Recovered grasping performance after stroke depends on interhemispheric frontoparietal connectivity.

Activity changes in the ipsi- and contralesional parietal cortex and abnormal interhemispheric connectivity between these regions are commonly observed after stroke, however, their significance for motor recovery remains poorly understood. We here assessed the contribution of ipsilesional and contralesional anterior intraparietal cortex (aIPS) for hand motor function in 18 recovered chronic stroke patients and 18 healthy control subjects using a multimodal assessment consisting of resting-state functional MRI, motor task functional MRI, online-repetitive transcranial magnetic stimulation (rTMS) interference, and 3D movement kinematics. Effects were compared against two control stimulation sites, i.e. contralesional M1 and a sham stimulation condition. We found that patients with good motor outcome compared to patients with more substantial residual deficits featured increased resting-state connectivity between ipsilesional aIPS and contralesional aIPS as well as between ipsilesional aIPS and dorsal premotor cortex. Moreover, interhemispheric connectivity between ipsilesional M1 and contralesional M1 as well as ipsilesional aIPS and contralesional M1 correlated with better motor performance across tasks. TMS interference at individual aIPS and M1 coordinates led to differential effects depending on the motor task that was tested, i.e. index finger-tapping, rapid pointing movements, or a reach-grasp-lift task. Interfering with contralesional aIPS deteriorated the accuracy of grasping, especially in patients featuring higher connectivity between ipsi- and contralesional aIPS. In contrast, interference with the contralesional M1 led to impaired grasping speed in patients featuring higher connectivity between bilateral M1. These findings suggest differential roles of contralesional M1 and aIPS for distinct aspects of recovered hand motor function, depending on the reorganization of interhemispheric connectivity.

Towards efficient motor imagery interventions after lower-limb amputation.

BACKGROUND: The therapeutic benefits of motor imagery (MI) are now well-established in different populations of persons suffering from central nervous system impairments. However, research on similar efficacy of MI interventions after amputation remains scarce, and experimental studies were primarily designed to explore the effects of MI after upper-limb amputations. OBJECTIVES: The present comparative study therefore aimed to assess the effects of MI on locomotion recovery following unilateral lower-limb amputation. METHODS: Nineteen participants were assigned either to a MI group (n = 9) or a control group (n = 10). In addition to the course of physical therapy, they respectively performed 10 min per day of locomotor MI training or neutral cognitive exercises, five days per week. Participants' locomotion functions were assessed through two functional tasks: 10 m walking and the Timed Up and Go Test. Force of the amputated limb and functional level score reflecting the required assistance for walking were also measured. Evaluations were scheduled at the arrival at the rehabilitation center (right after amputation), after prosthesis fitting (three weeks later), and at the end of the rehabilitation program. A retention test was also programed after 6 weeks. RESULTS: While there was no additional effect of MI on pain management, data revealed an early positive impact of MI for the 10 m walking task during the pre-prosthetic phase, and greater performance during the Timed Up and Go Test during the prosthetic phase. Also, a lower proportion of participants still needed a walking aid after MI training. Finally, the force of the amputated limb was greater at the end of rehabilitation for the MI group. CONCLUSION: Taken together, these data support the integration of MI within the course of physical therapy in persons suffering from lower-limb amputations.

Immersive VR for upper-extremity rehabilitation in patients with neurological disorders: a scoping review.

BACKGROUND: Neurological disorders, such as stroke and chronic pain syndromes, profoundly impact independence and quality of life, especially when affecting upper extremity (UE) function. While conventional physical therapy has shown effectiveness in providing some neural recovery in affected individuals, there remains a need for improved interventions. Virtual reality (VR) has emerged as a promising technology-based approach for neurorehabilitation to make the patient's experience more enjoyable. Among VR-based rehabilitation paradigms, those based on fully immersive systems with headsets have gained significant attention due to their potential to enhance patient's engagement. METHODS: This scoping review aims to investigate the current state of research on the use of immersive VR for UE rehabilitation in individuals with neurological diseases, highlighting benefits and limitations. We identified thirteen relevant studies through comprehensive searches in Scopus, PubMed, and IEEE Xplore databases. Eligible studies incorporated immersive VR for UE rehabilitation in patients with neurological disorders and evaluated participants' neurological and motor functions before and after the intervention using clinical assessments. RESULTS: Most of the included studies reported improvements in the participants rehabilitation outcomes, suggesting that immersive VR represents a valuable tool for UE rehabilitation in individuals with neurological disorders. In addition, immersive VR-based interventions hold the potential for personalized and intensive training within a telerehabilitation framework. However, further studies with better design are needed for true comparison with traditional therapy. Also, the potential side effects associated with VR head-mounted displays, such as dizziness and nausea, warrant careful consideration in the development and implementation of VR-based rehabilitation programs. CONCLUSION: This review provides valuable insights into the application of immersive VR in UE rehabilitation, offering the foundation for future research and clinical practice. By leveraging immersive VR's potential, researchers and rehabilitation specialists can design more tailored and patient-centric rehabilitation strategies, ultimately improving the functional outcome and enhancing the quality of life of individuals with neurological diseases.

Virtual reality and motor imagery for early post-stroke rehabilitation.

BACKGROUND: Motor impairment is a common consequence of stroke causing difficulty in independent movement. The first month of post-stroke rehabilitation is the most effective period for recovery. Movement imagination, known as motor imagery, in combination with virtual reality may provide a way for stroke patients with severe motor disabilities to begin rehabilitation. METHODS: The aim of this study is to verify whether motor imagery and virtual reality help to activate stroke patients' motor cortex. 16 acute/subacute (< 6 months) stroke patients participated in this study. All participants performed motor imagery of basketball shooting which involved the following tasks: listening to audio instruction only, watching a basketball shooting animation in 3D with audio, and also performing motor imagery afterwards. Electroencephalogram (EEG) was recorded for analysis of motor-related features of the brain such as power spectral analysis in the [Formula: see text] and [Formula: see text] frequency bands and spectral entropy. 18 EEG channels over the motor cortex were used for all stroke patients. RESULTS: All results are normalised relative to all tasks for each participant. The power spectral densities peak near the [Formula: see text] band for all participants and also the [Formula: see text] band for some participants. Tasks with instructions during motor imagery generally show greater power spectral peaks. The p-values of the Wilcoxon signed-rank test for band power comparison from the 18 EEG channels between different pairs of tasks show a 0.01 significance of rejecting the band powers being the same for most tasks done by stroke subjects. The motor cortex of most stroke patients is more active when virtual reality is involved during motor imagery as indicated by their respective scalp maps of band power and spectral entropy. CONCLUSION: The resulting activation of stroke patient's motor cortices in this study reveals evidence that it is induced by imagination of movement and virtual reality supports motor imagery. The framework of the current study also provides an efficient way to investigate motor imagery and virtual reality during post-stroke rehabilitation.

Association between lesion location and sensorimotor rhythms in stroke - a systematic review with narrative synthesis.

BACKGROUND: Stroke causes alterations in the sensorimotor rhythms (SMRs) of the brain. However, little is known about the influence of lesion location on the SMRs. Understanding this relationship is relevant for the use of SMRs in assistive and rehabilitative therapies, such as Brain-Computer Interfaces (BCIs).. METHODS: We reviewed current evidence on the association between stroke lesion location and SMRs through systematically searching PubMed and Embase and generated a narrative synthesis of findings. RESULTS: We included 12 articles reporting on 161 patients. In resting-state studies, cortical and pontine damage were related to an overall decrease in alpha (∼8-12 Hz) and increase in delta (∼1-4 Hz) power. In movement paradigm studies, attenuated alpha and beta (∼15-25 Hz) event-related desynchronization (ERD) was shown in stroke patients during (attempted) paretic hand movement, compared to controls. Stronger reductions in alpha and beta ERD in the ipsilesional, compared to contralesional hemisphere, were observed for cortical lesions. Subcortical stroke was found to affect bilateral ERD and ERS, but results were highly variable. CONCLUSIONS: Findings suggest a link between stroke lesion location and SMR alterations, but heterogeneity across studies and limited lesion location descriptions precluded a meta-analysis. SIGNIFICANCE: Future research would benefit from more uniformly defined outcome measures, homogeneous methodologies, and improved lesion location reporting.

Efficacy of functional electrical stimulation in rehabilitating patients with foot drop symptoms after stroke and its correlation with somatosensory evoked potentials-a crossover randomised controlled trial.

OBJECTIVE: The connectivity between somatosensory evoked potentials (SEPs) and cortical plasticity remains elusive due to a lack of supporting data. This study investigates changes in pathological latencies and amplitudes of SEPs caused by an acute stroke after 2 weeks of rehabilitation with functional electrical stimulation (FES). Furthermore, changes in SEPs and the efficacy of FES against foot drop (FD) stroke symptoms were correlated using the 10-m walk test and foot-ankle strength. METHODS: A randomised controlled two-period crossover design plus a control group (group C) was designed. Group A (n = 16) was directly treated with FES, while group B (n = 16) was treated after 2 weeks. The untreated control group of 20 healthy adults underwent repeated SEP measurements for evaluation only. RESULTS: The repeated-measures ANOVA showed a decrease in tibial nerve (TN) P40 and N50 latencies in group A after the intervention, followed by a decline in non-paretic TN SEP in latency N50 (p < 0.05). Moreover, compared to groups B and C from baseline to 4 weeks, group A showed a decrease in paretic TN latency P40 and N50 (p < 0.05). An increase in FD strength and a reduction in step cadence in group B (p < 0.05) and a positive tendency in FD strength (p = 0.12) and step cadence (p = 0.08) in group A were observed after the treatment time. The data showed a moderate (r = 0.50-0.70) correlation between non-paretic TN latency N50 and step cadence in groups A and B after the intervention time. CONCLUSION: The FES intervention modified the pathological gait in association with improved SEP afferent feedback. Registered on 25 February 2021 on ClinicalTrials.gov under identifier number: NCT04767360.

Non-invasive Brain Stimulation Techniques for the Improvement of Upper Limb Motor Function and Performance in Activities of Daily Living After Stroke: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of non-invasive brain stimulation (NiBS) such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcutaneous vagus nerve stimulation (taVNS) in upper limb stroke rehabilitation. DATA SOURCES: PubMed, Web of Science, and Cochrane databases were searched from January 2010 to June 2022. DATA SELECTION: Randomized controlled trials (RCTs) assessing the effects of "tDCS", "rTMS", "TBS", or "taVNS" on upper limb motor function and performance in activities of daily livings (ADLs) after stroke. DATA EXTRACTION: Data were extracted by 2 independent reviewers. Risk of bias was evaluated with the Cochrane Risk of Bias tool. DATA SYNTHESIS: 87 RCTs with 3750 participants were included. Pairwise meta-analysis showed that all NiBS except continuous TBS (cTBS) and cathodal tDCS were significantly more efficacious than sham stimulation for motor function (standardized mean difference [SMD] range 0.42-1.20), whereas taVNS, anodal tDCS, and both low and high frequency rTMS were significantly more efficacious than sham stimulation for ADLs (SMD range 0.54-0.99). NMA showed that taVNS was more effective than cTBS (SMD:1.00; 95% CI (0.02-2.02)), cathodal tDCS (SMD:1.07; 95% CI (0.21-1.92)), and Physical rehabilitation alone (SMD:1.46; 95% CI (0.59-2.33)) for improving motor function. P-score found that taVNS is best ranked treatment in improving motor function (SMD: 1.20; 95% CI (0.46-1.95)) and ADLs (SMD:1.20; 95% CI (0.45-1.94)) after stroke. After taVNS, excitatory stimulation protocols (intermittent TBS, anodal tDCS, and HF-rTMS) are most effective in improving motor function and ADLs after acute/sub-acute (SMD range 0.53-1.63) and chronic stroke (SMD range 0.39-1.16). CONCLUSIONS: Evidence suggests that excitatory stimulation protocols are the most promising intervention in improving upper limb motor function and performance in ADLs. taVNS appeared to be a promising intervention for stroke patients, but further large RCTs are required to confirm its relative superiority.

Can specific virtual reality combined with conventional rehabilitation improve poststroke hand motor function? A randomized clinical trial.

TRIAL OBJECTIVE: To verify whether conventional rehabilitation combined with specific virtual reality is more effective than conventional therapy alone in restoring hand motor function and muscle tone after stroke. TRIAL DESIGN: This prospective single-blind randomized controlled trial compared conventional rehabilitation based on physiotherapy and occupational therapy (control group) with the combination of conventional rehabilitation and specific virtual reality technology (experimental group). Participants were allocated to these groups in a ratio of 1:1. The conventional rehabilitation therapists were blinded to the study, but neither the participants nor the therapist who applied the virtual reality-based therapy could be blinded to the intervention. PARTICIPANTS: Forty-six patients (43 of whom completed the intervention period and follow-up evaluation) were recruited from the Neurology and Rehabilitation units of the Hospital General Universitario of Talavera de la Reina, Spain. INTERVENTION: Each participant completed 15 treatment sessions lasting 150 min/session; the sessions took place five consecutive days/week over the course of three weeks. The experimental group received conventional upper-limb strength and motor training (100 min/session) combined with specific virtual reality technology devices (50 min/session); the control group received only conventional training (150 min/session). RESULTS: As measured by the Ashworth Scale, a decrease in wrist muscle tone was observed in both groups (control and experimental), with a notably larger decrease in the experimental group (baseline mean/postintervention mean: 1.22/0.39; difference between baseline and follow-up: 0.78; 95% confidence interval: 0.38-1.18; effect size = 0.206). Fugl-Meyer Assessment scores were observed to increase in both groups, with a notably larger increase in the experimental group (total motor function: effect size = 0.300; mean: - 35.5; 95% confidence interval: - 38.9 to - 32.0; wrist: effect size = 0.290; mean: - 5.6; 95% confidence interval: - 6.4 to - 4.8; hand: effect size = 0.299; mean: - -8.9; 95% confidence interval: - 10.1 to - 7.6). On the Action Research Arm Test, the experimental group quadrupled its score after the combined intervention (effect size = 0.321; mean: - 32.8; 95% confidence interval: - 40.1 to - 25.5). CONCLUSION: The outcomes of the study suggest that conventional rehabilitation combined with a specific virtual reality technology system can be more effective than conventional programs alone in improving hand motor function and voluntary movement and in normalizing muscle tone in subacute stroke patients. With combined treatment, hand and wrist functionality and motion increase; resistance to movement (spasticity) decreases and remains at a reduced level. TRIALS REGISTRY: International Clinical Trials Registry Platform: ISRCTN27760662 (15/06/2020; retrospectively registered).

Quantitative Comparison of Hand Kinematics Measured with a Markerless Commercial Head-Mounted Display and a Marker-Based Motion Capture System in Stroke Survivors.

Upper-limb paresis is common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients' movements in ecological scenarios. These systems are, however, very expensive and not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. A total of 14 stroke patients executed ecologically relevant upper-limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest's and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1 (maximum distance: mean slope = 0.94 ± 0.1; peak velocity: mean slope = 1.06 ± 0.12). Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper-limb kinematic parameters in stroke patients.

The Benefits of Combining Bobath and Vojta Therapies in Infants with Motor Development Impairment-A Pilot Study.

Background: In infants presenting with motor development impairment, early kinesiotherapeutic interventions aim to normalise the pattern of movements and improve recovery. By applying Bobath and Vojta methods, we aimed to identify a combined approach regarding motor deficit in infants with neurological disabilities. Methods: We designed a prospective interventional study on 108 infants with motor developmental delay and applied Bobath, Vojta, or combined Bobath and Vojta therapy in three equal groups. Results: In the combined Bobath and Vojta group, complete motor recovery was achieved for 50% of the participants, with full recovery after six months, whereas in Bobath- or Vojta-only therapy groups, the total recovery for all participants was achieved at seven months. Regarding infants with muscular hypertonia, Bobath therapy initiation demonstrated complete recovery in 5 months in more than 50% of the cases, while for Vojta this was achieved in only 33.57% of the cases. Conclusions: The comparative evaluation conducted by analysing the data regarding the application of the Bobath and Vojta methods showed that combining these two therapies results in a shorter motor deficit recovery time than if a single therapy is applied. These findings have important implications for the selection of rehabilitation therapies in infants with neurological motor development issues.

Extended Poststroke Rehabilitation Combined with Cerebrolysin Promotes Upper Limb Motor Recovery in Early Subacute Phase of Rehabilitation: A Randomized Clinical Study.

Background and Objectives: The recovery of stroke patients with severe impairment is usually poor and limited and, unfortunately, under-investigated in clinical studies. In order to support neuroplasticity and modulate motor recovery, Cerebrolysin combined with rehabilitation treatment has proven effective in the acute stroke phase in moderate to severe motor impairment. The aim of this study was to determine the efficacy of extended poststroke rehabilitation combined with Cerebrolysin on upper limb motor recovery in subacute stroke patients with severe upper limb motor impairment. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted. Sixty patients at the early stage of severe sub-acute stroke who fulfilled all eligibility criteria were randomly assigned to the Cerebrolysin group or placebo group (𝑛 = 30 each). Both groups, after conducting three weeks of conventional rehabilitation treatment five days per week, continued to perform conventional rehabilitation treatment three times per week until 90 days of rehabilitation treatment. The primary outcome measure was the Action Research Arm Test (ARAT), and the secondary outcomes were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) motor score, Barthel index (BI), and the National Institutes of Health Stroke Scale (NIHSS). The outcome data were evaluated before, after three weeks of treatment, and on the 90th day of rehabilitation treatment, and compared within groups and between the two groups. There were no adverse events. Results: Both groups showed a significant improvement (p < 0.001) over time in BI, FMA-UE, ARAT, and NIHSS scores. Patients receiving Cerebrolysin showed more significant improvement in post-stroke upper limb motor impairment and functioning compared to the placebo group after only three weeks, and the trend was maintained after 90 days of follow up. Conclusion: Cerebrolysin delivered in the early subacute post-stroke phase added to extended conventional rehabilitation treatment is beneficial and improves motor functional recovery in patients with severe motor impairment, especially on the paretic upper extremity.

No evidence for motor-recovery-related cortical connectivity changes after stroke using resting-state fMRI.

It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state (rs) functional MRI (fMRI). Here, we report a longitudinal data set collected from 19 patients with subcortical stroke and 11 controls. Patients were imaged up to five times over 1 year. We found no evidence, using rs-fMRI, for longitudinal poststroke cortical connectivity changes despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here, we argue instead that they are consistent with other emerging reasons to challenge the idea of motor-recovery-related cortical reorganization poststroke when conceived of as changes in connectivity between cortical areas.NEW & NOTEWORTHY We investigated longitudinal changes in functional connectivity after stroke. Despite substantial motor recovery, we found no differences in functional connectivity patterns between patients and controls, nor any changes over time. Assuming that rs-fMRI is an adequate method to capture connectivity changes between cortical regions after brain injury, these results provide reason to doubt that changes in cortico-cortical connectivity are the relevant mechanism for promoting motor recovery.

Relation Between EEG Measures and Upper Limb Motor Recovery in Stroke Patients: A Scoping Review.

Current clinical practice does not leverage electroencephalography (EEG) measurements in stroke patients, despite its potential to contribute to post-stroke recovery predictions. We review the literature on the effectiveness of various quantitative and qualitative EEG-based measures after stroke as a tool to predict upper limb motor outcome, in relation to stroke timeframe and applied experimental tasks. Moreover, we aim to provide guidance on the use of EEG in the assessment of upper limb motor recovery after stroke, suggesting a high potential for some metrics in the appropriate context. We identified relevant papers (N = 16) from databases ScienceDirect, Web of Science and MEDLINE, and assessed their methodological quality with the Joanna Briggs Institute (JBI) Critical Appraisal. We applied the Preferred Reporting Systems for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) Framework. Identified works used EEG to identify properties including event-related activation, spectral power in physiologically relevant bands, symmetry in brain dynamics, functional connectivity, cortico-muscular coherence and rhythmic coordination. EEG was acquired in resting state or in relation to behavioural conditions. Motor outcome was mainly evaluated with the Upper Limb Fugl-Meyer Assessment. Despite great variability in the literature, data suggests that the most promising EEG quantifiers for predicting post-stroke motor outcome are event-related measures. Measures of spectral power in physiologically relevant bands and measures of brain symmetry also show promise. We suggest that EEG measures may improve our understanding of stroke brain dynamics during recovery, and contribute to establishing a functional prognosis and choosing the rehabilitation approach.

Chemogenetic stimulation of proprioceptors remodels lumbar interneuron excitability and promotes motor recovery after SCI.

Motor recovery after severe spinal cord injury (SCI) is limited due to the disruption of direct descending commands. Despite the absence of brain-derived descending inputs, sensory afferents below injury sites remain intact. Among them, proprioception acts as an important sensory source to modulate local spinal circuits and determine motor outputs. Yet, it remains unclear whether enhancing proprioceptive inputs promotes motor recovery after severe SCI. Here, we first established a viral system to selectively target lumbar proprioceptive neurons and then introduced the excitatory Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus into proprioceptors to achieve specific activation of lumbar proprioceptive neurons upon CNO administration. We demonstrated that chronic activation of lumbar proprioceptive neurons promoted the recovery of hindlimb stepping ability in a bilateral hemisection SCI mouse model. We further revealed that chemogenetic proprioceptive stimulation led to coordinated activation of proprioception-receptive spinal interneurons and facilitated transmission of supraspinal commands to lumbar motor neurons, without affecting the regrowth of proprioceptive afferents or brain-derived descending axons. Moreover, application of 4-aminopyridine-3-methanol (4-AP-MeOH) that enhances nerve conductance further improved the transmission of supraspinal inputs and motor recovery in proprioception-stimulated mice. Our study demonstrates that proprioception-based combinatorial modality may be a promising strategy to restore the motor function after severe SCI.

Practical Machine Learning Model to Predict the Recovery of Motor Function in Patients with Stroke.

BACKGROUND: Machine learning (ML) is an artificial intelligence technique in which a system learns patterns and rules from a given data. OBJECTIVES: The objective of the study was to investigate the potential of ML for predicting motor recovery in stroke patients. METHODS: We analyzed data from 833 consecutive stroke patients using 3 ML algorithms: deep neural network (DNN), random forest, and logistic regression. We created a practical ML model using the most common data measured in almost all rehabilitation hospitals as input data. Demographic and clinical data, including modified Brunnstrom classification (MBC) and functional ambulation classification (FAC), were collected when patients were transferred to the rehabilitation unit (8-30 days) and 6 months after stroke onset and were used as input data. Motor outcomes at 6 months after stroke onset of the affected upper and lower extremities were classified according to MBC and FAC, respectively. Patients with an MBC of <5 and an FAC of <4 at 6 months after stroke onset were considered to have a "poor" outcome, whereas those with MBC ≥5 and FAC ≥4 were considered to have a "good" outcome. RESULTS: The area under the curve (AUC) for the DNN model for predicting motor function was 0.836 for the upper and lower limb motor functions. For the random forest and logistic regression models, the AUCs were 0.736 and 0.790 for the upper and lower limb motor functions, respectively. The AUCs for the random forest and logistic regression models were 0.741 and 0.795 for the upper and lower limb motor functions, respectively. CONCLUSION: Although we used simple and common data that can be obtained in clinical practice as variables, our DNN algorithm was useful for predicting motor recovery of the upper and lower extremities in stroke patients during the recovery phase.

Clinical outcomes report in different brachial plexus injury surgeries: a systematic review.

Brachial plexus injury is a lesion that results in loss of function of the arm, and there are multiple ways of surgically approaching its treatment. Controlled trials that compare all surgical repair strategies and their clinical outcomes have not been performed. A systematic review was conducted to identify all articles that reported clinical outcomes in different surgeries (nerve transfer, nerve graft, neurolysis, end-to-end, multiple interventions, and others). Advanced search in PubMed was performed using the Mesh terms "brachial plexus injury" as the main topic and "surgery" as a subtopic, obtaining a total of 2153 articles. The clinical data for eligibility extraction was focused on collecting motor, sensory, pain, and functional recovery. A statistical analysis was performed to find the superior surgical techniques in terms of motor recovery, through the assessment of heterogeneity between groups, and of relationships between surgery and motor recovery. The frequency and the manner in which clinical outcomes are recording were described. The differences that correspond to the demographics and procedural factors were not statistically significant among groups (p > 0.05). Neurolysis showed the highest proportion of motor recovery (85.18%), with significant results between preoperative and post-operative motor assessment (p = 0.028). The proportion of motor recovery in each group according to the surgical approach differed significantly (X2 = 82.495, p = 0.0001). The motor outcome was the most reported clinical outcome (97.56%), whereas the other clinical outcomes were reported in less than 15% of the included articles. Unexpectedly, neurolysis, a technique displaced by new surgical alternatives such as nerve transfer/graft, demonstrated the highest proportion of motor recovery. Clinical outcomes such as pain, sensory, and functional recovery were infrequently reported. These results introduce the need to re-evaluate neurolysis through comparative clinical trials, as well as to standardize the way in which clinical outcomes are reported.

Robotic Biofeedback for Post-Stroke Gait Rehabilitation: A Scoping Review.

This review aims to recommend directions for future research on robotic biofeedback towards prompt post-stroke gait rehabilitation by investigating the technical and clinical specifications of biofeedback systems (BSs), including the complementary use with assistive devices and/or physiotherapist-oriented cues. A literature search was conducted from January 2019 to September 2022 on Cochrane, Embase, PubMed, PEDro, Scopus, and Web of Science databases. Data regarding technical (sensors, biofeedback parameters, actuators, control strategies, assistive devices, physiotherapist-oriented cues) and clinical (participants' characteristics, protocols, outcome measures, BSs' effects) specifications of BSs were extracted from the relevant studies. A total of 31 studies were reviewed, which included 660 stroke survivors. Most studies reported visual biofeedback driven according to the comparison between real-time kinetic or spatiotemporal data from wearable sensors and a threshold. Most studies achieved statistically significant improvements on sensor-based and clinical outcomes between at least two evaluation time points. Future research should study the effectiveness of using multiple wearable sensors and actuators to provide personalized biofeedback to users with multiple sensorimotor deficits. There is space to explore BSs complementing different assistive devices and physiotherapist-oriented cues according to their needs. There is a lack of randomized-controlled studies to explore post-stroke stage, mental and sensory effects of BSs.

Cognitive Reserve Modifies the Relationship Between Neural Function, Neural Injury and Upper-Limb Recovery After Stroke.

OBJECTIVE: To investigate whether cognitive reserve modifies the relationship between functional connectivity, lesion volume, stroke severity and upper-limb motor impairment and recovery in stroke survivors. METHODS: Ten patients with first-ever ischemic middle cerebral artery stroke completed the Cognitive Reserve Index Questionnaire at baseline. Upper-limb motor impairment and functional connectivity were assessed using the Fugl-Meyer Assessment and electroencephalography respectively at baseline and 3-months post-stroke. A debiased weighted phase lag index was computed to estimate functional connectivity between electrodes. Partial least squares (PLS) regression identified a connectivity model that maximally predicted variance in the degree of upper-limb impairment. Regression models were generated to determine whether cognitive reserve modified the relationship between neural function (functional connectivity), neural injury (lesion volume), stroke severity (National Institutes of Health Stroke Scale) and upper-limb motor impairment at baseline and recovery at 3-months (Fugl-Meyer Assessment). RESULTS: The addition of cognitive reserve to a regression model with a dependent variable of upper-limb motor recovery and independent variables of functional connectivity between the ipsilesional motor cortex and parietal cortex, stroke severity and lesion volume improved model efficiency (∆BIC=-7.07) despite not reaching statistical significance (R2=0.90, p=0.07). Cognitive reserve did not appear to improve regression models examining motor impairment at baseline. CONCLUSIONS: Preliminary observations suggest cognitive reserve might modify the relationship between neural function, neural injury, stroke severity and upper-limb motor recovery. Further investigation of cognitive reserve in motor recovery post-stroke appears warranted.

The Gigantocellular Reticular Nucleus Plays a Significant Role in Locomotor Recovery after Incomplete Spinal Cord Injury.

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions.SIGNIFICANCE STATEMENT Following unilateral hemisection of the spinal cord, reticulospinal projections are destroyed on the injured side, resulting in impaired locomotion. Over time, a high degree of recovery can be observed in lesioned animals, like in human hemicord patients. In the rat, recovery is accompanied by pronounced spontaneous plasticity of axotomized and spared reticulospinal axons. We demonstrate the causative relevance of locally rewired as well as compensatory reticulospinal plasticity for the recovery of locomotor functions following spinal hemisection, using chemogenetic tools to selectively silence newly formed connections in behaviorally recovered animals. Moving from a correlative to a causative understanding of the role of neuroanatomical plasticity for functional recovery is fundamental for successful translation of treatment approaches from experimental studies to the clinics.

Functional connectome reorganization relates to post-stroke motor recovery and structural and functional disconnection.

Motor recovery following ischemic stroke is contingent on the ability of surviving brain networks to compensate for damaged tissue. In rodent models, sensory and motor cortical representations have been shown to remap onto intact tissue around the lesion site, but remapping to more distal sites (e.g. in the contralesional hemisphere) has also been observed. Resting state functional connectivity (FC) analysis has been employed to study compensatory network adaptations in humans, but mechanisms and time course of motor recovery are not well understood. Here, we examine longitudinal FC in 23 first-episode ischemic pontine stroke patients and utilize a graph matching approach to identify patterns of functional connectivity reorganization during recovery. We quantified functional reorganization between several intervals ranging from 1 week to 6 months following stroke, and demonstrated that the areas that undergo functional reorganization most frequently are in cerebellar/subcortical networks. Brain regions with more structural and functional connectome disruption due to the stroke also had more remapping over time. Finally, we show that functional reorganization is correlated with the extent of motor recovery in the early to late subacute phases, and furthermore, individuals with greater baseline motor impairment demonstrate more extensive early subacute functional reorganization (from one to two weeks post-stroke) and this reorganization correlates with better motor recovery at 6 months. Taken together, these results suggest that our graph matching approach can quantify recovery-relevant, whole-brain functional connectivity network reorganization after stroke.