The proposed research will continue to examine alterations in brain structure and function associated with chronic alcoholism. The newly proposed studies build and expand upon recent findings of abnormalities in brain systems controlling specific affective (emotional) and conative (intentional) behaviors associated with this devastating condition. Long-range objectives are: (1) to understand the nature and cerebral bases of neurobehavioral dysfunction in abstinent long-term alcoholic individuals;(2) to clarify the contributions of altered emotional perception and intentional behaviors to alcohol-related cognitive decline;and (3) to determine the nature and scope of gender differences in any observed deficits and intact skills. Based upon a theoretical framework that views alcoholism-related brain abnormalities as encompassing an interrelated multi-component brain-reward network, the studies will continue to combine neurobehavioral measures with structural and functional brain imaging to provide in vivo correlative information on regional brain differences before, during, and after exposure to emotional stimuli. Conative modulation of emotional and nonemotional responses also will be measured. Throughout the research, the studies will examine the possibility that despite structural or functional deficiencies in some brain regions of alcoholics, there may be compensatory participation of other brain regions, which allows the affected individuals to maintain behavioral adequacy. Gender-specific compensatory shifts in regional involvement will be explored. Participants will be abstinent alcoholic men and women, ages 18-55, and nonalcoholic men and women group-matched on age, education, and IQ. Primary regions of interest (ROIs) include prefrontal cortex (and associated white matter connections), and medial temporal areas, which together constitute a neural system intrinsic to emotion, reward, and intentional behaviors. In concert with the use of functional magnetic resonance imaging (fMRI) during emotion- and reward-related tasks, we will conduct structural MRI analyses that include morphometric assessment of brain regions involved in fronto-limbic emotion and reward circuits, and diffusion tensor magnetic resonance imaging (DT-MRI) will be applied to assess coherence of white matter tracts connecting frontal regions with limbic, ventral striatal, and posterior cerebral systems. Neurobehavioral and psychophysiological (electrodermal) measures will be recorded concurrently with central hemodynamic (fMRI) changes in order to examine the coupling between autonomic and central measures of behavior. Overall, the aim is to sharpen distinctions among neurobehavioral sequelae and/or predisposing factors of alcoholism in men and women, and to contribute valuable information about the associated neurobiology of cognitive aspects of emotion and intention deficits in alcoholism.

Public Health Relevance

Emotion dysregulation may underlie addictive disorders such as alcoholism, which in turn may further alter emotional states. Alcoholism-related abnormalities in brain centers controlling emotional perception and regulation may differ for men and women, and can differentially alter the course of alcoholism directly, by affecting sensitivity to feedback, as well as the ability to make economic, social, and health-related decisions. The proposed research will address these issues using neurobehavioral tests in concert with measures of brain structure and function.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neurotoxicology and Alcohol Study Section (NAL)
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Matochik, John A
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Boston University
Anatomy/Cell Biology
Schools of Medicine
United States
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Blum, Kenneth; Oscar-Berman, Marlene; Demetrovics, Zsolt et al. (2014) Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS). Mol Neurobiol 50:765-96
Berkinbayev, S; Rysuly, M; Mussayev, A et al. (2014) Apolipoprotein Gene Polymorphisms (APOB, APOC111, APOE) in the Development of Coronary Heart Disease in Ethnic Groups of Kazakhstan. J Genet Syndr Gene Ther 5:216
Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra D et al. (2014) Hypothesizing dopaminergic genetic antecedents in schizophrenia and substance seeking behavior. Med Hypotheses 82:606-14
Blum, Kenneth; Han, David; Femino, John et al. (2014) Systematic evaluation of "compliance" to prescribed treatment medications and "abstinence" from psychoactive drug abuse in chemical dependence programs: data from the comprehensive analysis of reported drugs. PLoS One 9:e104275
Blum, Kenneth; Schoenthaler, Stephen J; Oscar-Berman, Marlene et al. (2014) Drug abuse relapse rates linked to level of education: can we repair hypodopaminergic-induced cognitive decline with nutrient therapy? Phys Sportsmed 42:130-45
Blum, Kenneth; Oscar-Berman, Marlene; Waite, Roger L et al. (2014) A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain. J Genet Syndr Gene Ther 5:213
Gold, Mark S; Blum, Kenneth; Oscar-Berman, Marlene et al. (2014) Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children? Postgrad Med 126:153-77
Blum, Kenneth; Oscar-Berman, Marlene; Femino, John et al. (2013) Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note. J Addict Res Ther 4:
Braverman, E; Oscar-Berman, M; Lohmann, R et al. (2013) Low and Normal IGF-1 Levels in Patients with Chronic Medical Disorders (CMD) is Independent of Anterior Pituitary Hormone Deficiencies: Implications for Treating IGF-1 Abnormal Deficiencies with CMD. J Genet Syndr Gene Ther 4:
Archer, T; Oscar-Berman, M; Blum, K et al. (2013) Epigenetic Modulation of Mood Disorders. J Genet Syndr Gene Ther 4:

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