A PARAMETRIC STUDY OF PREFRONTAL CORTEX INVOLVEMENT IN HUMAN WORKING-MEMORY

Although recent neuroimaging studies suggest that prefrontal cortex (P BC) is involved in working memory (WM), the relationship between PFC a ctivity and memory load has not yet been well-described in humans. Her e we use functional magnetic resonance imaging (fMRI) to probe PFC act ivity during a sequential letter task in which memory load was varied in an incremental fashion. In all nine subjects studied, dorsolateral and left inferior regions of PFC were identified that exhibited a line ar relationship between activity and WM load. Furthermore, these same regions were independently identified through direct correlations of t he fMRI signal with a behavioral measure that indexes WM function duri ng task performance. A second experiment, using whole-brain imaging te chniques, both replicated these findings and identified additional bra in regions showing a Linear relationship with load, suggesting a distr ibuted circuit that participates with PFC in subserving WM. Taken toge ther, these results provide a ''dose-response curve'' describing the i nvolvement of both PFC and related brain regions in WM function, and h ighlight the benefits of using graded, parametric designs in neuroimag ing research. (C) 1997 Academic Press.