2012 Theses Doctoral

An Investigation of the Neural Correlates of Working Memory in Healthy Individuals and Individuals With Schizophrenia

Van Snellenberg, Jared Xavier

Individuals with schizophrenia exhibit substantial deficits in their ability to perform working memory (WM) tasks, and these deficits have a critical impact on health and life outcomes for these patients, and may be fundamental to the neurophysiological basis of the disorder itself. However, neuroimaging investigations into the nature of these deficits in these patients over the last decade and a half have been stymied by inconsistent findings that leave no clear answer as to their cognitive or neural basis. One hypothesis that has been proposed to account for these inconsistent findings is that the response of some brain regions subserving WM task performance to parametrically increasing WM load, most critically dorsolateral prefrontal cortex, may in fact be non-monotonic in nature; that is, at sufficiently high loads activation in these regions may begin to decrease.

If true, this could account for the inconsistent findings in comparisons of patients with schizophrenia and matched controls, as the two groups may be at different points along this putative activation-load 'inverted-U' curve, resulting in different findings depending on the degree of load utilized in any given study. To date, this hypothesis has not been directly tested; however, I report here the results of a series of studies using the self-ordered working memory task that clearly demonstrate such an 'inverted-U' in healthy participants that is absent in patients with schizophrenia. The pattern of findings in the studies reported here are consistent with healthy individuals switching from WM-mediated strategies to long-term memory-mediated strategies as WM load is increased, while patients with schizophrenia fail to make this switch, instead attempting to utilize WM to subserve task performance even when their WM capacity is exceeded.