Learned Motor Patterns Are Replayed in Human Motor Cortex during Sleep.

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep. A 36-year-old man with tetraplegia secondary to cervical spinal cord injury enrolled in the ongoing BrainGate brain-computer interface pilot clinical trial had two 96-channel intracortical microelectrode arrays placed chronically into left precentral gyrus. Single- and multi-unit activity was recorded while he played a color/sound sequence matching memory game. Intended movements were decoded from motor cortical neuronal activity by a real-time steady-state Kalman filter that allowed the participant to control a neurally driven cursor on the screen. Intracortical neural activity from precentral gyrus and 2-lead scalp EEG were recorded overnight as he slept. When decoded using the same steady-state Kalman filter parameters, intracortical neural signals recorded overnight replayed the target sequence from the memory game at intervals throughout at a frequency significantly greater than expected by chance. Replay events occurred at speeds ranging from 1 to 4 times as fast as initial task execution and were most frequently observed during slow-wave sleep. These results demonstrate that recent visuomotor skill acquisition in humans may be accompanied by replay of the corresponding motor cortex neural activity during sleep.SIGNIFICANCE STATEMENT Within cortex, the acquisition of information is often followed by the offline recapitulation of specific sequences of neural firing. Replay of recent activity is enriched during sleep and may support the consolidation of learning and memory. Using an intracortical brain-computer interface, we recorded and decoded activity from motor cortex as a human research participant performed a novel motor task. By decoding neural activity throughout subsequent sleep, we find that neural sequences underlying the recently practiced motor task are repeated throughout the night, providing direct evidence of replay in human motor cortex during sleep. This approach, using an optimized brain-computer interface decoder to characterize neural activity during sleep, provides a framework for future studies exploring replay, learning, and memory.

Controlling an effector with eye movements: The effect of entangled sensory and motor responsibilities.

Restoring arm and hand function has been indicated by individuals with tetraplegia as one of the most important factors for regaining independence. The overall goal of our research is to develop assistive technologies that allow individuals with tetraplegia to control functional reaching movements. This study served as an initial step toward our overall goal by assessing the feasibility of using eye movements to control the motion of an effector in an experimental environment. We aimed to understand how additional motor requirements placed on the eyes affected eye-hand coordination during functional reaching. We were particularly interested in how eye fixation error was affected when the sensory and motor functions of the eyes were entangled due to the additional motor responsibility. We recorded participants' eye and hand movements while they reached for targets on a monitor. We presented a cursor at the participant's point of gaze position which can be thought of as being similar to the control of an assistive robot arm. To measure eye fixation error, we used an offline filter to extract eye fixations from the raw eye movement data. We compared the fixations to the locations of the targets presented on the monitor. The results show that not only are humans able to use eye movements to direct the cursor to a desired location (1.04 ± 0.15 cm), but they can do so with error similar to that of the hand (0.84 ± 0.05 cm). In other words, despite the additional motor responsibility placed on the eyes during direct eye-movement control of an effector, the ability to coordinate functional reaching movements was unaffected. The outcomes of this study support the efficacy of using the eyes as a direct command input for controlling movement.

Epidural stimulation with locomotor training ameliorates unstable blood pressure after tetraplegia. A case report.

A male with C7 complete tetraplegia participated in 14 weeks of body weight supported treadmill training (BWSTT) combined with spinal cord epidural stimulation (SCES), 4 weeks of no intervention, and two more weeks of BWSTT + SCES. The participant presented with unstable resting seated blood pressure (BP; 131/66 mmHg). After retrospective analysis, resting systolic BP decreased and diastolic BP increased, yielding a safe mean arterial BP. There was a fivefold increase in BWSTT bouts per session, and percentage of body weight support decreased to 69%. BWSTT + SCES safely and effectively regulated resting BP and mitigated symptoms of orthostatic intolerance. These effects were not maintained after 4 weeks without training.

Sensing and decoding the neural drive to paralyzed muscles during attempted movements of a person with tetraplegia using a sleeve array.

Motor neurons convey information about motor intent that can be extracted and interpreted to control assistive devices. However, most methods for measuring the firing activity of single neurons rely on implanted microelectrodes. Although intracortical brain-computer interfaces (BCIs) have been shown to be safe and effective, the requirement for surgery poses a barrier to widespread use that can be mitigated by instead using noninvasive interfaces. The objective of this study was to evaluate the feasibility of deriving motor control signals from a wearable sensor that can detect residual motor unit activity in paralyzed muscles after chronic cervical spinal cord injury (SCI). Despite generating no observable hand movement, volitional recruitment of motor units below the level of injury was observed across attempted movements of individual fingers and overt wrist and elbow movements. Subgroups of motor units were coactive during flexion or extension phases of the task. Single digit movement intentions were classified offline from the electromyogram (EMG) power [root-mean-square (RMS)] or motor unit firing rates with median classification accuracies >75% in both cases. Simulated online control of a virtual hand was performed with a binary classifier to test feasibility of real-time extraction and decoding of motor units. The online decomposition algorithm extracted motor units in 1.2 ms, and the firing rates predicted the correct digit motion 88 ± 24% of the time. This study provides the first demonstration of a wearable interface for recording and decoding firing rates of motor units below the level of injury in a person with motor complete SCI.NEW & NOTEWORTHY A wearable electrode array and machine learning methods were used to record and decode myoelectric signals and motor unit firing in paralyzed muscles of a person with motor complete tetraplegia. The myoelectric activity and motor unit firing rates were task specific, even in the absence of visible motion, enabling accurate classification of attempted single-digit movements. This wearable system has the potential to enable people with tetraplegia to control assistive devices through movement intent.

Toward Consensus in Assessing Upper Limb Muscle Strength and Pinch and Grip Strength in People With Tetraplegia Having Upper Limb Reconstructions.

OBJECTIVES: To reach agreement on standardized protocols for assessing upper limb strength and grip and pinch force for upper limb reconstructive surgery for tetraplegia. METHODS: Selected members of an expert panel composed of international therapists formed at the 2018 International Congress for Upper Limb Surgery for Tetraplegia conducted a literature review of current practice that identified gaps and inconsistencies in measurement protocols and presented to workshop attendees. To resolve discrepancies, a set of questions was presented to workshop attendees who voted electronically. Consensus was set at 75% agreement. RESULTS: For manual muscle testing, consensus was reached for using the Medical Research Council scale, without plus or minus, and the use of resistance through range when testing grade 4 and grade 5 strength. Pectoralis major and serratus anterior should be routinely tested, however there was no consensus on other shoulder muscles. Grip and pinch strength should be tested according to the American Society of Hand Therapists positioning. For grip strength, either the Jamar or Biometrics dynamometer expressed in kilograms should be used. For grip and pinch strength, three measurements should be performed at each testing. No consensus was reached on a device for pinch strength. CONCLUSION: This work is an important step to enable comparable data in the future. Further consensus methods will work toward developing more comprehensive guidelines in this population. Building international consensus for pre- and postoperative measures of function supports objective evaluation of novel therapies and interpretation of multicenter studies.

Acute non-traumatic tetraparesis - Differential diagnosis.

INTRODUCTION: Potentially life-threatening disorders may present in the emergency department with acute tetraparesis, and their recognition is crucial for an appropriate management and timely treatment. Our review aims to systematize the differential diagnosis of acute non-traumatic tetraparesis. RESULTS: Causes of tetraparesis can be classified based on the site of defect: upper motor neuron (UMN), peripheral nerve, neuromuscular junction or muscle. History of present illness should include the distribution of weakness (symmetric/asymmetric or distal/proximal/diffuse) and associated clinical features (pain, sensory findings, dysautonomia, and cranial nerve abnormalities such as diplopia and dysphagia). Neurological examination, particularly tendon reflexes, helps further in the localization of nerve lesions and distinction between UMN and lower motor neuron. Ancillary studies include blood and cerebral spinal fluid analysis, neuroaxis imaging, electromyography, muscle magnetic resonance and muscle biopsy. CONCLUSIONS: Acute tetraparesis is still a debilitating and potentially serious neurological condition. Despite all the supplementary ancillary tests, the neurological examination is the key to achieve a correct diagnosis. The identification of life-threatening neurologic disorders is pivotal, since failing to identify patients at risk of complications, such as acute respiratory failure, may have catastrophic results.

Non-Dolichoectatic Vertebral Artery Compression of the Medulla: A Comprehensive Literature Review.

OBJECTIVE: Vertebral artery compression of the medulla is a rare vascular finding that causes a variety of clinical presentations, from asymptomatic to neurological disability. This article presents the largest literature review to date on medullary compression of the vertebral arteries. METHODS: An English literature search was performed using the PubMed database and the keywords vertebral artery tortuosity, vertebral artery compression, and medullary compression. RESULTS: A comprehensive literature search yielded 68 patients (57% male) with medullary compression by an intracranial vertebral artery (ICVA). The left side of the medulla was compressed in 44, the right side in 19, and bilateral in 7. The most common clinical symptom was weakness - 26 patients (36%) - 6 had quadriparesis and 6 had hemiparesis. 21 patients reported imbalance; 12 various sensory symptoms; 4 patients were asymptomatic. CONCLUSIONS: Understanding the anatomy of the vasculature can help mitigate future debilitating stroke symptoms. Concrete guidelines for revascularization surgery in symptomatic patients may also be effective. Future studies are needed to further clarify the prevalence, natural history, vascular etiology, and treatment of this condition, including asymptomatic patients and the likelihood that they will develop further neurological signs and disability.

Severe acute myopathy following SARS-CoV-2 infection: a case report and review of recent literature.

BACKGROUND: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION: We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.

Extended post-exercise hyperthermia in athletes with a spinal cord injury.

OBJECTIVES: Determine the extent and underlying causes of post-exercise hyperthermia in athletes with a spinal cord injury following exercise. DESIGN: Observational. METHODS: Thirty-one males (8 with tetraplegia [TP; C5-C8], 7 with high paraplegia [HP; T1-T5], 8 with low paraplegia [LP; T6-L1] and 8 able-bodied [AB]), recovered in 35°C/50%RH for 45min after 30-min of exercise at a metabolic heat production (Hprod) of 4.0W/kg (AB vs TP) or 6.0W/kg (AB vs HP vs LP). Esophageal (Tes), gastrointestinal (Tgi) and skin temperatures, Hprod, local sweat rate (LSR) and mean arterial pressure were measured. RESULTS: TP maintained a higher Tes (38.05°C [95% CI: 37.83°C, 38.28°C], AB: 36.77°C [36.56°C, 36.98°C], p<0.001) and Tgi (TP: 38.36°C [38.15°C, 38.58°C], AB: 37.26°C [37.04°C, 37.47°C], p<0.001), with peak values observed 45min post-exercise. Core temperatures all declined in HP, LP and AB, but HP maintained a higher Tes than AB (p=0.030), and higher Tgi than LP and AB (p=0.019). No differences in post-exercise Hprod were observed between TP and AB (p=0.264), or HP, LP and AB (p=0.124). Evaporative heat loss was estimated to be zero in TP, while back LSR was greater in HP than LP (p=0.009). Minimal dry heat loss occurred in SCI groups (TP: 9W/m2 [6, 12], HP: 4W/m2 [1, 6], LP: 2W/m2 [0, 5]). CONCLUSIONS: Substantial post-exercise hyperthermia is evident in TP (∼1.4°C hotter than AB after 45min of post-exercise recovery) due to minimal evaporation. HP have delayed post-exercise thermoregulatory recovery whereas LP respond similarly to AB.

[Nerve transfer in patients with tetraplegia: improvement in hand function]. / Zenuwtransfer bij patiënten met een tetraplegie.

Reconstruction of arm and hand function in patients with a cervical spinal cord injury can improve their quality of life. Elbow extension, wrist extension, grip function and opening of the hand can be reconstructed. Traditionally, this has been done through tendon transpositions. Nerve transfer is a new technique. A functioning motor nerve branch is moved and connected to a muscle or muscle group damaged by the spinal cord injury. This technique has several advantages. Multiple functions can be restored by one nerve transfer, no long-term hand-rehabilitation is required and there is no risk of adhesions of the transposition. The most important disadvantage is the recovery time, as a results of the slow ingrowth of the nerve transfer, which takes at least 12 to 18 months. For each spinal cord injury patient, an individual action plan must be made, because not every patient has the same options and these are sometimes very limited.

Diverse manifestations of a sickle cell crisis.

We describe the case of a 21-year-old man with a background of sickle cell disease (SCD) who was on acute presentation in a sickle cell crisis required immediate intensive care admission with red blood cell exchange and ventilatory support. He had right frontal lobe infarcts and extensive bilateral deep white matter lesions most likely secondary to fat embolism. Inpatient investigations demonstrated a patent foramen ovale, explaining the route of spread of the fat embolus. He then had a transcatheter closure of the atrial defect. The patient needed prolonged inpatient rehabilitation. He was discharged from hospital in a wheelchair secondary to severe lower limb neurology and bilateral knee heterotopic ossification. He lives with the possibility of early onset dementia and cognitive decline, requiring constant care. The case highlights the multiple manifestations of SCD and their diverse and debilitating consequences.

Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord.

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.

Auditory cues reveal intended movement information in middle frontal gyrus neuronal ensemble activity of a person with tetraplegia.

Intracortical brain-computer interfaces (iBCIs) allow people with paralysis to directly control assistive devices using neural activity associated with the intent to move. Realizing the full potential of iBCIs critically depends on continued progress in understanding how different cortical areas contribute to movement control. Here we present the first comparison between neuronal ensemble recordings from the left middle frontal gyrus (MFG) and precentral gyrus (PCG) of a person with tetraplegia using an iBCI. As expected, PCG was more engaged in selecting and generating intended movements than in earlier perceptual stages of action planning. By contrast, MFG displayed movement-related information during the sensorimotor processing steps preceding the appearance of the action plan in PCG, but only when the actions were instructed using auditory cues. These results describe a previously unreported function for neurons in the human left MFG in auditory processing contributing to motor control.

Myeloradiculoneuropathy due to vitamin B12 deficiency: an unusual clinical and radiological presentation.

A 42-year-old man from rural India presented with asymmetric progressive paraparesis mimicking compressive dorsal myelopathy, followed by distal upper limb, truncal and neck-flexor weakness, further complicated by acute urinary retention. His sensory deficits were marked by loss of joint position sense (JPS) and graded loss of vibration sense, along with a definite sensory level. Deep tendon jerks were hypo-to-areflexic, plantar was bilaterally extensor. He had become less attentive and occasionally failed to keep track with conversations. A syndromic diagnosis of myeloradiculoneuropathy with cognitive impairments was made. Further tailored investigations revealed vitamin B12 deficiency with positive anti-parietal cell antibody. Diagnosis of subacute combined cord degeneration (SACD) was confirmed. Neuro-imaging revealed intramedullary intensity changes only along lateral aspect of spinal cord instead of characteristic posterior involvement. Following parenteral vitamin B12 supplementation, patient started showing improvement in motor power and subjective sensory symptoms. His bladder symptoms persisted initially, however recovered finally after 6 months.

Classification of Congenital Zika Syndrome: Muscle Tone, Motor Type, Body Segments Affected, and Gross Motor Function.

Aim: To identify abnormalities in muscle tone and motor function associated with congenital Zika syndrome (CZS).Method: A cross-sectional observational study involving 96 children (55 males) with CZS at a mean (SD) age 35.2 ± 2.9 months. Children's muscle tone was investigated using the pull to sit, scarf sign, shoulder suspension and ventral suspension tests and the modified Ashworth scale (MAS). Motor impairment was determined using the Gross Motor Function Classification System (GMFCS) and body segments most affected with motor impairment.Results: 58 (60,5%) children tested positive for ≥1 maneuver used to evaluate muscle tone, while 38 (39.5%) tested negative in all the tests. MAS score was >0 for at least one of the appendicular muscles in 91 children (94.8%). In 88 children (91.7%), all four limbs were affected.Conclusion: Findings suggestive of axial hypotonia and appendicular hypertonia associated with severe motor impairment were prevalent in children with CZS.

An investigation into the validity and reliability of the Chinese version of Spinal Cord Independence Measure III (SCIM III).

OBJECTIVE: To investigate the validity and reliability of a Chinese version of Spinal Cord Independence Measure III (SCIM III) in individuals with spinal cord injury. DESIGN: Study on psychometric properties. SETTING: An inpatient rehabilitation facility in China. SUBJECTS: 102 participants with spinal cord injury. Mean (SD) age was 48.8 (15.6) years; tetraplegia/paraplegia ratio was 50/52; median time post injury was 2 months. INTERVENTION: SCIM III was translated into Chinese. Chinese versions of Barthel Index and SCIM III were filled out for each participant by Rater 1. SCIM III was then administered by Rater 2 after 24 hours (n = 67) and 7 days (n = 65). MAIN MEASURES: Validity, inter-rater/test-retest reliability, and internal consistency of the Chinese version of SCIM III. RESULTS: The total scores between the two raters were similar (mean ± SD: 33.8 ± 25.8 vs 33.8 ± 25.5, P = 0.95). Total agreement between the raters in each item was >80%, with both Pearson and intraclass correlation coefficients >0.97 (P < 0.01) for each subscale and total score. The Pearson correlation coefficients of the two independent assessments performed by Rater 2 were also >0.97 (P < 0.01) for each subscale and the total score. Cronbach α was >0.7 for each subscale and the total score for both raters. High consistency was found between Barthel Index and SCIM III total scores (Pearson correlation coefficient = 0.88, P < 0.01). CONCLUSION: The Chinese version of SCIM III is valid and reliable for the functional assessment of patients with SCI.

Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia.

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI. During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. During AIH, participants were exposed to brief alternating episodes of hypoxic inspired gas (1 min episodes of 9% O2) and room air (1 min episodes of 20.9% O2). We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses of hand motoneurons can be potentiated by AIH. The possibility of different thresholds for physiological vs behavioral gains needs to be considered during combinatorial treatments.

Is Guillain-Barrè syndrome triggered by SARS-CoV-2? Case report and literature review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for coronavirus disease 2019 (COVID-19). Respiratory and gastrointestinal manifestations of SARS-CoV-2 are well described, less defined is the clinical neurological spectrum of COVID-19. We reported a case of COVID-19 patient with acute monophasic Guillain-Barré syndrome (GBS), and a literature review on the SARS-CoV-2 and GBS etiological correlation. CASE DESCRIPTION: A 68 years-old man presented to the emergency department with symptoms of acute progressive symmetric ascending flaccid tetraparesis. Oropharyngeal swab for SARS-CoV-2 tested positive. Neurological examination showed bifacial nerve palsy and distal muscular weakness of lower limbs. The cerebrospinal fluid assessment showed an albuminocytologic dissociation. Electrophysiological studies showed delayed distal latencies and absent F waves in early course. A diagnosis of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) subtype of GBS was then made. CONCLUSIONS: Neurological manifestations of COVID-19 are still under study. The case we described of GBS in COVID-19 patient adds to those already reported in the literature, in support of SARS-CoV-2 triggers GBS. COVID-19 associated neurological clinic should probably be seen not as a corollary of classic respiratory and gastrointestinal symptoms, but as SARS-CoV-2-related standalone clinical entities. To date, it is essential for all Specialists, clinicians and surgeons, to direct attention towards the study of this virus, to better clarify the spectrum of its neurological manifestations.

Caring for Patients with Spinal Cord Injuries.

The column in this issue is supplied by Juan Jose Olivero, MD, who was a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program before his retirement in 2019. Dr. Olivero obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas. He currently serves on the journal's editorial board and is editor of the "Points to Remember" section.