Systems and methods of combined tonic DBS and random DBS

The present disclosure provides systems and methods for combining tonic deep brain stimulation (DBS) and random DBS. A system includes a stimulation lead including a plurality of contacts, and an implantable pulse generator (IPG) communicatively coupled to the stimulation lead and configured to cause tonic stimulation to be delivered using one contact of the plurality of contacts, and cause random stimulation to be delivered using a subset of the remaining contacts of the plurality of contacts.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to deep brain stimulation (DBS) systems, and more particularly to combining tonic and random stimulation.

BACKGROUND ART

Deep brain stimulation (DBS) is an established neuromodulation therapy for the treatment of movement disorders, and has been shown to improve cardinal motor symptoms of Parkinson's Disease (PD), such as bradykinesia, rigidity, and tremors. These improvements generally occur within a few minutes of initiation of stimulation, and disappear within a similar timeframe after stimulation is discontinued. DBS may include using tonic stimulation to deliver high-frequency isochronal electrical pulses (e.g., at a pulse frequency of 130-180 Hertz (Hz) with a pulse width of 20-200 microseconds) through a single contact electrode implanted in the Basal ganglia thalamo-cortical “motor circuit” of the brain.

In brain activity, abnormal synchronization of neuronal activity is an indicator of various movement disorders, such as PD. Studies have shown that PD is associated with increase oscillations in the beta band, which has been associated with bradykinesia and rigidity. Further, research has suggested that such abnormal synchronization may be disrupted by delivering short sequences of stimulation pulses through different electrodes activated at different times in random order. This may provide sustained amelioration of rigidity and bradykinesia, especially after multiple stimulation sessions. However such random stimulation may not be as effective as tonic stimulation, and may not ameliorate tremors, which may be severely disabling for a patient.

BRIEF SUMMARY OF THE DISCLOSURE

In one embodiment, the present disclosure is directed to a deep brain stimulation (DBS) system for delivering a combination of tonic stimulation and random stimulation. The DBS system includes a stimulation lead including a plurality of contacts, and an implantable pulse generator (IPG) communicatively coupled to the stimulation lead and configured to cause tonic stimulation to be delivered using one contact of the plurality of contacts, and cause random stimulation to be delivered using a subset of the remaining contacts of the plurality of contacts.

In another embodiment, the present disclosure is directed to an implantable pulse generator (IPG) for use with a deep brain stimulation (DBS) system for delivering a combination of tonic stimulation and random stimulation. The IPG includes a memory device, and a controller communicatively coupled to the memory device, the controller configured to cause stimulation to be delivered to a patient using a plurality of contacts of a stimulation lead coupled to the IPG by causing tonic stimulation to be delivered using one contact of the plurality of contacts, and causing random stimulation to be delivered using a subset of the remaining contacts of the plurality of contacts.

In another embodiment, the present disclosure is directed to a method of applying a combination of tonic stimulation and random stimulation using a stimulation lead including a plurality of contacts. The method includes delivering tonic stimulation using one contact of the plurality of contacts, and delivering random stimulation using a subset of the remaining contacts of the plurality of contacts.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure provides systems and methods for combining tonic and random stimulation in a deep brain stimulation (DBS) system. A stimulation lead includes a plurality of contacts. An implantable pulse generator (IPG) communicatively coupled to the stimulation lead causes tonic stimulation to be delivered using one contact of the plurality of contacts, and cause random stimulation to be delivered using a subset of the remaining contacts of the plurality of contacts. The applied stimulation yields the benefits of both random and tonic stimulation.

Neurostimulation systems are devices that generate electrical pulses and deliver the pulses to nerve tissue of a patient to treat a variety of disorders. One category of neurostimulation systems is deep brain stimulation (DBS). In DBS, electrical pulses are delivered to parts of a subject's brain, for example, for the treatment of movement and effective disorders such as PD and essential tremor.

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 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 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 within a subcutaneous pocket created during the implantation procedure.

The pulse generator is typically implemented using a metallic housing that encloses circuitry for generating the electrical pulses, control circuitry, communication circuitry, a rechargeable 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 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. IPG150typically includes a metallic housing 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 field generated by the current driven through primary coil166. Current is then induced in secondary coil. The current induced in the coil of the implantable pulse generator is rectified and regulated to recharge 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 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, 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., 130 Hz), an inter-burst frequency (e.g., 3-20 Hz), and a delay between a first and second 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 St. Jude Medical, Inc. (Plano, Tex.).

The systems and methods described herein use both tonic DBS and random DBS to facilitate treating symptoms of PD and other movement and effective disorders. Further, the embodiments described herein exploit the cumulative effects of multiple random DBS stimulation sessions, ultimately reducing overall stimulation needs of patients. Specifically, tonic DBS is delivered using one or more contacts (i.e., electrodes) and parameters identified during therapy optimization, and a subset of the remaining available contacts are used to deliver a randomized stimulation pattern. A subset may include all of the remaining available contacts or less than all of the remaining available contacts. The tonic and randomized stimulation patterns are interleaved to prevent the therapeutic effect of tonic DBS from being compromised by discontinuities associated with random DBS. Accordingly, tonic DBS and random DBS are combined to achieve the advantages of both.

FIG. 2is a schematic diagram illustrating application of tonic DBS using a stimulation lead202. Stimulation lead202may be used, for example, with neurostimulation system100(shown inFIG. 1) to apply the tonic DBS. In this embodiment, stimulation lead202includes a distal segment204that includes a first contact206, a second contact208, a third contact210, and a fourth contact212. Alternatively, distal segment204may include any suitable number of contacts, or electrodes. Contacts206,208,210, and212may be, for example, ring electrodes or segmented electrodes. Stimulation lead202may be positioned, for example, within a subthalamic nucleus (STN) of the patient.

In this embodiment, to apply tonic DBS, third contact210delivers stimulation pulses214at a constant frequency (e.g., 130 Hertz (Hz)). Although in this embodiment, third contact210delivers stimulation, alternatively, any of contacts206,208,210, and212may be used to deliver stimulation. The contact used to deliver tonic stimulation may be selected, for example, during a therapy optimization session.

FIG. 3is a schematic diagram illustrating application of random DBS using stimulation lead202. Stimulation lead202may be used, for example, with neurostimulation system100(shown inFIG. 1) to apply the random DBS.

As shown inFIG. 3, to apply random DBS, first contact206functions as an anode, and second, third and fourth contacts208,210, and212deliver bursts220of stimulation in a random or pseudorandom pattern. Alternatively, another of contacts206,208,210, and212may function as the anode. In this embodiment, each burst220of stimulation includes multiple pulses214(e.g., five pulses214) delivered at a constant intraburst frequency (e.g., 130 Hz). Alternatively, each burst220may include any number and arrangement of pulses214that enables stimulation lead202to function as described herein. That is, any suitable temporal arrangement of pulses within one burst220and/or any suitable spatial location of bursts220(i.e., the order in which contacts deliver subsequent bursts220) may be utilized.

In this embodiment, random stimulation is delivered in cycles230. A cycle230is the time duration during which a burst220is delivered from each of the available contacts208,210, and212. A sub-cycle232is the time duration during which one of available contacts208,210, and212delivers a burst220. In this embodiment, the random DBS includes a sequence of three ON cycles230followed by two OFF cycles230(i.e., cycles where no stimulation is delivered). Alternatively, the random DBS may include any suitable arrangement of ON and OFF cycles230.

FIG. 4is a schematic diagram illustrating application of a combination of tonic DBS and random DBS using stimulation lead202. Stimulation lead202may be used, for example, with neurostimulation system100(shown inFIG. 1) to apply the combination of tonic and random DBS.

In the embodiment shown inFIG. 4, delay periods between subsequent bursts220of random stimulation are used to deliver tonic stimulation. Combining random stimulation and tonic simulation facilitates controlling symptoms and achieving sustained desynchronization of abnormal oscillations simultaneously. In this embodiment, first, second, and fourth contacts206,208, and212deliver random stimulation, and third contact210delivers tonic stimulation. Alternatively, any configuration of contacts206,208,210, and212may be used to deliver the combination of random and tonic stimulation.

In one embodiment, to implement the combination of tonic DBS and random DBS shown inFIG. 4, IPG150generates, for each ON cycle230, a random permutation of first, second, and fourth contacts206,208, and212(i.e., the contacts not selected for tonic stimulation). IPG150may use an internal timer to measure the time passed with each sub-cycle232. Alternatively, IPG150may use the internal timer to measure a number of pulses214delivered as calculated from the intra-burst frequency, number of pulses214in a burst, and tonic DBS frequency. IPG150also uses a counter to keep track of the number of cycles230delivered.

At the beginning of an ON cycle230, the internal timer is started and IPG150causes a burst220of stimulation including a predetermined number of pulses214(e.g., five pulses) to be delivered at the same frequency and pulse width identified for tonic DBS, but using the first contact in the random permutation of first, second, and fourth contacts206,208, and212. For example, as shown inFIG. 4, IPG150causes second contact208to deliver a five-pulse burst220of stimulation.

After second contact208delivers burst220, IPG150causes the contact selected for tonic DBS (i.e., third contact210) to deliver tonic simulation until the internal timer determines the first sub-cycle232is complete. At that point, the internal timer is reset, and IPG150causes a burst220of stimulation to be delivered using the second contact in the random permutation of first, second, and fourth contacts206,208, and212. For example, as shown inFIG. 4, IPG150causes fourth contact212to deliver a five-pulse burst220of stimulation.

After fourth contact212delivers burst220, IPG150causes third contact210to deliver tonic simulation until the internal timer determines the second sub-cycle232is complete. At that point, the internal timer is reset, and IPG150causes a burst220of stimulation to be delivered using the third contact in the random permutation of first, second, and fourth contacts206,208, and212. For example, as shown inFIG. 4, IPG150causes first contact206to deliver a five-pulse burst220of stimulation. After first contact208delivers burst220, IPG150causes the contact selected for tonic DBS (i.e., third contact210) to deliver tonic simulation until the internal timer determines the third sub-cycle232is complete, representing the end of the ON cycle230.

At this point, the counter of IPG150is updated to reflect that one cycle230is complete, the internal timer is reset, and the next ON cycle230begins with a new permutation of first, second, and fourth contacts206,208, and212(i.e., the contacts not selected for tonic stimulation). This process repeats until a predetermined number of ON cycles230have been performed. Subsequently, IPG150causes the contact selected for tonic DBS (i.e., third contact210) to deliver tonic simulation for a predetermined number of OFF cycles230. Once the predetermined number of OFF cycles230are performed, the counter is reset, and the process repeats from the beginning (i.e., by starting an ON cycle230).

In another embodiment, to implement a combination of tonic DBS and random DBS, IPG150includes an internal memory storing a script. The script may be, for example, computer-readable instructions. The script includes timing of each burst220of random stimulation and the corresponding channel (e.g., selected from channels for first, second, and fourth contacts206,208, and212) used to deliver burst220. When stimulation is initiated, an internal timer in IPG150is started, and the contact selected for delivering tonic stimulation (e.g., third contact210) begins delivering tonic stimulation.

Tonic stimulation is delivered until the timing of a burst220specified in the script is reached, at which point the tonic DBS is temporarily stopped, and IPG150causes the burst220to be delivered using the channel indicated in the script (e.g., corresponding to one of first, second, and fourth contacts206,208, and212).

As soon as the burst220is delivered, tonic stimulation resumes until the internal timer reaches the next timing specified in the script. Once the last timing in the script is reached, the internal timer is reset and the sequence repeats.

FIG. 5is a schematic diagram illustrating application of a combination of tonic DBS and random DBS using stimulation lead202in accordance with an alternative embodiment. In the embodiment shown inFIG. 5, IPG150is capable of using multiple current sources. Accordingly, pulses214may be delivered simultaneously using multiple contacts.

In this embodiment, tonic stimulation is delivered continuously using the contact selected for tonic stimulation (e.g., third contract210), and bursts220of random stimulation are delivered using the remaining contacts (e.g., first, second, and fourth contacts206,208, and212) without interrupting the tonic stimulation. IPG150is programmed such that the contact selected for tonic stimulation delivers continuous tonic stimulation in accordance with predefined tonic DBS parameters (e.g., pulse width, amplitude, etc.). Further, IPG150is programmed such that the remaining contacts deliver random stimulation. In some embodiments, bursts220of random stimulation have different intensities, inter-burst frequencies, pulse widths, and/or number of pulses in a burst, depending on which contact is used to deliver the stimulation.

At the beginning of each ON cycle230, the contact selected for tonic stimulation begins delivering continuous tonic stimulation. Further, at the beginning of each ON cycle230, the order in which the remaining contacts apply bursts220of random stimulation is randomized, and the random DBS is delivered accordingly.

The embodiments described herein provide systems and methods for combining tonic and random stimulation in a deep brain stimulation (DBS) system. A stimulation lead includes a plurality of contacts. An implantable pulse generator (IPG) communicatively coupled to the stimulation lead causes tonic stimulation to be delivered using one contact of the plurality of contacts, and cause random stimulation to be delivered using a subset of the remaining contacts of the plurality of contacts. A subset may include all of the remaining contacts or less than all of the remaining contacts.

The systems and methods described herein facilitate improved symptom control while delivering random DBS. Further, benefits of tonic and random stimulation patterns are both achieved, facilitating sustained improvement in symptoms during periods where no stimulation is applied. The systems and methods described herein also facilitate saving battery power and increasing a therapeutic window, as low intensity stimulation is used. Using random stimulation also facilitates preventing patient adaptation to stimulation.