GABAergic modulation of conflict adaptation and response inhibition

Abstract

Adaptive behavior is only possible by stopping stereotypical actions to generate new plans according to internal goals. It is response inhibition --the ability to stop actions automatically triggered by exogenous cues-- that allows for the flexible interplay between bottom-up, stimulus driven behaviors, and top-down strategies. In addition to response inhibition, cognitive control draws on conflict adaptation, the facilitation of top-down actions following high conflict situations. It is currently unclear whether and how response inhibition and conflict adaptation depend on GABAergic signaling, the main inhibitory neurotransmitter in the human brain. Here, we applied a recently developed computational model (SERIA) to data from two studies (N=150 & 50) of healthy volunteers performing Simon and antisaccade tasks. One of these datasets was acquired under placebo-controlled pharmacological enhancement of GABAergic transmission (lorazepam, an allosteric modulator of the GABA-A receptor). Our model-based results suggest that enhanced GABA-A signaling boosts conflict adaptation but impairs response inhibition. More generally, our computational approach establishes a unified account of response inhibition and conflict adaptation in the Simon and antisaccade tasks and provides a novel tool for quantifying specific aspects of cognitive control and their modulation by pharmacology or disease. Author SummaryOur capacity to prepare for situations that afford conflicting responses (conflict adaptation) and to stop our immediate impulses in these scenarios (response inhibition) are the hallmark of cognitive control. As these abilities require both the stopping or slowing of response tendencies, a natural question is whether they are mediated by inhibitory neurotransmission in the brain. Here, we combined computational modeling with two experiments to investigate how conflict adaptation and response inhibition interact with each other (experiment 1) and how these are modulated by lorazepam (experiment 2), a positive modulator of the GABA-A receptor, one of the main inhibitory receptors in the human brain. Using our computational model to disentangle conflict adaptation and response inhibition, our results indicate that while lorazepam impaired response inhibition, it improved conflict adaptation. Thus, our results suggests that conflict adaptation is mediated by GABA-A neurotransmission.