| Summary: | This thesis is comprised of two functional MRI experiments, both of which used event-related designs to examine the patterns of activity associated with the temporally separate encoding, delay and response components of a variable-load working memory (WM) task. In experiment one, the patterns of load dependence associated with different components were assessed in healthy subjects. The majority of the regions activated during encoding were found to show a linear increase in activity with load. In contrast, the majority of the regions activated during responding did not show activity that increased linearly with load. In experiment two, we used the design developed in experiment one to delineate the effects of load on each WM component in patients with schizophrenia compared to non-patient controls. Contrasts for the average activity across memory load revealed that the two groups activated similar networks of regions for all components. For encoding, a reduced ability to increase activity with increasing load was found in the schizophrenic group. For the highest load delay condition, a reduced extent of activity was identified in the schizophrenic group in the left parietal cortex, a brain region implicated in short-term storage. For both phases, a greater degree of differential activity was associated with poorer performance, indicating that these activation differences are reflective of the neural abnormalities that underlie WM impairment. These findings support the notion that load dependent WM inefficiencies are present in schizophrenia. === Medicine, Faculty of === Graduate
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