title: Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted individuals.
abstract: Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting-state functional connectivity (rsFC) in neural circuits arising from the amygdala, a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state functional magnetic resonance imaging connectivity (6 min) was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry, separate seeds were derived for the left and right basolateral (BLA) and corticomedial (CMA) amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive-Compulsive Cocaine Use Scale and Personality Inventory. Relapse within the first 30 days post-treatment (n = 24) was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC) relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21). Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus) compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse , Baltimore, MD , USA.
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: McHugh
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse , Baltimore, MD , USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Demers
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse , Baltimore, MD , USA.
authors.forename: Betty Jo
authors.initials: BJ
authors.lastname: Salmeron
authors.affiliation: Avid Radiopharmaceuticals , Philadelphia, PA , USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Devous
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse , Baltimore, MD , USA.
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
authors.affiliation: VA North Texas Health Care System , Dallas, TX , USA ; Department of Psychiatry, University of Texas Southwestern Medical Center , Dallas, TX , USA.
authors.forename: Bryon
authors.initials: B
authors.lastname: Adinoff
keywords: addiction; amygdala; cocaine; connectivity; neuroimaging; prefrontal; relapse; ventromedial