On the functional role of striatal and anterior cingulate GABA+ in stimulus-response binding

Abstract

Successful response selection relies on constantly updating stimulus-response associations. The Theory of Event Coding (TEC) proposes that perception and action are conjointly coded in event files, for which fronto-striatal networks seem to play an important role. However, the exact neurobiochemical mechanism behind event file coding has remained unknown. We investigated the functional relevance of the striatal and anterior cingulate (ACC) GABAergic system using magnetic resonance spectroscopy (MRS). Specifically, the striatal and ACC concentrations of GABA+ referenced against N-acetylaspartate (NAA) were assessed in 35 young healthy males, who subsequently performed a standard event file task. As predicted by the TEC, the participants' responses were modulated by pre-established stimulus response bindings in event files. GABA+/NAA concentrations in the striatum and ACC were not correlated with the overall event binding effect. However, higher GABA+/NAA concentrations in the ACC were correlated with stronger event file binding processes in the early phase of the task. This association disappeared by the end of the task. Taken together, our findings show that striatal GABA+ levels does not seem to modulate event file binding, while ACC GABA+ seem to improve event file binding, but only as long as the participants have not yet gathered sufficient task experience. To the best of our knowledge, this is the first study providing direct evidence for the role of striatal and ACC GABA+ in stimulus-response bindings and thus insights into the brain structure-specific neurobiological aspects of the TEC.

Keywords: anterior cingulate cortex (ACC); gamma-aminobutyric acid (GABA); magnetic resonance spectroscopy (MRS); response selection; striatum; theory of event coding (TEC).