Long-Term Brain–Computer Interface Functional Electrical Stimulation Enhances Neuroplasticity and Functional Recovery in Elderly Stroke: A 4.5-Year Longitudinal Study Integrating Electroencephalography Biomarkers and Clinical Assessments
Shugeng Chen, Na Xie, Yurui Tang, Yanyun Ji, Zhijie He, Yuchun Wang, Xude Huang, Jianghong Fu, Mingyuan Ge, Qiang Liu, Mingfen Li, Qinqin Xiao, Ying Xu, Jing Wang, Jie Jia, Shumao Xu
Abstract
Stroke-induced motor and cognitive impairments substantially reduce the quality of life in elderly populations, driving the need for rehabilitation strategies that integrate neural plasticity and functional recovery. In this 4.5-year longitudinal study, we evaluated the efficacy of brain–computer interface combined with functional electrical stimulation (BCI-FES) versus FES only and conventional care (control) in 100 stroke survivors (60 to 90 years; 4,172 total screened, with 24 chronic-stage patients [>1 year post-onset] completing long-term follow-up). We integrated clinical metrics (Fugl-Meyer assessment [FMA], modified Barthel index [MBI], and Montreal Cognitive Assessment [MoCA]) with electroencephalography-based neurophysiological profiling to dissect recovery mechanisms. BCI-FES yielded superior and sustained improvements across all domains: motor function (FMA Δ = 4.5 ± 1.2 points, Cohen’s d = 1.2) versus FES (Δ = 1.7 ± 0.8, d = 0.4) and control (Δ = 0.9 ± 0.6, d = 0.2), functional independence (MBI Δ = 5.4 ± 1.5, d = 1.1) exceeding FES (Δ = 2.2 ± 1.1, d = 0.4) and control (Δ = 1.3 ± 0.5, d = 0.5), and cognitive function (MoCA Δ = 1.6 ± 0.5, d = 0.8 at 4 months), although cognitive gains declined to near baseline by 4.5 years. Hemorrhagic stroke patients showed exceptional BCI-FES responses, while ischemic patients exhibited higher variability. Neurophysiologically, BCI-FES induced theta (Cz and C4) and alpha (FC3 and CP3) power increases, with theta power at Cz strongly predicting FMA gains ( r = 0.68), and enhanced theta/alpha band functional connectivity (clustering coefficient +22%, local efficiency +18%, and small-world index +15%). Predictive modeling identified that an optimal treatment window (3 to 12 months post-onset with 10 to 15 weeks of therapy) maximizes recovery via peak neuroplasticity, and a responder profile (stroke duration <23 months) includes patients with residual plasticity (age <70, baseline MBI >40), predicting 76% of favorable outcomes. These findings establish BCI-FES as a transformative rehabilitation tool, driving dual-phase recovery via early cortical plasticity and sustained network coherence while highlighting the need for age-tailored cognitive maintenance strategies. This work redefines precision stroke care by merging clinical outcomes with mechanistic insights, positioning BCI-FES as the standard of care for diverse stroke subtypes.