Attention Deficit Disorder (ADHD) is a common neurodevelopmental disorder that defines a group of individuals with developmentally inappropriate levels of inattention and hyperactivity-impulsivity. Long-term follow-up studies indicate that ADHD persists into adulthood in 30-66 percent of cases. Neuropsychological studies have identified a wide range of cognitive deficits in ADHD, including impairments on measures of response inhibition, sustained attention/working memory, timing perception/reproduction, and conceptual reasoning, prompting the suggesting that ADHD is associated with abnormal functioning of the prefrontal cortex and its subcortical connections. As a result of significant technological advances in human brain imaging, it is now possible to identify functional brain abnormalities that may underlie the cognitive deficits in ADHD. The long-range goal of this project, therefore, is to apply whole-brain fMRI to better understand the brain- mediated neurocognitive deficits in ADHD adults and to elucidate the mechanisms of action of psychostimulants commonly used to treat this disorder. The first hypothesis to be tested is that, relative to healthy individuals, unmedicated ADHD subjects will evidence minimal or no task- induced regional brain activation in frontostriatal circuitry. The second hypothesis is that methylphenidate (M)P will produce increases in task- induced functional activity in frontostriatal circuity in both ADHD and normal subjects. Third, the investigator hypothesizes that MP will """"""""normalize"""""""" task-induced functional specificity in ADHD individuals relative to normal subjects.
Three specific aims will be addressed: 1) to determine the regional changes in functional brain activation in unmedicated ADHD adults in response to performing cognitive tasks involving response inhibition, working memory, timing perception/reproduction, and conceptual reasoning, 2) to determine the effects of MP on task-activated brain activation patterns in normal subjects using a double-blind, placebo-controlled, cross-over design, and 3) to determine the effects of MP on task-activated brain activation patterns in ADHD subjects using a double-blind, placebo-controlled, cross- over design. The proposed fMRI experiments, therefore, should not only enhance our understanding of the brain abnormalities associated with ADHD, but should also provide a general blueprint for evaluating the neurocognitive effects of drugs in normal and abnormal populations.
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