Neurorehabilitation and neural repair最新文献

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.

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.

BackgroundPost-brain injury autonomic dysfunction, mediated by frontal-vagal network (FVN) dysregulation, lacks noninvasive tools for functional mapping and targeted neuromodulation.ObjectiveTo characterize autonomic impairment after brain injury, testify left dorsolateral prefrontal cortex (DLPFC) as an FVN hub, and validate a closed-loop intermittent theta-burst stimulation coupled with heart rate variability monitoring (iTBS-HRV) paradigm for FVN assessment.MethodsThis exploratory, secondary analysis integrated data from 3 coordinated investigations conducted using a dual-modality platform that combined structural magnetic resonance imaging (MRI)-guided optical neuronavigation with real-time HRV biofeedback: (1) autonomic profiling through HRV analysis comparing 59 brain-injured patients with 30 healthy controls; (2) A randomized crossover trial using MRI-neuronavigation iTBS to compare left versus right DLPFC stimulation effects on HRV in 15 participants; and (3) a translation study applied closed-loop iTBS-HRV intervention in 17 patients to quantify FVN responsivity. Key HRV metrics: root-mean-square of successive RR intervals differences ([RMSSD]; vagal tone), (high-frequency [HF]), low-frequency (LF)/HF (sympathovagal balance), and standard deviation of RR intervals ([SDNN]; global variability).ResultsPatients showed severe autonomic dysfunction with reduced vagal tone (RMSSD: 18.6 ms vs 36.7 ms, P < .001) and global variability (SDNN: 21.3 ms vs 50.9 ms, P < .001). Left frontal lesions exacerbate sympathovagal imbalance (LF/HF ↑2.40, P < .05). Left DLPFC iTBS selectively enhanced vagal modulation (ΔHF%: +2.73, P < .01; ΔLF/HF: -1.60, P < .001), confirming lateralized hub function, while patients exhibited attenuated HRV responses (ΔRMSSD: 0.50 ms vs 3.34 ms in controls, P < .01).ConclusionThe dual-modality iTBS-HRV framework provides an effective approach for mapping FVN dysfunction and targeting the left DLPFC hub for neuromodulation after brain injury.

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.

Cognitive impairment is highly prevalent post-stroke and is associated with poor functional outcomes. Stroke experts have highlighted 2 fundamental barriers to progress in rehabilitation and research related to post-stroke cognitive impairment: (1) there is no agreed-upon definition of post-stroke cognitive impairment, and (2) there is no consensus on the appropriate screening and diagnostic procedures. In this paper, we will discuss recent progress and remaining challenges to developing a standard general definition and understanding of post-stroke cognitive impairment. We will provide recommendations to advance the definition of post-stroke cognitive impairment, informed by the steps taken to develop a general definition for mild cognitive impairment. Finally, we discuss the impact these advances might have on stroke rehabilitation, highlighting the potential impact on motor rehabilitation, as an example.

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.

BackgroundSpinocerebellar ataxia (SCA) is a degenerative cerebellar disease, causing progressive impairment of gait and balance in adults. To identify the ideal subjects for disease-modifying therapies it is critical to identify biomarkers for the earliest stages of SCA.ObjectiveWe investigated whether prefrontal cortex activity is increased during walking in in early SCA or in pre-manifest SCA compared to healthy control subjects.MethodsSixteen participants with genetically determined SCA and 15 age-matched healthy controls participated in the study. The SARA was administered by a movement disorders specialist before the gait assessment. An 8-channel, mobile, fNIRS, with 2 reference channels, was used to record changes in oxygenated hemoglobin (HbO₂) and deoxygenated hemoglobin within the PFC. Participants walked for 2-minutes at a comfortable pace while wearing wireless, inertial sensors to derive gait characteristics.ResultsOf the 16 individuals with SCA, 9 were classified as pre-manifest (SARA < 3) and 7 as early SCA (SARA < 10). PFC activity (HbO₂) while walking was greater than controls of similar age in people with SCA. Increased PFC activity was also present even in the pre-manifest stage of SCA. Increase in PFC activity was related to worse gait (double-support time and toe-out angle).ConclusionsPFC activity is increased in pre-manifest SCA, even when clinical scores are normal in the pre-manifest stage of the disease, and may serve as a biomarker that precedes onset of clinical disease. Increased PFC activity is consistent less automatic, cortical control of gait to compensate for impaired automatic, cerebellar control, even in early stages of ataxia.

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.

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.