PARALLELS IN AGE-RELATED CHANGES IN LEARNING AND THE CEREBELLUM





D. S. Woodruff-Pak

Temple University, Department of Psychology, 1701 North 13th Street, Philadelphia, PA 19122



Age-related changes in the cerebellum appear relatively early in mammals, and a cerebellar role has been demonstrated for many forms of cognition including associative learning, language, visual-spatial ability, and working memory. However, associations between age-related changes in the cerebellum and cognition are rarely investigated. Purkinje cells in cerebellar cortex and principal cells in deep cerebellar nuclei have been identified as the central integrating cells for a form of associative learning called classical eyeblink conditioning. Acquisition of conditioned eyeblink responses is significantly slower in rabbits with lesions to cerebellar cortex and in Purkinje cell deficient mice that loose all cerebellar cortical Purkinje cells. Correlations between Purkinje cell number and acquisition of conditioned responses (CRs) in rabbits are high and statistically significant, even when the age range is limited to young rabbits. In humans, significant age differences in MRI-assessed cerebellar volume appear in the age-decade of the 50s. Purkinje cells are the largest neurons in the cerebellum and contribute significantly to cerebellar volume. MRI-assessed cerebellar volume (corrected for total intracranial volume, TIV) was related to eyeblink conditioning (400 ms delay procedure) in older adults ranging in the age range of 77 to 95 years (r = 0.81, p < 0.01) and in young adults in the age range of 21 to 35 years (r = 0.58, p = 0.066). Between these two age groups there were statistically significant age differences in cerebellar volume (t(14) = 8.96; p < 0.001) and percentage of CRs (t(14) = 3.85; p < 0.002), but no age difference in TIV. Combining the young and older adult sample, the correlation between percentage of CRs and cerebellar volume (corrected for TIV) was 0.832 (p < 0.001). Cerebellar volume showed age-related deficits likely due to Purkinje cell loss. Individual differences in classical eyeblink conditioning are associated with differences in cerebellar volume indicating a cerebellar cortical role in facilitating this form of associative learning. Supported by grants from the Alzheimer's Association (IIRG-99-1690) and the Harry A. Stern Family Foundation.




Key words: Purkinje cells, classical conditioning, magnetic resonance imaging (MRI)







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