Is there a single underlying prefrontal mechanism?
This proposal is designed to test the hypothesis that deficits in both working memory and long term memory among patients with schizophrenia represent a single underlying disturbance in prefrontal cortex function. A growing literature suggests that patients with schizophrenia show cognitive deficits in at least two putatively different domains: working memory and long term memory. Further, deficits in working memory have typically been linked to an underlying disturbance in prefrontal cortex function, while deficits in long term memory (i.e., encoding and/or retrieval) have typically been associated with medial temporal/hippocampal deficits. However, among patients with schizophrenia, it is not yet clear that deficits in working memory and long term memory truly represent two distinct sets of cognitive deficits associated with different underlying neurobiological substrates. An alternative, potentially more parsimonious, hypothesis is that both working memory and long term memory deficits in schizophrenia reflect a dysfunction in the same underlying neurobiological mechanism: a disturbance in prefrontal cortex function.
The study proposed here is designed to test this hypothesis by using state-of-the-art functional magnetic resonance imaging (fMRI) techniques, including novel event-related methods. Specifically, we will assess the patterns of cortical function and dysfunction associated with the performance of both working memory and long term memory tasks in the same patients with schizophrenia and matched control subjects, during the same scanning session To our knowledge, this will be the first functional neuroimaging study in schizophrenia patients to simultaneously assess multiple cognitive domains, an approach that has the potential to vastly advance our understanding of the precise nature and mechanisms underlying cognitive deficits in schizophrenia.
Demonstrating that deficits in both working memory and long term memory (encoding and/or retrieval) stem from a single underlying disturbance in prefrontal cortex function would do much to simplify and clarify the literature on cognitive function in schizophrenia. Thus, success in this work would represent a significant advance in both our theoretical and empirical efforts, and could provide the groundwork for the development of powerful new behavioral, as well as neuroimaging probes of cognitive and neurobiological function in schizophrenia.
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