title: 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.
authors.affiliation: Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Zakiniaeiz
authors.affiliation: Department Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Dustin
authors.initials: D
authors.lastname: Scheinost
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Dongju
authors.initials: D
authors.lastname: Seo
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, United States; Department Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, United States; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D063132:Connectome / Q000379:methods*; D003463:Cues; D005260:Female; D005500:Follow-Up Studies; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007297:Inpatients; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012008:Recurrence; D055815:Young Adult
keywords: Addiction; Alcohol dependence; Cingulate cortex; Cue reactivity; Functional connectivity; Relapse