Deficits in impaired inhibitory control functions and in sustained goal-directed behavior have long been identified as key features of alcoholism. Alcohol-use disorders (AUD) are also associated with abnormalities in emotional processing, with a number of studies reporting that selective brain systems that engage the amygdala play a crucial role in a tendency to experience negative emotion and in promoting alcohol intake. Delineation of the interplay between voluntary cognitive control (conceived as an explicit or "top-down" process that require allocation of attentional resources) and emotional responsiveness (conceived as an implicit or "bottom-up" process) is fundamental for understanding behavioral regulation and emotionally motivated actions towards alcohol misuse. The extent to which excessive alcohol use contributes to deficits in cognitive control or to enhanced automatic responsiveness is unknown but can be interrogated experimentally by presentation of affectively laden stimuli. Our recent behavioral studies indicate both disturbed bottom-up processing of redundant sensory information and impaired top-down control of conflict resolution in chronic alcoholics, and lay the foundation for the proposed studies. The primary goal of this project is to identify the neural correlates of implicit bottom-up influences and top-down regulation of emotion and cognition in alcoholism through the use of functional magnetic resonance imaging (fMRI), conventional MRI, and diffusion tensor imaging (DTI), noninvasive, in vivo methods for studying the functional, macrostructural, and microstructural architecture of the brain.
The specific aims of this proposal are to (1) determine how chronic alcoholics differ from controls in component processes of attention-emotion regulation, (2) identify the neural correlates of attention-emotion systems in alcoholism with fMRI, and (3) determine the effects of alcoholism on relationships among regional microstructural brain status (DTI), functional brain networks (fMRI), gray matter foci (MRI), and performance measures. We propose a series of behavioral, structural, and functional MRI studies of attention-emotion processing to examine the extent to which alcoholics have selectively disrupted or preserved automatic bottom-up and attentional top-down control processing of emotional stimuli. The identification of sources of disruption of neural systems of attention and emotion should lead to an understanding of the impact of implicit and explicit control of behavior and has implications for developing interventions for improving cognitive behavioral therapies in individuals with AUD.

Public Health Relevance

Alcoholics, even when abstinent, often have to exert voluntary control to suppress the urge to drink. The purpose of this proposal is to use brain imaging to understand the neural basis of the drive to alcoholic drinking and its control, which in turn may lead to treatments for maintaining sobriety and preventing relapse.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Special Emphasis Panel (ZAA1-CC (02))
Program Officer
Matochik, John A
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Sri International
Menlo Park
United States
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Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf et al. (2015) Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease. Brain Imaging Behav 9:619-38
Schulte, Tilman; Maddah, Mahnaz; Muller-Oehring, Eva M et al. (2013) Fiber tract-driven topographical mapping (FTTM) reveals microstructural relevance for interhemispheric visuomotor function in the aging brain. Neuroimage 77:195-206
Muller-Oehring, Eva M; Schulte, Tilman; Rohlfing, Torsten et al. (2013) Visual search and the aging brain: discerning the effects of age-related brain volume shrinkage on alertness, feature binding, and attentional control. Neuropsychology 27:48-59
Muller-Oehring, E M; Jung, Y-C; Sullivan, E V et al. (2013) Midbrain-driven emotion and reward processing in alcoholism. Neuropsychopharmacology 38:1844-53
Schulte, Tilman; Muller-Oehring, Eva M; Sullivan, Edith V et al. (2012) Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men. Biol Psychiatry 71:269-78
Schulte, Tilman; Muller-Oehring, Eva M (2010) Contribution of callosal connections to the interhemispheric integration of visuomotor and cognitive processes. Neuropsychol Rev 20:174-90
Schulte, Tilman; Müller-Oehring, Eva M; Rohlfing, Torsten et al. (2010) White matter fiber degradation attenuates hemispheric asymmetry when integrating visuomotor information. J Neurosci 30:12168-78
Muller-Oehring, Eva M; Schulte, Tilman; Fama, Rosemary et al. (2009) Global-local interference is related to callosal compromise in alcoholism: a behavior-DTI association study. Alcohol Clin Exp Res 33:477-89
Muller-Oehring, Eva M; Schulte, Tilman; Kasten, Erich et al. (2009) Parallel interhemispheric processing in hemineglect: relation to visual field defects. Neuropsychologia 47:2397-408
Schulte, Tilman; Muller-Oehring, Eva M; Vinco, Shara et al. (2009) Double dissociation between action-driven and perception-driven conflict resolution invoking anterior versus posterior brain systems. Neuroimage 48:381-90

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