Acute calming effects of alcohol are associated with disruption of the salience network

The mood‐altering properties of alcohol are a key motivation for drinking, and people commonly report that they drink alcohol to alleviate stress or to relax. To date, the neural processes associated with the self‐reported calming effects of alcohol are not well understood. Existing data imply that alcohol may target and disrupt activity within anterior insula (aINS) and amygdala‐based neural networks, which are regions implicated in threat detection and anxious responding. The aims of the current study were (1) to examine the acute effect of alcohol upon functional connectivity within aINS and amygdala circuits and (2) to assess relationships between alcohol effects on functional connectivity and self‐reported subjective mood. Healthy men and women (N = 39) who reported regular binge drinking completed a within‐subjects, double‐blind, placebo‐controlled pharmacological functional magnetic resonance imaging experiment with i.v. infusions of either alcohol or placebo. Infusion profiles were personalized for each participant and raised breath alcohol concentration to 80 mg percent. Before, during and after infusions, participants rated their subjective mood (stimulation, sedation and calm). Results showed that alcohol dampened functional connectivity between bilateral aINS seed‐regions‐of‐interest and the dorsal anterior cingulate cortex (dACC), key nodes of the salience network. Additionally, the more that alcohol reduced right aINS‐dACC functional connectivity, the calmer participants felt during alcohol administration. Alcohol had no effect on amygdala functional connectivity. These findings suggest that alcohol disrupts aINS‐dACC functional connectivity, which may impair detection and appraisal of emotionally salient information and relate to acute relaxing effects of the drug. It is thought that alcohol may produce anxiolytic effects by downregulating limbic activity and disrupting functional connections between frontolimbic circuits that mediate salience processing. Here we show that alcohol infusions dampened functional connectivity between bilateral anterior insula and the dorsal anterior cingulate cortex, key nodes of the salience network, among hazardous drinkers. Furthermore, the more that alcohol reduced right anterior insula‐dorsal anterior cingulate cortex connectivity, the calmer participants felt during alcohol administration. Our findings suggest that alcohol disrupts salience determination, which may contribute to feelings of relaxation whi