Cerebellar Structure and Function in Alcoholism

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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.