Response inhibition processes are important for performance monitoring and are mediated via a network constituted by different cortical areas and basal ganglia nuclei. At the basal ganglia level, striatal GABAergic medium spiny neurons are known to be important for response selection, but the importance of the striatal GABAergic system for response inhibition processes remains elusive. Using a novel combination of behavioural, EEG and magnetic resonance spectroscopy (MRS) data we examine the relevance of the striatal GABAergic system for response inhibition processes. The study shows that striatal GABA levels modulate the efficacy of response inhibition processes. Higher striatal GABA levels were related to better response inhibition performance. We show that striatal GABA modulate specific subprocesses of response inhibition related to pre-motor inhibitory processes through the modulation of neuronal synchronization processes. To our knowledge this is the first study providing direct evidence for the relevance of the striatal GABAergic system for response inhibition functions and their cortical electrophysiological correlates in humans.

In day-to-day life, we need to apply strategies to cascade different actions for efficient unfolding of behaviour. While deficits in action cascading are examined extensively, almost nothing is known about the neuronal mechanisms mediating superior performance above the normal level. To examine this question, we investigate action control in airplane pilot trainees. We use a stop-change paradigm that is able to estimate the efficiency of action cascading on the basis of mathematical constraints. Behavioural and EEG data is analyzed along these constraints and integrated with neurochemical data obtained using Magnetic Resonance Spectroscopy (MRS) from the striatal gamma-aminobutyric acid (GABA) -ergic system. We show that high performance in action cascading, as exemplified in airplane pilot trainees, can be driven by intensified attentional processes, circumventing response selection processes. The results indicate that the efficiency of action cascading and hence the speed of responding as well as attentional gating functions are modulated by striatal GABA and Glutamate + Glutamine concentrations. In superior performance in action cascading similar increases in the concentrations of GABA and Glutamate + Glutamine lead to stronger neurophysiological and behavioural effects as compared to subjects with normal performance in action cascading.

Important issues for cognitive control are response selection processes, known to depend on fronto-striatal networks with recent evidence suggesting that striatal gamma-amino butyric acid (GABA) levels play an important role. Regional GABA concentrations have also been shown to modulate intrinsic connectivity, e.g. of the default mode network. However, the interrelation between striatal GABA levels, basal ganglia network (BGN) connectivity, and performance in cognitive control is elusive. In the current study, we measure striatal GABA levels using magnetic resonance spectroscopy (MRS) and resting state parameters using functional magnetic resonance imaging (fMRI). Resting state parameters include activity within the BGN, as determined by the low frequency power (LFP) within the network, and the functional connectivity between the BGN and somatomotor network (SMN). Specifically, we examine the interrelation between GABA, resting state parameters, and performance (i.e., accuracy) in conflict monitoring using a Simon task. Response control was affected by striatal GABA+ levels and activity within the BGN, especially when response selection was complicated by altered stimulus-response mappings. The data suggest that there are two mechanisms supporting response selection accuracy. One is related to resting state activity within the BGN and modulated by striatal GABA+ levels. The other is related to decreased cortico-striatal network connectivity, unrelated to the GABAergic system. The inclusion of all three factors (i.e., striatal GABA+ levels, activity within the BGN, and BGN-SMN network connectivity) explained a considerable amount of variance in task accuracy. Striatal neurobiochemical (GABA+) and parameters of the resting state BGN represent important modulators of response control.