Evaluation and adjustment of time-varying pulse patterns in spinal cord stimulator systems

Abstract

Methods, systems, and computer-implementable algorithms for determining time-varying pulses for a patient with an implantable stimulator device (ISD) are disclosed. At least one time-invariant tonic stimulation pulse parameter (e.g., amplitude, pulse width, or frequency) is modified by a modulation function to produce a time-varying pulse (TVP), and one or more measurements are made to determine the effectiveness of the TVP. The measurements can be objective and taken from the patient, and / or subjective and determined based on feedback from the patient. In one example, the objective measurements can include one or more features determined from an epidural spinal cord electrogram (ESG) signal detected by the ISD, which can include an evoked compound action potential. The one or more measurements are used to determine a score for the TVP, which is useful in selecting the best TVP for use with the patient, or for adjusting the modulation function applied to the tonic stimulation parameters.

Description

Technical Field

[0001] This application relates to implantable medical devices (IMDs), and more specifically, to techniques for determining optimal time-varying stimulation pulses for a given patient. Background Technology

[0002] Implantable neurostimulation devices are devices that generate electrical stimulation and deliver it to the body's nerves and tissues for the treatment of various biological diseases, such as pacemakers for treating arrhythmias, defibrillators for treating myocardial fibrillation, cochlear stimulators for treating deafness, retinal stimulators for treating blindness, muscle stimulators for generating coordinated limb movements, spinal cord stimulators for treating chronic pain, cortical and deep brain stimulators for treating motor and psychological disorders, and other neurostimulators for treating urinary incontinence, sleep apnea, shoulder subluxation, etc. The following description will generally focus on the use of the invention in spinal cord stimulation (SCS) systems (such as the system disclosed in U.S. Patent 6,516,227). However, the invention can be applied to any implantable neurostimulation device system.

[0003] SCS systems typically include an implantable pulse generator (IPG) 10, as shown in Figure 1. The IPG 10 includes a generally biocompatible conductive device housing 12 that houses the IPG's circuitry and a battery 14 for providing power to the IPG to function. The IPG 10 is coupled to tissue stimulation electrodes 16 via one or more electrode leads forming an electrode array 17. For example, one or more percutaneous leads 15 with annular or open-ring electrodes 16 supported on a flexible body 18 can be used. In another example, a paddle-shaped lead 19 provides the electrodes 16 positioned on one of its generally flat surfaces. Lead wires 20 within the leads are coupled to proximal contacts 21, which can be inserted into lead connectors 22 in a head 23 attached to the IPG 10, the head of which may include, for example, epoxy resin. Once inserted, the proximal contact 21 connects to the head contact 24 within the lead connector 22, which in turn couples to the stimulation circuitry 28 within the housing 12 via the feedthrough pin 25 and the housing feedthrough 26, which is described below.

[0004] In the illustrated IPG 10, there are 32 electrodes (E1 to E32) either separated between four percutaneous leads 15 or contained on a single paddle-shaped lead 19, and therefore the head 23 may include an 8-electrode lead connector 22 in a 2×2 array. However, the type and number of leads and the number of electrodes in the IPG are application-specific and can therefore vary. The conductive housing 12 may also include electrodes (Ec), and therefore the electrode array 17 may include one or more lead and housing electrodes 12. In SCS applications, one or more electrode leads are typically implanted in the spinal cord of a patient near the dura mater, preferably across the left and right sides of the patient's spine. Proximal contacts 21 then penetrate through the patient's tissue to reach distal locations, such as the hip where the IPG housing 12 is implanted, where they are coupled to the lead connector 22. In other examples of IPGs designed for direct implantation at sites requiring stimulation, the IPG may be leadless, with electrodes 16 instead appearing on the body of the IPG 10 for contact with the patient's tissue. In other solutions, one or more IPG leads can be integrated with and permanently connected to IPG 10. The goal of SCS therapy is to provide electrical stimulation from electrode 16 to relieve patient symptoms such as chronic back pain.

[0005] The IPG 10 may include an antenna 27a, allowing it to communicate bidirectionally with a number of external devices discussed later. The antenna 27a shown includes a conductive coil within the housing 12, although a coil antenna 27a may also be present in the head 23. When the antenna 27a is configured as a coil, communication with the external devices (FIG. 5) preferably occurs using near-field magnetic induction. The IPG 10 may also include a radio-frequency (RF) antenna 27b. The RF antenna 27b is shown within the head 23, but it may also be within the housing 12. The RF antenna 27b may include a patch, slot, or wire, and may operate as a monopole or dipole. The RF antenna 27b preferably communicates using far-field electromagnetic waves and can operate according to any number of known RF communication standards, such as Bluetooth, Zigbee, MICS, etc. The IPG 10 may also include an accelerometer 31 capable of detecting the orientation of the IPG 10 within the patient's body, which is useful for determining the patient's posture (e.g., standing, prone, supine, etc.).

[0006] Stimulation in the IPG 10 is typically provided by a series of waveforms (e.g., pulses), each of which may include multiple phases (such as 30a and 30b), as illustrated in the example of Figure 2A. Stimulation parameters typically include: amplitude (current A, although voltage amplitude V may also be used); frequency (F) (or period T, where T = 1 / F); pulse width (PW) of the phases of the waveform (such as 30a and 30b); electrodes 16 selected for providing stimulation; and the polarity of these selected electrodes, i.e., whether they act as anodes supplying current to the tissue or cathodes absorbing current from the tissue. These, along with other possible stimulation parameters, constitute the stimulation circuitry 28 in the IPG 10, which can be executed to provide therapeutic stimulation to the patient.

[0007] In the example of Figure 2A, electrode E1 has been selected as the anode (during the first phase 30a) and thus supplies a positive current of amplitude +A to the tissue. Electrode E2 has been selected as the cathode (again during the first phase 30a) and thus absorbs a corresponding negative current of amplitude -A from the tissue. However, more than one electrode may be selected as the anode at a given time, and more than one electrode may be selected as the cathode at a given time. The housing electrode Ec may also be selected as the anode or cathode, either alone or together with one or more lead-based electrodes.

[0008] As mentioned above, the IPG 10 includes a stimulation circuitry system 28 to generate a prescribed stimulus at the patient's tissue. Figure 3 An example of a stimulation circuit system 28 is shown, which includes one or more current sources 40. i and one or more current absorbers 42 i Source 40 i and absorber 42 i It can include digital-to-analog converters (DACs), and based on the positive (provided, anode) and negative (absorbed, cathode) currents they emit, it can be referred to as PDAC40. i and NDAC 42 i In the example shown, NDAC / PDAC 40 i / 42 i Dedicated (hardwired) to a specific electrode node ei39. For the reasons explained below, each electrode node ei39 is connected to electrode Ei16 via a DC blocking capacitor Ci38. PDAC 40 i and NDAC 42 i It may also include a voltage source.

[0009] Proper control of PDAC 40i and NDAC 42i allows either electrode 16 and housing electrode Ec 12 to act as an anode or cathode to generate a current through the patient tissue R, desired to have a good therapeutic effect. In the example shown and consistent with the first stage 30a of FIG2A, electrode E1 has been selected as the anode electrode to supply current +A to tissue R, and electrode E2 has been selected as the cathode electrode to absorb current -A from tissue R. Thus, PDAC 401 and NDAC 422 are activated and digitally programmed to generate the desired current A at the correct timing (e.g., according to the specified frequency F and pulse width PW). The power for the stimulation circuit system 28 is provided by a compliance voltage VH, as further described in U.S. Patent Application Publication 2013 / 0289665.

[0010] Other stimulation circuitry systems 28 can also be used in IPG 10. In an example not shown, a switching matrix can be located between one or more PDAC 40s. i Between and electrode node ei 39, and one or more NDAC 42 i Between the PDAC and the electrode nodes. The switching matrix allows one or more of the PDACs or one or more of the NDACs to be connected to one or more electrode nodes at a given time. Various examples of stimulation circuitry systems can be found in U.S. Patents 6,181,969, 8,606,362, 8,620,436, U.S. Patent Application Publications 2018 / 0071520 and 2019 / 0083796.

[0011] As described in U.S. Patent Application Publications 2012 / 0095529, 2012 / 0092031, 2012 / 0095519, 2018 / 0071516, and 2018 / 0071513, Figure 3 Many of the stimulation circuit systems 28 (including PDAC 40) i and NDAC 42 i The switch matrix (if present) and electrode nodes (ei 39) can be integrated on one or more application-specific integrated circuits (ASICs), the foregoing applications of which are incorporated herein by reference in their entirety. As explained in these references, one or more ASICs may also contain other circuitry useful in IPG 10, such as telemetry circuitry (for interfacing the chip with telemetry antennas 27a and / or 27b), circuitry for generating compliance voltage VH, various measurement circuitry, etc.

[0012] Figure 3The diagram also shows a DC blocking capacitor Ci 38 placed in series in the electrode current path between each of the electrode nodes ei 39 and the electrode Ei 16 (including the housing electrode Ec 12). The DC blocking capacitor 38 acts as a safety measure to prevent DC current from being injected into the patient's body, which would occur, for example, if a circuit fault exists in the stimulation circuitry system 28. The DC blocking capacitor 38 is typically provided off-chip (outside of one or more ASICs) and alternatively may be provided in or on a circuit board in the IPG 10 for integrating its various components, as explained in U.S. Patent Application Publication 2015 / 0157861.

[0013] Referring again to Figure 2A, the stimulation waveforms shown are biphasic, with each waveform comprising a first phase 30a followed by a second phase 30b of opposite polarity. (Although not shown, interphase periods during which no active current is driven may occur between phases 30a and 30b). By enabling the associated PDAC 40 i and NDAC 42 i The prescribed current is actively driven by the stimulation circuit system 28 in both stages 30a and 30b. The biphasic waveform is useful for actively recovering any charge that may be stored on capacitive elements in the current path (such as on the DC blocking capacitor 38). To recover all charge up to the end of the second stage 30b of each waveform (Vc1 = Vc2 = 0V), the first stage 30a and the second stage 30b are charged in a balanced manner at each electrode, where at electrode E1, the first stage 30a provides +Q (+A*PW) charge and the second stage 30b provides -Q (-A*PW) charge, and at electrode E2, the first stage 30a provides -Q charge and the second stage 30b provides +Q charge. In the example shown, this charge balance is achieved by using the same pulse width (PW) and the same amplitude (|A|) for each of the opposite polarities of stages 30a and 30b. However, phases 30a and 30b can also be charged in equilibrium at each electrode if the product of the amplitude and pulse width of the two phases 30a and 30b is equal, or if the area (their integral) under each phase is equal, as is known. Although not shown, the waveform can also be single-phase, meaning there is only one active phase, i.e., only the first phase 30a or the second phase 30b.

[0014] Figure 3 The stimulation circuitry system 28 is shown to include a passive recovery circuitry system, which is further described in U.S. Patent Application Publications 2018 / 0071527 and 2018 / 0140831. Specifically, a passive recovery switch 41 iIt can be attached to each of the electrode nodes ei 39 and used to passively recover any remaining charge on the DC blocking capacitor Ci 38 after the last pulse phase is emitted, i.e., after the second phase 30b if a biphase pulse is used, or after the single pulse phase if a single-phase pulse is used. Note that due to the RC nature of the circuit, in Figure 2A, the passive charge recovery during 30c is shown as a small exponential decay curve, and this current can be positive or negative depending on whether phase 30a or 30b has a charge advantage at a given electrode. If a single-phase pulse is used, these exponential decay curves will be larger.

[0015] Figure 4 illustrates the external experimental stimulation environment that can be used before IPG 10 implantation in a patient. During external experimental stimulation, stimulation can be attempted on the intended implantation patient without reaching the point of IPG 10 implantation. Alternatively, one or more experimental electrode arrays 17' (e.g., one or more experimental percutaneous leads 15 or experimental paddle leads 19) are implanted in the patient's tissue at a target location 52, such as within the spine as previously described. The proximal ends of one or more experimental electrode arrays 17' exit in incision 54 and are connected to an external experimental stimulator (ETS) 50. The ETS 50 typically mimics the operation of the IPG 10 and can therefore provide stimulation to the patient's tissue via its stimulation circuitry 58, which may be equivalent to or identical to the stimulation circuitry 28 in the IPG 10. The ETS 50 is typically worn externally by the patient for a short period (e.g., two weeks), which allows the patient and their clinician to experiment with different stimulation parameters in hopes of finding a stimulation procedure that alleviates the patient's symptoms (e.g., pain). If the external experimental stimulus proves successful, one or more experimental electrode arrays 17' are explanted, and the complete IPG 10 and permanent electrode array 17 (e.g., one or more percutaneous 15 or paddle 19 leads) are implanted as described above; if unsuccessful, one or more experimental electrode arrays 17' are simply explanted. Like the IPG 10, the ETS 50 may include one or more antennas to enable bidirectional communication with external devices (those shown in Figure 5). As previously described, such antennas may include a near-field magnetic induction coil antenna 56a and / or a far-field RF antenna 56b. The ETS 50 may also include a battery (not shown) for operational power.

[0016] Figure 5 illustrates various external devices capable of wirelessly transmitting data with the IPG 10 and ETS 50, including a patient-handheld external controller 60 and a clinician programmer 70. Two of devices 60 and 70 can be used to wirelessly transmit stimulation programs to the IPG 10 or ETS 50—that is, to program their stimulation circuitry systems 28 and 58 to generate stimulation at the desired amplitude and timing and at selected electrodes. Both devices 60 and 70 can also be used to adjust one or more stimulation parameters of the stimulation program currently being executed by the IPG 10 or ETS 50. Devices 60 and 70 can also wirelessly receive information from the IPG 10 or ETS 50, such as various status information.

[0017] External controller 60 may be as described, for example, in U.S. Patent Application Publication 2015 / 0080982, and may include a controller specifically designed to work with IPG 10 or ETS 50. External controller 60 may also include general-purpose mobile electronic devices, such as mobile phones already programmed using a Medical Device Application (MDA), allowing it to function as a wireless controller for IPG 10 or ETS 50, as described in U.S. Patent Application Publication 2015 / 0231402. External controller 60 includes a graphical user interface (GUI), preferably including means for inputting commands (e.g., buttons or selectable graphical icons) and a display 62, thereby allowing the patient the ability to control IPG 10 or ETS 50. The GUI of external controller 60 enables the patient to adjust stimulation parameters, although it may have limited functionality compared to the more powerful clinician programmer 70 described later. External controller 60 may have one or more antennas capable of communicating with IPG 10 and ETS 50. For example, the external controller 60 may have a near-field magnetic induction coil antenna 64a capable of wireless communication with coil antennas 27a or 56a in the IPG 10 or ETS 50. The external controller 60 may also have a far-field RF antenna 64b capable of wireless communication with RF antennas 27b or 56b in the IPG 10 or ETS 50.

[0018] The clinician programmer 70 is further described in U.S. Patent Application Publication 2015 / 0360038 and may include a computing device 72, such as a desktop, laptop, or notebook computer, tablet computer, mobile smartphone, mobile computing device of the Personal Data Assistant (PDA) type, etc. In Figure 5, the computing device 72 is shown as a laptop computer, which includes typical computer user interface devices such as a screen 74, mouse, keyboard, speakers, pen, printer, etc., all of which are not shown for convenience. Figure 5 also shows an accessory to the clinician programmer 70, typically serving as a stimulus controller specific to its operation (such as a communication "wand" 76 that can be coupled to a suitable port (e.g., USB port 79) on the computing device 72).

[0019] The antenna in the Clinician Programmer 70 used for communication with the IPG 10 or ETS 50 may vary depending on the type of antenna included in those devices. If the patient's IPG 10 or ETS 50 includes coil antennas 27a or 56a, the stick 76 may also include coil antenna 80a to establish near-field magnetic induction communication over short distances. In this case, the stick 76 can be attached near the patient, such as by placing the stick 76 in a patient-wearable belt or holster and close to the patient's IPG 10 or ETS 50. If the IPG 10 or ETS 50 includes RF antennas 27b or 56b, the stick 76, computing device 72, or both may similarly include RF antenna 80b to establish communication with the IPG 10 or ETS 50 over greater distances. The Clinician Programmer 70 can also communicate wirelessly or via a wired link provided at an Ethernet or network port with other devices and networks, such as the Internet.

[0020] To program the stimulation procedures or parameters for IPG 10 or ETS 50, a clinician interacts with a clinician programmer GUI 82 provided on a display 74 of computing device 72. As will be understood by those skilled in the art, GUI 82 can be rendered by executing clinician programmer software 84 stored in computing device 72, which may be stored in the device's non-volatile memory 86. Execution of the clinician programmer software 84 in computing device 72 may be facilitated by a controller circuitry 88, such as one or more microprocessors, microcomputers, FPGAs, DSPs, other digital logic structures, etc., capable of executing programs in the computing device and potentially including their own memory. In one example, controller circuitry 88 may include an i5 processor manufactured by Intel Corp., as described at https: / / www.intel.com / content / www / us / en / products / processors / core / i5-processors.html. In addition to executing the clinician programmer software 84 and presenting the GUI 82, this controller circuit 88 is also capable of communicating via antenna 80a or 80b to transmit stimulation parameters selected through the GUI 82 to the patient's IPG 10 or ETS 50.

[0021] The GUI of the external controller 60 can provide similar functionality because the external controller 60 can include the same or similar hardware and software programming as the clinician programmer 70. For example, the external controller 60 includes a controller circuit system 66 similar to the controller circuit system 88 in the clinician programmer 70, and can be similarly programmed using external controller software stored in the device memory. Summary of the Invention

[0022] A method for determining stimulation for a patient having an implantable stimulator device is disclosed, the method comprising: (a) applying different modulation functions to time-invariant pulse parameters to generate a plurality of different time-varying pulse waveforms, wherein each of the modulation functions modulates at least one of the time-invariant pulse parameters; (b) applying each of the time-varying pulse waveforms to the patient via the implantable stimulator device; (c) obtaining at least one measurement of each of the applied time-varying pulse waveforms; and (d) selecting one or more of the time-varying pulse waveforms for the patient based at least in part on at least one measurement.

[0023] In one example, the method further includes determining time-invariant pulse parameters for the patient as an initial step. In one example, at least one measurement obtained for each of the applied time-varying pulse waveforms indicates the effectiveness of the time-varying pulse waveform for the patient. In one example, the time-invariant pulse parameters include pulse amplitude, pulse width, and pulse frequency. In one example, each of the modulation functions is periodic to periodically modulate at least one of the time-invariant pulse parameters. In one example, at least one of the modulation functions is aperiodic. In one example, at least one aperiodic function arbitrarily modulates at least one of the time-invariant pulse parameters. In one example, at least one measurement of each of the applied time-varying pulse waveforms includes an objective measurement obtained from the patient. In one example, at least one objective measurement is obtained using an implantable stimulator device. In one example, the at least one objective measurement includes at least one feature derived from an electrospinal (ESG) signal sensed at the implantable stimulator device. In one example, at least one objective measurement includes at least one feature derived from one or more evoked compound action potentials sensed at the implantable stimulator device. In one example, the evoked compound action potential varies with modulation of at least one of the time-invariant pulse parameters, and at least one objective measurement quantifies the degree of variation in the evoked compound action potential. In one example, at least one objective measurement is obtained using a system separate from the implantable stimulator device. In one example, at least one measurement of each of the applied time-varying pulse waveforms includes a subjective measurement determined based on feedback from the patient. In one example, at least one subjective measurement includes a rating related to the patient's symptoms provided by the patient. In one example, at least one subjective measurement includes a stimulation threshold indicating the intensity of the stimulus perceived by the patient. In one example, at least one measurement of each of the applied time-varying pulse waveforms includes at least one objective measurement obtained from the patient and at least one subjective measurement determined based on feedback from the patient. In one example, step (d) includes determining a score for each of the applied time-varying pulse waveforms using at least one measurement obtained for that time-varying pulse waveform, and selecting one or more time-varying pulse waveforms for the patient using the determined scores. In one example, multiple measurements are obtained for each of the applied time-varying pulse waveforms, wherein each of the multiple measurements is weighted when determining the score for each of the applied time-varying pulse waveforms. In one example, the method uses an external device that communicates with an implantable stimulator device. In one example, step (a) is performed using the external device. In one example, at least one measurement of each of the applied time-varying pulse waveforms is received at the external device, and step (d) is performed using the external device.In one example, the method further includes (e) using an external device to program one or more selected implantable stimulator devices using a time-varying pulse waveform.

[0024] A method for modulating stimulation for a patient having an implantable stimulator device is disclosed, the method comprising: (a) applying a waveform comprising a time-varying pulse to the patient, wherein the time-varying pulse is formed by modulating at least one of a plurality of time-invariant pulse parameters of the pulse using a modulation function, wherein the modulation function includes at least one of a modulation shape or a modulation parameter determining the size of the modulation shape; (b) obtaining at least one measurement of the applied waveform; (c) using the at least one measurement to determine the effectiveness of the time-varying pulse for the patient; and (d) if the time-varying pulse is ineffective, adjusting the modulation function to modulate the time-varying pulse applied to the patient.

[0025] In one example, the method further includes determining time-invariant pulse parameters for the patient as an initial step. In one example, at least one measurement obtained for the waveform indicates the effectiveness of the time-varying pulse for the patient. In another example, the method further includes (e) repeating steps (a) through (d). In one example, the time-invariant pulse parameters include pulse amplitude, pulse width, and pulse frequency. In one example, the modulation function is periodic to periodically modulate at least one time-invariant pulse parameter. In one example, the modulation function is non-periodic. In one example, at least one non-periodic function arbitrarily modulates at least one of the time-invariant pulse parameters. In one example, at least one measurement of the applied waveform includes an objective measurement obtained from the patient. In one example, at least one objective measurement is obtained using an implantable stimulator device. In one example, the at least one objective measurement includes at least one feature derived from an electrospinal gestational stenosis (ESG) signal sensed at the implantable stimulator device. In one example, at least one objective measurement includes at least one feature derived from one or more evoked compound action potentials sensed at the implantable stimulator device. In one example, the evoked compound action potential varies as at least one of the time-invariant pulse parameters is modulated, and wherein at least one objective measurement quantifies the degree of variation of the evoked compound action potential. In one example, at least one objective measurement is obtained using a system separate from the implantable stimulator device. In one example, at least one measurement of the applied waveform includes a subjective measurement determined based on feedback from the patient. In one example, at least one subjective measurement includes a rating related to the patient's symptoms provided by the patient. In one example, at least one subjective measurement includes a stimulation threshold indicating the intensity of the stimulus perceived by the patient. In one example, at least one measurement of the applied waveform includes at least one objective measurement obtained from the patient and at least one subjective measurement determined based on feedback from the patient. In one example, step (c) includes determining a score of the applied waveform using at least one measurement and using that score to determine the effectiveness of the time-varying pulse for the patient. In one example, the effectiveness of the time-varying pulse for the patient is determined by comparing the score to at least one threshold. In one example, multiple measurements are obtained from a plurality of applied waveforms, wherein each of the plurality of measurements is weighted when determining the score of the applied time-varying pulse. In one example, the method uses an external device that communicates with the implantable stimulator device. In one example, at least one measurement of the applied waveform is received at the external device, and steps (c) and (d) are performed using the external device. In one example, the modulation function is adjusted by changing the modulation shape. In another example, the modulation function is adjusted by changing one or more modulation parameters.In one example, the modulation function is adjusted by adjusting at least one of the multiple time-invariant pulse parameters modulated by the modulation function.

[0026] The present invention may also exist in the form of a programmed external device (through its control circuitry) for implementing the above methods, a programmed IPG or ETS (through its control circuitry) for implementing the above methods, a system comprising a programmed external device and an IPG or ETS for implementing the above methods, or as a computer-readable medium for implementing the above methods stored in an external device or an IPG or ETS. Attached Figure Description

[0027] Figure 1 illustrates an implantable pulse generator (IPG) according to the prior art.

[0028] Figures 2A and 2B show examples of stimulation waveforms generated by an IPG or an external experimental stimulator (ETS) according to existing technology.

[0029] Figure 3 A stimulation circuit system that can be used for IPG or ETS according to the prior art is shown.

[0030] Figure 4 illustrates an ETS environment that can be used to provide stimulation prior to IPG implantation, based on existing technology.

[0031] Figure 5 illustrates various external devices that, according to existing technology, can communicate with IPG and ETS and program stimuli in them.

[0032] Figure 6A and Figure 6B The circuitry system in the IPG or ETS for providing stimulation pulses and for sensing electrospinal genomic (ESG) signals in the patient's tissues is shown.

[0033] Figure 7A The modulation of one or more time-invariant tonic stimulation parameters by a modulation function to generate a time-varying pulse (TVP) is shown. Figure 7B An example of a graphical user interface (GUI) that can be used to specify and define modulation functions is shown.

[0034] Figure 8 An example of a time-varying pulse (TVP) algorithm for determining one or more optimal TVPs for a patient is shown, wherein the algorithm uses one or more objective or subjective measurements to determine the patient’s TVP score.

[0035] Figure 9 An example of objective measurement results that can be used in the TVP algorithm is shown.

[0036] Figure 10An example is shown where the TVP algorithm can determine one or more optimal TVPs for a patient.

[0037] Figure 11 A closed-loop TVP algorithm is shown, which can be used to adjust the TVP prescribed for the patient. Detailed Implementation

[0038] In pulse generator systems, particularly spinal cord stimulator (SCS) pulse generator systems, an increasingly interesting development is the addition of sensing capabilities to supplement the stimulation provided by such systems. Therefore, IPG (such as...) Figure 6A The IPG 100 shown may include the ability to sense electrospinal genomic (ESG) signals in the patient’s tissues.

[0039] For example, and as explained in U.S. Patent Application Publication 2017 / 0296823, it may be beneficial to sense neural responses in neural tissue that have received stimulation from an SCS pulse generator within an ESG signal. One such neural response is an evoked compound action potential (ECAP). An ECAP comprises the cumulative response provided by the nerve fibers selected for stimulation and essentially includes the sum of the action potentials of the selected neural elements (ganglia or fibers) when they are "fired". Figure 6B The diagram shows an ECAP, which comprises multiple peaks, conventionally labeled P for positive peaks and N for negative peaks, where P1 comprises the first positive peak, N1 comprises the first negative peak, P2 comprises the second positive peak, and so on. Note that not all ECAPs will have such... Figure 6B The precise shape and number of peaks shown are because the shape of the ECAP is a function of the selected and the number and type of neural elements involved in its conduction. ECAPs are typically small signals and can have peak-to-peak amplitudes ranging from units to hundreds of microvolts, depending on the amplification gain and their location within the nervous system they are sensed in (brain, spinal cord, peripheral nervous system, somatic nervous system, motor element, or others).

[0040] In another example, sensing stimulation artifacts in the ESG signal—that is, voltages formed in the tissue as a result of stimulation—may be useful. Further details regarding the utility of sensing stimulation artifacts in an IPG system are disclosed in PCT application serial number PCT / US20 / 36667, filed June 8, 2020, which is incorporated herein by reference in its entirety. As explained in the '667 application, the ESG signal can include additional background signals generated by neural tissue even in the absence of stimulation.

[0041] Figure 6AA circuit system for the IPG 100 is shown, capable of providing stimulation and sensing electrospinal genomic (ESG) signals, which may include ECAP, stimulation artifacts, and other background signals just mentioned. (As previously stated, this circuit system could also exist in an ETS, although for simplicity, the discussion of its use in the IPG begins here). At the heart of the IPG's circuit system is controller circuitry 102, which may include a microcontroller (e.g., part number MSP430 manufactured by Texas Instruments), described in a datasheet at http: / / www.ti.com / microcontrollers / msp430-ultra-low-power-mcus / overview.html (which is incorporated herein by reference). Other types of controller circuitry may be used instead of the microcontroller, such as microprocessors, FPGAs, DSPs, or combinations thereof. Controller circuitry 102 may also be formed, wholly or partially, in one or more application-specific integrated circuits (ASICs), such as those previously described and incorporated.

[0042] The IPG 100 also includes a stimulation circuit system 28 that generates stimulation at electrode 16, which may include the stimulation circuit system 28 previously shown. Figure 3 Bus 118 provides digital control signals from controller circuitry 102 (and possibly from feature extraction algorithm 140, described below) to one or more PDACs 40. i Or NDAC 42 i This generates a current or voltage of the specified amplitude (A) and correct timing (PW, F) for the stimulation pulse. As previously mentioned, the DAC can be powered between the compliance voltage VH and ground. As previously mentioned, but not in Figure 6A As shown, a switch matrix can be positioned between the PDAC and electrode node 39, and between the NDAC and the electrode node, to route its output to one or more of the electrodes, including the conductive housing electrode 12 (Ec). Control signals for the switch matrix, if present, can also be carried by bus 118. Note that the current path to electrode 16 includes the previously described DC blocking capacitors 38, which provide safety by preventing unintentional DC current supply to the electrodes and to the patient's tissue. Passive recovery switch 41 i ( Figure 3 It can also exist, but for simplicity, it is... Figure 6A It is not shown in the document.

[0043] The IPG 100 also includes a sensing circuitry 115, and one or more of the electrodes 16 can be used to sense ESG signals. At this point, each electrode node 39 can also be coupled to a sense amplifier circuitry 110. Under the control of the bus 114, a multiplexer 108 can select one or more electrodes as sensing electrodes by coupling one or more electrodes to the sensing amplifier circuitry 110 at a given time, as explained further below. Although only one multiplexer 108 and sense amplifier circuitry 110 are shown in Figure 4A, there can be more than one. For example, there can be four pairs of multiplexers 108 / sense amplifier circuitry 110, each capable of operating within one of the four timing channels supported by the IPG 100 to provide stimulation. The sensed signal is preferably converted into a digital signal by one or more analog-to-digital converters (ADCs) 112, which can sample the waveform, for example, at 50 kHz. The ADC 112 can also be located within the controller circuitry 102, particularly where the controller circuitry 102 has an A / D input. The multiplexer 108 can also provide a fixed reference voltage Vamp to the sense amplifier circuit 110, which is useful in single-ended sense mode.

[0044] To avoid bypassing the safety provided by the DC blocking capacitor 38, the input of the sense amplifier circuitry 110 is preferably taken from electrode node 39, and thus the DC blocking capacitor 38 is positioned between electrode 16, in which the signal is sensed, and electrode node 39. However, the DC blocking capacitor 38 will allow the AC signal component to pass while blocking the DC component, and therefore the AC signal will still be easily sensed by the sense amplifier circuitry 110. In other examples, the signal can be sensed directly at electrode 16 without passing through the intermediate capacitor 38.

[0045] As shown, the feature extraction algorithm 140 is programmed into the controller circuitry 102 to receive and analyze digitized ESG signals. Those skilled in the art will understand that the feature extraction algorithm 140 may include instructions that can be stored on a non-transitory machine-readable medium, such as magnetic, optical, or solid-state memory within the IPG 100 (e.g., stored in association with the controller circuitry 102).

[0046] Feature extraction algorithm 140 operates within IPG 100 to determine one or more features, generally by analyzing the magnitude and shape of the sensed signal. For ECAP as described above, feature extraction algorithm 140 can determine one or more ECAP features (EFx), which may include, but are not limited to:

[0047] • The height of any peak present in ECAP (e.g., H_N1);

[0048] • Peak-to-peak height between any two peaks (such as H_PtoP from N1 to P2);

[0049] • Peak height ratio (e.g., H_N1 / H_P2);

[0050] • Peak width of any peak (e.g., full width half maximum (FWHM N1) of N1);

[0051] • The area under any peak (e.g., A_N1);

[0052] • Total area (A_tot), including the area under the positive peak minus or plus the area under the negative peak, also known as the area under the curve;

[0053] • The length of any portion of the ECAP curve (e.g., the length of the curve from P1 to N2, L_P1 to N2).

[0054] • Any time that limits at least a portion of the duration in ECAP (e.g., the time from P1 to N2, t_P1toN2);

[0055] • The time delay from stimulus to ECAP emission indicates the neural conduction velocity of ECAP, which may vary in different types of neural tissue;

[0056] • The rate of change of any of the previous features, for example, the difference between the previous value of the feature and the new value of the feature during the new stimulus period;

[0057] • Any mathematical combination or function of these variables (e.g., H_N1 / FWHM_N1 typically specifies the quality factor of peak N1);

[0058] • Any simplified version of a previous feature that serves as a proxy for a specified feature. For example, instead of the area under the curve, the sum of the absolute values ​​of the sensed samples within a specified time interval; or instead of using the Euclidean distance over the time interval to calculate the length of the curve, which is calculated as the sum of the absolute values ​​of the differences between consecutively sensed samples; or instead of the height from N1 to P2 (H_PtoP), the maximum value minus the minimum value over the specified time interval, also known in statistics as the range of the sensed samples over the specified time interval. Such simplified features can be directly extracted using hardware in the IPG.

[0059] • Any of the previous characteristics calculated at any time interval t1 and t2, where t1 is the start of the time interval and t2 is the end of the time interval, and where t1 and t2 may refer to the start of the stimulus pulse.

[0060] The feature extraction algorithm 140 can also identify one or more stimulus artifact features (SAFx), as explained in the '667 application above.

[0061] Once the feature extraction algorithm 140 has determined one or more of these features, it can modulate the stimulation provided by the IPG 100, for example, by providing new data to the stimulation circuitry system 28 via bus 118. This is further explained in U.S. Patent Application Publications 2017 / 0296823 and 2019 / 0099602, which use ECAP features to modulate the stimulation. In a simple example, the feature extraction algorithm 140 may examine the height of the ECAP (e.g., its peak-to-peak voltage) or the height of the ESG signal within any predetermined time interval (e.g., 0.6 ms to 2.2 ms) and modulate the amplitude I of the stimulation current in a closed-loop manner to attempt to maintain the height or the height of the ECAP within that interval to a desired value. The '667 application combined above discloses that the features of stimulation artifacts within the ESG signal can also be used to control the stimulation.

[0062] Conventional neuromodulation therapy employs low- to mid-frequency (e.g., F < 1500 Hz) electrical stimulation pulse trains to effectively induce action potentials at the desired activation rate from the electrical pulses (e.g., a single pulse can induce a burst of action potential, or multiple pulses can be integrated over time to induce an action potential). These stimulation pulse trains are typically tetanic, meaning the amplitude (A), pulse width (PW), and frequency (F) are fixed, as shown in Figure 2A. However, it is known that neural tissue can acclimate, adapt, and / or become accustomed to continuous tetanic input, resulting in a diminishing neural response over time.

[0063] Recently, high-frequency stimulation (e.g., F = 1.5 kHz to 50 kHz) has been used to block or disrupt spontaneously occurring action potentials within nerve fibers, which can be used for pain management. Although the underlying mechanisms by which high-frequency stimulation provides effective pain relief are unclear, it has been hypothesized that neurotransmitter depletion, desynchronization of multiple neurons, and the generation of random noise may explain this success. However, high-frequency stimulation is disadvantageous because it consumes excessive energy, thus requiring the IPG100 to have a larger battery 14 (if the battery is permanent) or to be recharged more frequently (if it is rechargeable).

[0064] To address this concern, the art has taught (e.g., see U.S. Patent Application Publication 2017 / 0266447, which is incorporated herein by reference in its entirety) that it is useful to additionally modulate a tonic stimulation pulse (having a fixed amplitude, pulse width, and frequency) to provide stimulation to SCS patients. Specifically, the prior art teaches that modulation function 150 can be applied to one or more of the stimulation parameters used during tonic stimulation to produce a waveform of pulse variation, such as... Figure 7A Several examples (150a to 150c) are shown. This modulation function 150 provides a time-varying stimulation pulse to the patient, and therefore can mitigate or prevent loss of therapeutic response that may be caused by neural tissue's compliance, adaptation, and / or habituation to the stimulation. Moreover, assuming that the use of the modulation function 150 provides significant pain management for the patient (even at lower frequencies), it provides a solution that is more energy-efficient and does not burden the IPG's battery 14.

[0065] Modulation function 150 includes a modulation shape and one or more modulation parameters that determine the size of the modulation shape, and is applied to one or more tetanic stimulation parameters. Note that in Figure 7A In this process, the appropriate tetanic stimulation parameters (e.g., amplitude, pulse width, frequency) for a particular patient may already be known and may have been determined during the fitting process. This fitting process may involve trying various stimulation parameters on an implanted patient (e.g., with IPG 100) using a clinician programmer 70 (Figure 5) or other external device to determine which parameters work best for the patient. Successful assessment of the various stimulation parameters may involve the use of subjective measurements, such as by receiving feedback from the patient on how the stimulation parameters affect their symptoms. Successful assessment of the various stimulation parameters may also involve the use of objective measurements obtained from the patient, such as by assessing one or more ECAP characteristics or other measurable parameters, as described in U.S. Patent Application Publication 2020 / 0230410, which is incorporated herein by reference in its entirety. Note that proper fitting of stimulation to the patient may also involve determining the appropriate electrode configuration, i.e., which electrodes in the electrode array should be active and the amplitude and polarity of these electrodes. Although not shown, tetanic stimulation parameters may also include an on-off duty cycle, which specifies the duration of repeated on (e.g., 100 ms, or some number of pulses) and the duration of off (e.g., 1 s) used for stimulation.

[0066] Assuming in Figure 7A In the example, the shunt pulse (not altered by modulation function 150) has an amplitude A of 4 mA, a pulse width PW of 500 μs, and a frequency F of 200 Hz. Figure 7AThe modulation function 150a in the example modulates the amplitude of the tetanic stimulus pulse, and thus modulates the constant amplitude (4mA) of the tetanic pulse. In this example, the shape of the modulation function 150a is triangular, and therefore the amplitude of the pulse gradually tilts up and down. However, this is just one example of the modulation shape, and different shapes can be used. For example, Figure 7A The right side shows sine, ramp, step, and even arbitrary modulation shapes. Although not shown, modulation shapes can also include various statistical distribution functions, such as Poisson, uniform, Gibbs, Gaussian, Borel, or Boltzmann distributions.

[0067] Modulation function 150a ( Figure 7A A modulator-demodulator (Amax) is applied to the amplitude of the pulse to define a series of continuous pulses with time-varying amplitudes, as shown. The modulation function is defined and sized by various modulation parameters (such as Amax and Amin) that specify the maximum and minimum amplitudes of the pulses. For example, Amax can be equal to the specified amplitude of the pulse (4mA), while Amin will be smaller (e.g., 2.5mA). Amax and Amin can also include scalars applied to the amplitude of the pulse (e.g., multiplied by the amplitude of the pulse). For example, Amax can be equal to 1 to produce the pulse with the highest amplitude (e.g., 4mA * 1 = 4mA), while Amin can be equal to 0.625 to produce the pulse with the lowest amplitude (e.g., 4mA * 0.625 = 2.5mA). Another modulation parameter, Amid, can be defined as a value (or scalar) between the maximum and minimum values. For example, if Amid is between Amax and Amin, it will include a value of 3.25mA, or a scalar of 0.8125. Amid can be defined by the modulation function, and for example, can include a value such that the area of ​​the modulation function on Amid is equal to the area of ​​the modulation function under Amid. In this respect, if the shape of the modulation function 150 is asymmetric, then Amid is not necessarily between Amin and Amax. Amid can also be defined as the mean or median of the distribution of amplitude values ​​generated by the modulation function over time, regardless of whether the modulation function is periodic or aperiodic.

[0068] While not strictly necessary, the modulation shape of a modulation function can be inherently periodic (repetitive) and can have a modulation frequency FM, which is another modulation parameter specifying how quickly the modulation changes. As an example, in the case of amplitude modulation, F... M It is the frequency at which a pulse of a given amplitude will repeat, such as Figure 7AAs shown. FM is preferably lower than the frequency F of each direct pulse, and can vary, for example, between 0.1 and 20 Hz, or even at lower or higher frequencies as technology evolves, achieving faster sampling frequencies with low power consumption. Similarly, in the case of pulse width modulation or frequency modulation, F... M It is the frequency of pulse repetition given a pulse width or frequency, and so on. Figure 7A As shown.

[0069] Modulation function 150a can be applied to modulate the amplitude of all types of direct current pulses. Figure 7A In the various waveforms shown, the pulses are biphase, and more specifically, symmetrical biphase pulses with opposite polarities but the same amplitude and pulse width. Asymmetrical biphase pulses can also be used. Additionally, the pulses can be monophase and can include the use of passive charge recovery, as discussed previously.

[0070] The triangular-shaped modulation function 150b modulates different tetanic stimulation parameters, particularly the pulse width of the tetanic pulse. Modulation function 150b is applied to the tetanic pulse width to define a pulse with a pulse width that varies over time, as shown. Modulation function 150b is defined and its magnitude is determined by various modulation parameters, and again specifies the maximum pulse width value (PWmax), the minimum pulse width value (PWmin), and the midpoint (PWmid) pulse width value. For example, if the tetanic pulse has a nominal pulse width of 500 μs, then PWmin and PWmax can be set to 300 μs and 600 μs respectively (i.e., scalars from 0.6 to 1.2), where PWmid is 450 μs (a scalar of 0.9). As previously stated, modulation function 150b can have different shapes and can be applied to different types of pulses, and can be periodic with a modulation frequency F. M Modulation function 150c is similar, but the tetanic stimulation parameters of the frequency are changed. For example, if the tetanic pulse nominally has a frequency of 200 Hz, Fmin and Fmax can be set to 100 Hz and 300 Hz (i.e., scalars of 0.5 and 1.5), respectively, where Fmid includes 200 Hz (a scalar of 1.0). Although not shown, the modulation function can also be applied to other tetanic stimulation parameters, such as the switching duty cycle described previously.

[0071] Despite Figure 7A Not shown, but note that more than one stimulus parameter can be modulated at any given time. For example, the amplitude (150a) can be modulated, while the pulse width (150b) and / or frequency (150c) are also modulated. This modulation can occur at different time scales, that is, for each time scale F E They can be different.

[0072] Figure 7B A graphical user interface (GUI) 160 (such as an external controller 60 or a clinician programmer 70 (Figure 5)) that can be presented on an external device and used to control the stimulation provided by the IPG 100 is shown. In this GUI 160, the user can define the modulation function 150 to be applied to the tetanic stimulation pulse. It is assumed here that the tetanic stimulation pulse (e.g., A, PW, f) has already been defined for the patient elsewhere in the GUI 160 (during the adaptation process), although the definition of the tetanic stimulation pulse can also be used... Figure 7B The same screen shown in the figure is used. In GUI 160, the user can select one or more modulation shapes (162), and one or more tetanic stimulation parameters (163) to which the shape (modulation function) will be applied. The user can also select one or more modulation parameters (164) to determine the magnitude of the modulation function 150 of the desired shape.

[0073] Suppose the user wants to limit such as Figure 7A The modulation function 150a described in the text is used to modulate the amplitude. Figure 7B The user can select the triangle shape and associated amplitude modulation parameters. For example, the user can input the maximum and minimum amplitudes of 4.0 and 2.5 mA (or scalars, such as 1 and 0.625 as mentioned above). The software in the external device (e.g., 84 in Figure 5) can then determine the midpoint of 3.25 mA (or the scalar of 0.8125) and the percentage (e.g., 23%) around which the modulation function will span. Note that 3.25 + 0.23(3.25) = 4 mA, and 3.25 - 0.23(3.25) = 2.5 mA. Alternatively, the user can specify the midpoint and spread, where the software works in reverse to calculate the maximum and minimum values. The user can also select the modulation frequency F. M (e.g., 0.5Hz). Once the modulation function 150 is defined, the software (e.g., 84 in Figure 5) can automatically compile appropriate program instructions to allow the IPG 100 to generate tetanic stimulation pulses modulated by the modulation function 150. Alternatively, the modulation function 150 can be provided to the IPG 100 along with the tetanic stimulation parameters, leaving it to the controller circuitry 102 of the IPG 100. Figure 6A This is used to form time-varying modulated pulses.

[0074] Although the generation of the time-varying pulse waveform has so far been described as involving the application of modulation function 150 to one or more tetanic stimulation parameters, this is not strictly necessary. Instead, the time-varying pulse can be specified in any way and can also include randomly varying or even arbitrarily varying pulses. In this respect, the time-varying pulse does not need to be limited relative to the tetanic stimulation parameters modulated by modulation function 150.

[0075] Figure 8 Algorithm 170 is shown for evaluating and determining one or more optimal time-varying pulses (TVPs) for a given patient. N candidate TVPs (TVP1 to TVPn) are shown, and they will be tested on a given patient with IPG 100 (or ETS). The previously described GUI 160 can be used. Figure 7A and Figure 7B TVP can be defined in one or more ways. A given TVP is measured once or multiple times during its application to a patient, and such measurements can be objective or subjective in nature. Figure 8 The diagram illustrates numerous objective measurements (OMa, OMb, etc.) that can be performed on each TVP, just as there are many different subjective measurements (SMa, SMb, etc.). Algorithm 170 can use one or more objective measurements, as well as one or more subjective measurements. Alternatively, Algorithm 170 can use only one or more objective measurements, or only one or more subjective measurements. Ultimately, Algorithm 170 uses one or more objective and / or subjective measurements to calculate a score (Sx) for each TVP, which is used to determine the optimal one or more TVPs for the patient during treatment, as explained further below. In one example, Algorithm 170 can be executed during the patient fitting process and can therefore be implemented in the software 84 (Figure 5) of the clinician programmer 70. Preferably, Algorithm 170 is executed after determining the appropriate tetanic stimulation parameters (e.g., amplitude, pulse width, frequency) for the patient.

[0076] Preferably, each of the TVPs to be tested during TVP algorithm 170 is different, resulting in the application of different time-varying pulse waveforms to the patient. TVPs can be made different by changing the modulation function 150 applied to the tetanic stimulation parameters. For example, the shape of the modulation function 150 can be changed, with TVP1 using a triangular modulation function 150, TVP2 using a sinusoidal function, etc. Furthermore, TVPs can be made different by changing the modulation parameters used to determine the size of the modulation shape. For example, TVP1 can set specific values ​​(or scalars) for Amax and Amin. TVP2 can change Amin to different values, and TVP3 can change Amax to different values, which is also useful for changing Amid and span. Modulation frequency F MIt can also be changed between different TVPs. Furthermore, the TVP can be made different by applying the modulation function 150 to different one of the tetanic stimulation parameters (e.g., A, PW, or F). For example, TVP1 might involve using a first modulation function (150a) with varying amplitude. Figure 7A TVP2 may involve using a second modulation function (150b) that changes the pulse width. Figure 7A TVP3 may involve the use of a third modulation function with altered frequencies. To emphasize the points raised above, TVP can be defined without applying modulation function 150 to other tetanic stimuli, and at this point, TVP can be differentiated in ways that do not necessarily involve changing the modulation function itself. The TVP to be attempted during the execution of TVP algorithm 170 can be determined based on clinical experience (e.g., based on previous use that is understood to be most relevant to the patient's symptoms).

[0077] As mentioned above, one or more objective measurements can be performed during the application of each TVP to a patient. These measurements may include, for example, one or more characteristics of the ESG signal sensed by the patient's IPG 100 or ETS. These ESG characteristics may include ECAP characteristics (see reference below). Figure 9 (As explained further in detail), ECAP threshold, stimulus artifact characteristics, or background signal characteristics. The ECAP threshold is defined as the minimum amplitude required for the IPG to detect an ECAP response. Other objective measures indicative of patient symptoms, such as pain in SCS applications, can also be used by the TVP algorithm 170. Such objective measurements may not include measurements performed using the patient's IPG or ETS. For example, EEG, heart rate, blood pressure, and respiratory rate can all include objective measurements that can be used by the TVP algorithm 170. Such measurements can be performed by medical devices other than the patient's IPG or ETS and can be provided to an external device (e.g., clinician programmer 70) executing the TVP algorithm 170. For example, if blood pressure is used as an objective measurement, the patient's blood pressure reading can be transmitted (via wired or wireless) to the clinician programmer 70. Measurements of patient posture can also include objective measurements, as posture can affect patient symptoms and be optimally applied to patient treatment. In this regard, the accelerometer 31 in the IPG (Figure 1) can also be consulted.

[0078] During the application of each TVP to a patient, one or more subjective measurements may also be performed. These subjective measurements depend on patient feedback and are therefore inherently subjective. The results of these subjective measurements can be input by the clinician into the clinician programmer 70 so that they can be received by the TVP algorithm 170. Alternatively, the patient can input subjective measurement results using the clinician programmer 70 or their external patient controller 60.

[0079] As an example of subjective measurement results, for a given TVP, a patient can provide a pain score indicating the degree to which the TVP affects the patient's symptoms (e.g., 1 indicates good pain relief and 10 indicates poor pain relief). Patients can also rate the quality of their sensations or provide indications of how well the TVP addresses or covers the patient's symptoms. In short, subjective measurement results can include various ratings provided by the patient related to their symptoms. Other subjective measurement results that can also be rated by the patient and used with the TVP algorithm 170 include: pain duration, frequency of pain attacks, duration of pain attacks, intensity of pain attacks, estimated body volume of the pain area during a pain attack, duration of patient-specific activities (previously reduced or affected by pain), activity that triggered a pain attack, satisfaction rating, etc.

[0080] Additionally, subjective measurements can include various thresholds, such as the abnormal sensory threshold (Pth) at which the patient can perceive the stimulus (abnormal sensation), or the discomfort threshold (Dth) at which the stimulus is too strong. For example, during each TVP, the amplitude of the stimulus can be modulated, where the abnormal sensory threshold includes the lowest amplitude (or other measure of energy) at which the patient can perceive the stimulus. The discomfort threshold can include the highest amplitude (or other measure of energy) at which the patient can tolerate it. In short, Pth and Dth comprise stimulus thresholds that indicate the intensity of the stimulus perceived by the patient and are used to guide the selection of modulation parameters for TVP. Note that TVPs can also be used for subsensory SCS therapy, meaning that no stimulus is perceived by the patient, but the stimulus still changes over time.

[0081] Figure 9 Further details are described regarding objective measurements collected from ECAPs that can be measured by the patient's IPG or ETS, which can be used by the TVP algorithm 170, and the effect of time-varying modulation on these measurements is shown. In this example, a specific ECAP feature (i.e., the area under the curve of the ECAP (μV*s) (“ECAP area”)) is measured as a function of time. Figure 9 In the diagram, for ease of explanation, several area values ​​from several stimulus pulses are averaged. The shape of the sinusoidal modulation function (see...) Figure 7AA sinusoidal modulation function is applied to a tetanic stimulation pulse with a modulation frequency FM of 0.5 Hz, where the modulation amplitude (top), pulse width (middle), and frequency (bottom) are applied. As can be seen, the area of ​​the ECAP (which is generally related to the size of the ECAP) varies periodically in accordance with the periodicity of the modulation function. The ECAP area is larger during periods where the modulation produces pulses with higher amplitudes, longer pulse widths, or higher frequencies; and smaller during periods where the modulation produces pulses with lower amplitudes, shorter pulse widths, or lower frequencies. Although... Figure 9 The ECAP region is shown as a relevant feature, but it can be expected that other ECAP features (such as those mentioned above) will also be affected by the applied modulation.

[0082] Figure 9 The data in the diagram illustrates many potential objective measurements that can be used in the TVP algorithm 170, such as the maximum, minimum, and average ECAP area. Similarly, other features outside the ECAP area can also be used. Other objective measurements indicative of the degree to which modulation influences a feature can also be determined. The difference between the maximum and minimum areas (the span between them) provides such a measurement. The span of this feature (or other feature) can be normalized using an average value, i.e., (max–min) / avg. This can be useful because different modulation schemes may affect ECAP features differently. For example, when… Figure 9 When amplitude modulation is used, the average value is relatively low (1000), but the span (1500-500) is high, resulting in a normalized span of 1. When pulse width modulation is used, the average value is high (1500), but the span is low (1750-1250), resulting in a normalized span of 0.33. When frequency modulation is used, the average value is still high (1600), and the span is still low (1700-1500), resulting in a normalized span of 0.125. These normalized spans indicate that, in this example, amplitude modulation has the greatest impact on the resulting ECAP, which may or may not be desirable for the patient depending on the circumstances. Pulse width modulation has a smaller impact on the resulting ECAP, while frequency modulation has an even smaller impact. This could certainly be due to the use of... Figure 9 The diagram shows specific modulation parameters for three different types of modulation. In short, objective measurements can include any measure that quantifies the degree of variance in the measured response (such as the variance in ECAP characteristics).

[0083] Figure 9It also shows that for a given metric, there may exist preferred values ​​that lead to optimal clinical outcomes. For example, when using amplitude modulation, it is known that optimal clinical outcomes are observed when the ECAP area varies within a specific range, such as from 800 to 1200. When using frequency modulation, it is also known that optimal clinical outcomes are observed when the ECAP area varies within a range (e.g., from 1650 to 1700), such as... Figure 9 As shown. At this point, it can be seen from... Figure 9 Another objective metric collected and used in TVP algorithm 170 is the degree to which a particular modulation scheme produces an ECAP region (or other feature) within such a preferred region. TVP algorithm 170 may calculate or determine a fit metric (another objective measurement) that quantifies the degree to which the obtained ECAP region matches these preferred regions or other desired ECAP region thresholds, or a fit metric for any other feature extracted from the ECAP response within the ESG.

[0084] Once the relevant objective and / or subjective measurements have been determined for each TVP tested, the TVP algorithm 170 can calculate a score for each, and Figure 10 A simple example is shown. In this example, the algorithm uses an objective measurement, specifically the normalized span of the ECAP area, which is referenced earlier. Figure 9 An explanation has been provided. Furthermore, two subjective measurements were used, specifically the pain score and the perceived threshold Pth. Similarly, many other objective and / or subjective measurements, such as those described above, can be used, and the use of these three measurements is merely a simple example.

[0085] In this example, Algorithm 170 calculates the TVP score based on the measurement results, and this can happen in several different ways. Figure 10 In the TVP algorithm, the three measurements are weighted by multiplying each measurement by weights w1, w2, and w3. The values ​​of the weights used in the TVP algorithm can be set empirically to emphasize the importance of each measurement in the total score calculation. Figure 10 In the example, w1 = 1, w2 = -0.05, and w3 = -0.1, which generally tends to normalize each measurement result to approximately the same amplitude. The weights w2 and w3 are negative because they are applied to measurements that represent worse results at higher values ​​(i.e., lower pain scores and Pth would be preferred). Figure 10In the score calculation example, the weighted measurements are then summed. In this example, it is assumed that a higher score indicates a better result, although a lower score can also indicate better performance, depending on how the scores are calculated. If a single measurement is used by the TVP algorithm 170, note that the score for each TVP can be determined by that single measurement, or include that single measurement.

[0086] The TVP algorithm 170 shows that TVP2 is the most effective treatment for the patient (-0.35), followed by TVP1 (-0.57), TVP4 (-0.58), and TVP3 (-0.67). Therefore, the TVP algorithm 170 indicates that TVP2 provides the optimal modulation function 150 for the tetanic stimulation parameters to be applied to the patient, and thus should be used for future patients. However, the TVP algorithm 170 can be repeated for patients from time to time to see if a better TVP can ultimately be determined for the patient. Such retesting may be necessary depending on tissue scarring (which can occur up to 6 months post-surgery), electrode lead migration within the patient, or to test the patient using updated TVPs developed by clinicians over time.

[0087] Once a TVP has been selected for the patient after the fitting procedure, it may be desirable to continue modulating the TVP to provide modulation in a closed-loop manner. This can be guaranteed because circumstances may change after the fitting procedure. As previously mentioned, the lead may migrate within the patient, or scar tissue may cause changes in the efficacy of the prescribed stimulation over time. Furthermore, modulation of the TVP can be guaranteed based on the patient's posture or activity, which constantly alters the actual distance between the electrode and the spinal cord. Respiration and heart rate can also change this distance. In some patients, these changes can produce variations in the therapeutic effect of the stimulation on the back column activation and the stimulation of the stimulation, both for treatments based on sensory abnormalities that the patient can perceive and for treatments without sensory abnormalities that the patient cannot perceive.

[0088] Figure 11 A closed-loop TVP algorithm 180 is shown, which can help regulate the modulation provided by a specified TVP. Due to its closed-loop nature, it is contemplated that the closed-loop TVP algorithm 180 will operate as software in the patient's IPG or ETS and by a controller circuitry system (e.g., 102) in such a device. Figure 6A The closed-loop algorithm 180 can operate without communicating with external devices such as clinician program 70 or patient external controller 60 (Figure 5). In other words, the TVP algorithm 180 operating in IPG or ETS can also receive input from such external devices or other external sources, as explained further below.

[0089] In step 182, it is assumed that the closed-loop TVP algorithm 180 begins with a given TVP for the patient (such as the TVP most effective for the patient selected using the previously described TVP algorithm 170). Furthermore, the TVP specified here (though not strictly necessary) is defined by a modulation function 150 applied to at least one tetanic stimulation parameter A, PW, and f. The modulation function 150, as previously described, will have a specific shape and modulation parameters, and will modulate one or more of the tetanic stimulation parameters.

[0090] In step 184, and similarly to what has been described with respect to TVP algorithm 170, closed-loop TVP algorithm 180 receives one or more measurement results. As previously described, measurement results may include one or more objective measurement results and / or one or more subjective measurement results, such as those previously described. In a preferred example, closed-loop TVP algorithm 180 will receive objective measurement results. This may be expected to allow algorithm 180 to operate automatically without requiring subjective input from the patient. Furthermore, such objective measurements are preferably those performed by the IPG or ETS itself, which again allows algorithm 180 to operate more easily within the IPG or ETS. That is, algorithm 180 may receive objective measurement results from other external medical devices, and such measurement results may, for example, be wirelessly transmitted to IPG 100 for consideration. Furthermore, algorithm 180 may also (e.g., wirelessly) receive subjective measurement results from the patient. For example, the patient may input pain scores, sensory quality ratings, or other qualitative factors or ratings (patient-specific information) into his / her external patient controller 60, which may in turn be received by algorithm 180 in the IPG or ETS as subjective measurement results. In addition, where communication between a given IPG or ETS and the external controller 60 is readily available, the closed-loop TVP algorithm 180 can also operate at least partially in the clinician programmer 70 or the external controller 60, while the TVP adjustment determined by the algorithm 180 is transmitted to the IPG or ETS.

[0091] In step 186, algorithm 180 uses one or more measurements from step 184 to calculate the TVP score, similar to what was previously described in conjunction with TVP algorithm 170. As previously mentioned, the score can be determined by a single subjective or objective measurement, or include a single subjective or objective measurement, such as the ECAP area metric described earlier. Then, in step 186, the obtained score can be evaluated by the algorithm to see if the TVP is adequately effective or needs adjustment. At this point, algorithm 180 can be programmed with at least one threshold and can use this threshold to determine if the current TVP score has worsened. Assuming a higher score indicates a better result, step 186 can query whether the current score has fallen below the threshold (or, if a lower score is preferred, whether the current score is above the threshold). In another example, two thresholds can be used to define an upper and lower limit for the expected score, effectively defining the expected score range between the two thresholds. If the score is too high (above the upper threshold) or too low (below the lower threshold), algorithm 180 can conclude that the TVP has worsened and needs adjustment.

[0092] If the score does not worsen at step 186 (e.g., does not exceed a threshold), the closed-loop algorithm 180 can conclude that TVP modulation is not needed at this time and can wait in step 190 until another measurement is required. In one example, step 190 may include a time delay, such as 10 minutes, which sets the frequency at which the algorithm 180 will perform measurements and potentially TVP modulation. Additionally or alternatively, the algorithm in step 190 may wait for an event indicating a change to occur, thereby relating it to the additional measurement result at step 184. In only one example, the algorithm 180 may receive input from the accelerometer 31 of the IPG (Figure 1), which allows the algorithm 180 to determine whether the patient has changed posture or is participating in a specific activity. As mentioned above, changes in posture or activity may affect stimulation therapy and warrant the need for stimulation modulation. The algorithm 180 may also receive additional input indicating the need for another measurement result at step 184.

[0093] If the score is worse at step 186 (e.g., exceeding a threshold), algorithm 180 can proceed to step 188, where TVP adjustment can be performed. In a preferred example, algorithm 180 will adjust one aspect of modulation function 150 at step 188, which may include changing the shape of the modulation, changing one or more modulation parameters, and / or changing the tetanic stimulation parameters to which modulation function 150 is applied (e.g., by applying the modulation function to the pulse width instead of the amplitude). A completely new modulation function may be chosen instead of adjusting the prescribed modulation function 150 at step 188, although this is practically no different from adjusting the original modulation function. Modulation parameters that can be adjusted at step 188 may include the span of the modulation function (e.g., maximum-minimum) and the midpoint of the modulation function (e.g., mid). For example, when the modulation function is applied to the frequency of the tetanic stimulation pulse, Fmid (the average frequency averaged over the modulation period (T = 1 / FM), or, for a non-periodic modulation function, the average frequency averaged over the time interval) may be adjusted in step 188 if it is desired to keep the score within the threshold band, below the upper threshold, or above the lower threshold. Alternatively, the frequency span Fmax-Fmin can be the parameter adjusted in step 188, or any other modulation parameter.

[0094] The adjustment of the modulation function made by the closed-loop TVP algorithm 180 at step 188 is preferably intelligent. For example, the adjustment made at step 188 may depend on information noticed during the execution of the TVP algorithm 170 during the adaptation process, which can be programmed into the algorithm 180. The adjustment made at step 188 may also depend on or be constrained by the originally defined modulation function, such that any adjustment does not deviate too aggressively from this original function. Once the modulation function has been adjusted at step 188, a new measurement can be taken again at step 184 to see if the score has improved. If so, the algorithm 180 may wait at step 190, or it may proceed to step 188 to try other modulation function adjustments, etc.

[0095] In another embodiment, one or more thresholds used in step 186 can be automatically updated based on long-term values ​​of one or more measurements used to determine the score. For example, if the ECAP area is the only feature used to determine the score, it can be averaged over a short time window spanning 1 to 5 consecutive modulation intervals (e.g., 1 to 5T = 1 / FM), while the threshold for the score can be averaged over a longer time window spanning minutes, hours, or days (e.g., >5T). This allows algorithm 180 to adapt to changes caused by disease progression, scar tissue development, and lead migration within the patient.

[0096] Various aspects of the disclosed technology (including processes that can be implemented in the IPG or ETS or in external devices such as a clinician programmer or an external controller (such as GUI 160, TVP algorithm 170, and closed-loop TVP algorithm 180)) can be formulated and stored as instructions in a computer-readable medium associated with such a device, such as magnetic, optical, or solid-state storage. The computer-readable medium having such stored instructions may also include devices readable by the clinician programmer or external controller, such as in a memory stick or removable disk, and may reside elsewhere. For example, the computer-readable medium may be associated with a server or any other computer device, thereby allowing instructions to be downloaded, for example, to the clinician programmer system or external controller, or to the IPG or ETS via the Internet.

[0097] Although specific embodiments of the invention have been shown and described, the foregoing discussion is not intended to limit the invention to these embodiments. It will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention. Therefore, the invention is intended to cover alternatives, modifications, and equivalents that may fall within the spirit and scope of the invention as defined by the claims.

Claims

1. An external device for determining stimulation for a patient having an implantable stimulator device, comprising: The control circuit system is programmed to (a) Applying different modulation functions to time-invariant pulse parameters to generate multiple different time-varying pulse waveforms, wherein each of the modulation functions modulates at least one of the time-invariant pulse parameters; (b) causing the implantable stimulator device to apply each of the time-varying pulse waveforms in the time-varying pulse waveform to the patient through the implantable stimulator device; (c) Obtain at least one measurement of an evoked compound action potential (ECAP) induced by nerve fibers in the tissue of the selected patient when each of the time-varying pulse waveforms in the time-varying pulse waveforms is applied, wherein the at least one measurement obtained for each of the applied time-varying pulse waveforms indicates the effectiveness of the time-varying pulse waveform for the patient; as well as (d) Selecting one or more time-varying pulse waveforms from the time-varying pulse waveforms for the patient, based at least in part on the at least one measurement result. The ECAP has a maximum area and a minimum area, and the at least one measurement result includes the difference between the maximum area and the minimum area.

2. The external device according to claim 1, wherein the time-invariant pulse parameters include pulse amplitude, pulse width, and pulse frequency.

3. The external device according to claim 2, wherein each of the modulation functions is periodic to periodically modulate at least one of the time-invariant pulse parameters.

4. The external device according to claim 2, wherein at least one of the modulation functions is aperiodic.

5. The external device of claim 1, wherein at least one measurement result is obtained using the implantable stimulator device.

6. The external device of claim 5, wherein each at least one measurement includes at least one feature derived from an electrospinal genomic (ESG) signal sensed at the implantable stimulator device, or at least one feature derived from one or more evoked compound action potentials sensed at the implantable stimulator device.

7. The external device of claim 1, wherein the at least one measurement result is obtained using a system separate from the implantable stimulator device.

8. The external device of claim 1, wherein the at least one measurement result of each time-varying pulse waveform in the applied time-varying pulse waveform further includes a subjective measurement result determined based on feedback from the patient.

9. The external device of claim 8, wherein the at least one subjective measurement result includes a rating provided by the patient in relation to the patient's symptoms or a stimulation threshold indicating the intensity of a stimulus perceived by the patient.

10. The external device according to claim 1, wherein step (d) includes The fraction of each time-varying pulse waveform in the applied time-varying pulse waveform is determined using the at least one measurement obtained for the time-varying pulse waveform, and The determined score is used to select one or more time-varying pulse waveforms from the time-varying pulse waveforms for the patient.

11. The external device of claim 10, wherein a plurality of measurement results are obtained for each of the applied time-varying pulse waveforms, wherein each of the plurality of measurement results is weighted when determining the fraction of each of the applied time-varying pulse waveforms.

12. The external device according to any one of claims 1 to 11, wherein the control circuitry is further programmed to (e) program the implantable stimulator device using one or more selected time-varying pulse waveforms from the time-varying pulse waveforms.

13. The external device of claim 1, wherein the ECAP has an average area, and wherein the difference is normalized using the average area.

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