Altered Effective Connectivity During Threat Anticipation in Individuals With Alcohol Use Disorder

BACKGROUND: A developing theory and recent research suggest that heightened reactivity to uncertain stressors or threats may be an important individual difference factor that facilitates excessive drinking as a means of avoidancebased coping and characterizes individuals with current and past alcohol use disorder (AUD). Neuroimaging studies of unpredictable threat processing have repeatedly demonstrated activation of the anterior insula, anteromedial thalamus, and dorsal anterior cingulate cortex. In the current study, we aimed to understand how these 3 regions function as a network during anticipation of unpredictable threat (and predictable threat). METHODS: Participants were 43 adults (ages 21-30) with AUD and 26 healthy control participants. Functional magnetic resonance imaging and dynamic causal modeling were used to study interregional effective connectivities and predictable and unpredictable threat-related modulations thereof within this network. Parametric empirical Bayesian modeling was used to conduct between-group comparisons in effective connectivities. RESULTS: During unpredictable threat trials, the increased projection from the right anteromedial thalamus to the right anterior insula was significantly present only in the AUD group. This directional influence was stronger among individuals who consumed more drinks per week on average. As expected, we found no group differences in modulatory changes to effective connectivities during predictable threat trials. CONCLUSIONS: To our knowledge, this is the first study to examine directional interactions between key frontolimbic regions during anticipation of unpredictable and predictable threat and demonstrate the importance of bottom-up thalamic-insular projections during unpredictable threat processing in AUD. Prospective studies are warranted to determine whether this association is causal.