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Figure 2. Examples of the extent of WMH from individual subjects in this study. WMH load is expressed as percent of total cranial volume.

Verbal Working Memory Task

Accuracy was very high for both low- and high-load conditions. Mean accuracy was 0.94 (SD = .05) for the low-load condition and 0.88 (SD = .07) for the high-load condition. Performance was not significantly corre- lated with age (low load: R = .463; p = .08; high load R = .280, p = .32). Correlations between performance and global WMH volume were as follows: low load; R = .421, p = .12; high load; R = .469, p = .08, and correlations between performance and dorsal PFC WMH were as follows: low load; R = .144, p = .62; high load; R = .419, p = .12.

fMRI Results Episodic Memory Task

Group activations. Figure 3A depicts group-averaged activations during the episodic memory task. This anal- ysis revealed significant regions of activation in the right middle frontal gyrus (BA 9), right inferior frontal gyrus (BA 44/45/47), anterior cingulate gyrus (BA 32), posteri- or cingulate gyrus (BA 23/29/31), bilateral medial tem- poral lobes (hippocampus, BA 28/36), and right parietal cortex (BA 7/40) (for a complete summary of significant activations, see Table 2).

Global WMH and PFC activity. Global WMH volume was marginally negatively correlated with right ventral PFC activity (R = .453, p = .09). Global WMH volume was not significantly correlated with right or left dorsal PFC activity (R = .403, p = .13; R = .309, p = .27) or left ventral PFC (R = .373, p = .17) activity.

Dorsal PFC WMH and brain activity. To test the prediction that dorsal PFC WMH may be associated with decreased recruitment of PFC and other brain regions that are functionally related to PFC, we first correlated measures of dorsal PFC WMH volume with activity in the PFC ROIs. As shown in Table 3, dorsal PFC WMH volume was strongly negatively correlated with activations in dorsal and left ventral PFC, with a similar trend evident in right ventral PFC.

We then correlated dorsal PFC WMH volume with parameter estimates indexing activation in other cor- tical regions that are recruited during episodic re- trieval. Previous functional imaging studies suggest that in addition to dorsal and ventral PFC activity, episodic retrieval is also associated with medial tem- poral lobe (MTL), anterior cingulate (BA 24/32), pos- terior cingulate (BA 23/29/30), and posterior parietal (BA 40) cortex activity (see Tisserand & Jolles, 2003; Buckner & Wheeler, 2001; Cabeza & Nyberg, 2000). Consistent with these studies, we observed activations in these areas and delineated additional ROIs based on the group-averaged activation maps. As seen in Table 3, dorsal PFC WMH volumes were also nega- tively correlated with activation in bilateral MTL, ante- rior cingulate cortex (BA 32), and right parietal cortex (BA 7/40) activity. To a lesser extent, there was also an association with posterior cingulate cortex activity (BA 23/29/31).

Verbal Working Memory

Group activations. Group activations for the high-load condition are depicted in Figure 3B. This analysis revealed

Nordahl et al.


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