The overall goal of the proposed research is to develop the use of functional magnetic resonance imaging (FMRI) for identifying the brain location of specific components of human memory, for characterizing the cognitive operations computed by those components, and for examining the status of those components in patients with impaired memory due to global amnesia and in healthy people with age-associated variability in memory performance. FMRI is a noninvasive technique with good spatial and temporal resolution that detects localized, endogenous brain state changes. Comparison of changes between two experimental conditions allows for a fine-grained linkage between specific cognitive operations and specific neural systems that is observable in single subjects. We report in Preliminary Studies results showing that we have identified with FMRI a specific brain region, left inferior prefrontal cortex (LIPC) or Brodmann's areas 45, 46, and 47, that is activated by semantic encoding of words; these results are consistent with recent positron emission tomography (PET) findings for groups of subjects. Further, we have shown that the same UPC region activated by semantic encoding retains word-specific memory for that encoding operation when subjects re-encode words. These findings indicate that FMRI can provide reliable measures of frontal-lobe contributions to human memory, and we build on those findings for the following aims: (1) to identify the cognitive operations performed by the UPC area; (2) to identify the kind of memory formed in the UPC region; (3) to identify right-frontal regions associated with the retrieval of memories; (4) to examine the link between encoding and language asymmetries in patients with Wada- validated dominance for language; (5) to examine whether encoding of memories in the LIPC is intact or impaired in parents with global amnesia; (6) to examine the status of LIPC function in aging as it relates to memory performance; (7) to continue developing the FMRI techniques that have already proven useful for localizing semantic and memory operations in single subjects. FMRI may become a major tool in understanding the brain basis of cognition and memory and changes in those important areas of human ability in normal aging and in disease.
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