(1)A 0.5 mg intravenous dose of scopolamine did not alter the global glucose metabolic rates of young and older normals. In the younger normals, studied while performing a task requiring sustained attention, the most prominent effects were in those regions of the brain hypothesized to be part of the brain's attention network, e.g. the thalamus and cingulate cortex. In the older subjects, at rest, thalamic affects were not apparent, but decreases in the frontal cortex were observed. Neither group showed changes consistent with changes seen in Alzheimer's Disease. Thus, lesions of the muscarinic cholinergic system are not likely to contribute to the hypometabolic changes seen in Alzheimer's Disease, and that the sensitivity of frontal cortex functional activity to muscarinic blockade may be responsible for the increased sensitivity of older subjects to the memory impairing affects of scopolamine. (2)The dose and time dependency of the affects on regional blood flow in normals of the administration of the high affinity central benzodiazepine receptor agonist was evaluated. Lorazepam decreased blood flow to a large number of brain regions including the cingulate, thalamus and corpus striatum in a dose dependent manner which was reversed by the benzodiazepine antagonist flumazenil. Having been validated, regional blood flow responses can now be used to evaluate benzodiazepine receptor sensitivity in the variety of neuropsychiatric disorders in which this pathway has been implicated. (3) We examined regional brain activities in dyslexia during a tonal memory task. We found diminished activation in right frontotemporal regions in the presence of normal left mid to anterior temporal cortex activation. These results support hypothesized underlying deficits in rapid temporal processing and probable involvement of both right and left temporal cortex in severe dyslexia.
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