Whereas stroke and traumatic brain injury affect only a fraction of the population, there is a type of brain dysfunction that will affect us all if we live long enough---normal aging. As we age, the anatomical and functional integrity of our brain declines as do our cognitive abilities. Even if relatively mild, this decline impacts a large number of the population. The development of any rational remedial approach depends on a clear understanding of the effects of aging on the neural basis of cognition. In humans these effects can be revealed using functional neuroimaging techniques such as functional MRI (fMRI), which can directly link age-related cognitive deficits to changes in brain activity. One of the cognitive functions most affected by aging is relational memory. Older adults'memory deficits are twice as large on relational memory (RM) than on item memory (IM). Whereas IM refers to remembering what happened in the past, RM refers to remembering the associated information of where, when, and how. It is known that RM is more dependent on the medial temporal lobes (MTL) and the prefrontal cortex (PFC) than IM, but the contributions of various MTL and PFC regions to different forms of RM are unclear. It is also uncertain how these contributions change as a function of aging. Moreover, the neural bases of critical factors modulating the effects of aging on RM, such as the role of pre-existent knowledge and interference, are largely unknown. We propose to conduct five fMRI studies to address these issues. In particular, we have four specific aims: (1) Compare the neural correlates of different forms of RM in younger and older adults. Study 1 will compare featural, spatial, and temporal-order RM, Study 2 will compare featural and semantic RM, and Study 3 will compare associations between similar vs. different kinds of stimuli;(2) Reveal the neural correlates of factors affecting semantic RM in younger and older adults. Study 4 will investigate the role of pre-existent semantic associations and Study 5, the role of proactive interference;(3) Clarify the neural correlates of RM encoding and retrieval in younger and older adults. To accomplish this aim, all five fMRI studies proposed will compare encoding and retrieval activity directly within-subjects;(4) Investigate the interaction between PFC and MTL during RM in younger and older adults. Age-related RM deficits may reflect a disconnection between PFC and MTL regions. To investigate this issue, we will relate age-related changes in RM performance to changes in PFC-MTL connectivity, both in terms of function (correlation in activity) and anatomy (white-matter integrity measured with diffusion tensor imaging). Taken together, the results of these studies will clarify the neural correlates of age-related deficits in RM and will have important implications for the promotion of health.
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