Pattern Separation Memory Research Articles

Atypical pattern separation memory and its association with restricted interests and repetitive behaviors in autistic children.

Memory challenges remain understudied in childhood autism. Our study investigates one specific aspect of memory function, known as pattern separation memory, in autistic children. Pattern separation memory refers to the critical ability to store unique memories of similar stimuli; however, its role in childhood autism remains largely uncharted. Our study first uncovered that the pattern separation memory was significantly reduced in autistic children, and then showed that reduced memory performance was linked to their symptoms of repetitive, restricted interest and behavior. We also identified distinct subgroups with profiles of reduced and increased generalization for pattern separation memory. More than 72% of autistic children showed a tendency to reduce memory generalization, focusing heavily on unique details of objects for memorization. This focus made it challenging for them to identify commonalities across similar entities. Interestingly, a smaller proportion of autistic children displayed an opposite pattern of increased generalization, marked by challenges in differentiating between similar yet distinct objects. Our findings advance the understanding of memory function in autism and have practical implications for devising personalized learning strategies that align with the unique memory patterns exhibited by autistic children. This study will be of broad interest to researchers in psychology, psychiatry, and brain development as well as teachers, parents, clinicians, and the wider public.

Pilot study: Stress‐induced noradrenergic activity as potential indicator for practice effects — Association between acute stress, noradrenaline response and practice effects

AbstractBackgroundStress has both enhancing and impairing influences on memory performance. Interestingly, aging has been associated with changes in the stress system as well as a decline in memory performance. Reductions in memory practice effects have gained interest as a risk factor for future cognitive decline, yet research on how stress influences practice effects in older individuals is scarce. Considering the age‐related changes in the stress systems, it is conceivable that exposure to stressors may facilitate the identification of individuals with an absence or attenuation of practice effects.MethodA total of thirty healthy individuals aged 40‐70 years old were subjected to a pattern separation memory task with and without an acute cognitive stressor before encoding. Several salivary alpha amylase (SAA) samples were obtained at different time points as a proxy of noradrenaline activity. Using the change scores on the memory task, we divided participants in learners (exhibiting practice effects) and non‐learners (Figure 1A). Spearman correlation coefficients were calculated to examine the relation between practice effects and SAA levels. Subsequently, an age by SAA interaction on practice scores was explored with a linear model for SAA levels at all time points.ResultIn the entire group, higher baseline SAA levels correlated to worse practice effects (r s= ‐0.46, p=0.02) while controlling for age. The non‐learners showed significantly higher SAA scores at all time points compared to learners (table 1). The learners demonstrated a significant interaction between age and SAA levels after encoding (b=0.02, t=4.35,p=0.0019) on pattern separation difference scores controlled for SAA baseline levels (Figure 1B). No such interaction was observed for non‐learners (b=0.0009, t=0.56, p=0.6; Figure 1C).ConclusionThese results show that elevated baseline noradrenaline activation is associated with the absence of practice effects. Additionally, in learners practice effects were observed in middle‐aged individuals with relatively lower levels of noradrenergic activity. These findings suggest that noradrenergic system activation may be a promising indicator of imminent cognitive decline. Future research is needed to understand variability in noradrenaline activation and practice effects over the adult age span.

Comparison of male and female patients with amnestic mild cognitive impairment: Hippocampal hyperactivity and pattern separation memory performance.

Recent studies have suggested that sex confers a differential risk in the incidence and prevalence of Alzheimer's disease (AD) thought to be the result of the increased lifespan of women compared to men. However, other factors may contribute to risk beyond the effect of increased lifespan. This study examined the role of sex in hippocampal hyperactivity localized to the dentate gyrus (DG)/CA3 subregion of the hippocampus and associated episodic memory impairment, considered a characteristic feature of AD in patients with amnestic mild cognitive impairment (aMCI). While participants with aMCI showed decreased memory performance and increased activation in the DG/CA3 when compared to controls, no significant sex-related differences in performance or activation were observed. Although other factors may contribute to sex differences in the prevalence of AD these findings show that no sex differences are observed in hippocampal dysfunction characteristic of the aMCI phase of AD.

Acute stress-induced cortisol elevation during memory consolidation enhances pattern separation.

Stress is a potent modulator of brain function and particularly mnemonic processes. While chronic stress is associated with long-term deficits in memory, the effects of acute stress on mnemonic functions are less clear as previous reports have been inconsistent. Some studies suggest that cortisol, a stress hormone that modulates biological changes in response to stress, may enhance memory consolidation and impair memory retrieval. However, other studies report no effect of cortisol on either memory consolidation or retrieval. These discrepancies could be due to differences in the timing and sequencing of the experimental procedures or individual differences in participants’ stress response. In the present study, we examined the effect of increased cortisol levels due to acute stress, induced by the Trier Social Stress Test (TSST), on a pattern separation memory task while differentiating the distinct stages of memory processing and controlling for the effects of diurnal variation. Sixty-nine young adults completed a 2-d study in which subjects either underwent the TSST immediately following the encoding part of the memory task, targeting memory consolidation, or immediately prior to the recognition part of the memory task on the second day, targeting memory retrieval. Control subjects completed the same study procedures but underwent a control version of the TSST that did not induce a stress response. Mnemonic discrimination of highly similar stimuli was enhanced by stress induced during consolidation with better discrimination showing a significant correlation with increased cortisol responses. Stress induced during memory retrieval showed no significant effect on memory performance. These findings suggest that stress induced changes in cortisol differentially affect the consolidation and retrieval stages of memory function.

Effects of DNA methyltransferase inhibition on pattern separation performance in mice.

Enhancement of synaptic plasticity through changes in neuronal gene expression is a prerequisite for improved cognitive performance. Moreover, several studies have shown that DNA methylation is able to affect the expression of (e.g. plasticity) genes that are important for several cognitive functions. In this study, the effect of the DNA methyltransferase (DNMT) inhibitor RG108 was assessed on object pattern separation (OPS) task in mice. In addition, its effect on the expression of target genes was monitored. Administration of RG108 before the test led to a short-lasting, dose-dependent increase in pattern separation memory that was not present anymore after 48 h. Furthermore, treatment with RG108 did not enhance long-term memory of the animals when tested after a 24 h inter-trial interval in the same task. At the transcriptomic level, acute treatment with RG108 was accompanied by increased expression of Bdnf1, while expression of Bdnf4, Bdnf9, Gria1 and Hdac2 was not altered within 1 h after treatment. Methylation analysis of 14 loci in the promoter region of Bdnf1 revealed a counterintuitive increase in the levels of DNA methylation at three CpG sites. Taken together, these results indicate that acute administration of RG108 has a short-lasting pro-cognitive effect on object pattern separation that could be explained by increased Bdnf1 expression. The observed increase in Bdnf1 methylation suggests a complex interplay between Bdnf methylation-demethylation that promotes Bdnf1 expression and associated cognitive performance. Considering that impaired pattern separation could constitute the underlying problem of a wide range of mental and cognitive disorders, pharmacological agents including DNA methylation inhibitors that improve pattern separation could be compelling targets for the treatment of these disorders. In that respect, future studies are needed in order to determine the effect of chronic administration of such agents.

P203 Is more better? A protocol to investigate the (neural) effects of repeated vs. single tACS in healthy and pathological ageing

Introduction Healthy and pathological ageing, such as Alzheimer’s disease (AD), both co-occur with disruptions of neuronal activity in memory networks. A prodromal phase of AD is mild cognitive impairment (MCI). Transcranial current stimulation (tCS) has previously been implemented in various settings, showing to have beneficial influences on network connectivity. The recollection and hippocampal networks are vulnerable to AD-related pathology. Targeting these networks with tCS in an early phase may be a valid disease-delaying approach. The hippocampus cannot be stimulated directly, but is closely connected with the angular gyrus. By stimulating the angular gyrus during memory performance makes the recollection network more susceptible and therefore, we hypothesize that indirect effects might be detected in the hippocampus. Further, we will investigate the neural and cognitive effects of single vs multiple sessions. Knowledge about the (long-term) cognitive and neural mechanisms can give valuable insights and pave the ground for exploring tCS as a treatment option in future studies. Objectives We aim to investigate the neural changes underlying tACS on the angular gyrus in MCI patients and in healthy controls using simultaneous fMRI, and the effect of repeated vs. first-session tACS. Performance on a memory task will be compared between sessions. A hippocampus-driven pattern separation memory task will be implemented to investigate if tACS vs. sham during the encoding and consolidation phase has an influence on brain activation during subsequent retrieval. Transfer to a similar, non-practiced task will be assessed at follow-up. Patients & methods or materials & methods 20 MCI patients and 20 healthy controls will receive 1 sham-tACS session, 5 consecutive tACS-sessions, and one follow-up session. FMRI-scans will be obtained during sham, on the first and fifth active session and one week after the last active session. TACS will be applied online during encoding (task-fMRI) and consolidation (resting-state-fMRI) of a pattern separation task. Parallel task-versions will be used in randomized order to minimize learning effects. Within- and between group analyses will be conducted on both the fMRI-data (task and rs-fMRI) and the behavioural data (pattern separation performance). Download : Download high-res image (311KB) Download : Download full-size image

Therapeutic potential of IGF-I on hippocampal neurogenesis and function during aging.

In rats, learning and memory performance decline during normal aging, which is paralleled by a severe reduction of the levels of neurogenesis in the hippocampal dentate gyrus (DG). A promising therapeutic strategy to restore neurogenesis in the hippocampus of old rats and their spatial memory involves the use of insulin-like growth factor-I (IGF-I). The peptide exerts pleiotropic effects in the brain, regulating multiple cellular processes. Thus, 4-week intracerebroventricular (ICV) perfusion of IGF-I significantly restored spatial memory and hippocampal neurogenesis in old male rats. Similar results were achieved by ICV IGF-I gene therapy in aging female rats. Thus, the treatment seemed to increase the number of immature neurons in the DG of 28 mo old rats, which was paralleled by an increase in the accuracy of the animals to remember specific patterns, which is known as pattern separation memory. The DG is thought to be the main hippocampal structure involved in pattern separation memory and there is evidence that the level of neurogenesis in the DG is directly related to pattern separation performance in rodents. Summing up, IGF-I emerges as a promising restorative molecule for increasing hippocampal neurogenesis and memory accuracy in aged individuals and possibly, in neurodegenerative pathologies.

Overactive Pattern Separation Memory Associated with Negative Emotionality in Adults Diagnosed with Autism Spectrum Disorder.

Bowler et al. (Journal of Autism and Developmental Disorders 44(9):2355-2362. doi:10.1007/s10803-014-2105-y, 2014) have suggested that a specific memory impairment in autism spectrum disorders (ASD) arises from hippocampal failure to consolidate multiple related pieces of information. Twenty-four adults diagnosed with ASD and matched healthy controls completed a pattern separation memory task that is known to critically depend on hippocampal involvement. They additionally completed questionnaires regarding anxiety, depression, and behavioral motivation. Specific deficits in pattern separation were significantly correlated with negative emotionality; the best predictor of memory deficit was from a measure of achievement motivation that has also been associated with hyperactivity and impulsivity. In the context of impaired emotion regulation in ASD, there is a need for integrated cognitive, affective, and neural systems approaches to build targeted interventions.

A possible negative influence of depression on the ability to overcome memory interference

Pattern separation is a mechanism for encoding memories, whereby distinct memory representations are created for very similar stimuli and events. It has been proposed that depression negatively impacts pattern separation abilities. However, a link between depression and performance in memory tasks requiring pattern separation is still unclear even though it is well established that depression is associated with reduced declarative memory performance and decreased hippocampal volume. Accordingly, we designed a study to investigate the relationship between pattern separation performance and the severity of depression symptoms in an otherwise healthy population. Participants completed a pattern separation memory test and a set of questionnaires to gauge their level of depression. We found a negative relationship between depression scores and pattern separation scores. These results provide support for the idea that depression is negatively related to pattern separation performance.