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Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60-80 years) and 26 young participants (20-30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4-8 Hz) and synchronization in gamma (30-45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Fear memory is important for the survival of animals and is associated with certain anxiety disorders, such as posttraumatic stress disorder. A thorough understanding of the molecular mechanisms of fear memory, especially associative fear memory, is imperative. MicroRNA-138 (miR-138) is a widely distributed microRNA in the brain and is locally enriched at synaptic sites. The role of miR-138 in the formation of fear memory is still largely unknown. In this study, a contextual fear conditioning (CFC) paradigm, bioinformatic methods, a luciferase assay, real-time PCR and western blot were used to evaluate the detailed effects of miR-138 on fear memory. We found that miR-138 transiently decreased in the dorsal hippocampus (DH) after CFC training. Upregulation or downregulation of miR-138 in the DH with miR-138 agomir or antagomir treatment significantly impaired or enhanced the formation of CFC memory, respectively. Moreover, the effects of miR-138 in the DH on the formation of CFC memory were achieved by changing the expression of the downstream target gene calpain 1 (Capn1). Taken together, both the in-vitro evidence and the in-vivo evidence presented in this study support the involvement of miR-138 in CFC memory formation, at least partly via the regulation of Capn1-mediated synaptic plasticity changes. Therapeutic use of miR-138/Capn1 is promising as an alternative option in the treatment of fear memory-related anxiety disorders.

According to a neurocomputational theory of cognitive aging, senescent changes in dopaminergic modulation lead to noisier and less differentiated processing. The authors tested a corollary hypothesis of this theory, according to which genetic predispositions of individual differences in prefrontal dopamine (DA) signaling may affect associations between memory functions, particularly in old age. Latent correlations between factors of verbal episodic memory and spatial working memory were compared between individuals carrying different allelic variants of the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences DA availability in prefrontal cortex. In younger adults (n = 973), correlations between memory functions did not differ significantly among the 3 COMT genotypes (r = .35); in older adults (n = 1333), however, the correlation was significantly higher in Val homozygotes (r = .70), whose prefrontal DA availability is supposedly the lowest of all groups examined, than in heterozygotes and Met homozygotes (both rs = .29). Latent means of the episodic memory and working memory factors did not differ by COMT status within age groups. However, when restricting the analysis to the low-performing tertile of older adults (n = 443), we found that Val homozygotes showed lower levels of performance in both episodic memory and working memory than heterozygotes and Met homozygotes. In line with the neurocomputational theory, the observed dedifferentiation of memory functions in older Val homozygotes suggests that suboptimal dopaminergic modulation may underlie multiple facets of memory declines during aging. Future longitudinal work needs to test this conjecture more directly., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

The striatum and medial temporal lobe play important roles in implicit and explicit memory, respectively. Furthermore, recent studies have linked striatal dopamine modulation to both implicit as well as explicit sequence learning and suggested a potential role of the striatum in the emergence of explicit memory during sequence learning. With respect to aging, previous findings indicated that implicit memory is less impaired than explicit memory in older adults and that genetic effects on cognition are magnified by aging. To understand the links between these findings, we investigated effects of aging and genotypes relevant for striatal dopamine on the implicit and explicit components of sequence learning. Reaction time (RT) and error data from 80 younger (20-30 years) and 70 older adults (60-71 years) during a serial reaction time task showed that age differences in learning-related reduction of RTs emerged gradually over the course of learning. Verbal recall and measures derived from the process-dissociation procedure revealed that younger adults acquired more explicit memory about the sequence than older adults, potentially causing age differences in RT gains in later stages of learning. Of specific interest, polymorphisms of the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32, rs907094) and dopamine transporter (DAT, VNTR) genes showed interactive effects on overall RTs and verbal recall of the sequence in older but not in younger adults. Together our findings show that variations in genotypes relevant for dopamine functions are associated more with aging-related impairments in the explicit than the implicit component of sequence learning, providing support for theories emphasizing the role of dopaminergic modulation in cognitive aging and the magnification of genetic effects in human aging., (© 2013 Elsevier Ltd. All rights reserved.)

Aging compromises dopamine transporter (DAT) and receptor mechanisms in the frontostriatal circuitry. In a sample of 1288 younger and older adults, we investigated (i) whether individual differences in genotypes of the DAT gene (i.e., SLC6A3, the DAT variable number of tandem repeat 9/9, 9/10, and 10/10) and in the D2 receptor (DRD2) gene (i.e., the C957T [rs6277] CC and any T) interactively contribute to phenotype variations in episodic memory performance; and (ii) whether these genetic effects are magnified in older adults, because of considerable declines in the dopamine functions. Our results showed that carrying genotypes associated with higher levels of striatal synaptic dopamine (DAT 9/9) and higher density of extrastriatal D2 receptors (C957T CC) were associated with better backward serial recall, an episodic memory task with high encoding and retrieval demands. Critically, the gene-gene interaction effect was reliably stronger in older than in younger adults. In line with the resource modulation hypothesis, our findings suggest that aging-related decline in brain phenotypes (e.g., dopamine functions) could alter the relations between genotypes and behavioral phenotypes (e.g., episodic memory)., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Intraindividual trial-to-trial reaction time (RT) variability is commonly found to be higher in clinical populations or life periods that are associated with impaired cognition. In the present study, higher within-person trial-to-trial RT variability in a perceptual speed task is related to more forgetting and dedifferentiation of memory functions in older adults (aged 60-71 years). More specifically, our study showed that individuals in a high-variability group (n=175) forgot more memory scenes over a 1-week retention interval than individuals in the low-variability group (n=174). In contrast, slower RT speed was associated with poorer episodic memory in general, but unrelated to the amount of forgetting. Moreover, results from multiple group latent factor analyses showed that episodic memory and working memory functions were more highly correlated in the high-variability (r=.63) than in the low-variability (r=.25) group. Given that deficits in dopamine (DA) modulation may underlie increases in RT variability, the present findings are in line with (i) recent animal studies implicating DA in long-term episodic memory consolidation and (ii) neurocomputational work linking DA modulation of performance variability to dedifferentiation of cognitive functions in old age., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The structural and functional brain circuitries supporting episodic memory undergo profound reorganization in childhood and old age. We propose a two-component framework that combines and integrates evidence from child development and aging. It posits that episodic memory builds on two interacting components: (a) the strategic component, which refers to memory control operations, and (b) the associative component, which refers to mechanisms that bind different features of a memory episode into a compound representation. We hypothesize that: (a) children's difficulties in episodic memory primarily originate from low levels of strategic operations, and reflect the protracted development of the prefrontal cortex (PFC); (b) deficits in episodic memory performance among older adults originate from impairments in both strategic and associative components, reflecting senescent changes in the PFC and the medio-temporal lobes (MTL). Initial behavioral and neural evidence is consistent with both hypotheses. The two-component framework highlights the specificities of episodic memory in different age periods, helps to identify and dissociate its components, and contributes to understanding the interplay among maturation, learning, and senescence., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Individual differences in episodic memory are highly heritable. Several studies have linked a polymorphism in the gene encoding the KIBRA protein to episodic memory performance. Results regarding CLSTN2, the gene encoding the synaptic protein calsyntenin 2, have been less consistent, possibly pointing to interactions with other genes. Given that both KIBRA and CLSTN2 are expressed in the medial temporal lobe and have been linked to synaptic plasticity, we investigated whether KIBRA and CLSTN2 interactively modulate episodic memory performance (n=383). We replicated the beneficial effect of the KIBRA T-allele on episodic memory, and discovered that this effect increases with the associative demands of the memory task. Importantly, the memory-enhancing effect of the KIBRA T-allele was boosted by the presence of the CLSTN2 C-allele, which positively affected memory performance in some previous studies. In contrast, the presence of CLSTN2 C-allele led to reduced performance in subjects homozygous for the KIBRA C-allele. Overall, these findings suggest that KIBRA and CLSTN2 interactively modulate episodic memory performance, and underscore the need for delineating the interactive effects of multiple genes on brain and behavior., (2009 Elsevier Ltd. All rights reserved.)

Existing evidence suggests that the organization of cognitive functions may differentiate during development. We investigated two key components of executive functions, memory maintenance and inhibitory control, by applying latent factor models appropriate for examining developmental differences in functional associations among aspects of cognition. Two-hundred and sixty-three children (aged 4 to 14 years) were administered tasks that required maintaining rules in mind or inhibiting a prepotent tendency to respond on the same side as the stimulus. Memory maintenance and inhibitory control were not separable in children of 4-7 or 7-9.5 years, but were differentiated in an older group (9.5-14.5 years).

Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20-30 years) and 30 older (60-70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more "youth-like" load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.

We investigated lifespan differences of confidence calibration in episodic memory, particularly the susceptibility to high-confidence errors within samples of children, teenagers, younger adults, and older adults. Using an associative recognition memory paradigm, we drew a direct link between older adults' associative deficit and high-confidence errors. We predicted that only older adults would show high-confidence error even though their memory performance was at a similar level to that of children. Participants of all ages showed higher confidence following correct responses compared to incorrect responses, demonstrating the ability to calibrate subjective confidence in relation to memory accuracy. However, older adults were disproportionately more likely to indicate high confidence following erroneously remembered word pairs than participants of the other three age groups. Results are discussed in relation to the misrecollection account of high-confidence errors and ageing-related decline in hippocampus-dependent episodic memory functions.

The authors examined life-span differences in the maintenance of skilled episodic memory performance by assessing 100 individuals (10 -11, 12-13, 21-26, and 66-79 years old) 11 months after termination of an intensive multisession mnemonic training program (Y. Brehmer, S.-C. Li, V. Müller, T. von Oertzen, & U. Lindenberger, 2007). Skill maintenance was tested in 2 follow-up sessions, the first without and the second with mnemonic reinstruction. Younger and older adults' average performance levels were stable across time. In contrast, both younger and older children's memory performance improved beyond originally attained levels. Older adults' performance improved from the first to the second follow-up session, presumably profiting from instruction-induced skill reactivation. Results suggest that (a) skill maintenance is largely intact in healthy older adults, (b) older adults need environmental support to fully reactivate their former skill levels (cf. F. I. M. Craik, 1983), and (c) children adapt a skill learned 11 months ago to their increasing cognitive capabilities.

Memory plasticity, or the ability to improve one's memory performance through instruction and training, is known to decline during adulthood. However, direct comparisons among middle childhood, adulthood, and old age are lacking. The authors examined memory plasticity in an age-comparative multisession training study. One hundred and eight participants ages 9-10, 11-12, 20-25, and 65-78 years learned and practiced an imagery-based mnemonic technique to encode and retrieve words by location cues. Individuals of all ages were able to acquire and optimize use of the technique. Older adults and children showed similar baseline performance and improvement through mnemonic instruction. However, in line with tenets from life-span psychology (P. B. Baltes, 1987), children profited more from mnemonic practice and reached higher levels of final performance than did older adults.

In the course of their lives, individuals experience a myriad of events. Some of them leave stable traces, and others fade away quickly. Recent advances in functional imaging methods allow researchers to contrast neuronal patterns of remembered against not remembered events at initial encoding. Research on young adults using functional magnetic resonance imaging (fMRI), intracranial, and standard electroencephalographic (EEG) recordings has identified differences between remembered and not remembered items in patterns of medio-temporal and prefrontal brain activity. However, little is known about the ways in which such neuronal patterns of successful encoding evolve across the lifespan as a function of maturation, senescence, and the accumulation of experience. Here, we first review empirical evidence on neuronal correlates of successful memory from middle childhood to old age. Based on the observation that associative and strategic components of episodic memory seem to follow different age gradients, we propose a conceptual framework for predicting age changes in neuronal patterns of successful encoding.

Memory plasticity, or the ability to improve one's memory performance through instruction and training, is known to decline during adulthood. However, direct comparisons among middle childhood, adulthood, and old age are lacking. The authors examined memory plasticity in an age-comparative multisession training study. One hundred and eight participants ages 9-10, 11-12, 20-25, and 65-78 years learned and practiced an imagery-based mnemonic technique to encode and retrieve words by location cues. Individuals of all ages were able to acquire and optimize use of the technique. Older adults and children showed similar baseline performance and improvement through mnemonic instruction. However, in line with tenets from life-span psychology (P. B. Baltes, 1987), children profited more from mnemonic practice and reached higher levels of final performance than did older adults.

Previous studies have indicated that older adults have a special deficit in the encoding and retrieval of associations. The current study assessed this deficit using ecologically valid name-face pairs. In two experiments, younger and older participants learned a series of name-face pairs under intentional and incidental learning instructions, respectively, and were then tested for their recognition of the faces, the names, and the associations between the names and faces. Under incidental encoding conditions older adults' performance was uniformly lower than younger adults in all three tests, indicating age-related impairments in episodic memory representations. An age-related deficit specific to associations was found under intentional but not under incidental learning conditions, highlighting the importance of strategic associative processes and their decline in older adults. Separate analyses of hits and false alarms indicate that older adults' associative deficit originated from high false alarm rates in the associative test. Older adults' high false alarm rates potentially reflect their reduced ability to recollect the study-phase name-face pairs in the presence of intact familiarity with individual names and faces. [ABSTRACT FROM AUTHOR]

Background: While age-related increases of between-person variability in a variety of cognitive measures are commonly reported in cross-sectional studies, the nature of short-term intraindividual fluctuation in elderly people’s performance is relatively unexplored. Objective: The goal of the present study is to examine short-term fluctuations in elderly people’s sensorimotor functioning and their relations to individual differences in verbal and spatial memory. Methods: Fluctuations in old adults’ (mean = 75.71 years, SD = 6.93 years) sensorimotor performance were investigated by biweekly measurements spanning approximately 7 months. Sensorimotor performance was measured by three walking tasks, including the duration and the number of steps taken to walk a 360-degree circle and to walk 10 feet both at normal and fast pace. Performances of verbal and spatial memory were assessed by weekly measurements of digit memory span, memory for short text and spatial recognition. Results: The magnitude of intraindividual fluctuation in most sensorimotor and memory tasks examined was at least half as great as the level of individual differences across persons. In addition, intraindividual fluctuation in sensorimotor performance is a relatively stable individual attribute, which correlates positively with age and negatively with the levels of sensorimotor, text and spatial memory performance. Although a substantial amount of individual differences in intraindividual fluctuation was shared with mean performance level, variance component and hierarchical regression analyses showed that intraindividual fluctuation in walking steps added significant independent contribution over and above that given by level of performance in predicting text and spatial memory. Conclusion: Taking these results together, we suggest that intraindividual fluctuations in elderly people’s performance should not be ignored or simply treated as measurement error; rather, they are potentially important empirical variables for understanding sensory and cognitive aging and the nature of intraindividual response variations in general.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Identifies six problems brought up in Mewhort et al.'s critique of Lewandowsky and Murdock's model for serial recall based on the theory of distributed associative memory (TODAM). Exaggeration of fears arising from flaws in TODAM memory component; Implementation of deblurring mechanism to answer problems arising from response selection.

• Better memory and boundary processing during navigation in young vs. older adults. • Age × intervention interaction in medial temporal lobe activity. • L-DOPA enhanced boundary processing and spatial learning associated in older adults. • L-DOPA impaired young adults' memory performance during spatial navigation. • Overall, L-DOPA improved location-cue processing relative to boundary processing. Aging is associated with changes in spatial navigation behavior. In addition to an overall performance decline, older adults tend to rely more on proximal location cue information than on environmental boundary information during spatial navigation compared to young adults. The fact that older adults are more susceptible to errors during spatial navigation might be partly attributed to deficient dopaminergic modulation of hippocampal and striatal functioning. Hence, elevating dopamine levels might differentially modulate spatial navigation and memory performance in young and older adults. In this work, we administered levodopa (L-DOPA) in a double-blind within-subject, placebo-controlled design and recorded functional neuroimaging while young and older adults performed a 3D spatial navigation task in which boundary geometry or the position of a location cue were systematically manipulated. An age by intervention interaction on the neural level revealed an upregulation of brain responses in older adults and a downregulation of responses in young adults within the medial temporal lobe (including hippocampus and parahippocampus) and brainstem, during memory retrieval. Behaviorally, L-DOPA had no effect on older adults' overall memory performance; however, older adults whose spatial memory improved under L-DOPA also showed a shift towards more boundary processing under L-DOPA. In young adults, L-DOPA induced a decline in spatial memory performance in task-naïve participants. These results are consistent with the inverted-U-shaped hypothesis of dopamine signaling and cognitive function and suggest that increasing dopamine availability improves hippocampus-dependent place learning in some older adults. [ABSTRACT FROM AUTHOR]

The hippocampus and striatum are core neural circuits involved in spatial learning and memory. Although both neural systems support spatial navigation, experimental and theoretical evidence indicate that they play different roles. In particular, whereas hippocampal place cells generate allocentric neural representations of space that are sensitive to geometric information, striatum-dependent learning is influenced by local landmarks. How human aging affects these different neural representations, however, is still not well understood. In this paper, we combined virtual reality, computational modeling, and neuroimaging to investigate the effects of age upon the neural computation and representation of space in humans. We manipulated the geometry and local landmarks of a virtual environment and examined the effects on memory performance and brain activity during spatial learning. In younger adults, both behavior and brain activity in the medial-temporal lobe were consistent with predictions of a computational model of hippocampus-dependent boundary processing. In contrast, older adults' behavior and medial-temporal lobe activity were primarily influenced by local cue information, and spatial learning was more associated with activity in the caudate nucleus rather than the hippocampus. Together these results point to altered spatial representations and information processing in the hippocampal–striatal circuitry with advancing adult age, which may contribute to spatial learning and memory deficits associated with normal and pathological aging. [ABSTRACT FROM AUTHOR]

Attention and working memory are fundamental for selecting and maintaining behaviorally relevant information. Not only do both processes closely intertwine at the cognitive level, but they implicate similar functional brain circuitries, namely the frontoparietal and the frontostriatal networks, which are innervated by cholinergic and dopaminergic pathways. Here we review the literature on cholinergic and dopaminergic modulations of visual-spatial attention and visual working memory processes to gain insights on aging-related changes in these processes. Some extant findings have suggested that the cholinergic system plays a role in the orienting of attention to enable the detection and discrimination of visual information, whereas the dopaminergic system has mainly been associated with working memory processes such as updating and stabilizing representations. However, since visual-spatial attention and working memory processes are not fully dissociable, there is also evidence of interacting cholinergic and dopaminergic modulations of both processes. We further review gene-cognition association studies that have shown that individual differences in visual-spatial attention and visual working memory are associated with acetylcholine- and dopamine-relevant genes. The efficiency of these 2 transmitter systems declines substantially during healthy aging. These declines, in part, contribute to age-related deficits in attention and working memory functions. We report novel data showing an effect of dopamine COMT gene on spatial updating processes in older but not in younger adults, indicating potential magnification of genetic effects in old age. [ABSTRACT FROM AUTHOR]