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Table 4. Activations for Verbal Item Recognition Task at High-load Working Memory Task

Region

BA

x

y

z

t(15)

R. middle frontal gyrus

9/46

44

32

30

8.98

R. middle frontal gyrus

10

32

56

4

6.47

R. middle frontal gyrus

6

26

2

58

7.21

R. inferior frontal gyrus

45

32

28

4

8.06

R. precentral gyrus

4

48

10

50

7.27

L. middle frontal gyrus

9/46

36

38

10

8.21

L. middle frontal gyrus

10

38

54

4

4.67

L. middle frontal gyrus

6

38

6

40

7.65

L. inferior frontal gyrus

44

58

8

4

5.70

L. precentral gyrus

6

24

56

52

8.08

R. insula

30

16

22

10.33

L. insula

30

0

18

10.38

R. anterior cingulate gyrus

32

4

22

36

8.48

L. anterior cingulate gyrus

32

4

18

36

7.40

R. inferior parietal lobule

7

28

61

40

8.67

L. inferior parietal lobule

7

22

62

46

7.82

L. superior parietal lobule

7

12

62

50

7.43

R. middle occipital gyrus

18

20

84

0

7.99

L. middle occipital gyrus

19

24

80

20

8.49

R. fusiform gyrus

37

46

42

12

5.48

L. fusiform gyrus

37

44

40

14

9.39

Coordinates are transformed to a standard stereotactic space (MNI) to facilitate comparison with other imaging studies.

R = right; L = left.

evidence from diffusion tensor imaging studies that selective deterioration of frontal white matter tracts occurs in older individuals (Head et al., 2004; O’Sullivan et al., 2001). Consistent with these findings, we found that increased global WMH volume was associated with decreased bilateral dorsal PFC activity during a working memory task and modestly associated with right ventral PFC during episodic retrieval, suggesting that diffuse disconnection of white matter tracts throughout the brain may be a mechanism for disruption of PFC func- tion in aging. Moreover, we found that regional WMH in dorsal PFC was strongly associated with decreased PFC activity during both episodic retrieval and working memory performance. These results suggest that WMH located in dorsal PFC may be especially detrimental to PFC function in aging.

We additionally predicted that regional WMH within dorsal PFC would be associated with dysfunction in other brain regions that are functionally and anatomi-

426

Journal of Cognitive Neuroscience

Table 5. Activations for Verbal Item Recognition Task at

Low-load Working Memory Task

L. middle frontal gyrus

6

38

4

56

6.48

L. inferior frontal gyrus

45

52

20

24

4.88

L. precentral gyrus

4

46

4

46

6.22

R. anterior cingulate gyrus

24/32

2

12

24

6.37

L. anterior cingulate gyrus

24/32

4

8

34

5.96

R. inferior parietal lobule

7

34

60

50

6.00

L. inferior parietal lobule

7

22

62

44

5.25

L. inferior parietal lobule

40

42

44

34

4.97

R. fusiform gyrus

19

34

62

26

4.91

R. middle occipital gyrus

18

30

86

4

5.27

L. middle occipital gyrus

18

30

84

10

4.65

R. thalamus

18

2

6

5.47

Region

BA

x

y

z

t(15)

R. middle frontal gyrus R. inferior frontal gyrus R. precentral gyrus L. middle frontal gyrus

9/46 44 6 9/46

36 36 36 42

36 8 4 30

24 24 24 16

4.52 5.61 5.61 4.98

Coordinates are transformed to a standard stereotactic space (MNI) to facilitate comparison with other imaging studies.

cally linked to the PFC. For the episodic memory task, we were specifically interested in the circuitry between PFC and the MTL. One recent study reported an age- related change in hippocampal–prefrontal connectivity during an episodic encoding task (Grady, McIntosh, & Craik, 2003). Our results showed that an increase in dorsal PFC WMH volume was associated with decrease in bilateral MTL activity, suggesting that connectivity between these areas may be disrupted.

For the working memory task, we were specifical- ly interested in the possibility that disruption of the prefrontal–parietal connections known to be involved in working memory processes (Chafee & Goldman-Rakic, 2000; Selemon & Goldman-Rakic, 1988) may occur. Indeed, we found that dorsal PFC WMH volume was also associated with bilateral parietal activation during the working memory task, suggesting that connectivity between the PFC and posterior parietal cortex may be disrupted.

Interestingly, we observed a strong association be- tween anterior cingulate cortex activation and dorsal PFC WMH in both the episodic retrieval and verbal working memory tests. The anterior cingulate is associ- ated with cognitive control processes, especially those involved in conflict resolution (Carter, Botvinick, & Cohen, 1999). Recent evidence suggests that functional connectivity between the anterior cingulate cortex and

Volume 18, Number 3

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