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R. parahippocampal gyrus

28/36

26

24

18

3.97

R. superior parietal lobule

7/40

36

52

52

5.17

R. inferior parietal lobule

40

32

50

30

5.56

R. middle occipital gyrus

19

48

76

4

11.26

L. middle occipital gyrus

19

42

74

8

7.38

the low-load condition, again, the pattern of results is similar, but the magnitude of the correlations was slightly lower than for the high-load condition.

Visual Sensory Control Task

To control for the possibility that nonspecific vascular changes associated with WMH fundamentally alter the BOLD response, we examined the effect of WMH vol- ume on visual cortex activation. The purpose of using a simple sensory task was to minimize any cognitive component that may alter brain activity. Thus, any relationship between visual cortex activity and WMH volume would presumably be explained by differences in hemodynamic response. As expected, group analyses revealed robust bilateral activations in the primary visual cortex (BA 17). An ROI was delineated and magnitude of

R. middle frontal gyrus

10 24

52

8

5.98

L. middle frontal gyrus

9/46 36

28

2

8.29

L. inferior frontal gyrus

45

46

28

12

6.10

L. medial frontal gyrus

6

2

8

62

4.94

L. precentral gyrus

4

40

4

34

7.92

L. precentral gyrus

6

48

4

18

5.75

L. middle frontal gyrus

10

28

48

2

6.98

R. cingulate gyrus

32

10

24

26

6.45

L. cingulate gyrus

32

6

20

34

8.71

L. posterior cingulate gyrus

23

10 54

12

4.77

R. posterior cingulate gyrus

29

12

44

10

4.06

L. and R. posterior cingulate

31/23

0

34

34

5.37

Coordinates are transformed to a standard stereotactic facilitate comparison with other imaging studies.

R = right; L = left.

space (MNI) to

Region

BA

x

y

z

t(15)

R. middle frontal gyrus R. inferior frontal gyrus R. posterior inferior frontal

9/46 47 44

44 34 38

42 22 8

24 6 30

4.69 6.21 4.77

28 32

10

7.93

24 32

10

5.34

Table 2. Activations for Episodic Retrieval Task

gyrus

gyrus

  • L.

    hippocampus

  • R.

    hippocampus

Episodic Retrieval

High-Load Working Memory

Low-Load Working Memory

L. dorsal PFC R. dorsal PFC L. ventral PFC R. ventral PFC L. MTL R. MTL ACC PCC L. parietal R. parietal

.563* .568* .602* .473 .512 .653** .618* .490 .393 .540*

.688** .661** .723** .575 .682** .599* .424

.565* .562* .626* .348 .556* .559* .584*

Table 3. Correlation Coefficients for Dorsal PFC WMH Volumes and Activity in Task-dependent Regions of Interest

PFC = prefrontal cortex; MTL = medial temporal lobe; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex; L = left; R = right.

*p < .05. **p < .01.

activity was correlated with WMH volume. There were no significant correlations between either global WMH volume or dorsal PFC WMH volume and activity in this region (all ps > .39).

DISCUSSION

The frontal aging hypothesis suggests that age-related cognitive decline is a consequence of selective degener- ation of the prefrontal cortex (Tisserand & Jolles, 2003; West, 1996), but the biological mechanism underlying these changes is unknown. In this study, we tested the hypothesis that disruption of white matter integrity associated with cerebrovascular disease may play a role in PFC dysfunction during episodic memory retrieval and verbal working memory in a group of cognitively normal elderly individuals. Our results show that PFC function is sensitive to both global WMH as well as regional dorsal PFC WMH. In addition, regional dorsal PFC WMH are associated with other brain areas that are functionally connected to PFC in a task-dependent manner. There was no relationship between WMH and visual cortex activity during a visual sensory task, sug- gesting that these correlations could not be attributed to global alterations in neurovascular coupling.

WMH are extremely prevalent in elderly individuals, and there is evidence that WMH have a selective effect on the frontal lobes, with reports of selective decreases in N-acetylaspartate levels (Schuff et al., 2003) and resting glucose metabolism in the frontal lobes (Tullberg et al., 2004; DeCarli et al., 1995). There is also some

Nordahl et al.

425

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