Our recent functional and structural magnetic resonance imaging (MRI), balance physiology, and neuropsychological studies point to cerebellar systems disruption as a principal neural mechanism underlying cognitive and motor dysfunction and processing inefficiency in chronic alcoholism. This alcoholism-induced brain pathology itself may change cognition and behavior in a manner that can perpetuate drinking. We now propose to combine sway path analysis to dissect physiological components of static balance control with high resolution structural MRI, diffusion tensor imaging (DTI), and functional MRI (fMRI) to examine the integrity of gray matter components of corticocerebellar circuits, white matter tracts linking them, and the pattern and extent of their functional activation. Our proposal aims to delineate the specific sites and neural mechanisms by which chronic alcohol use impairs cognition and balance. Recovering alcoholic men and women and age- and sex-matched controls will undergo balance testing and neuroimaging with MRI, DTI, and fMRI in a series of inter-related studies to address three specific aims: 1. Specify sources of interference that provoke postural instability in abstinent alcoholic men and women using force platform analysis. With sway path analysis, we will test whether benefits provided by a broad support base and vision to balance stabilization will be significantly reduced in alcoholics more than controls when challenged by a secondary task (mental calculation) while balancing. 2. Characterize the integrity of cerebellopontocortical circuitry with diffusion tensor imaging and cerebellar tissue with high resolution MR imaging. We will use DTI guided by fiber tracking and high resolution MR imaging to characterize the integrity of cerebellopontocortical circuitry and relate it to balance abnormality and to volumes of cerebellum and prefrontal cortex connected by these circuits. 3. Identify neural mechanisms of processing inefficiency with fMRI. We propose two fMRI experiments to identify neural systems underlying processing inefficiency in alcoholics. Our overarching hypothesis is that alcoholics can perform challenging tasks at normal levels by recruiting frontocerebellar systems in excess of those recruited by controls, and this would have the untoward outcome of reducing processing capacity available for simultaneous performance of other tasks, including maintenance of postural stability

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010723-11
Application #
7118282
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Witt, Ellen
Project Start
1996-04-01
Project End
2009-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
11
Fiscal Year
2006
Total Cost
$445,936
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Adeli, Ehsan; Kwon, Dongjin; Zhao, Qingyu et al. (2018) Chained regularization for identifying brain patterns specific to HIV infection. Neuroimage 183:425-437
Peterson, Eric T; Kwon, Dongjin; Luna, Beatriz et al. (2018) Distribution of brain iron accrual in adolescence: Evidence from cross-sectional and longitudinal analysis. Hum Brain Mapp :
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 :
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
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
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
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
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

Showing the most recent 10 out of 155 publications