OBJECTIVE: Upper extremity (UE) motor function loss is one of the most impactful consequences of stroke. Recently, brain-computer interface (BCI) systems have been utilized in therapy programs to enhance UE motor recovery after stroke, widely attributed to neuroplasticity mechanisms. However, the effect that the BCI's closed-loop feedback can have in these programs is unclear. The aim of this study was to quantitatively assess and compare the neuroplasticity effects elicited in stroke patients by a UE motor rehabilitation BCI therapy and by its sham-BCI counterpart. APPROACH: Twenty patients were randomly assigned to either the experimental group (EG), who controlled the BCI system via UE motor intention, or the control group (CG), who received random feedback. The elicited neuroplasticity effects were quantified using asymmetry metrics derived from electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) data acquired before, at the middle, and at the end of the intervention, alongside UE sensorimotor function evaluations. These asymmetry indexes compare the affected and unaffected hemispheres and are robust to lesion location variability. MAIN RESULTS: Most patients from the EG presented brain activity lateralization to one brain hemisphere, as described by EEG (8 patients) and fMRI (6 patients) metrics. Conversely, the CG showed less pronounced lateralizations, presenting primarily bilateral activity patterns. DTI metrics showed increased white matter integrity in half of the EG patients' unaffected hemisphere, and in all but 2 CG patients' affected hemisphere. Individual patient analysis suggested that lesion location was relevant since functional and structural lateralizations occurred towards different hemispheres depending on stroke site. SIGNIFICANCE: This study shows that a BCI intervention can elicit more pronounced neuroplasticity-related lateralizations than a sham-BCI therapy. These findings could serve as future biomarkers, helping to better select patients and increasing the impact that a BCI intervention can achieve. CLINICAL TRIAL: NCT04724824.
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