UC San Diego

Autobiographical memories are the mind's definition of self. The neural substrates of memory are therefore of tremendous scientific interest. Moreover, the impairment or loss of memory in dementia is a personal catastrophe that reverberates throughout the community and incurs enormous financial and emotional costs. The present dissertation addresses scientific and clinical interests in memory with a particular focus on an area of the brain- -the parietal cortex--that is active in memory retrieval and selectively vulnerable to dementia pathology. Chapter one describes a study using magnetoencephalography (MEG) that revealed an immediate parietal response in episodic retrieval. Chapter two discusses a repetition of the first study with another neuroimaging technique, functional magnetic resonance imaging (fMRI). The results from MEG and fMRI were combined to provide a more precise picture of the timing and localization of retrieval-related parietal activity, which onset simultaneously with a cue to retrieve and was most prominent in the intraparietal sulcus. Chapter three presents a novel method for analyzing the interregional functional correlations of the parietal cortex. This method preserves the unique anatomical features of individual subjects, allowing more accurate comparisons of functional correlations between healthy individuals and those with dementia. Chapter four describes results from application of the new analysis method to longitudinal data. Parietal and non-parietal functional correlations were contrasted in preclinical Huntington's disease and healthy adults, and the long-term stability of these correlation patterns was assessed in both populations. There proved to be little effect of preclinical Huntington's disease on functional correlations, but highly consistent group-level results over a one-year period in each population point to the potential of this technique as a quantitive clinical biomarker in dementia. Chapter five also reports results from application of the new method, in this case to resting fMRI data from patients with Parkinson's disease and Parkinson-related dementia. The strength of resting interregional fMRI correlations in demented patients was decreased relative to equivalent measurements in unimpaired elderly subjects, particularly within corticostriatal regions