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Focuses on the autobiographical memory in older adults regarding contextually specific episodic details. Overview of an instrument for quantifying episodic and semantic contributions to personal remote memory; Distinction between episodic and nonepisodic facets of autobiographical memory; Age effects on potentially separable components of autobiographical memory.

The purpose of this study was to investigate the effects of aging on memory for object identity and object location to determine whether aging affects both posterior neocortical areas that are domain-specific and other brain regions, such as pre-frontal cortex, that are involved in encoding and retrieval regardless of the information that is processed (domain-general). We used positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) in younger and older participants while they were engaged in encoding and retrieving information about object identity and object location. Compared to young adults, older adults showed decreased activation in domain-specific regions of inferior parietal and inferior temporal cortex while engaged in processing (encoding and retrieving) information about object location and object identity, respectively. This decreased specificity in the older adults was accompanied by greater domain-general activation in right prefrontal and premotor cortex during perceptual encoding than during retrieval. Conversely, the younger participants showed greater domain-general activation in right extrastriate cortex (Brodmann area (BA) 18) during retrieval. Moreover, we found that medial temporal and frontal lobes were synergistically activated in younger adults but not in older adults. The pattern of decreased specificity of activation in posterior neocortex with greater activation in anterior neocortex suggests that, with age, compensatory domain-general mechanisms in anterior neocortex are recruited to mitigate altered domain-specific processes. Thus, the results of the present study indicate that the relation between the presumed integrity of various structures, such as the hippocampus, prefrontal cortex, and posterior neocortex, and their pattern of activation, is a complex one that is influenced by age, by the perceptual and cognitive demands of the task and their interaction. [Copyright &y& Elsevier]

Summary The ability to represent the world accurately relies on simultaneous coarse and fine-grained neural information coding, capturing both gist and detail of an experience. The longitudinal axis of the hippocampus may provide a gradient of representational granularity in spatial and episodic memory in rodents and humans [ 1–8 ]. Rodent place cells in the ventral hippocampus exhibit significantly larger place fields and greater autocorrelation than those in the dorsal hippocampus [ 1, 9–11 ], which may underlie a coarser and slower changing representation of space [ 10, 12 ]. Recent evidence suggests that properties of cellular dynamics in rodents can be captured with fMRI in humans during spatial navigation [ 13 ] and conceptual learning [ 14 ]. Similarly, mechanisms supporting granularity along the long axis may also be extrapolated to the scale of fMRI signal. Here, we provide the first evidence for separable scales of representation along the human hippocampal anteroposterior axis during navigation and rest by showing (1) greater similarity among voxel time courses and (2) higher temporal autocorrelation in anterior hippocampus (aHPC), relative to posterior hippocampus (pHPC), the human homologs of ventral and dorsal rodent hippocampus. aHPC voxels exhibited more similar activity at each time point and slower signal change over time than voxels in pHPC, consistent with place field organization in rodents. Importantly, similarity between voxels was related to navigational strategy and episodic memory. These findings provide evidence that the human hippocampus supports an anterior-to-posterior gradient of coarse-to-fine spatiotemporal representations, suggesting the existence of a cross-species mechanism, whereby lower neural similarity supports more complex coding of experience. [ABSTRACT FROM AUTHOR]

Long-term memory disturbances are amongst the most common and disruptive cognitive symptoms experienced by breast cancer survivors following chemotherapy. To date, most clinical assessments of long-term memory dysfunction in breast cancer survivors have utilized basic verbal and visual memory tasks that do not capture the complexities of everyday event memories. Complex event memories, including episodic memory and autobiographical memory, critically rely on hippocampal processing for encoding and retrieval. Systemic chemotherapy treatments used in breast cancer commonly cause neurotoxicity within the hippocampus, thereby creating a vulnerability to memory impairment. We review structural and functional neuroimaging studies that have identified disruptions in the recollection network and related episodic memory impairments in chemotherapy-treated breast cancer survivors, and argue for the need to better characterize hippocampally mediated memory dysfunction following chemotherapy treatments. Given the importance of autobiographical memory for a person's sense of identity, ability to plan for the future, and general functioning, under-appreciation of how this type of memory is impacted by cancer treatment can lead to overlooking or minimizing the negative experiences of breast cancer survivors, and neglecting a cognitive domain that may benefit from intervention strategies.

Conditioned fear memories that are context-specific shortly after conditioning generalize over time. We exposed rats to a context reminder 30 d after conditioning, which served to reinstate context-specificity, and investigated how this reminder alters retrieval-induced activity in the hippocampus and anterior cingulate cortex (aCC) relative to a no reminder condition. c-Fos expression in dorsal CA1 was observed following retrieval in the original context, but not in a novel context, whether or not the memory was reactivated, suggesting that dCA1 retains the context-specific representation. c-Fos was highly expressed in aCC following remote memory testing in both contexts, regardless of reminder condition, indicating that aCC develops generalized representations that are insensitive to memory reactivation., (© 2020 Sekeres et al.; Published by Cold Spring Harbor Laboratory Press.)

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (>2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the distance to the goal in the newly learned campus, as well as in familiar environments when the future route contained many turns. By contrast retrosplenial cortex only tracked the distance to the goal in the familiar campus. All of these responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and underscore the notion that the hippocampus continues to play a role in navigation when detailed processing of the environment is needed for navigation., (© The Author(s) 2019. Published by Oxford University Press.)

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation., (© 2018 Wiley Periodicals, Inc.)

Cancer survivors who undergo chemotherapy for non-CNS tumours often report substantial cognitive disturbances that adversely affect quality of life, during and after treatment. The neurotoxic effects of anti-cancer drugs have been confirmed in clinical and pre-clinical research. Work with animals has also identified a range of factors and underlying mechanisms that contribute to chemotherapy-induced cognitive impairment. However, there is a continuing need to develop standard cognitive testing procedures for validation and comparison purposes, broaden the search for biological and neurochemical mechanisms, and develop improved animal models for investigating the combined effects of treatment, the disease, and other potential factors (e.g., age, stress). In this paper, a working group, formed under the auspices of the International Cognition and Cancer Task Force, reviews the state of pre-clinical research, formulates strategic priorities, and provides recommendations to guide animal research that meaningfully informs clinical investigations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A substantial number of cancer survivors who undergo chemotherapy report cognitive disturbances that severely limit daily function (chemobrain). Despite supportive neuropsychological evidence, there is controversy over whether cognitive impairment is caused by the chemotherapy or is the result of potentially confounding factors that include the disease itself, age, and psychological stress. Our research program, conducted on rodents, has confirmed that a range of cognitive processes, mediated in particular by hippocampal and prefrontal brain regions, are affected by anticancer drugs in combination with tumor development and that many of the effects are long lasting. This work has also provided evidence of protective factors (cognitive reserve, physical exercise, environmental enrichment) and the potential of pharmacological treatment (donepezil) interventions in reducing these effects. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Prior representations affect future learning. Little is known, however, about the effects of recollective or familiarity-based representations on such learning. We investigate the ability to reuse or reassociate elements from recollection- and familiarity-based associations to form new associations. Past neuropsychological research suggests that hippocampal, and presumably recollective, representations are more flexible than extra-hippocampal, presumably familiarity-based, representations. We therefore hypothesize that the elements of recollective associations, as opposed to familiarity-based representations, may be more easily manipulated and decoupled from each other, and facilitate the formation of new associations. To investigate this hypothesis we used the AB/AC learning paradigm. Across two recall studies we observed an advantage in learning AC word pairs if AB word pairs were initially recollected. Furthermore, AB word pairs were more likely to intrude during a final AC test if those AB word pairs were initially familiarity-based. A third experiment using a recognition version of the AB/AC paradigm ruled out the possibility that our findings were due to memory strength. Our results support the idea that elements in recollective associative traces may be more discretely coded, leading to their flexible use, whereas elements in familiarity-based associative traces are less flexible., (© 2017 Ozubko et al.; Published by Cold Spring Harbor Laboratory Press.)

Drugs used to treat cancer have neurotoxic effects that often produce memory loss and related cognitive deficits. In a test of the hypothesis that chemotherapy-induced cognitive impairment is related to a loss of inhibitory control, rats injected with a combination of methotrexate+5-fluouracil or equal volumes of saline, were administered a retroactive interference task in which memory for a learned discrimination problem was tested under conditions of high- and low-interference. The drugs had no effect on original learning or on re-learning the discrimination response when there was little interference, but the chemotherapy group was severely impaired in the hippocampus-sensitive, high-interference memory test. The impaired performance correlated significantly with reduced neurogenesis in the hippocampus. The failure to suppress interfering influences is consistent with a breakdown in pattern separation, a process that distinguishes and separates overlapping neural representations of experiences that have a high degree of similarity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Food combinations have been associated with lower incidence of Alzheimer's disease. We hypothesized that a combination whole-food diet containing freeze-dried fish, vegetables, and fruits would improve cognitive function in TgCRND8 mice by modulating brain insulin signaling and neuroinflammation. Cognitive function was assessed by a comprehensive battery of tasks adapted to the Morris water maze. Unexpectedly, a "Diet × Transgene" interaction was observed in which transgenic animals fed the whole-food diet exhibited even worse cognitive function than their transgenic counterparts fed the control diet on tests of spatial memory (p < 0.01) and strategic rule learning (p = 0.034). These behavioral deficits coincided with higher hippocampal gene expression of tumor necrosis factor-α (p = 0.013). There were no differences in cortical amyloid-β peptide species according to diet. These results indicate that a dietary profile identified from epidemiologic studies exacerbated cognitive dysfunction and neuroinflammation in a mouse model of familial Alzheimer's disease. We suggest that normally adaptive cellular responses to dietary phytochemicals were impaired by amyloid-beta deposition leading to increased oxidative stress, neuroinflammation, and behavioral deficits., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Chemotherapy, used for the treatment of cancer, often produces cognitive impairment that has been related to suppression of neurogenesis. Physical exercise, which promotes neurogenesis, is known to improve cognitive function in neurologically challenged animals and humans. It is unknown whether exercise similarly protects against chemotherapy-induced cognitive impairment and whether recovery of neurogenesis is a critical factor., Objective: The present study investigated the relationship between hippocampal neurogenesis and cognitive performance in chemotherapy-treated rats that engaged in different amounts of physical activity., Methods: Groups of rats, housed individually in standard cages or in specially designed cages that allowed unlimited access to a running wheel, received three injections of the chemotherapeutic drugs methotrexate and 5-fluorouracil, or equal volumes of saline. They were then administered the following cognitive tests in a water maze: (1) spatial memory (SM), (2) cued memory, (3) non-matching to sample (NMTS) rule learning; (4) delayed NMTS (DNMTS). Hippocampal neurogenesis was quantified by counting doublecortin-expressing cells in the dentate gyrus., Results: Chemotherapy administered to rats in standard cages resulted in a significant reduction in hippocampal neurogenesis and impaired performance on the SM, NMTS, and DNMTS tasks. In rats receiving chemotherapy and housed in exercise cages, neurogenesis was not suppressed and cognitive performance was similar to controls., Conclusions: Physical exercise can reduce cognitive deficits that result from chemotherapy and this effect is mediated, at least in part, by preventing suppression of drug-induced hippocampal neurogenesis. The results suggest benefits of exercise in preventing or treating cognitive impairment associated with chemotherapy.

This review evaluates three current theories--Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In this study, we report changes in psychosocial function in two groups of older adults that participated in the experimental trial of our cognitive rehabilitation program. The results, based on tests that measured a range of psychosocial attributes, showed that, following training, participants improved in terms of overall well-being, as well as in specific areas that included perceived happiness, coping strategies, and quality of life. An important finding was that improvements were also observed in long-term follow-up testing. Both groups benefited from training, but the effect was greater in the group that received training before undergoing a control procedure. The results, which show that the benefits of our rehabilitation program extend into the psychosocial domain, underscore the potentially important relationship between psychosocial factors and cognitive performance in older adults.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.

This study reports the effects of a 12-week multimodular cognitive rehabilitation training program on memory performance in two groups of older adults. In the Memory Training module, participants were instructed on the nature of memory and how to improve memory performance; internal and external strategies were described and practiced over the training sessions. Memory performance was assessed by four tests: Alpha Span, Brown-Peterson, Hopkins Verbal Learning Test - Revised (HVLT-R), and Logical Stories. One group received training on entry into the study (Early Training Group, ETG), the other after a 3-month delay (Late Training Group, LTG). The results showed no training-related improvement in working memory (Alpha Span), primary memory (Brown-Peterson, HVLT-R), or recognition memory (HVLT-R). While the most direct analyses of a training effect (analyses of covariance) rarely demonstrated significant effects, exploratory analyses provided some evidence for a training benefit in several measures of secondary memory (Logical Stories; HVLT-R) and strategic processing (Brown-Peterson; Logical Stories; HVLT-R). Positive results were largely restricted to the ETG, possibly because the LTG lost motivation as a consequence of their delayed training. The results need to be treated with caution, but are promising for the rehabilitation of memory functioning in older adults.

Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.

This study provides an introduction to, and overview of, several papers that resulted from a randomized control trial that evaluated a new cognitive rehabilitation protocol. The program was designed to improve general strategic abilities in ways that would be expressed in a broad range of functional domains. The trial, which was conducted on a sample of older adults who had experienced normal age-related cognitive decline, assessed performance in the following domains: memory, goal management, and psychosocial status. The general rationale for the trial, the overall experimental design, and the approach to statistical analyses that are relevant to each paper are described here. The results for each functional domain are reported in separate papers in this series.

Higher education is associated with less age-related decline in cognitive function, but the mechanism of this protective effect is unknown. The authors examined the effect of age on the relation between education and brain activity by correlating years of education with activity measured using functional MRI during memory tasks in young and older adults. In young adults, education was negatively correlated with frontal activity, whereas in older adults, education was positively correlated with frontal activity. Medial temporal activity was associated with more education in young adults but less education in older adults. This suggests that the frontal cortex is engaged by older adults, particularly by the highly educated, as an alternative network that may be engaged to aid cognitive function., (((c) 2005 APA, all rights reserved).)