Sex Differences in Distributed Error-Related Neural Activation in Problem-Drinking Young Adults

Background Detecting and responding to errors is central to goal-directed behavior and cognitive control and is thought to be supported by a network of structures that includes the anterior cingulate cortex and anterior insula. Sex differences in the maturational timing of cognitive control systems create differential periods of vulnerability for psychiatric conditions, such as substance use disorders. Methods We examined sex differences in error-related activation across an array of distributed brain regions during a Go/No-Go task in young adults with problem alcohol use (N=69; 34 females; M=19.4 years). Regions of interest previously linked to error-related activation, including anterior cingulate cortex, insula, and frontoparietal structures, were selected in a term-based meta-analysis. Individual differences in their responses to false alarm (FA) inhibitory errors relative to “go” trials (FA>GO) and correct rejections (FA>CR) were indexed using multivariate summary measures derived from principal components analysis. Results FA>GO and FA>CR activation both revealed a first component that explained the majority of the variance across error-associated regions and displayed the strongest loadings on salience network structures. Compared to females, males exhibited significantly higher levels of the FA>GO component but not the FA>CR component. Conclusions Males exhibit greater salience network activation in response to inhibitory errors, which could be attributed to sex differences in error-monitoring processes or to other functions (e.g., novelty detection). The findings are relevant for the further characterization of sex differences in cognitive control and may have implications for understanding individual differences in those at risk for substance use or other cognitive control disorders.