Basal Ganglia, Cerebellum, and Higher Cortical Function

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

DESCRIPTION (provided by applicant): The classical view is that the outputs from the basal ganglia and cerebellum project to a region of the ventrolateral thalamus that ultimately influences a single cortical area, the primary motor cortex. In contrast, the basal ganglia and cerebellum receive input from multiple areas of the cerebral cortex located in the frontal, parietal, and temporal lobes. This view contributed to the concept that the basal ganglia and cerebellum perform a sensorimotor transformation on the diverse cortical input they receive. The results of this processing are then used to generate and control movement at the level of the motor cortex. New anatomical findings have required a reappraisal of this functional construct. For example, we have shown that the outputs from the basal ganglia and cerebellum project not only to primary motor and premotor areas of cortex, but also to selected portions of prefrontal, posterior parietal and inferotemporal cortex. Thus, it is now clear that the outputs from the basal ganglia and cerebellum influence more widespread regions of the cerebral cortex than previously suspected. In general, we have seen that cortical areas that project to the input stage of basal ganglia and cerebellar processing also are the target of basal ganglia and cerebellar output. This and other observations have led us to hypothesize that a major organizational feature of basal ganglia and cerebellar anatomy is their participation in closed 'loop' circuits with multiple cortical areas. We now propose to test whether this functional architecture extends to other regions of the cerebral cortex that are known to provide input to the basal ganglia and cerebellum. For example, anterior cingulate and orbital frontal cortex are major sources of input to the basal ganglia. Similarly, widespread areas of the posterior parietal cortex which were not examined in our prior studies are major sources of input to the cerebellum. We will use retrograde transneuronal transport of neurotropic viruses to test whether the output nuclei of the basal ganglia and cerebellum project back upon these areas of cortex. It is known that abnormal activity in basal ganglia and cerebellar loops with motor areas of cortex results in hypo-and hyperkinetic movements. Likewise, abnormal activity in loops with cingulate, orbital frontal, and posterior parietal cortex could lead to a broad range of psychiatric and neurological symptoms such as those associated with depression, obsessive-compulsive disorder, Parkinson's and Huntington's Disease. When these loops are functioning normally, they could provide the neural substrate for basal ganglia and cerebellar involvement in cognitive, emotional and perceptual domains. Thus, the results of these experiments could have important implications for concepts regarding basal ganglia and cerebellar contributions to normal and abnormal behavior.