RESUMEN
Behavioral flexibility and goal-directed behavior heavily depend on fronto-striatal networks. Within these circuits, gamma-aminobutyric acid (GABA) and glutamate play an important role in (motor) response inhibition, but it has remained largely unclear whether they are also relevant for cognitive inhibition. We hence investigated the functional role of these transmitters for cognitive inhibition during cognitive flexibility. Healthy young adults performed two paradigms assessing different aspects of cognitive flexibility. Magnetic resonance spectroscopy (MRS) was used to quantify GABA+ and total glutamate/glutamine (Glx) levels in the striatum and anterior cingulate cortex (ACC) referenced to N-acetylaspartate (NAA). We observed typical task switching and backward inhibition effects, but striatal and ACC concentrations of GABA+/NAA and Glx/NAA were not associated with cognitive flexibility in a functionally relevant manner. The assumption of null effects was underpinned by Bayesian testing. These findings suggest that behavioral and cognitive inhibition are functionally distinct faculties, that depend on (at least partly) different brain structures and neurotransmitter systems. While previous studies consistently demonstrated that motor response inhibition is modulated by ACC and striatal GABA levels, our results suggest that the functionally distinct cognitive inhibition required for successful switching is not, or at least to a much lesser degree, modulated by these factors.
RESUMEN
In substance use and addiction, inhibitory control is key to ignoring triggers, withstanding craving and maintaining abstinence. In amphetamine-type stimulant (ATS) users, most research focused on behavioral inhibition, but largely neglected the equally important subdomain of cognitive interference control. Given its crucial role in managing consumption, we investigated the relationship between interference control and chronic ATS use in adults. A database search (Pubmed & Web of Science) and relevant reviews were used to identify eligible studies. Effect sizes were estimated with random effects models. Subgroup, meta-regression, and sensitivity analyses explored heterogeneity in effect sizes. We identified 61 studies (53 datasets) assessing interference control in 1873 ATS users and 1905 controls. Findings revealed robust small effect sizes for ATS-related deficits in interference control, which were mainly seen in methamphetamine, as compared to MDMA users. The differential effects are likely due to tolerance-induced dopaminergic deficiencies (presumably most pronounced in methamphetamine users). Similarities between different ATS could be due to noradrenergic deficiencies; but elucidating their functional role in ATS users requires further/more research.