Brain atrophy in long-term abstinent alcoholics who demonstrate impairment on a simulated gambling task

We recently demonstrated impairment on the Simulated Gambling Task (SGT) in long-term abstinent alcoholics (AbsAlc). Brain regions that have been shown to be necessary for intact SGT performance are the ventromedial prefrontal cortex (VMPFC) and the amygdala; patients with VMPFC or amygdalar damage demonstrate SGT impairments similar to those of substance abusing populations. We examined these brain regions, using T1-weighted MRIs, in the 101 participants from our previous study using voxel-based morphometry (VBM). VBM was performed using a modification we developed [Fein, G., Landman, B., Tran, H., Barakos, J., Moon, K., Di Sclafani, V., Shumway, R., 2006. Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs. Neuroimage] of Baron's procedure, [], in which we use skull-stripped images as input. We also restricted the analysis to a ROI consisting of the amygdala and VMPFC as defined by the Talairach Daemon resource. Compared to the controls, the AbsAlc participants had significant foci of reduced gray matter density within the amygdala. Thus, SGT decision-making deficits are associated with reduced gray matter in the amygdala, a brain region previously implicated in similar decision-making impairments in neurological samples. This structurally based abnormality may be the result of long-term alcohol abuse or dependence, or it may reflect a pre-existing factor that predisposes one to severe alcoholism. From an image analysis perspective, this work demonstrates the increased sensitivity that results from using skull-stripped inputs and from restricting the analysis to a ROI. Without both of these methodological advances, no statistically significant finding would have been forthcoming from this work.

[1]  S. Rauch,et al.  Inhibited and Uninhibited Infants "Grown Up": Adult Amygdalar Response to Novelty , 2003, Science.

[2]  W. Bickel,et al.  Shortened time horizons and insensitivity to future consequences in heroin addicts. , 1998, Addiction.

[3]  Bennett A. Landman,et al.  Statistical parametric mapping of brain morphology: Sensitivity is dramatically increased by using brain-extracted images as inputs , 2006, NeuroImage.

[4]  Laura Mickes,et al.  Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects. , 2002, Archives of neurology.

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

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

[7]  M. Davis,et al.  Footshock-induced sensitization of electrically elicited startle reflexes. , 1989, Behavioral neuroscience.

[8]  Hanna Damasio,et al.  Decision-making and addiction (part I): impaired activation of somatic states in substance dependent individuals when pondering decisions with negative future consequences , 2002, Neuropsychologia.

[9]  Itamar Kahn,et al.  The Role of the Amygdala in Signaling Prospective Outcome of Choice , 2002, Neuron.

[10]  G. Fein,et al.  Cognitive performance in long-term abstinent alcoholic individuals. , 2006, Alcoholism, clinical and experimental research.

[11]  W. Bickel,et al.  Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. , 1999, Journal of experimental psychology. General.

[12]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[13]  Stephen M. Smith,et al.  Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis , 2002, NeuroImage.

[14]  S. Kiebel,et al.  An Introduction to Random Field Theory , 2003 .

[15]  Karl J. Friston,et al.  Human Brain Function , 1997 .

[16]  Steven W Anderson,et al.  Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers , 2001, Neuropsychologia.

[17]  R. Rogers,et al.  Effects of beta-adrenoceptor blockade on components of human decision-making , 2004, Psychopharmacology.

[18]  G. Fein,et al.  Cognitive performance in long-term abstinent elderly alcoholics. , 2007, Alcoholism, clinical and experimental research.

[19]  G. Fein,et al.  Impairment on a simulated gambling task in long-term abstinent alcoholics. , 2004, Alcoholism, clinical and experimental research.

[20]  Christian Enzinger,et al.  MTI of white matter hyperintensities. , 2005, Brain : a journal of neurology.

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

[22]  C. Patrick,et al.  Emotion and psychopathy: startling new insights. , 1994, Psychophysiology.

[23]  Daniel Tranel,et al.  Exploring the neurological substrate of emotional and social intelligence. , 2003, Brain : a journal of neurology.

[24]  E. Murray,et al.  The amygdala and reward , 2002, Nature Reviews Neuroscience.

[25]  Carlo Contoreggi,et al.  Drug abusers show impaired performance in a laboratory test of decision making , 2000, Neuropsychologia.

[26]  George Fein,et al.  Controlling for premorbid brain size in imaging studies: T1-derived cranium scaling factor vs. T2-derived intracranial vault volume , 2004, Psychiatry Research: Neuroimaging.

[27]  A. Bechara,et al.  Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward? , 2002, Neuropsychologia.

[28]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[29]  A. Damasio,et al.  Insensitivity to future consequences following damage to human prefrontal cortex , 1994, Cognition.

[30]  J E Steinmetz,et al.  Decision-making biases, antisocial personality, and early-onset alcoholism. , 2000, Alcoholism, clinical and experimental research.

[31]  Joseph E LeDoux,et al.  The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  A. Pfefferbaum,et al.  A profile of neuropsychological deficits in alcoholic women. , 2002, Neuropsychology.

[33]  Gregory P. Lee,et al.  Different Contributions of the Human Amygdala and Ventromedial Prefrontal Cortex to Decision-Making , 1999, The Journal of Neuroscience.

[34]  M. Butters,et al.  The neuropsychological consequences of abstinence among older alcoholics: a cross-sectional study. , 2000, Alcoholism, clinical and experimental research.

[35]  P. Finn,et al.  Motivation, working memory, and decision making: a cognitive-motivational theory of personality vulnerability to alcoholism. , 2002, Behavioral and cognitive neuroscience reviews.

[36]  A. Damasio,et al.  Deciding Advantageously Before Knowing the Advantageous Strategy , 1997, Science.

[37]  J. Steinmetz,et al.  Early-onset alcoholism with conduct disorder: go/no go learning deficits, working memory capacity, and personality. , 2002, Alcoholism, clinical and experimental research.

[38]  L. Ketonen Neuroimaging of the aging brain. , 1998, Neurologic clinics.

[39]  A. Damasio,et al.  Role of the Amygdala in Decision‐Making , 2003, Annals of the New York Academy of Sciences.

[40]  Jerome R Busemeyer,et al.  Psychological processes underlying risky decisions in drug abusers. , 2005, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[41]  S. Kollins,et al.  Delay discounting is associated with substance use in college students. , 2003, Addictive behaviors.

[42]  Mortimer Mishkin,et al.  Chapter 12 – THE AMYGDALA: SENSORY GATEWAY TO THE EMOTIONS , 1986 .

[43]  E. Murray,et al.  Control of Response Selection by Reinforcer Value Requires Interaction of Amygdala and Orbital Prefrontal Cortex , 2000, The Journal of Neuroscience.

[44]  T. Robbins,et al.  Decision-making deficits in drug addiction , 2002, Trends in Cognitive Sciences.

[45]  Monique Ernst,et al.  Decision-making in a Risk-taking Task: A PET Study , 2002, Neuropsychopharmacology.

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

[47]  Jerome R Busemeyer,et al.  Cognitive modeling analysis of decision-making processes in cocaine abusers , 2004, Psychonomic bulletin & review.

[48]  S. Mitchell,et al.  Measures of impulsivity in cigarette smokers and non-smokers , 1999, Psychopharmacology.

[49]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[50]  F. Gunning-Dixon,et al.  The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. , 2000, Neuropsychology.

[51]  Cheuk Y. Tang,et al.  Differential amygdala activation during emotional decision and recognition memory tasks using unpleasant words: an fMRI study , 2001, Neuropsychologia.

[52]  F. Crews,et al.  Alcoholic neurobiology: changes in dependence and recovery. , 2005, Alcoholism, clinical and experimental research.

[53]  Michael Davis Neural Systems Involved in Fear‐Potentiated Startle , 1989, Annals of the New York Academy of Sciences.

[54]  A. Bechara,et al.  Neurobiology of decision-making: risk and reward. , 2001, Seminars in clinical neuropsychiatry.

[55]  T. Robbins,et al.  Contrasting Roles of Basolateral Amygdala and Orbitofrontal Cortex in Impulsive Choice , 2004, The Journal of Neuroscience.

[56]  S. Rauch,et al.  Investigating the pathogenesis of posttraumatic stress disorder with neuroimaging. , 2001, The Journal of clinical psychiatry.