Connectivity between the BNST and insula during abstinence from alcohol use disorder
Alcohol use disorder (AUD) affects over 15 million Americans and remains exceptionally difficult to treat, with the majority of individuals relapsing within a year of initiating treatment. Much of this difficulty is thought to arise from the symptoms of anxiety and depression experienced by individuals with AUD during abstinence, as these symptoms are common triggers of relapse. Rodent work has identified a key pathway that regulates these abstinence-induced symptoms between the insula and the bed nucleus of the stria terminalis (BNST). Little is known, however, about the BNST-insula pathway in humans. The goal of this project is to 1) characterize a normative pattern of BNST-insula connectivity in humans; 2) identify differences in BNST-insula connectivity in abstinence; and 3) investigate the relationship between BNST-insula connectivity and anxiety and depressive symptoms during abstinence. Given known differences in connectivity and function between the anterior and posterior insula, this project evaluated both structural and resting state BNST connectivity with the anterior and posterior insula separately. To determine normative connectivity, BNST connectivity with anterior insula was compared to connectivity with the posterior insula in individuals without a psychiatric diagnosis. The anterior insula was shown to have greater structural and resting state BNST connectivity than the posterior insula. To investigate differences in BNST-insula connectivity during abstinence, 20 abstinent individuals with AUD and 20 controls completed structural and resting state scans and questionnaires capturing anxiety and depression symptoms. The results suggest a moderate effect of abstinence, where abstinent individuals did not show normative BNST-anterior insula resting state connectivity but had greater posterior insula structural connectivity with the BNST. In the abstinence group, depression symptoms were positively associated with BNST structural connectivity with both the anterior and posterior insula but not resting state connectivity. Anxiety symptoms in the abstinence group were not associated BNST structural or resting state connectivity with the anterior or posterior insula. These results provide evidence for normative BNST-insula connectivity in humans, which differs in abstinence, offering critical translational insights into the neural basis of abstinence and potential opportunities for treatment.