Neurorehabilitation and neural repair最新文献

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.

AimsSerum soluble low-density lipoprotein receptor-related protein 1 (sLRP1) has been implicated in the severity of ischemia-reperfusion injury in experimental stroke models. Its potential prognostic value in ischemic stroke recovery warrants further investigation. This study aims to explore the association between serum sLRP1 levels and functional outcome improvement from 3 to 12 months following acute ischemic stroke (AIS).MethodsWe included patients hospitalized for AIS within 24 hours of symptom onset. Serum sLRP1 levels at admission were analyzed for their association with functional outcome improvement, defined as a ≥1-point decrease in the modified Rankin Scale (mRS) score between 3 and 12 months. Multivariate binary logistic regression was employed to adjust for potential confounders. Improvements in predictive performance by including sLRP1 were assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).ResultsA total of 171 patients were enrolled (median age: 65 years; 64.9% male). Functional outcome improvement was observed in 53 patients (31.0%). After adjusting for confounding factors, patients in the second and third tertiles of sLRP1 had significantly lower odds of functional outcome improvement compared to those in the lowest tertile (Tertile 2, odds ratio [OR] 0.19, 95% confidence interval [CI]: 0.08-0.49, P = .001; Tertile 3, OR 0.10, 95% CI: 0.03-0.27, P < .001). Incorporating sLRP1 into predictive models alongside conventional factors significantly enhanced reclassification accuracy (NRI = 46%, P = .004; IDI = 4%, P = .014).ConclusionsLower serum sLRP1 levels at admission are independently associated with functional outcome improvement after AIS. These findings suggest that modulating sLRP1 may represent a promising therapeutic strategy to enhance recovery in stroke patients.

BackgroundShort-term maintenance of phonological information is critical for language production and comprehension, and is often impaired in stroke survivors with aphasia.ObjectiveIn this pilot study, we investigated whether brain oscillatory activity underlying phonological short-term memory (pSTM) can be influenced by transcranial alternating current stimulation (tACS) in stroke survivors with aphasia (SWA).MethodsIn a within-subject, single-blinded, sham-controlled study, 13 SWA received theta-tACS (4-7 Hz) targeting left temporoparietal and inferior frontal regions across 3 tACS conditions (in-phase, anti-phase, and sham; 20 minutes each). Participants completed an adaptive delayed match-to-sample task with spoken consonant-vowel strings (2-8 syllables) before, during, and after stimulation. The primary outcome was change in pSTM capacity (ie, number of syllables maintained over a 5-second delay), estimated using a linear interpolation approach. We hypothesized that in-phase tACS would enhance, and anti-phase tACS would disrupt, pSTM capacity relative to sham.ResultsLME analyses reveal significant interactions between tACS condition and block (F(4, 91.9) = 2.65, P = .038), and post-hoc estimated marginal means comparisons show increased pSTM capacity during in-phase tACS versus sham (estimate = 0.71, t(92) = 2.26, P = .040) and anti-phase (estimate = 0.75, t(92) = 2.44, P = .040) conditions, only during the stimulation period. Differences between anti-phase and sham-tACS were not significant (estimate = -0.04, P = .901). Individual response to tACS was variable, with only 60% of SWA responding.ConclusionsThis study supports in-phase theta-tACS positively impacts pSTM. Larger studies are needed to confirm these findings and evaluate lasting effects to increase clinical relevance.

IntroductionFunctional electrical stimulation (FES) may enhance the impact of locomotor training on walking impairments following spinal cord injury (SCI).ObjectiveThis systematic review (PROSPERO: CRD42023435210) evaluated the therapeutic effectiveness of FES-assisted locomotor training (FALT) on improving walking speed and endurance for individuals with motor incomplete SCI (iSCI).MethodsDatabases (MEDLINE, EMBASE, CINAHL) were searched for interventional studies of FALT in iSCI that assessed the therapeutic effects on walking speed and/or endurance when the FES was not active. Study characteristics and findings were extracted, summarized, and narratively synthesized. Risk of bias was assessed using the Cochrane tools for interventional studies. Random effects meta-analyses were conducted to generate standardized pooled effect sizes for both outcomes.ResultsThirteen studies were identified: 4 randomized controlled trials (RCTs) and 9 pre-post tests. RCTs scored low (n = 1 study), intermediate (n = 1), and high (n = 2) on the RoB2, and all pre-post tests studies (n = 9) scored high on the ROBINS-I. Meta-analyses of 3 RCTs found that treadmill-based FALT was associated with a small, non-significant effect on walking speed (n = 76 participants; Hedge's g: -0.01; 95% CI: -0.46, 0.43; P = .96) and a small, non-significant effect on walking endurance (n = 71; Hedge's g: 0.20; 95% CI: -0.25, 0.65; P = .39) when compared to control conditions.DiscussionThis review did not find evidence that FALT improves walking speed or endurance for people with iSCI relative to other types of locomotor training. Future trials of FALT for SCI should aim to better standardize and report training dose and stimulation parameters to improve comparability.

Background: Clinical practice guidelines for walking recovery post-stroke recommend high aerobic intensity training, which usually involves walking at fast speeds. However, the acute effect of fast speeds on the neuromuscular control of walking is unclear.

Objectives: (1) Assess the criterion validity of the Dynamic Motor Control Index (WalkDMC) as a measure of coactivation post-stroke. (2) Assess acute speed-dependent coactivation post-stroke. (3) Assess how clinical characteristics shape the speed-dependent coactivation response. (4) Assess the relationship between heart rate and coactivation post-stroke. We hypothesized that WalkDMC is correlated with function and impairment measures. We also hypothesize that coactivation measured via the WalkDMC increases for speeds above or below self-selected speeds (SSS).

Methods: 32 chronic stroke survivors and 17 age and sex-matched controls walked at SSS, fast, and slow speeds. EMGs were measured bilaterally on 7 lower extremity muscles. We used non-negative matrix factorization to calculate WalkDMC. We used regression to assess the relationship between WalkDMC, speed, heart rate, and clinical outcomes.

Results: WalkDMC was correlated with clinical outcomes, supporting its criterion validity. We observed a quadratic relationship between speed and coactivation: for the paretic extremity, the predicted speed that would lead to the lowest coactivation was ~120% higher than SSS. Slow speeds consistently increased coactivation in controls and participants post-stroke. Coactivation in the paretic extremity was significantly predicted by speed, balance, and impairment.

Conclusions: Our results suggest that increased speeds lead to differential improvements in coactivation in the paretic and non-paretic extremities. These results may inform speed prescriptions for HIT interventions.

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.

BackgroundStroke is the leading cause of long-term disability, making the search for successful rehabilitation treatment one of the most important public health issues. A better understanding of the neural mechanisms underlying impairment and recovery is critical for optimizing treatments. Objective: We studied the longitudinal changes in brain oscillatory modes, linked to GABAergic system activity, and determined their importance for residual upper-limb motor functions and recovery.MethodsTranscranial Magnetic Stimulation (TMS) was combined with scalp Electroencephalography (EEG) to analyze TMS-induced brain oscillations in a cohort of 66 stroke patients in the acute (N = 60), early (N = 48), and late subacute stages (N = 37).ResultsA data-driven parallel factor analysis (PARAFAC) approach to tensor decomposition extracted brain oscillatory modes, which significantly evolved longitudinally across stroke stages (permutation tests, p_Bonf < 0.05). Notably, the observed decrease of the α-mode, known to be linked with GABAergic system activity, was mainly driven by the recovering patients and was supportive of stroke recovery at the group level (Bayesian Kendall correlation, moderate to strong statistical evidence).ConclusionsOverall, longitudinal evaluation of brain modes provides novel insights into functional reorganization of brain networks after a stroke. Notably, we propose that the observed α-mode decrease could correspond to a beneficial disinhibition toward the late subacute stage that fosters plasticity and facilitates recovery. These results confirm the relevance of future individual and direct monitoring of post-stroke modulations in inhibitory system activity, with the ultimate goal of designing electrophysiological biomarkers and refining therapies based on personalized neuromodulation.

BackgroundFunctional mobility is essential for maintaining independence and relies on both motor and cognitive processes. Although the impact of motor impairments on functional mobility in stroke survivors has been extensively studied, the influence of post-stroke cognitive impairments has been largely overlooked. The aim of the current study is 2-fold. First, to determine the impact of post-stroke cognitive impairments on functional mobility across a broad spectrum of tasks. Second, to determine if cognitive impairment has a differential impact on various forms of mobility.MethodForty individuals with stroke (20 cognitively normal and 20 cognitively impaired) and 30 healthy older adults participated in the study. Participants performed cognitive, motor, and mobility assessments. Cognitive tests included global and domain-specific assessments on an extensive neuropsychological battery. Motor tests included the Modified Rankin Scale and strength assessments. Functional mobility included the assessment of balance, overground walking, and driving in a simulator.ResultsFindings indicated that stroke survivors with cognitive impairment demonstrated significant deteriorations in functional mobility across multiple domains, compared to both cognitively normal stroke survivors and healthy older adults. Cognitive impairment significantly interferes with functional mobility, with driving showing greatest deterioration compared to balance and walking performance. Notably, this impact is independent of the level of disability and motor strength.ConclusionCognitive impairments in stroke survivors are associated with significant mobility disturbances, with the most pronounced deficits in driving performance. This study highlights the importance of including and prioritizing cognitive evaluation and intervention for enhancing functional mobility and independence in stroke survivors.