RATIONALE: Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. OBJECTIVES: This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. METHODS: Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. RESULTS: There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater leftdorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. CONCLUSIONS: These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
RCT Entities:
RATIONALE: Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. OBJECTIVES: This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. METHODS: Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. RESULTS: There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. CONCLUSIONS: These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
Authors: Rita Z Goldstein; Nelly Alia-Klein; Dardo Tomasi; Jean Honorio Carrillo; Thomas Maloney; Patricia A Woicik; Ruiliang Wang; Frank Telang; Nora D Volkow Journal: Proc Natl Acad Sci U S A Date: 2009-05-28 Impact factor: 11.205
Authors: Soyoung Q Park; Thorsten Kahnt; Anne Beck; Michael X Cohen; Raymond J Dolan; Jana Wrase; Andreas Heinz Journal: J Neurosci Date: 2010-06-02 Impact factor: 6.167
Authors: Andreas Heinz; Jana Wrase; Thorsten Kahnt; Anne Beck; Zohra Bromand; Sabine M Grüsser; Thorsten Kienast; Michael N Smolka; Herta Flor; Karl Mann Journal: Alcohol Clin Exp Res Date: 2007-05-04 Impact factor: 3.455
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Authors: Warren B Logge; Richard W Morris; Andrew J Baillie; Paul S Haber; Kirsten C Morley Journal: Psychopharmacology (Berl) Date: 2019-02-20 Impact factor: 4.530