Catecholaminergic Modulation of Metacontrol Is Reflected in Aperiodic EEG Activity and Predicted by Baseline GABA+ and Glx Concentrations.

The ability to balance between being persistent versus flexible during cognitive control is referred to as "metacontrol" and reflected in the exponent of aperiodic neural activity. Theoretical considerations suggest that metacontrol is affected by the interplay of the GABAergic, glutamatergic, and catecholaminergic systems. Moreover, evidence suggests that fronto-striatal structures play an important role. Yet, the nexus between neurobiochemistry and structural neuroanatomy when it comes to the foundations of metacontrol is not understood. To examine this, we investigated how an experimental manipulation of catecholaminergic signaling via methylphenidate (MHP) and baseline levels of GABA and glutamate in the anterior cingulate cortex (ACC), supplementary motor area (SMA), and striatum as assessed via MR spectroscopy altered task performance and associated aperiodic activity (assessed via EEG) during a conflict monitoring task. We investigated N = 101 healthy young adults. We show that the EEG-aperiodic exponent was elevated during task performance, as well as during cognitively challenging task conditions requiring more persistent processing and was further enhanced by MPH administration. Correlation analyses also provided evidence for an important role of individual characteristics and dispositions as reflected by the observed role of GABA+ and Glx baseline levels in the ACC, the SMA, and the striatum. Our observations point to an important role of catecholamines in the amino acid neurotransmitter-driven regulation of metacontrol and task-specific (changes in) metacontrol biases. The results suggest an interplay of the GABA/Glx and the catecholaminergic system in prefrontal-basal ganglia structures crucial for metacontrol.