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.
Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are the most commonly used methods of non-invasive transcranial brain stimulation that has been abbreviated by previous authors as either as NIBS or NTBS. Here we use NIBS since it seems to be the most common term at the present time. When it was first introduced in 1985, TMS was employed primarily as a tool to investigate the integrity and function of the human corticospinal system (Barker et al., 1985). Single pulse stimulation was used to elicit motor evoked potentials (MEPs) that were easily evoked and measured in contralateral muscles (Rothwell et al., 1999). The robustness and repeatability of measures of conduction time, stimulation threshold and “hot spot” location allowed TMS to be developed into a standard tool in clinical neurophysiology.
As we review below, a number of NIBS protocols can lead to effects on brain excitability that outlast the period of stimulation. These may reflect basic synaptic mechanisms involving long-term potentiation (LTP)- or long-term depression (LTD)-like plasticity, and because of this there has been great interest in using the methods as therapeutic interventions in neurological and psychiatric diseases. Furthermore, recently they are more frequently applied to modify memory processes and to enhance cognitive function in healthy individuals. However, apart from success in treating some patients with depression (Lefaucheur et al., 2014; Padberg et al., 2002, 1999), there is little consensus that they have improved outcomes in a clinically meaningful fashion in any other conditions. The reason for this is probably linked to the reason why many other protocols failed to reach routine clinical neurophysiology: they are too variable both within and between individuals to make them practically useful in a health service setting (Goldsworthy et al., 2014; Hamada et al., 2013; Lopez-Alonso et al., 2014, 2015).
Below we review the evidence for the mechanisms underlying the “neuroplastic” effects of NIBS, and then consider the problems in reproducibility and offer some potential ways forward in research. […]