Network analysis of brain activations in working memory: Behavior and age relationships

Forty-six middle-aged female subjects were scanned using functional Magneti c Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual. forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimu li during both the encoding and recognition periods. Additional increases d uring memory recognition were seen in right prefrontal regions, replicating a now-common finding (for reviews, see Fletcher et al. (1997) Trends Neuro sci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supp orting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry wa s not qualified by the type of material being processed. A few sites demons trated higher activity levels during the rehearsal period, in the absence o f any new stimuli, including the medial extrastriate, precuneus, and the me dial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acq uired outside the scanner. Correlations between brain scores and behavior s cores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Square s [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323- 327], was then used to extract component effects from this large set of uni variate correlations. Results indicated that better memory performance outs ide the scanner was associated with higher activity at specific sites withi n the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the ri ght medial temporal lobe; older subjects tended to activate more than young er subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen wit h aging. Microsc. Res. Tech. 51:64-74, 2000. (C) 2000 Wiley-Liss, Inc.