Alcohol use disorders exact a substantial toll on America's public health especially with respect to brain structure and its myriad functions. The goal of this proposal is to increase understanding of the nature and potential mechanisms of alcoholism-induced brain injury using advanced magnetic resonance brain imaging that could guide rehabilitation strategies and inform treatment development. Current concepts of diseases of the brain suggest that different diseases affect specific neurocircuitry connecting disparate reaches of the brain. Converging evidence from human in vivo and postmortem studies of chronic alcoholism strongly implicate disruption of frontocerebellar circuitry as a principal contributor to the characteristic pattern of alcoholism-related impairment. Although animal studies have identified the neuroanatomy of cerebrocerebellar circuits relevant to alcoholism, recent human neuroimaging experiments have demonstrated functional cerebrocerebellar circuitry that does not necessarily have a known neuroanatomy. These intrinsic connectivity networks (ICN) can be identified with in vivo functional connectivity MR imaging (fcMRI). In addition to examining the known cerebrocerebellar anatomy, identification of intrinsic neurocircuitry could provide basic science insight into mechanisms underlying selective impairments and fundamental information for developing behavioral or pharmacological therapies and approaches for improving processing efficiency and compensation for associated dysfunction. The goal of this hypothesis-driven proposal is to determine the integrity of cerebrocerebellar ICNs, their functional significance, and the influence of alcohol-induced neuropathology on these networks. The three specific aims are:
Specific Aim 1 : To elucidate the status of intrinsic and activated functional cerebellar networks using resting state fcMRI and task-activated fMRI Specific Aim 2: To determine the impact of alcoholism-induced degradation of the neuroanatomy (identified with MRI and diffusion tensor imaging, DTI) and cerebral blood perfusion (measured with arterial spin labeling, ASL) on task-activated and intrinsic connectivity networks involving frontocerebellar circuitry Specific Aim 3: To examine the motor and cognitive ramifications of intrinsic network status identified with fcMRI.

Public Health Relevance

Alcohol use disorders exact a substantial toll on America's public health especially as it affects the brain and its many functions. The goal of this proposal is to increase the understanding of the nature and potential biological mechanisms of alcoholism-induced brain injury, which may well contribute to difficulties in achieving and maintaining sobriety. Advanced magnetic resonance brain imaging used to specify where alcoholic injury occurs in the brain and how injury impairs function should guide insights for rehabilitation strategies and treatment development.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AA010723-16
Application #
8299382
Study Section
Special Emphasis Panel (ZRG1-IFCN-C (02))
Program Officer
Matochik, John A
Project Start
1996-04-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
16
Fiscal Year
2012
Total Cost
$494,398
Indirect Cost
$135,877
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Alba-Ferrara, L; Müller-Oehring, E M; Sullivan, E V et al. (2016) Brain responses to emotional salience and reward in alcohol use disorder. Brain Imaging Behav 10:136-46
Le Berre, Anne-Pascale; Sullivan, Edith V (2016) Anosognosia for Memory Impairment in Addiction: Insights from Neuroimaging and Neuropsychological Assessment of Metamemory. Neuropsychol Rev 26:420-431
Le Berre, Anne-Pascale; Müller-Oehring, Eva M; Kwon, Dongjin et al. (2016) Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates. Cortex 81:192-202
Sullivan, Edith V; Zahr, Natalie M; Rohlfing, Torsten et al. (2015) Cognitive demands during quiet standing elicit truncal tremor in two frequency bands: differential relations to tissue integrity of corticospinal tracts and cortical targets. Front Hum Neurosci 9:175
Fama, Rosemary; Sullivan, Edith V (2015) Thalamic structures and associated cognitive functions: Relations with age and aging. Neurosci Biobehav Rev 54:29-37
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
Pfefferbaum, Adolf; Sullivan, Edith V (2015) Cross-sectional versus longitudinal estimates of age-related changes in the adult brain: overlaps and discrepancies. Neurobiol Aging 36:2563-7
Jung, Young-Chul; Schulte, Tilman; Müller-Oehring, Eva M et al. (2014) Synchrony of anterior cingulate cortex and insular-striatal activation predicts ambiguity aversion in individuals with low impulsivity. Cereb Cortex 24:1397-408
Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra et al. (2014) Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: comparison of effects in France and the United States. Hum Brain Mapp 35:4635-53
Fama, Rosemary; Rosenbloom, Margaret J; Sassoon, Stephanie A et al. (2014) Thalamic volume deficit contributes to procedural and explicit memory impairment in HIV infection with primary alcoholism comorbidity. Brain Imaging Behav 8:611-20

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