Connecting the dots: Harnessing dual-site transcranial magnetic stimulation to assess the causal influence of medial frontal areas on the motor cortex

Abstract

Dual–site transcranial magnetic stimulation (TMS) has been widely exploited to probe the influence of cortical structures on the primary motor cortex (M1). However, several issues remain open, notably regarding the use of this approach on areas of the medial frontal cortex – including the supplementary motor area (SMA) and the ventromedial prefrontal cortex (vmPFC) – known to play a fundamental role in motor behavior. First, the few TMS studies that have targeted SMA have mostly focused on short inter–stimulation intervals (6–8 ms), supposed to recruit cortico–cortical circuits. There is a current lack of data on the nature of the influence (i.e., facilitatory vs. suppressive) of SMA stimulation on M1 when probed with longer intervals (10–15 ms), thought to recruit more indirect cortico-subcortico–cortical circuits. Second, it is unclear whether the facilitatory influence of SMA stimulation previously reported with short intervals reflects the recruitment of cortico–cortical circuits (as commonly assumed) or results from the summation of volleys descending from SMA and M1 at the spinal level. Third, dual–site TMS has never been used to date to probe the influence of the vmPFC on M1, putatively due to the presumed difficulty of reaching the former area with magnetic fields. Here, we show that SMA stimulation facilitates motor activity with a 12 ms interval. Additionally, our data reveal that the facilitatory influence of SMA stimulation observed with short intervals does not result from spinal interactions. Finally, we show that vmPFC stimulation induces a moderate suppressive effect on M1, both with short and with long inter–stimulation intervals.