Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals

Abstract

Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome). Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC) participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.

Imaging resilience and recovery in alcohol dependence

“…). Two recent prospective studies reported altered cingulate cortex connectivity during individualized imaginary scripts provoking either alcohol‐, stress‐associated or neutral states in AD . Those patients who showed greater posterior cingulate connectivity during alcohol imagery, or less anterior, mid‐cingulate connectivity during neutral trials, showed longer abstinence during the following 90 days and resembled healthy controls.…”

“…We found nine relevant fMRI studies investigating the role of cognitive functions seen commonly in AD, such as executive, motivational aspects of behavior and emotion processing (for reviews, see ).…”

Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

“…This has been associated with impairment of executive function, reward-directed behavior, and conditioning, all of which have been implicated in impulsivity, compulsive drug use, and addiction [31–33]. More recently, Zakiniaeiz et al demonstrated that the cingulate cortex may be a key region in the disruption of functional connectivity during cue-induced processing, while changes in its function may serve as a marker of subsequent alcohol relapse [34]. …”

Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents

“…Consistent with prior studies (Garrison et al, 2016; Zakiniaeiz et al, 2017), connectivity analysis focused on the 2.5-minute imagery period (2-minute script and 0.5-minute quiet imagery), where the same cue trial imagery periods were concatenated for a total of approximately 5 minutes of data for each cue state.…”