Paired-pulse TMS and scalp EEG reveal systematic relationship between inhibitory GABAa signaling in M1 and fronto-central cortical activity during action stopping.

By stopping actions even after their initiation, humans can flexibly adapt ongoing behavior to changing circumstances. The neural processes underlying the inhibition of movement during action stopping are still controversial. In the 90s, a fronto-central event-related potential (ERP) was discovered in the human EEG response to stop signals in the classic stop-signal task, alongside a proposal that this "stop-signal P3" reflects an inhibitory process. Indeed, both amplitude and onset of the stop-signal P3 relate to overt behavior and movement-related EEG activity in ways predicted by the dominant models of action-stopping. However, neither EEG nor behavior allow direct inferences about the presence or absence of neurophysiological inhibition of the motor cortex, making it impossible to definitively relate the stop-signal P3 to inhibition. Here, we therefore present a multimethod investigation of the relationship between the stop-signal P3 and GABAergic signaling in primary motor cortex, as indexed by paired-pulse transcranial magnetic stimulation (TMS). In detail, we measured short-interval intracortical inhibition (SICI), a marker of inhibitory GABAa activity in M1, in a group of 41 human participants who also performed the stop-signal task while undergoing EEG recordings. In line with the P3-inhibition hypothesis, we found that subjects with stronger inhibitory GABA activity in M1 also showed both faster onsets and larger amplitudes of the stop-signal P3. This provides direct evidence linking the properties of this ERP to a true physiological index of motor system inhibition. We discuss these findings in the context of recent theoretical developments and empirical findings regarding the neural implementation of motor inhibition.NEW & NOTEWORTHY The neural mechanisms underlying rapid action stopping in humans are subject to intense debate, in part because recordings of neural signals purportedly reflecting inhibitory motor control are hard to directly relate to the true, physiological inhibition of motor cortex. For the first time, the current study combines EEG and transcranial magnetic stimulation (TMS) methods to demonstrate a direct correspondence between fronto-central control-related EEG activity following signals to cancel an action and the physiological inhibition of primary motor cortex.