Alcohol use disorders exact a substantial toll on America's public health especially with respect to brain structure and its functions. The goal of this expanded research plan is to identify mechanisms of alcoholism- induced brain injury using advanced magnetic resonance brain imaging (MRI) that could guide rehabilitation strategies and ultimately inform pharmacological treatment development. Alcoholism's dynamic cycle of remission and relapse can result in compromised functioning, selectively destructive to problem solving, working memory, visuospatial abilities, and gait and balance. Converging evidence strongly implicates disruption of frontocerebellar circuitry as a principal contributor to the characteristic pattern of alcoholism- related impairment. Findings generated from the current research revealed this circuitry comprises multiple dissociable loops, each subserving different cognitive or motor functions. We also established which loops are affected and which are spared in alcoholism and have discovered instatement of novel functional connections associated with good performance and longer sobriety in recovering alcoholics. In addition to these task-activated findings, our resting-state (rs) fMRI studies identified intrinsic functional connectivity networks that are affected and others that are spared in alcoholics. Our pursuit now will be to test whether network recruitment can be redirected from disrupted nodes and networks to alternative functional circuitry for overcoming selective dysfunction. Proposed are 3 specific aims with testable hypotheses:
Specific Aim 1 : To elucidate the status with short-term abstinence and change with sustained abstinence or relapse of resting-state intrinsic and task-activated functional cerebellar networks;
Specific Aim 2 : To determine the impact of sustained sobriety or relapse on alcoholism-induced degradation ofthe neuroanatomy and cerebral blood perfusion on task-activated and intrinsic connectivity networks involving frontocerebellar circuitry;
Specific Aim 3 : To examine the motor and cognitive ramifications of sobriety-related or reIapse-related changes measured in intrinsic network connectivity identified with rsfMRI.

Public Health Relevance

Alcohol use disorders exact a substantial toll on America's public health especially with respect to its untoward effect on brain structure and its functions. Using advanced neuroimaging, we expect to gain knowledge about what brain systems sustain injury from alcoholism and to differentiate the affected from the unaffected systems. Success in this research endeavor could guide rehabilitation strategies, inform pharmacological treatment development, and aid initiation and maintenance of sobriety.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Matochik, John A
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Stanford University
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Adeli, Ehsan; Kwon, Dongjin; Zhao, Qingyu et al. (2018) Chained regularization for identifying brain patterns specific to HIV infection. Neuroimage 183:425-437
Sullivan, Edith V; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. JAMA Psychiatry 75:474-483
Pfefferbaum, Adolf; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection. Biol Psychiatry Cogn Neurosci Neuroimaging 3:844-859
Kwon, Dongjin; Pfefferbaum, Adolf; Sullivan, Edith V et al. (2018) Regional growth trajectories of cortical myelination in adolescents and young adults: longitudinal validation and functional correlates. Brain Imaging Behav :
Park, Sang Hyun; Zhang, Yong; Kwon, Dongjin et al. (2018) Alcohol use effects on adolescent brain development revealed by simultaneously removing confounding factors, identifying morphometric patterns, and classifying individuals. Sci Rep 8:8297
Fama, Rosemary; Le Berre, Anne-Pascale; Hardcastle, Cheshire et al. (2017) Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism. Addict Biol :
Zahr, Natalie M; Pfefferbaum, Adolf; Sullivan, Edith V (2017) Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders. Neuropharmacology 122:189-200
Sullivan, Edith V (2017) Contributions to Understanding the Neuropsychology of Alcoholism: An INS Legacy. J Int Neuropsychol Soc 23:843-859
Le Berre, Anne-Pascale; Müller-Oehring, Eva M; Schulte, Tilman et al. (2017) Deviant functional activation and connectivity of the right insula are associated with lack of awareness of episodic memory impairment in nonamnesic alcoholism. Cortex 95:15-28
Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V (2017) Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research. Alcohol Clin Exp Res 41:1432-1443

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