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Fronto-striatal functional connectivity during response inhibition in alcohol dependence

Authors

  • Kelly E. Courtney,

    1. Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
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  • Dara G. Ghahremani,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA
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  • Lara A. Ray

    Corresponding author
    1. Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA
    • Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
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Correspondence to: Lara A. Ray, Psychology Department, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA. E-mail: lararay@psych.ucla.edu

Abstract

Poor response inhibition has been implicated in the development of alcohol dependence, yet little is known about how neural pathways underlying cognitive control are affected in this disorder. Moreover, endogenous opioid levels may impact the functionality of inhibitory control pathways. This study investigated the relationship between alcohol dependence severity and functional connectivity of fronto-striatal networks during response inhibition in an alcohol-dependent sample. A secondary aim of this study was to test the moderating effect of a functional polymorphism (A118G) of the μ-opioid receptor (OPRM1) gene. Twenty individuals with alcohol dependence (six females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent blood oxygen level-dependent functional magnetic resonance imaging while performing a Stop-Signal Task. The relationship between alcohol dependence severity and functional connectivity within fronto-striatal networks important for response inhibition was assessed using psychophysiological interaction analyses. Analyses revealed greater alcohol dependence severity was associated with weaker functional connectivity between the putamen and prefrontal regions (e.g. the anterior insula, anterior cingulate and medial prefrontal cortex) during response inhibition. Furthermore, the OPRM1 genotype was associated with differential response inhibition-related functional connectivity. This study demonstrates that individuals with more severe alcohol dependence exhibit less frontal connectivity with the striatum, a component of cognitive control networks important for response inhibition. These findings suggest that the fronto-striatal pathway underlying response inhibition is weakened as alcoholism progresses.

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