Frontal White Matter Integrity Predictors of Adult Alcohol Treatment Outcome

BACKGROUND Previous research has associated abnormalities in frontal lobe functioning with alcohol relapse. In this study, we used diffusion tensor imaging to investigate whether frontal white matter integrity measured at the start of treatment differs between persons with alcohol use disorders (AUD) who sustain treatment gains and those who return to heavy use after treatment. METHODS Forty-five treatment-seeking AUD inpatients and 30 healthy control subjects were included in the study. Six months after completing treatment, 16 of the AUD participants had resumed heavy use (RHU) and 29 others remained abstinent or drank minimally (treatment sustainers [TS]). Voxel-wise group comparisons (TS vs. RHU) were performed on fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity maps generated from each subject's diffusion tensor imaging scan at the start of treatment. RESULTS We found significantly lower FA and significantly higher RD in the frontal lobes of the RHU group, relative to the TS group. The RHU group data are consistent with previous reports of abnormal frontal white matter tract abnormalities in persons with AUD. CONCLUSIONS It is possible that the lower FA and higher RD in the RHU group reflect microstructural injury to frontal circuitries, and these may underlie the reduced cognitive control amid heightened reward sensitivity associated with resumption of heavy drinking.

[1]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[2]  H. Flor,et al.  Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics , 2004, Psychopharmacology.

[3]  R. Rogers,et al.  Risk-taking on tests sensitive to ventromedial prefrontal cortex dysfunction predicts early relapse in alcohol dependency: a pilot study. , 2005, The Journal of neuropsychiatry and clinical neurosciences.

[4]  C. Wheeler-Kingshott,et al.  About “axial” and “radial” diffusivities , 2009, Magnetic resonance in medicine.

[5]  A. Bechara The role of emotion in decision-making: Evidence from neurological patients with orbitofrontal damage , 2004, Brain and Cognition.

[6]  JaneR . Taylor,et al.  Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli , 1999, Psychopharmacology.

[7]  Stefan Gazdzinski,et al.  Cortical thickness, surface area, and volume of the brain reward system in alcohol dependence: relationships to relapse and extended abstinence. , 2011, Alcoholism, clinical and experimental research.

[8]  W. Miller,et al.  How effective is alcoholism treatment in the United States? , 2001, Journal of studies on alcohol.

[9]  A. Pfefferbaum,et al.  Disruption of Brain White Matter Microstructure by Excessive Intracellular and Extracellular Fluid in Alcoholism: Evidence from Diffusion Tensor Imaging , 2005, Neuropsychopharmacology.

[10]  K O Lim,et al.  In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism. , 2000, Alcoholism, clinical and experimental research.

[11]  N. Volkow,et al.  Drug addiction: the neurobiology of disrupted self-control. , 2006, Trends in molecular medicine.

[12]  J. Finney,et al.  Explaining abstinence rates following treatment for alcohol abuse: a quantitative synthesis of patient, research design and treatment effects. , 1996, Addiction.

[13]  K. Hutchison Substance use disorders: realizing the promise of pharmacogenomics and personalized medicine. , 2010, Annual review of clinical psychology.

[14]  K. Adams,et al.  Cross-study comparisons of self-reported alcohol consumption in four clinical groups. , 1981, The American journal of psychiatry.

[15]  Rita Z. Goldstein,et al.  Role of Dopamine, the Frontal Cortex and Memory Circuits in Drug Addiction: Insight from Imaging Studies , 2002, Neurobiology of Learning and Memory.

[16]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[17]  D. Donovan Assessment issues and domains in the prediction of relapse. , 1996, Addiction.

[18]  O. Parsons,et al.  Prediction of resumption of drinking in posttreatment alcoholics. , 1991, The International journal of the addictions.

[19]  Andreas Heinz,et al.  Quantitative EEG (QEEG) predicts relapse in patients with chronic alcoholism and points to a frontally pronounced cerebral disturbance , 1998, Psychiatry Research.

[20]  L. Frank Characterization of anisotropy in high angular resolution diffusion‐weighted MRI , 2002, Magnetic resonance in medicine.

[21]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[22]  Nikos Makris,et al.  Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism. , 2008, Alcoholism, clinical and experimental research.

[23]  G Fein,et al.  Cortical gray matter loss in treatment-naïve alcohol dependent individuals. , 2002, Alcoholism, clinical and experimental research.

[24]  O. Parsons,et al.  Does neuropsychological test performance predict resumption of drinking in posttreatment alcoholics? , 1990, Addictive behaviors.

[25]  M A Schuckit,et al.  Stress, vulnerability and adult alcohol relapse. , 1995, Journal of studies on alcohol.

[26]  A. Pfefferbaum,et al.  Global-local interference is related to callosal compromise in alcoholism: a behavior-DTI association study. , 2009, Alcoholism, clinical and experimental research.

[27]  Thorsten Kahnt,et al.  Brain activation elicited by affectively positive stimuli is associated with a lower risk of relapse in detoxified alcoholic subjects. , 2007, Alcoholism, clinical and experimental research.

[28]  A. Damasio The somatic marker hypothesis and the possible functions of the prefrontal cortex. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[29]  Bernd Saletu,et al.  Differences in brain function between relapsing and abstaining alcohol-dependent patients, evaluated by EEG mapping. , 2004, Alcohol and alcoholism.

[30]  D. Meyerhoff,et al.  Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence. , 2010, Journal of studies on alcohol and drugs.

[31]  K. Tessner,et al.  Neural Circuitry Associated with Risk for Alcohol Use Disorders , 2010, Neuropsychology Review.

[32]  M. Burmeister,et al.  Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. , 2009, Alcoholism, clinical and experimental research.

[33]  Khader M Hasan,et al.  Reduced Anterior Corpus Callosum White Matter Integrity is Related to Increased Impulsivity and Reduced Discriminability in Cocaine-Dependent Subjects: Diffusion Tensor Imaging , 2005, Neuropsychopharmacology.

[34]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[35]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[36]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[37]  K O Lim,et al.  Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. , 1992, Alcoholism, clinical and experimental research.

[38]  Edith V. Sullivan,et al.  Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism , 2006, Neurobiology of Aging.

[39]  L. Cermak,et al.  Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging. , 1991, Alcoholism, clinical and experimental research.

[40]  D. Le Bihan,et al.  Diffusion tensor imaging: Concepts and applications , 2001, Journal of magnetic resonance imaging : JMRI.

[41]  Rita Z. Goldstein,et al.  Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. , 2002, The American journal of psychiatry.

[42]  D. Meyerhoff,et al.  Combined neuroimaging, neurocognitive and psychiatric factors to predict alcohol consumption following treatment for alcohol dependence. , 2008, Alcohol and alcoholism.

[43]  T. Robbins Dissociating executive functions of the prefrontal cortex. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[44]  I. Grant,et al.  Normal neuropsychological abilities of alcoholic men in their late thirties. , 1979, The American journal of psychiatry.

[45]  Orin C. Davis,et al.  Amygdala volume associated with alcohol abuse relapse and craving. , 2008, The American journal of psychiatry.

[46]  Rajita Sinha,et al.  Altered impulse control in alcohol dependence: neural measures of stop signal performance. , 2009, Alcoholism, clinical and experimental research.

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

[48]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[49]  A. Yamaura,et al.  Alcohol consumption and frontal lobe shrinkage: study of 1432 non-alcoholic subjects , 2001, Journal of neurology, neurosurgery, and psychiatry.

[50]  E. Sullivan,et al.  Corpus callosal microstructural integrity influences interhemispheric processing: a diffusion tensor imaging study. , 2005, Cerebral cortex.

[51]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[52]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[53]  H. Fitzgerald,et al.  Developmental Evidence for at Least Two Alcoholisms , 1994, Annals of the New York Academy of Sciences.

[54]  Rajita Sinha,et al.  Association of frontal and posterior cortical gray matter volume with time to alcohol relapse: a prospective study. , 2011, The American journal of psychiatry.

[55]  P. Poulet,et al.  Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging , 2006, Journal of neuroscience research.

[56]  T. Patterson,et al.  Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury. , 2001, Alcoholism, clinical and experimental research.

[57]  D. Kivlahan,et al.  Clinical limitations of neuropsychological testing in predicting treatment outcome among alcoholics. , 1984, Alcoholism, clinical and experimental research.

[58]  K. Zilles,et al.  Subcortical correlates of craving in recently abstinent alcoholic patients. , 2001, The American journal of psychiatry.

[59]  K. Marinković,et al.  Alcohol: Effects on Neurobehavioral Functions and the Brain , 2007, Neuropsychology Review.

[60]  R. Hales,et al.  J Neuropsychiatry Clin Neurosci , 1992 .

[61]  N. Volkow,et al.  Neurocircuitry of Addiction , 2010, Neuropsychopharmacology.

[62]  W. Miller,et al.  What predicts relapse? Prospective testing of antecedent models. , 1996, Addiction.

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

[64]  X. Noël,et al.  Contribution of frontal cerebral blood flow measured by (99m)Tc-Bicisate spect and executive function deficits to predicting treatment outcome in alcohol-dependent patients. , 2002, Alcohol and alcoholism.

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

[66]  L C Sobell,et al.  Reliability of a timeline method: assessing normal drinkers' reports of recent drinking and a comparative evaluation across several populations. , 1988, British journal of addiction.

[67]  Michael H. Buonocore,et al.  Cognitive Control and White Matter Callosal Microstructure in Methamphetamine-Dependent Subjects: A Diffusion Tensor Imaging Study , 2009, Biological Psychiatry.

[68]  Janet B W Williams Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[69]  Daniel Tranel,et al.  Asymmetric Functional Roles of Right and Left Ventromedial Prefrontal Cortices in Social Conduct, Decision-Making, and Emotional Processing , 2002, Cortex.

[70]  S. Allsop,et al.  The process of relapse in severely dependent male problem drinkers. , 2000, Addiction.

[71]  Stefan Gazdzinski,et al.  Tract-based spatial statistics (TBSS) of diffusion tensor imaging data in alcohol dependence: Abnormalities of the motivational neurocircuitry , 2009, Psychiatry Research: Neuroimaging.