Neurorehabilitation and neural repair最新文献

BackgroundThe Coma Recovery Scale-Revised (CRS-R) is the reference standard for diagnosing disorders of consciousness after severe brain injury. Rating scale categories for the 6 CRS-R items have been operationalized to diagnostic criteria for states of consciousness, but the validity of these diagnostic categories has not been examined in non-traumatic brain injury.

Objective: This study evaluates the hierarchy of CRS-R rating scale categories (RSCs) in individuals with disorders of consciousness due to non-traumatic brain injury.

Methods: We analyzed 4562 CRS-R assessments from 410 individuals using a partial credit Rasch model. We assessed reproducibility, structural validity, measurement accuracy, and conceptual validity by examining RSC alignment with the Aspen Consensus Criteria.

Results: All CRS-R items fit the Rasch model, with high Wright's person separation reliability (0.94) and strata (3.8), indicating strong measurement precision. The Visual and Motor items exhibited disordered rating scale thresholds. Several RSCs currently aligned with the unresponsive wakefulness syndrome showed comparable mean category measures to RSCs aligned with the minimally conscious state.

Conclusions: The CRS-R demonstrated strong reproducibility and validity in patients with non-traumatic brain injury, but may require refinement due to disordered thresholds. Consistent with literature in traumatic brain injury, our findings suggest that diagnostic criteria may need to be revised to better align with the constellation of behavioral features that are actually observed at different levels of neurorecovery. Specifically, RSC 4 on Auditory (consistent command following) and 3 on Arousal (Attention) may indicate emergence from the minimally conscious state.

BackgroundPost-stroke physical activity (PA) behavior may partly explain inter-individual differences in cortical and sub-cortical brain volumes and brain age estimates.ObjectiveTo investigate longitudinal associations of post-stroke PA behavior with structural brain MRI features.

Methods: Data were from a multicenter longitudinal cohort study. PA estimates were based on accelerometer measurements. Separate linear mixed models assessed average daily step count at 18 and 36 months, and longitudinal PA trajectory groups as measured at 3, 18, and 36 months after stroke, as primary and secondary exposures. Dependent variables included brain age gap (BAG), representing the discrepancy between brain MRI predicted age and chronological age, and MRI-based cortical, hippocampal, and thalamic volumes at 18- and 36 months post-stroke. Models accounted for age, sex, education, stroke severity, intracranial volume, and MRI scanner.

Results: We included 146 participants (age, mean [SD]: 70.3 [11.1]; 45.7% female) with predominantly mild strokes. Every +1000 steps/day were associated with -1.15 (95% CI: -1.76 to -0.53) lower BAG, 2.63 mL (95% CI: 0.31-5.00) larger cortical volume, and 0.07 mL (95% CI: 0.03-0.11) larger hippocampal volume. The association between step/day and thalamic volume was curvilinear, with the largest volumes observed at 4700 steps/day. Out of 4 PA trajectory groups, participants in the most active group had -7.44 years (95% CI: -2.86 to -12.01) lower BAG and 0.90 mL (95% CI: 1.48-0.33) larger thalamic volumes than the least active group.

Conclusions: Higher PA levels post-stroke were associated with larger brain volumes and younger-appearing brains.

BackgroundThe amount of walking practice may influence locomotor recovery in individuals with motor incomplete spinal cord injury (iSCI), although the contributions of exercise intensity are not well established.ObjectiveThe purpose of this blinded-assessor randomized trial was to determine the contributions of exercise intensity on locomotor outcomes in individuals >6 months following iSCI.MethodsAmbulatory individuals post-iSCI with walking speeds <1.0 m/s were assigned to ≤30 sessions of either high-intensity training (HIT: >70% heart rate [HR] reserve or ratings of perceived exertion [RPE] ≥15) or low-intensity training (LIT; <40% HR reserve; RPE ≤13). Assessments were performed at baseline, post-training, and at 3-month follow-up evaluation, with primary outcomes of fastest walking speeds over 10 m and during graded treadmill exercise tests, and secondary clinical and metabolic outcomes.ResultsOf 65 participants screened, 53 were randomized to HIT (n = 28) or LIT (n = 25) and completed 1489/1590 (94%) planned training sessions. Peak HRs and RPEs were greater during HIT (both P < .001). Changes in fastest gait speeds overground were not significantly different between HIT and LIT when using Bonferroni corrections (α = .025; mean post-training differences: 0.11 m/s [95% CI: 0.04-0.17 m/s], P = .031), although gains in peak treadmill speed were significant (mean differences: 0.25 m/s [0.15-0.34 m/s], p < .001]. Secondary outcomes of 6-minute walk test (P = .002) and combined measures of peak metabolic capacity and efficiency (P < .001) were also greater with HIT.ConclusionGreater gains in peak treadmill speed, 6-minute walk, and selected metabolic outcomes were observed with HIT versus LIT in individuals with iSCI.Trial Registrationhttps://clinicaltrials.gov/; Unique Identifier: NCT03714997.

BackgroundUnderstanding individual variability in response to interventions is essential for developing personalized treatment strategies. In rare and clinically heterogeneous conditions like primary progressive aphasia (PPA), predicting treatment response is particularly challenging due to varying clinical manifestations. In this study, we aimed to identify and analyze predictors of individual language response to transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus (IFG), using a novel, robust analytic approach focused on treatment effect heterogeneity.MethodsWe compared the ability of predicting individual effect (active vs sham tDCS during 20-minute sessions on weekdays for 3 weeks; active: 2 mA current across electrodes; sham: current ramped down after 30 seconds), using demographic and clinical patient characteristics (eg, PPA variant and disease progression, baseline language performance) or volumetric fMRI data versus functional connectivity (from resting-state fMRI) in the cohort of 36 patients.ResultsFunctional connectivity alone had the highest predictive value for outcomes, explaining 62% of the variance of the tDCS effect in generalization (semantic fluency) and 75% of the main outcome (written naming), contrasted with <15% (for semantic fluency) and <23% (for written naming) of variance predicted by demographic and clinical patient characteristics or volumetric data. Patients with higher baseline functional connectivity within the left IFG (between pars opercularis and pars triangularis) were most likely to benefit from tDCS both in generalization (semantic fluency) as well as in the main outcome (written naming). In addition, patients with higher baseline FC between the middle temporal pole and superior temporal gyrus, were most likely to show generalization effects of tDCS.ConclusionsThe present study showcases the importance of a baseline functional connectivity scan in predicting tDCS outcomes, and points toward a precision medicine approach in neuromodulation studies. The study has important implications for clinical trials and practice, providing a statistical method that addresses heterogeneity in patient populations and allowing accurate prediction and enrollment of those who will most likely benefit from specific interventions.

BackgroundAccurate and objective assessment of motor performance is critical for effective stroke rehabilitation. While wrist-worn accelerometers are widely accepted as a valid tool for evaluating upper-limb motor performance, they primarily capture arm and forearm movements, overlooking hand and finger activity. This limitation reduces their ability to detect changes in distal function, hindering the broader integration of wearable-based motor performance metrics into clinical practice.ObjectiveTo determine whether finger-worn accelerometers, which capture both proximal and distal movements of the upper limbs, offer a more comprehensive assessment of motor performance by comparing their convergent validity with that of wrist-worn accelerometers.MethodsBilateral accelerometer data were collected from 24 stroke survivors using finger-worn and wrist-worn devices as they performed unscripted daily activities in a simulated home environment. Motor performance metrics from both sensor locations were analyzed for correlations with the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and sensitivity to differences in motor performance across impairment levels.ResultsFinger-worn accelerometer metrics showed stronger correlations with FMA-UE scores than those from wrist-worn sensors, largely due to their ability to capture fine hand movements. Additionally, finger-worn sensors demonstrated greater sensitivity in detecting performance differences between mildly and moderately impaired individuals.ConclusionsBy capturing both proximal and distal movements, finger-worn accelerometers demonstrate stronger convergent validity with standardized measures of post-stroke motor impairment compared to wrist-worn accelerometers. These findings highlight their potential for providing a more comprehensive assessment of motor performance in stroke survivors.

Background and PurposeThis Point of View paper offers a commentary on challenges and opportunities discussed during the 6th International Brain Stimulation Conference held in February 2025 in Kobe, Japan, with a focus on the clinical application of repetitive transcranial magnetic stimulation (rTMS) in post-stroke rehabilitation. We argue that the major barrier lies in the field's overreliance on standardized, one-size-fits-all protocols and its reluctance to embrace personalization in the pursuit of precision.ResultsDuring the conference, 2 research cultures were evident: the "Systematicists," who rely on conventional clinical trials, and the "Personalizers," who tailor non-invasive brain stimulation (NIBS) protocols to individual patient characteristics. This dichotomy reflects a broader challenge: how can we reconcile the need for standardization with the demand for personalization in translational research? The future of NIBS may lie in patient-specific, biomarker-driven neuromodulatory protocols that incorporate deep phenotyping and brain state-dependent stimulation, such as closed-loop TMS guided by Hebbian plasticity principles. This approach recognizes that post-stroke recovering brain is a 4-dimensional structure, shaped by space and time, which contributes to substantial intra- and inter-individual variability.ConclusionUnderstanding how NIBS interacts with each uniquely recovering brain is essential. Addressing this complexity remains a challenge for designing rigorous clinical trials and moving the field closer to effective, personalized integration in stroke rehabilitation. By delineating key components of personalization, we aim to reframe the discussion from "if" NIBS works to "for whom, for what and why, for where and when, and how" it can facilitate clinically meaningful recovery.

Background: People with stroke often have persistent balance impairments that have a profound impact on mobility and daily life independence. Several studies have been conducted to identify stroke-related deficits in neuromuscular responses to balance perturbations. Yet, the majority of these studies involved low-intensity, non-stepping perturbations, whereas falling typically occurs at high-intensity perturbations where stepping is a key saving strategy.

Objective: We aimed to identify deficits in muscle coordination patterns of reactive stepping in people with supratentorial stroke (PwS).

Methods: We included 32 PwS, who performed multidirectional stepping responses with their paretic and non-paretic leg. We determined step quality, and performed muscle synergy analysis to characterize stance- and swing-leg muscle coordination patterns.

Results: We observed smaller leg angles in PwS in lateral, posterolateral and posterior directions, particularly with the paretic leg. Muscle synergy analysis yielded a set of 5 synergies in both groups for the swing VAF_Paretic = 0.84 ± 0.02, VAF_Non-Paretic = 0.84 ± 0.02) and stance leg VAF_Paretic = 0.85 ± 0.02, VAF_Non-Paretic = 0.84 ± 0.02). Three synergies were less frequently represented during paretic step execution. In addition, for the synergy with prominent gluteus medius involvement, underrepresentation was associated with lower Fugl-Meyer lower-extremity scores.

Conclusions: The finding of deficient synergy structure and activation during reactive stepping complements and extends insights into balance related impairments after stroke. As the key next step, the methodology presented here allows identifying whether training-induced gains in reactive step quality are related to optimization of pre-existing coordination patterns, or whether some degree of behavioral restitution (i.e., return to "normal" coordination patterns) may still be possible.

ObjectiveResearchers have focused on gamma rhythm stimulation, particularly at 40 Hz, to enhance endogenous gamma oscillations and improve cognitive function and outcomes in Alzheimer's disease (AD). However, some studies disputed these findings. This review aimed to systematically analyze recent randomized controlled trials on the effects of gamma stimulation on cognitive function in AD and to perform a meta-analysis to assess the efficacy, safety, and differences between brain and sensory stimulation.MethodsA systematic search was conducted in PubMed, Web of Science, Ovid-Embase, and Ovid-MEDLINE from their inception to April 2024. A meta-analysis was performed to evaluate adverse events and cognitive function assessed using AD Assessment Scale-Cognitive Subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Face-Name Association Test (FNAT). Subgroup analyses were performed to explore the heterogeneity between the brain and sensory stimulation.ResultsEight studies involving 291 participants were included. Meta-analysis demonstrated a large benefit in cognitive function: FNAT (standardized mean difference [SMD] = 3.76; 95% confidence interval [CI] = 2.52-4.99; I² = 65%), MMSE (SMD = 3.09; 95% CI = 2.37-3.82; I² = 0%), ADAS-cog (SMD = -4.16; 95% CI = -6.60 to -2.62; I² = 0%), and MoCA (SMD = 2.17; 95% CI = -0.54 to 4.88; I² = 0%). There were no significant differences in adverse events between the intervention and sham groups (P = .06), suggesting the safety of gamma stimulation.ConclusionThis review highlights the safety and benefits of gamma stimulation for cognitive improvement in patients with AD, with sensory stimulation proving safe even in individuals with epilepsy.

Background: After stroke, ankle proprioceptive deficits are common and do not typically correlate with ankle weakness. Some studies report that these deficits correlate with gait function, supporting the importance of somatosensory input for gait control. Others have not found a relationship, possibly due to use of coarse proprioception measures. Robotic assessments of proprioception offer improved consistency and sensitivity.

Objective: To establish relationships between ankle proprioception, gait function, and ankle motor in stroke survivors.

Methods: We studied 39 individuals in the chronic phase of stroke using 2 robotic tests, Crisscross and Joint Position Reproduction (JPR), to quantify ankle proprioception. We examined associations of these measures with gait speed (10-meter walk test) and gait endurance (6-minute walk test). We also analyzed correlations with lower extremity motor impairment, including robotic measures of ankle strength (MVC) and active range of motion (AROM), and the lower extremity Fugl-Meyer exam (LEFM).

Results: Impaired ankle proprioception was present in 87% of participants. Crisscross error weakly correlated with the 10mWT gait speed (ρ = -0.20, P = 0.23) and 6MWT distance (ρ = -0.28, P = .089). JPR error weakly correlated with 10mWT gait speed (ρ = -0.29, P = .092) and significantly correlated with 6MWT distance (ρ = -0.34, P = .04). No significant correlations were observed between ankle proprioceptive error and MVC, AROM, or LEFM (P > 0.2).

Conclusion: These results confirm the presence of a weak relationship between ankle proprioception and gait after stroke that is independent of several common measures of motor impairment.