Driving while intoxicated (DWI) with alcohol is a major public health problem. Despite this, there is relatively little documentation of the inter-relationship of alcohol's effects on a). brain function, b). driving behavior c). the hierarchy of cognitive operations mediating driving performance and d. the dose-relatedness of these effects. Driving is a complex 'whole' behavior that is best studied both directly, in a """"""""top-down"""""""" fashion and """"""""bottom up"""""""" by examining simpler, cognitive component tasks. Simulated driving offers a direct, reproducible, quantitative in-lab means to assess normal and impaired driving, that can be used with functional magnetic resonance imaging (fMRI) to quantify associated brain changes. The proposed research will address all these aspects in a multidisciplinary project based on Groeger's (2000) cognitive model of driving. We have collected a significant amount of relevant pilot data. We will focus on characterizing alcohol's acute effects on behavior and brain function in a series of controlled, within-subject, human studies of persons admitted to an inpatient CRC for 5 days. We will evaluate double-blind dose-responses of several alcohol doses vs placebo on: 1) behavioral performance during tasks of visual working memory, divided visual attention and simulated driving, 2) profiles of subjective intoxication and impairment and (3) task-related fMRI brain patterns. To examine their interrelationships, the different outcome measures will be assessed in close temporal proximity. Different experiments will examine 1) dose-response effects of alcohol and 2) their effects in the presence vs absence of alcohol tolerance. These studies will provide valuable information about 1) cerebral activation patterns and mechanisms of neurocognitive performance on driving and related tasks, 2) effects of alcohol on this cerebral activation, 3) the effects of alcohol on behavior observed during several neurocognitive tasks, including simulated driving, and 4) inter-relationships among localized brain function, neurocognitive task demands, and pharmacology as determinants of alcohol -produced driving impairments. To conduct this research, we have assembled a unique team with expertise in experimental drug abuse paradigms, cognitive neuroscience, quantitative fMRI and behavior assessment. The PI's laboratory has developed novel fMRI analysis paradigms and driving simulation software. Together, these allow dissection of alcohol's effects on the multiple overlapping neural circuits associated with performance of complex, driving-related cognitive tasks.
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