Pulse generator system for promoting asynchronous firing of recruited neuron populations

Abstract

Disclosed is a pulse generator system that promotes asynchronous firing of recruited neuronal populations, including an implantable pulse generator (IPG) that is capable of sensing the degree of synchronous firing of recruited neurons in a patient's tissue and modifying a stimulation program to promote asynchrony and reduce paresthesia. The evoked compound action potential (ECAP) of the recruited neurons is sensed by at least one non-active electrode as a measure of synchrony. An ECAP algorithm operable in the IPG evaluates the shape of the ECAP and determines one or more ECAP shape parameters that indicate whether the recruited neurons are firing synchronously or asynchronously. If the shape parameters indicate significant synchrony, the ECAP algorithm can adjust the stimulation program to promote asynchronous firing.

Description

[0001] This application is a divisional application of the patent application with the application number "201780024374.9", the application date "February 10, 2017", and the title "Pulse Generator System for Promoting Desynchronized Firing of Recruited Neural Populations". Technical Field

[0002] The present invention generally relates to medical device systems, and more particularly to a pulse generator system operable to promote desynchronized firing of recruited neural populations. Background Art

[0003] Implantable stimulation devices deliver electrical stimulation to nerves and tissues for treating various biological disorders, such as a pacemaker for treating arrhythmias; a defibrillator for treating cardiac fibrillation; a cochlear stimulator for treating deafness; a retinal stimulator for treating blindness; a muscle stimulator for generating coordinated limb movement; a spinal cord stimulator for treating chronic pain; a cortical and deep brain stimulator (DBS) for treating movement and psychological disorders; and other nerve stimulators for treating urinary incontinence, sleep apnea, shoulder subluxation, etc. The following description will generally focus on the use of the present invention within a spinal cord stimulation (SCS) system (such as that disclosed in U.S. Patent 6,516,227). However, the present invention may find applicability in any implantable medical device (IPG) or any IPG system (such as the deep brain stimulation (DBS) system disclosed in USP 9,119,964).

[0004] An SCS system typically includes an implantable pulse generator (IPG) 10 shown in Figure 1A and 1B in plan view and cross-sectional view. The IPG 10 includes a biocompatible device housing 30 configured for implantation in patient tissue that holds the circuitry and battery 36 ( Figure 1B ) required for the IPG to function. The IPG 10 is coupled to electrodes 16 via one or more electrode leads 14 forming an electrode array 12. The electrodes 16 are configured to contact the patient's tissue and are carried on a flexible body 18 that also houses respective lead wires 20 coupled to each electrode 16. The lead wires 20 are also coupled to a proximal contact 22 that can be inserted into a lead connector 24 in a head 28 fixed to the IPG 10, which may include, for example, epoxy resin. Once inserted, the proximal contact 22 connects to a head contact 26 in the lead connector 24, which in turn is coupled to circuitry (connections not shown) within the housing 30 via an electrode feedthrough pin 34 through an electrode feedthrough 32.

[0005] In the illustrated IPG 10, there are 32 lead electrodes (E1-E32) separated between four leads 14, where the head 28 includes a 2×2 array of lead connectors 24 to receive the proximal ends of the leads. However, the number of leads and electrodes in the IPG is proprietary and can thus vary. In SCS applications, the electrode leads 14 are typically implanted close to the dura mater in the patient's spinal cord, and when using a four-lead IPG 10, these leads can be split into two on each of the right and left sides. The proximal contacts 22 are tunneled through the patient tissue to a distal location, such as the buttock where the IPG housing 30 is implanted, at which point they are coupled to the lead connectors 24. As Figure 1A also shown, one or more flat paddle leads 15 can also be used with the IPG 10, and in the illustrated example, 32 electrodes 16 are positioned on one of the generally flat surfaces of the head 17 of the paddle lead, which surface will face the dura mater upon implantation. In other IPG examples designed for direct implantation at the site requiring stimulation, the IPG can be leadless, having electrodes 16 carried by the housing of the IPG instead for contacting the patient's tissue.

[0006] As Figure 1B shown in the cross-section of, the IPG 10 includes a printed circuit board (PCB) 40. Electrically coupled to the PCB 40 is a battery 36, which in this example is rechargeable; other circuitry 46 coupled to the top and / or bottom surfaces of the PCB 40 includes a microcontroller or other control circuitry required for IPG operation; telemetry antennas 42a and / or 42b for wirelessly transmitting data to an external controller 50 ( Figure 2 ) ; a charging coil 44 for wirelessly receiving a magnetic charging field from an external charger (not shown) for recharging the battery 36; and electrode feedthrough pins 34 (connected to circuitry not shown). If the battery 36 is permanent and non-rechargeable, the charging coil 44 would be unnecessary.

[0007] Either or both of the telemetry antennas 42a and 42b can be used to transmit data transcutaneously through the patient's tissue to an external device, such as Figure 2The external controller 50 shown in. The shapes of the antennas 42a and 42b and the electromagnetic fields they employ are different. The telemetry antenna 42a includes a coil that can communicate bidirectionally with an external device via a magnetic induction communication link that includes a magnetic field typically less than 10 MHz and is operable in its near field to communicate at a distance of, for example, 12 inches or less. The telemetry antenna 42b includes a short-range radio frequency (RF) antenna that operates in accordance with short-range RF communication standards and their potential modulation schemes and protocols to communicate bidirectionally with an external device along a short-range RF communication link. The short-range RF communication link typically operates using far-field electromagnetic waves in the range of approximately 10 MHz to 10 GHz and allows devices to communicate at a distance of approximately 50 feet or less. Short-range RF standards operable with the antenna 42b include, for example, Bluetooth, BLE, NFC, Zigbee, WiFi (802.11x), and Medical Implant Communication Service (MICS) or Medical Device Radio Communication Service (MDRS). The short-range RF antenna 42b can take any number of well-known forms for electromagnetic antennas (such as patches, slots, wires, etc.) and can operate as a dipole or a monopole. The IPG 10 can include both the coil antenna 42a and the short-range RF antenna 42b to expand the types of external devices with which the IPG 10 can communicate, although the IPG 10 can also include only one of the antennas 42a and 42b.

[0008] As referenced Figure 3 As explained, implanting the IPG 10 within a patient is typically a multi-step process. The first step involves implanting the distal end of one or more leads 14 or 15 having electrodes 16 through a temporary incision 62 in the patient's tissue 5 into the patient's spine 60. (For simplicity, in Figure 3Only two leads 14 with a total of 16 electrodes 16 are shown. The proximal ends of leads 14 or 15, including the proximal contacts 22, extend outwardly from the incision 62 (i.e., outside the patient) and ultimately connect to an external test stimulator (ETS) 70. The ETS 70 is used during the test stimulation phase to provide stimulation to the patient, which can, for example, last for about two weeks. To facilitate the connection between the lead 14 or 15 and the ETS 70, an ETS extender cable 80 can be used, which includes a socket 82 for receiving the proximal contact 22 of the lead 14 or 15 (similar to the lead connector 24 in the IPG 10) and a connector 84 for mating with the port 72 on the ETS 70, thus allowing the ETS 70 to communicate individually with each electrode 16. Once connected to the lead 14 or 15, the ETS 70 can then be attached to the patient in a convenient manner during the test stimulation phase, such as by placing the ETS 70 in a belt worn by the patient (not shown). The ETS 70 includes a housing 73 for its control circuit, antenna, etc., and the housing 73 is not configured to be implanted in the patient's tissue.

[0009] The ETS 70 essentially mimics the operation of the IPG 10 to provide stimulation to the implanted electrodes 16 and thus includes a battery within its housing and stimulation and communication circuitry similar to that provided in the IPG 10. Thus, the ETS 70 allows for the verification of the effectiveness of the stimulation therapy for the patient, such as whether the treatment has alleviated the patient's symptoms (e.g., pain). The test stimulation using the ETS 70 also allows for the determination of one or more specific stimulation programs that are likely to be useful for the patient once the IPG 10 is later implanted within the patient. The stimulation program can specify, for example, which electrodes 16 are active and used to deliver stimulation pulses; whether these active electrodes are used as anodes or cathodes; the current or voltage amplitude (A) of the stimulation pulse; the pulse width (PW) of the stimulation pulse; and the frequency (f) of the stimulation pulse, as well as other parameters.

[0010] Figure 3 The clinician programmer system can generally also be used by the clinician to communicate with and program the IPG 10 once the IPG 10 is fully implanted within the patient. This communication will again occur via the communication link 92. Thus, the clinician programmer system can be used during the patient examination, for example, to update the stimulation program that the IPG 10 is running.

[0011] Figure 4An example of a stimulation pulse as defined by a particular stimulation program is shown. As shown, and as is typical in an IPG, each stimulation pulse is biphasic, meaning it includes a first pulse phase, followed essentially immediately by a pulse phase of opposite polarity. The pulse width (PW) can include the duration of either individual pulse phase as shown, or can include the entire duration of the biphasic pulse (including both pulse phases).

[0012] Biphasic pulses are useful because the second pulse phase can actively recover any charge that gradually builds up after the first pulse phase resides on the capacitance (such as the DC blocking capacitor 107 discussed later with respect to Figure 7 ). In the example stimulation program shown, electrode E4 is selected as the anode electrode, while electrode E5 is selected as the cathode electrode at the same time. The pulses shown include pulses of constant current, and note that the amplitude of the current at any point in time is equal but opposite, such that the current injected into the patient tissue through one electrode (e.g., E4) is removed from the tissue by the other electrode (E5). Also note that the areas of the first pulse phase and the second pulse phase are equal, ensuring active charge recovery of the same amount of charge during each pulse phase. Although not shown, more than two electrodes can be effective at any given time. For example, electrode E4 can include an anode providing a +10 mA current pulse amplitude, while electrodes E3 and E5 can both include cathodes having -7 mA and -3 mA current pulse amplitudes, respectively.

[0013] Referring again to Figure 3 , the stimulation program executed by the ETS 70 can be provided or adjusted via a wired or wireless link 92 (shown wirelessly) from the clinician programmer 90. As shown, the clinician programmer 90 includes a computer-type device and can communicate wirelessly with the ETS 70 via the link 92, which can include a magnetic induction or short-range RF telemetry scheme as already described. If the clinician programmer 90 lacks a communication antenna, the communication head or communication stick 94 can be wired to a computer having a communication antenna. Thus, the ETS 70 and the clinician's programmer 90 and / or its communication head 94 can include antennas compliant with the selected telemetry scheme. The clinician programmer 90 can be as described in U.S. Patent Application Publication 2015 / 0360038. The external controller 50 ( Figure 2 ) can also communicate with the ETS 70 to allow the patient device to provide or adjust the stimulation program of the ETS 70.

[0014] At the end of the trial stimulation phase, a decision is made whether to abandon the stimulation treatment or whether to provide such as Figure 1A and 1BThe permanent IPG 10 shown in FIG. is provided to the patient. If it is determined that the stimulation therapy is not effective for the patient, the lead 14 or 15 can be removed from the patient's spine 60 and the incision 62 closed during other surgeries.

[0015] In contrast, if the stimulation therapy is effective, the IPG 10 can be permanently implanted within the patient as discussed above. (In this case, "permanent" generally refers to the service life of the IPG 10, which may be from several years to several decades, at which time the IPG 10 will need to be removed and a new IPG 10 implanted). Thus, the IPG 10 will be implanted in the correct location (e.g., the buttock) and connected to the lead 14 or 15, and then the temporary incision 62 can be closed and the ETS 70 is not required. The result is a fully implanted stimulation therapy regimen. If one or more specific stimulation programs have been determined during the trial stimulation phase, it / they can be programmed into the IPG 10 using the external programmer 50 or the clinician programmer 90 and subsequently modified wirelessly. SUMMARY OF THE INVENTION

[0016] A medical device is disclosed which, in one example, includes: a plurality of electrodes configured to provide stimulation to patient tissue; and control circuitry configured to: control a stimulation circuit to emit stimulation pulses according to a stimulation program using at least two active electrodes, detect a neuronal response to the stimulation pulses at at least one non-active electrode among the plurality of electrodes, and determine at least one measure of the synchrony of the neuronal response, and adjust the stimulation program in response to at least one measure of the synchrony to promote asynchrony of the neuronal response.

[0017] The neuronal response can include an evoked compound action potential (ECAP). The control circuitry can be configured to: determine at least one measure of the synchrony of the neuronal response by determining at least one shape parameter of the ECAP (such as one or more of the ECAP height or width). The control circuitry can be configured to: compare at least one measure of the synchrony of the neuronal response with at least one threshold, and if the comparison of at least one measure and at least one threshold indicates synchronous neuronal firing, adjust the stimulation program to promote asynchrony of the neuronal response. The control circuitry can include a microcontroller programmed with an algorithm configured to detect a neuronal response to the stimulation pulses and determine at least one measure of the synchrony, and adjust the stimulation program to promote asynchrony of the neuronal response. The algorithm can also be configured to select at least one non-active electrode with respect to at least two active electrodes.

[0018] The control circuit may further include at least one amplifier for receiving neuron responses from at least one non-active electrode, and may further include at least one analog-to-digital converter to receive the output of at least one amplifier and digitize the amplifier neuron responses.

[0019] The control circuit may be configured to adjust the stimulation program to promote asynchrony of neuron responses by adjusting one or more stimulation parameters, including which electrodes are active to be used as anodes or cathodes; the current or voltage amplitude of the stimulation pulse; the pulse width of the stimulation pulse; and the frequency of the stimulation pulse.

[0020] The control circuit may be configured to: adjust the stimulation program to promote asynchrony of neuron responses by adding one or more additional anode electrodes or one or more cathodes that emit one or more additional pulses to at least two active electrodes. The energy of the adjusted stimulation pulse and the one or more additional pulses may be equal to the energy of the stimulation pulse before adjustment.

[0021] One or more additional pulses may have the same pulse width and timing as the stimulation pulse, or one or more additional pulses may not overlap with the stimulation pulse or may only partially overlap with the stimulation pulse. One or more additional pulses may have a different frequency and / or a different pulse width from the stimulation pulse.

[0022] The control circuit may also be configured to adjust the stimulation program to promote asynchrony of neuron responses by adjusting the amplitude of the stimulation pulse at at least two active electrodes, wherein the amplitude of each stimulation pulse is adjusted to have a plurality of different amplitudes. Alternatively, the stimulation pulse may have a first frequency, and each stimulation pulse may be adjusted to a group of a plurality of different stimulation pulses, wherein the different stimulation pulses in each group have a second frequency higher than the first frequency.

[0023] The medical device may further include a housing for accommodating the control circuit, wherein the medical device includes an implantable pulse generator, and the housing is configured for implantation in the tissue of a patient. Alternatively, the medical device may further include an enclosure for accommodating the control circuit, wherein the medical device includes an external test stimulator, such as an external test stimulator (ETS), and the enclosure is not configured for implantation in the tissue of a patient.

[0024] Also disclosed is a system that includes a machine - implementable algorithm, where the algorithm, when executed, is configured to: control a stimulation circuit in a medical device to deliver stimulation pulses according to a stimulation program using at least two active electrodes; and detect a neuronal response to at least one stimulation pulse at at least one non - active electrode among a plurality of electrodes; determine at least one measure of the synchrony of the neuronal response; and adjust the stimulation program in response to at least one measure of synchrony to promote asynchrony of the neuronal response. A medical device having a plurality of electrodes configured to provide stimulation to a patient's tissue may also be included as part of the system.

[0025] In this system, the algorithm may be stored on a non - transitory machine - readable medium within the medical device, where the algorithm is configured to be executed within the medical device. The system may also include an external system configured to communicate with the medical device, and may further include a user - interface program executable on the external system, the user - interface program being configured to present options to allow a user of the external system to command the medical device to implement the algorithm in the medical device. The user - interface program may also be configured to allow the user to prohibit the use of the algorithm in the medical device.

[0026] The system may also further include an external system configured to communicate with the medical device, where the algorithm is stored on a non - transitory machine - readable medium within the external system, and where the algorithm is configured to be executed within the external system. The external system may also include communication circuitry configured to: receive a detected neuronal response to at least one stimulation pulse at at least one non - active electrode among a plurality of electrodes; and send one or more control instructions to cause the medical device to adjust the stimulation program to promote asynchrony of the neuronal response. The external system may include a clinician programmer system or a handheld external controller for the medical device.

[0027] In this system, the medical device may also include a housing for accommodating a control circuit, where the medical device includes an implantable pulse generator, and the housing is configured for implantation in a patient's tissue. Alternatively, the medical device may also include an enclosure for accommodating the control circuit, where the medical device includes an external stimulator, and the enclosure is not configured for implantation in a patient's tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1A and 1B An implantable pulse generator (IPG) according to the prior art is shown in a plan view and a cross - sectional view, respectively.

[0029] Figure 2 A handheld external controller for communicating with the IPG according to the prior art is shown.

[0030] Figure 3Shows a clinician programming system for communicating with an IPG or an external test stimulator (ETS) according to the prior art.

[0031] Figure 4 Shows an original stimulation program considered effective for a patient according to the prior art.

[0032] Figure 5 Shows a graph of the action potential of a neuron according to the prior art.

[0033] Figure 6 Shows an electric field generated in patient tissue for recruiting neurons to fire according to the prior art.

[0034] Figure 7 Shows an improved IPG according to an example of the present invention, which includes a control circuit programmed using an evoked compound action potential (ECAP) algorithm and also includes a sensing circuit for sensing ECAP at a sensing electrode.

[0035] Figure 8A and 8B Shows an original stimulation program according to an example of the present invention, the generation of the resulting ECAP (accompanied by examples of the resulting synchronous ECAP and asynchronous ECAP), and the detection of the ECAP by the ECAP algorithm in the improved IPG.

[0036] Figure 9 Shows a flowchart of the ECAP algorithm according to an example of the present invention.

[0037] Figure 10A and 10B Shows a first way according to an example of the present invention, in which the ECAP algorithm can adjust the original stimulation program to promote asynchronous firing of recruited neurons by adding effective electrodes.

[0038] Figure 11A and 11B Shows a second way according to an example of the present invention, in which additional effective electrodes generate pulses that do not overlap with the pulses in the original stimulation program.

[0039] Figure 12A and 12B Shows a third way according to an example of the present invention, in which additional effective electrodes generate pulses that overlap with the pulses in the original stimulation program.

[0040] Figure 13A and 13B Shows a fourth way according to an example of the present invention, in which additional effective electrodes generate pulses having a frequency different from the pulses in the original stimulation program.

[0041] Figure 14A and 14B shows a fifth way according to an example of the present invention without using additional active electrodes, wherein the amplitude of the pulses in the original stimulation program is modified.

[0042] Figure 15A and 15B shows a sixth way according to an example of the present invention without using additional active electrodes, wherein the pulse width of the pulses in the original stimulation program is modified. Detailed Description

[0043] In particular with regard to SCS therapy, there is evidence that when compared to stimulation pulses of lower frequency, providing stimulation pulses at a relatively high frequency (e.g., >1 kHz) can have therapeutic benefits. In particular, it has been reported that higher frequency stimulation can reduce certain side effects that may accompany lower frequency stimulation. In particular, higher frequency stimulation can reduce paresthesia - a prickling or tingling sensation.

[0044] The benefits of high frequency stimulation are related to the inherent limitations regarding the frequencies at which neurons can respond to stimulation. When neurons are recruited by electrical stimulation, they will fire an action potential - that is, the neurons will "fire". Figure 5 shows an action potential for a typical neuron. If electrical recruitment causes the resting state of the neuron (e.g., -70 mV as measured from inside the cell) to exceed a threshold (e.g., -55 mV), the neuron will depolarize ("A"), repolarize ("B"), and refract ("C") before resting again. If the electrical stimulation continues, the neuron will fire again at some later time. Note that for a given neuron, the amplitude of the action potential does not change; in other words, the action potential does not vary with the intensity of the stimulation. Instead, strong stimulation will increase the frequency at which the action potential is fired.

[0045] However, there are limitations to how fast a given neuron can fire. The shape and size of each neuron are unique and thus can fire at its inherent maximum frequency. Consider Figure 6 , which shows Figure 4 an example where electrodes E4 and E5 on lead 14 are used to generate pulses. This stimulation creates an electric field in the volume 95 of patient tissue 5 around the selected electrodes. Some neurons within the electric field volume 95 will be recruited and fire, particularly those neurons close to the cathode electrode E5. It is hoped that the sum of the neurons firing within volume 95 will mask the signal indicating pain, thus providing the desired treatment.

[0046] If high-frequency stimulation is used that is typically above the maximum frequency at which a neuron can fire (and if the stimulation is appropriately strong), then the neurons recruited within volume 95 will not be able to fire at the frequency of the stimulation. Instead, each neuron will be limited to firing at its maximum frequency, which will also be different for each neuron. Thus, the firing of the neurons within volume 95 will be asynchronous with the firing of different neurons at different times. In contrast, if low-frequency stimulation is used that is typically below the maximum neuron frequency, then the neurons recruited within volume 95 will all fire at the frequency of the stimulation and simultaneously. In other words, the neurons will fire synchronously.

[0047] In addition, synchronous firing of neurons at low frequencies is the cause of the unwanted side effect of paresthesia, and asynchronous firing at higher frequencies mitigates this effect. However, this is unfortunate because providing stimulation pulses at high frequencies is not a simple matter. For example, high-frequency stimulation requires the circuit in the IPG 10 that generates the pulses to also switch at high frequencies. High-frequency switching of the IPG's circuit is more power-consuming and thus requires a higher draw from the IPG battery 36. Therefore, the battery 36 must either be made larger to increase the IPG size or the battery must be wirelessly charged more frequently, both of which are undesirable.

[0048] Accordingly, an IPG or an ETS is provided that is capable of sensing the degree to which the recruited neurons are firing synchronously. Preferably, the sensed synchrony is also used by the IPG in a closed-loop manner to modify the original stimulation program that the IPG is executing, which otherwise typically provides good therapeutic results for the patient (although it may have the side effect of paresthesia). In one example, the neuronal response to the original stimulation program, specifically the evoked compound action potential (ECAP) of the recruited neurons, is sensed as a measure of synchrony. At least one non-active electrode senses the resulting ECAP, which is digitized and sent to the control circuit of the IPG. The ECAP algorithm evaluates the shape of the ECAP and determines one or more ECAP shape parameters that indicate whether the recruited neurons are firing synchronously or asynchronously. If the shape parameters indicate a high degree of synchrony, the ECAP algorithm can adjust the stimulation program in one or more ways to promote asynchronous firing, thereby reducing paresthesia. The ECAP algorithm can operate to adjust the original stimulation program even if it is otherwise operable at a typically low frequency (<1 kHz), although it can also be used to evaluate and promote asynchrony at higher frequencies.

[0049] Figure 7 An improved IPG 100 operable as just described is shown. Although described in the context of the IPG 100, it should be recognized that the present invention can also be embodied in an external stimulator, such as an external trial stimulator (e.g., ETS 70, Figure 3) which typically mimics the operation of the IPG, as previously explained.

[0050] The IPG 100 includes a control circuit 102 into which the ECAP algorithm 124 can be programmed, which may include a microcontroller, such as a part number MSP430 manufactured by Texas Instruments, which is described in the data sheet at http: / / www.ti.com / lsds / ti / microcontroller / 16-bit_msp430 / overview.page?DCMP=MCU_other&HQS=msp430. Other types of control circuits can also be used in place of the microcontroller, such as a microprocessor, FPGA, DSP, or a combination of these, etc. As described in U.S. Patent Application Publication 2012 / 0095529 and USP 9,061,140 and 8,768,453, the control circuit can also be formed in whole or in part in one or more application-specific integrated circuits (ASICs).

[0051] The bus 118 provides digital control signals to one or more digital-to-analog converters (DACs) 104, which are used to generate a current or voltage of a specified amplitude (A) for the stimulation pulses and have the correct timing (PW, f). As shown, the DAC includes a PDAC that supplies (source) current to one or more selected anode electrodes and an NDAC that sinks (sink) current from one or more selected cathode electrodes. The switch matrix 106 is used to route one or more PDACs and one or more NDACs to any electrode 16 via the bus 116 and thus effectively select the anode and cathode electrodes. In short, the buses 118 and 116 typically set the stimulation program that the IPG 100 is running. The shown circuit for generating the stimulation pulses and delivering them to the electrodes is just one example. Other methods can be found in, for example, USP 8,606,362 and 8,620,436.

[0052] Note that the current path to the electrode 16 includes the previously mentioned DC-blocking capacitor 107, which is known to provide additional safety by preventing the inadvertent supply of DC current to the electrode and the patient's tissue. As discussed earlier, when a stimulation current is provided, a capacitor such as this can become charged, providing power for the use of biphasic pulses.

[0053] Preferably, any of the electrodes 16 can be used to sense the previously described ECAPs, and thus each electrode can also be coupled to at least one sense amplifier 110. In the example shown, all electrodes share a single sense amplifier 110, and thus any one sense electrode can be coupled to the sense amplifier 110 at a given time of each multiplexer 108, as controlled by the bus 114. However, this is not strictly necessary, and instead each electrode can be coupled to its own dedicated sense amplifier 110. The analog waveforms including the ECAPs, described further below, are preferably converted to digital signals by an analog-to-digital converter 112, which can also reside within the control circuit 102.

[0054] Note that the connection of the electrode 16 to one or more sense amplifiers 110 preferably occurs through a DC-blocking capacitor 107, such that the capacitor is between the electrode and the one or more sense amplifiers. This is preferred in order not to disrupt the safety provided by the DC-blocking capacitor 107.

[0055] Once the digitized ECAP is received at the control circuit 102, it is processed by the ECAP algorithm 124 to determine one or more ECAP shape parameters. Figure 7 The waveform on the right in shows the basic shape of the ECAP. Different from the action potential shown for the Figure 5 individual neurons in, the ECAP measured outside the cell will be inverted, but otherwise will generally be similar in shape to the signal action potential. As the name implies, the ECAP comprises a composite (sum) of various action potentials as emitted from multiple neurons, and thus its magnitude will depend on how many neurons are firing. Generally, the ECAP can vary between 100 microvolts and several tens of millivolts. Note that the DC-blocking capacitor 107 through which the ECAP passes will remove any DC component in the signal, and thus its reference is 0 volts. If necessary, the sensed ECAP signal can be level-shifted to occur within a range that can be processed by the electronics in the IPG 100 (such as between 3 volts and ground).

[0056] Figure 8A and 8B shows a specific stimulation program, the generation of the resulting ECAP, and the detection of the ECAP. As before, the stimulation program is defined by various stimulation parameters (such as the specific amplitude, pulse width, and frequency of the pulses), although these parameters are not labeled in Figure 8B As Figure 4What occurs is that, in the example stimulation program shown, electrode E4 is selected to be used as the anode (+), and electrode E5 as the cathode (-). Assume that this particular stimulation program has been selected as a stimulation program that generally provides good therapeutic results for a particular patient (although it may have the side effect of paresthesia). This can be said to include the "original" stimulation program, which may have been determined during the ETS test ( Figure 3 ) or otherwise.

[0057] Once stimulation begins (at time = 0), an ECAP will be generated, which includes the sum of the action potentials of the recruited neurons and thus fires in the electric field volume 95. As Figure 8A shown, the ECAP will conduct through the patient's tissue at a speed of approximately 5 cm / 1 ms via neuronal conduction. In the example shown, the ECAP moves to the right, in the direction towards the brain. However, the ECAP will also move in other directions towards the patient's periphery.

[0058] A single sensing electrode (S) has been selected to sense the ECAP as it moves past, and in this example the sensing electrode is electrode E9. The selection of the appropriate sensing electrode can be determined by an ECAP algorithm 124 operable in the control circuit 102 based on a number of factors. For example, it is preferred that the sensing electrode S be reasonably selected with respect to the effective electrode such that by the time the sensing electrode can sense the ECAP, the electric field 95 generated around the effective electrode will have ceased. This simplifies the ECAP detection at the sensing electrode because the voltage present in the electric field 95 will not interfere with and potentially obscure the ECAP. In this regard, the ECAP algorithm 124 is useful for knowing: the pulse width of the stimulation program, the range of magnitudes of the electric field 95 (which can be estimated), the speed at which the ECAP is expected to travel, and the distances between the electrodes 16 in the electrode array 12, such as along a particular straight lead 14 or paddle lead 15 ( Figure 1A ).

[0059] For example, in Figure 8AIn this case, assume that the pulse width (for both phases of the biphasic pulse) is 0.5 ms as shown, and the electrode E9 is typically 2.5 cm away (d) from the active electrodes (and thus their electric field 95). When the ECAP is formed in the electric field 95 at the start of the stimulation at time = 0, it will reach the electrode E9 after some delay 130 according to the speed at which the ECAP moves (e.g., 5 cm / 1 ms). In other words, the ECAP will start passing through the sensing electrode E9 at 0.5 ms. Since the stimulation pulse and the electric field 95 will have stopped at this time, the sensing electrode E9 should not sense any voltage related to the electric field and should only sense the ECAP. Therefore, the ECAP algorithm 124 can be enabled to sense the ECAP at time = 0.5 ms after the start of the stimulation pulse. This enabling can be controlled by: controlling the multiplexer 108 via the bus 114 ( Figure 7 ) to pass the input from the sensing electrode E9 to the sense amplifier 110, the ADC 112, and ultimately to the ECAP algorithm 124. The sensing can continue for as long as desired to detect at least some aspects of the resulting ECAP shape. For example, the sensing can continue for a sufficient length of time (which can include, for example, 3 ms) to allow detection of the polarization and refraction peaks in the ECAP.

[0060] It should be noted that it is not strictly necessary for sensing to occur at an electrode that will not experience interference from the electric field 95, since masking techniques can be used to subtract the voltage present in the electric field. Such masking techniques are described, for example, in M. Hughes, “Fundamentals of Clinical ECAP Measures in Cochlear Implants: Part 1: Use of the ECAP in Speech Processor Programming (2nd Ed.),” Audiology Online (November 8, 2010) (http: / / www.audiologyonline.com / articles / fundamentalsclinicalecapmeasuresin846); and I. Akhoun et al., “Electrically Evoked Compound Action Potential Artifact Rejection by Independent Component Analysis: Technique Validation,” Hearing Research 302, pp. 60 - 73 (2013). Such masking techniques can allow the selection of an electrode closer to the active electrodes (e.g., E6) as the sensing electrode.

[0061] In addition, the ECAP algorithm 124 can also select more than one electrode to be used as sensing electrodes. For example, the ECAP algorithm 124 can sense the traveling ECAP at electrodes E6, E7, E8, E9, etc. This will require timing control because E6 will be sensed before E7, etc., and may also require circuit changes to accommodate sensing ECAP at different electrodes at overlapping time points. For example, in this example, each electrode may require its own timing control (multiplexer 108), and its own sensing amplifier 110 and ADC 112, although this is not shown in Figure 7 it.

[0062] An aspect that may affect sensing of ECAP in the IPG 100 relates to passive charge recovery. As discussed earlier, it is preferred to use biphasic pulses in the IPG to actively recover charge during the second pulse phase, which may have been established across a capacitive element (such as the DC-blocking capacitor 107) during the first pulse phase. Since active charge recovery may not be perfect, the IPG 100 can additionally include passive charge recovery implemented by a switch 122 as shown in Figure 7 . The passive charge recovery switch 122 is controlled by a bus 120 issued from the control circuit 102 and is used to connect the inner plate of the DC-blocking capacitor 107 to a common potential (Vref). When this occurs, the DC-blocking capacitor 107 is connected in parallel between the common potential and the patient tissue, which helps to balance the charge across the capacitor and thus recover any remaining charge. As shown by the small, exponentially decreasing waveform in Figure 8B , passive charge recovery using the switch 122 typically occurs after the last phase of each stimulation pulse. Additionally, passive charge recovery may overlap in time with the period during which ECAP sensing is enabled in other ways. This may result in problems for ECAP sensing because it places the common potential on the input of the multiplexer carrying the ECAP signal. Therefore, the control circuit 102 will preferably not close the passive recovery switch 122 associated with the sensing electrode being sensed, although all other switches 122 may be closed. Alternatively, the control circuit can only close the switches coupled to the active electrodes (E4, E5). Once the ECAP has been sensed, if needed, the control circuit 102 can return to closing the switch 122 of the sensing electrode.

[0063] Figure 8BShows ECAP as sensed under two assumptions: First, when the neurons recruited within the electric field 95 fire in a substantially synchronous manner; second, when the recruited neurons fire in a substantially asynchronous manner, which, as previously noted, is theoretically desired to reduce side effects such as paresthesia. Note that the ECAP shapes are different for these two conditions. In the synchronous case, the recruited neurons typically fire simultaneously, and thus their cumulative effect results in a waveform with higher and sharper peaks, that is, where its height H1 is relatively large and its full width at half maximum FWHM1 is relatively small. In contrast, in the asynchronous case, the recruited neurons fire at different times, and thus their cumulative effect results in a waveform with smaller and wider peaks, where H2 is relatively small and FWHM2 is relatively large. Other parameters can also be used to analyze ECAP, such as various slopes, timing of the peaks, etc., but for simplicity, the shape parameters H and FWHM are shown.

[0064] Although only one ECAP is shown for each condition as shown in Figure 8B it should be understood that an ECAP will be generated at the start of each stimulus pulse. Thus, the ECAP algorithm 124 can make more than one ECAP measurement—for example, after several consecutive pulses—and average the shape parameters (e.g., H, FWHM) for each pulse. The shape parameters of the measured ECAPs taken at different sensing electrodes (e.g., at E6, E7, etc.) can also be averaged.

[0065] Once the ECAP has been measured and its shape parameters determined, the ECAP algorithm 124 can evaluate these shape parameters to discern the extent to which the stimulation appears synchronous or asynchronous, and can automatically adjust the original stimulation program in one or more ways to try and promote asynchrony. By comparing the shape parameters to thresholds, for example by comparing the height H of the ECAP to a first threshold T1, and / or by comparing the width of the ECAP (e.g., FWHM) to a second threshold T2, the degree of synchrony can be determined in a simple example. Additionally, other shape parameters can be used, and more than one shape parameter can be considered when determining synchrony. If it is determined that the ECAP is too synchronous, e.g., if H > T1, and / or if FWHM < T2, the original stimulation program can be adjusted in one or more ways to try and promote asynchrony.

[0066] Figure 9An example of the operation of the ECAP algorithm 124 is shown, and many of its steps have been discussed above, but are reviewed here for completeness. Prior to operation of the ECAP algorithm, an original stimulation program that is effective for the patient has preferably been selected (step 140). However, this is not strictly necessary, and instead the ECAP algorithm 124 can be used to determine an original stimulation program, for example, one that initially appears to provide good asynchrony during the ETS phase, but which can be further modified later.

[0067] As described above, once the original stimulation program is selected, the ECAP algorithm 124 can select one or more electrodes to use as sensing electrodes (S) (step 142). Stimulation can then be provided using the original stimulation program (step 144), and one or more ECAPs can be measured at the sensing electrodes (S) (step 146). As noted above, multiple ECAPs can be measured. For one or more ECAPs, at least one ECAP shape parameter (e.g., H, FWHM) can be determined (step 148), and if necessary, averaged from multiple ECAPs. The ECAP algorithm 124 can then evaluate the one or more shape parameters to determine the degree of synchronization of the firing of the recruited neurons (step 150), which can involve comparing the parameters to one or more thresholds, as described earlier.

[0068] If the stimulation appears to provide significant asynchronous firing, the ECAP algorithm 124 may return to step 144 and continue to provide the stimulation program without adjustment, although the process may continue to monitor the ECAP and make adjustments in the future if necessary. If the stimulation appears to provide significant synchronous firing, the stimulation program may be adjusted, and then the stimulation program may be adjusted. Figures 10A - 15B The manner of doing so is discussed. In general, adjustments can involve adjusting any stimulation parameter, including which electrodes 16 will be active; whether those active electrodes are used as anodes or cathodes; the current or voltage amplitude (A) of the stimulation pulses; the pulse width (PW) of the stimulation pulses; and the frequency (f) of the stimulation pulses. After the adjustments, one or more ECAPs can be measured again (step 146), one or more shape parameters determined (step 148), and evaluated (step 150) to see if significant desynchronization has been achieved. If not, the stimulation program can be adjusted again and the process repeated.

[0069] Note that after adjusting the stimulation (step 152), optional step 154 may include asking the patient how the adjustment feels, such as whether the adjustment seems to have reduced side effects such as paresthesia. If so, the ECAP algorithm 124 may be stopped at this time (step 156), where the adjustment settings are used for the patient's new stimulation program. Alternatively, the ECAP algorithm 124 may be allowed to continue to see if an even better treatment outcome can be achieved.

[0070] Although the ECAP algorithm 124 may simply always be operable in the IPG 100 or ETS, it may be more prudent to make it operable only at different times to improve the originally selected stimulation program for a given patient. Any external system that can communicate with the IPG 100 or ETS (such as Figure 3 the clinician programmer system or Figure 2 the patient external controller 50) can be used to implement the occasional use of the ECAP algorithm 124. Although not shown, such an external system can be programmed using a user interface program executable on an external device configured to communicate with the medical device, and the user interface program, when executed, is configured to present options to allow a user of the external system (e.g., on its screen or display) to command the medical device to implement the ECAP algorithm 124 and also possibly prohibit the use of the algorithm.

[0071] In addition, at least some parts or all of the ECAP algorithm 124 may operate on an external system. For example, the communication circuit of the external system may receive the detected neural response (ECAP); determine the shape parameters and evaluate them for relative synchrony; determine how to adjust the original stimulation program to promote asynchrony; and send one or more control instructions to cause the medical device to adjust the stimulation program accordingly. The use of the ECAP algorithm 124 in combination with a clinician programming system as an external system may occur during the ETS phase or even after the IPG has been fully implanted, such as when the patient meets with the clinician for an examination.

[0072] Those skilled in the art will understand that the ECAP algorithm 124 and / or any supporting user interface program will include instructions that can be stored on a non-transitory machine-readable medium (such as magnetic, optical, or solid-state memory). Such memory can be within the IPG or ETS itself (i.e., stored in association with the control circuit 102), within the external system, or be readable by an external system (such as a memory stick or disk). Such memory can also include those within the Internet or other network servers (such as the server of the implantable medical device manufacturer or the application store server, which can be downloaded to the external system).

[0073] As noted, the ECAP algorithm 124 adjusts the raw stimulation program to promote asynchrony (step 152, Figure 9 ) can occur in several different ways, some of which are shown in Figures 10A to 15B . Although these ways are described separately for simplicity, it should be noted that any of the ways can be used in combination.

[0074] In Figure 10A and 10B , a first way is shown in which the ECAP algorithm 124 can adjust the patient's raw stimulation program to achieve improved asynchrony. In this example, the ECAP algorithm 124 adds an additional active electrode to the stimulation program. In particular, electrode (E3) has been added as an additional anode to the raw stimulation program (which again includes E4 as the anode and E5 as the cathode in the simple example). This additional anode (E3) is preferably close to the other active electrodes (E4, E5) to be generally consistent with the location of the desired treatment, but this is not necessary. In the example shown, the amplitude of the additional anode E3 is equal to the amount (X) by which the amplitude of anode E4 is decreased. Thus, the adjustment of the stimulation program by the ECAP algorithm 124 in this example does not change the energy used to provide the stimulation pulses, although this is not strictly required. Anode E4 can maintain its original amplitude, with the amplitude of E3 set in other ways. In any case, note that the cathode current at the cathode electrode E5 may or may not need to be adjusted to restore the sum of the anode currents at E4 and E3. In this example, note that the additional anode E3 additionally has the same timing (pulse width and frequency) as the original active electrodes E4 and E5.

[0075] As shown in Figure 10A and when compared with Figure 8A , it can be seen that adding the anode electrode E3 changes the magnitude and shape of the electric field 95 formed in the patient's tissue. Thus, and at different lengths along the lead, different neurons will be recruited, which should generally increase the asynchrony of the resulting ECAP. Although not shown, as previously explained, the ECAP algorithm 124 can verify whether this adjustment actually increases the asynchrony by detecting the shape of the resulting ECAP at one or more specified sense electrodes (e.g., E9; Figure 8B ). (For simplicity, in Figure 10BThe ECAP obtained at the sensing electrode S is not shown in [the figure]. If an increased asynchrony is sensed and the patient is expected to report good treatment outcomes and fewer paresthesias, the ECAP algorithm 124 can remain running and be adjusted in the future as needed, or the ECAP algorithm 124 can stop running and the adjustment can be set to a new stimulation program for the patient. If an increased asynchrony is not sensed, the ECAP algorithm 124 can continue to run for other adjustments, such as by selecting other additional anodes or cathodes, by changing their amplitudes, or by other means discussed later.

[0076] Although not shown in Figure 10A and 10B it is recognized that yet another anode can be added by the ECAP algorithm 124 to attempt to increase asynchrony, or one or more additional cathodes can also be added. For example, E3 and / or E6 can be added as additional cathodes.

[0077] In Figure 10A and 10B 's example, the additional anode or cathode electrodes emit pulses with the same timing as the timing specified by the original stimulation program. However, as shown in Figure 11A and 11B such additional electrodes can also emit at different timings. In this example, the ECAP algorithm 124 again adds the additional anode electrode E3 to attempt to increase asynchrony, but the pulses at E3 are emitted after the pulses otherwise provided by the original stimulation program at electrodes E4 and E5, such that they do not overlap. Note that the ECAP algorithm 124 simultaneously modifies the cathode electrode E5 to provide a return path for the added anode current emitted by the additional anode E3. Although not shown, a different cathode electrode can be selected to complement the additional anode electrode E3. In fact, because the additional anode pulses at E3 are non-overlapping, the complementary cathode pulses can include any electrode, including E4, even if E4 otherwise operates as an anode in the original stimulation program. Additionally, although the additional anode electrodes are seen to emit pulses having a pulse width equal to that used in the original stimulation program, the additional anode pulse width (PWa) can be different.

[0078] As shown in Figure 11AAs shown, the example generates two electric fields at two different times: a first field 95a formed during the original pulses (E4 and E5), and a second field 95b formed by pulses involving additional anodes (E3 and E5). Thus, different electric fields will recruit different neurons, and different neurons will fire at different time points. This will increase asynchrony, as can be verified by the ECAP algorithm 124, which is desired to have good therapeutic effects and reduced side effects. Similarly, although not shown, the ECAP algorithm 124 can select one or more additional anodes or one or more additional cathodes to attempt to increase asynchrony. Additional other pulses that do not overlap with the pulses at E3, E4, or E5 can also be emitted, although this is not shown.

[0079] Figure 12A and 12B shows another way in which the ECAP algorithm 124 can attempt to increase asynchrony by selecting additional anode or cathode electrodes that emit pulses that are at least partially overlapping with the pulses of the original stimulation program that are different from Figure 11A and 11B In particular and as shown, the first phase of the pulse at the additional anode E3 overlaps with the second phase of the original stimulation pulse. This is not strictly necessary; the first phase of the additional pulse can also overlap with the first phase of the original pulse. Additionally, as Figure 11A and 11B occurred in, the pulse width (PWa) of the additional pulse can again be different from the pulse width of the original pulse. Again, this strategy produces different electric fields between fields 95a and 95b at different time points, thereby recruiting different neurons at different time points and promoting asynchrony. Additional overlapping pulses can also be added.

[0080] Figure 13A and 13B shows an example in which the additional anode emits pulses having a frequency (f2) different from the frequency (f1) of the original stimulation pulse. Additionally, this will recruit neurons at different times, thereby promoting asynchrony. Additionally, the modifications discussed in conjunction with the previous examples (using other additional anodes or one or more additional cathodes, different pulse widths, overlapping or non - overlapping pulses, etc.) can also be used here.

[0081] As shown here, promoting asynchrony by the ECAP algorithm 124 may not involve adjustment of the original stimulation program involving the use of additional anodes or cathodes. Instead, the adjustment can involve adjustment of the use of the original effective electrodes (e.g., E4 and E5), and the first example is shown in Figure 14A and 14B As Figure 14BAs shown, the ECAP algorithm 124 has adjusted the amplitudes (A) of the original pulses so that they are different at different time points. In particular, the pulses have been adjusted to have multiple different amplitudes, and in this example the pulses have been divided into portions having amplitudes A1 and A2. As shown, A1 and A2 are each the same amount below and above the original amplitude A, and thus require the same energy as the original pulses, but again this is not strictly necessary. The portion of the pulse having amplitude A1 produces an electric field 95a of a first volume (or intensity), while at the same time amplitude A2 produces a larger volume (or greater intensity) field 95b, which will recruit additional neurons, thus promoting asynchrony in neuron firing.

[0082] In Figure 15A and 15B the example of, the adjustment provided by the ECAP algorithm 124 again only involves the original active electrodes E4 and E5, but where the pulse width of the original stimulus pulse is adjusted from PW to PW1. In this example, the pulse width PW1 is approximately half of the original pulse width PW, and thus two biphasic pulses can be formed within the same duration. While this is merely an example, more than two pulses can be formed, and the pulses formed by the adjustment do not need to occupy the same duration as the original pulse. In fact, it is noted that the original pulse in this example has been adjusted to a pulse train (G) having a higher frequency (f2) than the frequency (f1) of the original stimulus pulse, in an attempt to increase asynchrony.

Claims

1. A medical stimulation system, comprising: A medical device, including a plurality of electrodes configured to provide stimulation to a patient's tissue; And A machine-implementable algorithm, wherein the algorithm, when executed, is configured to (a) Control a stimulation circuit in the medical device to emit stimulation pulses according to a stimulation program using at least two active electrodes among the plurality of electrodes, and detect a neuronal response to at least one of the stimulation pulses at at least one non-active electrode among the plurality of electrodes; (b) Determine a first parameter and a second parameter of the neuronal response, compare the first parameter with a first threshold, and compare the second parameter with a second threshold; (c) If the first parameter is higher than the first threshold and the second parameter is lower than the second threshold, control the stimulation circuit to use at least two active electrodes among the plurality of electrodes to adjust the stimulation program to emit adjusted pulses, and detect a neuronal response to at least one of the adjusted pulses at the at least one non-active electrode, and repeat step (b); and (d) If the first parameter is lower than the first threshold and the second parameter is higher than the second threshold, stop adjusting the stimulation program.

2. The medical stimulation system according to claim 1, wherein, The first parameter includes the height of the neuronal response, and wherein the second parameter includes the width of the neuronal response.

3. The medical stimulation system according to claim 1, wherein, The algorithm is stored on a non-transitory machine-readable medium within the medical device, and wherein the algorithm is configured to be executed within the medical device.

4. The medical stimulation system according to claim 3, further comprising: An external system configured to communicate with the medical device.

5. The medical stimulation system according to claim 4, further comprising: A user interface program executable on the external system, wherein the user interface program is configured to present options that allow a user of the external system to command the medical device to implement the algorithm in the medical device.

6. The medical stimulation system according to claim 5, wherein, The user interface program is further configured to allow the user to prohibit the use of the algorithm in the medical device.

7. The medical stimulation system according to claim 4, wherein The algorithm is stored on a non-transitory machine-readable medium within the external system, and wherein the algorithm is configured to be executed within the external system.

8. The medical stimulation system according to claim 7, wherein, The external system further includes a communication circuit configured to perform the following operations: Receive a first neuronal response and a second neuronal response from the medical device, and Send one or more control instructions to control the stimulation circuit in the medical device.

9. The medical stimulation system according to claim 8, wherein, The external system includes a clinician programmer system or a handheld external controller for the medical device.

10. The medical stimulation system according to claim 1, wherein, The medical device includes an implantable pulse generator or an external stimulator.

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