WO2017139606A1

WO2017139606A1 - System and method for controlling the propagation direction of electrical stimulation along a nerve fiber

Info

Publication number: WO2017139606A1
Application number: PCT/US2017/017411
Authority: WO
Inventors: Peng CONG; Stephen O'driscoll; Anil Kumar Ram RAKHYANI
Original assignee: Verily Life Sciences, LLC
Priority date: 2016-02-12
Filing date: 2017-02-10
Publication date: 2017-08-17

Abstract

A system and method for neuromodulation is provided. The system includes two or more microparticles implantable in a series along the length of a nerve fiber, and a central controller that is operatively coupled to the two or more microparticles. The central controller is configured to instruct at least one of the microparticles to deliver an electrical impulse to the nerve fiber to stimulate it. Each of the microparticles includes either a stimulation electrode configured to deliver the electrical impulse to the nerve fiber, or a sensor configured to monitor neural activity. In some implementations, at least one of the microparticles includes a stimulation electrode and a sensor. The central controller includes a power system configured to wirelessly deliver power to the microparticles, and a processing system configured to provide stimulation parameters to the microparticles that stimulate the nerve fiber. In some implementations, the processing system is configured to process any sensed neural activity and update the stimulation parameters accordingly.

Description

SYSTEM AND METHOD FOR CONTROLLING THE PROPAGATION DIRECTION OF ELECTRICAL STIMULATION ALONG A NERVE FIBER

BACKGROUND

Related Applications

[0001 ] This application claims priority to U.S. Provisional Application No. 62/294,612, filed February 12, 2016, which is incorporated herein by reference in the entirety.

Technical Field

[0002] The present disclosure relates generally to neuromodulation, and more particularly, to systems and methods for controlling the direction of propagation of electrical stimulation of neural tissue.

Background Description

[0003] Neuromodulation relates to the modulation of nerve activity by delivering electrical or pharmaceutical agents directly to a target neural tissue.

Neuromodulation holds promise for treating or improving a number of physiological conditions, for example, depression, urinary incontinence, heart failure conditions, chronic pain. Parkinson's disease, etc. In particular, electrical stimulation of different types of neural tissue can provide treatment for a number of different physiological disorders, for example, deep brain stimulation (DBS) to treat Parkinson s disease, sacral nerve stimulation to treat pelvic disorders and incontinence, spinal cord stimulation to treat ischemic disorders, and vagus nerve stimulation to treat epilepsy, chronic depression, inflammation resulting from arthritis or Crohn^'s disease, etc.

[0004] One challenge of neuromodulation is the side effects caused by unwanted excitation of neural tissue surrounding the target area. For example, when the vagus nerve is electrically stimulated, the stimulations reach not only the brain targets, but also organs downstream, which can lead to many medical complications.

[0005] Thus, there remains a need to control the propagation direction of electrical stimulation applied to neural tissue. Improved control of the propagation direction of electrical stimulation will not only improve the therapeutic efficacy of neuromodulation, but also minimize side effects. SUMMARY

[0006] The present disclosure is directed to systems and methods for controlling the propagation direction of electrical stimulation applied to neural tissue for neuromodulation.

[0007] One aspect of the present disclosure is a system for neuromodulation. The system may comprise two or more microparticles implantable in a series along the length of a target nerve fiber, wherein at least one of the two or more

microparticles may comprise a stimulation electrode configured to transmit an electrical impulse to the target nerve fiber. The system may further comprise a central controller operatively coupled to the two or more microparticles. The central controller may comprise a wireless communication system configured to

communicate with each of the two or more microparticles, and a processor configured to control the operation of the two or more microparticles. The processor may be configured to provide a stimulation parameter to the stimulation electrode of the at least one of the two or more microparticles.

[0008] Another aspect of the present disclosure is a method for

neuromodulation. The method may comprise operatively coupling a central controller to a neuromodulation device comprising two or more microparticles provided in a series along the length of a target nerve fiber, wherein at least one of the two or more microparticles may comprise a stimulation electrode that transmits an electrical impulse to the target nerve fiber. The method may also comprise delivering a stimulation parameter from the central controller to the at least one of the two or more microparticles that comprises a stimulation electrode. The method may further comprise applying an electrical impulse through the stimulation electrode to the target nerve fiber based on the stimulation parameter. In certain embodiments, the neuromodulation may have no therapeutic effect. For instance, the neuromodulation may be for the sole purpose of detecting the response based on the stimulation parameter, as discussed further below.

[0009] Other embodiments of this disclosure are contained in the

accompanying drawings, description, and claims. Thus, this summary is exemplary only, and is not to be considered restrictive.

BRIEF DESCRIPTION OF. DRAWINGS [0010] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate the disclosed embodiments and together with the description, serve to explain the principles of the various aspects of the disclosed embodiments. In the drawings:

[001 1 ] Fig. 1 is a schematic of a neuromodulation system, according to an exemplary embodiment;

[00 2] Fig. 2 is a schematic illustration of a central controller, according to an exemplary embodiment; and

[0013] Fig. 3 is a schematic illustration of a microparticle, according to an exemplary embodiment.

[0014] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosed embodiments, as claimed.

DETAILED -Pts CSRlPTlQN

[0015] Reference will now be made to certain embodiments consistent with the present disclosure, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like parts.

[0016] A microparticle as described herein may be defined as a

submillimeter implantable device, submillimeter device, or implantable device having an average diameter below 500 microns.

[0017] Neuromodulation as described herein may be defined as electrical stimulation of nerve fibers or nerve tissue for triggering, amplifying, inhibiting or blocking propagation of action potentials along nerve fibers. The electrical stimulation may be carried out by transmitting of electrical impulses along the nerve fiber, as described herein.

[0018] The present disclosure describes systems and methods for electrical stimulation of a target neural tissue. The system may comprise a central controller and two or more microparticles that communicate with the central controller. The two or more microparticles may be implanted on a target nerve fiber to provide electrical stimulation. The number of implanted microparticles may vary based on the application and/or the length of the target nerve fiber. For example, the number of microparticles may range from two to about 100 or more. Examples of target nerve fibers include, but are not limited to, the cranial nerves (e.g. , the vagus nerve), spinal nerves (i.e., the sciatic nerve), etc. The central controller may be positioned remote from the microparticles. Two or more electrodes may be integrated on the

microparticles to provide electrical impulses to the target nerve fiber.

[0019] In exemplary embodiments, the microparticles may also be used as sensors to monitor neural activity. In some embodiments, the microparticles may have integrated electrodes for providing electrical stimulation and on-chip sensors for monitoring applied stimulation and neural response. In some embodiments, the microparticles may only have sensing capabilities. In such embodiments, traditional neurological electrodes may be used to apply stimulation and the microparticles may be used for monitoring neural activity.

[0020] Each of the microparticles may be a small, standalone platform equipped with wireless power and communication capability. In exemplary embodiments, a microparticle may have submi!limeter dimension. In one such embodiment, a microparticle may be approximately 500 pm in diameter. In some embodiments, for example, the average diameter of a microparticle may be about 500 pm to about 400 μιη, about 400 pm to about 300 pm, about 300 pm to about 200 pm, or about 200 pm or less.

[0021 ] Due to the submillimeter dimension of the microparticles, one or more microparticles may be implanted individually on the target nerve fiber with minima! tissue damage or trauma to the target area. The small size of the microparticles may facilitate focusing of the electrical stimulation on the target tissue, which may reduce unwanted stimulation of surrounding tissue area, and thus may minimize side effects. The submillimeter size of the microparticles may also allow placement of the microparticles directly on the nerve fiber or in very close proximity to it, which in turn may allow use of low stimulation voltages. This is important because use of large stimulation voltages may atrophy the neural structures over time. In exemplary embodiments, the stimulation voltages applied by the microparticles may be lower than the voltages applied by any traditional microelectrode or cuff electrode.

[0022] Further, the small size of the microparticles may allow placement in small structures, for example, in branched dendrites or axon structures. Traditional neurological electrodes, for example, planar, microwire. or cuff electrodes, are larger in size compared to the microparticles of the present disclosure, and therefore, these traditional electrodes are generally placed on larger nerve bundles or nerve fibers. However, stimulation of large fibers could implicate neural structures not intended for a particular therapy and result in unwanted side effects. For example, stimulation of the large fibers of the vagus nerve for epilepsy treatment is known to cause heart arrhythmias. Neural activity sensed from a large fiber is also more difficult to interpret because of the large amount of data collected.

[0023] To control propagation direction of an electrical stimulation, two or more microparticles may be implanted in a series along the length of a target nerve fiber. The distance between the microparticles is determined by the length of the nerve fiber, the intended neuromodulation treatment, the stimulation parameters, etc. In some embodiments, two or more microparticles are equally spaced apart along the length of the nerve fiber. In some embodiments, the two or more microparticles are non-uniformly spaced along the nerve fiber.

[0024] Electrical impulses may be applied simultaneously or in sequence by the two or more microparticles to deliver the necessary stimulation to the nerve fiber. Stimulation by two or more microparticles may guide the electrical impulses along the nerve fiber, and thereby allow better control of the propagation direction of the stimulation. The electrical stimulation may be applied according to a preprogrammed pattern/sequence that is controlled by the central controller. Different stimulation parameters (e.g. , voltages, current, frequency, etc.) may be used for different therapies. In exemplary embodiments, each microparticle has a unique identifier, so that it can be individually activated or stimulated by the central controller. A series of such microparticles may allow for delivery of complex stimulation protocols at multiple locations along the nerve fiber. The unique identifier on each microparticle may also be used to sense response from a select location on the target nerve fiber.

[0025] In exemplary embodiments, the central controller may be a portable device. In one such embodiment, the central controller may be a handheld device. In another embodiment, the controller may be a wearable device. In yet another embodiment, the controller may be a clinical-scale device that may be positioned near the bedside of a patient receiving a neuromodulation treatment.

[0026] In exemplary embodiments, the central controller may be used to provide signals for wirelessly powering the microparticles. The microparticles may have a supercapacitor, a battery, or some other type of charging system that may be charged wirelessly by the central controller. In some embodiments, optical powering using an array of photovoltaic ceils may be used to power the embedded electronics of an implanted microparticle or recharge its battery.

[0027] In exemplary embodiments, the centra! controller may have communication capabilities for receiving signals (e.g. , sensed neural activity) from the implanted microparticles, and for providing instructions (e.g., stimulation protocols) to the microparticles. In some embodiments, the controller is wirelessly connected to the microparticles. In other embodiments, the central controller is connected through long wires/leads to the implanted microparticles. The stimulation protocols may be transmitted by the controller to the microparticles either wireless or through wired connections. The sensed responses from the microparticles may also be transmitted from the microparticles to the controller either wirelessly or through wired connections.

[0028] In exemplary embodiments, the central controller may have a microprocessor to process and/or analyze the sensed responses delivered by the microparticles. In some embodiment, the sensed responses are transferred wirelessly or through a wired connection from the central controller to a remote processing device for further processing and/or analysis. In exemplary embodiments, the controller may be able to adjust the stimulation parameters based on the sensed responses. In such embodiments, the microparticles and the controller may function in a feedback loop to monitor stimulation responses in real-time and to adaptively adjust stimulation parameters.

[0029] In exemplary embodiments, the central controller may have a memory device to store the sensed responses. The memory device may also be used to store the stimulation protocols. In some embodiments, the sensed responses are transferred wirelessly or through a wired connection from the central controller to a remote storage device.

[0030] In exemplary embodiments, the microparticles may have on-chip electronics to pre-process the acquired neural activity signals prior to transmitting the signals to the central controller. In such embodiments, the microparticles may include amplifiers, analog-to-digital converters, multiplexers, and other electronic circuitry to pre-process the acquired neural signals.

[0031] Fig. 1 shows a schematic diagram of a neuromodu!ation system 100, according to an exemplary embodiment of the present disclosure. Neuromodulation system 100 may include a controller, which will be referred to herein as a central controller 102. Neuromodulation system 100 may also include two or more microparticles 104 that are operatively coupled to central controller 102.

Neuromodulation system 100 may communicate with the microparticles 104 via data links 106. In some embodiments, data links 106 comprise wireless connections. In other embodiments, data links 106 comprise wires or leads that connect central controller 102 and microparticles 104. Central controller 102 and microparticles 104 send and receive informational signals back and forth, which may include, for example, data, instructions, protocols, configurations, and the like. When the term information or informational signal(s) is used herein, this may refer to one or more of the categories of information listed above. In exemplary embodiments, the informational signals may comprise stimulation parameters, e.g., voltage, current, time, etc. , and sensed neural activity.

[0032] In some embodiments, neuromodulation system 100 may include a single central controller 102 and a plurality of microparticles 104. In some

embodiments, neuromodulation system 100 may include multiple central controllers 102 and multiple microparticles 104. In such embodiments, each central controller 102 may be connected to two or more microparticles 104. The number of central controllers 102 and the number of microparticles 104 connected to each central controller 02 may be determined and/or adjusted based on a number of variables, including for example, the target neural tissue that is to be stimulated, the function of the neural tissue that is to be stimulated, the distance between microparticles 104, the amount of stimulation voltage that is to be applied, and the size and power of central controller 102.

[0033] Fig. 2 shows a schematic of central controller 102, according to an exemplary embodiment. Central controller 102 may include a processing system 108, a communication system 1 10, and a power system 1 12. !n exemplary embodiments, processing system 108 may control the overall operation of central controller 102 and coordinate the operation of the microparticles 104.

Communication system 1 10 may send informational signals to microparticles 104 and receive informational signals from microparticles 104 via datalinks 106. Power system 1 12 may power the central controller 102 and power the microparticles 104 using wireless energy transmission. In exemplary embodiments, power system 1 12 may provide power to microparticles 104 through electromagnetic, acoustic, or optical waves. [0034] In some embodiments, central controller 102 may include additional components not shown, including for example, data ports, disk drives, a user interface, speaker(s), computer network interface(s), and indicator light(s), or display. In some embodiments, central controller 102 may be an intelligent signal processor which may have secured datalinks 106 with other devices over a wireless network.

[0035] Processing system 108 of central controller 102 may include one or more processors, including for example, a central processing unit (CPU) 1 14.

Processing system 108 may include additional components, for example, a memory device 1 16 for storing information, e.g. , program instructions, stimulation protocols, configurations, sensed response data, etc., to enable the control and overall operation of central controller 102 and the microparticles 104.

[0036] Communication system 1 10 may utilize a wired or wireless connection to communicate with microparticles 104. In exemplary embodiments, communication system 1 10 may utilize a variety of wireless data transmission methods for communicating back and forth with the microparticles 104. For example, in some embodiments, communication system 1 10 may utilize electromagnetics-based data transmission (e.g., radio data transmission, electromagnetic induction transmission, Bluetooth, near field communication (NFC), etc.), acoustic data transmission, optical data transmission (e.g. , infrared data transmission), or any other suitable

transmission methods. According to an exemplary embodiment, as shown in Fig. 2, communication system 1 10 of central controller 102 may utilize radio data

transmission and include among other things a data encoder 120, a data decoder 122, a transmitter and a receiver or a transceiver 124, and an antenna 125. In some embodiments, communication system 10 may include two antennas, for example, one receiver antenna and one transmitter antenna.

[0037] In exemplary embodiments, each microparticle 104 may be individually addressed by central controller 102 via communication system 1 1 1 , which may enable central controller 102 to independently communicate with each microparticle 104. Each microparticle 104 may be associated with a unique identifier to allow it to be accessed discretely by central controller 102. In some embodiments, each microparticle 104 may include a unique identification number programmed in non-volatile memory. In another embodiment, an identifier may be hard coded during fabrication as a unique part of the system. To address individual microparticle 104, communication system 1 10 of central controller 102 may modulated with a microparticle address and only the microparticle with matching address (after decoding) may respond to the activation.

[0038] Power system 1 12 may use wireless energy transmission to power microparticles 104. in some embodiments, power system 1 12 may utilize, for example, inductive coupling, resonant inductive coupling, radio frequency, or the like to wirelessly transmit power. According to an exemplary embodiment, as shown in Fig. 2, power system 1 12 may utilize resonant inductive coupling and may include a power source 126, an oscillator circuit 128, and a transmitting coil 130. Power source 126 may provide any suitable source of power, such as an AC source or a DC source. In some embodiments, the power source 126 may be, for example, a battery, a capacitor, a photovoltaic array, or the like. Oscillator circuit 128 may be powered by the power source 126 and may drive the transmitting coil 130. In some embodiments, the signal from the oscillator circuit 128 may be amplified by a power amplifier 132 which may be coupled through, for example, a capacitor, to the transmitting coil 130. The transmitting coil 130 may be mutually coupled with the receiving coils on the microparticles 104, which will be discussed in more detail below. The coupled coils may transfer electromagnetic energy from the transmitting coil 130 through the body tissue to the receiving coils of the implanted microparticles 104 by way of mutual induction.

[0039] Fig. 3 shows a schematic diagram of an individual microparticle 104, according to an exemplary embodiment. Microparticle 104 may include a processor 208, a communication system 210, a power system 212, and a stimulation/sensing system 214. Processor 208 may control the overall operation of the microparticle 104. Communication system 210 may communicate with central controller 102 by sending and receiving informational signals. The power system 212 may power the processing system 208, the communication system 210, and stimulation/sensing system 214 of microparticle 104.

[0040] The stimulation/sensing system 214 of microparticle 104 may be used to stimulate neural tissue and/or acquire neural activity signals. In one embodiment, stimulation/sensing system 214 may include an electrode 226 to deliver an electrical impulse to the neurai tissue on which microparticle 104 may be implanted. In another embodiment, stimulation/sensing system 214 may include a sensor 227 to sense neural activity from the neural tissue on which microparticle 104 may be implanted. In yet another embodiment, stimulation/sensing system 214 may include an electrode 226 to stimulate neural tissue and a sensor 227 to sense neural activity, as depicted in Fig. 3.

[0041] In one exemplary embodiment, the stimulation/sensing system 214 may be controlled via the processor 208 based on informational signals received from the central controller 102. For example, processor 208 may receive

informational signals containing instructions from central controller 102, and based on the instructions, processor 108 may operate stimulation/sensing system 214 (e.g., stimulate neural tissue or acquire neural activity signals).

[0042] In one exemplary embodiment, neural activity signals acquired by sensor 227 may be processed by processor 208 before it is transmitted to central controller 102. In another embodiment, raw neural activity signals may be

transmitted to central controller 102. In yet another embodiment, microparticle 104 may include additional electronic circuitry, e.g. , analog-to-digital converter, preamplifier, etc., to pre-process the sensed neural activity before it is processed by processor 208 or transmitted to central controller 102 for processing.

[0043] In exemplary embodiments, communication system 210 may utilize the same wireless data transmission method utilized by communication system 1 10 of the central controller 102. For example, communication system 210 may include one or more antennas, a transceiver, an encoder and a decoder. In some

embodiments, ail coding and decoding of the informational signals may be done by the central controller 102.

[0044] Power system 212 for microparticle 104, like power system 1 12 of central controller 102, may use wireless energy transmission, including, for example, inductive coupling, resonant inductive coupling, radio frequency (RF) link, or the like to wirelessly transmit energy. For example, power system 212 may utilize a wireless charging system to charge an on-chip battery using power received from central controller 102.

[0045] Electrode 226 of stimulation/sensing system 214 may stimulate a nerve fiber or portion of a nerve fiber positioned proximate to microparticle 104 by transmitting one or more electrical impulses. The electrical impulses may vary, for example, in power (e.g., voltage and/or current), amplitude, speed, duration, waveform, and frequency. The power of the electrical impulses may vary, for example, by varying either the voltage and/or current at which the impulses are transmitted. In exemplary embodiments, the stimulation voltage may be as low as 10-30 mV.

[0046] In exemplary embodiments, microparticles 04 may be implanted at or proximate to specific nerves or portions of a nerve that is to be stimulated. As discussed previously, the submillimeter size of microparticles 104 may enable more precise and refined placement of microparticles 104 at or near target neural tissue when compared to traditional electrodes that are an order of magnitude larger. The ability to place microparticles 104 more precisely may enable improved stimulation and sensing of neural tissue, and may avoid inadvertently stimulating non-target tissue.

[0047] In exemplary embodiments, two or more microparticles 104 may be implanted along the length of a target nerve fiber (e.g., the vagal nerve, the sciatic nerve, etc.) to control the direction of propagation of stimulation. For example, instead of providing stimulation impulse to one traditional neurological electrode and allowing the stimulation to propagate down the nerve fiber, two or more

microparticles 104 may be implanted along the length of the fiber. In exemplary embodiments, the two or more microparticles 104 may be implanted along the direction in which a stimulation impulse is intended to propagate.

[0048] In exemplary embodiments, the two or more microparticles 104 may be operated by central controller 102 in accordance with a stimulation or sensing protocol. In one embodiment, the two or more microparticles 104 may be activated serially by central controller 102 at specific time intervals in accordance with a predetermined stimulation or sensing protocol. In another embodiment, the two or more microparticles 104 may be activated simultaneously by central controller 02. In yet another embodiment, the two or more microparticles 104 may be activated in a pattern. For example, in some embodiments, different stimulation impulses (e.g. , impulses of different voltage, frequency, current, etc.) may be applied at different microparticle 104. In another embodiment, neural activity may be collected from different microparticles 104 at different times.

[0049] In exemplary embodiments, a stimulation protocol may include the parameters of the electrical impulses that are to be applied at each microparticle 104 in neuromodulation system 100. The stimulation protocol may also include the duration and frequency of stimulation, as well as the time intervals at which each microparticle 104 is to be stimulated (in case of serial or patterned stimulation), In some embodiments, the stimulation protocols are predetermined and stored in central controller 102. in other embodiments, the stimulation parameters are adaptive and are changed in response to the neural activity sensed by one or more microparticles 104. Similarly, in exemplary embodiments, a sensing protocol may include a pattern or sequence in which neural activity signals may be collected by implanted microparticles 104.

[0050] Stimulation by multiple microparticles 104 may allow the use of lower stimulation voltages at each microparticie 104 in comparison to the application of a single stimulation impulse of large magnitude. The use of lower stimulation voltages may reduce the possibility of trauma or atrophy of the target neural tissue.

Stimulation by two or more microparticles 104 implanted along the length of a nerve fiber may also help to control the propagation direction of resulting action potentials. Generally, action potentials propagate in both directions from a stimulation site. By implanting two or more microparticles 104 along a nerve fiber, propagation direction may be blocked in one direction, resulting in unidirectional action potentials. In some embodiments, unidirectional action potentials may be initiated by coordinating the spatial-temporal distribution of the current/voltage pulses applied through implanted microparticles 104.

[0051 ] The foregoing description has been presented for purposes of illustration. It is not exhaustive and is not limited to the precise forms or

embodiments disclosed. Modifications and adaptations will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed embodiment. Moreover, while illustrative embodiments have been described herein, the disclosure includes the scope of any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g. , of aspects across various embodiments), adaptations and/or alterations as would be appreciated by those skilled in the art based on the present disclosure. The limitations in the claims are to be interpreted broadly based on the language employed in the claims and not limited to examples described in the present specification or during the prosecution of the application. The examples are to be construed as non-exclusive. Furthermore, the steps of the disclosed methods may be modified in any manner, including by reordering steps and/or inserting or deleting steps. It is intended, therefore, that the specification and examples be considered as illustrative only, with a true scope and spirit being indicated by the following claims and their full scope of equivalents.

Claims

1 . A system for neuromodulation, comprising:

two or more microparticies implantable in a series along the length of a target nerve fiber, at least one of the two or more microparticies comprising a stimuiation electrode configured to transmit an electrical impulse to the target nerve fiber; and

a central controller operatively coupled to the two or more microparticies, the central controller comprising;

a wireless communication system configured to communicate with each of the two or more microparticies; and

a processor configured to control the operation of the two or more microparticies, wherein the processor is configured to provide a stimulation parameter to the stimulation electrode of the at least one of the two or more microparticies.

2. The system of claim 1 , wherein the central controller further comprises a power system configured to wirelessly deliver power to each of the two or more microparticies.

3. The system of claims 1 or 2, wherein each of the two or more microparticies further comprises a charging system configured to receive power wirelessly from the central controller.

4. The system of any of claims 1 to 3, wherein at least one of the two or more microparticies further comprises a sensor to receive a signal indicative of neural activity of the target nerve fiber.

5. The system of claim 4, wherein the at least one of the two or more

microparticies is configured to wirelessly transmit the received signal to the central controller.

6. The system of claim 5, wherein the processor is further configured to update the stimulation parameter based on the received signal transmitted to the central controller.

7. The system of claim 6, wherein processor is further configured to

communicate the updated stimulation parameter from the central controller to at least one of the two or more microparticles.

8. The system of any of claims 4 to 7, wherein at least one of the two or more microparticles comprises the sensor and the stimulation electrode.

9. The system of any of claims 4 to 8, wherein, in use, the two or more

microparticles are implanted in a series along the length of the target nerve fiber.

10. The system of claim 9, wherein, in use, the two or more microparticles are equally spaced apart along the length of the target nerve fiber.

1 1. The system of any of claims 9 to 10, wherein, in use, the two or more

microparticles are non-uniformly spaced along the length of the target nerve fiber.

12. The system of any of claims 1 to 1 1 wherein, in use, the central controller is positioned remote from the two or more microparticles.

13. The system of any of claims 1 to 12. wherein each of the two or more

microparticles is about 500 micrometers or less in diameter.

14. The system of any of claims 1 to 13, wherein each of the two or more

microparticles comprises a unique identification system that allows the central controller to individually address each of the two or more microparticles.

15. The system of any of claims 1 to 14, wherein the processor is configured to provide a stimulation parameter to the stimulation electrode of each of the two or more microparticles sequentially.

16. The system of any of claims 1 to 14, wherein the processor is configured to provide a stimulation parameter to the stimulation electrode of each of the two or more microparticles simultaneously.

17. The system of any of claims 1 to 14, wherein the processor is configured to provide a stimulation parameter to the stimulation electrode of each of the two or more microparticles non-sequentially.

18. A neuromodulation method, comprising:

operatively coupling a central controller to a neuromodulation device comprising two or more microparticles provided in a series along the length of a target nerve fiber, wherein at least one of the two or more microparticles comprises a stimulation electrode that transmits an electrical impulse to the target nerve fiber;

delivering a stimulation parameter from the central controller to the at least one of the two or more microparticles that comprises a stimulation electrode; and

applying an electrical impulse through the stimulation electrode to the target nerve fiber based on the stimulation parameter. 9. The method of claim 15, further comprising sensing neural activity of the

target nerve fiber through a sensor provided on at least one of the two or more microparticles.

20. The method of claim 16, wherein at least one of the two or more

microparticles performs a dual function of applying the electrical impulse and sensing neural activity.

21 . The method of claims 16 or 17, wherein the sensed neural activity is

wirelessly transmitted to the central controller.

22. The method of any of claims 16 to 18, wherein the stimulation parameter is updated based on the sensed neural activity transmitted to the central controller.

23. The method of claim 19, wherein the updated stimulation parameter is

delivered from the central controller to at least one of the two or more microparticles.

24 The method of any of claims 15 to 20, wherein the target nerve fiber is

stimulated sequentially at the two or more microparticles.

25. The method of any of claims 15 to 20, wherein the target nerve fiber is

stimulated simultaneously at the two or more microparticles.

26. The method of any of claims 15 to 20, wherein the target nerve fiber is

stimulated in a non-sequential pattern at the two or more microparticles.

27. The method of any of claims 15 to 23, further comprising delivering power wirelessly from the central controller to the two or more microparticles.

28 The method of any of claims 15 to 24, wherein the stimulation parameter is delivered wirelessly from the central controller to the at least one of the two or more microparticles that comprises a stimulation electrode.

29. A modified nerve to which the two or more microparticles of any one of claims 1 to 17 are attached, such that the two or more microparticles is in signaling contact with the nerve and so the nerve can be distinguished from the nerve in its natural state.

30. A modified nerve obtainable by stimulating neural activity of the nerve

according to any one of claims 15 to 28.

31. A method of controlling two or more microparticles of any one of claims 1 to 17 which are in signaling contact with a nerve, comprising a step of sending control instructions to the two or more microparticles, in response to which at least one of the two or more microparticles applies a stimulatory signal to the nerve.