Performance In Episodic Memory Tasks Research Articles

Leptin-based hexamers facilitate memory and prevent amyloid-driven AMPA receptor internalisation and neuronal degeneration.

Key pathological features of Alzheimer's disease (AD) include build-up of amyloid β (Aβ), which promotes synaptic abnormalities and ultimately leads to neuronal cell death. Metabolic dysfunction is known to influence the risk of developing AD. Impairments in the leptin system have been detected in AD patients, which has fuelled interest in targeting this system to treat AD. Increasing evidence supports pro-cognitive and neuroprotective actions of leptin and these beneficial effects of leptin are mirrored by a bioactive leptin fragment (leptin116-130 ). Here we extend these studies to examine the potential cognitive enhancing and neuroprotective actions of 8 six-amino acid peptides (hexamers) derived from leptin116-130 . In this study, we show that four of the hexamers (leptin116-121, 117-122, 118-123 and 120-125 ) replicate the ability of leptin to promote α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and facilitate hippocampal synaptic plasticity. Moreover, the pro-cognitive effects of the hexamers were verified in behavioural studies, with the administration of leptin117-122 enhancing performance in episodic memory tasks. The bioactive hexamers replicated the neuroprotective actions of leptin by preventing the acute hippocampal synapto-toxic effects of Aβ, and the chronic effects of Aβ on neuronal cell viability, Aβ seeding and tau phosphorylation. These findings provide further evidence to support leptin and leptin-derived peptides as potential therapeutics for AD.

Slow wave activity moderates the association between new learning and traumatic brain injury severity.

Sleep-wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep-wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity. Forty-two moderate to severe TBI participants, 12-47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, and sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performance. We found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performance than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performance: higher SWA was more strongly associated to better memory performance in more severe TBI compared to milder TBI. This study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.

Memory for neutral, emotional and trauma-related information in sexual abuse survivors

ABSTRACTPrevious studies have shown that trauma-exposed individuals, including survivors of sexual abuse, show inferior performance in episodic memory tasks compared to non-exposed controls. This, however, has mainly been tested using neutral content. Our goal in this study was to determine whether this relative impairment in episodic memory extends to generally emotional and trauma-related content. Twenty-seven sexual abuse survivors and 27 control women participated in the study. They listened to stories with three content types (neutral, generally emotional and trauma-related) and performed a free-recall task immediately and 30 minutes later. Sexual abuse survivors showed poorer recall of neutral material compared to control participants. Lower recall was also observed for generally emotional content. However, importantly, there was no difference between groups in the recall of trauma-related content. The main novel contribution of this study is the demonstration that verbal episodic memory is not impaired for non-autobiographical trauma-related content in sexual abuse survivors. We discuss how this could be explained by personal relevance and attentional capture.

Functional connectivity pattern during rest within the episodic memory network in association with episodic memory performance in bipolar disorder

In this study, we sought to examine the intrinsic functional organization of the episodic memory network during rest in bipolar disorder (BD). The previous work suggests that deficits in intrinsic functional connectivity may account for impaired memory performance. We hypothesized that regions involved in episodic memory processing would reveal aberrant functional connectivity in patients with bipolar disorder. We examined 21 patients with BD and 21 healthy matched controls who underwent functional magnetic resonance imaging (fMRI) during a resting condition. We did a seed-based functional connectivity analysis (SBA), using the regions of the episodic memory network that showed a significantly different activation pattern during task-related fMRI as seeds. The functional connectivity scores (FC) were further correlated with episodic memory task performance. Our results revealed decreased FC scores within frontal areas and between frontal and temporal/hippocampal/limbic regions in BD patients in comparison with controls. We observed higher FC in BD patients compared with controls between frontal and limbic regions. The decrease in fronto-frontal functional connectivity in BD patients showed a significant positive association with episodic memory performance. The association between task-independent dysfunctional frontal-limbic FC and episodic memory performance may be relevant for current pathophysiological models of the disease.

Beneficial effect of trait worry on episodic retrieval: A link overshadowed by trait anxiety

We investigated how individual differences in anxiety affect different forms of episodic retrieval. Specifically, we measured the level of trait anxiety and trait worry using well-known scales of these constructs and observed their impact on tasks requiring the recognition, cued recall or free recall of previously presented information. In a series of three experiments, using multiple linear regression analysis, we consistently found that trait anxiety and trait worry exert an opposite partial effect on free recall performance, a pattern referred to as suppression (e.g. McFatter, 1979, Tzelgov& Henik, 1991). Our results thus show that once the level of trait anxiety is controlled, higher levels of trait worry are associated with better performance in episodic memory tasks requiring effortful, strategic retrieval. We interpret our results using the cognitive avoidance theory of worry (Borkovec, Ray & Stober, 1998) and the attentional control theory of anxiety (Eysenck et al., 2007).

Lateral temporal hyper-activation as a novel biomarker of mild cognitive impairment

Memory dysfunction in mild cognitive impairment (MCI) due to Alzheimer's pathology is primarily associated with episodic memory deficits linked to deterioration of the medial temporal lobes (MTLs). Currently, there is a call to discover novel biomarkers of MCI in order to improve research criteria. Functional activation differences in MCI during episodic memory-task performance are often evidenced in the MTLs, and frontal and parietal lobes, but it has been suggested that examination of working memory (WM) differences may be more useful in detecting MCI. In the current study, MCI and control participants performed a complex WM span (CWMS) task while functional magnetic resonance imaging (fMRI) data were acquired. Results indicated hyper-activation of the lateral temporal lobes, MTLs, and frontal and parietal regions during encoding and maintenance, and hyper-activation of the lateral temporal, frontal, and parietal lobes during CWMS recall for the MCI participants. Medial and lateral temporal differences during encoding and maintenance are consistent with previous findings, but lateral temporal differences are often not elaborated upon. Hyper-activation of the lateral temporal lobes during WM encoding and maintenance, and also during recall, suggests that this region may provide valuable information regarding WM impairment in MCI and Alzheimer's. Given that whole-brain functional imaging of the MTLs is often limited due to artifact and partial voluming of sub-fields, examination of lateral temporal differences may provide a novel biomarker related to WM impairment in MCI.

Ensembles of human MTL neurons “jump back in time” in response to a repeated stimulus

Episodic memory, which depends critically on the integrity of the medial temporal lobe (MTL), has been described as "mental time travel" in which the rememberer "jumps back in time." The neural mechanism underlying this ability remains elusive. Mathematical and computational models of performance in episodic memory tasks provide a specific hypothesis regarding the computation that supports such a jump back in time. The models suggest that a representation of temporal context, a representation that changes gradually over macroscopic periods of time, is the cue for episodic recall. According to these models, a jump back in time corresponds to a stimulus recovering a prior state of temporal context. In vivo single-neuron recordings were taken from the human MTL while epilepsy patients distinguished novel from repeated images in a continuous recognition memory task. The firing pattern of the ensemble of MTL neurons showed robust temporal autocorrelation over macroscopic periods of time during performance of the memory task. The gradually-changing part of the ensemble state was causally affected by the visual stimulus being presented. Critically, repetition of a stimulus caused the ensemble to elicit a pattern of activity that resembled the pattern of activity present before the initial presentation of the stimulus. These findings confirm a direct prediction of this class of temporal context models and may be a signature of the mechanism that underlies the experience of episodic memory as mental time travel.

The effect of Neuregulin 1 on neural correlates of episodic memory encoding and retrieval

Neuregulin 1 (NRG1) has been found to be associated with schizophrenia. Impaired performance in episodic memory tasks is an often replicated finding in this disorder. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and medial temporal areas. Therefore, it is of interest whether genes associated with the disorder, such as NRG1, modulate episodic memory performance and its neural correlates.Ninety-four healthy individuals performed an episodic memory encoding and a retrieval task while brain activation was measured with functional MRI. All subjects were genotyped for the single nucleotide polymorphism (SNP) rs35753505 in the NRG1 gene. The effect of genotype on brain activation was assessed with fMRI during the two tasks.While there were no differences in performance, brain activation in the cingulate gyrus (BA 24), the left middle frontal gyrus (BA 9), the bilateral fusiform gyrus and the left middle occipital gyrus (BA 19) was positively correlated with the number of risk alleles in NRG1 during encoding. During retrieval brain activation was positively correlated with the number of risk alleles in the left middle occipital gyrus (BA 19).NRG1 genotype does modulate brain activation during episodic memory processing in key areas for memory encoding and retrieval. The results suggest that subjects with risk alleles show hyperactivations in areas associated with elaborate encoding strategies.

Applying an Exemplar Model to the Artificial-Grammar Task: Inferring Grammaticality from Similarity

We present three artificial-grammar experiments. The first used position constraints, and the second used sequential constraints. The third varied both the amount of training and the degree of sequential constraint. Increasing both the amount of training and the redundancy of the grammar benefited participants' ability to infer grammatical status; nevertheless, they were unable to describe the grammar. We applied a multitrace model of memory to the task. The model used a global measure of similarity to assess the grammatical status of the probe and captured performance both in our experiments and in three classic studies from the literature. The model shows that retrieval is sensitive to structure in memory, even when individual exemplars are encoded sparsely. The work ties an understanding of performance in the artificial-grammar task to the principles used to understand performance in episodic-memory tasks.

Ketamine Disrupts Frontal and Hippocampal Contribution to Encoding and Retrieval of Episodic Memory: An fMRI Study

The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine produces episodic memory deficits. We used functional magnetic resonance imaging to characterize the effects of ketamine on frontal and hippocampal responses to memory encoding and retrieval in healthy volunteers using a double-blind, placebo-controlled, randomized, within-subjects comparison of two doses of intravenous ketamine. Dissociation of the effects of ketamine on encoding and retrieval processes was achieved using two study-test cycles: in the first, items were encoded prior to drug infusion and retrieval tested, during scanning, on drug; in the second, encoding was scanned on drug, and retrieval tested once ketamine plasma levels had declined. We additionally determined the interaction of ketamine with the depth of processing that occurred at encoding. A number of effects upon task-dependent activations were seen. Overall, our results suggest that left frontal activation is augmented by ketamine when elaborative semantic processing is required at encoding. In addition, successful encoding on ketamine is supplemented by additional non-verbal processing that is incidental to task demands. The effects of ketamine at retrieval are consistent with impaired access to accompanying contextual features of studied items. Our findings show that, even when overt behaviour is unimpaired, ketamine has an impact upon the recruitment of key regions in episodic memory task performance.

Genetic Contributions to Individual Differences in Memory Performance

This paper discusses generally the potential effects of genetic markers on individual differences in cognitive performance. Research on the role of two genetic markers related to the immune system—complement factor C3 and haptoglobin—and one genetic marker—apolipoprotein E (ApoE)—and the interaction with environmental conditions of cognitive support at memory encoding and retrieval are discussed in particular. Data from an ongoing longitudinal study are used to illustrate that the two markers of the immune system are strongly associated with performance in episodic memory tasks, although there is no association to semantic memory. Cross-sectional data reveal a relatively weak association between apolipoprotein E and memory performance. Preliminary analyses of longitudinal data reveal a somewhat stronger association between this genetic marker and some aspects of episodic memory performance.