Reduced left executive control network functional connectivity is associated with alcohol use disorders.

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.

[1]  O. Parsons,et al.  Neurobehavioral sequelae of alcoholism. , 1993, Neurologic clinics.

[2]  A. Baddeley,et al.  Dual-task performance in dysexecutive and nondysexecutive patients with a frontal lesion. , 1997, Neuropsychology.

[3]  M. Lyvers.  "Loss of control" in alcoholism and drug addiction: a neuroscientific interpretation. , 2000, Experimental and clinical psychopharmacology.

[4]  D. Ghahremani,et al.  Fronto‐striatal functional connectivity during response inhibition in alcohol dependence , 2013, Addiction biology.

[5]  S. Taylor,et al.  Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia. , 2010, Schizophrenia bulletin.

[6]  Anne Beck,et al.  Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. , 2012, Archives of general psychiatry.

[7]  George Fein,et al.  Resting-state synchrony in long-term abstinent alcoholics. , 2013, Alcoholism, clinical and experimental research.

[8]  B. Desgranges,et al.  Genuine episodic memory deficits and executive dysfunctions in alcoholic subjects early in abstinence. , 2007, Alcoholism, clinical and experimental research.

[9]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[10]  Nora D. Volkow,et al.  Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex , 2004, Neuropsychologia.

[11]  M. H. Parks,et al.  Reduced fronto-cerebellar functional connectivity in chronic alcoholic patients. , 2012, Alcoholism, clinical and experimental research.

[12]  A. Pfefferbaum,et al.  Pattern of motor and cognitive deficits in detoxified alcoholic men. , 2000, Alcoholism, clinical and experimental research.

[13]  A. Pfefferbaum,et al.  Neurocircuitry in alcoholism: a substrate of disruption and repair , 2005, Psychopharmacology.

[14]  N. Volkow,et al.  Aging and Functional Brain Networks , 2011, Molecular Psychiatry.

[15]  M. J. Emerson,et al.  The Unity and Diversity of Executive Functions and Their Contributions to Complex “Frontal Lobe” Tasks: A Latent Variable Analysis , 2000, Cognitive Psychology.

[16]  V. Srinivasa Chakravarthy,et al.  What do the basal ganglia do? A modeling perspective , 2010, Biological Cybernetics.

[17]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[18]  A. Pfefferbaum,et al.  Neurocircuitry of emotion and cognition in alcoholism: contributions from white matter fiber tractography , 2010, Dialogues in clinical neuroscience.

[19]  Adolf Pfefferbaum,et al.  Disruption of functional connectivity of the default-mode network in alcoholism. , 2011, Cerebral cortex.

[20]  P. Skudlarski,et al.  Brain Connectivity Related to Working Memory Performance , 2006, The Journal of Neuroscience.

[21]  H. Moselhy,et al.  Frontal lobe changes in alcoholism: a review of the literature. , 2001, Alcohol and alcoholism.

[22]  R. Harris,et al.  Alcohol and the Brain , 2014 .

[23]  Justin L. Vincent,et al.  Disruption of Large-Scale Brain Systems in Advanced Aging , 2007, Neuron.

[24]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[25]  E. Bullmore,et al.  Behavioral / Systems / Cognitive Functional Connectivity and Brain Networks in Schizophrenia , 2010 .

[26]  D. Wegener,et al.  The problem of equivalent models in applications of covariance structure analysis. , 1993, Psychological bulletin.

[27]  G. Fein,et al.  Resting-state synchrony during early alcohol abstinence can predict subsequent relapse. , 2013, Cerebral cortex.

[28]  Yihong Yang,et al.  Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity , 2010, NeuroImage.

[29]  M. Husain,et al.  The functional role of the inferior parietal lobe in the dorsal and ventral stream dichotomy , 2009, Neuropsychologia.

[30]  O. Aasland,et al.  Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. , 1993, Addiction.

[31]  A. Turken,et al.  The Neural Architecture of the Language Comprehension Network: Converging Evidence from Lesion and Connectivity Analyses , 2011, Front. Syst. Neurosci..

[32]  S. Petersen,et al.  Development of distinct control networks through segregation and integration , 2007, Proceedings of the National Academy of Sciences.

[33]  W. Lishman.  Alcohol and the Brain , 1990, British Journal of Psychiatry.

[34]  J. Kril,et al.  Loss of vasopressin-immunoreactive neurons in alcoholics is dose-related and time-dependent , 1996, Neuroscience.

[35]  L. Becerra,et al.  Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. , 2010, Brain : a journal of neurology.

[36]  Mert R. Sabuncu,et al.  The influence of head motion on intrinsic functional connectivity MRI , 2012, NeuroImage.

[37]  A Pfefferbaum,et al.  Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics. , 1997, Alcoholism, clinical and experimental research.

[38]  Jessica A. Turner,et al.  COINS: An Innovative Informatics and Neuroimaging Tool Suite Built for Large Heterogeneous Datasets , 2011, Front. Neuroinform..

[39]  Rex E. Jung,et al.  A Baseline for the Multivariate Comparison of Resting-State Networks , 2011, Front. Syst. Neurosci..

[40]  Jessica A. Turner,et al.  Behavioral Interpretations of Intrinsic Connectivity Networks , 2011, Journal of Cognitive Neuroscience.

[41]  M. Oscar-Berman,et al.  Impairments of brain and behavior: the neurological effects of alcohol. , 1997 .

[42]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[43]  S. Petersen,et al.  Concepts and principles in the analysis of brain networks , 2011, Annals of the New York Academy of Sciences.

[44]  Marie T Banich,et al.  Resting-state activity in the left executive control network is associated with behavioral approach and is increased in substance dependence. , 2013, Drug and alcohol dependence.

[45]  N. Heather,et al.  Impaired Control Scale: cross-validation and relationships with treatment outcome. , 1998, Addiction.

[46]  O. Tervonen,et al.  Functional segmentation of the brain cortex using high model order group-PICA. , 2009, NeuroImage.

[47]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[48]  S. Rombouts,et al.  Reduced resting-state brain activity in the "default network" in normal aging. , 2008, Cerebral cortex.

[49]  M. Oscar-Berman,et al.  Patterns of prefrontal dysfunction in alcoholics with and without Korsakoff’s syndrome, patients with Parkinson’s disease, and patients with rupture and repair of the anterior communicating artery , 2006, Neuropsychiatric disease and treatment.

[50]  J. Kril,et al.  The cerebral cortex is damaged in chronic alcoholics , 1997, Neuroscience.

[51]  Torsten Rohlfing,et al.  Degradation of Association and Projection White Matter Systems in Alcoholism Detected with Quantitative Fiber Tracking , 2009, Biological Psychiatry.

[52]  Stephen M Smith,et al.  Correspondence of the brain's functional architecture during activation and rest , 2009, Proceedings of the National Academy of Sciences.

[53]  Soyoung Q. Park,et al.  Prefrontal Cortex Fails to Learn from Reward Prediction Errors in Alcohol Dependence , 2010, The Journal of Neuroscience.

[54]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Greicius,et al.  Decoding subject-driven cognitive states with whole-brain connectivity patterns. , 2012, Cerebral cortex.

[56]  G. Fein,et al.  Cognitive performance in treatment-naïve active alcoholics. , 2010, Alcoholism, clinical and experimental research.