Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica.

Here, we introduce the Tabulae Paralytica-a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

A Virtual Reality-Based Protocol to Determine the Preferred Control Strategy for Hand Neuroprostheses in People With Paralysis.

Hand neuroprostheses restore voluntary movement in people with paralysis through neuromodulation protocols. There are a variety of strategies to control hand neuroprostheses, which can be based on residual body movements or brain activity. There is no universally superior solution, rather the best approach may vary from patient to patient. Here, we propose a protocol based on an immersive virtual reality (VR) environment that simulates the use of a hand neuroprosthesis to allow patients to experience and familiarize themselves with various control schemes in clinically relevant tasks and choose the preferred one. We used our VR environment to compare two alternative control strategies over 5 days of training in four patients with C6 spinal cord injury: (a) control via the ipsilateral wrist, (b) control via the contralateral shoulder. We did not find a one-fits-all solution but rather a subject-specific preference that could not be predicted based only on a general clinical assessment. The main results were that the VR simulation allowed participants to experience the pros and cons of the proposed strategies and make an educated choice, and that there was a longitudinal improvement. This shows that our VR-based protocol is a useful tool for personalization and training of the control strategy of hand neuroprostheses, which could help to promote user comfort and thus acceptance.

The Promise of Endovascular Neurotechnology: A Brain-Computer Interface to Restore Autonomy to People With Motor Impairment.

ABSTRACT: This Joel A. DeLisa Lecture on endovascular brain-computer interfaces was presented by Dr Thomas Oxley on February 23, 2023, at the Association of Academic Physiatrists Annual Scientific Meeting. The lecture described how brain-computer interfaces replace lost physiological function to enable direct communication between the brain and external digital devices, such as computers, smartphones, and robotic limbs. Specifically, the potential of a novel endovascular brain-computer interface technology was discussed. The brain-computer interface uses a stent-electrode array delivered via the jugular vein and is permanently implanted in a vein adjacent to the motor cortex. In a first-in-human clinical trial, participants with upper limb paralysis who received the endovascular brain-computer interface could use the system independently and at home to operate laptop computers for various instrumental activities of daily living. A Food and Drug Administration-approved trial of the endovascular brain-computer interface in the United States is in progress. Future development of the system will provide recipients with continuous autonomy through digital access with minimal caregiver assistance. Physiatrists and occupational therapists will have a vital role in helping people with paralysis achieve the potential of implantable brain-computer interfaces.

A high-performance speech neuroprosthesis.

Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text1,2 or sound3,4. Early demonstrations, although promising, have not yet achieved accuracies sufficiently high for communication of unconstrained sentences from a large vocabulary1-7. Here we demonstrate a speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant-who can no longer speak intelligibly owing to amyotrophic lateral sclerosis-achieved a 9.1% word error rate on a 50-word vocabulary (2.7 times fewer errors than the previous state-of-the-art speech BCI2) and a 23.8% word error rate on a 125,000-word vocabulary (the first successful demonstration, to our knowledge, of large-vocabulary decoding). Our participant's attempted speech was decoded  at 62 words per minute, which is 3.4 times as fast as the previous record8 and begins to approach the speed of natural conversation (160 words per minute9). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for restoring rapid communication to people with paralysis who can no longer speak.

A high-performance neuroprosthesis for speech decoding and avatar control.

Speech neuroprostheses have the potential to restore communication to people living with paralysis, but naturalistic speed and expressivity are elusive1. Here we use high-density surface recordings of the speech cortex in a clinical-trial participant with severe limb and vocal paralysis to achieve high-performance real-time decoding across three complementary speech-related output modalities: text, speech audio and facial-avatar animation. We trained and evaluated deep-learning models using neural data collected as the participant attempted to silently speak sentences. For text, we demonstrate accurate and rapid large-vocabulary decoding with a median rate of 78 words per minute and median word error rate of 25%. For speech audio, we demonstrate intelligible and rapid speech synthesis and personalization to the participant's pre-injury voice. For facial-avatar animation, we demonstrate the control of virtual orofacial movements for speech and non-speech communicative gestures. The decoders reached high performance with less than two weeks of training. Our findings introduce a multimodal speech-neuroprosthetic approach that has substantial promise to restore full, embodied communication to people living with severe paralysis.

Intelligent Classification Technique of Hand Motor Imagery Using EEG Beta Rebound Follow-Up Pattern.

To apply EEG-based brain-machine interfaces during rehabilitation, separating various tasks during motor imagery (MI) and assimilating MI into motor execution (ME) are needed. Previous studies were focusing on classifying different MI tasks based on complex algorithms. In this paper, we implement intelligent, straightforward, comprehensible, time-efficient, and channel-reduced methods to classify ME versus MI and left- versus right-hand MI. EEG of 30 healthy participants undertaking motional tasks is recorded to investigate two classification tasks. For the first task, we first propose a "follow-up" pattern based on the beta rebound. This method achieves an average classification accuracy of 59.77% ± 11.95% and can be up to 89.47% for finger-crossing. Aside from time-domain information, we map EEG signals to feature space using extraction methods including statistics, wavelet coefficients, average power, sample entropy, and common spatial patterns. To evaluate their practicability, we adopt a support vector machine as an intelligent classifier model and sparse logistic regression as a feature selection technique and achieve 79.51% accuracy. Similar approaches are taken for the second classification reaching 75.22% accuracy. The classifiers we propose show high accuracy and intelligence. The achieved results make our approach highly suitable to be applied to the rehabilitation of paralyzed limbs.

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

A wireless controlled intelligent healthcare system for diplegia patients.

Rehabilitation engineering is playing a more vital role in the field of healthcare for humanity. It is providing many assistive devices to diplegia patients (The patients whose conditions are weak in terms of muscle mobility on both sides of the body and their paralyzing effects are high either in the arms or in the legs). Therefore, in order to rehabilitate such types of patients, an intelligent healthcare system is proposed in this research. The electric sticks and chairs are also a type of this system which was used previously to facilitate the diplegia patients. It is worth noting that a voice recognition system along with wireless control feature has been integrated intelligently in the proposed healthcare system in order to replace the common and conventional assistive tools for diplegia patients. These features will make the proposed system more user friendly, convenient and comfortable. The voice recognition system has been used for movements of system in any desired direction along with the ultrasonic sensor and light detecting technology. These sensors detect the obstacles and low light environment intelligently during the movement of the wheelchair and then take the necessary actions accordingly.

Does a combination treatment of repetitive transcranial magnetic stimulation and occupational therapy improve upper limb muscle paralysis equally in patients with chronic stroke caused by cerebral hemorrhage and infarction?: A retrospective cohort study.

ABSTRACT: The clinical presentation of stroke is usually more severe in patients with intracerebral hemorrhage (ICH) than in those with cerebral infarction (CI); recovery of stroke-related muscle paralysis is influenced and limited by the type of stroke. To date, many patients have been treated by neurorehabilitation; however, the changes in the recovery of motor paralysis depending on the type of stroke, ICH or CI, have not been established. This study aimed to determine this difference in improvement of upper extremity paralysis using 2-week in-hospital NovEl intervention Using Repetitive transcranial magnetic stimulation combined with Occupational therapy (NEURO).We scrutinized the medical records of all patients with poststroke (ICH or CI) upper extremity muscle paralysis using Fugl-Meyer assessments (FMAs) who had been admitted to 6 hospitals between March 2010 and December 2018 for rehabilitation treatment. This was a multiinstitutional, open-label, retrospective cohort study without control patients. We evaluated the effects of NEURO on patients with CI and ICH by dividing them into 2 groups according to the type of stroke, after adjustment for age, sex, dominant hand, affected hand side, time since stroke, and prediction of recovery capacity in the upper extremity.The study included 1716 (CI [n = 876] and ICH [n = 840]) patients who had undergone at least 2 FMAs and had experienced stroke at least 6 months before. The type of stroke had no effect on the outcomes (changes in the FMA-upper extremity score, F[4,14.0] = 2.05, P = .09, partial η2 = 0.01). Patients from all 5 groups equally benefited from the treatment (improvement in FMA scores) according to the sensitivity analysis-stratified analysis (F = 0.08 to 1.94, P > .16, partial η2 < 0.001).We conclude that NEURO can be recommended for chronic stroke patients irrespective of the type of stroke.

Adjustment effect during shoulder abduction training with the Hybrid Assistive Limb in a patient with postoperative C5 palsy.

Standard shoulder rehabilitation procedures for patients with postoperative C5 palsy have not yet been established. We applied a wearable robot suit hybrid assistive limb (HAL) for a patient with postoperative C5 palsy and conducted shoulder abduction training with HAL. A 65-year-old woman was diagnosed with postoperative C5 palsy after undergoing cervical spine surgery. Five days after surgery, shoulder abduction training with HAL was initiated. The shoulder abduction angle and power and trapezius and deltoid activities were evaluated. Ten rehabilitation sessions were conducted until 82 days after surgery. Shoulder abduction training was safely and effectively performed from the first session. Her shoulder abduction angle and power improved at every session, and she could fully elevate her arm without any compensatory motion after the 10th session. Shoulder HAL training suppressed the muscular activity of the trapezius and activated that of the deltoid, especially in the earlier stages of rehabilitation. Moreover, it had an adjustment effect for obtaining normal shoulder motion, which might have promoted smoother arm elevation using errorless motor learning. These findings suggest that HAL is a useful tool for shoulder rehabilitation in patients with postoperative C5 palsy.

Goal attainment in mobility after acute rehabilitation of mobility-restricting paralysis syndromes with regard to the ambulatory therapeutic level of participation NeuroMoves : A German national multicenter observational cohort study.

BACKGROUND: A central goal of rehabilitation in patients with paralysis syndromes after stroke or spinal cord injury (SCI) is to restore independent mobility as a pedestrian or wheelchair user. However, after acute rehabilitation, the mobility frequently deteriorates in the ambulatory setting, despite the delivery of rehabilitative interventions such as physical therapy or the prescription of assistive devices. The aim of the NeuroMoves study is to identify factors that are associated with changes of mobility in the ambulatory setting after acute inpatient rehabilitation, with a particular focus on participation according to the ICF (International Classification of Functioning, Disability and Health). METHODS: The NeuroMoves study is intended as a national multicenter observational cohort study with 9 clinical sites in Germany. A total of 500 patients with mobility-restricting paralysis syndromes (i.e. stroke or SCI) are to be recruited during acute inpatient rehabilitation prior to discharge to the ambulatory setting. Patients will have 8 months of follow-up in the ambulatory setting. Three study visits at the clinical sites (baseline, midterm, and final) are planned at 4-months intervals. The baseline visit is scheduled at the end of the acute inpatient rehabilitation. During the visits, demographical data, neurological, functional, quality of life, and implementation measures will be assessed. At baseline, each study participant receives an activity tracker (sensor for recording ambulatory mobility) along with a tablet computer for home use over the 8 months study duration. While mounted, the activity tracker records mobility data from which the daily distance covered by walking or wheelchair use can be calculated. Customized applications on the tablet computer remind the study participants to answer structured questionnaires about their health condition and treatment goals for physical therapy. Using the study participants' tablet, therapists will be asked to answer structured questionnaires concerning treatment goals and therapeutic measures they have applied. The primary analysis concerns the association between mobility (daily distance covered) and the degree of participation-oriented rehab interventions. Further exploratory analyses are planned. DISCUSSION: The findings could inform healthcare decision-making regarding ambulatory care in Germany focusing on mobility-promoting interventions for patients with mobility-restricting paralysis syndromes. STUDY REGISTRATION: German Clinical Trials Register, DRKS-ID: DRKS00020487 (18.02.2020).

Factors related to daily use of the paretic upper limb in patients with chronic hemiparetic stroke-A retrospective cross-sectional study.

AIMS: The present study aimed to determine factors associated with the frequency of paralyzed upper extremity (UE) use in chronic stroke patients with severe UE functional deficiency. METHODS: We retrospectively reviewed the medical records of 138 consecutive patients, and 117 was analyzed (median age, 55 [range, 18-85] years; median stroke duration, 24.5 [range, 7-302] months) with chronic hemiparetic stroke who were admitted to our hospital for intensive upper extremity rehabilitation. The mean Fugl-Meyer Assessment (FMA) UE score was 28.6. All of them are independent in their activity of daily living (ADL) and without remarkable cognitive deficits. Amount-of-use score of Motor Activity Log-14 (MAL-AOU) was applied as the index of daily use of affected UE. The following parameters were examined as the explanatory variables: demographics, proximal and distal sub-scores of FMA UE, Modified Ashworth Scale (MAS), and sensory function scores in the Stroke Impairment Assessment Set (SIAS). RESULTS: The median MAL-AOU score was 0.57 [range, 0.28-0.80]. Ordinal regression analysis revealed that FMA proximal, FMA distal, and SIAS sensory function (touch) were associated with AOU score of MAL-14 (Pseudo R-square = 0.460). CONCLUSION: Not only motor but also sensory function, especially tactile sensation, play a crucial role in the daily use of affected UE in chronic stroke patients with severe UE hemiparesis.

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.

Rehabilitation Protocol for Unilateral Laryngeal and Lingual Paralysis (Tapia Syndrome): Comment About "A Challenging Case of Tapia Syndrome After Total Thyroidectomy" By Ildem Deveci, Mehmet Surmeli, and Reyhan Surmeli.

Tapia syndrome is a rare complication after surgery, with ipsilateral paralysis of vocal cord and tongue due to extracranial involvement of recurrent laryngeal and hypoglossal nerves. Tapia's case report is extremely interesting for both the rarity of the reported cases and for the importance of an early rehabilitation. In a previous work, we reported a case of Tapia syndrome after cardiac surgery for aortic aneurysm, and the protocol of logopedic rehabilitation adopted. In the postoperative period, he developed severe dyspnea and dysphagia that required a tracheostomy and a logopedic rehabilitation therapy that led to a fast and efficient swallowing without aspiration after 47 sessions (less than 4 months). The progressive recovery of the function suggests aprassic nerve damage. However, the logopedic therapy is recommended to limit the possibility of permanent functional deficits and quickly recover swallowing and phonation.

Chronic nerve health following implantation of femoral nerve cuff electrodes.

BACKGROUND: Peripheral nerve stimulation with implanted nerve cuff electrodes can restore standing, stepping and other functions to individuals with spinal cord injury (SCI). We performed the first study to evaluate the clinical electrodiagnostic changes due to electrode implantation acutely, chronic presence on the nerve peri- and post-operatively, and long-term delivery of electrical stimulation. METHODS: A man with bilateral lower extremity paralysis secondary to cervical SCI sustained 5 years prior to enrollment received an implanted standing neuroprosthesis including composite flat interface nerve electrodes (C-FINEs) electrodes implanted around the proximal femoral nerves near the inguinal ligaments. Electromyography quantified neurophysiology preoperatively, intraoperatively, and through 1 year postoperatively. Stimulation charge thresholds, evoked knee extension moments, and weight distribution during standing quantified neuroprosthesis function over the same interval. RESULTS: Femoral compound motor unit action potentials increased 31% in amplitude and 34% in area while evoked knee extension moments increased significantly (p < 0.01) by 79% over 1 year of rehabilitation with standing and quadriceps exercises. Charge thresholds were low and stable, averaging 19.7 nC ± 6.2 (SEM). Changes in saphenous nerve action potentials and needle electromyography suggested minor nerve irritation perioperatively. CONCLUSIONS: This is the first human trial reporting acute and chronic neurophysiologic changes due to application of and stimulation through nerve cuff electrodes. Electrodiagnostics indicated preserved nerve health with strengthened responses following stimulated exercise. Temporary electrodiagnostic changes suggest minor nerve irritation only intra- and peri-operatively, not continuing chronically nor impacting function. These outcomes follow implantation of a neuroprosthesis enabling standing and demonstrate the ability to safely implant electrodes on the proximal femoral nerve close to the inguinal ligament. We demonstrate the electrodiagnostic findings that can be expected from implanting nerve cuff electrodes and their time-course for resolution, potentially applicable to prostheses modulating other peripheral nerves and functions. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923662 , retrospectively registered August 15, 2013.

Walking characteristics including mild motor paralysis and slow walking speed in post-stroke patients.

Walking speed is strongly influenced by the severity of motor paralysis in post-stroke patients. Nevertheless, some patients with mild motor paralysis still walk slowly. Factors associated with this difference in walking speed have not been elucidated. To confirm walking characteristics of patients with mild motor paralysis and slow walking speed, this study identified patient subgroups based on the association between the severity of motor paralysis and walking speed. Fugl-Meyer assessment synergy score (FMS) and the walking speed were measured (n = 42), and cluster analysis was performed based on the association between FMS and walking speed to identify the subgroups. FMS and walking speed were associated (ρ = 0.50); however, some patients walked slowly despite only mild motor paralysis. Cluster analysis using FMS and walking speed as the main variables classified patients into subgroups. Patients with mild motor paralysis (FMS: 18.4 ± 2.09 points) and slow walking speed (0.28 ± 0.14 m/s) exhibited poorer trunk stability, increased co-contraction of the shank muscle, and increased intramuscular coherence in walking compared to other clusters. This group was identified by their inability to fully utilize the residual potential of motor function. In walking training, intervention in instability and excessive cortical control may be effective.

Auditory Electrooculogram-based Communication System for ALS Patients in Transition from Locked-in to Complete Locked-in State.

Patients in the transition from locked-in (i.e., a state of almost complete paralysis with voluntary eye movement control, eye blinks or twitches of face muscles, and preserved consciousness) to complete locked-in state (i.e., total paralysis including paralysis of eye-muscles and loss of gaze-fixation, combined with preserved consciousness) are left without any means of communication. An auditory communication system based on electrooculogram (EOG) was developed to enable such patients to communicate. Four amyotrophic lateral sclerosis patients in transition from locked-in state to completely locked-in state, with ALSFRS-R score of 0, unable to use eye trackers for communication, learned to use an auditory EOG-based communication system. The patients, with eye-movement amplitude between the range of ±200µV and ±40µV, were able to form complete sentences and communicate independently and freely, selecting letters from an auditory speller system. A follow-up of one year with one patient shows the feasibility of the proposed system in long-term use and the correlation between speller performance and eye-movement decay. The results of the auditory speller system have the potential to provide a means of communication to patient populations without gaze fixation ability and with low eye-movement amplitude range.

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.