Neural activity and connectivity as predictors of the individual response to theta-burst stimulation over the motor cortex

Repetitive transcranial magnetic stimulation (rTMS) may alter cortical excitability beyond the stimulation period. However, response to rTMS may vary considerably between subjects. Here, we explored if brain activity and connectivity before stimulation can predict efficacy of excitatory intermittent theta-burst (iTBS) rTMS in healthy subjects. Methods: Nine right-handed volunteers participated in a within subject design on three different days. iTBS over the left M1 or sham stimulation over parieto-occipital cortex were applied. Effects were evaluated by means of motor evoked potentials (MEPs) using single-pulse TMS recorded for 25 min after stimulation. Neural activity and effective connectivity within key motor areas were assessed for a thumb abduction task with the right hand scanned with functional magnetic resonance imaging (fMRI). Results: 70% participants showed enhancement of cortical excitability of the stimulated hemisphere evaluated by single-pulse TMS after iTBS applied over M1 compared to sham stimulation up to 25 min (p=<0.01). A negative correlation between the amount of excitability enhancement and movement-related activity in M1 was observed. Subjects with lower levels of fMRI BOLD-signal before stimulation showed stronger facilitation after iTBS. In addition, subjects with higher connectivity within motor areas in the left hemisphere showed higher motor thresholds and lower MEP’s after real iTBS. Conclusion: These results suggest that the susceptibility of motor system to undergo synaptic plasticity-like processes induced by iTBS is related to the amount of neural activation during a motor task and to intra-hemispheric motor connections. This could be useful to predict which subjects will respond to iTBS or when applied with clinical purposes to predict which patients could benefit with the treatment.