AUTHOR=Gómez-A Alexander , Dannenhoffer Carol A. , Elton Amanda , Lee Sung-Ho , Ban Woomi , Shih Yen-Yu Ian , Boettiger Charlotte A. , Robinson Donita L. TITLE=Altered Cortico-Subcortical Network After Adolescent Alcohol Exposure Mediates Behavioral Deficits in Flexible Decision-Making JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.778884 DOI=10.3389/fphar.2021.778884 ISSN=1663-9812 ABSTRACT=

Behavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and resting-state functional connectivity MRI in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions statistically mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.