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

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.