Guangxu Xu

Background: Upper-limb dysfunction, particularly impaired distal hand function, remains one of the most disabling sequelae following a stroke. Soft robotic glove (SRG) training can provide repetitive and task-specific hand practice; however, its therapeutic effects may be limited by insufficient modulation of the damaged motor network. Transcranial temporal interference stimulation (tTIS), a novel non-invasive neuromodulation approach capable of targeting deeper neural circuits, may enhance post-stroke motor recovery by engaging cerebellar-related motor pathways and promoting network-level plasticity. Objective: This study investigated whether cerebellar tTIS combined with SRG training improves upper-limb motor function in patients with subacute stroke and explored the associated changes in cortical activation and resting-state functional connectivity (FC) using functional near-infrared spectroscopy (fNIRS). Method: In this prospective, single-center, randomized, sham-controlled pilot trial, 46 patients with first-ever subacute stroke were randomized 1:1 to the tTIS-SRG group ( n = 22) or the SRG group ( n = 22). Both groups received conventional rehabilitation and SRG training. The tTIS-SRG group additionally received active cerebellar tTIS, whereas the SRG group received sham stimulation, delivered once daily, 5 days per week, for 2 weeks. The primary outcome was the upper-limb motor function assessed by the Action Research Arm Test (ARAT), and the secondary outcome was activities of daily living (ADL) assessed by the modified Barthel Index (MBI). fNIRS was used to evaluate task-related cortical activation and resting-state functional connectivity before and after the intervention. This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2500107031). Results: Of the 46 randomized participants, 44 completed the trial and were included in the final analysis (22 per group). One participant in the tTIS-SRG group withdrew from the study due to hospital discharge, and one participant in the SRG group declined the final assessment for personal reasons. Participants in both groups showed improvements in ARAT and MBI scores following treatment. The tTIS-SRG group demonstrated a significantly greater improvement in ARAT scores than the SRG group ( Z = −2.955, p = 0.003), whereas the between-group difference in MBI change was not significant ( Z = −1.706, p = 0.088). fNIRS analysis revealed that false discovery rate (FDR)-corrected channel-level analysis identified greater oxyhemoglobin (HbO) changes in the tTIS-SRG group than in the SRG group in two channels located in the ipsilateral frontal pole area (FPA) and ipsilateral somatosensory cortex (SSC). No region of interest (ROI)-level comparison remained statistically significant after FDR correction. Although several channel-level comparisons reached nominal significance before correction, only two channels remained statistically significant after FDR correction. Conclusion: In this pilot trial, cerebellar tTIS combined with SRG training provided a more significant improvement in upper-limb motor recovery compared with SRG training alone in patients with subacute stroke. The observed clinical improvement was accompanied by enhanced task-related cortical activation and changes in motor-related functional connectivity. Larger multicenter trials with longer follow-up are needed to confirm the efficacy, durability, and underlying mechanisms of this combined intervention. Clinical trial registration: https://www.chictr.org.cn/searchprojEN.html , identifier ChiCTR2500107031.

Background: Closed-loop motor imagery brain-computer interface (MI-BCI) training may support post-stroke upper-limb rehabilitation by coupling motor intention with contingent multisensory feedback. This randomized pilot trial examined its feasibility, safety, short-term clinical effects, and exploratory EEG correlates in patients with subacute stroke. Methods: In this single-center, assessor-blinded, two-arm pilot trial, 40 patients with first-ever subcortical stroke in the subacute phase were randomized 1:1 to a BCI group or an active control group after a 2-day motor imagery familiarization phase. Both groups received routine medical management, standardized conventional rehabilitation, and dose-matched motor imagery-based hand training for 4 weeks. The BCI group received EEG-contingent closed-loop MI-BCI-assisted training with a soft rehabilitation glove, whereas the control group received non-EEG-contingent glove-assisted motor imagery training under matched training duration, task instructions, device exposure, and multisensory feedback. The primary outcome was the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE). Secondary outcomes included the Action Research Arm Test (ARAT) and Modified Barthel Index (MBI). Exploratory EEG outcomes included FFT%α and FFT%β during motor imagery. Clinical and EEG outcomes were analyzed using baseline-adjusted ANCOVA models, with week-4 values as dependent variables and corresponding baseline values as covariates. Results: All randomized participants completed the 4-week assessment. In baseline-adjusted ANCOVA models, the BCI group showed higher week-4 scores than the control group for FMA-UE (adjusted mean difference, 13.40 points; 95% CI, 10.71–16.08; p < 0.001), ARAT (7.31 points; 95% CI, 4.55–10.07; p < 0.001), and MBI (12.21 points; 95% CI, 8.55–15.87; p < 0.001). Exploratory EEG analyses also showed higher week-4 FFT%α and FFT%β in the BCI group, with adjusted mean differences of 6.78 percentage points (95% CI, 5.22–8.34; p < 0.001) and 3.95 percentage points (95% CI, 2.53–5.36; p < 0.001), respectively. No serious adverse events occurred. Conclusion: Closed-loop MI-BCI-assisted training was feasible and well tolerated in selected patients with subacute stroke. The observed short-term improvements in upper-limb impairment and activity capacity provide preliminary signals of potential benefit beyond dose-matched non-EEG-contingent feedback training. Exploratory EEG findings suggest task-related modulation of alpha- and beta-band sensorimotor rhythmic activity, but should be interpreted as hypothesis-generating rather than confirmatory evidence of neural reorganization. Larger multicenter trials with longer follow-up, rigorous neurophysiological analyses, and real-world upper-limb use outcomes are needed. Clinical Trial Registration: ChiCTR2400083992. https://www.chictr.org.cn/showproj.html?proj=229529

Objectives: To develop a machine learning (ML)-based prognostic model for predicting the risk of lower extremity deep vein thrombosis (DVT) after acute stroke, with an emphasis on limb functional assessments. Methods: We conducted a retrospective analysis of 225 acute stroke patients admitted within 15 days of onset between December 1, 2015, and April 30, 2025. Predictor variables were selected using collinearity diagnostics and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Three machine learning survival models—Gradient Boosting Machine (GBM), Random Survival Forest (RSF), and Generalized Linear Model (GLM)—were employed to identify the most effective model. The performance of the optimal ML model was compared with that of the traditional Cox proportional hazards model using the concordance index (C-index), cumulative/dynamic area under the curve (C/D AUC), and integrated Brier score (IBS). The optimal model was further interpreted using SurvSHAP(t). Results: Six variables were selected for the model: age, stroke type, gender, tension of the muscle, Brunnstrom stage (lower limb), and sitting balance. The RSF model, implemented using the Ranger algorithm, demonstrated superior performance, with an integrated Brier score (IBS) of 0.081 and a C-index of 0.841. Age and Brunnstrom stage (lower limb) were identified as the most influential predictors. Conclusion: We developed an ML-based prognostic model for predicting the risk of lower limb DVT after acute stroke. Age and Brunnstrom stage (lower limb) were the most significant predictors. This model shows promise for risk stratification in clinical practice.

Background and Objectives: Studies have shown that lung function and chronic obstructive pulmonary disease (COPD) are associated with functional outcome for several diseases, as well as the onset of stroke. However, the causal relationship between lung function, COPD and the functional outcome of ischemic stroke (IS) is unclear. The aim of this study was to investigate the causal relationship between lung function, COPD and IS functional outcomes using Mendelian randomization (MR). Methods: Lung function data were derived from the Genome-wide Association Study (GWAS) summary database. Data of COPD were derived from the national genetic factors data repository of the FinnGen project in Finland. The outcome data of IS function were obtained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) Network. Univariate MR analysis mainly used the inverse variance weighting (IVW) method, MR-Egger, weighted median method and two-sample Maximum Likelihood to evaluate the causal effects of lung function and COPD on the prognosis of IS. Sensitivity analyses were conducted by evaluating heterogeneity and potential pleiotropy. Additionally, multivariable MR analyses were employed to ascertain whether these effects were independent. Results: In univariate MR analyses, the estimates of IVW, MR-Egger, weighted median method and two-sample Maximum Likelihood analysis all showed that there was no genetic causal relationship between COPD, FVC, FEV1, FEV1/FVC, PEF and functional outcome after IS (P>0.05). Sensitivity analyses yielded no evidence of directional pleiotropy or substantial heterogeneity. Multivariable MR analyses demonstrated that, after adjustment for insomnia, smoking initiation, waist-to-hip ratio(WHR) or depression, both COPD and PEF exhibited a causal association with adverse functional outcome following IS. Conclusion: Our research indicated that at the level of genetic causality, no significant associations were observed between lung function indices (FEV1, FVC, FEV1/FVC, PEF) or COPD and functional outcome following IS. Our discovery may challenge the conventional notion that “improving lung function itself can efficiently promote the prognosis of IS function”. Future research needs to further explore other possible causal pathways and consider various factors comprehensively to develop more effective rehabilitation strategies after IS.

Purpose: Chronic non-specific low back pain (CNLBP) is a complex and heterogeneous condition, and it is necessary to explore new treatment approaches. We evaluated whether the addition of dry cupping therapy to guideline‑based conventional therapy would further improve clinical outcomes in CNLBP. Methods: Thirty-six patients with CNLBP were recruitedand randomly divided into two groups: the control group and the intervention group. The intervention group received cupping therapy in addition to the control group (core stabilization exercises, spinal manipulation and education) for 4 weeks. The primary outcome was the visual analog scale (VAS) for pain intensity. Secondary outcomes were the Roland Morris disability questionnaire (RMDQ), and pressure pain thresholds (PPT) at bilateral Shenshu (BL23), Qihaishu (BL24), and Dachangshu (BL25) acupuncture points. Results: At week 4 the between‑group difference in resting pain was trivial (median difference 0.0 cm, 95% CI − 1.0 to 1.0). Neither clinically important nor statistically significant differences were detected in disability or PPTs. Both groups improved substantially from baseline. Conclusion: In this randomized trial, adding dry cupping to conventional therapy offered no additional benefit over conventional therapy alone for pain, disability or PPT in CNLBP. Larger, multicentre trials with longer follow‑up and standardized negative pressures are warranted. Trial registration: ChiCTR2300069398, http://www.chictr.org.cn, Registration Date: March 15, 2023.

This study investigated the effects of Computerized Quadrato Motor Training (CQMT) on balance and executive function in both single- and dual-task conditions for stroke patients. Patients (n = 60) were randomized to three groups: conventional training (CT), exercise training (ET), and interactive motor-cognitive training (IT). All participants underwent CT. Besides, the ET group undertook step training, and the IT group underwent CQMT for four weeks. The assessments comprised balance function, executive function, lower limb strength, as well as self-efficacy of balance control. Balance function was assessed via the Pro-Kin system and standardized scales (Berg Balance Scale [BBS], Tinetti Assessment [POMA]). Executive function was assessed by the Trail Making Test (TMT-A / B) and Stroop test. Dual-task cost (DTC) derived from Timed Up-and-Go Test with/without cognitive loading (TUGT / TUGTcog). Balance self-efficacy was assessed by the Activities-specific Balance Confidence (ABC) Scale, with lower limb strength assessed by Five-Times Sit-to-Stand (FTSTS). After the intervention, the ET significantly showed improvement in the elliptical trajectory area, BBS, and gait performance compared to CT(P < 0.05). The IT group demonstrated significantly greater improvements in balance parameters (swing speed, elliptical trajectory area, trajectory lengths; P < 0.05) and functional outcomes (BBS, POMA, FTSTS, Dual-Task performance, TMT, Stroop, ABC; P < 0.01) compared to both CT and ET. The IT group showed significant positive correlations between TMT improvements and enhanced Dual-ask performance. Our findings demonstrate that CQMT, as an integrative motor-cognitive intervention, significantly improves balance and executive function in stroke patients, thereby filling a critical gap in the clinical application of QMT in stroke rehabilitation research. These findings validate the ‘guided plasticity facilitation’ theory, highlighting CQMT as a cost-effective and broadly applicable clinical training. Trial registration: The clinical trial was registered on 08/10/2023, with the registration number ChiCTR2300076424.

Introduction: Cognitive impairment after a stroke significantly affects patients' quality of life, yet not all strokes lead to such impairment, and the underlying reasons remain unclear. This study employs resting‐state functional magnetic resonance imaging (rs‐fMRI) to compare subcortical stroke patients with and without cognitive impairment. Our goal is to identify distinct abnormalities in regional brain spontaneous activity and functional connectivity (FC) to better understand the neural basis of post‐stroke cognitive outcomes.Methods: A total of 62 first‐ever non‐acute subcortical stroke patients were classified into post‐stroke with abnormal cognition (PSAC) and with normal cognition (PSNC) groups. Rs‐MRI was utilized to assess regional homogeneity (ReHo) in 32 PSAC, 30 PSNC, and 62 age‐ and sex‐matched healthy controls (HC). Then we performed the seed‐based whole‐brain FC analysis based on the ReHo results. A partial correlation analysis examined the relationship between altered ReHo or FC and Montreal Cognitive Assessment (MoCA) scores.Results: It showed varied activity in cognitive‐related brain regions in both stroke groups compared to HC, such as the right superior frontal gyrus, the right middle temporal gyrus, the right postcentral gyrus, and the left cerebellar lobules. The PSAC group had increased activity in the bilateral inferior temporal gyrus as well. Significant differences in activity were also found between PSAC and PSNC groups, with the PSAC group showing decreased activity in the left gyrus rectus (REC) and increased activity in cerebellar lobules. FC analysis revealed decreased connections in the PSAC group, particularly involving the left REC. Activity and FC in left REC and cerebellum also significantly correlated with MoCA scores.Conclusions: These findings suggest unique patterns of brain activity and connectivity in non‐acute subcortical stroke patients with cognitive impairment, shedding light on potential neural mechanisms underlying post‐stroke cognitive impairment. While the left REC may be a potential neural regulatory stimulus target in clinical applications.

Background: The perception of Subjective Visual Vertical (SVV) is crucial for postural orientation and significantly reflects an individual’s postural control ability, relying on vestibular, visual, and somatic sensory inputs to assess the Earth’s gravity line. The neural mechanisms and aging effects on SVV perception, however, remain unclear.Objective: This study seeks to examine aging-related changes in SVV perception and uncover its neurological underpinnings through functional near-infrared spectroscopy (fNIRS).Methods: In a comparative study of 19 young and 19 older adults, the standardized SVV task executed in Eprime 3.0 software evaluated participants’ SVV orientation and uncertainty. Cortical responses were monitored via fNIRS during the task, with block averaging analysis employed to delineate the associated hemodynamic responses. The study further correlated these neuroimaging findings with behavioral measures.Results: Young individuals exhibit superior accuracy and stability in perceiving the subjective visual vertical (SVV) direction. Neuroimaging data, adjusted for multiple comparisons using the false discovery rate, reveal activation of the right supramarginal gyrus (SMG) and the left dorsolateral superior frontal gyrus (SFGdor) in both age groups during SVV tasks. However, older participants show additional activation in regions such as the bilateral postcentral gyrus (PoCG) and the right middle frontal gyrus (MFG). Lateralization studies indicate that young participants predominantly exhibit right lateralization in sensory and dorsolateral prefrontal cortices, with left lateralization in the motor cortex. In contrast, elderly participants demonstrate bilateral dominance across sensory, dorsolateral prefrontal, and motor cortices. Correlational analyses link modified SVV metrics to the activation levels of various brain regions, with negative correlations observed in both age groups, and a unique positive correlation with the left inferior frontal gyrus of the triangular part (IFGtriang) in young participants.Conclusion: Young individuals outperform the older individuals in SVV performance due to age-related differences in brain functional patterns during the execution of vertical perception judgment. Both age groups activate the right SMG and left SFGdor, but the older individuals additionally activate regions such as bilateral PoCG and right MFG. While young people exhibit right-brain dominance, the older people rely on bilateral cognitive resources, indicating bilateral dominance. Except for the left IFGtriang in the young, higher activation in brain regions correlates with better SVV performance.