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 avoidance-based 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 (AIC), anteromedial (AM) thalamus and dorsal anterior cingulate cortex (dACC). The present study aimed to understand how these three regions function as a network during anticipation of unpredictable threat (and predictable threat).

Methods: Participants were 43 young adults (aged 21-30) with AUD and 26 healthy controls. Functional magnetic resonance imaging and dynamic causal modeling were used to study inter-regional 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 AM thalamus to the right AIC was significantly present only in the AUD group. This directional influence was stronger among individuals who on average consumed more drinks per week. 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 may be causal.