Human Cerebellar Function in Multiple Task Domains

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PROJECT SUMMARY The goal of this project is to extend our understanding of the cerebellum, and in particular, how this subcortical structure contributes to human cognition. Diverse lines of research provide compelling evidence that the cerebellum is not only involved in sensorimotor control, but also contributes to a range of cognitive functions. For example, the neuroimaging literature has produced maps of the cerebellum that exhibit a stable functional organization, with much of the cerebellar cortex showing hemodynamic changes that cannot be attributed to movement. Moreover, patients with cerebellar disorders exhibit behavioral impairments on tasks assessing cognitive and affective processing. However, our understanding of the functional role of the cerebellum in cognitive domains remains rudimentary: Functional hypotheses have either been largely descriptive or targeted to account for cerebellar function in a relatively narrow, task-specific manner. The research program outlined in this proposal is designed to address this issue, seeking to develop a mechanistic account of cerebellar function. Theoretically, the work will be guided by a novel hypothesis, namely that the cerebellum is essential for processing that requires the continuous transformation of an internal representation, or CoRT(continuous representational transformation). This hypothesis offers a parsimonious account of how the cerebellum supports performance in diverse task domains. In the context of sensorimotor control, CoRT would entail computations required to move a limb from one position to another and to anticipate the sensory consequences of that movement. In other task domains, the continuous transformation of an internal representation may optimize anticipatory behavior; for example, perception frequently involves the internal transformation of the sensory input to account for atypical viewpoints, and social judgments may benefit continuously simulating the intended actions of another individual. The research program will involve the integrated use of behavioral, computational, and neuroimaging studies. One major component of the behavioral work will focus on the performance of individuals with spinocerebellar ataxia (SCA). This work will involve traditional on-site experiments spanning a broad range of task domains to test the CoRT hypothesis, as well as an ambitious on-line testing program. Through an outreach program facilitated by SCA support networks and collaborations with an international team of researchers, the on-line program should produce a unique database to provide well-powered tests of functional hypotheses, and examine relationships between behavioral performance, etiology, and clinical ratings, and relate these measures with region-specific pathology in the cerebellum. A second major component will build on recent neuroimaging work with healthy young adults that has provided a comprehensive functional map of the human cerebellum though the use of a large battery of tasks. This approach will be used to explore constraints on the organization of the functional map by developing models of cortico-cerebellar connectivity and examining changes over the course of learning. As with the neuropsychological studies, the neuroimaging studies will yield a rich database to evaluate different functional hypotheses, as well as establish norms for comparison with atypical populations. !