This proposal is designed to test specific hypotheses regarding the functional role of different regions of prefrontal cortex (PFC) in both working memory (WM) and long-term memory (LTM) tasks. A growing literature has suggested the involvement of PFC in both WM and LTM. However, the findings within each memory domain have largely been considered independently of the other, such that functional interpretations of PFC activity are typically domain-specific.
We propose two hypothesis that suggest more parsimonious explanations, interpreting PFC function in terms that apply across memory domains. First, we suggest that dorsolateral PFC (DL-PFC) is involved in the representation and maintenance of task-relevant context. We further suggest that task manipulations which vary the demand on context representation and maintenance will modulate DL-PFC activity, regardless of whether the tsk putatively involves WM or LTM.
Second, we suggest that frontopolar PFC (FP-PFC) is involved in the representation and maintenance of higher-order goal information that can support and monitor the processing of lower-order subgoals. We further suggest that task manipulations which vary the demand on subgoal processing and monitoring will modulate activity in FP-PFC regardless of whether the task putatively involves WM or LTM. The studies proposed here will test these hypothesis by using state-of-the-art functional magnetic resonance imaging (fMRI) techniques, including novel event-related methods. Specifically, we will assess whether DL-PFC and FP-PFC activity can be modulated in either WM or LTM by selectively manipulating common task factors.
Success in this work would represent a significant advance in both our theoretical and empirical efforts. With regard to theoretical efforts, demonstrating that distinct PFC regions play specific and common functional roles across memory domains would provide an important integration of the literatures on PFC function, WM, and LTM. With regard to empirical efforts, this work would lay the groundwork for the development of powerful new behavioral, as well as neuroimaging probes of cognitive and neurobiological function in both healthy populations and in clinical populations suffering from memory impairments.

NIMH 1 R03 MH 61615-01