We propose to continue using magnetic resonance imaging (MRI), neuropsychological (NP), and event-related potential (ERP) testing to extend and refine our findings of CNS deficits associated with chronic alcoholism and aging. Our MRI studies of alcoholic man reveal volume loss in cortical gray and white matter, corpus callosum, hippocampus, and mammillary bodies and enlargement of cortical sulci and lateral and third ventricles. Older alcoholic men have gray matter volume deficits particularly striking in the prefrontal cortex. Electrophysiologically, the latency of P300, a physiological index of cognitive speed, is prolonged in alcoholic men with an exaggerated prolongation in older alcoholics; further, P300 latency and indices of tissue loss are significantly associated in alcoholics. Neuropsychologically, alcoholic men show deficits in executive abilities, short-term memory, fluency, and visuospatial abilities and especially severe deficits in balance. Our longitudinal studies demonstrate recovery of gray matter volume with abstinence and further reduction of white matter volume with continued drinking. For this competitive renewal, we propose the following studies: Study 1: fMRI experiments of localized brain activation during performance of auditory and visual working memory tasks. This study is designed to determine whether alcoholics show a pattern of cortical activation during working memory that is different from that observed in controls, and whether underlying structural deficits influence the pattern of fMRI activation. Study 2: Visual ERP and NP experiments of interhemispheric transfer time designed to assess the functional significance of corpus callosal thinning. Study 3: Continuation of our ongoing longitudinal study of alcoholic and control women. This study is designed to identify cross-sectional patterns of sparing and loss, their interaction with age and their comparability to findings in alcoholic men. Cross-sectional findings will be examined longitudinally to determine their interaction with alcohol consumption and the normal course of aging and to assess the extent to which deficits normalize with sobriety or are exacerbated with continued drinking. Study 4: A new longitudinal study in a new sample of older alcoholic men and women and their controls in order to extend, with refined anatomical and new functional measures, earlier findings.

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 #
5R37AA005965-16
Application #
2516794
Study Section
Special Emphasis Panel (ZRG4-ALTX-1 (01))
Project Start
1997-05-01
Project End
2001-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
16
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Sri International
Department
Type
DUNS #
City
Menlo Park
State
CA
Country
United States
Zip Code
94025
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
Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten et al. (2016) Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo. Psychopharmacology (Berl) 233:2675-86
Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk et al. (2016) Transient CNS responses to repeated binge ethanol treatment. Addict Biol 21:1199-1216
Zahr, Natalie M; Carr, Rebecca A; Rohlfing, Torsten et al. (2016) Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse. Psychiatry Res Neuroimaging 250:42-9
Park, Jae Mo; Josan, Sonal; Jang, Taichang et al. (2016) Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model. Magn Reson Med 75:973-84
Park, Jae Mo; Spielman, Daniel M; Josan, Sonal et al. (2016) Hyperpolarized (13)C-lactate to (13)C-bicarbonate ratio as a biomarker for monitoring the acute response of anti-vascular endothelial growth factor (anti-VEGF) treatment. NMR Biomed 29:650-9
Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra et al. (2015) Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States. Front Hum Neurosci 9:354
Cui, Changhai; Noronha, Antonio; Warren, Kenneth R et al. (2015) Brain pathways to recovery from alcohol dependence. Alcohol 49:435-52
Pfefferbaum, Adolf; Zahr, Natalie M; Mayer, Dirk et al. (2015) Dynamic responses of selective brain white matter fiber tracts to binge alcohol and recovery in the rat. PLoS One 10:e0124885
Park, Jae Mo; Josan, Sonal; Mayer, Dirk et al. (2015) Hyperpolarized 13C NMR observation of lactate kinetics in skeletal muscle. J Exp Biol 218:3308-18

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