The aim of this proposal is to apply transcranial magnetic stimulation (TMS) and functional MRI (fMRI) to refine models of healthy frontal lobe functioning in older adults. Frontal lobe functioning changes with increasing age. FMRI activation studies of young and older adults performing memory tasks demonstrate that older adults exhibit bilateral frontal lobe activation under conditions where young adults display unilateral activation. Older adults demonstrating bilateral activation more strongly demonstrate better memory. It has not been established whether these additional regions are involved in the task performed. TMS will be applied to disrupt focally regions more intensely recruited by older adults to determine whether those areas are necessary for memory processing. The first study applies a verbal working memory paradigm which in fMRI has demonstrated predominantly left frontal activation in young adults and bilateral activation in older adults. A previous TMS study suggested that transient right frontal involvement precedes left frontal involvement in young adults. If older adults demonstrate a different temporal pattern of right hemisphere recruitment, this could contribute to fMRI activation differences. The second and third studies extend to older adults a TMS study of episodic memory performed in young adults. Functional imaging research suggests that the left frontal lobe is more active during encoding than retrieval and the right frontal lobe is more active during retrieval than encoding. The previous TMS study demonstrated that in young adults, degree of disruption with TMS in the left versus right frontal lobes of young adults followed the predictions based on relative differences in functional activation. Because older adults demonstrate less lateralized functional activation in general, we hypothesize that TMS stimulation will disrupt performance equally in both hemispheres. Individual differences in the degree of asymmetry in frontal lobe fMRI activation will be associated with degree of performance disruption with right versus left TMS.
