This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Impairment in frontostriatally based executive tasks represents an overlapping feature in neurodegenerative and neurodevelopmental disorders affecting the cortico-striatal-pallido-thalamic loops (CSPTC) and related pathways, such as Parkinson's disease, Huntington's disease, Alzheimer's disease, minimal cognitive impairment, dystonia syndromes, Tourette's syndrome and schizophrenia spectrum disorders. However, the mechanism by which this cognitive impairment is mediated is likely to vary across diseases according to the primarily affected brain regions. Our general hypothesis, based on preliminary data, is that impaired activation of frontal and/or striatal regions is responsible for impaired prefrontal information processing in neurodegenerative diseases affecting CSTPC regions. By contrast impairment in the functional connectivity between the frontal cortex and the striatum is hypothesized to be responsible for impaired prefrontal information processing in neurodevelopmental disorders affecting CSTPC function. Using a combined neuropsychological and functional magnetic resonance imaging approach, we plan to study functional correlates of cognitive tasks involving mainly prefrontal information processing. Together, these studies will provide important information concerning the physiological mechanisms that underlie cognitive deficits in these disorders.
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