Age differences in the neural correlates of recollection: transient versus sustained fMRI effects.

Prior functional magnetic resonance imaging findings in young adults indicate that recollection-sensitive neural regions dissociate according to the time courses of their respective recollection effects. Here, we examined whether such dissociations are also evident in older adults. Young and older participants encoded a series of word-image pairs, judging which of the denoted objects was the smaller. At the test, participants judged whether each of a series of test words was old or new. If a word was old, the requirement was to recall the associated image and maintain it over a variable delay period. Older adults demonstrated significantly lower associative memory performance than young adults. Transient recollection effects were identified in the left hippocampus, medial prefrontal cortex, and posterior cingulate, while sustained effects were widespread across left lateral cortex and were also evident in the bilateral striatum. Except for those in the left insula, all effects were age-invariant. These findings suggest that both transient and sustained recollection effects are largely stable across much of the healthy adult life span.

Relationships between age, fMRI correlates of familiarity and familiarity-based memory performance under single and dual task conditions.

Using fMRI, we investigated the effects of age and divided attention on the neural correlates of familiarity and their relationship with memory performance. At study, word pairs were visually presented to young and older participants under the requirement to make a relational judgment on each pair. Participants were then scanned while undertaking an associative recognition test under single and dual (auditory tone detection) task conditions. The test items comprised studied, rearranged (words from different studied pairs) and new word pairs. fMRI familiarity effects were operationalized as greater activity elicited by studied pairs incorrectly identified as 'rearranged' than by correctly rejected new pairs. The reverse contrast was employed to identify 'novelty' effects. Behavioral familiarity estimates were equivalent across age groups and task conditions. Robust fMRI familiarity effects were identified in several regions, including medial and superior lateral parietal cortex, dorsal medial and left lateral prefrontal cortex, and bilateral caudate. fMRI novelty effects were identified in the anterior medial temporal lobe. Both familiarity and novelty effects were largely age-invariant and did not vary, or varied minimally, according to task condition. In addition, the familiarity effects correlated positively with a behavioral estimate of familiarity strength irrespective of age. These findings extend a previous report from our laboratory, and converge with prior behavioral reports, in demonstrating that the factors of age and divided attention have little impact on behavioral and neural estimates of familiarity.

Relationships between age, fMRI correlates of familiarity and familiarity-based memory performance under single and dual task conditions.

Using fMRI, we investigated the effects of age and divided attention on the neural correlates of familiarity and their relationship with memory performance. At study, word pairs were visually presented to young and older participants under the requirement to make a relational judgment on each pair. Participants were then scanned while undertaking an associative recognition test under single and dual (auditory tone detection) task conditions. The test items comprised studied, rearranged (words from different studied pairs) and new word pairs. fMRI familiarity effects were operationalized as greater activity elicited by studied pairs incorrectly identified as 'rearranged' than by correctly rejected new pairs. The reverse contrast was employed to identify 'novelty' effects. Behavioral familiarity estimates were equivalent across age groups and task conditions. Robust fMRI familiarity effects were identified in several regions, including medial and superior lateral parietal cortex, dorsal medial and left lateral prefrontal cortex, and bilateral caudate. fMRI novelty effects were identified in the anterior medial temporal lobe. Both familiarity and novelty effects were age-invariant and did not vary according to task condition. In addition, the familiarity effects correlated positively with a behavioral estimate of familiarity strength irrespective of age. These findings extend a previous report from our laboratory, and converge with prior behavioral reports, in demonstrating that the factors of age and divided attention have minimal impact on behavioral and neural estimates of familiarity.

The effects of age on neural correlates of recollection: transient versus sustained fMRI effects.

Prior fMRI findings in young adults indicate that recollection-sensitive neural regions dissociate according to the time courses of their respective recollection effects. Here, we examined whether such dissociations are also evident in older adults. Young and older participants encoded a series of word-object image pairs, judging which of the denoted objects was the smaller. At test, participants first judged whether a test word was old or new. For items judged old, they were required to recall the associated image and hold it in mind across a variable delay period. A post-delay cue denoted which of three judgments should be made on the retrieved image. Older adults demonstrated significantly lower associative memory performance than young adults. Replicating prior findings, transient recollection effects were identified in the left hippocampus, medial prefrontal cortex and posterior cingulate, while sustained effects were widespread across left lateral cortex and were also evident in the bilateral striatum. With the exception of those in the left insula, all effects were age-invariant. These findings add to the evidence that recollection-related BOLD effects in different neural regions can be temporally dissociated. Additionally, the findings suggest that both transient and sustained recollection effects are largely stable across much of the healthy adult lifespan.

Cortical thickness, gray matter volume, and cognitive performance: a crosssectional study of the moderating effects of age on their interrelationships.

In a sample comprising younger, middle-aged, and older cognitively healthy adults (N = 375), we examined associations between mean cortical thickness, gray matter volume (GMV), and performance in 4 cognitive domains-memory, speed, fluency, and crystallized intelligence. In almost all cases, the associations were moderated significantly by age, with the strongest associations in the older age group. An exception to this pattern was identified in a younger adult subgroup aged <23 years when a negative association between cognitive performance and cortical thickness was identified. Other than for speed, all associations between structural metrics and performance in specific cognitive domains were fully mediated by mean cognitive ability. Cortical thickness and GMV explained unique fractions of the variance in mean cognitive ability, speed, and fluency. In no case, however, did the amount of variance jointly explained by the 2 metrics exceed 7% of the total variance. These findings suggest that cortical thickness and GMV are distinct correlates of domain-general cognitive ability, that the strength and, for cortical thickness, the direction of these associations are moderated by age, and that these structural metrics offer only limited insights into the determinants of individual differences in cognitive performance across the adult lifespan.

Patterns of retrieval-related cortico-striatal connectivity are stable across the adult lifespan.

Memory retrieval effects in the striatum are well documented and robust across experimental paradigms. However, the functional significance of these effects, and whether they are moderated by age, remains unclear. We used functional magnetic resonance imaging paired with an associative recognition task to examine retrieval effects in the striatum in a sample of healthy young, middle-aged, and older adults. We identified anatomically segregated patterns of enhanced striatal blood oxygen level-dependent (BOLD) activity during recollection- and familiarity-based memory judgments. Successful recollection was associated with enhanced BOLD activity in bilateral putamen and nucleus accumbens, and neither of these effects were reliably moderated by age. Familiarity effects were evident in the head of the caudate nucleus bilaterally, and these effects were attenuated in middle-aged and older adults. Using psychophysiological interaction analyses, we observed a monitoring-related increase in functional connectivity between the caudate and regions of the frontoparietal control network, and between the putamen and bilateral retrosplenial cortex and intraparietal sulcus. In all instances, monitoring-related increases in cortico-striatal connectivity were unmoderated by age. These results suggest that the striatum, and the caudate in particular, couples with the frontoparietal control network to support top-down retrieval-monitoring operations, and that the strength of these inter-regional interactions is preserved in later life.

Divided attention at retrieval does not influence neural correlates of recollection in young or older adults.

Age-related decline in episodic memory has been partially attributed to older adults' reduced domain general processing resources. In the present study, we examined the effects of divided attention (DA) - a manipulation assumed to further deplete the already limited processing resources of older adults - on the neural correlates of recollection in young and older adults. Participants underwent fMRI scanning while they performed an associative recognition test in single and dual (tone detection) task conditions. Recollection effects were operationalized as greater BOLD activity elicited by test pairs correctly endorsed as 'intact' than pairs correctly or incorrectly endorsed as 'rearranged'. Detrimental effects of DA on associative recognition performance were identified in older but not young adults. The magnitudes of recollection effects did not differ between the single and dual (tone detection) tasks in either age group. Across the task conditions, age-invariant recollection effects were evident in most members of the core recollection network. However, while young adults demonstrated robust recollection effects in left angular gyrus, angular gyrus effects were undetectable in the older adults in either task condition. With the possible exception of this result, the findings suggest that DA did not influence processes supporting the retrieval and representation of associative information in either young or older adults, and converge with prior behavioral findings to suggest that episodic retrieval operations are little affected by DA.

Specific and general relationships between cortical thickness and cognition in older adults: a longitudinal study.

Prior studies suggest that relationships between regional cortical thickness and domain-specific cognitive performance can be mediated by the relationship between global cortical thickness and domain-general cognition. Whether such findings extend to longitudinal cognitive change remains unclear. Here, we examined the relationships in healthy older adults between cognitive performance, longitudinal cognitive change over 3 years, and cortical thickness at baseline of the left and right inferior frontal gyrus (IFG) and left and right hemispheres. Both right IFG and right hemisphere thickness predicted baseline general cognition and domain-specific cognitive performance. Right IFG thickness was also predictive of longitudinal memory change. However, right IFG thickness was uncorrelated with cognitive performance and memory change after controlling for the mean thickness of other ipsilateral cortical regions. In addition, most identified associations between cortical thickness and specific cognitive domains were nonsignificant after controlling for the variance shared with other cognitive domains. Thus, relationships between right IFG thickness, cognitive performance, and memory change appear to be largely accounted for by more generic relationships between cortical thickness and cognition. This article is part of the Virtual Special Issue titled "COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING". The full issue can be found on ScienceDirect athttps://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

Neural correlates of post-retrieval monitoring in older adults are preserved under divided attention, but are decoupled from memory performance.

Post-retrieval monitoring is associated with engagement of anterior cingulate and dorsolateral prefrontal cortex. Recent fMRI studies reported age-invariant monitoring effects in these regions and an age-invariant correlation between these effects and memory performance. The present study examined monitoring effects during associative recognition (difference in activity elicited by 'rearranged' and 'intact' test pairs) under single and dual (tone detection) task conditions in young and older adults (Ns = 28 per group). It was predicted that, for the older adults only, dual tasking would attenuate memory performance and monitoring effects and weaken their correlation. Consistent with this prediction, in the older group imposition of the secondary task led to lower memory performance and elimination of the relationship between monitoring effects and performance. However, the size of the effects did not differ between single and dual task conditions. The findings suggest that the decline in older adults' memory performance in the dual task condition resulted not from impaired monitoring, but from a different cause that also weakened the dependence of performance on monitoring.

Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults.

Prior fMRI studies have reported relationships between memory-related activity in the hippocampus and in-scanner memory performance, but whether such activity is predictive of longitudinal memory change remains unclear. Here, we administered a neuropsychological test battery to a sample of cognitively healthy older adults on three occasions, the second and third sessions occurring one month and three years after the first session. Structural and functional MRI data were acquired between the first two sessions. The fMRI data were derived from an associative recognition procedure and allowed estimation of hippocampal effects associated with both successful associative encoding and successful associative recognition (recollection). Baseline memory performance and memory change were evaluated using memory component scores derived from a principal components analysis of the neuropsychological test scores. Across participants, right hippocampal encoding effects correlated significantly with baseline memory performance after controlling for chronological age. Additionally, both left and right hippocampal associative recognition effects correlated negatively with longitudinal memory decline after controlling for age, and the relationship with the left hippocampal effect remained after also controlling for left hippocampal volume. Thus, in cognitively healthy older adults, the magnitude of hippocampal recollection effects appears to be a robust predictor of future memory change.

Age moderates the relationship between cortical thickness and cognitive performance.

Findings from cross-sectional and longitudinal magnetic resonance imaging (MRI) studies indicate that cortical thickness declines across the adult lifespan, with regional differences in rate of decline. Global and regional thickness have also been found to co-vary with cognitive performance. Here we examined the relationships between age, mean cortical thickness, and associative recognition performance across three age groups (younger, middle-aged and older adults; total n = 133). Measures of cortical thickness were obtained using a semi-automated method. Older age was associated with decreased memory performance and a reduction in mean cortical thickness. After controlling for the potentially confounding effects of head motion, mean cortical thickness was negatively associated with associative memory performance in the younger participants, but was positively correlated with performance in older participants. A similar but weaker pattern was evident in the relationships between cortical thickness and scores on four cognitive constructs derived from a neuropsychological test battery. This pattern is consistent with prior findings indicating that the direction of the association between cortical thickness and cognitive performance reverses between early and later adulthood. In addition, head motion was independently and negatively correlated with associative recognition performance in younger and middle-aged, but not older, participants, suggesting that variance in head motion is determined by multiple factors that vary in their relative influences with age.

Recollection-related increases in functional connectivity across the healthy adult lifespan.

In young adults, recollection-sensitive brain regions exhibit enhanced connectivity with a widely distributed set of other regions during successful versus unsuccessful recollection, and the magnitude of connectivity change correlates with individual differences in recollection accuracy. Here, we examined whether recollection-related changes in connectivity and their relationship with performance varied across samples of young, middle-aged, and older adults. Psychophysiological interaction analyses identified recollection-related increases in connectivity both with recollection-sensitive seed regions and among regions distributed throughout the whole brain. The seed-based approach failed to identify age-related differences in recollection-related connectivity change. However, the whole-brain analysis revealed a number of age-related effects. Numerous pairs of regions exhibited a main effect of age on connectivity change, mostly due to decreased change with increasing age. After controlling for recollection accuracy, however, these effects of age were for the most part no longer significant, and those effects that were detected now reflected age-related increases in connectivity change. A subset of pairs of regions also exhibited an age by performance interaction, driven mostly by a weaker relationship between connectivity change and recollection accuracy with increasing age. We conjecture that these effects reflect age-related differences in neuromodulation.

Independent contributions of fMRI familiarity and novelty effects to recognition memory and their stability across the adult lifespan.

The impact of age on the neural correlates of familiarity-driven recognition memory has received relatively little attention. Here, the relationships between age, the neural correlates of familiarity, and memory performance were investigated using an associative recognition test in young, middle-aged and older participants. Test items comprised studied, rearranged (items studied on different trials) and new word pairs. fMRI 'familiarity effects' were operationalized as greater activity for studied test pairs incorrectly identified as 'rearranged' than for correctly rejected new pairs. The reverse contrast was employed to identify 'novelty' effects. Estimates of familiarity strength were slightly but significantly lower for the older relative to the younger group. With the exception of one region in dorsal medial prefrontal cortex, fMRI familiarity effects (which were identified in medial and lateral parietal cortex, dorsal medial and left lateral prefrontal cortex, and bilateral caudate among other regions) did not differ significantly with age. Age-invariant 'novelty effects' were identified in the anterior hippocampus and the perirhinal cortex. When entered into the same regression model, familiarity and novelty effects independently predicted familiarity strength across participants, suggesting that the two classes of memory effect reflect functionally distinct mnemonic processes. It is concluded that the neural correlates of familiarity-based memory judgments, and their relationship with familiarity strength, are largely stable across much of the healthy adult lifespan.

The relationships between age, associative memory performance, and the neural correlates of successful associative memory encoding.

Using functional magnetic resonance imaging, subsequent memory effects (greater activity for later remembered than later forgotten study items) predictive of associative encoding were compared across samples of young, middle-aged, and older adults (total N = 136). During scanning, participants studied visually presented word pairs. In a later test phase, they discriminated between studied pairs, "rearranged" pairs (items studied on different trials), and new pairs. Subsequent memory effects were identified by contrasting activity elicited by study pairs that went on to be correctly judged intact or incorrectly judged rearranged. Effects in the hippocampus were age-invariant and positively correlated across participants with associative memory performance. Subsequent memory effects in the right inferior frontal gyrus (IFG) were greater in the older than the young group. In older participants only, both left and, in contrast to prior reports, right IFG subsequent memory effects correlated positively with memory performance. We suggest that the IFG is especially vulnerable to age-related decline in functional integrity and that the relationship between encoding-related activity in right IFG and memory performance depends on the experimental context.

The neural correlates of recollection and retrieval monitoring: Relationships with age and recollection performance.

The relationships between age, retrieval-related neural activity, and episodic memory performance were investigated in samples of young (18-29yrs), middle-aged (43-55yrs) and older (63-76yrs) healthy adults. Participants underwent fMRI scanning during an associative recognition test that followed a study task performed on visually presented word pairs. Test items comprised pairs of intact (studied pairs), rearranged (items studied on different trials) and new words. fMRI recollection effects were operationalized as greater activity for studied pairs correctly endorsed as intact than for pairs incorrectly endorsed as rearranged. The reverse contrast was employed to identify retrieval monitoring effects. Robust recollection effects were identified in the core recollection network, comprising the hippocampus, along with parahippocampal and posterior cingulate cortex, left angular gyrus and medial prefrontal cortex. Retrieval monitoring effects were identified in the anterior cingulate and right dorsolateral prefrontal cortex. Neither recollection effects within the core network, nor the monitoring effects differed significantly across the age groups after controlling for individual differences in associative recognition performance. Whole brain analyses did however identify three clusters outside of these regions where recollection effects were greater in the young than in the other age groups. Across-participant regression analyses indicated that the magnitude of hippocampal and medial prefrontal cortex recollection effects, and both of the prefrontal monitoring effects, correlated significantly with memory performance. None of these correlations were moderated by age. The findings suggest that the relationships between memory performance and functional activity in regions consistently implicated in successful recollection and retrieval monitoring are stable across much of the healthy adult lifespan.

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring.

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material. Test items were words that corresponded to studied words or the names of studied objects. Subjects indicated whether each test item was recollected, familiar, or novel. Reinstatement of information differentiating the encoding tasks was quantified both with a univariate analysis of the fMRI signal and with a multivoxel pattern analysis, using a classifier that had been trained to discriminate between the 2 classes of study episode. The results of these analyses converged to suggest that reinstatement did not differ according to age. Thus, there was no evidence that specificity of recollected information was reduced in older individuals. Additionally, there were no age effects in the magnitude of recollection-related modulations in regional activity or in the neural correlates of post-retrieval monitoring. Taken together, the findings suggest that the neural mechanisms engaged during successful episodic retrieval can remain stable with advancing age.

The effects of study task on prestimulus subsequent memory effects in the hippocampus.

Functional magnetic resonance imaging (fMRI) was employed to examine the effects of a study task manipulation on pre-stimulus activity in the hippocampus predictive of later successful recollection. Eighteen young participants were scanned while making either animacy or syllable judgments on visually presented study words. Cues presented before each word denoted which judgment should be made. Following the study phase, a surprise recognition memory test was administered in which each test item had to be endorsed as "Remembered," "Known," or "New." As expected, "deep" animacy judgments led to better memory for study items than did "shallow" syllable judgments. In both study tasks, pre-stimulus subsequent recollection effects were evident in the interval between the cue and the study item in bilateral anterior hippocampus. However, the direction of the effects differed according to the study task: whereas pre-stimulus hippocampal activity on animacy trials was greater for later recollected items than items judged old on the basis of familiarity (replicating prior findings), these effects reversed for syllable trials. We propose that the direction of pre-stimulus hippocampal subsequent memory effects depends on whether an optimal pre-stimulus task set facilitates study processing that is conducive or unconducive to the formation of contextually rich episodic memories.

Recollection-related increases in functional connectivity predict individual differences in memory accuracy.

Recollection involves retrieving specific contextual details about a prior event. Functional neuroimaging studies have identified several brain regions that are consistently more active during successful versus failed recollection-the "core recollection network." In the present study, we investigated whether these regions demonstrate recollection-related increases not only in activity but also in functional connectivity in healthy human adults. We used fMRI to compare time-series correlations during successful versus unsuccessful recollection in three separate experiments, each using a different operational definition of recollection. Across experiments, a broadly distributed set of regions consistently exhibited recollection-related increases in connectivity with different members of the core recollection network. Regions that demonstrated this effect included both recollection-sensitive regions and areas where activity did not vary as a function of recollection success. In addition, in all three experiments the magnitude of connectivity increases correlated across individuals with recollection accuracy in areas diffusely distributed throughout the brain. These findings suggest that enhanced functional interactions between distributed brain regions are a signature of successful recollection. In addition, these findings demonstrate that examining dynamic modulations in functional connectivity during episodic retrieval will likely provide valuable insight into neural mechanisms underlying individual differences in memory performance.

Pre-stimulus neural activity predicts successful encoding of inter-item associations.

fMRI was employed to investigate the relationship between pre-stimulus neural activity and associative encoding of words and pictures in humans. While undergoing scanning, subjects studied randomly interleaved word or picture pairs. A pre-stimulus cue preceded the presentation of each study pair and signaled whether it would comprise words or pictures. Memory for the study pairs was later tested with an associative recognition test, which comprised word or picture pairs presented either in the same (intact) or a different (rearranged) pairing as at study, along with pairs of new items. The critical fMRI contrast was between study activity associated with pairs later correctly judged intact and pairs incorrectly judged as rearranged. A key question was whether material-selective pre-stimulus encoding effects could be identified which overlapped regions selectively activated by the respective study material. Picture-selective pre-stimulus effects were identified in bilateral fusiform and the intraparietal sulcus (IPS), whereas word-selective effects could not be identified. Material-invariant pre-stimulus subsequent memory effects were also identified in several neocortical regions as well as in the hippocampus. Whereas the loci of the neocortical effects suggest that they reflect the benefit to encoding that accrues from engagement of cognitive control processes, their magnitude was negatively correlated across subjects with associative recognition performance and positively related to false alarm rate. Conversely, the hippocampal effects also predicted unique variance in associative memory and were negatively related to hit rate. It is suggested that the neocortical pre-stimulus effects may reflect encoding processes that increase familiarity of single items, whereas the hippocampal pre-stimulus effects are proposed to reflect either the encoding of task-irrelevant features or the retrieval of task-relevant information associated with the pre-stimulus cues. Overall, the results provide evidence that pre-stimulus processes may be deleterious, rather than beneficial, to associative encoding.

Sensitivity of negative subsequent memory and task-negative effects to age and associative memory performance.

The present fMRI experiment employed associative recognition to investigate the relationships between age and encoding-related negative subsequent memory effects and task-negative effects. Young, middle-aged and older adults (total n=136) were scanned while they made relational judgments on visually presented word pairs. In a later memory test, the participants made associative recognition judgments on studied, rearranged (items studied on different trials) and new pairs. Several regions, mostly localized to the default mode network, demonstrated negative subsequent memory effects in an across age-group analysis. All but one of these regions also demonstrated task-negative effects, although there was no correlation between the size of the respective effects. Whereas negative subsequent memory effects demonstrated a graded attenuation with age, task-negative effects declined markedly between the young and the middle-aged group, but showed no further reduction in the older group. Negative subsequent memory effects did not correlate with memory performance within any age group. By contrast, in the older group only, task-negative effects predicted later memory performance. The findings demonstrate that negative subsequent memory and task-negative effects depend on dissociable neural mechanisms and likely reflect distinct cognitive processes. The relationship between task-negative effects and memory performance in the older group might reflect the sensitivity of these effects to variations in amount of age-related neuropathology. This article is part of a Special Issue entitled SI: Memory.