The capacity to precisely time events is important for a variety of human activities. Several decades of research in animals and humans have advanced our knowledge of interval timekeeping mechanisms, so that now there is broad support for the view that some aspects of time are explicitly represented in the ventral nervous system. Despite this advancement, our knowledge of the neural systems supporting temporal cognition remains limited. It is the intent of this project, therefore, to use whole-brain fMRI to gain a comprehensive understanding of the brain systems that support temporal information processing. The proposed project consists of three aims.
The first aim will identify the functional neuroanatomy of an internalized timekeeping system operating across millisecond and second intervals using a time bisection task. A separate experiment will determine the neural systems supporting working memory (WM) components of temporal information processing by conducting fMR scanning during the delay period of a temporal comparison task.
The second aim will examine the role of dopaminergic and cholinergic systems in timekeeping and working memory aspects of interval timing. Two double-blind, placebo-controlled, crossover timekeeping and working memory aspects of interval timing. Two double-bind, placebo-controlled, crossover experiments will be conducted involving administration of methylphenidate, haloperidol, physostigmine, and scopolamine to health subjects performing time bisection and temporal WM tasks while undergoing fMR scanning.
The third aim will identify the nature of the interval timing deficits associated with basal ganglia dysfunction. This will be accomplished by conducting fMR imaging in unmedicated patients with Parkinson's disease (PD) and health elderly control subjects during the performance of perceptual and motor timing tasks. In an additional experiment, the effects of dopamine replacement on perceptual and motor timing tasks will be examined in a crossover drug trial involving PD patients on and off medication. The three aims of this project are designed to address fundamental cognitive neuroscience questions involving temporal information processing. The above experiments will also have clinical implications for a variety of neuropsychiatric disorders with established or presumed deficits in timing, including schizophrenia, Parkinson's and Huntington's disease, and Attention Deficit Hyperactivity Disorder.
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