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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007112-25
Application #
8266550
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Matochik, John A
Project Start
1987-07-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
25
Fiscal Year
2012
Total Cost
$1,034,684
Indirect Cost
$273,723
Name
Boston University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Blum, Kenneth; Simpatico, Thomas; Febo, Marcelo et al. (2016) Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs. Mol Neurobiol :
Sawyer, Kayle S; Oscar-Berman, Marlene; Mosher Ruiz, Susan et al. (2016) Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women. Alcohol Clin Exp Res 40:1262-72
Seitz, Johanna; Sawyer, Kayle S; Papadimitriou, George et al. (2016) Alcoholism and sexual dimorphism in the middle longitudinal fascicle: a pilot study. Brain Imaging Behav :
Blum, Kenneth; Febo, Marcelo; Badgaiyan, Rajendra D et al. (2016) Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape. Curr Neuropharmacol :
Sawyer, Kayle S; Poey, Alan; Ruiz, Susan Mosher et al. (2015) Measures of skin conductance and heart rate in alcoholic men and women during memory performance. PeerJ 3:e941
McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene et al. (2015) Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. J Behav Addict 4:106-15
Blum, Kenneth; Thanos, Peter K; Oscar-Berman, Marlene et al. (2015) Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction. J Reward Defic Syndr 1:95-104
Blum, Kenneth; Liu, Yijun; Wang, Wei et al. (2015) rsfMRI effects of KB220Zâ„¢ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med 127:232-41
Blum, Kenneth; Thanos, Peter K; Badgaiyan, Rajendra D et al. (2015) Neurogenetics and gene therapy for reward deficiency syndrome: are we going to the Promised Land? Expert Opin Biol Ther 15:973-85
Modestino, Edward Justin; Blum, Kenneth; Oscar-Berman, Marlene et al. (2015) Reward Deficiency Syndrome: Attentional/Arousal Subtypes, Limitations of Current Diagnostic Nosology, and Future Research. J Reward Defic Syndr 1:6-9

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