Objective. Combining repetitive transcranial magnetic stimulation (rTMS) with brain-computer interface (BCI) training can address motor impairment after stroke by down-regulating exaggerated inhibition from the contralesional hemisphere and encouraging ipsilesional activation. The objective was to evaluate the efficacy of combined rTMS+BCI, compared to sham rTMS+BCI, on motor recovery after stroke in subjects with lasting motor paresis. Approach. Three stroke subjects approximately one year post-stroke participated in three weeks of combined rTMS (real or sham) and BCI, followed by three weeks of BCI alone. Behavioral and electrophysiological differences were evaluated at baseline, after three weeks, and after six weeks of treatment. Main Results. Motor improvements were observed in both real rTMS+BCI and sham groups, but only the former showed significant alterations in inter-hemispheric inhibition in the desired direction and increased relative ipsilesional cortical activation from fMRI. In addition, significant improvements in BCI performance over time and adequate control of the virtual reality BCI paradigm were observed only in the former group. Significance. When combined, the results highlight the feasibility and efficacy of combined rTMS+BCI for motor recovery, demonstrated by increased ipsilesional motor activity and improvements in behavioral function for the real rTMS+BCI condition in particular. Our findings also demonstrate the utility of BCI training alone, as demonstrated by behavioral improvements for the sham rTMS+BCI condition. This study is the first to evaluate combined rTMS and BCI training for motor rehabilitation and provides a foundation for continued work to evaluate the potential of both rTMS and virtual reality BCI training for motor recovery after stroke.
Individuals with functional movement disorders (FMDs) account for 3–20% of all patients seen in movement-disorder clinics (1–3). There is no consensus treatment for FMDs (4–6). These movement disorders are not due to irreversible brain damage but their outcome is nonetheless poor: symptoms are persistent or worse after 1.5–7 years of follow-up in between 44 and 90% of patients (6, 7). FMDs generate major healthcare costs, as well as indirect costs due to unemployment and disability (8).
Recent studies suggest a beneficial effect of repeated supraliminal low-frequency transcranial magnetic stimulation (TMS) (i.e., TMS ≤ 1 Hz) on functional motor symptoms (9–14) [Ref. (15) for a review]. Among these studies, only one included a blinded assessment (11), and only one included a control group (sham treatment) (9). Focusing on FMDs more specifically, two studies showed a beneficial effect of supraliminal low-frequency TMS, with a mean improvement rate of 67% (11) and 97% (13). It is unclear whether the therapeutic benefit is due to cortical neuromodulation, i.e., to changes in cortical excitability and in connectivity between brain areas (15, 16). The alternative hypothesis is a cognitive-behavioral effect, a therapeutic effect that is linked to suggestion and/or motor relearning.
To address this issue, we blindly compared the therapeutic effect of repeated TMS and repeated root magnetic stimulation (RMS) in patients with FMDs. RMS was chosen as the control treatment to mimic TMS-induced movement without directly stimulating the cortex.