Neurorehabilitation and neural repair最新文献

The social life of locked-in syndrome (LIS) patients is significantly impacted by their difficulties to communicate. Consequently, researchers have started to explore how to decode intended speech from neural signals directly recorded from the cortex. The first studies in the late 2000s reported modest decoding accuracies. However, thanks to fast advances in machine learning, the most recent studies have reached decoding accuracies high enough to be optimistic about the clinical benefit of neural speech decoders in the near future. We first discuss the selection criteria for implanting a neural speech decoder in LIS patients, emphasizing the advantages and disadvantages associated with conditions such as brainstem stroke and amyotrophic lateral sclerosis. We examine the key design considerations for neural speech decoders, demonstrating how successful implantation requires careful optimization of multiple interrelated factors including language representation, cortical recording areas, neural features, training paradigms, and decoding algorithms. We then discuss current approaches and provide arguments for potential improvements in decoder design and implementation. Finally, we explore the crucial question of who should learn to use the neural speech decoder-the patient, the machine, or both. In conclusion, while neural speech decoders present promising avenues for improving communication for LIS patients, interdisciplinary efforts spanning neurorehabilitation, neuroscience, neuroengineering, and ethics are imperative to design future clinical trials.

Background: Vestibular dysfunction occurs in 30% to 70% of cases with multiple sclerosis (MS).

Objective: To compare the clinical and cost-effectiveness of a customized vestibular rehabilitation (VR) program with a generic booklet-based VR intervention in people with MS with clinical signs of vestibulopathy.

Methods: People with MS and symptoms of vertigo and/or imbalance were screened for vestibulopathy (n = 73). Seventy recruited participants were randomly allocated to a 12-week generic booklet-based home program with telephone support (n = 35) or a 12-week customized VR program (n = 35, 12 face-to-face sessions and a home exercise program). The primary clinical outcome was the Dizziness Handicap Inventory (DHI) at 26 weeks post-randomization. The primary economic endpoint was quality-adjusted life-years (QALYs). Secondary outcomes included vertigo severity, balance, gait, and perceived impact of physical symptoms in MS.

Results: There was no significant between-group difference in the DHI: mean reduction -1.76 (95% confidence interval -10.02, 6.50) at week 26 in favor of the customized group (P = .670). There were significant differences in favor of the customized group for vertigo symptom score, balance confidence, walking, and perceived impact of MS. Primary cost-effectiveness analysis showed customized VR to be less costly and more effective. However, removal of 2 cost outliers in sensitivity analysis resulted in a mean cost-per-QALY of £30 147. Customized VR was also cost-effective from a societal perspective.

Discussion: Impairment level improvements did not translate into functional improvements as measured by the DHI perhaps reflecting that vestibular dysfunction is one of several impairments in MS. The findings indicate the potential cost-effectiveness of the customized program.

Clinical trial registration: ISRCTN27374299.

BackgroundStroke often leads to long-term impairments in upper extremity motor function, including muscle weakness, spasticity, and abnormal joint synergies, which hinder independent joint control and daily activities.ObjectiveThis study examined multi-joint motor impairments and characterized abnormal synergy patterns post-stroke using a robotic exoskeleton.MethodsThe exoskeleton independently controlled shoulder, elbow, and wrist joints while measuring responses across all joints during horizontal plane movements. Fifty-three stroke survivors and 24 age-matched controls performed single-joint movements under constrained (fixed joints) and unconstrained (free joints) conditions. Coupled range of torques and range of motion at non-instructed joints were calculated relative to instructed joint movements and summarized in a 3 × 3 matrix.ResultsStroke survivors showed significantly higher coupling torques and motions at non-instructed joints compared to controls, with the greatest impairments in isolating distal movements, particularly in a proximal-to-distal gradient. Abnormal synergy patterns were systematically identified, revealing that stroke survivors exhibited two common patterns for shoulder and elbow tasks, marked by excessive coupling at neighboring joints. For wrist movement tasks, four distinct patterns emerged, involving excessive coupling at both shoulder and elbow joints.ConclusionThese findings demonstrate characteristic impairments in joint individuation and synergy following a stroke, providing a framework to understand motor deficits and guide rehabilitation strategies aimed at restoring joint-specific control.

BackgroundGravity confounds arm movement ability in post-stroke hemiparesis. Reducing its influence allows effective practice leading to recovery. Yet, there is a scarcity of wearable devices suitable for personalized use across diverse therapeutic activities in the clinic.ObjectiveIn this pilot study, we investigated the safety, feasibility, and efficacy of anti-gravity therapy using the ExoNET device in post-stroke participants.MethodsTwenty chronic stroke survivors underwent six, 45-minute occupational therapy sessions while wearing the ExoNET, randomized into either the treatment (ExoNET tuned to gravity-support) or control group (ExoNET tuned to slack condition). Clinical outcomes were evaluated by a blinded-rater at baseline, post, and 6-week follow-up sessions. Kinetic, kinematic, and patient experience outcomes were also assessed.ResultsNo significant effects were found between the treatment and control groups for Action Research Arm Test, Fugl-Meyer Upper Extremity, and Wolf Motor Function Test scores though the treatment group showed an improvement in Box and Blocks scores in the post-intervention session (effect size = 2.1, P = .04). Direct kinetic effects revealed a significant reduction in muscle activity during free exploration with an effect size of (-7.12%, P < .005) but no longitudinal kinetic or kinematic trends. Subject feedback suggested a generally positive perception of the anti-gravity therapy.ConclusionsAnti-gravity therapy with the ExoNET is a safe and feasible treatment for post-stroke rehabilitation. The device provided anti-gravity forces, did not encumber range of motion, and clinical metrics of anti-gravity therapy demonstrated improvements in gross manual dexterity. Further research is required to explore potential benefits in broader clinical metrics.Trial Registration:This study was registered at ClinicalTrials.gov (ID# NCT05180812).

BackgroundThe cerebellar cortex has gradually become a promising therapeutic target for improving motor recovery post-cerebral infarction, potentially dependent on the structural integrity of motor-related corticocerebellar pathways (CCP). However, the relationship between the imaging markers of motor-related CCP and motor prognosis remains inadequately explored. Utilizing diffusion tensor imaging (DTI), this study aims to longitudinally assess the role of motor-related CCP in predicting motor recovery for both upper and lower extremities following cerebral infarction.MethodsTwenty-nine patients with right middle cerebral artery (MCA) infarction underwent 2 DTI scans 7 to 14 and 30 days after onset, and 29 age-sex matched controls received 1 scan. Fractional anisotropy (FA) values were measured for corticospinal tract (CST) and CCP (cortico-pontocerebellar tract, CPCT; dentate-thalamocortical tract, DTCT; dorsal-spinocerebellar tract, DSCT). Multivariate regression analyses were performed to examine the relationships between DTI parameters and Fugl-Meyer Assessment (FMA).ResultsCompared to the control group, FA and FA asymmetry index (FA-AI) of CST, DTCT, and DSCT on the affected side were significantly reduced. In the linear regression model, the decreased FA-AI of DTCT was a strong predictor for upper FMA (R²_adj = 0.271, P = .022), while the FA-AI of DSCT independently predicted lower limb FMA (R²_adj = 0.400, P = .019).ConclusionsIn patients of MCA infarction, FA-AI of motor-related CCP may be a valuable imaging indicator for predicting motor outcomes. The DTI-assessed structural integrity of the cerebellar ascending fiber tracts (DTCT and DSCT) may correlate with the motor recovery of the upper and lower extremities, respectively.

Background: Optimizing moderate to severe upper limb recovery is likely to require a higher dose of rehabilitation training than is currently delivered, but the feasibility and acceptability of higher dose regimes is unclear in the early-stage post stroke. Objective: To determine the maximum time spent on upper limb rehabilitation in people with moderate to severe impairment in acute and early sub-acute stage of stroke, in a phase I dose-escalation study.

Methods: Participants were recruited using a 3+3 study design from 2 stroke units and rehabilitation centers in Belgium. Patients received standard care plus escalating doses of upper limb motor training at 4 dose time-on-task levels: 1 (40 minutes), 2 (67 minutes), 3 (100 minutes) and 4 (133 minutes). Treatment was provided for 3 daily sessions, starting with 3 participants at level 1 and if dose was completed based on dose-limiting toxicity criteria, it was escalated to the next level with 3 new participants.

Results: Eighteen participants were recruited (median days post-stroke: 7.5 [Q1:5; Q3: 23.3]) with a mean Fugl Meyer Assessment Upper Extremity score of 29.4 (SD: 11.2). The maximum tolerated time-on-task of upper limb rehabilitation was, 100 minutes per day, with an additional 35 minutes of routine upper limb therapy provided as part of standard care. Level of fatigue and rate of perceived exertion were highest at dose level 4, resulting in participants not completing the dose of 133 minutes.

Conclusions: Confirmative with existing literature using a different intervention, individuals with moderate to severe impairment in the early-stage of stroke, can tolerate higher doses of upper limb rehabilitation than those typically administered in standard care. These findings support future investigation into phase I/IIa dose-finding clinical trials exploring long-duration, high-intensity upper limb rehabilitation programs in the early post-stroke period.

Registration: NCT04973553 (July 22, 2021). https://classic.

Clinicaltrials: gov/ct2/show/NCT04973553.

BackgroundThe extent to which the cholinergic system contributes to gait impairments in Parkinson's disease (PD) remains unclear. Electroencephalography (EEG) alpha reactivity, which refers to change in alpha power over occipital electrodes upon opening the eyes, has been suggested as a marker of cholinergic function. We compared alpha reactivity between people with PD and healthy individuals and explored its potential association with gait measures.MethodsEyes-closed and eyes-open resting-state EEG data were recorded from 20 people with idiopathic PD and 19 healthy individuals with a 64-channel EEG system. Alpha reactivity was calculated as the relative change in alpha power (8-13 Hz) over occipital electrodes from eyes-closed to eyes-open. Gait spatiotemporal measures were obtained with an electronic walkway.ResultsAlpha reactivity was reduced in people with PD compared to healthy individuals (U = 105, P = .017); the rank-biserial correlation of .447 indicated a moderate effect size. When controlling for global cognition (Mini Mental State Examination), the group difference in alpha reactivity was no longer significant. Alpha reactivity associated with measures of gait variability only (ρ = -.437 to -.532).ConclusionsResting-state alpha reactivity is reduced in PD, suggesting impaired cholinergic function. Reduced alpha reactivity was associated with greater gait variability, indicating a role of the cholinergic system in the mechanisms underlying gait variability. Therefore, the cholinergic system may represent a target for treatments aiming to reduce gait variability and alpha reactivity should be further explored as an endpoint for clinical trials.

ObjectivesAssessment of sensorimotor cortex and tracts degeneration using novel diffusion tensor imaging (DTI) templates in patients with chronic spinal cord injury (SCI) and its correlation with clinical and neurophysiological findings.MethodsSex and age-matched 29 patients with chronic SCI (paraplegic: p-SCI; tetraplegic: t-SCI) and 29 healthy controls underwent neurophysiological assessment including motor evoked potentials (MEP). DTI was performed on 3 T magnetic resonance imaging scanner and postprocessed using Human Motor Area and Sensorimotor Area Tract Templates. DTI parameters were compared using analysis of covariance with post hoc Scheffé and Bonferroni corrections. Spearman's rank test was used for correlations with P < .05 considered significant.ResultsCompared to controls, all SCI patients showed significantly lower fractional anisotropy (FA) in several tracts (primary motor [M1], somatosensory [S1], pre-supplementary motor area [preSMA], and dorsal premotor [PMd]) and cortices (M1, pre-SMA, and S1). There were no differences in DTI parameters between p-SCI and t-SCI or p-SCI and controls. Compared to controls, t-SCI showed significantly decreased FA within M1 and S1 tracts. In t-SCI higher motor scores were associated with higher FA from ventral premotor area (PMv) tracts and cortex; higher sensory scores were associated with higher FA from S1 tracts. Positive correlations were found between MEP amplitudes from rectus femoris muscles and FA for M1, PMd, PMv, pre-SMA, SMA tracts, and PMv cortex.ConclusionsDTI shows remote degeneration of sensorimotor cortex and supraspinal tracts in SCI correlating with several clinical motor and sensory scores, and MEP parameters. DTI metrics have the potential to become biomarkers of remote degeneration.

BackgroundSpoken language and environmental sounds hold rich and nuanced meaning for the listener, but depend on accurate hearing of the soundscape, including the timing, volume, and contrasts of its component pitches. Sensorineural hearing loss with aging degrades these properties, leading to progressive disability.ObjectivesThis case study and review describe my experience and behavioral accommodations to progressive bilateral hearing loss, limited compensation with hearing aids, and the stuttering evolution of gains after a unilateral cochlear implant (CI).ResultsDespite increasingly powerful hearing aids over 25 years, spoken phonemes and words became increasingly muffled, misheard, and often dissipated into ambient background noise. The cognitive effort to extract meaning and mask my disability grew exhausting. I gradually eliminated many of my usual family, medical career, and social roles. To try to recover some communication-dependent activities, I sought a bionic solution. A right-sided CI initially carried an ambiguous, fizzling code and unrecognizable synthetic voices. With 8 months of auditory rehabilitation, I better deciphered conversational speech and ambient sounds. By audiological testing, I improved from 10% hearing accuracy of single words to 65%, typical of post lingual adult users. Better hearing in ambient noise and for what had been excessively rapid speech evolved out to 18 months, allowing me to re-engage in many of my daily roles.ConclusionsHearing loss beyond the compensation of aids deeply challenges quality of life. Auditory rehabilitation after cochlear implantation engages neuroplasticity to re-establish functional communication.

Background: Physical, cognitive, and psychosocial impairments experienced by individuals post-stroke detrimentally impact health-related quality of life (HRQoL). Rehabilitation interventions targeting the recovery of motor function aim to improve community reintegration and HRQoL. Aerobic exercise has also been shown to have global effects in individuals post-stroke, positively affecting motor and mood-related outcomes.

Objective: To determine the effects of forced-rate aerobic exercise (FE) coupled with upper extremity repetitive task practice (RTP) on HRQoL and mood in individuals post-stroke.

Methods: A rater blinded randomized clinical trial was conducted. Individuals ≥6 months post-stroke received 90-minute sessions of FE+RTP or time-matched RTP alone, 3×/week for 8 weeks. The Stroke Impact Scale (SIS), Patient-Reported Outcomes Measurement Information System (PROMIS-29), and Centers For Epidemiology Studies-Depression Scale (CES-D) were administered at baseline, end of treatment (EOT), EOT+6 months, and EOT+12 months.

Results: Sixty participants enrolled in the study and 57 completed the self-reported questionnaires (FE + RTP, N = 29; RTP alone, N = 28). Both groups improved significantly at each time point in the following SIS domains: physical problems, feelings, activities of daily living, mobility, hand use, meaningful activities, and overall recovery; and in the participation domain of PROMIS-29. Depressive symptomology as measured by CES-D improved from baseline to EOT+6. There were no significant group differences in any of the outcomes.

Conclusions: Both interventions were comparably effective in improving HRQoL despite the FE+RTP group receiving only half the dose of RTP compared to the control group (RTP only). Improvements were maintained up to 1 year post-intervention.