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 #
5R37AA010723-17
Application #
8494456
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
2013-07-01
Budget End
2014-06-30
Support Year
17
Fiscal Year
2013
Total Cost
$455,631
Indirect Cost
$125,629
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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
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
Zhang, Yong; Park, Sang Hyun; Pohl, Kilian M (2016) Joint Data Harmonization and Group Cardinality Constrained Classification. Med Image Comput Comput Assist Interv 9900:282-290
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
Zhang, Yong; Kwon, Dongjin; Esmaeili-Firidouni, Pardis et al. (2016) Extracting patterns of morphometry distinguishing HIV associated neurodegeneration from mild cognitive impairment via group cardinality constrained classification. Hum Brain Mapp 37:4523-4538
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
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
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

Showing the most recent 10 out of 73 publications