Neurostimulation methods and devices

Abstract

A therapy program is devised for a neurostimulation device by a computer program that receives an audio data stream of a music track for reproduction on an audio player device. The audio stream is analyzed to extract variables related to temporal variations in the music such as rhythm and tone data, wherein examples of tone data are melody and chords in the music track. The variables are then applied to a mathematical function that has the variables as parameters to generate the therapy program according to the variables extracted from the audio data stream. The therapy program is then applied to a neurostimulation device to treat the patient.

Description

[0001] Applicant: BIOTRONIK SE & Co. KG

[0002] Our Reference: 24.060P-WO

[0003] Date: 11.09.2025

[0004] NEUROSTIMULATION METHODS AND DEVICES

[0005] The invention relates to neurostimulation methods and devices.

[0006] A known form of neurostimulation is spinal cord stimulation (SCS) which is used for the treatment of chronic pain, such as back pain. SCS therapy uses an implanted SCS device, which is a specific type of implantable medical device (IMD), to apply therapeutic electric pulses to dorsal column fibers via electrodes implanted in the dorsal epidural space of a patient.

[0007] SCS patients sometimes experience therapy habituation. Therapy habituation describes the phenomenon when the initial pain relief experienced by the patient, e.g., in the first few weeks or months after receiving the SCS implant, starts to fade away.

[0008] Edhi, M.M., Heijmans, L., Vanent, K.N. et al. “Time-dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats.” Sci Rep 10, 20358 (2020). https: / / doi.org / 10.1038 / s41598-020-77212-w evaluated time-dynamic pulses (TDPs) such as amplitude modulation, pulse width modulation, sinusoidal rate modulation, and stochastic rate modulation in an animal model to test the hypothesis that modulated SCS using these TDPs leads to improved analgesia compared with conventional SCS therapy. Their results demonstrated that under the parameter settings tested in their study, all tested patterns, except pulse width modulation, significantly reversed mechanical hypersensitivity, with stochastic rate modulation achieving the highest efficacy, followed by the sinusoidal rate modulation. The anti-nociceptive effects of sinusoidal rate modulation on electroencephalogram (EEG) outlasted SCS duration on the behavioral and EEG levels. These results suggest that TDP modulation may improve clinical outcomes by reducing pain intensity and possibly improving the sensory experience. W02024002711 Al discloses an approach for avoiding therapy habituation by incorporating TDP modulation. The SCS controller automatically changes the stimulation parameters at regular or irregular time intervals of the order of days or weeks. The parameters that are changed include: the order in which the electrodes are stimulated and the stimulation frequency, amplitude, and duty cycle. For changing the stimulation parameters, the SCS controller may store multiple program modes and change the program mode from time to time.

[0009] The present disclosure recognizes that music can be a powerful tool for changing mood. Different tempos, melodies, and genres can evoke different emotions. It is therefore proposed to deliver neurostimulation therapy with a therapy program (TP) that has been modified according to a music-inferred pattern. Preferably, neurostimulation is delivered such that the music-inferred pattern is synchronized in real-time with the music playback. In particular, the neurostimulation pattern may be representative of the chosen music’s rhythms and / or time-varying tonal content (e.g., melody, chord progression).

[0010] According to one aspect of the disclosure, there is provided a computer program product for determining a TP for a neurostimulation device, the computer program product comprising a computer-readable storage medium having computer-readable program code embodied therewith, the computer-readable program code configured to: receive an audio data stream of a music track for reproduction on an audio player device; analyze the audio data stream to extract at least one variable related to temporal variations in the music; apply a function having the at least one variables as parameters to generate a TP for a neurostimulation device; outputting a signal to the neurostimulation device to deliver the TP to a patient.

[0011] According to a further aspect of the disclosure there is provided a method of treatment of the human body of a patient, the patient being fitted with a neurostimulation device, the method comprising:

[0012] 24.060P-WO / 11.09.2025 patient operation of a music player app to select a music track for reproduction on an audio player device; generating a TP for the neurostimulation device through use of the computer program product according to the above aspect of the disclosure; and delivering the TP to the patient.

[0013] In some embodiments, the TP is delivered to the patient in synchrony with the music track being played to the patient so that therapy elements are delivered simultaneously with musical elements being listened to by the patient, examples of said musical elements being rhythm and tone(s).

[0014] According to a third aspect of the disclosure there is provided a neurostimulation device, such as an SCS device, comprising: a first lead having a plurality of first electrodes for delivering first stimulation pulses to excitable tissue of a patient, a second lead having a plurality of second electrodes for delivering second stimulation pulses to excitable tissue of a patient; a driver circuit configured to generate the first and second stimulation pulses and apply them to the first and second leads respectively; a controller configured to control the driver circuit to apply the first and second stimulation pulses, wherein the driver circuit comprises: a plurality of first current sources and a first current sink connected to respective ones of the electrodes of the first lead; a plurality of second current sources and a second current sink connected to respective ones of the electrodes of the second lead; an electrical connection between the first and second leads to equalize potential between the first and second leads, thereby providing a common mode voltage reference.

[0015] This design of neurostimulation device enables two frequencies to be delivered simultaneously to two different leads of the same set of leads, and is scalable to higher numbers of leads, thereby allowing multi-tonal musical content such as chords to be transformed into a neurostimulation pattern for application to a set of neurostimulation leads.

[0016] 24.060P-WO / 11.09.2025 Applying music-inferred neurostimulation data, such as SCS patterns, is expected to increase therapy effectiveness and inhibit the tendency for habituation. Music preferences are unique to individuals. Using SCS or other neurostimulation patterns derived from music selected by a patient for playback could potentially create stimulation more attuned to their nervous system and improve pain relief compared to delivering stimulation following an arbitrary TDP modulation (e.g. stochastic rate modulation). Music has inherent variations in tempo, rhythm, and intensity. Inferring SCS or other neurostimulation patterns from music could enable dynamic adjustments to the stimulation based on individual needs and pain fluctuations. A patient’s selection of music for playback may also correlate with the patient’s mood or current pain perception. Moreover, familiar and pleasant music SCS patterns could make the SCS therapy or other neurostimulation therapy more engaging and motivating for the patient, leading to better adherence to treatment and better patient outcomes. Musical paradigms naturally span tonic and sub-perception frequencies delivering multimodal therapy while assisting with acclimation to possible paresthesia.

[0017] Listening to music triggers dopamine release in the brain, which can have mood-boosting and pain-relieving effects. Applying music-inferred SCS, or other neurostimulation patterns that are derived from patterns in the music being listened to, might indirectly leverage this mechanism, in particular if there is real time synchronization between the SCS or other neurostimulation patterns being applied to the patient and the music patterns being played to the patient, such as in terms of frequency mapping between notes in the music and applied neurostimulation frequency and beat mapping between the music rhythm and the neurostimulation pulses. The mapping of note frequencies to applied neurostimulation frequencies may follow single tones in the music (such as the melody) or multiple simultaneous tones in the music (such as notes of a chord). In other words, at any point in time, the neurostimulation therapy may have only a single frequency or multiple frequencies.

[0018] A patient’s music choice may likely correlate with the patient’s emotional state. Therefore, tailoring the SCS or other neurostimulation pattern to the patient’s music selection could provide more effective therapy and help manage pain-related anxiety or depression.

[0019] 24.060P-WO / 11.09.2025 If the patient’s response to the TP is monitored by providing the neurostimulation device with a sensing circuit, then the effects of TP on the patient can be monitored. This will enable, for example, the magnitude of pulses being applied to be adjusted to ensure they are above-threshold while not being unnecessarily high. In particular, in some embodiments, the sensing circuit is connected to the first and second leads and configured to measure a signal that occurs responsive to application of a stimulation pulse, the measurement signal including one or both of an evoked compound action potential (ECAP) component, and an evoked synaptic activity potential (ESAP) component.

[0020] The computer program product may be configured such that there is at least one music parameter derived from rhythm data of the music track, for example the TP’s neurostimulation pulses can be given timings that follow the rhythm data of the music track.

[0021] The computer program product may be configured such that there is at least one music parameter derived from tone data of the music track, for example one of the parameters may be for mono-tonal data derived from a melody in the music track and another of the parameters may be related to multi-tonal data derived from chords in the music track. Moreover, the tone data may be parameterized in terms of phases of a musical envelope with parameters of attack, decay, sustain and release. In particular, in certain embodiments the TP comprises neurostimulation pulses which modulate at least one of pulse amplitude, pulse width and pulse repetition frequency to follow the phases of the musical envelope.

[0022] According to an embodiment of the present invention, the neurostimulation is spinal cord stimulation, deep brain stimulation, peripheral nerve stimulation, vagus nerve stimulation or renal nerve stimulation.

[0023] This invention will now be further described, by way of example only, with reference to the accompanying drawings.

[0024] Figure 1 is a schematic diagram of an IMD with an SCS stimulator in a medical device communication system with standard architecture in which a patient remote controls SCS therapy delivery to a patient fitted with an IMD.

[0025] 24.060P-WO / 11.09.2025 Figure 2 is a schematic diagram showing an SCS stimulator attached to a lead arrangement of electrodes according to an embodiment of the invention.

[0026] Figures 3A and 3B are schematic views from the front and behind of a handheld touch screen computing device such as a smartphone or tablet which may function as the patient remote.

[0027] Figure 3C is a schematic block diagram of the functional components of the device of Figures 3A and Figure 3B.

[0028] Figure 4 is a flow diagram showing generation of a TP from an input audio data stream.

[0029] Figure 5 is a schematic diagram illustrating how current is applied to a set of leads during a mode of SCS therapy application according to another extension which takes account of chords in the music.

[0030] Figure 6 is a graph plotting voltage against time during SCS therapy for different relevant neural responses.

[0031] In the following detailed description, for purposes of explanation and not limitation, specific details are set forth in order to provide a better understanding of the present disclosure. It will be apparent to one skilled in the art that the present disclosure may be practiced in other embodiments that depart from these specific details.

[0032] An SCS device is a type of IMD that is used for chronic pain therapy of a patient. An SCS device uses electrical charge sent through electrodes on one or more leads implanted in the epidural space. Control parameters include at least: pulse width, frequency, amplitude and electrode selection. Additionally, duty cycling and burst stimulation can be introduced as further control parameters to modulate therapy and better manage battery consumption through the introduction of alternating periods of carrier and envelope stimulation.

[0033] 24.060P-WO / 11.09.2025 An IMD typically forms part of a medical device communication system (MDCS) that is configured to upload clinical data from the IMD on a continual basis via a MDCS to a remotely located data repository, which may be a data center. In an SCS device, clinical data includes both patient data relating to physiological monitoring of a patient's health, for example as collected by sensors of the IMD, and device data related to status and operation of the IMD, for example data logging each time an SCS device is used and at what stimulation level in terms of electrical pulse width and pulse frequency as well as control signals issued to the SCS device to optimize delivery of pain relief These clinical data can then be accessed by health care staff accessing the data center using suitably designed software applications. A treatment plan for a patient, a so-called TP, can then be decided upon based on analysis of these clinical data. The analysis may be expert analysis by a health care professional or computer-automated analysis with a software program, e.g., running on computing resource at a neuro-service data center, or a combination of both.

[0034] Figure 1 shows a standard architecture of a MDCS 1 for communication between an IMD 10 implanted in a patient and a remotely located data center 60, which is accessible to health care staff using suitable application software. The IMD 10 includes therapeutic components for patient treatment, such as an SCS device 11 (or another IMD stimulator) incorporating an implantable pulse generator (IPG) 100, and therapeutic components for patient monitoring, such as an IMD sensor 13. The IMD 10 further comprises chipsets providing computing and telecommunications resource in the form of memory 18, a processor 19 and a wireless personal area network (WPAN) transceiver 12. The IMD 10 is powered by an electrical energy source 14, in this example by a rechargeable battery 14. The IMD's rechargeable battery 14 of an implanted IMD can be charged in a contactless manner by a charger 23, for example a resonant inductive charger, which is placed on the patient's skin adjacent the implanted IMD 10 to charge its rechargeable battery 14. The charger 23 is itself provided with an energy source 24, here a rechargeable battery 24, as well as an external mains power connection 29, for example an external power jack, to power the charger 23 so that its rechargeable battery 24 can be recharged. Alternatively, the charger's battery 24 can be recharged wirelessly by placing the charger 23 on a mains-powered charging pad. The IMD WPAN transceiver 12 uses a suitable WPAN protocol such as Bluetooth Low Energy

[0035] 24.060P-WO / 11.09.2025 (BLE), Medical Implant Communication System (MICS) or Medical Device Radiocommunications Service (MedRadio), the latter two being almost identical protocols.

[0036] The patient is provided with a patient remote controller 30 (hereinafter also called “patient remote 30”), for example a smartphone with wireless transceivers 32, 35, 36 respectively for WPAN (e.g. BLE), LPWAN, cellular (e.g., 4G / LTE / 5G) and Wireless Local Area Network (WLAN) communication. If a smartphone is used as the patient remote 30, this is a smartphone that is possessed, e.g., owned, by the patient in which the IMD 10 is implanted and on which a software application ('app') is installed. The app is then a so-called Software as a Medical Device (SaMD) which is defined by the United States Food and Drug Administration (FDA) as software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device. A more traditional option is that the patient remote is a separate handheld device having the format of a remote controller similar to that familiar for television control or of a simple telephone handset of the pre-smartphone era.

[0037] The cellular transceiver 35 and WLAN transceiver 36 provide two different data communication paths for the patient remote 30 to upload clinical data from the IMD 10 via an internet connection 50 to a remotely located data center 60 (hereinafter also called “backend 60”) acting as repository for storage of clinical data and / or as a host for the services, for example a neuro-service data center. The remote's WLAN transceiver 36 can upload data to the backend 60 via a router 38 and a telephone line 40 (or telephone network 40) using a wired internet connection 50. The internet connection 50 may provide access to one or more distributed networks and / or cloud services. The remote's cellular transceiver 35 can upload data to the backend 60 via one or more cellular network base stations 42 (cellular towers), for example LPWAN-capable cellular network base station. In some cases, instead of a public communication network, a dedicated point-to-point transmission, e.g., via a dedicated telephone line, may be provided for uploading clinical data. In all these scenarios, uploading of clinical data from the IMD 10 to the backend 60 takes place via the intermediary of the patient remote 30, the latter thereby acting as a relay device.

[0038] 24.060P-WO / 11.09.2025 Health care staff, such as health care professionals (HCPs), clinical specialists and representatives and remote care team members have access to the backend 60 via suitable portals 70 with the aid of a software application running on the backend 60 and / or the portal 70 to provide the necessary user interfacing, diagnostics and so forth. At least one portal 70 is provided by at least one workstation for health care staff to access a data center, e.g., the backend 60. Analysis and diagnostic software may also be run at the backend 60 to analyze clinical data from individual patients or groups of patients.

[0039] Figure 2 is a schematic diagram showing the SCS device 11 of the IMD 10 attached to a lead arrangement 80 comprising multiple implantable percutaneous leads 1011 to 101N with each lead incorporating multiple electrodes 102. a to 102.h. In the illustrated example, there are multiple leads but in other examples there may be only one lead. The SCS device 11 comprises an electrode driver circuit 16 for providing a suitable drive current to each of the electrodes 102. a to 102.h according to a set of control parameters that follow a TP as controlled by a controller 15 which may be implanted wholly in hardware as a control circuit but may include a combination of hardware, firmware (e.g. programmable logic array(s)) and / or software elements. The controller 15 delivers control signals to the electrode driver circuit 16 according to a TP devised by a computer program running on the processor 19 (e.g., a microprocessor) of the IMD 10. The computer program is stored in the IMD’s memory 18. These hardware and software components operate collectively to provide an intelligent pulse generator to deliver electrical pulses to the electrodes 102. a to 102.h conforming to a particular set of parameters, including amplitude, pulse width, frequency and / or duty cycle to provide stimulation therapy. For SCS, the leads 1011 to 101N are implanted at or near a patient’s spinal cord to direct electrical charge into the patient’s tissue for spinal cord stimulation. The SCS device 11 is implanted subcutaneously.

[0040] An IMD’s electrode sensing circuit 17 is provided to collect electrical signals generated responsive to application of stimulation pulses from the electrodes 102. a to 102.h. These are the so-called evoked compound action potential (ECAP) signals. Application of a therapeutic electric pulse above a certain threshold voltage to a nerve trunk stimulates or ‘evokes’ a compound action potential (CAP), resulting in these signals being referred to as evoked CAPs (ECAPs). The ECAP signal is the summation of many action potentials from

[0041] 24.060P-WO / 11.09.2025 the individual axons in the nerve trunk. Measuring ECAP signals is useful for quantifying the effect of the neural stimulation. For example, in SCS the ECAP signal senses neural activation of the dorsal column fibers. An ECAP signal is recorded within a short time window after the beginning of a stimulus pulse, of the order of 100 microseconds, to ensure correlation of stimulus and response. After a certain stimulation threshold is attained ECAP signal amplitude increases linearly with the stimulus current before saturating at high levels. It is known to use the amplitude of ECAP signals as a control variable in a feedback loop to control an SCS device. The IMD electrode sensing circuit 17 is connected to supply the ECAP signals to a signal processing circuit 20 for processing the ECAP signals. The signal processing circuit 20 then supplies processed information regarding to the ECAP signals to the controller 15.

[0042] The controller 15 is configured to deliver therapy such as multiphase rotating electrode therapy, e.g., according to US10870000, the relevant contents of which are incorporated herein by reference, or W02024002711A1, the relevant contents of which are incorporated herein by reference. The controller 15 may store multiple therapy programs (TPs) in memory and is configured to select one of the TPs as appropriate, either itself or following an instruction from a clinical programmer or other external human intervention. The controller 15 may operate under user control from the patient remote 30 which is loaded with a suitable SaMD app for this purpose, which may be referred to as a therapy programming app.

[0043] Figures 3A and 3B are schematic perspective views from the front and behind of a handheld touch screen computing device such as a smartphone or tablet which may function as the patient remote 30. Figure 3C is a block diagram of the functional components of the device of Figures 3A and Figure 3B.

[0044] Referring to Figure 3A, the patient remote 30 has a smartphone or tablet format. The patient remote 30 is arranged in a housing with a front face (facing outwards from Figure 3A), a rear face and a bezel forming the edges of a substantially rectilinear object. The front face is mostly taken up with a touch screen display which combines a display 115 with a touch sensitive area 103. The touch screen enables the user to input commands to applications running on the patient remote through gestures. The front face also accommodates a

[0045] 24.060P-WO / 11.09.2025 mechanical key (or button) 104 and two touch sensor keys (or buttons) 106, 108, one either side of the mechanical key 104. The edges of the housing accommodate a mechanical rocker switch 110 for volume control and an on / off switch 112.

[0046] A front facing camera 111 for capturing stills or video images is arranged on the front face near the top of the housing facing forwards and has adjacent to it a microphone 105 for capturing audio and a speaker 107 for outputting audio.

[0047] Referring to Figure 3B, the rear view, a rear facing camera 114 for capturing stills or video images is arranged near the top of the housing facing backwards. A battery 116 is accommodated within the housing and constitutes a power supply (shown with dashed lines). The power supply further includes an external power input socket 118 which may be used for powering the device as well as charging the battery 116. Alongside the power input socket 118 at the bottom of the device there is another external connector in the form of an audio jack 120 for audio output. Further external interfaces may be provided including various ports, holders, and sockets for physical connections. With dotted lines we show two internal holders 122, 124 which may be for a SIM card and a memory card or further SIM card. The memory card is a kind of data storage device.

[0048] Referring to Figure 3C, this shows selected functional components of the patient remote 30. The patient remote 30 has radio components 130, input / output (I / O) components 140, one or more controllers 150 associated with one or more processors 160 and one or more memories 170, a power supply 180, sensor components 190 and external interfaces 200. The memory 170 is operable to store computer applications ('apps'), in particular a therapy programming app 162 and a music player app 163. Each app comprises software code portions that are loadable into and executable by the processor 160. The controller(s) 150 may include a touch sensor controller and a display controller, or a combined touch and display controller.

[0049] The processor(s) may comprise separate processing units for specialist tasks such as touch sensing, display drive, video processing, speech / audio analysis and / or speech / audio synthesis. The controller(s) and associated processor(s) and memory(ies) have the task of

[0050] 24.060P-WO / 11.09.2025 controlling the patient remote 30 and executing computer programs stored in the memory(ies). The memory(ies) may store computer applications for running on the computing device as well as collecting data from the various I / O devices. The controller(s) typically functions to control overall operation of the computing device, in addition to the operations associated with the application programs (‘apps’). The controller(s) processes signals, data, information and the like input or output through the above-mentioned components and / or runs application programs saved in the memory, thereby processing or providing a user with appropriate information and / or functions.

[0051] The radio components 130 includes the above-mentioned WPAN transceiver 32, LTE transceiver 35 and WLAN transceiver 36, as well as a GPS module 33. The I / O components 140 include a display capable of displaying content and also acting as part of a graphical user interface, wherein the display may be based on a suitable technology such as liquid crystal or organic light emitting diodes, as well as a position-sensitive touch sensor area overlaid on, or formed as an integral part of, the display to serve as part of a graphical user interface in conjunction with the display with optionally other touch sensor areas or buttons (e.g. on the reverse side or edge (bezel) of the device housing. Further I / O components, as previously mentioned, are front and rear facing cameras 111, 114 for capturing stills or video images, a microphone 105 for capturing audio, a speaker 107 for outputting audio and a haptic output embedded in the touch screen to provide tactile feedback. The sensing components include a gyroscope, an accelerometer, an ambient light sensor and a temperature sensor, for example. The external interfaces may include various ports and sockets for physical connections, such as a SIM card, wired LAN connectors, memory cards, audio jack socket, USB ports and so forth.

[0052] As mentioned above, the smartphone is loaded with a therapy programming app 162 for formulating and controlling delivery of a TP and a music player app 163, such as an audio or video streaming service. Upon a particular song being played on the music player app 163, typically by patient selection, the therapy programming app 162 receives the audio data stream of the music and processes it to create a TP. The therapy programming app 162 may be programmed to tap into the output of the music player app 163 via programming of a software development kit (SDK) for the operating system of the patient remote 30. The

[0053] 24.060P-WO / 11.09.2025 processing extracts parameters from the music and maps the extracted music parameters onto therapy parameters to devise the TP. Music parameters may include one or more of: beat, stomp, clap, pat, snap, attack decay, sustain release. The TP created from the audio data stream is then delivered to the patient through suitable wireless data communication between the patient remote 30 and the IMD 10. If a standard TP is already running, then the music- derived TP may supplant that TP for the duration of the song or the user’s active session playing songs from the music player app 163.

[0054] Figure 4 is a flow diagram showing this process of devising a TP for a neurostimulation device. In Step SI, the computer program of patient remote 30 receives an audio data stream of a music track as input. In Step S2, the audio stream is analyzed to extract variables related to temporal variations in the music such as rhythm and tone data, wherein examples of tone data are melody and chords in the music track. In Step S3, the variables are applied to a mathematical function that has the variables as parameters to generate the TP according to the variables extracted from the audio data stream. In Step S4, the TP is output to a neurostimulation device which delivers treatment to the patient according to the TP.

[0055] In embodiments in which the patient remote 30 is a separate handheld device and not integrated into a smartphone, then the music player app 163 will be hosted by the patient’s smartphone and the smartphone will also be loaded with the above-mentioned therapy programming app 162. However, in this case, the therapy programming app 162 will have the additional function of configuring the patient remote 30 to deliver the TP to the IMD 10 through wireless communication.

[0056] An extension of the basic implantation is to add a harmony derived component to the stimulation pattern of the TP by amplitude modulation. This may be done through applying the concept of a musical envelope. Notes played by particular instruments, in particular keyboard instruments, can be classified into an envelope with the phases of attack, decay, sustain and release (ADSR). Attack is the time taken for the rise of the note level from nil to peak. Decay is the time taken for the note level to reduce from the attack level to the sustain level. Sustain is the level maintained until the key is released. Release is the time taken for

[0057] 24.060P-WO / 11.09.2025 the level to decay to nil. The TP is then modified by amplitude modulation of the stimulation pulses according to the musical envelopes extracted from the music.

[0058] A further extension is to take account of overtones in the music, i.e., an integer multiple frequency above the fundamental frequency. When such overtones occur in the music, additional stimulation pulses are applied to the TP at multiples of the basic stimulation frequency set for the patient. For example, if the patient has a basic stimulation frequency of 300 Hz, then tones in the music at the fundamental frequency are applied at 300 Hz (or some offset from 300 Hz), whereas an n-th order overtone in the music is applied at a multiple of ‘n’ from the applied stimulation frequency, e.g., 600 Hz for a second order overtone (a.k.a. first harmonic).

[0059] Figure 5 illustrates a preferred embodiment of how current can be applied to a set of leads during a mode of SCS therapy application according to another extension which enables two frequencies to be delivered simultaneously to two different leads of the same set of leads. This is to allow a musical chord, which comprises multiple frequency components, to be transposed into respective multiple frequency components that are applied to respective leads 101. Multiple simultaneous “tones” are thus delivered via multiple electrodes 102.n to emulate music chords. We explain an example implementation in which two “tones” are applied to two leads 101. a and 101. b respectively. The same approach may be used with a higher number of leads, e.g., 3, 4, 5, 6, 7 or 8 leads. A first “tone” is applied to electrodes 102.a, 102.b and 102.c of lead 101. a respectively by first and second current source elements 501.a and 501.b, and a current sink element 500. A second “tone” is applied - simultaneously to the first “tone” - to electrodes 102. d, 102. e and 102.f of lead 101. b respectively by first and second current source elements 503. a and 503. b, and a current sink element 502. A common mode voltage reference connection 505 between the leads 101. a, 101. b enables the two frequencies to be applied simultaneously and share a common current return. The current amplitude 500 is the sum of the current amplitude on current sources 501.a and 501.b. The current amplitude 502 is the sum of the current amplitude on current sources 503. a and 503. b. A voltage 504 is applied to the inputs of both current sources 501. a, 501. b, 503. a, 503. b of each lead 101, a, 101. b. The common mode voltage reference connection 505 ensures compliance with the common mode voltage requirement for the current sources so

[0060] 24.060P-WO / 11.09.2025 that they each operate above their compliance voltages. This is further described in US2019255333A1, the relevant contents of which are incorporated herein by reference. The effect of the current sink elements is to reduce cross-talk between the respective pulse trains of the different tones as applied to the respective leads. This provides isolation between stimulation pulse trains which allows the multiple tones to be delivered simultaneously in a way that is possible with a single power supply. This is important since an IMD 100 typically relies on a single battery for its power supply. The use of current sink elements differs from multiphase rotating electrode therapy delivery where currents sink elements are not required.

[0061] Instead of the analog electronic design of Figure 5, it is possible to use a conventional analog electronic design for supplying stimulation pulses to the leads 101, in which case at any one time it is only possible to deliver one tone (frequency) to all the leads. This assumes the IMD 100 only has a single power supply. Another way to allow multiple tones to be delivered simultaneously to multiple leads of the same set of leads with a conventional analog electronic design is to provide the IMD 100 with multiple independent power supplies so that two or more leads (or groups of leads) are electrically independent of each other. Different individual leads (or groups of leads) are then supplied with power from different ones of the power supplies.

[0062] In another extension, ECAPs or evoked synaptic activity potentials (ESAPs) are sensed during application of a music-derived TP to the patient. ESAPs are a newly discovered gross potential thought to arise from activation of synapses between the sensory dorsal column fibers and inner neurons in the superficial dorsal hom (the site of the pain gate).

[0063] ESAP signals are a direct measure of spinal synaptic current in contrast to ECAP signals which measures the activity of dorsal column axons that occurs synchronously with SCS stimulation. ECAP is therefore an indirect measure of sensory processing in the dorsal hom whereas ESAP is a direct measure thereof.

[0064] According to this embodiment, the ECAP or ESAP signals are analyzed by signal processing based on parameters such as timing, frequency or rhythm to identify unique or therapeutically relevant response patterns. The ECAP signals are collected from the same

[0065] 24.060P-WO / 11.09.2025 vertebral segment to the site where the SCS stimulation is being applied and the ESAP signals are collected one or two vertebral segments inferior to the site where the SCS stimulation is being applied.

[0066] Figure 6 is a graph plotting voltage against time during SCS therapy for each of a stimulation artifact 600, an ECAP signal 601 and an ESAP signal 602. These are experimental plots obtained in a pre-clinical ovine experiment using SCS. The bottom trace shows the stimulation artifact 600. The middle trace shows the ECAP signal 601. The top trace shows the ESAP signal 602. The 50 mV y-axis scale for the ESAP signal 602 corresponds to 25 pV / div.

[0067] Present understanding in the art of SCS mechanisms of action suggests that SCS patterns, which maximally produce potentiation of the ESAP signal, will also maximize pain relief efficacy. This understanding can be applied in the present invention by using the ESAP signal as the control parameter in a feedback loop in order to measure the correlation between the music-derived TP and ESAP signals and use any detected correlation to maximize ESAP potentiation (e.g. slower tempo rhythms). Using the ESAP signals in this way in a feedback control loop can be applied to maximize parameters such as pain suppression and the emotional benefit of SCS therapy. The use of ESAP signals as a feedback parameter to control and optimize the SCS therapy offers an advantage over the use of ECAP signals owing to the more direct nature of the former compared to the latter. Nevertheless, ECAP signals may also be used as a feedback parameter either instead of ESAP signals or in combination therewith. Indeed, they may provide different clinically relevant feedback which may be complimentary in nature.

[0068] Other biomarkers, such as far-field electromyograms sensed between unused electrodes 102 or between an unused electrode 102 and the IMD 100 can be utilized to measure treatment benefits provided by coordinating or synchronizing in real time the SCS or other neurostimulation therapy being delivered with music being listened to by the patient, these treatment benefits being measured in terms of factors such as patient mood and patient- reported pain scores.

[0069] 24.060P-WO / 11.09.2025 In another preferred embodiment, artificial intelligence learning is applied to ESAP information to identify particularly therapeutically effective music timings, frequency sets, etc., which may be on a personalized basis, i.e., specific to an individual patient, or a group of patients with similar medical diagnosis. The TP creation algorithm may therefore be configured to generate TPs from a music data stream in a way that is most therapeutically effective for the patient.

[0070] Example 1

[0071] The patient profile is for multiphase rotating electrode therapy at a stimulation frequency of 300 Hz. The song is “We will rock you” by Queen.

[0072] Beats 1-16 (rhythm) :

[0073] 1. Stomp 400 Hz for 0.19 s

[0074] 2. Clap 200 Hz for 0.10 s

[0075] 3. Pat 300 Hz for 0.15 s

[0076] 4. Snap 500 Hz for 0.06 s

[0077] Beat 17 (melody):

[0078] 5. Increase the applied frequencies by 50 Hz for 0.5 s ("You");

[0079] Beats 18-33 (rhythm):

[0080] 6. Stomp 400 Hz for 0.19 s

[0081] 7. Clap 200 Hz for 0.10 s

[0082] 8. Pat 300 Hz for 0.15 s

[0083] 9. Snap 500 Hz for 0.06 s

[0084] Beat 34 (melody):

[0085] 10. Increase the applied frequencies by 100 Hz for 0.5 s ("Rock");

[0086] Beats 35-60 (rhythm):

[0087] 11. Stomp 400 Hz for 0.19 s

[0088] 12. Clap 200 Hz for 0.10 s

[0089] 13. Pat 300 Hz for 0.15 s

[0090] 14. Snap 500 Hz for 0.06 s

[0091] 24.060P-WO / 11.09.2025 Example 2 is a modification of Example 1 with additional amplitude modulation according to the ADSR approach described above as follows:

[0092] Amplitude modulation is applied to the stomps (total duration 0.19 s) as follows:

[0093] 1. Attack: 0.025 s

[0094] 2. Decay: 0.075 s

[0095] 3. Sustain: 0.07 s

[0096] 4. Release: 0.02 s

[0097] Amplitude modulation is applied to the claps (total duration 0.10 s) as follows:

[0098] 1. Attack: 0.02 s

[0099] 2. Decay: 0.04 s

[0100] 3. Sustain: 0.02 s

[0101] 4. Release: 0.02 s

[0102] Amplitude modulation is applied to the pats (total duration 0.15 s) as follows:

[0103] 1. Attack: 0.025 s

[0104] 2. Decay: 0.055 s

[0105] 3. Sustain: 0.05 s

[0106] 4. Release: 0.02 s

[0107] Amplitude modulation is applied to the snaps (total duration 0.06 s) as follows:

[0108] 1. Attack: zero

[0109] 2. Decay: 0.02 s

[0110] 3. Sustain: zero

[0111] 4. Release: 0.04 s

[0112] Example 3 is a modification of Example 1 (or Example 2) which incorporates the chord emulation as described above.

[0113] When there is an E tone, then apply a stimulation frequency of 220 Hz.

[0114] 24.060P-WO / 11.09.2025 When there is an A tone, then, to replicate the power chord structure, apply simultaneously stimulation frequencies of 220 Hz and 330 Hz to maintain the perfect fourth interval and thus emulate the riff.

[0115] 24.060P-WO / 11.09.2025 REFERENCE NUMERALS

[0116] I Medical Device Communication System (MDCS)

[0117] 10 Implantable Medical Device (IMD)

[0118] II IMD stimulator, e.g., SCS device with attached electrodes

[0119] 12 IMD wireless personal area network (WPAN) transceiver

[0120] 13 IMD sensor

[0121] 14 IMD electrical energy source

[0122] 15 IMD controller

[0123] 16 IMD electrode driver circuit

[0124] 17 IMD electrode sensing circuit

[0125] 18 IMD memory

[0126] 19 IMD processor

[0127] 20 signal processing circuit

[0128] 23 charger for IMD

[0129] 24 charger energy source

[0130] 29 charger external mains power connection

[0131] 30 computing device, like patient remote controller (patient remote), e.g., smartphone or tablet device

[0132] 32 smartphone wireless personal area network (WPAN) transceiver

[0133] 33 GPS sensor

[0134] 35 smartphone cellular transceiver (LTE)

[0135] 36 smartphone wireless local area network (WLAN) transceiver

[0136] 38 router

[0137] 40 telephone line / telephone network

[0138] 42 cellular network base station (cellular tower)

[0139] 50 internet connection

[0140] 60 remotely located data center (backend)

[0141] 70 portal

[0142] 80 lead arrangement

[0143] 100 Implantable Medical Device (IMD)

[0144] Wli to lOlN leads

[0145] 24.060P-WO / 11.09.2025 l02.h electrodes touch sensitive area mechanical key (or button) microphone (audio in) touch sensor key (or button), first loudspeaker (audio out) touch sensor key (or button), second mechanical rocker switch for volume control front facing camera on / off switch rear facing camera display battery external power input socket audio j ack (audio out) internal card holder, first internal card holder, second radio components input / output (I / O) components controller(s) processor(s) therapy programming app music player app memory (ies) power supply sensor components external interfaces current sink element current source element, first current source element, second current sink element current source element, first

[0146] 24.060P-WO / 11.09.2025 current source element, second voltage common mode voltage reference connection

[0147] 24.060P-WO / 11.09.2025

Claims

Claims1. A computer program product for determining a therapy program for a neurostimulation device, the computer program product comprising a computer-readable storage medium having computer-readable program code embodied therewith, the computer-readable program code configured to: receive an audio data stream of a music track for reproduction on an audio player device; analyze the audio data stream to extract at least one variable related to temporal variations in the music; apply a function having the at least one variable as parameters to generate a therapy program for a neurostimulation device; outputting a signal to the neurostimulation device to deliver the therapy program to a patient.

2. The computer program product of claim 1, wherein there is at least one music parameter derived from rhythm data of the music track.

3. The computer program product of claim 2, wherein the therapy program comprises neurostimulation pulses having timings that follow the rhythm data of the music track.

4. The computer program product of claim 1, 2 or 3, wherein there is at least one music parameter derived from tone data of the music track.

5. The computer program product of claim 4, wherein one of the parameters is for mono-tonal data derived from a melody in the music track.

6. The computer program product of claim 4 or 5, wherein two or more the parameters are for multi-tonal data derived from chords in the music track.24.060P-WO / 11.09.20257. The computer program product of claim 4, 5 or 6, wherein the tone data is parameterized in terms of phases of a musical envelope with parameters of attack, decay, sustain and release.

8. The computer program product of claim 7, wherein the therapy program comprises neurostimulation pulses which modulate at least one of pulse amplitude, pulse width and pulse repetition frequency to follow the phases of the musical envelope.

9. The computer program product of any one of the preceding claims, wherein the therapy program is generated in real time from the audio data stream.

10. The computer program product of any one of the preceding claims, wherein the therapy program is configured to provide spinal cord stimulation.

11. A method of treatment of the human body of a patient, the patient being fitted with a neurostimulation device, the method comprising: patient operation of a music player app to select a music track for reproduction on an audio player device; generating a therapy program for the neurostimulation device through use of the computer program product of any one of the preceding claims; and delivering the therapy program to the patient.

12. The method of claim 11, wherein said delivering is synchronized with said reproduction.

13. The method according to one of the preceding claims, wherein the neurostimulation is spinal cord stimulation, deep brain stimulation, peripheral nerve stimulation, vagus nerve stimulation or renal nerve stimulation.

14. A neurostimulation device comprising: a first lead (101 i) having a plurality of first electrodes (102) for delivering first stimulation pulses to excitable tissue;24.060P-WO / 11.09.2025a second lead (IOI2) having a plurality of second electrodes (102) for delivering second stimulation pulses to excitable tissue; a driver circuit (16) configured to generate the first and second stimulation pulses and apply them to the first and second leads (1011, 1012) respectively; a controller (15) configured to control the driver circuit to apply the first and second stimulation pulses, wherein the driver circuit (16) comprises: a plurality of first current sources and a first current sink connected to respective ones of the electrodes of the first lead (1011); a plurality of second current sources and a second current sink connected to respective ones of the electrodes of the second lead (1012); an electrical connection between the first and second leads (1011, IOI2) to equalize potential between the first and second leads, thereby providing a common mode voltage reference.

15. The neurostimulation device of claim 13, further comprising: a sensing circuit (17) connected to the first and second leads (1011, IOI2) and configured to measure a signal that occurs responsive to application of a stimulation pulse, the measurement signal having at least one of an evoked compound action potential, ECAP, component, and an evoked synaptic activity potential, ESAP, component.24.060P-WO / 11.09.2025

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