / stimulation (described elsewhere in the present disclosure) on and showing the biopotential data in a frequency domain. As described elsewhere in the present disclosure, the threshold may be determined from the biopotential data in the time domain and / or the frequency domain. The monitor tab may allow for adjustment of display options of the sensed data, e.g., input range, offset filter, sample size, smoothing, and / or a high-pass filter. These display options may only affect the visual data stream, and not the exported data.

[0242] In some implementations, the adaptive tab may include a configuration assistant for a clinician to build a patient-specific classifier. The patient-specific classifier may use patient-specific thresholds for sensor data, e.g., accelerometer data or EMG signals, that will activate a different mode of stimulation. For example, in the case of a biopotential classifier, the goal of the configuration assistant may be to create a patient-specific classifier to activate a different stimulation mode after a volitional pelvis floor contraction. The clinician may direct the patient to follow certain directions prompted by the configuration assistant, e.g., on a display device. For example, in the case of a biopotential classifier, the configuration assistant may prompt the patient to perform a sequence of pelvic floor squeezes, e.g., squeeze in 3 seconds, relax, squeeze again, etc.

[0243] Motion / posture sensors and / or bioelectrical sensors may collect data as the patient performs the prompted tasks, and the configuration assistant may automatically label the data. There may be separate configuration assistants for different classifiers, e.g., an inertial classifier or a biopotential classifier, with each configuration assistant having different prompted tasks for the patients to perform. The patient may be able to see the collected data displayed on a display device, e.g., a screen. The patient visualization of the data may allow for better data collection during the configuration process, as a patient may be able to observe how their activities are registered by the sensors, and may be able to adjust or correct how they are performing the tasks accordingly. For example, the patient may be directed to perform multiple squeezes in different positions, e.g., 3-5 squeezes while sitting and / or standing, with a relaxing period in between each squeeze, orto walk for a certain amount of time, e.g., 15-30 seconds. Once the data is collected and labelled, the configuration assistant may use a machine learning and / or artificial intelligence algorithm, e.g., Bayesian Optimization, to optimize one or more fine-tune parameters for filtering the raw signal data for classification. For example, the one or more parameters may include amplitude and / or smoothing ofthe data. The machine learning and / or artificial intelligence algorithm may determine and set a threshold for activating a different level, or mode, of stimulation. In some cases, the clinician may adjust the threshold manually, e.g., using a slider, to fine-tune the classifier based on their observations and / or the patient's preferences. The configuration assistant may be personalized between patients, for example, by asking the patient to perform a different set of tasks depending on which activities are more likely to result in incontinence events for that specific patient. For example, a patient may fill out a survey for understanding which activities specifically lead to incontinence events prior to undergoing the configuration assistant process and the configuration assistant may be adjusted accordingly.Data Aggregation

[0244] In some embodiments, certain usage data may be presented to the clinician and / or the patient, for example, on an external device such as a computer, smartphone, wearable device, etc. Figures 16A and 16B illustrate embodiments of a portion of a user interface showing certain usage data of two different patients, such as the total number of days in which the higher level stimulation was used for each hour of the 24-hour period between a certain time period. In the illustrated embodiment, the 24-hour day is illustrated as a circle 1600 with divided sections representing different hours of the day. The time period in which the usage data is collected may be represented by concentric rings 1604 within the circle 1602, with the outer rings representing the later days. In Figure 16A, the time period is 15 days. In Figure 16B, the time period is 24 days. The total number of days of higher level usage for every hour may be represented by the solid bars 1602 radiating from the center of the circle. The user interface as shown in Figures 16A and 16B may allow the clinician and / or the patient to more easily visualize the hours when the higher level is more likely to be triggered, which may help optimize the stimulation programs and adaptive profiles assigned to different hours of the day and make the therapy more patient specific. For example, the patient as shown in Figure 16A used the higher level at between about the 0730 hour and about the 1700 hour. In some cases, this patient may benefit from a lower threshold for triggering the higher level in those hours. In contrast, the patient as shown in Figure 16B used the higher level mostly between about the 0900 hour and about the 1000 hour. In some cases, this patient may benefit from assigning a background mode of a higher level during about the 0900 hour and about the 1000 hour.

[0245] Embodiments disclosed herein may advantageously provide aggregation of patient data to a centralized location. Figure 17 illustrates a data processing module 1700 for processing the aggregated data in a data repository 1702. In some embodiments, the processing may be offline. In the illustrated embodiment, the software program may be connected to the patient controller, which is in turn connected to the IPG wirelessly. As described elsewhere in the present disclosure, other communication pathways may be possible to transmit data stored on the data recorder of the IPG to the data repository. The IPG, controller, clinician software as shown in Figure 17 may incorporate any of the features of the IPG, controller and clinician software described elsewhere in the present disclosure. The IPG, controller and clinician software described elsewhere in the present disclosure may incorporate any of the features as shown in Figure 17.

[0246] In the processing module, the data, e.g., long term data, may be stored. Long term data may include data of, for example, one week, one month, three months, six months, one year, two years, five years, or any duration within a range defined by those values. The collected data may be used to refine the algorithms disclosed herein. The algorithm that may be refined may include, but are not limited to, classifier optimization, control validation, and / or data visualization.

[0247] In some embodiments, the machine learning models for the classifiers disclosed herein may be trained on one or more datasets in the collected long term data. In some instances, the one or more datasets may include data generated by one individual, or data generated by a population or segment thereof. In some cases, the data generated by an individual and / or the data generated by a population may include thresholds that indicated an incontinent event, stimulation parameters that prevented an incontinent event, etc. In some cases, these data may be obtained from the IPG, and used in characterizing and training a machine learning and / or artificial intelligence classifier as described elsewhere in the present disclosure. In some instances, the machine learning and / or artificial intelligence classifiers trained on or more datasets may then be downloaded to each patient's IPG to further improve the classifier's accuracy. In some instances, the datasets of one or more individuals may be pooled together as a training dataset where the individuals show characteristics of similarity between clinical presentation and parameters of excitatory / sensory input. In some cases, clinical presentation may include clinical incontinence type, clinical meta data, e.g., gender, age, past medical history, current medications taken, past surgical intervention, etc. In some cases, a pooled training datasets may be utilized for an individual during the initial period of training a device implanted into that individual.Incontinence

[0248] Described herein are devices, systems, and methods to prevent, treat, or otherwise ameliorate an episode of incontinence in an individual in need thereof by providing electrical stimulation, such as neurostimulation. The episode of incontinence may include urinary incontinence, fecal incontinence, or any combination thereof. The devices, systems and methods disclosed herein may treat a sub-type of incontinence. The sub-type of incontinence may include urge incontinence, stress incontinence, overflow incontinence, or mixed incontinence.

[0249] Urinary incontinence may be categorized into one of four main types: urge incontinence, stress incontinence, overflow incontinence, and mixed incontinence. Urge incontinence is often due to an overactive bladder (GAB). Individuals with urge incontinence have a strong and sudden need to urinate immediately, often leaving them with insufficient time to reach a bathroom. Stress urinary incontinence (SUI) is usually due to a poorly functioning urethral sphincter muscle or hypermobility of the urethra or bladder neck. An individual may experience stress incontinence during activities such as coughing, sneezing, laughing, lifting, or exercise. Overflow incontinence may typically be due to poor bladder contraction or blockage of the urethra. Mixed urinary incontinence (MUI) may involve features of stress and urge incontinence. Incontinence often involves neurological issues, including but not limited to impaired nerve conduction between the brain and / or the affected muscles, and nervous system conditions or injuries (e.g., multiple sclerosis or stroke), or mental confusion. Other causes of incontinence include but are not limited to weakness of pelvic or urethral muscles and pelvic prolapse.

[0250] Fecal incontinence, also referred to as bowel incontinence, is the loss of bowel control, causing an individual to pass stool unexpectedly from the rectum. Fecal incontinence is usually categorized into three main types: urge incontinence, passive incontinence and post-defecatory leakage (or a combination thereof). Individuals with urge incontinence have a strong and sudden need to defecate immediately, often leaving them with insufficient time to reach a bathroom. Passive fecal incontinence is when an individual passes feces without conscious awareness. Individuals suffering from passive incontinence cannot consciously control their bowel movements and stool can pass without their knowledge. Incontinence often involves neurological issues, including but not limited to impaired nerveconduction between the brain and / or the affected muscles, and nervous system conditions or injuries (e.g., multiple sclerosis or stroke), or mental confusion. Causes of fecal incontinence include but are not limited to nerve damage, anal sphincter muscle damage, constipation, diarrhea, surgery, loss of rectum storage capacity, rectal prolapse, and rectocele.

[0251] Electrical stimulation of muscles may be used to treat incontinence by training the pelvic floor muscles thereby improving strength and function of the muscle to control over urination and defecation. In some case, electrical stimulation may target the sacral nerve to improve control over urination and defecation. In some case, the electrical stimulation approaches may benefit from stimulation of an alternate target, such as the pudendal nerve.

[0252] Existing electrical stimulation approaches may be capable of delivering only a predetermined stimulation protocol and may not be able to adapt to the condition and circumstances of the individual during a particular episode of incontinence. This may result in overstimulation or under-stimulation of the target tissue, resulting in inadequate control over muscles involved in urination or bowel movements. Usually, traditional approaches to treating incontinence may not be able to mimic sufficiently an innate human response (e.g., reflex) to prevent an incontinence episode and may be insufficient. Individuals who have an incontinence episode may experience insufficient preventative response. The preventative response may include a muscle contraction of at least one pelvic floor muscle to prevent a leakage event in response to an increased intra-abdominal pressure. Individuals who experience stress incontinence may exhibit a delayed response in preventing an incontinence episode in response to a stress event. In some cases, individuals may experience stress incontinence related to urethral hypermobility (e.g., insufficient support) that may lead to an increased pressure transmitted to the bladder and subsequently an incontinence event.

[0253] A lack of voluntary control over micturition, defecation, incontinence, or any combination thereof is a problem that can impact quality of life and cause social embarrassment. Urinary and fecal incontinence may affect individuals of all ages. Usually, older individuals may exhibit a greater probability of incontinence with varied pathophysiology. Urinary incontinence, or loss of bladder control, and fecal incontinence, loss of control of bowel movements, often relate to neurological issues. Both urinary incontinence and fecal incontinence may involve injury, weakness, or overactivity of the pelvic floor muscles, including but not limited to the urethral and anal sphincter, and the nerves that innervate these muscles and involved organs, such as the bladder, rectum, or anus.

[0254] To treat or reduce symptoms of incontinence, electrical stimulation of the muscle, sacral nerve, and / or other pelvic nerves (e.g., the pudendal nerve) involved in incontinence has been used to improve control over micturition and bowel movements targeting the pudendal nerve, provides an improved approach to treating incontinence. Often, the pudendal nerve contributes to motor functions and mediating volitional contraction of the urethral and anal sphincter muscles in the preservation of continence. Targeting of the pudendal nerve may be combined with a closed-loop capability in some cases with time-dependent and / or dynamic adaptive control to provide a more effective treatment for incontinence. In some cases, individuals may control stimulation by a pelvic squeeze, wherein receiving a threshold EMG signal from the pelvic floor may activate electrical stimulation.

[0255] Current electrical stimulation therapies may include sacral neuromodulation (SNM) that may provide fixed patterns of stimulation to treat "urge” (the sudden need to urinate), but such stimulation may be unable to respond to the more common "stress” incontinent events, such as coughing, sneezing, and lifting. While SNM may reduce the frequency of incontinence episodes, the success of SNM may be limited in scope {e.g., not a cure) and maydecrease over time. Furthermore, SNM may not be suitable to treat individuals having stress incontinence or mixed urinary incontinence (with stress and urge incontinence). SNM may have high long-term costs in management of the electrical stimulation device and may require high level of skill and precision from the surgeon to place the lead on the sacral nerve. As such, targeting another nerve (such as the pudendal nerve as described herein), may provide an improved approach to treating incontinence.

[0256] Pudendal nerve stimulation may provide a more effective treatment for individuals having incontinence than SNM. In some cases, pudendal nerve stimulation may be an effective treatment for incontinence in individuals where SNM has failed. PNS may be more powerful than SNM because the pudendal nerve enters the spinal cord through S2, S3, and S4, while SNM only acts upon the S3 root. Pudendal nerve stimulation may provide an effective treatment for urinary incontinence. In some cases, the pudendal nerve may be an effective continence target for closed loop stimulation. The neuromodulation system disclosed herein may address the problems of existing electrical stimulation therapies disclosed herein and / or other problems.

[0257] In several embodiments, severe refractory urge incontinence is treated. For example, several embodiments treat this chronic condition that involves involuntary urine leakage resulting from a sudden and strong urge to urinate, which is considered refractory when there is no response to behavioral therapies or at least two medications.

[0258] Electrical stimulation as described herein may be used to treat incontinence instead of, or combined with, a pharmaceutical therapy. In several embodiments, a reduced drug dosage may be needed when combined with stimulation, thus reducing the side effects associated with a higher drug dose. Thus, the synergies of the combined approach may reduce reliance on medication, which in turn can reduce certain undesired side effects (including but not limited to dry mouth, dry eyes, constipation, cognitive side effects, etc.). In some embodiments, electrical stimulation as described herein is used with muscarinic receptor antagonists. In some embodiments, electrical stimulation as described herein is used with an anticholinergic drug. In some embodiments, electrical stimulation as described herein is used with one or more of fesoterodine, mirabegron, oxybutynin, solifenacin, tolterodine, trospium, and similar compounds. In some embodiments, electrical stimulation as described herein is used with botulinum or other toxin, hormones (such as estrogen), tricyclics, serotonin reuptake inhibitors, and norepinephrine reuptake inhibitors. By reducing side effects of drugs (e.g., with reduced dosages), drugs may be tolerated for a longer period of time and / or patient compliance may increase. In some embodiments, the combined use of electrical stimulation with pharmacologic therapy has synergistic effects. Electrical stimulation and drugs may both affect the acetylcholine pathway with beneficial, synergistic results according to several embodiments. For example, a drug may block muscarinic receptors while the stimulation may modulate neurotransmission, thus working together in a cooperative manner.Pain Control

[0259] The devices, systems, methods, and / or kits, described elsewhere herein, may treat pain in the pelvic region. Chronic pelvic pain (CPP) can impact quality of life, often causing episodes of severe discomfort and exacerbating pain. Common symptoms of CPP include but are not limited to neuropathic symptoms like paresthesia, numbness, burning, lancinating pain, in the pelvic, anus and / or genitals. Episodes of pain associated with CPP may frequently occur with sitting, urinating, defecating, or sexual intercourse and may be exacerbated with these activities.Approaches to treat CPP by electrically stimulating a large section of the affected area (e.g., pelvic area) or transcutaneously may have limited success at alleviating the symptoms of pain. As such, targeting specific nerves for electrical stimulation that is adapted to the individual's pain response may provide a highly efficacious treatment for CPP and other pain symptoms.

[0260] Many electrical nerve stimulation approaches currently used deliver a preset stimulation protocol (e.g., open-loop configuration) and usually are not able to adapt to the changing parameters of pain experienced by the individual. Pudendal nerve stimulation may provide an effective treatment for chronic pain. In some cases, the inability to adapt the stimulation can result in overstimulating or under stimulating the target area and lead to inefficient or inadequate pain management. Moreover, because treatments usually do not adapt to the changing parameters of pain, existing pain management often requires patient-actuation during bouts of exacerbating pain to provide pain relief. Therefore, it would be highly beneficial to provide electrical stimulation to peripheral nerve targets that adapt to innate feedback from the subject as conditions change (e.g., a closed-loop configuration). The time-dependent adaptive stimulation provided by the neuromodulation system disclosed herein may address the problems of existing electrical stimulation therapies for pain control and / or other problems. The patient can activate the electrical stimulation mode when needed using the system disclosed herein.

[0261] The systems, methods, and devices, described herein are directed to treating episodes of pain associated with chronic pelvic pain (CPP) or other conditions resulting in pelvic pain using peripheral nerve stimulation. In some embodiments, the systems, methods, and devices, comprise a closed-loop configuration. In some embodiments, adapted stimulation to the target nerves or tissue adjacent to the target nerve of a patient are provided by an implanted stimulator with an underlying physiological rationale comprising: (a) stimulating motor fibers to alter end organ muscle activity where peripheral pain is driven by spasm and / or hypertonicity (e.g., pelvic floor myalgia, some cases of bladder pain syndrome, and urethral pain associated with motor modulation); (b) stimulating larger diameter afferent fibers to modulate spinal gating of nociceptive signaling from peripheral foci of pain generation (e.g., interstitial cystitis, coccygodynia, and pelvic myalgia); (c) blocking nerve conduction (e.g., anodal block) to (i) directly block disease-related peripherally driven pain, and (ii) block noxious effects associated with providing the adapted stimulation, which facilitates higher charge delivery for therapeutic benefit; and any combination thereof.

[0262] Described herein are targeting one or more peripheral nerves based on the etiology of the pain condition with adapted electrical stimulation to reduce pain experienced by an individual. The stimulator electrodes may target different nerves (e.g., a first stimulator targeting a sacral nerve and a second stimulator targeting a pudendal nerve). In some embodiments, stimulating multiple nerves within the pelvic area may broaden the field of treatment in pain syndromes having diffuse areas of pain. In some embodiments, the electrical stimulation may be adapted to provide blocking and stimulation of electrical nerve signals on the same nerve. In some embodiments, stimulator electrodes may target one or more locations along a single nerve. Targeting multiple points along a single nerve may allow for improved control in the closed-loop modulation (e.g., a first stimulator implanted at or adjacent to a first anatomical site of a pudendal nerve and a second stimulator implanted at or adjacent to a second anatomical site of the pudendal nerve). In some embodiments, targeting a single nerve at multiple sites may permit both blocking and stimulation on the same nerve. In some embodiments, one, two or three branches of the pudendal nerve arestimulated. When two or more branches are stimulated, they may be stimulated simultaneously or in sequence. The same stimulation parameters may be used for two or more branches, or different stimulation parameters may be used.

[0263] In some embodiments, pudendal neuralgia, such as pudendal nerve entrapment (and after surgical decompression of entrapment), is treated using the electrical stimulation described herein. Use of a first stimulation level at or near the pudendal nerve with or without another stimulation level is used for such treatment in some embodiments. When additional modes are used, a patient may be able to activate a higher frequency, amplitude and / or pulse width or otherwise boost stimulation at, for example, the onset of pain and / or when the patient is about to engage in an activity that would otherwise likely cause pain.

[0264] Electrical stimulation as described herein may be used for pain in lieu of, or combined with, a pharmaceutical therapy. In several embodiments, a reduced drug dosage may be needed when combined with stimulation, thus reducing the side effects associated with a higher drug dose. Thus, the synergies of the combined approach may reduce reliance on pain medication, which in turn can reduce undesired side effects of opioids and other drugs (e.g., Gl issues, bleeding, constipation, addiction, etc.). By reducing side effects of drugs (e.g., with reduced dosages), drugs may be tolerated for a longer period of time and / or patient compliance may increase.Sexual Dysfunction

[0265] The devices, systems, methods, and / or kits, described elsewhere herein, may treat sexual dysfunction of a subject. Sexual dysfunction can impact quality of life and may prevent a person from experiencing satisfaction from a sexual activity. Generally, sexual dysfunction may be classified as a desire disorder (lack of sexual desire or interest in sex), an arousal disorder (inability to become physically aroused or excited during sexual activity, an orgasm disorder (delay or absence of orgasm), or a pain disorder (pain during intercourse), or a combination of these disorders. Sexual dysfunction may involve physical and psychological causes. Although sexual dysfunction may be treated using medication, a mechanical aid, psychotherapy, and behavioral treatments, such treatments may have undesired side effects, suffer from patient non-compliance, or are ineffective. For example, sexual dysfunction with a physical cause may be treated more effectively using several embodiments described herein.

[0266] A number of symptoms are associated with sexual dysfunction. In both men and women, symptoms of sexual dysfunction include but are not limited to a lack of interest in or desire for sex, inability to become aroused, and pain with intercourse. In women, some symptoms associated with sexual dysfunction include but are not limited to inability to achieve orgasm, inadequate vaginal lubrication before and during intercourse, and inability to relax the pelvic floor muscles surrounding the vagina to allow intercourse. In men, some symptoms associated with sexual dysfunction include but are not limited to erectile dysfunction (ED), retarded ejaculation, and premature ejaculation. ED may refer to the inability to achieve or maintain an erection suitable for intercourse. A retarded ejaculation may refer to absent or delayed ejaculation despite sufficient sexual stimulation. A premature ejaculation may refer to an inability to control the timing of ejaculation.

[0267] ED is the most common form of sexual dysfunction in men. It is estimated that 322 million men worldwide will be affected by ED by 2025. ED has various etiologies, including but not limited to vascular, hormonal, and neurogenic causes. Individuals having neurogenic causes of ED include individuals with spinal cord injuries (SCI) and men after radical prostatectomy. Global incidence of SCI ranges from 40-80 new case per million of populationper year, with 20-30 million men affected in the U.S. alone. A significant proportion of SCI individuals experiencing ED are young, where ED may significantly affect the quality of life.

[0268] To achieve an erection of the erectile tissue, contributions from both nervous and vascular components may be needed. A normal erection may rely on two reflex loops, pudendo-cavernosal reflex loop (for tumescence) and bulbocavernosus reflex loop (for rigidity). An adequate nerve activity may include release of nitric oxide (NO), leading to increase in cGMP, which in turn induce smooth muscle relaxation in the penile corpora. The nervous arrangement for an erection may be complex and may rely on both the somatic nervous systems (via pudendal nerve (PN)) and autonomic nervous systems (via cavernous nerve (ON)).

[0269] In some embodiments, the technology described herein (e.g., electrical stimulation such as neurostimulation) works synergistically with other therapies. For example, in some embodiments, sexual dysfunction is treated using neuromodulation and one or more of medication, mechanical aid, psychotherapy, and behavioral treatments. In some cases, the medication, also referred herein as medicament, includes a hormone, injection, pill, patch, or cream.

[0270] With respect to ED, examples include but are not limited to a phosphodiesterase type 5 (PDE5) inhibitor to increase blood flow to the penis; or injection papaverine, phentolamine, and / or Prostaglandin E1 (PGE1) at or near the erectile tissue. Often, PDE5 inhibitors are a first line treatment and include but are not limited to sildenafil, tadalafil, vardenafil, avanafil, lodenafil, udenafil, and mirodenafil. Although PDE5 inhibitors are effective in treating sexual function, discontinuation rates may be high, reported as high as 50% after 1-2 years of use. Intracavernosal injections with papaverine, phentolamine, and / or PGE1 may be administered to the patient if medication is ineffective. In some cases, intracavernosal injections may result in a high incidence of adverse effects, such as priapism, injection site pain, bruising. In some cases, high incidences of adverse effects lead to patient non-compliance. Mechanical aids include but are not limited to vacuum devices, penile implants, vaginal dilators, and vibrators. In some cases, penile prosthesis implantation may result in significant complications, such as infection, erosion and pain. As such, the effectiveness of certain treatment may be limited, especially for sexual dysfunction with a physical etiology and when patient compliance or response drops. Thus in several embodiments, the use of electrical stimulation, such as neurostimulation, is advantageous alone or when used in combination with other therapies. In such combined approaches, the undesired side effects of other therapies may be reduced or eliminated. For example, when electrical stimulation is combined with a pharmaceutical therapy, a reduced drug dose may be needed, thus reducing the side effects associated with a higher dose.

[0271] Several embodiments overcome difficulty in treating sexual dysfunction due to the complex organization of the nervous system involved in sexual function, such as erection, including but not limited to access to the pudendal and / or cavernous nerves. In several embodiments, electrical stimulation using electrodes at multiple nerves involved in sexual function, such as pudendal and cavernous nerves, may restore sexual function, such as erection. Electrical stimulation at both pudendal and cavernous nerves may be able to treat sexual dysfunction due to neurogenic (e.g., spinal cord injury, post-prostatectomy) or combined neurogenic / vascular etiology (e.g., diabetes mellitus, idiopathic). In some cases, the erection produced by electrostimulation may be potentiated by PDE5 inhibitor (PDE5I). In some cases, the mechanisms of action may be directly linked to PDE5I as PDE5I inhibits the degradation of the CGM by inhibiting NOS. Advantageously, in one embodiment, side effects from stimulation of somatic nervesare reduced because, for example, stimulation is strategically delivered in locations where the proportion of somatic nerves is low (e.g., surrounding the prostate apex, where somatic nerves represent approximately less than 5% of the autonomic nerves).

[0272] According to several embodiments, sexual dysfunction is treated by targeted peripheral stimulation and restoration and / or augmentation of reflex activity involved in sexual function. Adapted stimulation to the target tissue (e.g., nerves) may be provided by an implanted stimulator with an underlying physiological rationale to target both somatic nervous system (e.g., PN) and autonomic nervous system (e.g., CN), which are involved in erection and sexual function. In some embodiments, adapted stimulation to the target nerves or tissue adjacent to the target nerves of a patient may be provided by an implanted stimulator to target an autonomic nerve (e.g., CN), a somatic nerve (e.g., PN), or a combination thereof. The devices, systems, and methods described herein may be configured to restore erection in case of neurogenic (e.g., spinal cord injury, post-prostatectomy) and combined neurogenic / vascular etiology (e.g., diabetes mellitus, idiopathic). In some embodiments, the systems, methods, and devices may comprise a closed-loop configuration or another configuration disclosed herein for providing the electrical stimulation.

[0273] Electrical stimulation as described herein may be used for sexual dysfunction in lieu of, or combined with, a pharmaceutical therapy, such as hormone therapy, ED drugs, etc. In several embodiments, a reduced drug dosage may be needed when combined with electrical stimulation, thus reducing the side effects associated with a higher drug dose. Side effects include but are not limited to flushing, headaches, heartburn, priapism, vision changes, and cardiac issues. By reducing side effects of drugs (e.g., with reduced dosages), drugs may be tolerated for a longer period of time and / or patient compliance may increase.

[0274] Restless leg syndrome, restless genital syndrome, persistent genital arousal, and other somatosensory dysfunctions may also be treated using the electrical stimulation described herein. Nerve stimulation of the pudendal nerve and / or nerves or other tissue surrounding the pudendal nerve is used to treat these conditions in some embodiments using the components and parameters described herein.

[0275] Several embodiments of the electrical stimulation described herein involve nerve stimulation. In some embodiments, one or more nerves are stimulated together with other tissue types. Vibrations or vibratory stimulation, acoustic (ultrasound) stimulation, and / or other mechanical stimulation may be provided in conjunction with or instead of the electrical stimulation described herein. For example, in several embodiments, for the disclosure herein that describes electrodes and electrical stimulation, the term electrode can be replaced by effector, transducer, delivery element; and the term electrical stimulation can be replaced by vibratory, ultrasound, and / or mechanical stimulation or delivery.

[0276] In several embodiments, any one or more of the feedforward patient engagement, feedback, neural retraining, or tissue strengthening, stimulation using bilateral leads, stimulation based on Al trained classifiers, or combinations thereof as shown in PCT Application PCT / EP2025 / 080505, which is hereby incorporated by reference in its entirety, can be used with any one or more of the time-dependent programming, adaptive stimulation with flexible sensor input(s) selections for determining breakthrough signatures, personalized thresholds, additional patient safety and / or comfort features, or combinations thereof disclosed herein.

[0277] As used herein throughout this application, the terms "treatment”, "treating”, or "therapy” are used in reference to an intervention regimen for obtaining beneficial or desired results in the recipient. Beneficial or desired results include but are not limited to a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit may refer to reduction, eradication, or amelioration of symptoms or of an underlying disorder being treated. Also, a therapeutic benefit can be achieved with the reduction, eradication, or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. A prophylactic effect includes delaying, preventing, or eliminating the appearance of a disease or condition, delaying, or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof. For prophylactic benefit, a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease may undergo treatment, even though a diagnosis of this disease may not have been made.

[0278] Throughout this application, various embodiments may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0279] As used in the specification and claims, the singular forms "a”, "an” and "the” include plural references unless the context clearly dictates otherwise. For example, the term "a sample” includes a plurality of samples, including mixtures thereof and phrases such as "a device configured to” are intended to include one or more recited devices. Such one or more recited devices can also be collectively configured to carry out the stated recitations. For example, "a processor configured to carry out recitations A, B and C” can include a first processor configured to carry out recitation A working in conjunction with a second processor configured to carry out recitations B and C.

[0280] The terms "approximately,” "about,” and "substantially” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms "approximately”, "about”, and "substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount.

[0281] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0282] While certain embodiments of the present disclosure have been shown and described herein, such embodiments are provided by way of example only. The phrases "in one (or some) implementations”, "in one (or some) instances”, "in one (or some) cases” shall mean "in one (or some) embodiments”. It should be understood that various alternatives within the scope of the embodiments disclosed herein (such as structural and functional equivalents) described herein may be employed.

[0283] All publications, patent applications, issued patents, and other documents referred to in this specification are herein incorporated by reference as if each individual publication, patent application, issued patent,or other document was specifically and individually indicated to be incorporated by reference in its entirety. Definitions that are contained in text incorporated by reference are excluded to the extent that they contradict definitions in this disclosure.

[0284] The terms "comprising,” "including,” "having,” and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term "or” is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term "or” means one, some, or all of the elements in the list. Further, the term "each,” as used herein, in addition to having its ordinary meaning, can mean any subset of a set of elements to which the term "each” is applied. In several embodiments, the systems and methods may consist or consist essentially of the features and steps recited.

[0285] Conditional language used herein, such as, among others, "can,” "might,” "may,” "for example,” and the like, unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain examples include, while other examples do not include, certain features, elements and / or states. Thus, such conditional language is not generally intended to imply that features, elements and / or states are in any way required for one or more examples or that one or more examples necessarily include logic for deciding, with or without author input or prompting, whether these features, elements and / or states are included or are to be performed in any particular example.

[0286] Disjunctive language such as the phrase "at least one of X, Y, or Z,” unless specifically stated otherwise, is otherwise understood with the context as used in general to present that an item, term, etc., may be either X, Y, or Z, or any combination thereof (for example, X, Y, and / or Z). Thus, such disjunctive language is not generally intended to, and should not, imply that certain examples require at least one of X, at least one of Y, or at least one of Z to each be present.

[0287] Methods described herein also include an instruction to perform such method (or a step of such method) and systems may include instructions for use.

[0288] Many other variations than those described herein will be apparent from this disclosure. For example, certain acts, events, or functions of any of the algorithms described herein can be performed in a different sequence, can be added, merged, or left out altogether (for example, not all described acts or events are necessary for the practice of the algorithms). Moreover, acts or events can be performed concurrently, for example, through multithreaded processing, interrupt processing, or multiple processors or processor cores or on other parallel architectures, rather than sequentially. In addition, different tasks or processes can be performed by different machines and / or computing systems that can function together.

[0289] It is to be understood that not necessarily all such advantages can be achieved in accordance with any particular example of the examples disclosed herein. Thus, the examples disclosed herein can be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.

[0290] The various illustrative logical blocks, modules, and algorithm steps described in connection with the examples disclosed herein can be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks,modules, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. The described functionality can be implemented in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the disclosure.

[0291] The various illustrative logical blocks and modules described in connection with the examples disclosed herein can be implemented or performed by a machine, such as a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general purpose processor can be a microprocessor, but in the alternative, the processor can be a controller, microcontroller, or state machine, combinations of the same, or the like. A processor can include electrical circuit or digital logic circuit configured to process computer-executable instructions. In another example, a processor can include an FPGA or other programmable device that performs logic operations without processing computer-executable instructions. A processor can also be implemented as a combination of computing devices, for example, a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. A computing environment can include any type of computer system, including, but not limited to, a computer system based on a microprocessor, a mainframe computer, a digital signal processor, a portable computing device, a device controller, or a computational engine within an appliance, to name a few.

[0292] The steps of a method, process, or algorithm described in connection with the examples disclosed herein can be embodied directly in hardware, in a software module stored in one or more memory devices and executed by one or more processors, or in a combination of the two. A software module can reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of non-transitory computer-readable storage medium, media, or physical computer storage known in the art. An example storage medium can be coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium can be integral to the processor. The storage medium can be volatile or nonvolatile. The processor and the storage medium can reside in an ASIC.

Claims

WHAT IS CLAIMED IS:

1. A system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the system comprising:an implantable pulse generator comprising an actuator and a processor,wherein the processor is configured to control the actuator to generate an electrical stimulation of at least first, second, and third levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, and wherein the processor is further configured to:generate a background level of electrical stimulation, wherein the background level is the first level or the second level based on a time of a day,determine a breakthrough signature, andin response to determination of the breakthrough signature, generate the third level of electrical stimulation,wherein the third level is higher than the second level and the second level is higher than the first level.

2. The system of Claim 1 , wherein the first background level is run at nighttime and the second background level is run at daytime.

3. The system of Claim 1 , wherein the breakthrough signature is configured to be activated based on a time of the day.

4. The system of Claim 1, wherein the breakthrough signature is configured to be activated based on the patient's physiological rhythm.

5. The system of Claim 1, wherein the breakthrough signature is determined by artificial intelligence.

6. The system of Claim 1, wherein delivering the third level of electrical stimulation in response to determination of the breakthrough signature is configured to reduce or prevent habituation.

7. The system of Claim 1, wherein the breakthrough signature comprises a tap on the location of the implantable pulse generator.

8. The system of Claim 7, wherein the implantable pulse generator comprises a motion / posture sensor configured to detect the tap on the implantable pulse generator.

9. The system of Claim 8, wherein the tap is detected in response to a reading of the motion / posture sensor exceeding a personalized sensor threshold, wherein the personalized sensor threshold comprises patient-specific tap sensitivity.

10. The system of Claim 7, wherein the breakthrough signature further comprises a postural change in response to a reading of the motion / posture sensor exceeding a personalized sensor threshold.

11. The system of Claim 7, wherein the breakthrough signature further comprises a muscle contraction in response to a reading of a bioelectrical sensor exceeding a personalized sensor threshold, the bioelectrical sensor located on the one or more electrode leads.

12. The system of any of Claims 9-11, wherein the personalized sensor threshold is determined based at least in part on patient-specific data using artificial intelligence or machine learning.

13. The system of any of Claims 1-7, wherein determination of a different breakthrough signature is configured to trigger a fourth level of electrical stimulation different from the first, second, and third levels.

14. The system of any of Claims 1-7, wherein the stimulation works synergistically with and / or reduces one or more side effects of a pharmaceutical therapy.

15. A system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the system comprising:an implantable pulse generator comprising at least one processor,wherein the at least one processor is configured to generate an electrical stimulation of at least first and second levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, and wherein the processor is further configured to:generate the first level or the second level based on a time of a day,determine a breakthrough signature of the patient, andin response to determination of the breakthrough signature, generate the third level of electrical stimulation,wherein the third level is different than the first level and the second level of stimulation .

16. The system of Claim 15, wherein the breakthrough signature is determined in response to a personalized sensor threshold being met, wherein the personalized sensor threshold is determined based at least in part on patientspecific data associated with the breakthrough signature collected from the patient.

17. The system of Claim 15, wherein the breakthrough signature is determined by artificial intelligence.

18. The system of Claim 15, wherein the first background level is run at nighttime and the second background level is run at daytime.

19. The system of Claim 15, wherein the breakthrough signature is configured to be activated based on a time of the day.

20. The system of Claim 15, wherein the breakthrough signature is configured to be activated based on the patient's physiological rhythm.

21. The system of Claim 15, wherein delivering the third level of electrical stimulation in response to determination of the breakthrough signature is configured to reduce or prevent habituation.

22. The system of Claim 15, wherein breakthrough signature comprises a tap on the implantable pulse generator detected in response to a reading of a motion sensor exceeding a personalized sensor threshold, the motion sensor located on the implantable pulse generator, wherein the personalized threshold comprises patient-specific tap sensitivity.

23. The system of Claim 15, wherein the breakthrough signature further comprises a postural change in response to a reading of a posture sensor exceeding a personalized sensor threshold, the posture sensor located on the implantable pulse generator.

24. The system of Claim 15, wherein the breakthrough signature comprises a muscle contraction in response to a reading of a bioelectrical sensor exceeding a personalized sensor threshold, the bioelectrical sensor located on the one or more electrode leads.

25. The system of any of Claims 15-24, wherein the personalized sensor threshold is further determined based on incontinence triggering events specific to the patient.

26. The system of any of Claims 15-24, wherein determination of a different breakthrough signature is configured to trigger a fourth level of electrical stimulation different from the first, second, and third levels.

27. The system of any of Claims 15-24, wherein the target nerve comprises a pudendal nerve.

28. The system of any of Claims 15-24, wherein the stimulation works synergistically with a pharmaceutical therapy.

29. The system of any of Claims 15-24, wherein the stimulation reduces one or more side effects of a pharmaceutical therapy.

30. The system of any of the preceding claims, wherein the personalized neuromodulation is configured to preemptively stop an incontinence event.

31. The system of Claim 30, wherein the personalized neuromodulation is configured to preemptively stop an urge urinary incontinence event and a stress urinary incontinence event.

32. The system of Claim 30, wherein the personalized neuromodulation is configured to preemptively stop a fecal incontinence event.

33. The system of any of the preceding claims, wherein the personalized neuromodulation is configured to train pain.

34. A method for delivering personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the method comprising:determining a first breakthrough signature of a patient;determining a second breakthrough signature of the patient;determining a third breakthrough signature of the patient,wherein the first breakthrough signature comprises a postural or motion change of the patient,wherein the second breakthrough signature comprises a muscle contraction of the patient, wherein the third breakthrough signature comprises patient notification;providing at least three levels of stimulation,wherein a first level is a first background level,wherein a second level is a second background level,wherein at least a third level is triggered by at least one of the first, second, or third breakthrough signatures, andwherein the at least third level is higher than the second level and the second level is higher than the first level; andoutputting stimulation at the first or second background level based at least in part on a time of a day unless the third level is triggered.

35. A neuromodulation system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the system comprising:an implantable pulse generator including a processor, the processor configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of at least first, second, and third levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, and wherein the processor is further configured to:determine a first breakthrough signature of a patient;determine a second breakthrough signature of the patient;determining a third breakthrough signature of the patient; andoutput stimulation at the first or second background level based at least in part on a time of a day unless the third level is triggered,wherein the first breakthrough signature comprises a postural or motion change of the patient,wherein the second breakthrough signature comprises a muscle contraction of the patient, wherein the third breakthrough signature comprises patient notification;providing at least three levels of stimulation,wherein the first level is a first background level,wherein the second level is a second background level,wherein at least the third level is triggered by at least one of the first, second, or third breakthrough signatures, andwherein at least the third level is higher than the second level and the second level is higher than the first level.

36. A system configured to deliver personalized neuromodulation, the system comprising:a memory device configured to store instructions; anda hardware processor configured to execute the instructions to:output a graphical user interface comprising a programs element, a breakthrough signature settings element, and a program assignment element,wherein the programs element comprises a library of user-configured stimulation programs, andwherein the program assignment element comprises a plurality of time windows; create user-configured stimulation instructions by:receiving a first user input on the graphical user interface to assign a first background program of the library of stimulation programs to a first time window of the program assignment element,receiving a second user input on the graphical user interface to assign a second background program of the library of stimulation programs to a second time window of the program assignment element,receiving a third user input on the graphical user interface to assign a first breakthrough signature to the first time window, andreceiving a fourth user input on the graphical user interface to assign a second breakthrough signature to the second time window, andtransmit the user-configured stimulation instructions to an implantable pulse generator implanted in a patient's body upon establishing connection with the implantable pulse generator such that:in the first time window, the implantable pulse generator is configured to implement the first background program until a third program from the library of stimulation programs is triggered by determination of the first breakthrough signature, andin the second time window, the implantable pulse generator is configured to implement the second background program until the third program is triggered by determination of the second breakthrough signature, andwherein the second background program comprises a higher stimulation level than the first background program, and the third program comprises a higher stimulation level than the second background program.

37. A method for delivering personalized neuromodulation, the method comprising:outputting a graphical user interface comprising a programs element, a breakthrough signature settings element, and a program assignment element,wherein the programs element comprises a library of user-configured stimulation programs, andwherein the program assignment element comprises a plurality of time windows; creating user-configured stimulation instructions by:receiving a first user input on the graphical user interface to assign a first background program of the library of stimulation programs to a first time window of the program assignment element,receiving a second user input on the graphical user interface to assign a second background program of the library of stimulation programs to a second time window of the program assignment element,receiving a third user input on the graphical user interface to assign a first breakthrough signature to the first time window, andreceiving a fourth user input on the graphical user interface to assign a second breakthrough signature to the second time window, andtransmitting the user-configured stimulation instructions to an implantable pulse generator implanted in a patient's body upon establishing connection with the implantable pulse generator such that:in the first time window, the implantable pulse generator is configured to implement the first background program until a third program from the library of stimulation programs is triggered by determination of the first breakthrough signature, andin the second time window, the implantable pulse generator is configured to implement the second background program until the third program is triggered by determination of the second breakthrough signature, andwherein the second background program comprises a higher stimulation level than the first background program, and the third program comprises a higher stimulation level than the second background program.

38. A system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the system comprising:an implantable pulse generator including a processor, the processor configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of at least first, second, and third levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, and wherein the processor is further configured to:deliver a background level of electrical stimulation, wherein the background level is the first level or the second level based on a time of a day,determine a breakthrough signature by assessing a personalized sensor threshold of the patient, andin response to determination of the breakthrough signature, deliver the third level of electrical stimulation,wherein the third level is higher than the second level and the second level is higher than the first level, andwherein the personalized sensor threshold is determined based at least in part on patientspecific data associated with the breakthrough signature collected from the patient.

39. A method for delivering personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the method comprising:providing electrical stimulation of at least first, second, and third levels;delivering a background level of electrical stimulation, wherein the background level is the first level or the second level based on a time of a day,determining a breakthrough signature by assessing a personalized sensor threshold of the patient, andin response to determination of the breakthrough signature, delivering the third level of electrical stimulation,wherein the third level is higher than the second level and the second level is higher than the first level, andwherein the personalized sensor threshold is determined based at least in part on patient-specific data associated with the breakthrough signature collected from the patient.

40. A system configured to deliver personalized neuromodulation using breakthrough signatures, the system comprising:an implantable pulse generator including a processor, the processor configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of different levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, wherein the processor is further configured to be triggered from a background level of electrical stimulation to one or more higher levels of electrical stimulation for a first duration in response to determining a first instance of a breakthrough signature, andwherein, after the first duration the processor is configured to resume the background level for at least a second duration and ignore determination of a second instance of the breakthrough signature in the second duration.

41. A method for delivering personalized neuromodulation using breakthrough signatures, the method comprising:outputting a background level of electrical stimulation;determining a first instance of a breakthrough signature;in response to determining the first instance, triggering from the background level of electrical stimulation to one or more higher levels of electrical stimulation for a first duration; andupon resuming the background level of electrical stimulation after the first duration, ignoring determination of a second instance of the breakthrough signature in the second duration.

42. A system configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the system comprising:an implantable pulse generator including a motion sensor and a processor, the processor configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of different levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient,and wherein the one or more electrode leads further comprise a biopotential sensor,wherein the processor is further configured to:output a background level of electrical stimulation;in response to determining only a first breakthrough signature of the patient based on readings of the motion sensor, increase the electrical stimulation from the background level to one or more higher levels;in response to determining only a second breakthrough signature of the patient based on readings of the biopotential sensor, increase the electrical stimulation from the background level to the one or more higher levels, andin response to determining both the first breakthrough signature and the second breakthrough signature, only respond to the second breakthrough signature.

43. A method for delivering personalized neuromodulation using breakthrough signatures to treat a pelvic condition, the method comprising:outputting a background level of electrical stimulation;in response to determining only a first breakthrough signature of the patient based on readings of a motion sensor, increasing the electrical stimulation from the background level to one or more higher levels;in response to determining only a second breakthrough signature of the patient based on readings of a biopotential sensor, increasing the electrical stimulation from the background level to the one or more higher levels, andin response to determining both the first breakthrough signature and the second breakthrough signature, only responding to the second breakthrough signature.

44. A method of differentiating muscle contractions based on a patient's posture for delivering personalized neuromodulation using breakthrough signatures, the method comprising:providing a first biopotential breakthrough signature and a second biopotential breakthrough signature,wherein the first biopotential breakthrough signature is a first muscle contraction and the second biopotential breakthrough signature is a second muscle contraction,wherein the first muscle contraction and the second muscle contraction are detected using a biopotential sensor located on one or more electrode leads implanted in the patient's body;determining the patient's posture using a posture sensor located on an implantable pulse generator implanted in the patient's body; andbased on the patient's posture, activating one of the first or second biopotential breakthrough signature,wherein the patient's posture comprises at least two of a supine position, a prone position, a left lateral recumbent position, a right lateral recumbent position, standing, or sitting, andwherein in response to the first or second biopotential breakthrough signature, an electrical stimulation delivered to the patient is configured to increase from a background level to one or more higher levels.

45. A neuromodulation system configured to differentiate muscle contractions based on a patient's posture for delivering personalized neuromodulation using breakthrough signatures, the system comprising:an implantable pulse generator including a posture sensor and a processor, the processor configured to execute instructions stored on a non-transitory computer readable storage medium to generate an electrical stimulation of different levels; andone or more electrode leads in electrical communication with the processor,wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, the one or more electrode leads further comprising a biopotential sensor; andwherein the processor is further configured to:provide a first biopotential breakthrough signature and a second biopotential breakthrough signature,wherein the first biopotential breakthrough signature is a first muscle contraction and the second biopotential breakthrough signature is a second muscle contraction, wherein the first muscle contraction and the second muscle contraction are detected using the biopotential sensor;determine the patient's posture using the posture sensor; andbased on the patient's posture, activate one of the first or second biopotential breakthrough signature,wherein the patient's posture comprises at least two of a supine position, a prone position, a left lateral recumbent position, a right lateral recumbent position, standing, or sitting, andwherein in response to the first or second biopotential breakthrough signature, increase the electrical stimulation from a background level to one or more higher levels.

46. A generator for generating an electrical stimulation, the generator comprising:a memory device; anda processor to execute instructions stored on a non-transitory computer readable storage medium to generate the electrical stimulation of at least first, second, and third levels, wherein the first level is a first background level, wherein the second level is a second background level, and wherein the third level is higher than the second level and the second level is higher than the first level,wherein the generator is in electrical communication with one or more electrode leads, wherein the one or more electrode leads comprise at least one stimulation electrode configured to deliver the electrical stimulation to a target nerve or tissue adjacent to the target nerve of a patient, andwherein the processor is further configured to:determine a first breakthrough signature of a patient;determine a second breakthrough signature of the patient;determining a third breakthrough signature of the patient; andgenerate electrical stimulation at the first or second background level based at least in part on a time of a day unless the third level is triggered,wherein the first breakthrough signature comprises a postural change of the patient, wherein the second breakthrough signature comprises a muscle contraction of the patient, wherein the third breakthrough signature comprises patient notification;providing at least three levels of stimulation, andwherein the third level is triggered by at least one of the first, second, or third breakthrough signatures.

47. A method for generating electrical stimulation for neuromodulation, the method comprising:determining a first breakthrough signature of a patient;determining a second breakthrough signature of the patient;determining a third breakthrough signature of the patient,wherein the first breakthrough signature comprises a postural change of the patient, wherein the second breakthrough signature comprises a muscle contraction of the patient, wherein the third breakthrough signature comprises patient notification; and generating the electrical stimulation at a first or second background level based at least in part on a time of a day unless a third level is triggered,wherein the third level is higher than the second background level and the second background level is higher than the first background level, andwherein the third level is triggered by at least one of the first, second, or third breakthrough signatures.

48. A system configured to deliver personalized neuromodulation using breakthrough signatures to treat a condition, the system comprising:at least one processor configured to generate a stimulation of at least first and second levels; and one or more effectors to deliver the stimulation to a target nerve or tissue adjacent to the target nerve of a patient, andwherein the processor is further configured to:generate the first level or the second level based on a time of a day,determine a breakthrough signature of the patient, andin response to determination of the breakthrough signature, deliver the third level of stimulation,wherein the effectors comprise one or more of a transducer, piezoelectric element, electrode, or other stimulation delivery mean, or a combination thereof; andwherein the stimulation comprises one or more of vibratory, ultrasound, mechanical, electrical stimulation, or a combination thereof., andwherein the condition is optionally incontinence, a pelvic disorder, pain, or sexual dysfunction.

49. A generator configured to deliver personalized neuromodulation using breakthrough signatures to treat a pelvic condition, wherein the electrical stimulation comprises stimulations of at least first and second levels generatedbased on a time of a day, and wherein a third level of electrical stimulation is generated in response to determining a breakthrough signature, wherein the third level is different than the first level and the second level of stimulation, wherein the generator or sensor are partially or fully implantable or non-implantable.

50. The use of any of the systems or generators according to the preceding claims for the treatment of incontinence, sexual dysfunction, pelvic disorders, and / or pain.

51. A device for charging any of the systems or generators according to the preceding claims, wherein the device comprises an inductive battery charger.

52. A system and method according to any of the preceding claims for the treatment of pelvic pain.

53. A system and method according to any of the preceding claims for the treatment of sexual dysfunction.

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