Latency and amplitude of the stop-signal P3 event-related potential are related to inhibitory GABA_aactivity in primary motor cortex

Abstract

By stopping actions even after their initiation, humans can adapt their ongoing behavior rapidly to changing environmental circumstances. The neural processes underlying the implementation of rapid action-stopping are still controversially discussed. In the early 1990s, a fronto-central P3 event-related potential (ERP) was identified in the human EEG response following stop-signals in the classic stop-signal task, accompanied by the proposal that this ERP reflects the “inhibitory” side of the purported horse-race underlying successful action-stopping. Later studies have lent support to this interpretation by finding that the amplitude and onset of the stop-signal P3 relate to both overt behavior and to movement-related EEG activity in ways predicted by the race model. However, such studies are limited by the ability of EEG to allow direct inferences about the presence (or absence) of true, physiologically inhibitory signaling at the neuronal level. To address this, we here present a cross-modal individual differences investigation of the relationship between the features stop-signal P3 ERP and GABAergic neurotransmission in primary motor cortex (M1, as measured by paired-pulse transcranial magnetic stimulation). Following recent work, 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 inhibitory control during action-stopping.

The Pause-then-Cancel model of human action-stopping: Theoretical considerations and empirical evidence

“…Moreover, Nguyen et al (2019) observed that P3 amplitude scaled with force measurements during failed stopping, so that smaller P3s were associated with greater force (and therefore greater response error). The P3's links to the motor system have been further corroborated in a study by Hynd et al (2020), which demonstrated that P3 amplitude relates to inhibitory GABA activity in motor cortex: subjects with higher levels of inhibitory GABAa activity (measured using short-interval intracortical inhibition) showed larger and earlier P3 ERPs following stop signals.…”

Hold your horses: Differences in EEG correlates of inhibition in cancelling and stopping an action

“…Whereas such correlations between inhibition performance and N2/P3 ERPs and the related time-frequency patterns are robust and reproducible, similar correlations have also been reported between these EEG indices and multiple other behavioral measures, thus questioning their specificity in indexing inhibitory processes per se (Huster et al, 2020). Hence, EEG correlates could either truly reflect a, say, "pure" inhibitory process (Hynd et al, 2020;Wessel and Aron, 2015), or the processing of the conflict required to inhibit action (Enriquez-Geppert et al, 2010), or a contextual update of the situation requiring a sporadic action revision (Waller et al, 2019). Thus, studying inhibition-related EEG patterns in tasks known to differ in the engaged action-control processes, as it is the case for discrete and rhythmic actions, may provide additional information to a functional interpretation of these EEG correlates.…”

Hold your horses: Differences in EEG correlates of inhibition in cancelling and stopping an action

“…Whereas such correlations between inhibition performance and N2/P3 ERPs and the related timefrequency patterns are robust and reproducible, similar correlations have also been reported between these EEG indices and multiple other behavioral measures, thus questioning their specificity in indexing inhibitory processes per se (Huster et al, 2020). Hence, EEG correlates could either truly reflect a, say, "pure" inhibitory process (Hynd et al, 2020;Wessel & Aron, 2015), or the processing of the conflict required to inhibit action (Enriquez-Geppert et al, 2010), or a contextual update of the situation requiring an sporadic action revision (Waller et al, 2019). Thus, studying inhibition-related EEG patterns in tasks known to differ in the engaged action-control processes, as it is the case for discrete and rhythmic actions, may provide additional information to a functional interpretation of these EEG correlates.…”