This research will investigate alterations in brain structure and function associated with chronic alcoholism, and explore possible compensatory adaptations in the brain, wherein unaffected regions assume functions of ineffective regions. The proposed studies build and expand upon our recent findings of abnormalities in brain systems controlling specific affective (emotional) and conative (volitional/intentional) behaviors associated with this devastating condition, especially with respect to gender differences in deficits and intact skills. Based upon a theoretical framework that views alcoholism-related brain abnormalities as encompassing interrelated multi- component brain networks, the studies will combine neurobehavioral measures with brain structure, diffusion (dMRI), and functional magnetic resonance imaging (fMRI) to provide in vivo correlative information on regional brain differences before, during, and after exposure to affective and reward-related stimuli. Specific objectives are to test the following hypotheses regarding mesocorticolimbic circuitry involved in emotion and reward sensitivity, and cerebro-cerebellar networks intrinsic to intentional planning, controlling, and executing responses: (1) alcoholic men and women show differences in abnormal cerebral structural and functional connectivity; (2) alcoholic men and women show different dMRI patterns of abnormal white matter tracts in these networks as disclosed by the powerful Connectome scanner; and (3) novel multimodal analysis will demonstrate Group and Gender effects across imaging and neurobehavioral domains. Throughout, 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 regions, which allows alcoholic individuals to maintain adequate levels of behavior. Compensatory modifications will be reflected principally in brain regions where task-related fMRI activation is stronger for alcoholic than for controls, or appears in regions not similarly active in controls. Gender-specific compensatory shifts and patterns of regional involvement also will be investigated. Participants will be abstinent alcoholic men and women, ages 25-75, and age-equivalent nonalcoholic controls. In concert with fMRI during emotion- and reward-related tasks, including tasks sensitive to response volition, we will conduct structural MRI analyses that include morphometric assessment of brain regions involved in emotion, reward acquisition and loss, and conative behavior. Additionally, dMRI will be applied to assess coherence of white matter tracts connecting frontal regions with limbic, ventral striatal, and posterior cerebral systems, an with the cerebellum. Behavioral responses will be recorded concurrently with central hemodynamic (fMRI) measures, and all of the findings will be linked to measures of alcohol history and neuropsychological performance and combined in multimodal analyses. Overall, the aim is to sharpen distinctions among neurobehavioral sequelae and predisposing factors of alcoholism in men and women, and to contribute valuable insights regarding the associated neurobiology of disordered emotion and intention.

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 feedbac, as well as the ability to make economic, social, and health-related decisions. The proposed research will address these issues using novel multimodal analyses of brain structure and function across neuroimaging and neurobehavioral domains.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Xu, Benjamin
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Boston University
Anatomy/Cell Biology
Schools of Medicine
United States
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Sawyer, Kayle S; Maleki, Nasim; Papadimitriou, George et al. (2018) Cerebral white matter sex dimorphism in alcoholism: a diffusion tensor imaging study. Neuropsychopharmacology 43:1876-1883
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