Weakened Effective Connectivity Related to Electroacupuncture in Stroke Patients with Prolonged Flaccid Paralysis: An EEG Pilot Study.

Flaccid paralysis in the upper extremity is a severe motor impairment after stroke, which exists for weeks, months, or even years. Electroacupuncture treatment is one of the most widely used TCM therapeutic interventions for poststroke flaccid paralysis. However, the response to electroacupuncture in different durations of flaccid stage poststroke as well as in the topological configuration of the cortical network remains unclear. The objectives of this study are to explore the disruption of the cortical network in patients in different durations of flaccid stage and observe dynamic network reorganization during and after electroacupuncture. Resting-state networks were constructed from 18 subjects with flaccid upper extremity by partial directed coherence (PDC) analysis of multichannel EEG. They were allocated to three groups according to time after flaccid paralysis: the short-duration group (those with flaccidity for less than two months), the medium-duration group (those with flaccidity between two months and six months), and the long-duration group (those with flaccidity over six months). Compared with short-duration flaccid subjects, weakened effective connectivity was presented in medium-duration and long-duration groups before electroacupuncture. The long-duration group has no response in the cortical network during electroacupuncture. The global network measures of EEG data (sPDC, mPDC, and N) indicated that there was no significant difference among the three groups. These results suggested that the network connectivity reduced and weakly responded to electroacupuncture in patients with flaccid paralysis for over six months. These findings may help us to modulate the formulation of electroacupuncture treatment according to different durations of the flaccid upper extremity.

Standardizing fatigue-resistance testing during electrical stimulation of paralysed human quadriceps muscles, a practical approach.

BACKGROUND: Rapid onset of muscular fatigue is still one of the main issues of functional electrical stimulation (FES). A promising technique, known as distributed stimulation, aims to activate sub-units of a muscle at a lower stimulation frequency to increase fatigue-resistance. Besides a general agreement on the beneficial effects, the great heterogeneity of evaluation techniques, raises the demand for a standardized method to better reflect the requirements of a practical application. METHODS: This study investigated the fatigue-development of 6 paralysed quadriceps muscles over the course of 180 dynamic contractions, evaluating different electrode-configurations (conventional and distributed stimulation). For a standardized comparison, fatigue-testing was performed at 40% of the peak-torque during a maximal evoked contraction (MEC). Further, we assessed the isometric torque for each electrode-configuration at different knee-extension-angles (70°-170°, 10° steps). RESULTS: Our results showed no significant difference in the fatigue-index for any of the tested electrode-configurations, compared to conventional-stimulation. We conjecture that the positive effects of distributed stimulation become less pronounced at higher stimulation amplitudes. The isometric torque produced at different knee-extension angles was similar for most electrode-configurations. Maximal torque-production was found at 130°-140° knee-extension-angle, which correlates with the maximal knee-flexion-angles during running. CONCLUSION: In most practical applications, FES is intended to initiate dynamic movements. Therefore, it is crucial to assess fatigue-resistance by using dynamic contractions. Reporting the relationship between produced torque and knee-extension-angle can help to observe the stability of a chosen electrode-configuration for a targeted range-of-motion. Additionally, we suggest to perform fatigue testing at higher forces (e.g. 40% of the maximal evoked torque) in pre-trained subjects with SCI to better reflect the practical demands of FES-applications.

Sum of phase-shifted sinusoids stimulation prolongs paralyzed muscle output.

Neuroprostheses that activate musculature of the lower extremities can enable standing and movement after paralysis. Current systems are functionally limited by rapid muscle fatigue induced by conventional, non-varying stimulus waveforms. Previous work has shown that sum of phase-shifted sinusoids (SOPS) stimulation, which selectively modulates activation of individual motor unit pools (MUPs) to lower the duty cycle of each while maintaining a high net muscle output, improves joint moment maintenance but introduces greater instability over conventional stimulation. In this case study, implementation of SOPS stimulation with a real-time feedback controller successfully decreased joint moment instability and further prolonged joint moment output with increased stimulation efficiency over open-loop approaches in one participant with spinal cord injury. These findings demonstrate the potential for closed-loop SOPS to improve functionality of neuroprosthetic systems.

Effectiveness of Hydrotherapy on Balance and Paretic Knee Strength in Patients With Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of the study was to compare the effects of hydrotherapy and land-based conventional therapy on postural balance and knee strength in stroke patients. DESIGNS: A comprehensive search was done via databases (PubMed, EMBASE, and Web of Science) until April 12, 2019, to select randomized controlled trials. The methodological quality was assessed by the PEDro scale. Berg Balance Scale was pooled as the primary outcome and Forward Reach Test, Timed Up and Go test, and paretic knee flexor and knee extensor torque as secondary outcomes. RESULTS: Eleven articles were included. Pooled results showed that hydrotherapy was more beneficial in stroke patients on Berg Balance Scale (mean difference = 1.60, 95% confidence interval = 1.00 to 2.19), Forward Reach Test (mean difference = 1.78, 95% confidence interval = 0.73 to 2.83), Timed Up and Go test (mean difference = -1.41, 95% confidence interval: -2.44 to 0.42), and knee extensor torque (mean difference = 6.14, 95% confidence interval = 0.59 to 11.70) than conventional therapy. In subgroup analysis according to stroke-onset duration, hydrotherapy for chronic stroke patients exhibited significant effectiveness on Berg Balance Scale (mean difference = 1.61, 95% confidence interval = 1.00-.21); no significant effect was observed in subacute stroke patients (mean difference = 1.04, 95% confidence interval = -2.62 to 4.70). CONCLUSION: Stroke patients showed improvement in postural balance and paretic knee extensor strength with hydrotherapy. Hydrotherapy exhibited significant effects on improving postural balance in chronic patients than in subacute patients.

Health-related quality of life and mental health of adolescents with cerebral palsy in rural Bangladesh.

AIM: To assess the health-related quality of life (HRQoL) and mental health of adolescents with cerebral palsy (CP) in rural Bangladesh. METHODS: Case-control study of adolescents with CP (10 to ≤18-years) and age and sex matched controls without disability. Primary caregivers were included for proxy report. HRQoL was measured with Bengali versions CP Quality of Life-Teens (CPQoL-Teens) and KIDSCREEN-27. Mental health was measured with Strengths and Difficulties Questionnaire (SDQ). RESULTS: 154 cases and 173 controls matched on age and sex participated (mean age 15.1 (1.6) and 14.9 (1.6) respectively; female n = 48, n = 55 respectively, p>0.05). CPQoL-Teens was administered to adolescents with CP only; mean outcomes ranged from 38.5 (27.4) to 71.5 (16.1) and 'feelings about functioning' was poorest domain for both self- and proxy-report groups. KIDSCREEN-27 was administered to adolescents with CP and controls; adolescents with CP mean outcomes ranged from 25.9 (12.2) to 48.7 (10.56) and were significantly poorer than controls, mean difference 4.3 (95% CI 0.7 to 7.8) to 16.7 (95% CI 14.5 to 18.5), p<0.05. 'Peers and social support' was poorest domain for all groups. In regards to mental health, adolescents with CP reported significantly poorer mean SDQ than peers without disability, mean difference 0.7 (95% CI 0.3 to 1.1) to 7.8 (95% CI 6.7 to 8.9), p<0.05; and were for self-report 7.8 (95% CI 2.6 to 23.0) and proxy-report 12.0 (95% CI 6.9 to 20.9) times more likely to report 'probable' range 'total difficulties' score. Individual item analysis of CPQoL-Teens and KIDSCREEN-27 identified unique areas of concern for adolescents with CP related to pain, friendships, physical activity and energy, what may happen later in life, and feelings about having CP. Financial resources were of concern for both cases and controls. INTERPRETATION: Adolescents with CP in rural Bangladesh are at high risk of poor HRQoL and mental health problems. Effort to reduce the disparity between adolescents with CP and those without disability should consider wellbeing holistically and target dimensions including physical, psychological and social wellbeing. Specific interventions to alleviate modifiable aspects of HRQoL including pain, social isolation, and physical in-activity are recommended.

Restoring Movement in Paralysis with a Bioelectronic Neural Bypass Approach: Current State and Future Directions.

Bioelectronic medicine is a rapidly growing field that explores targeted neuromodulation in new treatment options addressing both disease and injury. New bioelectronic methods are being developed to monitor and modulate neural activity directly. The therapeutic benefit of these approaches has been validated in recent clinical studies in various conditions, including paralysis. By using decoding and modulation strategies together, it is possible to restore lost function to those living with paralysis and other debilitating conditions by interpreting and rerouting signals around the affected portion of the nervous system. This, in effect, creates a bioelectronic "neural bypass" to serve the function of the damaged/degenerated network. By learning the language of neurons and using neural interface technology to tap into critical networks, new approaches to repairing or restoring function in areas impacted by disease or injury may become a reality.

Stimulation of paralysed quadriceps muscles with sequentially and spatially distributed electrodes during dynamic knee extension.

BACKGROUND: During functional electrical stimulation (FES) tasks with able-bodied (AB) participants, spatially distributed sequential stimulation (SDSS) has demonstrated substantial improvements in power output and fatigue properties compared to conventional single electrode stimulation (SES). The aim of this study was to compare the properties of SDSS and SES in participants with spinal cord injury (SCI) in a dynamic isokinetic knee extension task simulating knee movement during recumbent cycling. METHOD: Using a case-series design, m. vastus lateralis and medialis of four participants with motor and sensory complete SCI (AIS A) were stimulated for 6 min on both legs with both electrode setups. With SES, target muscles were stimulated by a pair of electrodes. In SDSS, the distal electrodes were replaced by four small electrodes giving the same overall stimulation frequency and having the same total surface area. Torque was measured during knee extension by a dynamometer at an angular velocity of 110 deg/s. Mean power of the left and right sides (PmeanL,R) was calculated from all stimulated extensions for initial, final and all extensions. Fatigue is presented as an index value with respect to initial power from 1 to 0, whereby 1 means no fatigue. RESULTS: SDSS showed higher PmeanL,R values for all four participants for all extensions (increases of 132% in participant P1, 100% in P2, 36% in P3 and 18% in P4 compared to SES) and for the initial phase (increases of 84%, 59%, 66%, and 16%, respectively). Fatigue resistance was better with SDSS for P1, P2 and P4 but worse for P3 (0.47 vs 0.35, 0.63 vs 0.49, 0.90 vs 0.82 and 0.59 vs 0.77, respectively). CONCLUSION: Consistently higher PmeanL,R was observed for all four participants for initial and overall contractions using SDSS. This supports findings from previous studies with AB participants. Fatigue properties were better in three of the four participants. The lower fatigue resistance with SDSS in one participant may be explained by a very low muscle activation level in this case. Further investigation in a larger cohort is warranted.

Thyrotoxic Periodic Paralysis with Hypokalemia in an Adult Male from Nepal: A Case Report.

Thyrotoxic periodic paralysis is rare complication of hyperthyroidism characterized by the sudden onset of hypokalemia and muscle paralysis. It is typically present in young Asian males. There are very few literatures regarding the occurrence of thyrotoxic hypokalemic periodic paralysis in Nepal. We reported a case of a 35-year-old male presented with the chief complaints of weakness of all four limbs of 1 day duration. He was diagnosed as a case of hyperthyroidism in the past, received treatment for 6 months and left medications on his own 6 months ago. Evaluation during admission revealed severe hypokalemia with serum potassium level 1.3mEq/l and high serum Triiodothyronine (>20.00µg/L) and low serum Thyroid Stimulating Hormone (<0.01µg/L). Potassium supplements resolved muscle weakness and the patient was restarted with anti-thyroid drugs. Hence, hypokalemic paralysis is a reversible cause of paralysis and high index of suspicion as well as timely interventions are required to prevent potential harm. Keywords: hyperthyroidism; hypokalemia; muscle paralysis; thyrotoxic periodic paralysis.

Acute flaccid paralysis: Do not forget beriberi neuropathy.

We aimed to elucidate characteristics of beriberi neuropathy (BB) in a general hospital (GH) setting. Nerve conduction studies (NCS), cross-referenced with clinical records of patients admitted to a GH (May 2011-July 2017), were reviewed for diagnosis of BB. Thirteen patients (age range 23-64 years; five women) were diagnosed with BB. Eleven were incarcerated (2-24 months) at time of index event. Eleven reported prior, severe anorexia (2-6 months); five reported significant weight loss, three had recurrent vomiting, and three reported alcohol misuse. Commonest presentation was weakness (12/13); nine had symptom evolution over ≥3 weeks. At nadir, 11/13 could not walk independently. Other features included numbness/paraesthesiae (10/13), dysautonomia (6/13), vocal cord dysfunction/dysphagia (4/13), nystagmus (3/13). Pain was not prominent. Cerebrospinal fluid, tested in five patients, was acellular; one showed mildly increased protein. NCS showed predominantly sensorimotor, axonal polyneuropathy, rarely asymmetric. Only one patient had sural-sparing pattern. All received high dose thiamine. Two of the thirteen received intravenous immunoglobulin for suspicion of Guillain-Barré syndrome (GBS). Eleven improved to independent ambulation. One patient died from pulmonary embolism; one was lost to follow-up. Two of the thirteen had residual neurocognitive effects; both misused alcohol. Besides GBS, BB is an important cause of acute to subacute flaccid paralysis, especially in incarcerated patients and those with significant dietary deprivation. Features favoring BB over GBS are ≥3 weeks of symptoms, nystagmus, confusion, vocal cord dysfunction, volume overload, normal spinal fluid, elevated lactate, and absence of sural-sparing pattern in NCS.

Targeted neurotechnology restores walking in humans with spinal cord injury.

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.

Comparison of recovery patterns of gait patterns according to the paralyzed side in Korean stroke patients: Protocol for a retrospective chart review.

INTRODUCTION: In Traditional Korean Medicine (TKM), diseases on the left or right side of the human body have been treated differently according to the theory of Donguibogam, which is an encyclopedic source for TKM. In the Wind chapter of Donguibogam, left hemiparesis due to stroke is called Tan, a sort of Hyeol-Byeong, and right hemiparesis due to stroke is called Tan, a sort of Gi-Byeong. As neuroscience develops, it has been shown that the functions of the left and right hemispheres differ, as do the symptoms caused by differently located lesions in the brain. In light of these recent findings and the theory of Donguibogam, it may be useful when treating patients in clinical practice to consider the side of the human body on which symptoms appear. The aim here is to establish whether side-dependent treatments are more effective in treating patients with symptoms on different sides of the body. Specifically, this exploratory study investigates changes in gait pattern among stroke patients with hemiparesis or hemiplegia during gait recovery. METHODS: To develop this protocol, a retrospective review of charts will be used to assess differences in gait recovery patterns among stroke patients with left or right hemiparesis, using gait analysis systems that include GAITRite, G-walk, and Treadmill. The data will be selected from gait analysis performed more than twice in the period from September 1, 2017 to June 31, 2018 at Wonkwang University Gwangju Hospital (WKUGH). RESULTS: The primary outcomes include spatiotemporal parameters obtained using GAITRite (FAP, velocity, step length, swing time, and stance time); symmetric parameters obtained using G-walk (tilt, obliquity, and pelvis rotation symmetry); and center of pressure (COP) area and velocity as measured by Treadmill. DISCUSSION: This will be the first study to analyze the gait recovery pattern of stroke patients according to the paralyzed side by comparing spatiotemporal, symmetric, and COP parameters using gait analysis systems. Like all retrospective studies, the present research was subject to certain limitations related to bias (selection bias, recall bias, misclassification bias, confounding value bias), difficulty in assessing temporal relationships, and small sample size. However, these limitations were of less significance here because gait parameters and body side of symptoms of hemiplegia or hemiparesis are relatively clear. CONCLUSION: If the use of gait analysis systems (GAITRite, G-walk, and Treadmill) confirms differences in gait recovery pattern among stroke patients according to the paralyzed side, the findings will provide essential evidence for differential treatment of stroke patients on that basis.

Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia.

Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis1-3. Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS)4. Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.

Acute Effects of Drugs on Caenorhabditis elegans Movement Reveal Complex Responses and Plasticity.

Many drugs act very rapidly - they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs on C. elegans movement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hr. We found a wide variety of acute responses. Many compounds cause rapid paralysis which may be permanent or followed by one or more recovery phases. The recoveries are not the result of some generic stress response but are specific to the drug e.g., recovery from paralysis due to a neuroactive drug requires neurotransmitter pathways whereas recovery from a metabolic inhibitor requires metabolic changes. Finally, we also find that acute responses can vary greatly across development and that there is extensive natural variation in acute responses. In summary, acute responses are sensitive probes of the ability of biological networks to respond to drug treatment and these responses can reveal the action of unexplored pathways.

Paralytic and nonparalytic muscle adaptations to exercise training versus high-protein diet in individuals with long-standing spinal cord injury.

This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.8 ± 6.3 yr postinjury; 6 Comb-Ex and 5 HP diet) completed the study. Comb-Ex training occurred 3 days/wk and consisted of upper body resistance training (RT) in addition to neuromuscular electrical stimulation (NMES)-induced-RT for paralytic VL muscle. Strength training was combined with high-intensity arm-cranking exercises (1-min intervals at 85-90%, V̇o2peak) for improving cardiovascular endurance. For the HP diet intervention, protein and fat each comprised 30%, and carbohydrate comprised 40% of total energy. Clinical tests and muscle biopsies were performed 24 h before and after the last exercise or diet session. The Comb-Ex intervention increased Type IIa myofiber distribution and CSA in VL muscle and Type I and IIa myofiber CSA in deltoid muscle. In addition, Comb-Ex increased lean thigh mass, V̇o2peak, and upper body strength ( P < 0.05). These results suggest that exercise training is required to promote favorable changes in paralytic and nonparalytic muscles in individuals with long-standing SCI, and adequate dietary protein consumption alone may not be sufficient to ameliorate debilitating effects of paralysis. NEW & NOTEWORTHY This study is the first to directly compare the effects of an isocaloric high-protein diet and combination exercise training on clinical and molecular changes in paralytic and nonparalytic muscles of individuals with long-standing spinal cord injury. Our results demonstrated that muscle growth and fiber-type alterations can best be achieved when the paralyzed muscle is sufficiently loaded via neuromuscular electrical stimulation-induced resistance training.

Brain-Computer Interfaces With Multi-Sensory Feedback for Stroke Rehabilitation: A Case Study.

Conventional therapies do not provide paralyzed patients with closed-loop sensorimotor integration for motor rehabilitation. This work presents the recoveriX system, a hardware and software platform that combines a motor imagery (MI)-based brain-computer interface (BCI), functional electrical stimulation (FES), and visual feedback technologies for a complete sensorimotor closed-loop therapy system for poststroke rehabilitation. The proposed system was tested on two chronic stroke patients in a clinical environment. The patients were instructed to imagine the movement of either the left or right hand in random order. During these two MI tasks, two types of feedback were provided: a bar extending to the left or right side of a monitor as visual feedback and passive hand opening stimulated from FES as proprioceptive feedback. Both types of feedback relied on the BCI classification result achieved using common spatial patterns and a linear discriminant analysis classifier. After 10 sessions of recoveriX training, one patient partially regained control of wrist extension in her paretic wrist and the other patient increased the range of middle finger movement by 1 cm. A controlled group study is planned with a new version of the recoveriX system, which will have several improvements.

Cracking the neural code, treating paralysis and the future of bioelectronic medicine.

The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our overall health. Scientists and engineers have been working for decades to tap into this network and 'crack the neural code' by decoding neural signals and learning how to 'speak' the language of the nervous system. Progress has been made in developing neural decoding methods to decipher brain activity and bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and for diagnosing brain-related diseases such as Parkinson's and Alzheimer's disease. In a recent first-in-human study involving paralysis, a paralysed male study participant regained movement in his hand, years after his injury, through the use of a bioelectronic neural bypass. This work combined neural decoding and neurostimulation methods to translate and re-route signals around damaged neural pathways within the central nervous system. By extending these methods to decipher neural messages in the peripheral nervous system, status information from our bodily functions and specific organs could be gained. This, one day, could allow real-time diagnostics to be performed to give us a deeper insight into a patient's condition, or potentially even predict disease or allow early diagnosis. The future of bioelectronic medicine is extremely bright and is wide open as new diagnostic and treatment options are developed for patients around the world.

Method to test the long-term stability of functional electrical stimulation via multichannel electrodes (e.g., applicable for laryngeal pacing) and to define best points for stimulation: in vivo animal analysis.

The study aim was to identify and analyze intramuscular electrically sensitive points. Electrically sensitive points are herein defined as positions, which allow muscles stimulation with a minimum possible fatigue for a maximum amount of time. A multichannel array electrode was used which could be interesting to retain the function of larynx muscle after paralysis. Eight array electrodes were implanted in the triceps brachii muscle of four rats. While being under anesthesia, the animals were intramuscularly stimulated at 16 different positions. Sihler's staining technique was used to make visible the nerves routes and the intramuscular position of the individual electrode plate. The positions of the motor end plates were determined by means of multichannel-electromyography. The positions that allow longest stimulation periods are located close to the points where the nerves enter the muscle. Stimulation at the position of the motor end plates does not result in stimulation periods above average. Locations initially causing strong muscle contractions are not necessarily identical to the ones allowing long stimulation periods. The animal model identified the stimulation points for minimal possible muscle fatigue stimulation as being located close to the points of entrance of the nerve into the muscle. Stimulation causing an initially strong contraction response is no indication of optimal location of the stimulation electrode in terms of chronic stimulation. The array electrode of this study could be interesting as a stimulation electrode for a larynx pacemaker.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Postcontraction hyperemia after electrical stimulation: potential utility in rehabilitation of patients with upper extremity paralysis.

The purpose of this study was to compare postcontraction hyperemia after electrical stimulation between patients with upper extremity paralysis caused by upper motor neuron diseases and healthy controls. Thirteen healthy controls and eleven patients with upper extremity paralysis were enrolled. The blood flow in the basilic vein was measured by ultrasound before the electrical stimulation of the biceps brachii muscle and 30 s after the stimulation. The stimulation was performed at 10 mA and at a frequency of 70 Hz for 20 s. The mean blood flow in the healthy control group and in upper extremity paralysis group before the electrical stimulation was 60 ± 20 mL/min (mean ± SD) and 48 ± 25 mL/min, respectively. After the stimulation, blood flow in both groups increased to 117 ± 23 mL/min and 81 ± 41 mL/min, respectively. We show that it is possible to measure postcontraction hyperemia using an ultrasound system. In addition, blood flow in both groups increased after the electrical stimulation because of postcontraction hyperemia. These findings suggest that evaluating post contraction hyperemia in patients with upper extremity paralysis can assess rehabilitation effects.

Automatic determination of EMG-contaminated components and validation of independent component analysis using EEG during pharmacologic paralysis.

OBJECTIVE: Validate independent component analysis (ICA) for removal of EMG contamination from EEG, and demonstrate a heuristic, based on the gradient of EEG spectra (slope of graph of log EEG power vs log frequency, 7-70 Hz) from paralysed awake humans, to automatically identify and remove components that are predominantly EMG. METHODS: We studied the gradient of EMG-free EEG spectra to quantitatively inform the choice of threshold. Then, pre-existing EEG from 3 disparate experimental groups was examined before and after applying the heuristic to validate that the heuristic preserved neurogenic activity (Berger effect, auditory odd ball, visual and auditory steady state responses). RESULTS: (1) ICA-based EMG removal diminished EMG contamination up to approximately 50 Hz, (2) residual EMG contamination using automatic selection was similar to manual selection, and (3) task-induced cortical activity remained, was enhanced, or was revealed using the ICA-based methodology. CONCLUSION: This study further validates ICA as a powerful technique for separating and removing myogenic signals from EEG. Automatic processing based on spectral gradients to exclude EMG-containing components is a conceptually simple and valid technique. SIGNIFICANCE: This study strengthens ICA as a technique to remove EMG contamination from EEG whilst preserving neurogenic activity to 50 Hz.