Brain activation elicited by affectively positive stimuli is associated with a lower risk of relapse in detoxified alcoholic subjects.

BACKGROUND Stimuli that are regularly associated with alcohol intake (AI) may acquire incentive salience, while other reinforcers can be devalued. We assessed whether brain activation elicited by (1) alcohol associated, (2) affectively positive, and (3) negative versus neutral stimuli is associated with the subsequent risk of relapse. METHODS Twelve detoxified alcoholic subjects (6 women and 6 men) and 12 age-matched and gender-matched healthy control subjects were assessed with functional magnetic resonance imaging (fMRI) and a fast single-event paradigm using standardized affective and alcohol-associated pictures. Patients were followed for 6 months and AI was recorded. RESULTS In alcoholic subjects, compared with healthy control subjects, (1) alcohol-related versus neutral visual stimuli elicited increased activation in the prefrontal (PFC; BA 6 and 10) and cingulate cortex (BA 23 and 24), precuneus and adjacent parietal cortex; (2) positive versus neutral stimuli elicited increased activation in the anterior cingulate cortex (ACC; BA 24), PFC (BA 10), ventral striatum and thalamus; and (3) negative versus neutral stimuli elicited increased activation in the PFC (BA 10). Seven alcoholic subjects relapsed. Within the follow-up period of 6 months, the number of subsequent drinking days (DD) and the amount of AI were inversely correlated with brain activation elicited by positive versus neutral stimuli in the thalamus (DD: r=-0.63, p=0.03; AI: r=-0.63, p=0.03) and in the ventral striatum (DD: r=-0.60, p=0.04; AI: r=-0.48, p=0.11). CONCLUSIONS In this study, brain activation elicited by briefly presented alcohol-associated stimuli was not associated with the prospective risk of relapse. Unexpectedly, alcoholic subjects displayed increased limbic brain activation during the presentation of affectively positive but not negative stimuli, which may reflect a protective factor in detoxified alcoholic subjects.

[1]  H. Flor,et al.  Development of alcohol-associated cues and cue-induced brain activation in alcoholics , 2002, European Psychiatry.

[2]  G. Koob,et al.  Plasticity of reward neurocircuitry and the 'dark side' of drug addiction , 2005, Nature Neuroscience.

[3]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[4]  M. Yücel,et al.  Addiction, a condition of compulsive behaviour? Neuroimaging and neuropsychological evidence of inhibitory dysregulation. , 2004, Addiction.

[5]  Brian Knutson,et al.  Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics , 2007, NeuroImage.

[6]  D J Rohsenow,et al.  Does Urge To Drink Predict Relapse After Treatment? , 1999, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[7]  Andreas Heinz,et al.  Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI. , 2006, Alcoholism, clinical and experimental research.

[8]  M. Bradley,et al.  Measuring emotion: the Self-Assessment Manikin and the Semantic Differential. , 1994, Journal of behavior therapy and experimental psychiatry.

[9]  D. Kahneman,et al.  Functional Imaging of Neural Responses to Expectancy and Experience of Monetary Gains and Losses tasks with monetary payoffs , 2001 .

[10]  R. Anton,et al.  The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. , 1995, Alcoholism, clinical and experimental research.

[11]  J. Lorberbaum,et al.  From the Departments Of , 2022 .

[12]  N. Volkow,et al.  Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans , 1999, Journal of psychopharmacology.

[13]  Richard Longabaugh,et al.  Concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) and AUDIT zones in defining levels of severity among out-patients with alcohol dependence in the COMBINE study. , 2006, Addiction.

[14]  W. Miller,et al.  The reliability of Form 90: an instrument for assessing alcohol treatment outcome. , 1997, Journal of studies on alcohol.

[15]  A. Kelley,et al.  Intake of saccharin, salt, and ethanol solutions is increased by infusion of a mu opioid agonist into the nucleus accumbens , 2002, Psychopharmacology.

[16]  M. D’Esposito,et al.  The neural basis of the central executive system of working memory , 1995, Nature.

[17]  A. Heinz,et al.  Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. , 2005, Archives of general psychiatry.

[18]  F. D. Del Boca,et al.  Measurement of drinking behavior using the Form 90 family of instruments. , 1994, Journal of studies on alcohol. Supplement.

[19]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[20]  L. Parsons,et al.  Neurobiological mechanisms in the transition from drug use to drug dependence , 2004, Neuroscience & Biobehavioral Reviews.

[21]  B. Carter,et al.  Is craving the source of compulsive drug use? , 1998, Journal of psychopharmacology.

[22]  A. Meyer-Lindenberg,et al.  5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression , 2005, Nature Neuroscience.

[23]  Nikolaus R. McFarland,et al.  Striatonigrostriatal Pathways in Primates Form an Ascending Spiral from the Shell to the Dorsolateral Striatum , 2000, The Journal of Neuroscience.

[24]  Mathias Schreckenberger,et al.  Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. , 2004, The American journal of psychiatry.

[25]  H. Flor,et al.  Standardized stimuli to assess drug craving and drug memory in addicts , 2000, Journal of Neural Transmission.

[26]  J S Fowler,et al.  Decreases in dopamine receptors but not in dopamine transporters in alcoholics. , 1996, Alcoholism, clinical and experimental research.

[27]  Matcheri S Keshavan,et al.  Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism , 2001, Biological Psychiatry.

[28]  Gregory G. Brown,et al.  fMRI BOLD response to alcohol stimuli in alcohol dependent young women. , 2004, Addictive behaviors.

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

[30]  Paul Cumming,et al.  Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients. , 2005, The American journal of psychiatry.

[31]  A. Heinz,et al.  Dopamine and the diseased brain. , 2006, CNS & neurological disorders drug targets.

[32]  E. Stein,et al.  Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. , 2000, The American journal of psychiatry.

[33]  D. F. Braus,et al.  Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics , 2001, Journal of Neural Transmission.

[34]  Mark Slifstein,et al.  Alcohol Dependence Is Associated with Blunted Dopamine Transmission in the Ventral Striatum , 2005, Biological Psychiatry.

[35]  G. Chiara Nucleus accumbens shell and core dopamine: differential role in behavior and addiction , 2002, Behavioural Brain Research.

[36]  G. Chiara,et al.  Drug Addiction as a Disorder of Associative Learning: Role of Nucleus Accumbens Shell/Extended Amygdala Dopamine , 1999, Annals of the New York Academy of Sciences.

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

[38]  G. Brüning,et al.  Adaptive changes of dopamine-D2 receptors in rat brain following ethanol withdrawal: a quantitative autoradiographic investigation. , 1992, Alcohol.

[39]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[40]  S. Dworkin,et al.  Modifications of dopamine D1 receptor complex in rats self-administering cocaine. , 1998, European journal of pharmacology.

[41]  K. Luan Phan,et al.  Subjective rating of emotionally salient stimuli modulates neural activity , 2003, NeuroImage.

[42]  L. Kozlowski,et al.  The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. , 1991, British journal of addiction.

[43]  W. Miller,et al.  Examining the effects of alcoholism typology and AA attendance on self-efficacy as a mechanism of change. , 2006, Journal of studies on alcohol.

[44]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[45]  W. Miller,et al.  Comparison of Timeline Follow-Back and Averaging Methods for Quantifying Alcohol Consumption in Treatment Research , 1994, Assessment.

[46]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[47]  N. Volkow,et al.  The neural basis of addiction: a pathology of motivation and choice. , 2005, The American journal of psychiatry.

[48]  Christian Büchel,et al.  Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter , 2005, Nature Neuroscience.

[49]  M. Bradley,et al.  Emotional arousal and activation of the visual cortex: an fMRI analysis. , 1998, Psychophysiology.

[50]  A. L. Dixon,et al.  Dopamine antagonist modulation of amphetamine response as detected using pharmacological MRI , 2005, Neuropharmacology.

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

[52]  K. Berridge,et al.  Opioid site in nucleus accumbens shell mediates eating and hedonic ‘liking’ for food: map based on microinjection Fos plumes , 2000, Brain Research.

[53]  H A Skinner,et al.  Reliability of alcohol use indices. The Lifetime Drinking History and the MAST. , 1982, Journal of studies on alcohol.

[54]  Brian Knutson,et al.  Dissociation of reward anticipation and outcome with event-related fMRI , 2001, Neuroreport.

[55]  Arno Villringer,et al.  Dysfunction of ventral striatal reward prediction in schizophrenia , 2006, NeuroImage.