Incomplete spinal cord injury (iSCI) disrupts signal transmission at the level of injury (LOI) and in higher brain structures, weakening intracortical circuits and impairing movement initiation. A potential approach to target intracortical circuits is to deliver transcranial magnetic stimulation (TMS) during motor intention, known as movement-related cortical stimulation (MRCS). We hypothesize that delivering TMS during motor intention will enhance corticospinal excitability (CE) and improve muscle activation below the LOI. One participant with chronic severe iSCI participated in a crossover study followed by five consecutive treatment sessions. First, we investigated the impact of TMS intensity (subthreshold vs. suprathreshold) on CE when delivered 50 ms before movement. The participant then received five consecutive days of MRCS with active subthreshold TMS for 15-20 min. Experiment 1: CE was assessed before and after sham, suprathreshold, and subthreshold MRCS (1-wk washout), targeting the abductor hallucis muscle. Experiment 2: CE and volitional motor unit recruitment were measured at baseline, the start of each session and 3- and 7-day follow-up. Corticomotor maps were assessed at baseline and post 3- and 7-day follow-up. Subthreshold MRCS increased CE compared with sham and suprathreshold MRCS. Five days of subthreshold MRCS increased CE, motor maps, and volitional motor unit recruitment, with improvements lasting up to the 3-day follow-up and remaining above baseline at day 7. These findings suggest that timed cortical stimulation with movement intention may enhance signal transmission in iSCI below the LOI. Future research is needed to determine if MRCS can prime intracortical circuitry before therapy to improve motor function.NEW & NOTEWORTHY We demonstrate that five consecutive days of movement-related cortical stimulation can enhance corticospinal excitability, expand motor maps, and improve volitional motor unit recruitment in a person with severe incomplete spinal cord injury. These results support the brain's adaptive capacity following spinal cord injury, despite limited motor drive to the muscle, and corroborate the potential to improve motor function by targeting higher-order networks during volitional motor intention with noninvasive brain stimulation.

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.

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.

Background: Repetitive peripheral sensory stimulation (RPSS) followed by 4- hour task-specific training improves upper limb motor function in subjects with stroke who experience moderate to severe motor upper limb impairments. Obectives: Here, we compared effects of RPSS versus sham followed by a shorter duration of training in subjects with moderate to severe motor impairments in the chronic phase after stroke. Design and setting: Single-center, randomized, placebo-controlled, parallelgroup clinical trial. Methods: We compared effects of 18 sessions of either 1.5 hours of active RPSS or sham followed by a supervised session of 30-minutes of functional electrical stimulation (FES) and 45-minutes of task-specific training (TST) of the paretic upper limb. In both groups, subjects were instructed to perform functional tasks at home, without supervision. The primary outcome measure was the Wolf Motor Function Test (WMFT) after six weeks of treatment. Grasp and pinch strength were secondary outcomes. Results: In intention-to-treat analysis, WMFT improved significantly in both active and sham groups at 3 and 6 weeks of treatment. Grasp strength improved significantly in the active, but not in the sham group, at 3 and 6 weeks. Pinch strength improved significantly in both groups at 3 weeks, and only in the active group at 6 weeks. Conclusions: RPSS enhanced hand strength in chronic stroke. Despite the short duration of supervised training (2.75 hours/session), changes in WMFT in both groups were comparable to those reported after longer, more intensive training protocols. These findings are relevant to settings that impose constraints in duration of direct contact between therapists and patients.

Introduction Repetitive peripheral sensory stimulation (RPSS) followed by 4-hour task-specific training (TST) improves upper limb motor function in subjects with stroke who experience moderate to severe motor upper limb impairments. Here, we compared effects of RPSS vs sham followed by a shorter duration of training in subjects with moderate to severe motor impairments in the chronic phase after stroke. Methods This single-center, randomized, placebo-controlled, parallel-group clinical trial compared effects of 18 sessions of either 1.5 h of active RPSS or sham followed by a supervised session that included 45 min of TST of the paretic upper limb. In both groups, subjects were instructed to perform functional tasks at home, without supervision. The primary outcome measure was the Wolf Motor Function Test (WMFT) after 6 weeks of treatment. Grasp and pinch strength were secondary outcomes. Results In intention-to-treat analysis, WMFT improved significantly in both active and sham groups at 3 and 6 weeks of treatment. Grasp strength improved significantly in the active, but not in the sham group, at 3 and 6 weeks. Pinch strength improved significantly in both groups at 3 weeks, and only in the active group at 6 weeks. Conclusions The between-group difference in changes in WMFT was not statistically significant. Despite the short duration of supervised treatment, WMFT improved significantly in subjects treated with RPSS or sham. These findings are relevant to settings that impose constraints in duration of direct contact between therapists and patients. In addition, RPSS led to significant gains in hand strength. Trial Registry Name: Peripheral Nerve Stimulation and Motor Training in Stroke Clinical Trials.gov identifier: NCT0265878 https://clinicaltrials.gov/ct2/show/NCT02658578

Implantable motor neuroprosthetic systems can restore function to individuals with significant disabilities, such as spinal cord injury, stroke, cerebral palsy, and multiple sclerosis. Neuroprostheses provide restored functionality by electrically activating paralysed muscles in coordinated patterns that replicate (enable) controlled movement that was lost through injury or disease. It is important to consider the general topology of the implanted system itself. The authors demonstrate that the wired multipoint implant technology is practical and feasible as a basis for the development of implanted multi-function neuroprosthetic systems. The advantages of a centralised power supply are significant. Heating due to recharge can be mitigated by using an actively cooled external recharge coil. Using this approach, the time required to perform a full recharge was significantly reduced. This approach has been demonstrated as a practical option for regular clinical use of implanted neuroprostheses.

Introduction: Peripheral sensory stimulation (PSS) administered for 2 hours prior to intensive task-oriented motor training delivered for 4 hours, over 10 days, leads to clinically significant benefits in subjects with stroke and moderate to severe upper limb motor impairment, compared to sham PSS. Whether similar results can be obtained with less intensive training programs remains to be determined. Methods: Twenty subjects with stroke in the chronic phase (>6m) and moderate to severe upper limb motor impairments were randomized to treatment with either 1.5h active PSS or sham, followed by functional electrical stimulation (FES) and task-specific training (TST) in sessions administered three times per week over six weeks. FES lasted for 30 minutes and TST, for 45 minutes. The primary outcome was the difference in performance in the Wolf Motor Function Test. The data were analyzed with a generalized estimating equations model with factors “group” (active or sham) and “time” (baseline, three and six weeks after starting treatment). Results: There were significant effects of “time” (Wald Chi-square = 16.5, p<0.001) and interaction between “group” and “time” (Wald Chi-square = 10.4, p=0.005) for the Wolf Motor Function Test, Functional Ability Scale. Post-hoc Bonferroni-corrected analyses showed a statistically significant improvement in performance between baseline and three weeks after beginning of treatment in the active (p=0.001) but not in the sham group (p=0.912). The difference between performance at baseline and six weeks after beginning of treatment almost reached statistically significance in the active (p=0.058) but not in the sham (p>0.999) group. Conclusions: These results are relevant for the design of larger clinical trials involving durations of interventions that are more easily implemented in clinical practice than rehabilitation protocols lasting for 6 hours per day. The study is ongoing.

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. 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. 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). 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.

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.

The history of neuromuscular electrical stimulation has been well documented. Depending upon how far back in time one chooses to go, it is clear that the field has a checkered past. It is generally agreed that the experiments of Volta, Galvani, and Lyden demonstrated the early potential of activating neural tissue by electrical currents. However, over the following decades individuals who we now most likely would describe as charlatans claimed miracle cures from the delivery of electricity to various parts of the human anatomy. The lack of a regulatory body and reimbursement mechanism enabled these individuals to make incredibly spurious claims and find desperate patients who would accept these treatments and had the capability to pay for them. It is safe to say that the more recent applications now achieving true clinical impact are not a direct result of this early experimentation. The modern-day approach to electrical stimulation of human tissue was born from the evolution of electronic technology, the development of implantable devices within the body, a growing understanding of modern physiology and anatomy, and successful collaborations between physicians and engineers.

Neuroprostheses can be used to move paralyzed limbs through the coordinated electrical activation of multiple muscles. Specifically, implantable motor neuroprostheses are used to provide hand grasping and reach for tetraplegic spinal cord injured individuals. Typical motor neuroprosthetic systems consist of stimulating electrodes, a stimulator, an external controller, and an input sensor. Grasp function is provided through patterned electrical stimulation of the paralyzed forearm and hand muscles. Control of grasp opening and closing is provided proportionally by utilizing residual joint movement, such as shoulder or wrist movement, or by recording the myoelectric signal from muscles under voluntary control. Over 250 individuals have received implanted systems for hand control. The outcomes have been consistently positive in every subject tested to date. Paralyzed individuals can regain the ability to perform daily activities such as eating, writing, brushing teeth, and reaching overhead. Future neuroprosthetic systems are expected to be modular and provide multiple functions to each individual.

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.

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.

Introduction: Transcranial direct current stimulation (tDCS) and somatosensory stimulation in the form of peripheral sensory stimulation (PSS) have emerged as potential powerful tools to enhance motor performance or increase effects of motor training in stroke victims. Objectives: To compare effects of active PSS+tDCS, tDCS alone, PSS alone and sham PSS+tDCS as add-on interventions to motor training in patients with stroke and moderate to severe upper limb impairments. Methods: Patients > 6 months post-stroke underwent four different interventions, in a cross-over design: repetitive training of wrist extension of the paretic arm preceded by either active PSS (median, ulnar and radial nerves), active anodal tDCS of the affected hemisphere, sham PSS+tDCS or active PSS+tDCS. Before and after each session, the following outcomes were blindly evaluated in the paretic upper limb: range of movement (ROM) of wrist extension (primary outcome); ROM of wrist flexion, grasp and pinch strength. Measures were compared with analysis of variance with repeated measures (ANOVARM) with factors “session” and “time”. Results: After screening 2499 patients, 22 subjects were included in the study (14 men). The mean age (± standard deviation) was 55.2±12.9 years and the mean time from stroke, 5.3±5.6 years. The mean Fugl-Meyer score for the paretic upper limb was 37±7.9. Two patients were excluded (one dropped out and one received botulinum toxin treatment). There was a significant effect of “time” (F=4.6, p=0.046), but no effects of “session” or interaction “session x time” in regard to grasp force. There were no significant effects of “session”, “time” or interaction “session x time” in regard to ROM of wrist extension, wrist flexion, or pinch force. Conclusions: Repetitive training of wrist extension specifically improved grasp force and did not influence other outcomes. PSS+tDCS, tDCS alone or PSS alone did not potentiate the effect of training.