Dramatic changes to well-known places go unnoticed.

How well do we know our city? It turns out, much more poorly than we might imagine. We used declarative memory and eye-tracking techniques to examine people's ability to detect modifications to real-world landmarks and scenes in Toronto locales with which they have had extensive experience. Participants were poor at identifying which scenes contained altered landmarks, whether the modification was to the landmarks' relative size, internal features, or relation to surrounding context.

Episodic Memory and Recollection Network Disruptions Following Chemotherapy Treatment in Breast Cancer Survivors: A Review of Neuroimaging Findings.

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.

Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions.

A wide range of cognitive deficits, including memory loss associated with hippocampal dysfunction, have been widely reported in cancer survivors who received chemotherapy. Changes in both white matter and gray matter volume have been observed following chemotherapy treatment, with reduced volume in the medial temporal lobe thought to be due in part to reductions in hippocampal neurogenesis. Pre-clinical rodent models confirm that common chemotherapeutic agents used to treat various forms of non-CNS cancers reduce rates of hippocampal neurogenesis and impair performance on hippocampally-mediated learning and memory tasks.

Reminders activate the prefrontal-medial temporal cortex and attenuate forgetting of event memory.

Replicas of an aspect of an experienced event can serve as effective reminders, yet little is known about the neural basis of such reminding effects. Here we examined the neural activity underlying the memory-enhancing effect of reminders 1 week after encoding of naturalistic film clip events. We used fMRI to determine differences in network activity associated with recently reactivated memories relative to comparably aged, non-reactivated memories.

Reminders reinstate context-specificity to generalized remote memories in rats: relation to activity in the hippocampus and aCC.

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.

Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors.

Background: Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy.

Design: This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'.

Hippocampal and Retrosplenial Goal Distance Coding After Long-term Consolidation of a Real-World Environment.

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.

The hippocampus is critical for value-based decisions guided by dissociative inference.

The hippocampus supports flexible decision-making through memory integration: bridging across episodes and inferring associations between stimuli that were never presented together ('associative inference'). A pre-requisite for memory integration is flexible representations of the relationships between stimuli within episodes (AB) but also of the constituent units (A,B). Here we investigated whether the hippocampus is required for parsing experienced episodes into their constituents to infer their re-combined within-episode associations ('dissociative inference').

Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans.

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.

Multiple Scales of Representation along the Hippocampal Anteroposterior Axis in Humans.

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].

Chemotherapy and cognition: International cognition and cancer task force recommendations for harmonising preclinical research.

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.

The hippocampus and related neocortical structures in memory transformation.

Episodic memories are multifaceted and malleable, capable of being transformed with time and experience at both the neural level and psychological level. At the neural level, episodic memories are transformed from being dependent on the hippocampus to becoming represented in neocortical structures, such as the medial prefrontal cortex (mPFC), and back again, while at the psychological level, detailed, perceptually rich memories, are transformed to ones retaining only the gist of an experience or a schema related to it. Trace Transformation Theory (TTT) initially proposed that neural and psychological transformations are linked and proceed in tandem.

Prior knowledge modulates the neural substrates of encoding and retrieving naturalistic events at short and long delays.

Congruence with prior knowledge and incongruence/novelty have long been identified as two prominent factors that, despite their opposing characteristics, can both enhance episodic memory. Using narrative film clip stimuli, this study investigated these effects in naturalistic event memories - examining behaviour and neural activation to help explain this paradox. Furthermore, we examined encoding, immediate retrieval, and one-week delayed retrieval to determine how these effects evolve over time.

Chemotherapy and cognitive impairment: An animal model approach.

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.

Neurobiological Mechanisms of Chemotherapy-induced Cognitive Impairment in a Transgenic Model of Breast Cancer.

Animal studies have reinforced clinical reports of cognitive impairment in cancer survivors following chemotherapy but, until now, all pre-clinical research in this area has been conducted on normal rodents. The present study investigated the effects of chemotherapy on cognition and underlying biological mechanisms in the FVB/N-Tg (MMTV-neu) 202 Mul/J mouse, a well-characterized transgenic model of breast cancer that has similarities to the tumorigenesis which occurs in humans. Tumor-bearing and control mice received three weekly injections of a combination of methotrexate + 5-fluorouracil, or an equal volume of saline.

Early-Age Running Enhances Activity of Adult-Born Dentate Granule Neurons Following Learning in Rats.

Cognitive reserve, the brain's capacity to draw on enriching experiences during youth, is believed to protect against memory loss associated with a decline in hippocampal function, as seen in normal aging and neurodegenerative disease. Adult neurogenesis has been suggested as a specific mechanism involved in cognitive (or neurogenic) reserve. The first objective of this study was to compare learning-related neuronal activity in adult-born versus developmentally born hippocampal neurons in juvenile male rats that had engaged in extensive running activity during early development or reared in a standard laboratory environment.

The influence of recollection and familiarity in the formation and updating of associative representations.

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.

Environmental enrichment protects against cognitive impairment following chemotherapy in an animal model.

Clinical studies indicate that up to 70% of cancer patients who receive chemotherapy experience cognitive impairment. The present study investigated environmental enrichment as a protective factor against the adverse effects of anticancer drugs on cognitive and biological processes in an animal model. Adult rats were housed in group cages with environmental stimulation or in standard cages for 3 months, before receiving 3 weekly injections of methotrexate + 5-fluorouracil, or equal volumes of saline.

Forgetting Patterns Differentiate Between Two Forms of Memory Representation.

For decades, there has been controversy about whether forgetting is caused by decay over time or by interference from irrelevant information. We suggest that forgetting occurs because of decay or interference, depending on the memory representation. Recollection-based memories, supported by the hippocampus, are represented in orthogonal patterns and are therefore relatively resistant to interference from one another.

Recovering and preventing loss of detailed memory: differential rates of forgetting for detail types in episodic memory.

Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired, while memory for central details is relatively spared.

Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation.

The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it.

Ill-defined problem solving in amnestic mild cognitive impairment: linking episodic memory to effective solution generation.

It is well accepted that the medial temporal lobes (MTL), and the hippocampus specifically, support episodic memory processes. Emerging evidence suggests that these processes also support the ability to effectively solve ill-defined problems which are those that do not have a set routine or solution. To test the relation between episodic memory and problem solving, we examined the ability of individuals with single domain amnestic mild cognitive impairment (aMCI), a condition characterized by episodic memory impairment, to solve ill-defined social problems.

Memory loss in chemotherapy-treated rats is exacerbated in high-interference conditions and related to suppression of hippocampal neurogenesis.

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.