title: Reduced left executive control network functional connectivity is associated with alcohol use disorders.
abstract: BACKGROUND
  Altered functional connectivity in critical networks has been associated with chronic alcohol abuse. In turn, changes in connectivity in executive control networks (ECNs) may undermine the ability to control alcohol consumption. It was hypothesized that network connectivity would be reduced in individuals with problematic alcohol use (ALC) compared with controls and that diminished network connectivity would be associated with greater failure to control drinking.
  
  
  METHODS
  Resting-state functional magnetic resonance imaging was analyzed to identify 14 previously identified intrinsic connectivity networks (ICNs) using a priori regions of interest in cases ranging from binge drinkers to those with severe alcohol use disorder, as well as control subjects. Analyses tested for differences in network connectivity strength between 255 ALC cases and 87 age- and gender-matched controls. Further, structural equation analysis, using 383 ALC cases, tested whether functional connectivity strength mediated the relationship between years of regular drinking and alcohol problems.
  
  
  RESULTS
  The age- and gender-matched analysis showed that ALC had significantly lower network connectivity strength than controls in the left executive control (LECN), basal ganglia, and primary visual networks. For all ALC, LECN connectivity strength is negatively correlated with failed control and alcohol disorder severity. Edges connecting parietal regions with dorsolateral prefrontal, middle frontal, and temporal regions within the LECN drove these relationships. A positive association between years of drinking and severity of alcohol problems was mediated by reduced ECN connectivity.
  
  
  CONCLUSIONS
  This study reports relationships between network strength and problematic alcohol use, suggesting that chronic drinking negatively impacts brain connectivity, specifically in the LECN. Altered functional connectivity, related to chronic alcohol abuse, may contribute to the etiology of alcohol dependence and relapse.
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Weiland
authors.forename: Amithrupa
authors.initials: A
authors.lastname: Sabbineni
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.forename: Angela D
authors.initials: AD
authors.lastname: Bryan
authors.forename: Rex E
authors.initials: RE
authors.lastname: Jung
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mayer
authors.forename: Kent E
authors.initials: KE
authors.lastname: Hutchison
mesh_terms: D000328:Adult; D019973:Alcohol-Related Disorders / Q000175:diagnosis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
keywords: Alcohol Dependence; Executive Control; Functional Connectivity; Functional Network; Resting State