Multi-session delivery of synchronous rTMS and sensory stimulation induces long-term plasticity

BackgroundCombining training or sensory stimulation with non-invasive brain stimulation has shown to improve performance in healthy subjects and improve brain function in patients after brain injury. However, the plasticity mechanisms and the optimal parameters to induce long-term and sustainable enhanced performance remain unknown. ObjectiveThis work was designed to identify the protocols of which combining sensory stimulation with repetitive transcranial magnetic stimulation (rTMS) will facilitate the greatest changes in fMRI activation maps in the rats primary somatosensory cortex (S1). MethodsSeveral protocols of combining forepaw electrical stimulation with rTMS were tested, including a single stimulation session compared to multiple, daily stimulation sessions, as well as synchronous and asynchronous delivery of both modalities. High-resolution fMRI was used to determine how pairing sensory stimulation with rTMS induced short and long-term plasticity in the rat S1. ResultsAll groups that received a single session of rTMS showed short-term increases in S1 activity, but these increases did not last three days after the session. The group that received a stimulation protocol of 10 Hz forepaw stimulation that was delivered simultaneously with 10 Hz rTMS for five consecutive days demonstrated the greatest increases in the extent of the evoked fMRI responses compared to groups that received other stimulation protocols. ConclusionsOur results provide direct indication that pairing peripheral stimulation with rTMS induces long-term plasticity, and this phenomenon appears to follow a time-dependent plasticity mechanism. These results will be important to lead the design of new training and rehabilitation paradigms and training towards achieving maximal performance in healthy subjects. HighlightsO_LIA single rTMS session induced short-term changes but they were not sustainable C_LIO_LIMulti-session delivery of rTMS paired with sensory stimulation induced long-term plasticity C_LIO_LIrTMS paired with sensory stimulation induced plasticity via time-dependent mechanism C_LIO_LIDelivery of sensory stimulation only did not induce long-term plasticity C_LI