 |
 Previous Article | Next Article 
Volume 17, Number 1,
Issue of January 1, 1997
pp. 391-400
Copyright ©1997 Society for Neuroscience
Age-Related Differences in Neural Activity during Memory Encoding
and Retrieval: A Positron Emission Tomography Study
Roberto Cabeza1,
Cheryl
L. Grady1,
Lars Nyberg2,
Anthony R. McIntosh1,
Endel Tulving1,
Shitij Kapur1, 3,
Janine M. Jennings1,
Sylvain Houle3, and
Fergus I. M. Craik1
1 Rotman Research Institute of Baycrest Centre,
University of Toronto, Toronto, Ontario, Canada M6A 2E1,
2 Department of Psychology, University of Umeå, S-90187
Umeå, Sweden, and 3 PET Centre, Clarke Institute of
Psychiatry, University of Toronto, Toronto, Ontario, Canada M6A 2E1
 ABSTRACT
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- DISCUSSION
- CONCLUSIONS
- FOOTNOTES
- REFERENCES
ABSTRACT 
Positron emission tomography (PET) was used to compare regional
cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling
word pairs. A multivariate partial-least-squares (PLS) analysis of the
data was used to identify age-related neural changes associated with
(1) encoding versus retrieval and (2) recognition versus recall. Young
subjects showed higher activation than old subjects (1) in left
prefrontal and occipito-temporal regions during encoding and (2) in
right prefrontal and parietal regions during retrieval. Old subjects
showed relatively higher activation than young subjects in several
regions, including insular regions during encoding, cuneus/precuneus
regions during recognition, and left prefrontal regions during recall.
Frontal activity in young subjects was left-lateralized during encoding
and right-lateralized during recall [hemispheric encoding/retrieval
asymmetry (HERA)], whereas old adults showed little frontal activity
during encoding and a more bilateral pattern of frontal activation
during retrieval. In young subjects, activation in recall was higher
than that in recognition in cerebellar and cingulate regions, whereas
recognition showed higher activity in right temporal and parietal
regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in
other regions. Taken together, the results indicate that advanced age
is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1)
age-related decreases in local regional activity, which may signal less
efficient processing by the old, and (2) age-related increases in
activity, which may signal functional compensation.
Key words:
positron emission tomography;
cerebral blood flow;
aging;
memory;
encoding;
retrieval;
recognition;
recall;
frontal lobes;
functional reorganization;
functional compensation
INTRODUCTION
Compared to young adults, elderly adults perform
poorly on a variety of memory tasks (for review, see Light, 1991 ; Craik
and Jennings, 1992; Verhaeghen et al., 1993). In particular, old adults are impaired on episodic memory tests (Tulving, 1983), which involve retrieval of information about previously experienced events. These
age-related memory deficits probably reflect anatomical and
physiological deterioration of the aging brain (Kemper, 1984; Creasey
and Rapoport, 1985; Coleman and Flood, 1987). New functional neuroimaging techniques, such as positron emission tomography (PET),
now make it possible to study age-related differences in neural
activity in vivo while subjects are performing memory
tasks.
Using PET, Grady et al. (1995) measured regional cerebral blood flow
(rCBF) in young and old subjects while they were intentionally learning
(encoding) and subsequently recognizing faces. During encoding, young
subjects showed increased rCBF in the left prefrontal and right
hippocampal regions, but old subjects did not show reliable activation
in either of these two regions. During recognition, both young and old
subjects showed increased blood flow in right prefrontal cortex, in
keeping with similar observations concerning episodic retrieval in many
previous PET studies (for review, see Tulving et al., 1994; Nyberg et
al., 1996a; Cabeza and Nyberg, in press).
In another PET study of memory and aging, Schacter et al. (1996)
scanned young and old subjects while they were recalling previously
studied words. Both groups showed increased blood flow in hippocampal
regions. In contrast, young adults but not older adults showed
activation in anterior frontal regions. This result contrasts with the
finding of Grady et al. (1995) of similar levels of frontal activation
during recognition in young and old subjects. The differences in the
outcomes of the two studies may be related to different measures of
retrieval: recognition by Grady et al. (1995) and recall by Schacter et
al. (1996). It is known that older people are particularly impaired on
recall (Craik and McDowd, 1987), and it is widely believed that the
integrity of frontal lobe structures is more critical for recall than
for recognition (Moscovitch, 1992).
In this experiment, we used PET to compare rCBF in young and old
volunteers while they studied word pairs, and during subsequent recognition and recall of the encoded information. The design of the
experiment allowed us to examine age-related differences in activation
during both encoding and retrieval (cf. Grady et al., 1995) and to
compare retrieval in recall and in recognition (cf. Schacter et al.,
1996). Furthermore, we were interested in identifying brain regions
that show more activation for old than young adults. Grady et al.
(1994) found some of these regions in perceptual tasks in which old
subjects performed as accurately as young subjects, whereas Grady et
al. (1995) did not find them in a recognition memory task in which old
subjects performed significantly worse than young adults. In the
present study, we explored the issue in a group of high-functioning
elderly who displayed a good level of memory performance.
MATERIALS AND METHODS
Subjects. The subjects were 12 young adults (6 male,
6 female; age range 19-31 years, mean age 26 years) and 12 old adults (5 male, 7 female; age range 67-75 years, mean age 70 years). All
subjects were right-handed and had no history of neurological or
psychiatric illness. None of the subjects was taking medication or had
a condition that could affect cerebral blood flow (e.g., high blood
pressure), with the exception of one old subject who suffered from mild
hypothyroidism. Young subjects were mainly undergraduate and graduate
students of the University of Toronto, and old subjects were
high-functioning community-dwelling individuals. All old subjects were
college-educated, and half were selected from among the highest scorers
in an elderly volunteer subject pool at the University of Toronto. As
Table 1 indicates, the two groups were matched in
education, self-rated health, and word fluency but differed in
vocabulary (higher in old subjects) and recall on the California Verbal
Learning Test (CVLT; higher in young subjects). The study was approved
by the Human Subject Use Committee of the University of Toronto and the
Baycrest Centre.
Table 1.
Demographic and neuropsychological
data
|
Young Ss |
Older
Ss |
|
| Age |
25.7 |
70.5* |
| Education
(years) |
17.8 |
16.0 |
| Self-rated health (1 = bad, 5 = excellent) |
4.67 |
4.58 |
| Vocabulary (Mill
Hill) |
22.3 |
28.3* |
| Word fluency (FAS) |
50.5 |
48.2 |
| Recall
(California Verbal Learning Test) |
| List A: trial
1 |
10.6 |
8.8 |
| List A: total trials
1-5 |
70.2 |
57.7* |
| List B: recall |
10.2 |
7.1* |
| List A:
short-delay recall |
14.0 |
11.1* |
| List A: short-delay cued
recall |
15.0 |
11.8* |
|
|
*
p < 0.05.
|
|
Procedure. Subjects were seen in the PET laboratory twice.
During the first visit, they completed a health questionnaire, performed the required neuropsychological tests (Mill Hill, CVLT, and
FAS), and practiced the tasks to be performed during the experiment (with different words than those used during the experiment proper). During the second session, anywhere from 3 to 7 d later, they underwent eight PET scans, one every 11 min. On each scan, the subjects
saw a succession of 24 word pairs on a computer screen, presented at
the rate of 5 sec/pair (4 sec on the screen, 1 sec interval). Subjects
always responded to every pair by speaking a single word. Different
sets of 24 word pairs were used in each scan. The sets were assigned to
the eight scans in a randomly determined order for half of the
subjects, and in the opposite order for the other half.
The eight scans corresponded to four cognitive tasks, each repeated
once. The first and last scans were always baseline Reading tasks:
subjects read each pair of words silently and spoke aloud the second
member of the pair. The other three tasks Encoding, Recognition, and
Recallare summarily described in Table 2 in terms of
the visual display, instructions describing cognitive activity, and the
required verbal response. The results of comparisons between the
baseline Reading task and the three other tasks for the group of young
subjects have been reported elsewhere (Cabeza et al., in press; Kapur
et al., in press). The purpose of this report is to present the data on
encoding, recognition, and recall for the old subjects and to compare
these with those of the young group. The ordering of the tasks under
scrutiny here was (1)
recognition-encoding-recall-recall-encoding-recognition for half
of the subjects, and (2)
recall-encoding-recognition-recognition-encoding-recall for the
other half. The mirror-image pattern controlled for linear order
effects.
Table 2.
Conditions
| Task |
Visual
input |
Verbal output |
Condensed
instructions |
|
| Encoding |
parents-piano |
piano |
Read
the first word silently and the second word aloud, and try to remember
the pair by noting meaningful relations between the two
words. |
| Recognition |
parents-piano |
piano or
pass |
If you think the second word is the original one, read it
aloud; otherwise, say
pass |
| Recall |
parents-word? |
piano or
pass |
If you can remember the original second word, say it
aloud; otherwise say pass |
|
During the intervals before recall and recognition scans, subjects
studied the pairs to be tested during the scan under the same
instructions as in the encoding task. To attenuate differences in task
difficulty between recognition and recall, the study list was presented
once for recognition and twice for recall, faster for recognition (1 pair every 4 sec) than for recall (every 5 sec), and more separated
from the test for recognition (5 min interval) than for recall (2 min).
These differences in procedure were selected on the basis of the
results of pilot studies. Reducing difficulty differences does not
eliminate the main qualitative differences between recall and
recognition tasks (e.g., recall involves generation while recognition
does not), but it may alter some of the processing differences that
exist between these tests in conditions in which recall is more
demanding than recognition. After the eight scans, subjects were given
"delayed" recognition and cued-recall tests for all of the words
presented during the reading and encoding scans. The significance level
for the analyses of behavioral data were set at 0.05.
The presentation of each set of pairs started 35-45 sec before the
beginning of the 60 sec PET scan and finished 15-25 sec after the end
of the scan. In the recall test, subjects were presented with the first
word of each of the 24 studied pairs together with an invariant second
word, as shown in Table 2, and they responded either with the correct
word from the study list or with "pass." In the recognition test,
the 18 word pairs in the middle of the sequence, coincident with the
actual scan, were all "old," having been seen in the study list.
The second word in the three studied pairs at the beginning of the list
(before the start of the scan) and in three pairs near the end of the
list (after the end of the scan) was replaced by a lure word. Thus, in
both recall and recognition, all items during the 60 sec scan window
were potentially capable of prompting successful retrieval.
PET methods. PET scans were obtained with a
GEMS-Scanditronix PC2048-15B head scanner using a bolus injection of 40 mCi (1.48 GBq) of 15O-H2O. The analyses of PET
data involved four steps.
First, using Statistical Parametric Mapping (SPM95) software (Wellcome
Department of Cognitive Neurology, London, UK) implemented in Matlab
(Mathworks Inc., Sherborn, MA), the different images from each subject
were (1) realigned to the first image, using a rigid body
transformation, (2) transformed into a standard space (Talairach and
Tournoux, 1988), and (3) smoothed using an isotropic Gaussian kernel of
15 mm FWHM (Friston et al., 1991, 1995).
Second, the value for each pixel in the images of each subject was
divided by the average global CBF for the subject in the task (Fox et
al., 1988) and reduced by the average value for the pixel across all
tasks (Moeller and Strother, 1991). The latter adjustment reduces
intergroup errors of registration and other global group differences.
The resulting corrected values, therefore, show a proportional CBF
change above and below zero, with zero representing the average value
for the pixel across all tasks.
Third, a partial-least-squares analysis (PLS) (McIntosh et al., 1996)
was performed on the data from the encoding, recognition, and recall
tasks (the two scans in each task were averaged together). PLS is a
multivariate method that has been adapted recently to analyze
neuroimaging data. It uses all of the information contained within the
images, and all of the information about the experimental design, in a
single analytic step, making it more sensitive for detecting changes in
activity than conventional univariate image subtraction methods. In
most cases, the results from PLS and univariate subtractions will
identify similar areas, but PLS will identify additional areas because
of the increased sensitivity. For the present dataset, PLS was used to
address the following question: "Is there a pattern of task-related
image-wide activity that distinguishes young and old subjects?" PLS
is designed to describe the relation between some exogenous source,
such as experimental design or behavioral measures, and the functional
brain images. In the case of the experimental design, it does so by
first computing the cross-covariance between a matrix containing
contrast vectors that code the experimental design and all of the
voxels in each image for all subjects in all tasks. The
cross-covariance matrix is then decomposed using singular value
decomposition yielding pairs of latent variables. The first element of
the pair represents a linear combination of contrasts that has the
largest relation to (is most covariant with) the brain images, and the
other element of the pair is a weighted linear combination of voxels
that is most closely related to that combination of contrasts. (Because this image is derived from a singular value decomposition, it is called
a singular image, and the values for these voxels are called
saliences.) Stated somewhat differently, the first pair extracted
represents the largest experimental effect and identifies both the
contrast, or the combination of contrasts, representing the effect and
the collection of voxels showing the effect. The brain image extracted
can be interpreted, therefore, as depicting the nodes of a distributed
system that is most affected by the manipulation. Successive extraction
of latent variables will account for progressively less of the
cross-covariance of the contrasts and images until all covariance is
accounted for. Subject scores on the latent variables are derived by
multiplying each individual image within a task by the voxel weights
for a spatial pattern and summing across the cross-products. This gives
a single score for each subject in each scan condition. Distribution of
scores with respect to scan conditions was tested for significance
using multiple linear regression of the scores on scan contrasts with the probabilities assigned using permutation tests. PLS contrasts included only task and group × task interactions; the group main effect is degenerate (zero), because it was partialed out through the
mean adjustment.
Fourth, to clarify possible task × age interactions, 3 × 2 ANOVAs (encoding, recognition, recall tasks × young, old
subjects) were performed on the corrected and adjusted rCBF values for
the activated regions. Whereas the question addressed by PLS is asked at the level of the entire image, the ANOVAs were used to ask the
question: "What is the relative contribution of a particular voxel to
a singular image?" Similarly, PLS can be thought as providing an
omnibus test of significance for task main effects and interactions, and the voxel-wise ANOVAs operate as a post hoc test
to elucidate the interactions. Because the mean adjustment of rCBF
controlled for the main effect of group, only the main effects of tasks
and the tasks × group interaction are reported. Additionally,
pairwise contrasts between the conditions differentiated by each latent variable were performed separately in each group.
RESULTS
Behavioral data
Behavioral results are shown in Table 3.
Recognition was higher than recall, and differences between the two age
groups did not reach statistical significance. On performance during
the scans, a 2 (age: young vs old) × 2 (test: recall vs recognition) ANOVA yielded a significant main effect of test (F = 11.7, p < 0.003), a nonsignificant effect of age, and
a nonsignificant test × age interaction. An ANOVA on performance
after the scans also yielded a significant main effect of test
(F = 106.4, p < 0.0001), with no
reliable effect of age or interaction. Although the age effect was not
significant, it should be noted that the magnitude of the effect on
performance after the scans is in line with many behavioral studies and
might have been significant with a larger sample of subjects.
Table 3.
Behavioral data
|
Young
Ss |
Older Ss |
|
| Performance during the scans |
| Recognition
(hits-false
alarms) |
0.86 |
0.86 |
| Recall |
0.78 |
0.76 |
| Post-scans
testsa |
| Recognition (hits-false
alarms) |
0.82 |
0.74 |
| Recall |
0.39 |
0.26 |
|
|
a
Tests of words presented during
the encoding scans.
|
|
PET data
To simplify the description of PET results, we use the following
terminology. Higher rCBF during encoding than during retrieval will be
referred as encoding activation, and the opposite pattern as
retrieval activation. Higher rCBF during recognition than
during recall will be described as recognition activation,
and the converse as recall activation. Lower rCBF in old
than in young subjects will be referred to as age-related
decrease, and higher rCBF in old than in young subjects will be
described as age-related increase. Interactions between task
and age are labeled accordingly. For example, higher rCBF in encoding
than in retrieval but less so for old than young subjects is referred
to as age-related decrease in encoding, and so forth.
The PLS analysis identified four patterns of rCBF changes across tasks
(LV1 to LV4). These were all significant at p < 0.002 according to the permutation tests and accounted for 50, 28, 14, and
8%, respectively, of the cross-block covariance. LV1 and LV3 were
similar in that they identified regions showing primarily encoding/retrieval differences in blood flow (see Fig.
1). They differed in that LV1 showed relevant regions as
affected particularly by the young subjects, whereas LV3 depicted
regions associated with marked encoding/retrieval × age
interactions in rCBF. LV2 and LV4 identified regions showing primarily
blood flow differences between recognition and recall (see Fig.
2). LV2 differentiated between recognition and recall
primarily in young subjects, and LV4 differentiated between recognition
and recall primarily in old subjects.
Fig. 1.
The graphs on the left correspond
to scores for the first (LV 1) and third (LV
3) patterns of activation identified by the PLS analysis. On
the right, the brain regions in which rCBF was positively (white) and negatively (black)
associated to these patterns are shown overlaid on a standard MRI
template of SPM 95. The horizontal slices are at intervals of 4 mm,
from  28 mm below the AC-PC line (top left slice) to
40 mm above the AC-PC line (bottom right
slice).
[View Larger Version of this Image (96K GIF file)]
Fig. 2.
Scores and brain regions associated with LV
2 and LV 4. See legend to Figure 1.
[View Larger Version of this Image (95K GIF file)]
The positive and negative saliences of LV1 and LV3 are listed in
Table 4, and their rCBF changes are illustrated in
Figure 3. The positive saliences of LV1 correspond to
encoding activations (Fig. 3, 1-7). As
indicated by the significant age × task interactions (see Table
4), encoding activations were generally stronger in young adults than
in old adults. This idea is confirmed by pairwise contrasts between
encoding and retrieval (average of recall and recognition) performed
separately in each group (see the two rightmost columns of Table 4). In
particular, encoding activations in left prefrontal, left precentral,
left occipital, and right fusiform regions were significant in young
but not in old subjects. In contrast, encoding activations in right
Sylvian regions were significant in both groups. The negative saliences
of LV1 correspond to retrieval activations (Fig. 3,
10-15), such as right frontal, parietal, temporal, and midbrain regions. Retrieval activations tended to be
weaker in old adults. This was especially so for a medial right prefrontal cortex (Fig. 3, 10), where the old group did not
show a significant difference between retrieval and encoding.
Fig. 3.
Changes in adjusted rCBF across tasks for young
and old subjects in regions positively
(1-7) and negatively
(10-15) associated with LV1 and in
regions positively (17-20) and
negatively (21-24) associated
with LV3. The top number in each graph corresponds to a
saliency number in Table 4. Below this number, the
hemisphere (Left or Right), a brain
region (e.g., insula), and/or a Brodmann area are indicated.
[View Larger Version of this Image (45K GIF file)]
LV3 identified regions showing marked encoding/retrieval × age
interactions in rCBF. These regions can be classified into four groups.
(1) There were regions showing encoding activations in the young but
not in the old, such as the superior anterior cingulate (Fig. 3,
21) and the left temporal cortex (Fig. 3, 22). In
these two regions, rCBF in old adults was higher during retrieval than
during encoding. (2) There were regions showing retrieval activations
in the young but not in the old, such as the inferior anterior
cingulate (Fig. 3, 17) and the right medial frontal
pole (the same region identified by LV1; Fig. 3, 10). In old
subjects, the inferior anterior cingulate was more activated during
encoding than during retrieval. (3) There were regions showing encoding activations in the old but not in the young, such as bilateral insular
regions (Fig. 3, 18, 19) and the right occipital
cortex (Fig. 3, 20). (4) There were regions showing
retrieval activations in the old but not in the young, such the
cuneus/precuneus region (Fig. 3, 23) and the left prefrontal
cortex (Fig. 3, 24). The cuneus/precuneus region was
particularly active during recognition, whereas the left prefrontal
cortex was especially active during recall. In young subjects, the
cuneus/precuneus region did not show a significant task effect, and the
left prefrontal was more active during encoding than during
retrieval.
The positive and negative saliences of LV2 and LV4 are listed in Table
5, and their rCBF changes are illustrated in Figure 4. LV2 identified regions that were differentially
involved during recognition and recall, primarily in young subjects
(see Fig. 4, 1-8). The positive saliences of LV2
are those regions showing recall activations (Fig. 4,
1-5), such as cerebellar and cingulate regions.
The negative saliences of LV2 correspond to regions showing recognition
activations (Fig. 4, 6-8), such as right
temporal and parietal regions. In young adults, the regions associated with LV2 generally showed a "V" (positive saliences) or an
"inverted-V" (negative saliences) pattern of rCBF, in which
encoding and recall are both differentiated from recognition. In old
adults, this pattern was weak or nonexistent for most of these regions.
As indicated by the pairwise contrasts in Table 5, the rCBF differences between recall and recognition identified by LV2 were pronounced in
young adults and smaller or nonsignificant in old adults.
Fig. 4.
Changes in adjusted rCBF across tasks for young
and old subjects in regions positively
(1-5) and negative
(6-8) associated with LV2 and in regions
positively (9) and negatively
(10-12) associated with LV3. The
top number in each graph corresponds to a saliency
number in Table 5. Below this number, the hemisphere (Left or Right), a brain region (e.g.,
cerebellum), and/or a Brodmann area are indicated.
[View Larger Version of this Image (31K GIF file)]
Finally, LV4 identified regions showing rCBF differences between
recognition and recall in old subjects and no significant change in
young subjects (see Fig. 4, 9-12). Regions in
the right prefrontal cortex (Fig. 4, 9), right striatum
(Fig. 4, 10) and left insula (Fig. 4, 12) were
involved differently during recognition and recall by young and old
subjects. A right anterior cingulate region (Fig. 4,
11)more anterior than the left anterior cingulate differentiating recognition and recall in young subjects (Fig. 4,
2)showed a recall activation in old subjects but not in
young subjects.
DISCUSSION
The extensive data just presented are complex in detail but simple
as a whole: old adults showed smaller differences in localized neuronal
activity than young adults in some brain regions and larger differences
in others. Age-related regional decreases in activation are usually
interpreted as reflecting less efficient cognitive processing in old
adults (Grady et al., 1994, 1995; Madden et al., 1996; Schacter et al.,
1996). This interpretation may also apply to the present study, even if
behavioral performance differences between the two groups were less
striking in this study than in other comparable studies. First, PET can
be more sensitive to cognitive dysfunction than behavioral tests and
can detect, for example, brain metabolic reductions in Alzheimer's patients even when behavioral impairments are not yet apparent (Grady
et al., 1988). Second, the effect of age-related decreases in
activation in some brain regions may have been compensated for by
age-related increases in activation in other brain regions (Grady et
al., 1994). Alternatively, rather than interpreting age-related
decreases in activation in terms of processing deficiency and
age-related increases in activation in terms of functional compensation, different activation patterns in young and old subjects could be interpreted as indicating that the two groups performed the
tasks differently, either by using a different strategy or by
implementing the same strategy in different ways. Although we favor the
first interpretation, we acknowledge that the second interpretation is
also possible.
Relation of aging to encoding activations
Age-related decreases in encoding occurred primarily in left
prefrontal and bilateral occipito-temporal regions. Consistent with the
results of Grady et al. (1995), young adults differentially engaged the
left prefrontal cortex during encoding but old adults did not. The
involvement of the left prefrontal cortex during encoding has been
observed repeatedly in PET studies (see, for example, Fletcher et al.,
1995; Haxby et al., 1996) (for review, see Nyberg et al., 1996a; Cabeza
and Nyberg, in press) and has been attributed to semantic processing
(see, for example, Kapur et al., 1994). As for occipito-temporal
regions, they are part of a ventral visual pathway involved in object
perception (Ungerleider and Mishkin, 1982) and also seem to be involved
in the encoding of new information in monkeys (Horel et al., 1987;
Miller et al., 1991; Colombo and Gross, 1994) and humans (Haxby et al.,
1996). Thus, age-related reductions in left prefrontal and left
occipito-temporal regions suggest altered encoding processes in old
adults.
Age-related increases in encoding occurred in bilateral insular
regions. Although some age-related increases may reflect functional compensation, it is possible that others signal use of less effective cognitive strategies. A possible method for deciding between positive or negative interpretations of age-related increases is to correlate rCBF in the region in question with cognitive performance. Because of
small variability in memory performance, such correlations were
generally nonsignificant in the present study. In the case of the right
insula, however, there was a significant negative correlation
(r = 0.56, p < 0.004; see Fig.
5) between rCBF during the encoding scans and
performance in the "delayed" recall test (for similar correlation
analyses, see Cahill et al., 1996). This result suggests that the
involvement of insular regions in old subjects, as well as in young
subjects, may be disruptive rather than beneficial. A possible
interpretation is that the recruitment of this region reflects a lack
of inhibition. There is evidence that inhibitory processes influence
task performance (Nyberg et al., 1996b) and that inhibition deficits
play a role in cognitive aging (Hasher and Zacks, 1988).
Fig. 5.
Significant negative correlation
(r = 0.56, p < 0.004)
between adjusted rCBF in the right insula (xyz = 42, 18, 16) during the encoding scans and behavioral performance in
the delayed recall test.
[View Larger Version of this Image (24K GIF file)]
Relation of aging to retrieval activations
Age-related decreases in retrieval occurred in several regions,
including right prefrontal areas and right parietal regions. The
age-related reduction in rCBF in the right prefrontal is consistent with the results of Schacter et al. (1996), and the reduction in the
right parietal is consistent with the results of Grady et al. (1995).
Activations in these two regions are commonly found in PET studies of
episodic memory retrieval (for review, see Cabeza and Nyberg, in
press). The right prefrontal cortex is assumed to play a role in
supporting or guiding retrieval (Kapur et al., 1995; Nyberg et al.,
1995; Schacter et al., 1996), and the parietal cortex is assumed to be
involved in the access to distributed "storage" systems (Andreasen
et al., 1995). Accordingly, age-related reductions in right prefrontal
and right parietal regions suggest altered retrieval operations in
older adults. It should be noted, however, that in terms of the number
of regions for which age × task interactions were seen,
age-related reductions in retrieval were not as pronounced as
age-related reductions in encoding. This pattern is consistent with the
results of Grady et al. (1995) and with the conclusions drawn from
cognitive studies comparing encoding and retrieval deficits in older
adults (see, for example, Craik and Simon, 1980).
Age-related increases in retrieval occurred in two regions: the
cuneus/precuneus region during recognition and the left prefrontal cortex during recall. PET evidence suggests that cuneus/precuneus plays
a role in memory retrieval (Andreasen et al., 1995; Buckner et al.,
1995; Fletcher et al., 1995; Kapur et al., 1995; Petrides et al.,
1995). It is conceivable, therefore, that old adults' memory
performance benefited from the recruitment of this region. The left
prefrontal cortex is usually engaged in semantic memory retrieval tasks
(Tulving et al., 1994; Nyberg et al., 1996a), such as generating words
from semantic memory (see, for example, Petersen et al., 1989). Because
cued-recall involves a semantic memory component (the generation of
candidate responses) and an episodic memory component (the selection
the target), old adults may have compensated for deficits in the
episodic memory component (e.g., in the right prefrontal cortex)
through the superior semantic memory component (e.g., in left
prefrontal cortex).
More generally, frontal activity in young adults was left-lateralized
during encoding and right-lateralized during recall, whereas old adults
showed little frontal activity during encoding and a more bilateral
pattern of frontal activation during retrieval. The lateralized pattern
shown by young subjects is typically observed in PET studies of
episodic memory, and it has been described in terms of a
hemispheric encoding/retrieval asymmetry (HERA) model (Tulving et al., 1994; Nyberg et al., 1996a). The present results indicate that the typical asymmetrical encoding/retrieval pattern does
not hold in old age. In a PET study, it was found that unilateral localization of cognitive tasks in the left frontal lobe is shifted to
the right hemisphere when the left is damaged (Buckner et al., 1996).
It has also been reported that bilateral activationwith involvement
of regions homologous to the ones responsible for normal functionmay
facilitate recovery after brain injury (Engelien et al., 1995).
Although an interpretation in terms of functional compensation is
consistent with the fact that old subjects performed at the same level
as young subjects during the scans despite age-related decreases during
both encoding and retrieval, the data reported here do not allow us to
determine whether bilateral frontal activity in old subjects, as well
as age-related increase in the cuneus/precuneus region, was beneficial
or detrimental to memory performance.
Relation of aging to recognition and recall activations
LV2 identified recall activations primarily in cerebellar and
cingulate regions and recognition activations mainly in right parietal
and temporal regions. Age-related decreases occurred in both
recognition and recall. We have no ready explanation for the
age-related decreases in recognition. Recall activations may be related
to the demand to generate an appropriate response in recall but not in
recognition (for a more detailed discussion, see Cabeza et al., in
press). Consistent with this idea, these regions were also engaged
during encoding (see Fig. 4, 1-4), which involved a generation component as well. On this view, the present results might indicate that old subjects have difficulties with the
generative process in recall, an idea that is in line with some
theories of cognitive aging (e.g., Craik, 1983). However, the fact that
old adults showed weaker recognition/recall differences in LV2 cannot
be separated from the fact that they showed recognition/recall differences in other brain regions in LV4 (see Fig. 4,
9-12). Thus, rather than interpreting the
results of LV2 in terms of deficient (or less flexible) processing in
old adults, the combined results of LV2 and LV4 suggest that young and
old adults performed recognition and recall tasks in a different way
and, therefore, showed differential involvement of distinct brain
regions. Because we attenuated performance differences between recall
and recognition, it is a problem for future research to investigate
age-related rCBF differences in conditions in which recall is much more
demanding than recognition.
CONCLUSIONS
Old adults showed smaller differences in neuronal activity than
young adults in some brain regions and larger differences in other in
other regions. Age-related reductions occurred primarily in left
prefrontal and temporo-occipital regions during encoding and right
prefrontal regions during retrieval. These reductions suggest altered
memory networks during both encoding and retrieval, but particularly
during encoding where age-related reductions were more pronounced.
Age-related increases may reflect the use of inadequate strategies in
old adults (e.g., in insular regions during encoding), or they may
signal beneficial compensatory activity (e.g., in the cuneus/precuneus
region during recognition and the left prefrontal cortex during
recall). Further work is necessary to evaluate these interpretations
and to determine exactly how activity in these recruited areas is
related to behavior.
FOOTNOTES
Received July 31, 1996; revised Oct. 2, 1996; accepted Oct. 3, 1996.
This work was supported by a post-doctoral fellowship of the
International Human Frontier Science Program to R.C., grants from the
National Alliance for Research on Schizophrenia and Depression and the
Medical Research Council to S.K., and an endowment by Anne and Max
Tanenbaum to E.T. We thank Douglas Hussey, Kevin Cheung, and Corey
Jones for technical assistance.
Correspondence should be addressed to Roberto Cabeza, Rotman Research
Institute of Baycrest Centre, 3560 Bathurst Street, North York,
Ontario, Canada M6A 2E1.
REFERENCES
-
Andreasen NC,
O'Leary DS,
Arndt S,
Cizadlo T,
Hurtig R,
Rezai K,
Watkins GL,
Ponto LLB,
Hichwa RD
(1995)
Short-term and long-term verbal memory: a positron emission tomography study.
Proc Natl Acad Sci USA
92:5111-5115 .
[Abstract/Free Full Text]
-
Buckner RL,
Petersen SE,
Ojemann JG,
Miezin FM,
Squire LR,
Raichle ME
(1995)
Functional anatomical studies of explicit and implicit memory retrieval tasks.
J Neurosci
15:12-29 .
[Abstract]
-
Buckner RL,
Corbetta M,
Schatz J,
Raichle ME,
Petersen SE
(1996)
Preserved speech abilities and compensation following prefrontal damage.
Proc Natl Acad Sci USA
93:1249-1253 .
[Abstract/Free Full Text]
-
Cabeza R, Nyberg L (1996) Imaging cognition: an empirical
review of PET studies with normal subjects. J Cognit Neurosci, in
press.
-
Cabeza R, Kapur S, Craik FIM, McIntosh AR, Houle S, Tulving
E (1996) Functional neuroanatomy of recall and recognition: a
PET study of episodic memory. J Cognit Neurosci, in press.
-
Cahill L, Haier RJ, Fallon J, Alkire M, Tang C, Keator D, Wu J, McGaug
JL (1996) Amygdala activity at encoding correlated with
long-term free recall of emotional information. Proc Natl Acad Sci USA,
in press.
-
Coleman PD,
Flood DG
(1987)
Neuron numbers and dendritic extent in normal aging and Alzheimer's disease.
Neurobiol Aging
8:521-545 .
[Web of Science][Medline]
-
Colombo M,
Gross CG
(1994)
Responses of inferior temporal cortex and hippocampal neurons during delayed matching to sample in monkeys (Macaca fascicularis).
Behav Neurosci
108:443-455 .
[Web of Science][Medline]
-
Craik FIM
(1983)
On the transfer of information from temporary to permanent memory.
Philos Trans R Soc Lond [Biol]
302:341-359.
-
Craik FIM,
Jennings JM
(1992)
Human memory.
In: Handbook of aging and cognition (Craik FIM,
Salthouse TA,
eds), pp 51-109. Hillsdale, NJ: Erlbaum.
-
Craik FIM,
McDowd JM
(1987)
Age differences in recall and recognition.
J Exp Psychol
13:474-479.
-
Craik FIM,
Simon E
(1980)
Age differences in memory: the roles of attention and depth of processing.
In: New directions in memory and aging (Poon LW,
Fozard JL,
Cermak LS,
Arenberg D,
Thompson LW,
eds), pp 95-112. Hillsdale, NJ: Erlbaum.
-
Creasey H,
Rapoport SI
(1985)
The aging human brain.
Ann Neurol
17:2-10 .
[Web of Science][Medline]
-
Devinsky O,
Morrell MJ,
Vogt BA
(1995)
Contributions of anterior cingulate cortex to behaviour.
Brain
118:279-306 .
[Abstract/Free Full Text]
-
Engelien A,
Silbersweig D,
Stern E,
Huber W,
Doring W,
Frith C,
Frackowiak RS
(1995)
The functional anatomy of recovery from auditory agnosia: a PET study of sound categorization in a neurological patient and normal controls.
Brain
118:1395-1409 .
[Abstract/Free Full Text]
-
Fletcher PC,
Frith CD,
Grasby PM,
Shallice T,
Frackowiak RSJ,
Dolan RJ
(1995)
Brain systems for encoding and retrieval of auditory-verbal memory: an in vivo study in humans.
Brain
118:401-416 .
[Abstract/Free Full Text]
-
Fox PT,
Mintun MA,
Reiman EM,
Raichle ME
(1988)
Enhanced detection of focal brain responses using intersubject averaging and change distribution analysis of subtracted PET images.
J Cereb Blood Flow Metab
8:642-653 .
[Web of Science][Medline]
-
Friston KJ,
Frith CD,
Liddle PF,
Frackowiak RSJ
(1991)
Comparing functional (PET) images: the assessment of significant change.
J Cereb Blood Flow Metab
11:690-699 .
[Web of Science][Medline]
-
Friston KJ,
Holmes AP,
Worsley KJ,
Poline J-P,
Frith CD,
Frackowiak RSJ
(1995)
Statistical parametric maps in functional imaging: a general linear approach.
Hum Brain Mapp
2:189-210.
-
Grady CL,
Haxby JV,
Horwitz B,
Sundaram M,
Berg G,
Schapiro MB,
Friedland RP,
Rapoport SI
(1988)
A longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type.
J Clin Exp Neuropsychol
10:576-596 .
[Web of Science][Medline]
-
Grady CL,
Maisog JM,
Horwitz B,
Ungerleider LG,
Mentis MJ,
Salerno JA,
Pietrini P,
Wagner E,
Haxby JV
(1994)
Age-related changes in cortical blood flow activation during visual processing of faces and location.
J Neurosci
14:1450-1462 .
[Abstract]
-
Grady CL,
McIntosh AR,
Horwitz B,
Maisog JM,
Ungerleider LG,
Mentis MJ,
Pietrini P,
Schapiro MB,
Haxby JV
(1995)
Age-related reductions in human recognition memory due to impaired memory encoding.
Science
269:218-221 .
[Abstract/Free Full Text]
-
Hasher L,
Zacks RT
(1988)
Working memory, comprehension and aging: a review and a new view.
Psychol Learn Motiv
22:193-225.
-
Haxby JV,
Ungerleider LG,
Horwitz B,
Maisog JM,
Rapoport SL,
Grady CL
(1996)
Face encoding and recognition in the human brain.
Proc Natl Acad Sci USA
93:922-927 .
[Abstract/Free Full Text]
-
Horel JA,
Pytko-Joiner DE,
Voytko ML,
Salsbury K
(1987)
The performance of visual tasks while segments of the inferotemporal cortex are suppressed by cold.
Behav Brain Res
23:29-42 .
[Web of Science][Medline]
-
Kapur S,
Rose R,
Liddle PF,
Zipursky RB,
Brown GM,
Stuss D,
Houle S,
Tulving E
(1994)
The role of left prefrontal cortex in verbal processing: semantic processing or willed action?
NeuroReport
5:2193-2196 .
[Web of Science][Medline]
-
Kapur S,
Craik FIM,
Jones C,
Brown GM,
Houle S,
Tulving E
(1995)
Functional role of the prefrontal cortex in memory retrieval: a PET study.
NeuroReport
6:1880-1884 .
[Web of Science][Medline]
-
Kapur S, Tulving E, Cabeza R, McIntosh RA, Houle S, Craik
FIM (1996) Neural correlates of intentional learning of
verbal materials: a PET study in humans. Cognit Brain Res, in
press.
-
Kemper T
(1984)
Neuroanatomical and neuropathological changes in normal aging and in dementia.
In: Clinical neurology of aging (Albert M,
ed), pp 9-52. New York: Oxford UP.
-
Light LL
(1991)
Memory and aging: four hypotheses in search of data.
Annu Rev Psychol
42:333-376 .
[Web of Science][Medline]
-
Madden DJ,
Turkington TG,
Coleman RE,
Provenzale JM,
DeGrado TR,
Hoffman JM
(1996)
Adult age differences in regional cerebral blood flow during visual word identification: evidence from H215O PET.
Neuroimage
3:127-142.[Web of Science][Medline]
-
McIntosh AR,
Bookstein FL,
Haxby JV,
Grady CL
(1996)
Spatial pattern analysis of functional brain images using partial least squares.
Neuroimage
3:143-157.[Web of Science][Medline]
-
Miller EK,
Li L,
Desimone R
(1991)
A neural mechanism for working and recognition memory in inferior temporal cortex.
Science
254:1377-1379 .
[Abstract/Free Full Text]
-
Moeller JR,
Strother SC
(1991)
A regional covariance approach to the analysis of functional patterns in positron emission tomographic data.
J Cereb Blood Flow Metab
11:A121-A135 .
[Web of Science][Medline]
-
Moscovitch M
(1992)
Memory and working-with-memory: a component process model based on modules and central systems.
J Cognit Neurosci
4:257-267.[Web of Science]
-
Nyberg L,
Tulving E,
Habib R,
Nilsson L-G,
Kapur S,
Houle S,
Cabeza R,
McIntosh AR
(1995)
Functional brain maps of retrieval mode and recovery of episodic information.
NeuroReport
7:249-252 .
[Web of Science][Medline]
-
Nyberg L,
Cabeza R,
Tulving E
(1996a)
PET studies of encoding and retrieval: the HERA Model.
Psychonom Bull Rev
3:134-147.
-
Nyberg L,
McIntosh AR,
Cabeza R,
Nilsson L-G,
Houle S,
Habib R,
Tulving E
(1996b)
Network analysis of positron emission tomography regional cerebral blood flow data: ensemble inhibition during episodic memory retrieval.
J Neurosci
16:3753-3759 .
[Abstract/Free Full Text]
-
Paus T,
Petrides M,
Evans AC,
Meyer E
(1993)
Role of the human anterior cingulate cortex in control of oculomotor, manual, and speech responses: a positron emission tomography study.
J Neurophysiol
70:453-469 .
[Abstract/Free Full Text]
-
Petersen SE,
Fox PT,
Posner MI,
Mintum M,
Raichle ME
(1989)
Positron emission tomographic studies of the processing single words.
J Cognit Neurosci
1:153-170.
-
Petrides M,
Alivisatos B,
Evans A
(1995)
Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information.
Proc Natl Acad Sci USA
92:5803-5807 .
[Abstract/Free Full Text]
-
Schacter DL,
Alpert NM,
Savage CR,
Rauch SL,
Albert MS
(1996)
Conscious recollection and the human hippocampal formation: evidence from positron emission tomography.
Proc Natl Acad Sci USA
93:321-326 .
[Abstract/Free Full Text]
-
Schacter DL,
Savage CR,
Alpert NM,
Rauch SL,
Albert MS
(1996)
The role of hippocampus and frontal cortex in age-related memory changes: a PET study.
NeuroReport
7:1165-1169 .
[Web of Science][Medline]
-
Talairach J,
Tournoux P
(1988)
In: A co-planar stereotactic atlas of the human brain. Stuttgart: Thieme.
-
Tulving E
(1983)
In: Elements of episodic memory. London: Oxford UP.
-
Tulving E,
Kapur S,
Craik FIM,
Moscovitch M,
Houle S
(1994)
Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.
Proc Natl Acad Sci USA
91:2016-2020 .
[Abstract/Free Full Text]
-
Ungerleider LG,
Mischkin M
(1982)
Two cortical visual systems.
In: Analysis of visual behavior (Ingle DJ,
Goodale MA,
Mansfield RJW,
eds), pp 549-589. Cambridge, MA: MIT.
-
Verhaeghen P,
Marcoen A,
Goossens L
(1993)
Facts and fiction about memory aging: A quantitative integration of research findings.
J Gerontol
48:157-171.
This article has been cited by other articles:
|
|
|
|
 
J. Ghajar and R. B. Ivry
The Predictive Brain State: Asynchrony in Disorders of Attention?
Neuroscientist,
June 1, 2009;
15(3):
232 - 242.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. E. Strangman, R. Goldstein, T. M. O'Neil-Pirozzi, K. Kelkar, C. Supelana, D. Burke, D. I. Katz, S. L. Rauch, C. R. Savage, and M. B. Glenn
Neurophysiological Alterations During Strategy-Based Verbal Learning in Traumatic Brain Injury
Neurorehabil Neural Repair,
March 1, 2009;
23(3):
226 - 236.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Duarte, R. N. Henson, and K. S. Graham
The Effects of Aging on the Neural Correlates of Subjective and Objective Recollection
Cereb Cortex,
September 1, 2008;
18(9):
2169 - 2180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ghajar and R. B. Ivry
The Predictive Brain State: Timing Deficiency in Traumatic Brain Injury?
Neurorehabil Neural Repair,
May 1, 2008;
22(3):
217 - 227.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. L. Paxton, D. M. Barch, C. A. Racine, and T. S. Braver
Cognitive Control, Goal Maintenance, and Prefrontal Function in Healthy Aging
Cereb Cortex,
May 1, 2008;
18(5):
1010 - 1028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. W. Davis, N. A. Dennis, S. M. Daselaar, M. S. Fleck, and R. Cabeza
Que PASA? The Posterior-Anterior Shift in Aging
Cereb Cortex,
May 1, 2008;
18(5):
1201 - 1209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Boyle, R. S. Wilson, J. A. Schneider, J. L. Bienias, and D. A. Bennett
Processing resources reduce the effect of Alzheimer pathology on other cognitive systems
Neurology,
April 22, 2008;
70(17):
1534 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Putnam, G. S. Wig, S. T. Grafton, W. M. Kelley, and M. S. Gazzaniga
Structural Organization of the Corpus Callosum Predicts the Extent and Impact of Cortical Activity in the Nondominant Hemisphere
J. Neurosci.,
March 12, 2008;
28(11):
2912 - 2918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. C. Lee, A. W. S. Leung, P. T. Fox, J.-H. Gao, and C. C. H. Chan
Age-related differences in neural activities during risk taking as revealed by functional MRI
Soc Cogn Affect Neurosci,
March 1, 2008;
3(1):
7 - 15.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Wylie, J. J. Foxe, and T. L. Taylor
Forgetting as an Active Process: An fMRI Investigation of Item-Method-Directed Forgetting
Cereb Cortex,
March 1, 2008;
18(3):
670 - 682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Grady, H. Yu, and C. Alain
Age-Related Differences in Brain Activity Underlying Working Memory for Spatial and Nonspatial Auditory Information
Cereb Cortex,
January 1, 2008;
18(1):
189 - 199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Morcom, J. Li, and M. D. Rugg
Age Effects on the Neural Correlates of Episodic Retrieval: Increased Cortical Recruitment with Matched Performance
Cereb Cortex,
November 1, 2007;
17(11):
2491 - 2506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Velanova, C. Lustig, L. L. Jacoby, and R. L. Buckner
Evidence for Frontally Mediated Controlled Processing Differences in Older Adults
Cereb Cortex,
May 1, 2007;
17(5):
1033 - 1046.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Minati, M. Grisoli, and M. G. Bruzzone
MR Spectroscopy, Functional MRI, and Diffusion-Tensor Imaging in the Aging Brain: A Conceptual Review
J Geriatr Psychiatry Neurol,
March 1, 2007;
20(1):
3 - 21.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. Maccotta, R. L. Buckner, F. G. Gilliam, and J. G. Ojemann
Changing Frontal Contributions to Memory Before and After Medial Temporal Lobectomy
Cereb Cortex,
February 1, 2007;
17(2):
443 - 456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Sharp, S. K. Scott, M. A. Mehta, and R. J.S. Wise
The Neural Correlates of Declining Performance with Age: Evidence for Age-Related Changes in Cognitive Control
Cereb Cortex,
December 1, 2006;
16(12):
1739 - 1749.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. G. Dobbins and S. Han
Isolating Rule- versus Evidence-Based Prefrontal Activity during Episodic and Lexical Discrimination: a Functional Magnetic Resonance Imaging Investigation of Detection Theory Distinctions
Cereb Cortex,
November 1, 2006;
16(11):
1614 - 1622.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Fridriksson, K. L. Morrow, D. Moser, and G. C. Baylis
Age-Related Variability in Cortical Activity During Language Processing.
J Speech Lang Hear Res,
August 1, 2006;
49(4):
690 - 697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Persson, L. Nyberg, J. Lind, A. Larsson, L.-G. Nilsson, M. Ingvar, and R. L. Buckner
Structure-Function Correlates of Cognitive Decline in Aging
Cereb Cortex,
July 1, 2006;
16(7):
907 - 915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Fera, T. W. Weickert, T. E. Goldberg, A. Tessitore, A. Hariri, S. Das, S. Lee, B. Zoltick, M. Meeter, C. E. Myers, et al.
Neural Mechanisms Underlying Probabilistic Category Learning in Normal Aging
J. Neurosci.,
December 7, 2005;
25(49):
11340 - 11348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Rajah and M. D'Esposito
Region-specific changes in prefrontal function with age: a review of PET and fMRI studies on working and episodic memory
Brain,
September 1, 2005;
128(9):
1964 - 1983.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Vandenberghe and J Tournoy
Cognitive aging and Alzheimer's disease
Postgrad. Med. J.,
June 1, 2005;
81(956):
343 - 352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E. Anderson, K. Lynch, E. Zarahn, N. Scarmeas, R. Van Heertum, H. Sackeim, J. R. Moeller, and Y. Stern
H215O PET Study of Impairment of Nonverbal Recognition With Normal Aging
J Neuropsychiatry Clin Neurosci,
May 1, 2005;
17(2):
192 - 200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Stern, C. Habeck, J. Moeller, N. Scarmeas, K. E. Anderson, H. J. Hilton, J. Flynn, H. Sackeim, and R. van Heertum
Brain Networks Associated with Cognitive Reserve in Healthy Young and Old Adults
Cereb Cortex,
April 1, 2005;
15(4):
394 - 402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Y. Shan, J. Z. Liu, V. Sahgal, B. Wang, and G. H. Yue
Selective Atrophy of Left Hemisphere and Frontal Lobe of the Brain in Old Men
J. Gerontol. A Biol. Sci. Med. Sci.,
February 1, 2005;
60(2):
165 - 174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Petrella, B. A. Townsend, A. P. Jha, L. A. Ziajko, M. J. Slavin, C. Lustig, S. J. Hart, and P. M. Doraiswamy
Increasing Memory Load Modulates Regional Brain Activity in Older Adults as Measured by fMRI
J Neuropsychiatry Clin Neurosci,
February 1, 2005;
17(1):
75 - 83.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Pennanen, C Testa, M P Laakso, M Hallikainen, E-L Helkala, T Hanninen, M Kivipelto, M Kononen, A Nissinen, S Tervo, et al.
A voxel based morphometry study on mild cognitive impairment
J. Neurol. Neurosurg. Psychiatry,
January 1, 2005;
76(1):
11 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Rossi, C. Miniussi, P. Pasqualetti, C. Babiloni, P. M. Rossini, and S. F. Cappa
Age-Related Functional Changes of Prefrontal Cortex in Long-Term Memory: A Repetitive Transcranial Magnetic Stimulation Study
J. Neurosci.,
September 8, 2004;
24(36):
7939 - 7944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. L. Chee and W. C. Choo
Functional Imaging of Working Memory after 24 Hr of Total Sleep Deprivation
J. Neurosci.,
May 12, 2004;
24(19):
4560 - 4567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Cabeza, S. M. Daselaar, F. Dolcos, S. E. Prince, M. Budde, and L. Nyberg
Task-independent and Task-specific Age Effects on Brain Activity during Working Memory, Visual Attention and Episodic Retrieval
Cereb Cortex,
April 1, 2004;
14(4):
364 - 375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Head, R. L. Buckner, J. S. Shimony, L. E. Williams, E. Akbudak, T. E. Conturo, M. McAvoy, J. C. Morris, and A. Z. Snyder
Differential Vulnerability of Anterior White Matter in Nondemented Aging with Minimal Acceleration in Dementia of the Alzheimer Type: Evidence from Diffusion Tensor Imaging
Cereb Cortex,
April 1, 2004;
14(4):
410 - 423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Madden, W. L. Whiting, J. M. Provenzale, and S. A. Huettel
Age-related Changes in Neural Activity during Visual Target Detection Measured by fMRI
Cereb Cortex,
February 1, 2004;
14(2):
143 - 155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Maguire and C. D. Frith
Aging affects the engagement of the hippocampus during autobiographical memory retrieval
Brain,
July 1, 2003;
126(7):
1511 - 1523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Buckner
Functional-Anatomic Correlates of Control Processes in Memory
J. Neurosci.,
May 15, 2003;
23(10):
3999 - 4004.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Grady, A. R. McIntosh, S. Beig, M. L. Keightley, H. Burian, and S. E. Black
Evidence from Functional Neuroimaging of a Compensatory Prefrontal Network in Alzheimer's Disease
J. Neurosci.,
February 1, 2003;
23(3):
986 - 993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gazzaley and M. D'Esposito
The Contribution of Functional Brain Imaging to Our Understanding of Cognitive Aging
Sci. Aging Knowl. Environ.,
January 29, 2003;
2003(4):
pe2 - 2.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. M. Daselaar, D. J. Veltman, S. A. R. B. Rombouts, J. G. W. Raaijmakers, and C. Jonker
Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects
Brain,
January 1, 2003;
126(1):
43 - 56.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Morcom, C. D. Good, R. S. J. Frackowiak, and M. D. Rugg
Age effects on the neural correlates of successful memory encoding
Brain,
January 1, 2003;
126(1):
213 - 229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B Levine, R Cabeza, A R McIntosh, S E Black, C L Grady, and D T Stuss
Functional reorganisation of memory after traumatic brain injury: a study with H2150 positron emission tomography
J. Neurol. Neurosurg. Psychiatry,
August 1, 2002;
73(2):
173 - 181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V.S. Mattay, F. Fera, A. Tessitore, A.R. Hariri, S. Das, J.H. Callicott, and D.R. Weinberger
Neurophysiological correlates of age-related changes in human motor function
Neurology,
February 26, 2002;
58(4):
630 - 635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Dade, R. J. Zatorre, and M. Jones-Gotman
Olfactory learning: convergent findings from lesion and brain imaging studies in humans
Brain,
January 1, 2002;
125(1):
86 - 101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Valla, J. D. Berndt, and F. Gonzalez-Lima
Energy Hypometabolism in Posterior Cingulate Cortex of Alzheimer's Patients: Superficial Laminar Cytochrome Oxidase Associated with Disease Duration
J. Neurosci.,
July 1, 2001;
21(13):
4923 - 4930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Grady, M. L. Furey, P. Pietrini, B. Horwitz, and S. I. Rapoport
Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease
Brain,
April 1, 2001;
124(4):
739 - 756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. DeCarli, B. L. Miller, G. E. Swan, T. Reed, P. A. Wolf, and D. Carmelli
Cerebrovascular and Brain Morphologic Correlates of Mild Cognitive Impairment in the National Heart, Lung, and Blood Institute Twin Study
Arch Neurol,
April 1, 2001;
58(4):
643 - 647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Cabeza, S. M. Rao, A. D. Wagner, A. R. Mayer, and D. L. Schacter
Can medial temporal lobe regions distinguish true from false? An event-related functional MRI study of veridical and illusory recognition memory
PNAS,
March 29, 2001;
(2001)
81082698.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. Calautti, C. Serrati, and J-C. Baron
Effects of Age on Brain Activation During Auditory-Cued Thumb-to-Index Opposition : A Positron Emission Tomography Study
Stroke,
January 1, 2001;
32(1):
139 - 146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Della-Maggiore, A. B. Sekuler, C. L. Grady, P. J. Bennett, R. Sekuler, and A. R. McIntosh
Corticolimbic Interactions Associated with Performance on a Short-Term Memory Task Are Modified by Age
J. Neurosci.,
November 15, 2000;
20(22):
8410 - 8416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sailer, J. Dichgans, and C. Gerloff
The influence of normal aging on the cortical processing of a simple motor task
Neurology,
October 10, 2000;
55(7):
979 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Levisohn, A. Cronin-Golomb, and J. D. Schmahmann
Neuropsychological consequences of cerebellar tumour resection in children: Cerebellar cognitive affective syndrome in a paediatric population
Brain,
May 1, 2000;
123(5):
1041 - 1050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Grady, A. R. McIntosh, M. N. Rajah, S. Beig, and F. I.M. Craik
The Effects of Age on the Neural Correlates of Episodic Encoding
Cereb Cortex,
December 1, 1999;
9(8):
805 - 814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Backman, J. L. R. Andersson, L. Nyberg, B. Winblad, A. Nordberg, and O. Almkvist
Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease
Neurology,
June 1, 1999;
52(9):
1861 - 1861.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Esposito, B. S. Kirkby, J. D. Van Horn, T. M. Ellmore, and K. F. Berman
Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation
Brain,
May 1, 1999;
122(5):
963 - 979.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Shaywitz, B. A. Shaywitz, K. R. Pugh, R. K. Fulbright, P. Skudlarski, W. E. Mencl, R. T. Constable, F. Naftolin, S. F. Palter, K. E. Marchione, et al.
Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women During Working Memory Tasks
JAMA,
April 7, 1999;
281(13):
1197 - 1202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Mcintosh and F. Gonzalez-Lima
Large-Scale Functional Connectivity in Associative Learning: Interrelations of the Rat Auditory, Visual, and Limbic Systems
J Neurophysiol,
December 1, 1998;
80(6):
3148 - 3162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Cabeza, S. M. Rao, A. D. Wagner, A. R. Mayer, and D. L. Schacter
Can medial temporal lobe regions distinguish true from false? An event-related functional MRI study of veridical and illusory recognition memory
PNAS,
April 10, 2001;
98(8):
4805 - 4810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Memory
