Systems and methods for burst waveforms with anodic-leading pulses

The present disclosure provides systems and methods for generating burst waveforms. An implantable neurostimulation system includes an implantable stimulation lead including a plurality of contacts, and an implantable pulse generator communicatively coupled to the stimulation lead. The pulse generator is configured to generate a waveform including a burst that includes a leading anodic pulse followed by alternating cathodic pulses and anodic pulses, each cathodic pulse in the burst having a greater amplitude than the previous cathodic pulse.

A. FIELD OF THE DISCLOSURE

The present disclosure relates generally to neurostimulation systems, and more particularly to burst waveforms for neurostimulation systems.

B. BACKGROUND ART

Neurostimulation is an established neuromodulation therapy for the treatment of chronic pain and movement disorders. For example, neurostimulation has been shown to improve cardinal motor symptoms of Parkinson's Disease (PD), such as bradykinesia, rigidity, and tremors. Types of neurostimulation include deep brain stimulation (DBS), spinal cord stimulation (SCS), peripheral nerve stimulation, and Dorsal Root Ganglion (DRG) stimulation.

Burst waveforms have demonstrated success in SCS, and are actively being investigated in DRG stimulation and DBS therapies. A burst waveform typically includes a “burst” including a plurality of pulses each having an associated pulse width, with an intra-burst frequency defining the timing between the plurality of pulses within the burst. The burst repeats at an inter-burst frequency.

At least some known burst waveforms include cathodic-leading pulses, because cathodic-leading pulses may be more likely to activate axons near the electrode applying the simulation. However, it may be possible to achieve equal or improved success using anodic-leading pulses.

BRIEF SUMMARY OF THE DISCLOSURE

In one embodiment, the present disclosure is directed to an implantable neurostimulation system for generating burst waveforms. The neurostimulation system includes an implantable stimulation lead including a plurality of contacts, and an implantable pulse generator communicatively coupled to the stimulation lead and configured to generate a waveform including a burst that includes a leading anodic pulse followed by alternating cathodic pulses and anodic pulses, each cathodic pulse in the burst having a greater amplitude than the previous cathodic pulse.

In another embodiment, the present disclosure is directed to an implantable pulse generator for generating burst waveforms. The pulse generator includes a memory device, and a processor coupled to the memory device, the processor configured to generate a waveform including a burst that includes a leading anodic pulse followed by alternating cathodic pulses and anodic pulses, each cathodic pulse in the burst having a greater amplitude than the previous cathodic pulse.

In another embodiment, the present disclosure is directed to a method of applying neurostimulation. The method includes generating, using an implantable pulse generator, a waveform including a burst that includes a leading anodic pulse followed by alternating cathodic pulses and anodic pulses, each cathodic pulse in the burst having a greater amplitude than the previous cathodic pulse, and applying the waveform to a patient using an implantable stimulation lead coupled to the implantable pulse generator.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure provides systems and methods for generating burst waveforms. An implantable neurostimulation system includes an implantable stimulation lead including a plurality of contacts, and an implantable pulse generator communicatively coupled to the stimulation lead. The pulse generator is configured to generate a waveform including a burst that includes a leading anodic pulse followed by alternating cathodic pulses and anodic pulses, each cathodic pulse in the burst having a greater amplitude than the previous cathodic pulse.

Neurostimulation systems are devices that generate electrical pulses and deliver the pulses to nervous tissue of a patient to treat a variety of disorders. One category of neurostimulation systems is deep brain stimulation (DBS). In DBS, pulses of electrical current are delivered to target regions of a subject's brain, for example, for the treatment of movement and effective disorders such as PD and essential tremor. Another category of neurostimulation systems is spinal cord stimulation (SCS) which is often used to treat chronic pain such as Failed Back Surgery Syndrome (FBSS) and Complex Regional Pain Syndrome (CRPS).

Neurostimulation systems generally include a pulse generator and one or more leads. A stimulation lead includes a lead body of insulative material that encloses wire conductors. The distal end of the stimulation lead includes multiple electrodes, or contacts, that intimately impinge upon patient tissue and are electrically coupled to the wire conductors. The proximal end of the lead body includes multiple terminals (also electrically coupled to the wire conductors) that are adapted to receive electrical pulses. In DBS systems, the distal end of the stimulation lead is implanted within the brain tissue to deliver the electrical pulses. The stimulation leads are then tunneled to another location within the patient's body to be electrically connected with a pulse generator or, alternatively, to an “extension.” The pulse generator is typically implanted in the patient within a subcutaneous pocket created during the implantation procedure.

The pulse generator is typically implemented using a metallic housing (or can) that encloses circuitry for generating the electrical stimulation pulses, control circuitry, communication circuitry, a rechargeable or primary cell battery, etc. The pulse generating circuitry is coupled to one or more stimulation leads through electrical connections provided in a “header” of the pulse generator. Specifically, feedthrough wires typically exit the metallic housing and enter into a header structure of a moldable material. Within the header structure, the feedthrough wires are electrically coupled to annular electrical connectors. The header structure holds the annular connectors in a fixed arrangement that corresponds to the arrangement of terminals on the proximal end of a stimulation lead.

Referring now to the drawings, and in particular toFIG.1, a stimulation system is indicated generally at100. Stimulation system100generates electrical pulses for application to tissue of a patient, or subject, according to one embodiment. System100includes an implantable pulse generator (IPG)150that is adapted to generate electrical pulses for application to tissue of a patient. Alternatively, system100may include an external pulse generator (EPG) positioned outside the patient's body. IPG150typically includes a metallic housing (or can) that encloses a controller151, pulse generating circuitry152, a battery153, far-field and/or near field communication circuitry154, and other appropriate circuitry and components of the device. Controller151typically includes a microcontroller or other suitable processor for controlling the various other components of the device. Software code is typically stored in memory of IPG150for execution by the microcontroller or processor to control the various components of the device.

IPG150may comprise one or more attached extension components170or be connected to one or more separate extension components170. Alternatively, one or more stimulation leads110may be connected directly to IPG150. Within IPG150, electrical pulses are generated by pulse generating circuitry152and are provided to switching circuitry. The switching circuit connects to output wires, traces, lines, or the like (not shown) which are, in turn, electrically coupled to internal conductive wires (not shown) of a lead body172of extension component170. The conductive wires, in turn, are electrically coupled to electrical connectors (e.g., “Bal-Seal” connectors) within connector portion171of extension component170. The terminals of one or more stimulation leads110are inserted within connector portion171for electrical connection with respective connectors. Thereby, the pulses originating from IPG150and conducted through the conductors of lead body172are provided to stimulation lead110. The pulses are then conducted through the conductors of lead110and applied to tissue of a patient via electrodes111. Any suitable known or later developed design may be employed for connector portion171.

For implementation of the components within IPG150, a processor and associated charge control circuitry for an implantable pulse generator is described in U.S. Pat. No. 7,571,007, entitled “SYSTEMS AND METHODS FOR USE IN PULSE GENERATION,” which is incorporated herein by reference. Circuitry for recharging a rechargeable battery of an implantable pulse generator using inductive coupling and external charging circuits are described in U.S. Pat. No. 7,212,110, entitled “IMPLANTABLE DEVICE AND SYSTEM FOR WIRELESS COMMUNICATION,” which is incorporated herein by reference.

An example and discussion of “constant current” pulse generating circuitry is provided in U.S. Patent Publication No. 2006/0170486 entitled “PULSE GENERATOR HAVING AN EFFICIENT FRACTIONAL VOLTAGE CONVERTER AND METHOD OF USE,” which is incorporated herein by reference. One or multiple sets of such circuitry may be provided within IPG150. Different pulses on different electrodes may be generated using a single set of pulse generating circuitry using consecutively generated pulses according to a “multi-stimset program” as is known in the art. Alternatively, multiple sets of such circuitry may be employed to provide pulse patterns that include simultaneously generated and delivered stimulation pulses through various electrodes of one or more stimulation leads as is also known in the art. Various sets of parameters may define the pulse characteristics and pulse timing for the pulses applied to various electrodes as is known in the art. Although constant current pulse generating circuitry is contemplated for some embodiments, any other suitable type of pulse generating circuitry may be employed such as constant voltage pulse generating circuitry.

Stimulation lead(s)110may include a lead body of insulative material about a plurality of conductors within the material that extend from a proximal end of lead110to its distal end. The conductors electrically couple a plurality of electrodes111to a plurality of terminals (not shown) of lead110. The terminals are adapted to receive electrical pulses and the electrodes111are adapted to apply stimulation pulses to tissue of the patient. Also, sensing of physiological signals may occur through electrodes111, the conductors, and the terminals. Additionally or alternatively, various sensors (not shown) may be located near the distal end of stimulation lead110and electrically coupled to terminals through conductors within the lead body172. Stimulation lead110may include any suitable number and type of electrodes111, terminals, and internal conductors.

Controller device160may be implemented to recharge battery153of IPG150(although a separate recharging device could alternatively be employed). A “wand”165may be electrically connected to controller device through suitable electrical connectors (not shown). The electrical connectors are electrically connected to coil166(the “primary” coil) at the distal end of wand165through respective wires (not shown). Typically, coil166is connected to the wires through capacitors (not shown). Also, in some embodiments, wand165may comprise one or more temperature sensors for use during charging operations.

The patient then places the primary coil166against the patient's body immediately above the secondary coil (not shown), i.e., the coil of the implantable medical device. Preferably, the primary coil166and the secondary coil are aligned in a coaxial manner by the patient for efficiency of the coupling between the primary and secondary coils. Controller device160generates an AC-signal to drive current through coil166of wand165. Assuming that primary coil166and secondary coil are suitably positioned relative to each other, the secondary coil is disposed within the magnetic field generated by the current driven through primary coil166. Current is then induced by a magnetic field in the secondary coil. The current induced in the coil of the implantable pulse generator is rectified and regulated to recharge the battery of IPG150. The charging circuitry may also communicate status messages to controller device160during charging operations using pulse-loading or any other suitable technique. For example, controller device160may communicate the coupling status, charging status, charge completion status, etc.

External controller device160is also a device that permits the operations of IPG150to be controlled by a user after IPG150is implanted within a patient, although in alternative embodiments separate devices are employed for charging and programming. Also, multiple controller devices may be provided for different types of users (e.g., the patient or a clinician). Controller device160can be implemented by utilizing a suitable handheld processor-based system that possesses wireless communication capabilities. Software is typically stored in memory of controller device160to control the various operations of controller device160. Also, the wireless communication functionality of controller device160can be integrated within the handheld device package or provided as a separate attachable device. The interface functionality of controller device160is implemented using suitable software code for interacting with the user and using the wireless communication capabilities to conduct communications with IPG150.

Controller device160preferably provides one or more user interfaces to allow the user to operate IPG150according to one or more stimulation programs to treat the patient's disorder(s). Each stimulation program may include one or more sets of stimulation parameters including pulse amplitude, pulse width, pulse frequency or inter-pulse period, pulse repetition parameter (e.g., number of times for a given pulse to be repeated for respective stimset during execution of program), etc. In the methods and systems described herein, stimulation parameters may include, for example, a number of pulses in a burst (e.g., 3, 4, or 5 pulses per burst), an intra-burst frequency (e.g., 500 Hz), an inter-burst frequency (e.g., 40 Hz), and a delay between the pulses in a burst (e.g., less than 1 millisecond (ms)).

IPG150modifies its internal parameters in response to the control signals from controller device160to vary the stimulation characteristics of stimulation pulses transmitted through stimulation lead110to the tissue of the patient. Neurostimulation systems, stimsets, and multi-stimset programs are discussed in PCT Publication No. WO 2001/093953, entitled “NEUROMODULATION THERAPY SYSTEM,” and U.S. Pat. No. 7,228,179, entitled “METHOD AND APPARATUS FOR PROVIDING COMPLEX TISSUE STIMULATION PATTERNS,” which are incorporated herein by reference. Example commercially available neurostimulation systems include the EON MINI™ pulse generator and RAPID PROGRAMMER™ device from Abbott Laboratories.

The systems and methods described herein facilitate generating and delivering burst stimulation waveforms with anodic-leading pulses. These stimuli may be stored in a generator (e.g., IPG150or an external pulse generator), such that the generator ensures that each pulse is delivered in a specific order, after a specific interval following a previous pulse, with each pulse having a specific amplitude and duration. The waveforms described herein may provide improved stimulation in DBS, SCS, peripheral nerve stimulation, and DRG stimulation systems.

FIG.2is a block diagram of one embodiment of a computing device200that may be used to generate burst stimulation waveforms as described herein. Computing device200may be included, for example, within an IPG (e.g., IPG150) or an external pulse generator.

In this embodiment, computing device200includes at least one memory device210and a processor215that is coupled to memory device210for executing instructions. In some embodiments, executable instructions are stored in memory device210. In the illustrated embodiment, computing device200performs one or more operations described herein by programming processor215. For example, processor215may be programmed by encoding an operation as one or more executable instructions and by providing the executable instructions in memory device210.

Processor215may include one or more processing units (e.g., in a multi-core configuration). Further, processor215may be implemented using one or more heterogeneous processor systems in which a main processor is present with secondary processors on a single chip. In another illustrative example, processor215may be a symmetric multi-processor system containing multiple processors of the same type. Further, processor215may be implemented using any suitable programmable circuit including one or more systems and microcontrollers, microprocessors, reduced instruction set circuits (RISC), application specific integrated circuits (ASIC), programmable logic circuits, field programmable gate arrays (FPGA), and any other circuit capable of executing the functions described herein.

In the illustrated embodiment, memory device210is one or more devices that enable information such as executable instructions and/or other data to be stored and retrieved. Memory device210may include one or more computer readable media, such as, without limitation, dynamic random access memory (DRAM), read-only memory (ROM), electrically erasable programmable read-only memory (EEPROM), static random access memory (SRAM), a solid state disk, and/or a hard disk. Memory device210may be configured to store, without limitation, application source code, application object code, source code portions of interest, object code portions of interest, configuration data, execution events and/or any other type of data.

Computing device200, in the illustrated embodiment, includes a communication interface240coupled to processor215. Communication interface240communicates with one or more remote devices, such as a clinician or patient programmer. To communicate with remote devices, communication interface240may include, for example, a wired network adapter, a wireless network adapter, a radio-frequency (RF) adapter, and/or a mobile telecommunications adapter.

As noted above, burst waveforms have demonstrated success in SCS, and are actively being investigated in DRG stimulation and DBS therapies.

FIG.3is a graph300illustrating an example of a first known burst waveform302. In this example, waveform302includes a burst304of five pulses306that are passively charged cathodic pulses, with each pulse having a width of 1000 microseconds (μs). Cathodic pulses are generated by active circuitry of the implantable pulse generator as opposed to mere passive discharge of built-up charge as observed in some known spinal cord stimulation systems. An intra-burst frequency between pulses306in burst304is set to 500 Hz for SCS, and may be adjusted for DRG stimulation, peripheral nerve stimulation, and DBS applications. Further, in this example, burst304repeats at an inter-burst frequency of 40 Hz for SCS applications, which may be adjusted based on user preferences or for other applications.

FIG.4is a graph400illustrating an example of a second known burst waveform402. Waveform402includes a burst404of five pulses406that are cathodic pulses, with each pulse having a width of 1000 μs. Waveform402includes an intra-burst frequency of 300 Hz.

Waveform402differs from waveform302in multiple ways. For example, waveform302uses a relatively long pulse width combined with a relatively high intra-burst frequency to assure progressive charge accumulation within bursts304. Further, waveform302employs passive discharge, which also ensures charge accumulation within bursts304. In contrast, in waveform402, each pulse406is completely discharged with active symmetric anodic square pulses408. Overall, the charge accumulation within bursts304of waveform302guarantees a non-linear charge buildup, which may be advantageous over waveform402.

At least some known stimulation schemes (such as waveform302and waveform402) use cathodic-leading pulses because they are more likely than anodic-leading pulses to activate axons nearby the stimulation electrode. This may suggest that anodic-leading pulses are less effective, or require higher current amplitude to function properly. However, not all anodic-leading pulses are equivalent.

For example, if an anodic-leading pulse has a relatively small amplitude and a relatively long pulse width, the pulse will not activate any axons (instead, it will hyperpolarize some axons), such that a second, subsequent cathodic pulse activates axons. This may be referred to as “anodic break stimulation”. That is, the leading anodic pulse acts as a pre-conditioning pulse for the subsequent cathodic pulse. This stimulation scheme has been demonstrated to effectively activate neuronal elements near the electrode, comparable to results observed when using cathodic-leading pulses. For example, various waveforms and their effects on neuronal activation near the stimulation electrode are shown and described in “In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice” by Kevin C. Stieger et al. inJ Neurosci Res.2020; 98:2072-2095 (2020).

One advantage of using an anodic break stimulation scheme is that the scheme can activate both neurons near the electrode and distal neurons whose fibers of passage pass by the electrode. This may be particularly desirable for many neuromodulation applications. For example, in DBS for the subthalamic nucleus (STN), both the STN cells and fibers that pass by the STN can provide therapy for alleviating Parkinsonian symptoms. Therefore, if a stimulation scheme can activate both the neurons nearby and the passing fibers, it may be a desirable stimulation scheme.

As described in detail below, the systems and methods described herein provide a waveform with an anodic-leading pulse and progressively growing cathodic pulses. This waveform may be referred to as an “anodic-leading progressive burst”. The waveform mimics the bursting and charge buildup of waveform302, but also takes advantage of the anodic break stimulation scheme. This has the potential to activate more neuronal elements near the site of stimulation, while also providing the advantageous non-linear charge buildup of waveform302.

FIG.5is a graph500illustrating one embodiment of an anodic-leading progressive burst waveform502. Waveform502includes a leading anodic pulse504with a fixed pulse width and amplitude.

Subsequent to leading anodic pulse504, waveform502includes alternating cathodic pulses506and anodic pulses508. In this embodiment, anodic pulses508each have the same pulse width and amplitude as leading anodic pulse504. Further, cathodic pulses506each have the same pulse width, but the amplitude grows with each subsequent cathodic pulse506.

Leading anodic pulse504and anodic pulses508may have a pulse width in a range from 400 μs to 1000 μs, for example, and an amplitude in a range from 12.5% to 50% of the amplitude of the first cathodic pulse506. Further, cathodic pulses506may each have a pulse width in a range from 60 μs to 400 μs. For each burst510, waveform502may include, for example, two to eight total anodic pulses (including leading anodic pulse504and anodic pulses508), each anodic pulse followed by a corresponding cathodic pulse506. Alternatively, any suitable parameters may be used.

In the embodiment shown inFIG.5, the leading pulse of waveform502is anodic. However, those of skill in the art will appreciate that in a bipolar or multipolar simulation implementation, reference electrodes/return electrodes may exhibit waveform502in the opposite polarity (i.e., leading with a cathodic pulse).

Referring back to the embodiment ofFIG.5, to compensate for any additional charges accumulated due to the progressively growing cathodic pulses506, a passive discharge512follows the last cathodic pulse506in burst510. Further, in the embodiments described herein, the anodic pulse width is longer than the cathodic pulse width, and the charge output by leading anodic pulse504is less than or equal to the charge output by the first cathodic pulse506. That is, the product of the amplitude and pulse width for leading anodic pulse504is less than or equal to the product of the amplitude and pulse width for the first cathodic pulse506.

Similar to waveform302, depending on the particular application, the inter-burst frequency, the intra-burst frequency, and the pulse amplitudes of waveform502may be modified as appropriate.

In the example shown inFIG.5, waveform502has an anodic pulse width of 1000 μs, a cathodic pulse width of 300 μs, an anodic pulse amplitude of 0.25 milliamps (mA), a first cathodic pulse amplitude of 1.0 mA, a cathodic pulse growth rate of 20% (i.e., the amplitude of each cathodic pulse is 20% larger than the amplitude of the immediately preceding cathodic pulse), an inter-phase gap of 100 μs, and an inter-burst frequency of 500 Hz. Alternatively, any suitable parameters may be used.

Waveform502provides an alternative technique of implementing charge buildup in bursting stimulation patterns, while utilizing an anodic-break stimulation scheme to improve stimulation of neuronal elements near the stimulation electrode. Waveform502may provide improved results in SCS, DRG stimulation, peripheral nerve stimulation, and DBS applications.

The embodiments described herein provide systems and methods for generating burst waveforms. An implantable neurostimulation system includes an implantable stimulation lead including a plurality of contacts, and an implantable pulse generator communicatively coupled to the stimulation lead. The pulse generator is configured to generate a waveform including a burst that includes a leading anodic pulse followed by alternating cathodic pulses and anodic pulses, each cathodic pulse in the burst having a greater amplitude than the previous cathodic pulse.