Neuroprosthesis for individuals with spinal cord injury.

OBJECTIVE: Individuals who sustain a traumatic spinal cord injury (SCI) often have a loss of multiple body systems. Significant functional improvement can be gained by individual SCI through the use of neuroprostheses based on electrical stimulation. The most common actions produced are grasp, overhead reach, trunk posture, standing, stepping, bladder/bowel/sexual function, and respiratory functions. METHODS: We review the fundamental principles of electrical stimulation, which are established, allowing stimulation to be safely delivered through implanted devices for many decades. We review four common clinical applications for SCI, including grasp/reach, standing/stepping, bladder/bowel function, and respiratory functions. Systems used to implement these functions have many common features, but are also customized based on the functional goals of each approach. Further, neuroprosthetic systems are customized based on the needs of each user. RESULTS & CONCLUSION: The results to date show that implanted neuroprostheses can have a significant impact on the health, function, and quality of life for individuals with SCI. A key focus for the future is to make implanted neuroprostheses broadly available to the SCI population.

Design and Testing of Stimulation and Myoelectric Recording Modules in an Implanted Distributed Neuroprosthetic System.

Implantable motor neuroprostheses can restore functionality to individuals with neurological disabilities by electrically activating paralyzed muscles in coordinated patterns. The typical design of neuroprosthetic systems relies on a single multi-use device, but this limits the number of stimulus and sensor channels that can be practically implemented. To address this limitation, a modular neuroprosthesis, the "Networked Neuroprosthesis" (NNP), was developed. The NNP system is the first fully implanted modular neuroprosthesis that includes implantation of all power, signal processing, biopotential signal recording, and stimulating components. This paper describes the design of stimulation and recording modules, bench testing to verify stimulus outputs and appropriate filtering and recording, and validation that the components function properly while implemented in persons with spinal cord injury. The results of system testing demonstrated that the NNP was functional and capable of generating stimulus pulses and recording myoelectric, temperature, and accelerometer signals. Based on the successful design, manufacturing, and testing of the NNP System, multiple clinical applications are anticipated.

Myoelectric signal from below the level of spinal cord injury as a command source for an implanted upper extremity neuroprosthesis - a case report.

Implanted motor neuroprostheses offer significant restoration of function for individuals with spinal cord injury. Providing adequate user control for these devices is a challenge but is crucial for successful performance. Electromyographic (EMG) signals can serve as effective control sources, but the number of above-injury muscles suitable to provide EMG-based control signals is very limited. Previous work has shown the presence of below-injury volitional myoelectric signals even in subjects diagnosed with motor complete spinal cord injury. In this case report, we present a demonstration of a hand grasp neuroprosthesis being controlled by a user with a C6 level, motor complete injury through EMG signals from their toe flexor. These signals were successfully translated into a functional grasp output, which performed similarly to the participant's usual shoulder position control in a grasp-release functional test. This proof-of-concept demonstrates the potential for below-injury myoelectric activity to serve as a novel form of neuroprosthesis control.

Design and testing of a 96-channel neural interface module for the Networked Neuroprosthesis system.

BACKGROUND: The loss of motor functions resulting from spinal cord injury can have devastating implications on the quality of one's life. Functional electrical stimulation has been used to help restore mobility, however, current functional electrical stimulation (FES) systems require residual movements to control stimulation patterns, which may be unintuitive and not useful for individuals with higher level cervical injuries. Brain machine interfaces (BMI) offer a promising approach for controlling such systems; however, they currently still require transcutaneous leads connecting indwelling electrodes to external recording devices. While several wireless BMI systems have been designed, high signal bandwidth requirements limit clinical translation. Case Western Reserve University has developed an implantable, modular FES system, the Networked Neuroprosthesis (NNP), to perform combinations of myoelectric recording and neural stimulation for controlling motor functions. However, currently the existing module capabilities are not sufficient for intracortical recordings. METHODS: Here we designed and tested a 1 × 4 cm, 96-channel neural recording module prototype to fit within the specifications to mate with the NNP. The neural recording module extracts power between 0.3-1 kHz, instead of transmitting the raw, high bandwidth neural data to decrease power requirements. RESULTS: The module consumed 33.6 mW while sampling 96 channels at approximately 2 kSps. We also investigated the relationship between average spiking band power and neural spike rate, which produced a maximum correlation of R = 0.8656 (Monkey N) and R = 0.8023 (Monkey W). CONCLUSION: Our experimental results show that we can record and transmit 96 channels at 2ksps within the power restrictions of the NNP system and successfully communicate over the NNP network. We believe this device can be used as an extension to the NNP to produce a clinically viable, fully implantable, intracortically-controlled FES system and advance the field of bioelectronic medicine.

Evolution of Neuroprosthetic Approaches to Restoration of Upper Extremity Function in Spinal Cord Injury.

Background: Spinal cord injury (SCI) occurring at the cervical levels can result in significantly impaired arm and hand function. People with cervical-level SCI desire improved use of their arms and hands, anticipating that regained function will result in improved independence and ultimately improved quality of life. Neuroprostheses provide the most promising method for significant gain in hand and arm function for persons with cervical-level SCI. Neuroprostheses utilize small electrical currents to activate peripheral motor nerves, resulting in controlled contraction of paralyzed muscles. Methods: A myoelectrically-controlled neuroprosthesis was evaluated in 15 arms in 13 individuals with cervical-level SCI. All individuals had motor level C5 or C6 tetraplegia. Results: This study demonstrates that an implanted neuroprosthesis utilizing myoelectric signal (MES)-controlled stimulation allows considerable flexibility in the control algorithms that can be utilized for a variety of arm and hand functions. Improved active range of motion, grip strength, and the ability to pick up and release objects were improved in all arms tested. Adverse events were few and were consistent with the experience with similar active implantable devices. Conclusion: For individuals with cervical SCI who are highly motivated, implanted neuroprostheses provide the opportunity to gain arm and hand function that cannot be gained through the use of orthotics or surgical intervention alone. Upper extremity neuroprostheses have been shown to provide increased function and independence for persons with cervical-level SCI.

Characterization of Volitional Electromyographic Signals in the Lower Extremity After Motor Complete Spinal Cord Injury.

BACKGROUND: Previous studies have demonstrated the presence of intact axons across a spinal cord lesion, even in those clinically diagnosed with complete spinal cord injury (SCI). These axons may allow volitional motor signals to be transmitted through the injury, even in the absence of visible muscle contraction. OBJECTIVE: To demonstrate the presence of volitional electromyographic (EMG) activity below the lesion in motor complete SCI and to characterize this activity to determine its value for potential use as a neuroprosthetic command source. METHODS: Twenty-four subjects with complete (AIS A or B), chronic, cervical SCI were tested for the presence of volitional below-injury EMG activity. Surface electrodes recorded from 8 to 12 locations of each lower limb, while participants were asked to attempt specific movements of the lower extremity in response to visual and audio cues. EMG trials were ranked through visual inspection, and were scored using an amplitude threshold algorithm to identify channels of interest with volitional motor unit activity. RESULTS: Significant below-injury muscle activity was identified through visual inspection in 16 of 24 participants, and visual inspection rankings were well correlated to the algorithm scoring. CONCLUSIONS: The surface EMG protocol utilized here is relatively simple and noninvasive, ideal for a clinical screening tool. The majority of subjects tested were able to produce a volitional EMG signal below their injury level, and the algorithm developed allows automatic identification of signals of interest. The presence of this volitional activity in the lower extremity could provide an innovative new command signal source for implanted neuroprostheses or other assistive technology.

Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.

BACKGROUND: People with chronic tetraplegia, due to high-cervical spinal cord injury, can regain limb movements through coordinated electrical stimulation of peripheral muscles and nerves, known as functional electrical stimulation (FES). Users typically command FES systems through other preserved, but unrelated and limited in number, volitional movements (eg, facial muscle activity, head movements, shoulder shrugs). We report the findings of an individual with traumatic high-cervical spinal cord injury who coordinated reaching and grasping movements using his own paralysed arm and hand, reanimated through implanted FES, and commanded using his own cortical signals through an intracortical brain-computer interface (iBCI). METHODS: We recruited a participant into the BrainGate2 clinical trial, an ongoing study that obtains safety information regarding an intracortical neural interface device, and investigates the feasibility of people with tetraplegia controlling assistive devices using their cortical signals. Surgical procedures were performed at University Hospitals Cleveland Medical Center (Cleveland, OH, USA). Study procedures and data analyses were performed at Case Western Reserve University (Cleveland, OH, USA) and the US Department of Veterans Affairs, Louis Stokes Cleveland Veterans Affairs Medical Center (Cleveland, OH, USA). The study participant was a 53-year-old man with a spinal cord injury (cervical level 4, American Spinal Injury Association Impairment Scale category A). He received two intracortical microelectrode arrays in the hand area of his motor cortex, and 4 months and 9 months later received a total of 36 implanted percutaneous electrodes in his right upper and lower arm to electrically stimulate his hand, elbow, and shoulder muscles. The participant used a motorised mobile arm support for gravitational assistance and to provide humeral abduction and adduction under cortical control. We assessed the participant's ability to cortically command his paralysed arm to perform simple single-joint arm and hand movements and functionally meaningful multi-joint movements. We compared iBCI control of his paralysed arm with that of a virtual three-dimensional arm. This study is registered with ClinicalTrials.gov, number NCT00912041. FINDINGS: The intracortical implant occurred on Dec 1, 2014, and we are continuing to study the participant. The last session included in this report was Nov 7, 2016. The point-to-point target acquisition sessions began on Oct 8, 2015 (311 days after implant). The participant successfully cortically commanded single-joint and coordinated multi-joint arm movements for point-to-point target acquisitions (80-100% accuracy), using first a virtual arm and second his own arm animated by FES. Using his paralysed arm, the participant volitionally performed self-paced reaches to drink a mug of coffee (successfully completing 11 of 12 attempts within a single session 463 days after implant) and feed himself (717 days after implant). INTERPRETATION: To our knowledge, this is the first report of a combined implanted FES+iBCI neuroprosthesis for restoring both reaching and grasping movements to people with chronic tetraplegia due to spinal cord injury, and represents a major advance, with a clear translational path, for clinically viable neuroprostheses for restoration of reaching and grasping after paralysis. FUNDING: National Institutes of Health, Department of Veterans Affairs.

Infection Rates of Electrical Leads Used for Percutaneous Neurostimulation of the Peripheral Nervous System.

BACKGROUND: Percutaneous neurostimulation of the peripheral nervous system involves the insertion of a wire "lead" through an introducing needle to target a nerve/plexus or a motor point within a muscle. Electrical current may then be passed from an external generator through the skin via the lead for various therapeutic goals, including providing analgesia. With extended use of percutaneous leads sometimes greater than a month, infection is a concern. It was hypothesized that the infection rate of leads with a coiled design is lower than for leads with a noncoiled cylindrical design. METHODS: The literature was retrospectively reviewed for clinical studies of percutaneous neurostimulation of the peripheral nervous system of greater than 2 days that included explicit information on adverse events. The primary endpoint was the number of infections per 1,000 indwelling days. RESULTS: Forty-three studies were identified that met inclusion criteria involving coiled (n = 21) and noncoiled (n = 25) leads (3 studies involved both). The risk of infection with noncoiled leads was estimated to be 25 times greater than with coiled leads (95% confidence interval [CI] 2 to 407, P = 0.006). The infection rates were estimated to be 0.03 (95% CI 0.01 to 0.13) infections per 1,000 indwelling days for coiled leads and 0.83 (95% CI 0.16 to 4.33) infections per 1,000 indwelling days for noncoiled leads (P = 0.006). CONCLUSIONS: Percutaneous leads used for neurostimulation of the peripheral nervous system have a much lower risk of infection with a coiled design compared with noncoiled leads: approximately 1 infection for every 30,000 vs. 1,200 indwelling days, respectively.

Challenges and opportunities in restoring function after paralysis.

Neurotechnology has made major advances in development of interfaces to the nervous system that restore function in paralytic disorders. These advances enable both restoration of voluntary function and activation of paralyzed muscles to reanimate movement. The technologies used in each case are different, with external surface stimulation or percutaneous stimulation generally used for restoration of voluntary function, and implanted stimulators generally used for neuroprosthetic restoration. The opportunity to restore function through neuroplasticity has demonstrated significant advances in cases where there are retained neural circuits after the injury, such as spinal cord injury and stroke. In cases where there is a complete loss of voluntary neural control, neural prostheses have demonstrated the capacity to restore movement, control of the bladder and bowel, and respiration and cough. The focus of most clinical studies has been primarily toward activation of paralyzed nerves, but advances in inhibition of neural activity provide additional means of addressing the paralytic complications of pain and spasticity, and these techniques are now reaching the clinic. Future clinical advances necessitate having a better understanding of the underlying mechanisms, and having more precise neural interfaces that will ultimately allow individual nerve fibers or groups of nerve fibers to be controlled with specificity and reliability. While electrical currents have been the primary means of interfacing to the nervous system to date, optical and magnetic techniques under development are beginning to reach the clinic, and provide great opportunity. Ultimately, techniques that combine approaches are likely to be the most effective means for restoring function, for example combining regeneration and neural plasticity to maximize voluntary activity, combined with neural prostheses to augment the voluntary activity to functional levels of performance. It is a substantial challenge to bring any of these techniques through clinical trials, but as each of the individual techniques is sufficiently developed to reach the clinic, these present great opportunities for enabling patients with paralytic disorders to achieve substantial independence and restore their quality of life.

A novel command signal for motor neuroprosthetic control.

BACKGROUND: Neuroprostheses can restore functions such as hand grasp or standing to individuals with spinal cord injury (SCI) using electrical stimulation to elicit movements in paralyzed muscles. Implanted neuroprostheses currently use electromyographic (EMG) activity from muscles above the lesion that remain under volitional control as a command input. Systems in development use a networked approach and will allow for restoration of multiple functions but will require additional command signals to control the system, especially in individuals with high-level tetraplegia. OBJECTIVE: The objective of this study was to investigate the feasibility of using muscles innervated below the injury level as command sources for a neuroprosthesis. Recent anatomical and physiological studies have demonstrated the presence of intact axons across the lesion, even in those diagnosed with a clinically complete SCI; hence, EMG activity may be present in muscles with no sign of movement. METHODS: Twelve participants with motor complete SCI were enrolled and EMG was recorded with surface electrodes from 8 muscles below the knee in each leg. RESULTS: Significant activity was evident in 89% of the 192 muscles studied during attempted movements of the foot and lower limb. At least 2 muscles from each participant were identified as potential command signals for a neuroprosthesis based on 2-state, threshold classification. CONCLUSIONS: Results suggest that voluntary activity is present and recordable in below lesion muscles even after clinically complete SCI.

Design and testing of an advanced implantable neuroprosthesis with myoelectric control.

An implantable stimulator-telemeter (IST-12) was developed for applications in neuroprosthetic restoration of limb function in paralyzed individuals. The IST-12 provides 12 stimulation channels and two myoelectric signal (MES) channels. The MES circuitry includes a two-channel multiplexer, preamplifier, variable gain amplifier/bandpass filter, full-wave rectifier, and bin integrator. Power and control signals are transmitted from an external control unit to the IST-12 through an inductive link. Recorded MES signals are telemetered back to the external control unit through the same inductive link. Following bench testing, one device was implanted chronically in a dog for 15 months and evaluated. Conditions were identified in which MES could be recorded with minimal stimulus artifact. The ability to record MES in the presence of stimulation was verified, confirming the potential of the IST-12 to be used as a myoelectric controlled neuroprosthesis.

Training to improve volitional muscle activity in clinically paralyzed muscles for neuroprosthesis control.

Neuroprostheses are devices that use electrical stimulation to activate paralyzed muscles in a coordinated manner to restore functional movements. These systems utilize a voluntarily-generated command signal for control of function. Current command signals include electromyographic (EMG) activity from muscles above the injury level that remain under volitional control. In individuals with cervical level spinal cord injury (SCI), these signal sources are limited in number. Our recent research suggests that volitional muscle activity from below the injury level in individuals with motor complete spinal cord injury may be a viable source of command information. The signals from these muscles are small, and therefore the goal of this study is to determine if training using visual feedback can improve the quality of these muscle signals. Results to date indicate that training with visual feedback can increase both the magnitude and consistency of EMG signals in clinically paralyzed muscles.

Wireless wearable controller for upper-limb neuroprosthesis.

The objective of this project was to develop a wireless, wearable joint angle transducer to enable proportional control of an upper-limb neuroprosthesis by wrist position. Implanted neuroprostheses use functional electrical stimulation to provide hand grasp to individuals with tetraplegia. Wrist position is advantageous for control because it augments the tenodesis grasp and can be implemented bilaterally. Recently developed, fully implantable multichannel stimulators are battery-powered and use wireless telemetry to control stimulator outputs. An external wrist controller was designed for command signal acquisition for people with cervical-level spinal cord injury to control this implantable stimulator. The wearable controller, which uses gigantic magnetoresistive sensing techniques to measure wrist position, is worn on the forearm. A small dime-sized magnet is fixed to the back of the hand. Results indicate that the device is a feasible control method for an upper-limb neuroprosthesis and could be reduced to a small "wristwatch" size for cosmesis and easy donning.

Designing the optical interface of a transcutaneous optical telemetry link.

Optical telemetry has long been an option for transcutaneous data transfer and has been used in various types of implanted systems. This telemetry modality and the efficiency of these optical links are becoming ever more important as higher bandwidth sources such as cortical recording arrays are being implemented in implanted systems. The design of the transmitter-skin-receiver interface (the "optical interface") is paramount to the operation of a transcutaneous optical telemetry link. This interface functions to achieve sufficient receiver signal power for data communication. This paper describes a mathematical analysis and supporting data that quantitatively describes the relationship between the primary interface design parameters. These parameters include the thickness of the skin through which the light is transmitted, the size of the integration area of the optics, the degree of transmitter-receiver misalignment, the efficiency of the optics system, and the emitter power. The particular combination of these parameters chosen for the hardware device will determine the receiver signal power and, therefore, the data quality for the link. This paper demonstrates some of the tradeoffs involved in the selection of these design parameters and provides suggestions for link design. This analysis may also be useful for transcutaneous optical powering systems.

An implanted upper-extremity neuroprosthesis using myoelectric control.

PURPOSE: The purpose of this study was to evaluate the potential of a second-generation implantable neuroprosthesis that provides improved control of hand grasp and elbow extension for individuals with cervical level spinal cord injury. The key feature of this system is that users control their stimulated function through electromyographic (EMG) signals. METHODS: The second-generation neuroprosthesis consists of 12 stimulating electrodes, 2 EMG signal recording electrodes, an implanted stimulator-telemeter device, an external control unit, and a transmit/receive coil. The system was implanted in a single surgical procedure. Functional outcomes for each subject were evaluated in the domains of body functions and structures, activity performance, and societal participation. RESULTS: Three individuals with C5/C6 spinal cord injury received system implantation with subsequent prospective evaluation for a minimum of 2 years. All 3 subjects demonstrated that EMG signals can be recorded from voluntary muscles in the presence of electrical stimulation of nearby muscles. Significantly increased pinch force and grasp function was achieved for each subject. Functional evaluation demonstrated improvement in at least 5 activities of daily living using the Activities of Daily Living Abilities Test. Each subject was able to use the device at home. There were no system failures. Two of 6 EMG electrodes required surgical revision because of suboptimal location of the recording electrodes. CONCLUSIONS: These results indicate that a neuroprosthesis with implanted myoelectric control is an effective method for restoring hand function in midcervical level spinal cord injury.

Rehabilitation Medicine Summit: Building Research Capacity--executive summary.

The advancement of medical science depends on the production, availability, and utilization of new information generated by research. A successful research enterprise depends not only on a carefully designed agenda that responds to clinical and societal needs but also on the research capacity necessary to perform the work. Research that is likely to enhance clinical practice presupposes the existence of a critical mass of investigators working as teams in supportive environments. Unfortunately, far too little research capacity of that kind exists in rehabilitation medicine to ensure a robust future for the field. The "Rehabilitation Medicine Summit: Building Research Capacity" was conceptualized as a way of fashioning a long-term plan to foster the required developments.

Rehabilitation Medicine Summit: Building Research Capacity: executive summary.

The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were: (1) researchers; (2) research culture, environment, and infrastructure; (3) funding; (4) partnerships; and (5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called to pursue the agendas outlined in this report.

Rehabilitation Medicine Summit: building research capacity.

The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were: (1) researchers; (2) research culture, environment, and infrastructure; (3) funding; (4) partnerships; and (5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called to pursue the agendas outlined in this report.