Free water-corrected fractional anisotropy of the fornix and parahippocampal cingulum predicts longitudinal memory change in cognitively healthy older adults.

Prior studies have reported inconsistent results regarding the relationships between the integrity of the fornix and parahippocampal cingulum and both memory performance and longitudinal change in performance. In the present study, we examined associations in a sample of cognitively healthy older adults between free water-corrected fractional anisotropy (FA) metrics derived from the fornix and cingulum, baseline memory performance, and 3-year memory change. Neither fornix nor cingulum FA correlated with memory performance at baseline. By contrast, FA of each tract was predictive of memory change, such that greater FA was associated with less longitudinal decline. These associations remained significant after controlling for FA of other white matter tracts and for performance in other cognitive domains. Furthermore, fornix and cingulum FA explained unique variance in memory change. These results suggest that free water-corrected measures of fornix and parahippocampal cingulum integrity are reliable predictors of future memory change in cognitively healthy older adults. The findings for the fornix in particular highlight the utility of correcting for free water when estimating diffusion tensor imaging metrics of white matter integrity.

Neural correlates of retrieval success and precision: an fMRI study.

Prior studies examining the neural mechanisms underlying retrieval success and precision have yielded inconsistent results. Here, their neural correlates were examined using a memory task that assessed precision for spatial location. A sample of healthy young adults underwent fMRI scanning during a single study-test cycle. At study, participants viewed a series of object images, each placed at a randomly selected location on an imaginary circle. At test, studied images were intermixed with new images and presented to the participants. The requirement was to move a cursor to the location of the studied image, guessing if necessary. Participants then signaled whether the presented image as having been studied. Memory precision was quantified as the angle between the studied location and the location selected by the participant. A precision effect was evident in the left angular gyrus, where BOLD activity covaried across trials with location accuracy. Multi-voxel pattern analysis also revealed a significant item-level reinstatement effect for high-precision trials. There was no evidence of a retrieval success effect in the angular gyrus. BOLD activity in the hippocampus was insensitive to both success and precision. These findings are partially consistent with prior evidence that success and precision are dissociable features of memory retrieval.

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.

Effects of age on the neural correlates of encoding source and item information: An fMRI study.

The effects of age on encoding-related neural activity predictive of accurate item and source memory judgments were examined with fMRI, with an a priori focus of the inferior frontal gyrus (IFG) and hippocampus. During a scanned study phase, young and older adults viewed a series of pictures of objects and made one of two judgments on each object. At test, which occurred outside of the scanner, an 'old/new' judgment on each test item was followed, for those items endorsed old, by a source judgment querying the study task. Neural activity predictive of accurate subsequent item and source memory judgments was identified in bilateral IFG, several other cortical regions and bilateral hippocampus. Cortical effects were graded in the young group (source > item > miss) but predicted item memory only in the older group. Hippocampal effects exclusively predicted source memory, and the magnitude of these effects did not reliably differ between the age groups. In the older group only, IFG and hippocampal encoding effects were positively correlated across participants with memory performance. Similar findings were evident in the extra-IFG regions demonstrating encoding effects. With the exception of the age-dependent relationship identified for hippocampal encoding effects, the present findings are broadly consistent with those from prior aging studies that employed verbal memoranda and tests of associative recognition. Thus, they extend these prior findings to include non-verbal materials and a different operationalization of episodic recollection. Additionally, the present findings suggest that the sensitivity in older adults of IFG encoding effects to subsequent memory performance reflects a more general tendency for cortical encoding effects to predict memory performance in this age group.

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.

Pharmacokinetic and tissue distribution study of eight volatile constituents in rats orally administrated with the essential oil of Artemisiae argyi Folium by GC-MS/MS.

Artemisia argyi is commonly used as a remedy for gynecological and respiratory disease in traditional Chinese medicine. The essential oil is considered as the major active ingredients of A. argyi, mainly composed of eucalyptol, α-thujone, camphor, borneol, bornyl acetate, eugenol, ß-caryophyllene, and caryophyllene oxide, while limited study addresses the in vivo disposition of these volatile ingredients. In present study, a rapid, sensitive and selective GC-MS/MS method has been developed and validated for the quantification of the eight volatile constituents in rat plasma and tissues after orally dosing with the essential oil of Artemisiae Argyi Folium (AAEO) using naphthalene as an internal standard (IS). The analytes were extracted from biosamples by liquid-liquid extraction with hexane/ethyl acetate. The GC separation was achieved on a TG-5SILMS column (30 m × 0.25 mm, 0.25 µm film thickness) and MS detection was performed on selective reaction monitoring (SRM) mode. The assay had a lower limit of quantification (LLOQ) less than 2 ng/ml for the analytes with good linearity (r ≥ 0.9907). Their disposition profile in rat plasma and tissues was characterized after orally giving AAEO, and the data revealed the analytes underwent rapid absorption from GI tract and were mainly transferred to the liver, heart, kidney, lung, and spleen with prompt elimination. The results provided a meaningful basis for guiding the pharmacodynamic study and clinical applications of this herbal medicine.

The effects of age on neural correlates of recognition memory: An fMRI study.

Studies examining the effects of age on the neural correlates of recognition memory have yielded mixed results. In the present study, we employed a modified remember-know paradigm to compare the fMRI correlates of recollection and familiarity in samples of healthy young and older adults. After studying a series of words, participants underwent fMRI scanning during a test phase in which they responded "remember" to a test word if any qualitative information could be recollected about the study event. When recollection failed, participants signaled how confident they were that the test item had been studied. Young and older adults demonstrated statistically equivalent estimates of recollection and familiarity strength, while recognition memory accuracy was significantly lower in the older adults. Robust, age-invariant fMRI effects were evident in two sets of a priori defined brain regions consistently reported in prior studies to be sensitive to recollection and familiarity respectively. In addition, the magnitudes of 'familiarity-attenuation effects' in perirhinal cortex demonstrated age-invariant correlations with estimates of familiarity strength and memory accuracy, replicating prior findings. Together, the present findings add to the evidence that the neural correlates of recognition memory are largely stable across much of the healthy human adult lifespan.

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.

Differences between young and older adults in unity and diversity of executive functions.

Miyake and colleagues (2000) identified three independent but correlated components of executive function in young adults - set shifting, inhibition, and updating. The present study compared the factor structure in young adults to two groups of older adults (ages 60-73 and 74-98). A three-factor model of shifting, inhibition and updating was confirmed in young adults, but the factors were weakly or uncorrelated. In both older groups, a two-factor solution was indicated, updating/inhibition and shifting, which were moderately correlated in young-older adults, and strongly correlated in the old-older group. A nested factors model in the oldest group revealed a common factor, which loaded on all but one of the tests, and a shifting-specific factor. We concluded that in young adulthood, shifting, updating and inhibition may operate relatively independently. As people age and processing becomes less efficient, they may rely increasingly on general executive control processes, reallocating their limited resources to optimize performance.

Electrophysiological correlates of the perceptual fluency effect on recognition memory in different fluency contexts.

The present study used event-related potentials (ERPs) to investigate the contribution of perceptual fluency to recognition memory in different fluency contexts. In a recognition memory test with a modified remember-know paradigm, we employed conceptually impoverished items (kaleidoscope images) as stimuli and manipulated the perceptual fluency of recognition test cues through masked repetition priming. There were two fluency context conditions. In the random fluency context (RC) condition, primed and unprimed trials were randomly inter-mixed. In the blocked fluency context (BC) condition, primed and unprimed trials were grouped into blocks. Behavioral results showed that priming elevated the incidence of remember hits and the accuracy of remember judgements in the RC condition; no such effects were evident in the BC condition. In addition, priming effects on reaction times were found only for remember hit responses in the RC condition. The ERP results revealed an early100-200 ms effect related to masked repetition priming, which took the form of greater positivity for primed than unprimed trials. This effect was modulated neither by fluency context or response type. The present findings suggest that perceptual fluency induced by masked repetition priming affects recollection-related memory judgments in a specific fluency context and indicate that relative, rather absolute, fluency plays a critical role in influencing recognition memory judgments.

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.

Self-Reference enhances memory for multi-element events judged likely to happen in young and older adults.

We investigated whether the strategy of self-reference can benefit memory for multi-element events, a kind of relational memory that is relatively less studied but highly relevant to daily life. Young and older adults imagined different person-object-location events with reference to themselves and two famous others (i.e., George Clooney and Oprah Winfrey), rated the likelihood that each event would happen, and then completed incidental memory tests on different pairs of elements within the event. We found that self-reference enhanced memory for object-location and person-object pairs in both age groups. Such self-reference effects were observed consistently only for events rated as likely to happen. There was also an overall memory advantage for the higher-likelihood events, which did not differ between young and older adults. Further, the self-reference effects were not correlated with memory functioning in either age group. Retrieval of within-event associations showed a significant level of dependency, which did not differ as a function of reference condition or likelihood category. These findings highlight the ways in which self-reference and prior knowledge improve relational memory, and suggest that the advantage of self-reference is not attributable to increased dependence of elements within complex events.

Self-reference enhances relational memory in young and older adults.

The present study investigated the influence of self-reference on two kinds of relational memory, internal source memory and associative memory, in young and older adults. Participants encoded object-location word pairs using the strategies of imagination and sentence generation, either with reference to themselves or to a famous other (i.e., George Clooney or Oprah Winfrey). Both young and older adults showed memory benefits in the self-reference conditions compared to other-reference conditions on both tests, and the self-referential effects in older adults were not limited by low memory or executive functioning. These results suggest that self-reference can benefit relational memory in older adults relatively independently of basic memory and executive functions.

The role of retrieval mode and retrieval orientation in retrieval practice: insights from comparing recognition memory testing formats and restudying.

The effectiveness of retrieval practice for aiding long-term memory, referred to as the testing effect, has been widely demonstrated. However, the specific neurocognitive mechanisms underlying this phenomenon remain unclear. In the present study, we sought to explore the role of pre-retrieval processes at initial testing on later recognition performance by using event-related potentials (ERPs). Subjects studied two lists of words (Chinese characters) and then performed a recognition task or a source memory task, or restudied the word lists. At the end of the experiment, subjects received a final recognition test based on the remember-know paradigm. Behaviorally, initial testing (active retrieval) enhanced memory retention relative to restudying (passive retrieval). The retrieval mode at initial testing was indexed by more positive-going ERPs for unstudied items in the active-retrieval tasks than in passive retrieval from 300 to 900 ms. Follow-up analyses showed that the magnitude of the early ERP retrieval mode effect (300-500 ms) was predictive of the behavioral testing effect later on. In addition, the ERPs for correctly rejected new items during initial testing differed between the two active-retrieval tasks from 500 to 900 ms, and this ERP retrieval orientation effect predicted differential behavioral testing gains between the two active-retrieval conditions. Our findings confirm that initial testing promotes later retrieval relative to restudying, and they further suggest that adopting pre-retrieval processing in the forms of retrieval mode and retrieval orientation might contribute to these memory enhancements.

Neural correlates of familiarity and conceptual fluency in a recognition test with ancient pictographic characters.

Familiarity and conceptual priming refer to distinct memory expressions and are subtypes of explicit memory and implicit memory, respectively. Given that the neural events that produce conceptual priming may in some cases promote familiarity, distinguishing between neural signals of these two types of memory may further our understanding of recognition memory mechanisms. Although FN400 event-related potentials observed during recognition tests have often been ascribed to familiarity, much evidence suggests that they should instead be ascribed to conceptual fluency. To help resolve this controversy, we studied potentials elicited by unrecognizable ancient Chinese characters. These stimuli were categorized as high or low in meaningfulness based on subjective ratings. Conceptual priming was produced exclusively by repetition of characters high in meaningfulness. During a recognition test in which recollection was discouraged, FN400 old-new effects were observed, and amplitudes of the FN400 potentials varied inversely with familiarity confidence. However, these effects were absent for old items given low meaningfulness ratings. For both high and low meaningfulness, late positive (LPC) potentials were found in old-new comparisons, and LPC amplitudes were greater when higher familiarity confidence was registered during the recognition test. These findings linked familiarity and conceptual fluency with different brain potentials - LPC and FN400, respectively - and provide additional evidence that explicit memory and implicit memory have distinct neural substrates.