Search

Cognitive abilities are hypothesized to affect survival and life span in nonhuman animals. However, most tests of this hypothesis have relied on interspecific comparisons of indirect measures of cognitive ability, such as brain size. We present direct evidence that individual variation in cognitive abilities is associated with differences in life span in a wild food caching bird. We measured the spatial cognitive abilities and tracked the life span of 227 mountain chickadees ( Poecile gambeli ) in their natural environment and found that individuals with better spatial learning and memory abilities involved in food caching lived longer. These results confirm that enhanced cognitive abilities can be associated with longer life in wild animals and that selection on cognitive abilities can lead to increased life span.

The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the lifespan is unclear. One cognitive domain that is affected early in the course of Alzheimer's disease is spatial cognition, yet the evidence for APOE-related changes in spatial cognition is mixed. In this meta-analysis we assessed the impact of carrying the APOE4 allele on five subdomains of spatial cognition across the lifespan. We included studies of healthy human participants where an APOE4-carrier group (heterozygous or homozygous) could be compared to a homozygous group of APOE3-carriers. We identified 156 studies in total from three databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review. APOE4 carriers scored significantly lower than APOE3 carriers (θˆ = -.08 [-.14, -.02]) on tests of spatial long-term memory; this effect was very small and was not modulated by age. On other subdomains of spatial cognition (spatial construction, spatial working memory, spatial reasoning, navigation) there were no effects of genotype. Overall, our results demonstrate that the APOE4 allele exerts little influence on spatial cognitive abilities in healthy adults., (Copyright © 2024. Published by Elsevier Ltd.)

Menopause is an endocrine shift leading to increased vulnerability for cognitive impairment and dementia risk factors, in part due to loss of neuroprotective circulating estrogens. Systemic replacement of estrogen post-menopause has limitations, including risk for estrogen-sensitive cancers. A promising therapeutic approach therefore might be to deliver estrogen only to the brain. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in ovariectomized mice (a surgical menopause model). We treated mice with the prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17β-estradiol only in the brain. Young and middle-aged C57BL/6 J mice received ovariectomy and subcutaneous implant containing vehicle or DHED and underwent cognitive testing to assess memory after 1-3.5 months of treatment. Low and medium doses of DHED did not alter metabolic status in middle-aged mice. In both age groups, DHED treatment improved spatial memory in ovariectomized mice. Additional testing in middle-aged mice showed that DHED treatment improved working and recognition memory in ovariectomized mice. These results lay the foundation for future studies determining if this intervention is as efficacious in models of dementia with comorbid risk factors., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Moderate physical exercise has positive effects on memory. The present study aimed to investigate the impact of long-term exercise on spatial memory in developing mice, as well as its association with the cholinergic system, antioxidant activities, apoptosis factor, and BDNF/PI3K/Akt/CREB pathway in the brain. In this study, Y maze and Novel object recognition (NOR) tests were employed to assess the impact of long-term voluntary exercise on memory. The cholinergic system, antioxidant activities, and apoptosis factors in the brain were quantified using Elisa. Additionally, western blot analysis was conducted to determine the expression of relevant proteins in the BDNF/PI3K/Akt/CREB pathway. The findings demonstrated that prolonged voluntary wheel running exercise enhanced memory in developing mice, concomitant with increased catalase (CAT) activity and decreased malondialdehyde (MDA) levels in the brain. Moreover, it could also increase the hippocampal acetylcholine (ACh) content and suppress the expression of neuronal apoptosis protein. Additionally, exercise also upregulated the expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphoinositide 3 kinases (PI3K), Akt, cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These findings suggest that long-term voluntary wheel running exercise improves the spatial memory of developing mice by modulating the cholinergic system, antioxidant activities, apoptosis factors, and activating the BDNF/PI3K/Akt/CREB pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite considerable research into the structure of cognition in non-human animal species, there is still much debate as to whether animal cognition is organised as a series of discrete domains or an overarching general cognitive factor. In humans, the existence of general intelligence is widely accepted, but less work has been undertaken in animal psychometrics to address this question. The relatively few studies on non-primate animal species that do investigate the structure of cognition rarely include tasks assessing social cognition and focus instead on physical cognitive tasks. In this study, we tested 36 wild Western Australian magpies (Gymnorhina tibicen dorsalis) on a battery of three physical (associative learning, spatial memory, and numerical assessment) and one social (observational spatial memory) cognitive task, to investigate if cognition in this species fits a general cognitive factor model, or instead one of separate physical and social cognitive domains. A principal component analysis (PCA) identified two principal components with eigenvalues exceeding 1; a first component onto which all three physical tasks loaded strongly and positively, and a second component onto which only the social task (observational spatial memory) loaded strongly and positively. These findings provide tentative evidence for separate physical and social cognitive domains in this species, and highlight the importance of including tasks assessing both social and physical cognition in cognitive test batteries., (© 2024. The Author(s).)

Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, is well recognized for its antioxidant properties, blood glucose regulation, and fat mass reduction capability. However, its effect on the central nervous system remains unclear. Here, we investigated the effects of oligonol on brain in a high-fat diet (HFD) fed mouse model, and SH-SY5Y neuronal cells and primary cultured cortical neuron under insulin resistance conditions. HFD mice were orally administered oligonol (20 mg/kg) daily, and SH-SY5Y cells and primary cortical neurons were pretreated with 500 ng/mL oligonol under in vitro insulin resistance conditions. Our findings revealed that oligonol administration reduced blood glucose levels and improved spatial memory function in HFD mice. In vitro data demonstrated that oligonol protected neuronal cells and enhanced neural structure against insulin resistance. We confirmed RNA sequencing in the oligonol-pretreated insulin-resistant SH-SY5Y neuronal cells. Our RNA-sequencing data indicated that oligonol contributes to metabolic signaling and neurite outgrowth. In conclusion, our study provides insights into therapeutic potential of oligonol with respect to preventing neuronal cell damage and improving neural structure and cognitive function in HFD mice., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Sporting experience plays a pivotal role in shaping exercise habits, with a mutually reinforcing relationship that enhances cognitive performance. The acknowledged plasticity of cognition driven by sports necessitates a comprehensive examination. Hence, this study delves into the dynamic intricacies of the prefrontal cortex, exploring the impact of orienteering experience on cognitive performance. Our findings contribute empirical evidence regarding the functional activation of specific brain regions bridging the nexus between experiential factors and cognitive capabilities. In this cross-sectional study, a cohort of forty-nine athletes was enrolled to meticulously examine behavioral variances and prefrontal cortex dynamics among orienteering athletes of varying experience levels across diverse non-specialized scenarios. These investigations involved the utilization of functional near-infrared spectroscopy (fNIRS) to detect alterations in oxygenated hemoglobin (HbO2). The high-experience expert group exhibited neurological efficiency, demonstrating significantly diminished brain activation in the dorsolateral prefrontal, left ventral lateral prefrontal, and right orbitofrontal regions compared to the low-experience group. Within the low-experience novice group, superior performance in the spatial memory task was observed compared to the mental rotation task, with consistently lower reaction times across all conditions compared to the high-experience group. Notably, cerebral blood oxygenation activation exhibited a significant reduction in the high-experience expert group compared to the low-experience novice group, irrespective of task type. The dorsolateral prefrontal lobe exhibited activation upon task onset, irrespective of experience level. Correct rates in the spatial memory task were consistently higher than those in the mental rotation task, while brain region activation was significantly greater during the mental rotation task than the spatial memory task." This study elucidates disparities in prefrontal cortex dynamics between highly seasoned experts and neophyte novices, showcasing a cognitive edge within the highly experienced cohort and a spatial memory advantage in the inexperienced group. Our findings contribute to the comprehension of the neural mechanisms that underlie the observed cognitive advantage and provide insights into the forebrain resources mobilized by orienteering experience during spatial cognitive tasks.", (© 2024. The Author(s).)

Substantial progress has been made in understanding the genetic architecture of phenotypes involved in a variety of evolutionary processes. Behavioral genetics remains, however, among the least understood. We explore the genetic architecture of spatial cognitive abilities in a wild passerine bird, the mountain chickadee (Poecile gambeli). Mountain chickadees cache thousands of seeds in the fall and require specialized spatial memory to recover these caches throughout the winter. We previously showed that variation in spatial cognition has a direct effect on fitness and has a genetic basis. It remains unknown which specific genes and developmental pathways are particularly important for shaping spatial cognition. To further dissect the genetic basis of spatial cognitive abilities, we combine experimental quantification of spatial cognition in wild chickadees with whole-genome sequencing of 162 individuals, a new chromosome-scale reference genome, and species-specific gene annotation. We have identified a set of genes and developmental pathways that play a key role in creating variation in spatial cognition and found that the mechanism shaping cognitive variation is consistent with selection against mildly deleterious non-coding mutations. Although some candidate genes were organized into connected gene networks, about half do not have shared regulation, highlighting that multiple independent developmental or physiological mechanisms contribute to variation in spatial cognitive abilities. A large proportion of the candidate genes we found are associated with synaptic plasticity, an intriguing result that leads to the hypothesis that certain genetic variants create antagonism between behavioral plasticity and long-term memory, each providing distinct benefits depending on ecological context., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol. Neurocognitive performance outcomes were assessed using the Cambridge Neuropsychological Test Automated Battery, with the Profile of Mood States questionnaire, and the Bond-Lader Visual Analogue Scale used to assess subjective state and mood. CannEpil increased Total Errors in Spatial Span and Correct Latency (median) in Pattern Recognition Memory, while also increasing Efficiency Score (lower score indicates greater efficiency) relative to placebo (all p < .05). Subjective Contentedness (p < .01) and Amicability (p < .05) were also increased at around 2.5 h post dosing, relative to placebo. Drowsiness or sedative effect was reported by 23 % of participants between three to six hours post CannEpil administration. Plasma concentrations of CBD, THC, and their metabolites were not significantly correlated with any observed alterations in neurocognition, subjective state, or adverse event occurrence. An acute dose of CannEpil impairs select aspects of visuospatial working memory and delayed pattern recognition, while largely preserving mood states among healthy individuals. Intermittent reports of drowsiness and sedation underscore the inter-individual variability of medicinal cannabis effects on subjective state. (ANZCTR; ACTRN12619000932167; https://www.anzctr.org.au)., Competing Interests: Declaration of competing interest AH is supported by a Rebecca L Cooper Al and Val Rosenstrauss Fellowship (GNT: F2021894). BM, SC, CS, BS, and LD have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Working memory is typically measured with specifically designed psychological tasks. When evaluating the validity of working memory tasks, we commonly focus on the reliability of the outcome measurements. Only rarely do we focus on how participants experience these tasks. Accounting for lived experience of working memory task may help us better understand variability in working memory performance and conscious experience in general. We replicated recently established protocols for the phenomenological investigation of working memory using the visual span task. We collected subjective reports from eighteen healthy participants (10 women) aged 21 to 35 years. We observed that working memory can be phenomenologically characterized at three different time scales: background feelings, strategies, and tactics. On the level of tactics, we identified transmodality (i.e., how one modality of lived experience can be transformed into another one) as the central phenomenological dynamic at play during working memory task performance., Competing Interests: Declaration of Competing Interest GR consults for and holds equity in Neumora Therapeutics and Manifest Technologies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The contribution of working memory to mathematics has been extensively studied. It has been proposed that verbal working memory (VWM) and visual-spatial working memory (VSWM) have distinct contributions, but results have been inconclusive. Here, we hypothesized that VWM and VSWM contribute differentially to separate sub-domains of mathematics. To test this hypothesis, we enrolled 199 primary school students and measured their VWM and VSWM with number/letter/matrix backward span tasks, and tested mathematics performance with simple subtraction, complex subtraction, multi-step calculation and number series completion, while controlling for several aspects of cognition. We found that while letter backward span had a significant contribution to complex subtraction, multi-step computation and number series completion, number backward span only had a significant contribution to multi-step computation, and matrix span had no effect on any math task. These results suggest that only VWM associated with complex mathematics, which might reflect verbal rehearsal. In contrast, VSWM does not appear to associated with mathematics., (© 2023 The British Psychological Society.)

We introduce a large-scale neurocomputational model of spatial cognition called 'Spacecog', which integrates recent findings from mechanistic models of visual and spatial perception. As a high-level cognitive ability, spatial cognition requires the processing of behaviourally relevant features in complex environments and, importantly, the updating of this information during processes of eye and body movement. The Spacecog model achieves this by interfacing spatial memory and imagery with mechanisms of object localisation, saccade execution, and attention through coordinate transformations in parietal areas of the brain. We evaluate the model in a realistic virtual environment where our neurocognitive model steers an agent to perform complex visuospatial tasks. Our modelling approach opens up new possibilities in the assessment of neuropsychological data and human spatial cognition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Based on previous results the cognitive profile of patients with obsessive-compulsive disorder (OCD) is determined by the impairment of executive and visual-spatial memory functions. The Rey-Osterrieth Complex Figure (ROCF) is a widely used tool for examining visual-spatial memory disorders. Several scoring systems can be used to evaluate the ROCF and the most widespread is the original Osterrieth evaluation system. The Boston Qualitative Scoring System (BQSS) is a new, much more detailed scoring system than the Osterrieth, which allows both quantitative and a more detailed qualitative analysis of ROCF. In our study, we analyzed the copying and immediate recall performance of 24 OCD and 24 age- and education-matched healthy control subjects using the Osterrieth and BQSS scoring systems. Our research had two main goals, (1) to examine the diff erences in visualspatial memory performance shown by the OCD group compared to the control group, and (2) to compare the Osterrieth and BQSS scoring systems in one clinical sample. Based on both the Osterrieth and BQSS scoring systems, our results show that the OCD group performed significantly worse in the recall phase, but not in the copy phase. According to our results both scoring systems can be effectively used to examine the functioning of visual-spatial memory in OCD patients. While the Osterrieth evaluation system is faster and more widespread, the BQSS scoring system examines detailed qualitative aspects in addition to quantitative indicators.

Increased spatial processing demands, e.g., working memory loads, which include capacity load and resolution load, may interfere with postural stability. To date, there has been little evidence to demonstrate whether capacity load and resolution load affect postural stability. Therefore, this study manipulated capacity load and resolution load in a spatial working memory task to examine how postural stability is affected. Sixteen healthy young participants were tested in a dual-task paradigm that consisted of a postural task with a tandem Romberg stance and a spatial working memory task with different capacity loads and resolution loads in different sessions. Participants were required to detect a salient change (45° in low resolution) or a subtle change (15° in high resolution) in the bar orientation as a resolution load. Capacity load was manipulated by storing the number of bars, with two bars in low capacity and four in high capacity. The results showed significant interactions between capacity load and resolution load on dual-task effects of sway velocity. In the low-resolution condition, the dual-task effects of anteroposterior and mediolateral sway velocity were significantly lower in the high capacity than in the low capacity, yet no significant differences occurred in the high-resolution load condition. Our results suggest that increased capacity loads interfere with postural stability only in low-resolution loads while dual-tasking., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Antisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential has generated hope for Alzheimer's disease (AD). We previously described that ablating SNCA encoding for α-synuclein (αSyn) in a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction of αSyn expression using ASO SNCA could be therapeutic in a mouse model of AD. The efficacy of the ASO SNCA was measured via immunocytochemistry, RT-qPCR and western blotting. To assess spatial learning and memory, ASO SNCA or PBS-injected APP and non-transgenic (NTG) mice, and separate groups of SNCA-null mice, were tested on the Barnes circular maze. Hippocampal slice electrophysiology and transcriptomic profiling were used to explore synaptic function and differential gene expression between groups. Reduction of SNCA transcripts alleviated cognitive deficits in male transgenic animals, but surprisingly, not in females. To determine the functional cause of this differential effect, we assessed memory function in SNCA-null mice. Learning and memory were intact in male mice but impaired in female animals, revealing that the role of αSyn on cognitive function is sex-specific. Transcriptional analyses identified a differentially expressed gene network centered around EGR1, a central modulator of learning and memory, in the hippocampi of SNCA-null mice. Thus, these novel results demonstrate that the function of αSyn on memory differs between male and female brains., (© 2022. The Author(s).)

Background: A range of cognitive tasks can interfere with postural control, particularly in older adults. In the case of spatial tasks, the spatial alignment between the task and postural control can incur dual-task costs separately from task load. It has been suggested that spatial tasks incur dual-task costs because accessing the visuospatial sketchpad component of working memory reduces the capacity to utilize external visual information for postural control., Research Question: We investigated whether the spatial alignment between a cognitive and a postural control task can affect postural stability even when visual perception is not involved in either task and task load does not differ between aligned and non-aligned conditions. We predicted that any such effect would be greater in older people and in a more challenging stance., Methods: Fifty healthy adults (27 aged 20-35, 23 aged 59-88) with no history of balance or cognitive difficulties performed a mental navigation task while standing in open or closed stance with eyes closed. The mental navigation task was presented in a reference plane that was either aligned or non-aligned to the horizontal reference plane in which the posture control system controlled the position of the body's center of gravity. Task performance was measured as accuracy and response time and postural sway as anteroposterior (AP) and mediolateral (ML) sway velocity., Results: The older group were less accurate in the mental navigation task, and both groups had higher AP and ML sway velocity in closed stance. When standing in the more challenging stance, the older group had higher AP sway velocity while performing the mental navigation task in the non-aligned than the aligned reference plane condition., Significance: The spatial configuration compatibility between a cognitive task and postural control can affect postural stability even when visual information is not being used for either task and task load is unchanged., (Copyright © 2022 Elsevier B.V. All rights reserved.)

David Sherry's pioneering work on the neuroecology of spatial memory has three characteristics that could inspire studies on other cognitive processes: it was grounded in a robust prior literature in psychology and neuroscience; it identified several natural history contexts in which repeated independent evolution of spatial memory differences had occurred in different clades; it involved a precise cognitive ability with a precise neural substrate. We discuss the application of these three principles to a more domain-general trait-innovation. We argue that targeting the caudolateral nidopallium and its connected areas, favoring problem-solving over reversal learning as an experimental assay, and focusing on situations that involve environmental change, such as urbanization and invasion, can help the study of innovation progress, like the field of spatial memory has since 1989., (© 2021. The Psychonomic Society, Inc.)

Introduction: Western diets, including those consisting of saturated fats, simple sugars and processed foods, is rising at an unprecedented rate. These lead to obesity and metabolic diseases, and possibly cognitive deficits. Exploring this, recent studies demonstrate marked impairment in spatial learning in rodents exposed to high-sugar diets. We utilised advanced touchscreen technology to assess several spatial and non-spatial components of cognition in rats chronically exposed to a high sucrose diet., Methods: Male Wistar rats received 70 ml of 10% sucrose solution each day, or control tap water, persisting for the experiment duration (total n = 32). After 5 weeks of diet, rats performed Pairwise Discrimination, Location Discrimination, or Progressive Ratio tasks on automated touchscreens, and performance compared between groups., Results: Sucrose rats consumed all the sugar solution provided to them, and had significantly increased caloric intake, compared to controls (p < 0.0001). However, in all tests, we found no significant difference in cognitive performance between Sucrose and Control treated rats. This included the number of trials for acquisition, and reversal, in Pairwise Discrimination, and number of trials required to complete Location Discrimination (p > 0.05 for all outcomes). No differences were observed in perseverative behaviour, motivation levels, or processing speed., Conclusion: Our study found no evidence to suggest that chronic consumption of sucrose impairs cognition, including both spatial and non-spatial learning tasks. These findings suggest that not all aspects of spatial cognition are negatively impacted by high sugar diet in rodents, and that particular use of touchscreen technology may probe different aspects of cognition than traditional tasks., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In previous research, we found that chronic-intermittent ethanol administration (CIEA), a model of binge drinking, impaired emotional memory in mice, and this impairment was counteracted by the anti-inflammatory drug indomethacin. In the present study, we evaluated the effects of CIEA on spatial memory and cognitive flexibility in adolescent mice of both sexes. Animals were randomly assigned to one of four groups for each sex: SS (saline + saline), SA (saline + alcohol), SI (saline + indomethacin), and AI (alcohol + indomethacin). They were injected with saline, ethanol (3 g/kg) or indomethacin (10 mg/kg) for the first three days of each week, throughout three weeks. 96 h after treatment, subjects learnt a standard water maze task on five consecutive days (4-day training and 1-day probe trial). One day later, mice underwent a reversal task for evaluating spatial cognitive flexibility. Animals receiving alcohol (SA and AI groups) did not differ from controls (SS groups) during the standard task, but animals treated with indomethacin performed better than controls, both in the acquisition trials and the probe trial. During the reversal task, no significant differences between alcohol groups and controls were observed, but the indomethacin group showed significant lower escape latencies than controls. No sex differences were found in either task. In conclusion, binge drinking does not impair spatial memory or spatial cognitive flexibility, while the anti-inflammatory indomethacin improves both, showing that the effects of alcohol and indomethacin on spatial memory (dependent on hippocampus) are different to those they exert on emotional memory (dependent on amygdala)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The underlying hypothesis that motivates research into the relationship between ecology, cognition, and the hippocampus is that selection to solve problems in nature shapes cognition through changes in the hippocampus. This hypothesis has been explored almost exclusively in mammals and birds. However, if one is interested in the principles that shape the evolution of vertebrate cognition, work in amphibians is essential. To address this gap, we have developed a research program contrasting cognitive abilities and hippocampal neurobiology in two species of frog with distinct social and spatial ecologies. We have found that the poison frog Dendrobates auratus, a diurnal species whose interactions with the physical and social environment are complex, is more adept and flexible at spatial learning and learned inhibition than the túngara frog, a nocturnal species that lacks complex interactions with the spatial and social environment. Because spatial learning and learned inhibition are closely associated with hippocampal function in other vertebrates, we used RNA sequencing to characterize molecular differences in the hippocampus of the two species. We have found that D. auratus has greater levels of expression of genes associated with neurogenesis, synaptic plasticity, and cellular activity, and lower levels of expression of genes associated with apoptosis, compared to the túngara frog. Our studies are consistent with the idea that D. auratus, with their more complex social and spatial ecology, have enhanced hippocampally dependent cognitive abilities compared to túngara frogs. Further characterization of the features of hippocampal neurobiology that confer distinctive cognitive abilities will help elucidate the neural features that are necessary for the evolution of enhanced hippocampally dependent cognition., (© 2022 S. Karger AG, Basel.)

The infant and fetus may be exposed to cyanuric acid (CA) via several different routes into the diet or milk product as well as deliberate contamination. Previous findings indicated chronic CA treatment caused neurotransmission and synaptic impairment in the early developing hippocampus. This study was designed to characterize the effects of different doses (10 mg/kg, 20 mg/kg and 40 mg/kg) of CA exposure on the developing fetus. Pregnant rats were intraperitoneally exposed to CA during the entire period of gestation and male offspring were selected for water maze task, neural recording and N-methyl-d-aspartate (NMDA) receptor detection around the eighth postnatal week. We found that CA exposure impaired the learning and memory function in a dose-dependent manner. The paired-pulse ratio (PPR) and GluN2A-dependent long-term potentiation (LTP) at the Schaffer collateral-CA1 pathway were affected in CA-exposed rats. Remarkably, hippocampal levels of NMDA-GluN2A, but not NMDA-GluN2B, were significantly decreased. Meanwhile, the spine density of hippocampal CA1 neurons was not altered by the CA exposure. Our findings are consistent with the hypothesis that CA treatment during the prenatal period produces deficits in spatial cognition by disrupting hippocampal synaptic function., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

New neurons are abnormal in the adult hippocampus of Alzheimer's disease (AD) mouse models. The effects of modulating adult neurogenesis on AD pathogenesis differ from study to study. We reported recently that ablation of adult neural stem cells (aNSCs) was associated with improved memory in AD models. Here, we found that long-term potentiation (LTP) was improved in the hippocampus of APP/PS1 mice after ablation of aNSCs. This effect was confirmed in hAPP-J20 mice, a second AD mouse model. On the other hand, we found that exposure to enriched environment (EE) dramatically increased the number of DCX + neurons, promoted dendritic growth, and affected the location of newborn neurons in the dentate gyrus of APP/PS1 mice, and EE exposure significantly ameliorated memory deficits in APP/PS1 mice. Together, our data suggest that both inhibiting abnormal adult neurogenesis and enhancing healthy adult neurogenesis could be beneficial for AD, and they are not mutually exclusive., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

During the last decades, graphitic carbon nitride (g-C3N4) has attracted increasing attention in several biomedical fields. In this study, the effects of sulfur-doped g-C3N4 (TCN) on cognitive function and histopathology of hippocampus were investigated in mice. The characteristics of synthetized sample were evaluated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and energy dispersive X-ray (EDX). Twenty-four male NMRI mice received vehicle, TCN at doses of 50, 150, or 500 mg/kg via gavage for one week. Morris water maze test was done to assess the cognitive function at day 14 post TCN administration. Nissl staining was used to determine the number of dark cells in the hippocampus. Immunostaining against NeuN, GFAP, and Iba1 was done to evaluate the neuronal density and levels of glial activation, respectively. Behavioral tests indicated that TCN reduces the spatial learning and memory in a dose-dependent manner. Histological evaluations showed an increased level of neuronal loss and glial activation in the hippocampus of TCN treated mice at doses of 150 and 500 mg/kg. Overall, our data indicate that TCN induces the cognitive impairment that is partly mediated via its exacerbating impacts on neuronal loss and glial activation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aged rodents have been used as preclinical models of age-associated cognitive decline. Most of those models displayed substantial impairments in learning and memory. The initial, more subtle changes that precede more severe losses in cognitive abilities have not been well characterized. Here, we established a model detecting initial subtle cognitive changes by comparing the performance of moderately aged Oncins France Strain A Sprague Dawley rats with young rats in the Morris water maze (MWM) and the Open Field (OF) test. Both age groups improved their performance during the training period at a similar rate; however, the older rats performed worse in several parameters measured in the MWM. Our results suggest that already at the age of 18-20 months rats show changes in their approach to solve the spatial memory task while their ability to learn is not yet diminished. The disparate spatial information processing of the moderately aged rats provides a novel animal model for early age-related cognitive alterations that could be useful to test the effect of early intervention strategies. Moreover, our results suggest that the sensitivity of cognitive tests in the elderly could be substantially enhanced if they assess both the improvement after several trials, and the strategy used to solve a certain task., (Copyright © 2021 Elsevier Inc. All rights reserved.)

High titers of anti-NMDAR1 autoantibodies in brain cause anti-NMDAR1 encephalitis that displays psychiatric symptoms of schizophrenia and/or other psychiatric disorders in addition to neurological symptoms. Low titers of anti-NMDAR1 autoantibodies are reported in the blood of a subset of the general human population and psychiatric patients. Since ~0.1-0.2% of blood circulating antibodies cross the blood-brain barriers and antibodies can persist for months and years in human blood, it is important to investigate whether chronic presence of these blood circulating anti-NMDAR1 autoantibodies may impair human cognitive functions and contribute to the development of psychiatric symptoms. Here, we generated mice carrying low titers of anti-NMDAR1 autoantibodies in blood against a single antigenic epitope of mouse NMDAR1. Mice carrying the anti-NMDAR1 autoantibodies are healthy and display no differences in locomotion, sensorimotor gating, and contextual memory compared to controls. Chronic presence of the blood circulating anti-NMDAR1 autoantibodies, however, is sufficient to impair T-maze spontaneous alternation in the integrity of blood-brain barriers across all 3 independent mouse cohorts, indicating a robust cognitive deficit in spatial working memory and/or novelty detection. Our studies implicate that chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies may impair cognitive functions in both the general healthy human population and psychiatric patients., Competing Interests: The authors declare no conflict of interest.

Visuospatial memory (VSM) performance depends on intrinsic (biopsychosocial parameters) and extrinsic (space) factors. We aimed at characterizing the determinants of VSM performance according to space. Young healthy adults, 20 males and 41 females (23 ± 3 years old), were assessed for VSM performance through a pathway learning task, in reaching (eCorsi Block Tapping task) and walking space (Virtual Walking Corsi Task). We evaluated psychosocial factors through seven questionnaires - Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, Profile of the Mood States, 2 nd edition, short version, Coping Inventory for Stressful Situations, Measurement of Ambiguity Tolerance, Motives for Physical Activities Measure-Revised, mental rotation capabilities and locomotor characteristics (physical activity level through embedded trackers and the International Physical Activity Questionnaire, and gait parameters). The most explanatory biopsychosocial determinants of VSM performance were i) mental rotation capabilities and fatigue indicator in reaching space, and ii) mental rotation capabilities and physical activity level (tracked active energy expenditure only) in walking space. These results suggest that specific parameters should be preferred for the evaluation and strengthening of VSM capabilities in both reaching or walking spaces., (Copyright © 2020. Published by Elsevier B.V.)

Leucine-rich repeat (LRR) transmembrane proteins have been directly linked to neurodevelopmental and cognitive disorders. We have previously shown that the LRR transmembrane protein, leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), is a physiological regulator of dendrite complexity of hippocampal pyramidal neurons and social behavior. In this study, we performed a battery of behavioral tests to evaluate spatial memory and cognitive capabilities in Lrig1 mutant mice. The cognitive assessment demonstrated deficits in recognition and spatial memory, evaluated by novel object recognition and object location tests. Moreover, we found that Lrig1-deficient mice present specific impairments in the processing of similar but not dissimilar locations in a spatial pattern separation task, which was correlated with an enhanced dendritic growth and branching of Doublecortin-positive immature granule cells of the dentate gyrus. Altogether, these findings indicate that Lrig1 plays an essential role in controlling morphological and functional plasticity in the hippocampus., (© 2021 Wiley Periodicals LLC.)

Study of the neural code for space in rodents has many insights to offer for how mammals, including humans, construct a mental representation of space. This code is centered on the hippocampal place cells, which are active in particular places in the environment. Place cells are informed by numerous other spatial cell types including grid cells, which provide a signal for distance and direction and are thought to help anchor the place cell signal. These neurons combine self-motion and environmental information to create and update their map-like representation. Study of their activity patterns in complex environments of varying structure has revealed that this "cognitive map" of space is not a fixed and rigid entity that permeates space, but rather is variably affected by the movement constraints of the environment. These findings are pointing toward a more flexible spatial code in which the map is adapted to the movement possibilities of the space. An as-yet-unanswered question is whether these different forms of representation have functional consequences, as suggested by an enactivist view of spatial cognition., (© 2021. The Author(s).)

The potential harmful effects of polypharmacy (concurrent use of 5 or more drugs) are difficult to investigate in an experimental design in humans. Moreover, there is a lack of knowledge on sex-specific differences on the outcomes of multiple-drug use. The present study aims to investigate the effects of an eight-week exposure to a regimen of five different medications (metoprolol, paracetamol, aspirin, simvastatin and citalopram) in young adult female mice. Polypharmacy-treated animals showed significant impairment in object recognition and fear associated contextual memory, together with a significant reduction of certain hippocampal proteins involved in pathways necessary for the consolidation of these types of memories, compared to animals with standard diet. The impairments in explorative behavior and spatial memory that we reported previously in young adult male mice administered the same polypharmacy regimen were not observed in females in the current study. Therefore, the same combination of medications induced different negative outcomes in young adult male and female mice, causing a significant deficit in non-spatial memory in female animals. Overall, this study strongly supports the importance of considering sex-specific differences in designing safer and targeted multiple-drug therapies.

This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

Protein prenylation is a post-translational lipid modification that governs a variety of important cellular signaling pathways, including those regulating synaptic functions and cognition in the nervous system. Two enzymes, farnesyltransferase (FT) and geranylgeranyltransferase type I (GGT), are essential for the prenylation process. Genetic reduction of FT or GGT ameliorates neuropathology but only FT haplodeficiency rescues cognitive function in transgenic mice of Alzheimer's disease. A follow-up study showed that systemic or forebrain neuron-specific deficiency of GGT leads to synaptic and cognitive deficits under physiological conditions. Whether FT plays different roles in shaping neuronal functions and cognition remains elusive. This study shows that in contrast to the detrimental effects of GGT reduction, systemic haplodeficiency of FT has little to no impact on hippocampal synaptic plasticity and cognition. However, forebrain neuron-specific FT deletion also leads to reduced synaptic plasticity, memory retention, and hippocampal dendritic spine density. Furthermore, a novel prenylomic analysis identifies distinct pools of prenylated proteins that are affected in the brain of forebrain neuron-specific FT and GGT knockout mice, respectively. Taken together, this study uncovers that physiological levels of FT and GGT in neurons are essential for normal synaptic/cognitive functions and that the prenylation status of specific signaling molecules regulates neuronal functions.

Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother-infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F 2 ) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (postnatal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F 2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex-dependent manner., (© 2020 International Society for Developmental Neuroscience.)

Background: Psychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision-making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied., Methods: We examined the acute effects of LSD (100 µg) alone and in combination with the 5-HT2A antagonist ketanserin (40 mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery., Results: Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence the quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits., Conclusions: The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.

Objectives: Visual field defects due to hemi- or quadrantanopia after stroke represent an under-recognized neurological symptom with inefficient instruments for neurorehabilitation to date. We here examined the effects of training in a virtual reality (VR) supermarket on cognitive functions, depressive symptoms, and subjective cognitive complaints in patients with hemianopia/quadrantanopia and healthy controls., Methods: During a 14-day rehabilitation program, 20 patients and 20 healthy controls accomplished a real-life-like shopping task in a VR supermarket. A comparison between pre- and post-training standard neuropsychological measures, depressive symptoms, and subjective memory complaints allowed us to assess a putative transfer of rehabilitation effects from the training tasks to specific cognitive functions., Results: The results indicate that VR training may improve performance not only in the trained task but also in specific neuropsychological functions. After the training, both patients and controls showed improved performances in visual scanning, mental rotation, visuoconstruction, and cognitive flexibility. Moreover, depressive symptoms were attenuated in both groups. In the patient group compared to the control group, the training particularly resulted in improved visual memory retrieval and reduced memory complaints., Conclusions: The results of the current study suggest that VR training can improve particularly visual-spatial skills in patients with hemianopia or quadrantanopia. Our study thus introduces an interesting novel treatment approach to improve cognitive functions relevant to daily life in stroke patients with visual field defects.

A combination of aged garlic, ginger, and chili peppers extracts (AGC) was studied by high-performance liquid chromatography, 2,2-diphenyl-1-picrylhydrazyl, and ferric-reducing antioxidant assays, and oxidative stress markers were analyzed in Aβ1-42-induced rats. The AGC was orally administered to Wistar rats at doses of 125, 250, and 500 mg/kg body weight (AGC125, AGC250, AGC500, respectively) for 64 days. At day 56, Aβ1-42 was injected via both sides of the lateral ventricles. The effects of the AGC on spatial and recognition memory were examined using a Morris water maze and novel object recognition tasks. Rats induced with Aβ1-42 exhibited obvious cognitive deficits, as demonstrated by their increased escape latency time (ET) and decreased retention time (RT) and percentage of discriminative index (DI). When compared with the control group, all AGC-treated rats showed significantly shorter ETs and higher DIs during the 5-min delay testing phase. Rats treated with AGC250 also had significantly longer RTs. Administration of Aβ1-42 significantly increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in the rat brain homogenate. Pretreatment with the AGC caused significant increases in SOD, GPx, and CAT activities, as well as a significant decrease in MDA in the rat brain homogenates after Aβ-induced neurotoxicity. Our results suggested that an AGC may ameliorate cognitive dysfunction in Aβ-treated rats due to its role in the upregulation of SOD, GPx, and CAT.

Many occupations require operations during the night-time when the internal circadian clock promotes sleep, in many cases resulting in impairments in cognitive performance and brain functioning. Here, we use a rat model to attempt to identify the biological mechanisms underlying such impaired performance. Rats were exposed to forced activity, either in their rest-phase (simulating night-shift work; rest work) or in their active-phase (simulating day-shift work; active work). Sleep, wakefulness and body temperature rhythm were monitored throughout. Following three work shifts, spatial memory performance was tested on the Morris Water Maze task. After 4 weeks washout, the work protocol was repeated, and blood and brain tissue collected. Simulated night-shift work impaired spatial memory and altered biochemical markers of cerebral cortical protein synthesis. Measures of daily rhythm strength were blunted, and sleep drive increased. Individual variation in the data suggested differences in shift work tolerance. Hierarchical regression analyses revealed that type of work, changes in daily rhythmicity and changes in sleep drive predict spatial memory performance and expression of brain protein synthesis regulators. Moreover, serum corticosterone levels predicted expression of brain protein synthesis regulators. These findings open new research avenues into the biological mechanisms that underlie individual variation in shift work tolerance.

Objectives: To study the effect of anodal transcranial direct stimulation (atDCS) of the right dorsolateral prefrontal cortex (DLPFC) on cognitive function and side effects in patients with mild cognitive impairment., Design: Experimental double-blind randomized, sham-controlled trial., Setting: Department of Rehabilitation Medicine, King Chulalongkorn Memorial Hospital PARTICIPANTS: Volunteers (N=45) with mild cognitive impairment., Interventions: Not applicable., Main Outcome Measures: The atDCS group (n=23) were stimulated at 2 mA for 20 minutes with the anode on the right DLPFC and the cathode on the left supraorbital area. The control group (n=22) received placebo stimulation. Baseline cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery test. Participants were treated 3 times per week for 4 weeks (12 sessions). Cognitive function and side effects were assessed immediately after the first stimulation, the last session, and 4 weeks after treatment., Results: Cambridge Neuropsychological Test Automated Battery results revealed a significant improvement in the accuracy of the visual sustained attention (VSA) in the atDCS group at all 3 time points, the spatial working memory and visual memory (VM) immediately after the first stimulation, and a decreased VM reaction time after 12 sessions. A long-lasting effect on VSA and VM were found 4 weeks after treatment., Conclusions: Anodal tDCS over the right DLPFC enhanced the VSA, spatial working memory, and VM accuracy after the first stimulation and reduced the reaction time of VM after 12 sessions. A long-lasting effect on VSA and VM was found 4 weeks after treatment. This study corroborated atDCS as a safe technique to improve cognitive function., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Past research has largely ignored children's ability to conjointly manipulate spatial and temporal information, but there are indications that the capacity to do so may provide important support for reasoning about causal processes. We hypothesised that spatial-temporal thinking is central to children's ability to identify the invisible mechanisms that tie cause and effect together in continuous casual processes, which are focal in primary school science and crucial to understanding of the natural world. We investigated this in two studies (N = 107, N = 124), employing two methodologies, one shorter, the other more in depth. Further tasks assessed spatial-temporal (flow of liquid, extrapolation of relative speed, distance-time-velocity), spatial (two mental rotation, paper folding), verbal (expressive vocabulary), and nonverbal (block design) ability. Age dependent patterns were detected for both causal and predictor tasks. Two spatial-temporal tasks were unique and central predictors of children's causal reasoning, especially inference of mechanism. Nonverbal ability predicted the simpler components of causal reasoning. One mental rotation task predicted only young children's causal thinking. Verbal ability became significant when the sample included children from a wide range of socioeconomic backgrounds. Causal reasoning about continuous processes, including inferences of causal mechanism, appears to be within the reach of children from school entry age, but mechanism inference is uncommon. Analytic forms of spatial-temporal capacity seem to be important requirements for children to progress to this rather than merely perceptual forms., Competing Interests: The authors have declared that no competing interests exist.

Osteocalcin, known as a bone gla protein, is considered a regulator of energy metabolism and behavior in its undercarboxylated form (ucOC). Antiresorptive drugs, such as alendronate, reduce serum level of ucOC. The purpose of the current study was to verify if alendronate might impact on energy metabolism and animal behavior by reducing ucOC level and to find out if the presence of metabolic alterations would further worsen these potential adverse effects. Four groups of male Wistar rats (12 per group) were used: a control group, a group receiving high-fat high-fructose diet (HFHF), a group treated with alendronate, and a group receiving alendronate and HFHF. Alendronate was administered subcutaneously in a dose of 50 mcg/kg thrice weekly. Study duration was 15 weeks. Animals were tested for locomotion, anxiety and spatial memory. Glucose and insulin tolerance tests evaluated the glucose metabolism. Visceral obesity was assessed by the weight of right retroperitoneal fat pads. Concentration of ucOC was measured in the serum. Alendronate reduced serum ucOC concentration, increased fasting blood glucose level, and worsened insulin sensitivity. It did not increase visceral adiposity. Fat index was negatively correlated with ucOC in all animals and in the alendronate-treated rats. Alendronate worsened spatial memory of the animals and ucOC levels correlated positively with their cognitive performance.

Background : Two different species of sage, Salvia officinalis and Salvia lavandulaefolia , have demonstrated activities in cognitive function during preclinical and clinical studies related to impaired health situations or single administration. Different memory processes have been described to be significantly and positively impacted. Objective: Our objective is to explore the potential of these Salvia, and their additional activities, in healthy situations, and during prolonged administration, on memory and subsequent mechanisms of action related to putative effects. Design: This mouse study has implicated four investigational arms dedicated to control, Salvia officinalis aqueous extract, Salvia lavandulaefoli a -encapsulated essential oil and a mix thereof (Cognivia™) for 2 weeks of administration. Cognitive functions have been assessed throughout Y-maze and Morris water maze models. The impact of supplementation on lipid peroxidation, oxidative stress, neurogenesis, neuronal activity, neurotrophins, neurotrophin receptors, CaM kinase II and glucocorticoid receptors has been assessed via post-interventional tissue collection. Results: All Salvia groups had a significant effect on Y-maze markers on day 1 of administration. Only the mix of two Salvia species demonstrated significant improvements in Morris water maze markers at the end of administration. Considering all biological and histological markers, we did not observe any significant effect of S. officinalis , S. lavandulaefoli a and a mix of Salvia supplementation on lipid peroxidation, oxidative stress and neuronal plasticity (neurogenesis, neuronal activity, neurotrophins). Interestingly, CaM kinase II protein expression is significantly increased in animals supplemented with Salvia. Conclusion: The activities of Salvia alone after one intake have been confirmed; however, a particular combination of different types of Salvia have been shown to improve memory and present specific synergistic effects after chronic administration in healthy mice., Competing Interests: Nexira funded this work. Financial support was provided to INRA/Nutribrain to conduct the experiments (service provision). ALD, CL, SL, VP and CJ report no disclosures. Nexira funds DG.

The present experiment was conducted to examine the cognitive processes underlying mental perspective taking in remembered environments. Participants learned a layout of everyday objects from multiple randomly chosen perspectives. They were then blindfolded and tested for their spatial knowledge by having them point to unseen object locations from imagined perspectives. The acoustic display of a first object name informed participants about the to-be-imagined position, a second object name about the to-be-imagined heading, before a third object name identified the target they should point to with a joystick. The choice of object triplets allowed for independent variation of head-direction disparity (HDD), i.e., the difference in heading direction between real and imagined perspective, and object direction disparity (ODD), i.e., the egocentric shift of target object direction between real and imagined perspectives. Results revealed a consistent pattern of monotonic increasing detrimental effects of HDD (0°, 60°, 120°, 180°) and ODD (0-45°, 46-90°, 91-135°, 136-180°). The independent variation of HDD and ODD disclosed a third source of extra processing costs that could be traced back to allocentric differences in target object direction (ODD allo ). A SOA-interval (1, 3, or 5 s) before target presentation allowed participants to save on overall pointing times and errors but did not allow them to reduce incremental costs from HDD, ODD ego , or ODD allo . The present results reveal that multiple overlapping spatial interference conflicts between real and imagined spatial perspectives are the most important source of additional processing costs in mental perspective taking in remembered environments., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Elucidating the multi-faceted relationship between cognitive competence and affective states is a major pursuit in behavioral sciences. Mood disorders constitute a good research model for this question, as cognitive impairment may accompany clinical depression and persist after full remission. This suggests cognitive dysfunction as an etiological factor of depression, rather than an epiphenomenon. Complementing clinical studies, animal models utilizing well-controlled, systematic paradigms are essential to elucidate the complex relationship between cognitive competence and affective states. In current set of experiments, we investigated the extent to which cognitive competence determines the stress response in Wistar rats by utilizing two well-established spatial memory paradigms with different degrees of complexity together with the forced swim test. We revealed that rats with low cognitive competence as assessed by learning performance in the Y-Maze, but not in the radial arm maze, were significantly more vulnerable to behavioral despair. In contrast, rats with high cognitive competence were resilient to the negative effects of the forced swim test, irrespective of the spatial memory task used. These results point to a nonlinear relationship between spatial memory performance and behavioral despair, suggesting that different types of cognitive functioning may have differential effects on affective processes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The study aims to establish demographically corrected, pediatric norms for the computerized Delayed Matching to Sample (DMS) test, a measure of "visual matching ability and short-term visual recognition memory, for non-verbalisable problems". The DMS was administered to n = 184 children aged 5.10 to 14.5 years old. The DMS is a 4-choice recognition task of non-verbal, abstract patterns. The child has "to select, among four different choice patterns, the one that matches a complex visual pattern presented," i.e., (the target stimulus). The DMS consists of two conditions: a) the overt condition in which the target stimulus and four choice patterns are shown simultaneously and b) the covert condition, in which the choice patterns are shown after the target pattern is covered. The DMS test provides three outcome measures: the accuracy score (i.e., the number of correct patterns selected), latency (i.e., the response speed) and the probability of making an error after an incorrect response. These outcome measures were calculated for both conditions and for both conditions combined. Results showed that demographic variables, such as age, sex, and/or level of parental education (LPE) affected scores on these outcome measures. Based on these data, demographically corrected norms were established for all outcome measures, per condition and for both conditions combined.

Sequential activity is seen in the hippocampus during multiple network patterns, prominently as replay activity during both awake and sleep sharp-wave ripples (SWRs), and as theta sequences during active exploration. Although various mnemonic and cognitive functions have been ascribed to these hippocampal sequences, evidence for these proposed functions remains primarily phenomenological. Here, we briefly review current knowledge about replay events and theta sequences in spatial memory tasks. We reason that in order to gain a mechanistic and causal understanding of how these patterns influence memory and cognitive processing, it is important to consider how these sequences influence activity in other regions, and in particular, the prefrontal cortex, which is crucial for memory-guided behavior. For spatial memory tasks, we posit that hippocampal-prefrontal interactions mediated by replay and theta sequences play complementary and overlapping roles at different stages in learning, supporting memory encoding and retrieval, deliberative decision making, planning, and guiding future actions. This framework offers testable predictions for future physiology and closed-loop feedback inactivation experiments for specifically targeting hippocampal sequences as well as coordinated prefrontal activity in different network states, with the potential to reveal their causal roles in memory-guided behavior., (© 2017 Wiley Periodicals, Inc.)

Deficits in prefrontal cortex (PFC) GABAergic neurotransmission are linked to cognitive impairments seen in schizophrenia and other disorders, and pharmacological reduction of PFC GABA A transmission disrupts processes including working and spatial memory. This provides an opportunity to examine whether compounds capable of neutralizing GABAergic dysfunction may ameliorate these cognitive deficits. PFC dopamine (DA) D 1 receptor activation enhances GABA transmission, raising the possibly that direct or indirect agonists of DA D 1 receptors would be effective in reversing working memory and other forms of cognitive deficits. To test this, male rats were pre-treated with two drugs that augment PFC D 1 signalling before PFC infusion of the GABA A antagonist, bicuculline (50 ng) and assessment of spatial working and reference memory function. A moderate dose of the full D 1 agonist SKF-81297 (0.1 mg/kg) completely reversed PFC GABA hypofunction-induced working memory deficits assessed in an delayed-response task, whereas lower and higher doses (0.05 and 0.3 mg/kg respectively) were associated with mild improvements or deleterious effects. Treatment with the tetrahydroprotoberberine d-govadine (0.5 or 1.0 mg/kg), a synthetic compound known to enhance DA release selectively in the PFC, also significantly improved delayed-response working memory function induced by PFC GABA A antagonism. Furthermore, administration of the optimal dose of both drugs led to a partial rescue of PFC GABA hypofunction-induced reference and short-term spatial memory impairments assessed on a radial maze task. These findings suggest that modulation of PFC DA signalling via actions on the DA D 1 receptor represents a promising therapeutic strategy for working memory and other cognitive impairments observed in psychiatric disorders, including those with causes that extend beyond DA dysfunction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and dementia with no effective treatment. Here, we investigated a novel compound from oats named avenanthramide-C (Avn-C), on AD-related memory impairment and behavioral deficits in transgenic mouse models. Acute hippocampal slices of wild-type or AD transgenic mice were treated with Avn-C in the presence or absence of oligomeric Aβ 42 . LTP analyses and immunoblotting were performed to assess the effect of Avn-C on Aβ-induced memory impairment. To further investigate the effect of Avn-C on impaired memory and Aβ pathology, two different AD transgenic mice (Tg2576 and 5XFAD) models were orally treated with either Avn-C or vehicle for 2 weeks. They were then assessed for the effect of the treatment on neuropathologies and behavioral impairments. Avn-C reversed impaired LTP in both ex vivo- and in vivo-treated AD mice hippocampus. Oral administration (6 mg/kg per day) for 2 weeks in AD mice leads to improved recognition and spatial memory, reduced caspase-3 cleavage, reversed neuroinflammation, and to accelerated glycogen synthase kinase-3β (pS9GSK-3β) and interleukin (IL-10) levels. Avn-C exerts its beneficial effects by binding to α1A adrenergic receptors to stimulate adenosine monophosphate-activated kinase (AMPK). All of the beneficial effects of Avn-C on LTP retrieval could be blocked by prazosin hydrochloride, a specific inhibitor of α1A adrenergic receptors. Our findings provide evidence, for the first time, that oats' Avn-C reverses the AD-related memory and behavioral impairments, and establish it as a potential candidate for Alzheimer's disease drug development.

Little is known about the molecular mechanisms of cognitive deficits in psychiatric disorders. CAMDI is a psychiatric disorder-related factor, the deficiency of which in mice results in delayed neuronal migration and psychiatrically abnormal behaviors. Here, we found that CAMDI-deficient mice exhibited impaired recognition memory and spatial reference memory. Knockdown of CAMDI in hippocampal neurons increased the amount of internalized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) and attenuated the chemical long-term potentiation (LTP)-dependent cell surface expression of AMPAR. KIBRA was identified as a novel CAMDI-binding protein that retains AMPAR in the cytosol after internalization. KIBRA inhibited CAMDI-dependent Rab11 activation, thereby attenuating AMPAR cell surface expression. These results suggest that CAMDI regulates AMPAR cell surface expression during LTP. CAMDI dysfunction may partly explain the mechanism underlying cognitive deficits in psychiatric diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: Cognitive disturbances occur early in Huntington's disease (HD) and place a significant burden on the lives of patients and family members. Whilst these impairments are typically attributed to deterioration of the frontal-striatal pathways, accumulating evidence suggests that hippocampal dysfunction may also contribute to such impairments. Here, we employ a novel spatial memory task that has previously been shown to elicit impairments in individuals with focal hippocampal lesions, as a means to further investigate the role of hippocampal dysfunction in HD., Method: Sixty-four individuals participated in the study, including 32 healthy controls, 11 patients with diagnosed HD and 16 premanifest HD gene carriers. We also included an additional control group of 5 individuals with focal unilateral basal ganglia lesions. Participants undertook a task that measured perception and short-term spatial memory using computer-generated visual scenes., Results: HD patients experienced significant impairments in spatial perception and memory, which strongly correlated with disease burden score (DBS). Premanifest gene carriers performed at a similar level to healthy controls throughout all aspects of the task indicating that the effects seen in the HD patients represent a deterioration in function. Interestingly, basal ganglia lesion patients were not impaired in any aspects of the task., Conclusion: There is evidence of significant deficits in hippocampal-dependent spatial cognition in HD that cannot be explained as a function of degeneration to the basal ganglia. The impairments were greatest in individuals with higher DBSs, suggesting that deficits relate to the disease process in HD., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Post-navigation awake quiescence, relative to task engagement, benefits the accuracy of a new "cognitive map". This effect is hypothesized to reflect awake quiescence, like sleep, being conducive to the consolidation and integration of new spatial memories. Sleep has been shown to improve cognitive map accuracy over time. It remained unknown whether awake quiescence can induce similar time-related improvements in new cognitive maps, or whether it simply counteracts their decay. We examined this question via two experiments. In Experiment 1, using an established cognitive mapping paradigm, we reveal that map accuracy for a virtual town was significantly better in people whose memory was probed after 10 min of post-navigation awake quiescence or ongoing cognitive engagement, relative to those whose memory was probed shortly after initial navigation. In Experiment 2, using a newly developed cognitive mapping task that involved a more complex and real-life virtual town, we again found that map accuracy was superior in those whose memory was probed after 10 min of awake quiescence than those who were tested soon after navigation. These findings indicate that actual improvements in human memories are not restricted to sleep. Thus, contrary to conventional wisdom and theories, the passage of (day)time need not always result in forgetting., (© 2019 Wiley Periodicals, Inc.)

Introduction: In recent years, there have been many works devoted to the study of the effects of sex hormones on cognitive function. Clinical studies have found that inmenopausal women, the tendency to develop type 2 diabetes will increase, the spatial and short-term working memory worsens, and there is a tendency to develop depression. The findings suggest that estrogens are involved in the mechanisms of insulin resistance in tissues, in the synthesis of mediators in the catecholaminergic systems of the brain, but many questions remain unresolved., The Aim: Therefore, the aim of our study was to establish the effect of estrogens on the indices of spatial memory in ovariectomized and old rats against the background of the development of experimental diabetes., Material and Methods: The study was conducted on 30 adult rats females 4-5 months and 20 months. The study groups were ovariectomized and reproduced experimental type 2 diabetes mellitus with protamine sulfate. The study of spatial memory was carried out in an eight-sleeved radial labyrinth., Results and Conclusions: Results and conclusions: Ovariectomy caused the deterioration of spatial memory relative to the living control group, and diabetes mellitus aggravated pathological changes. The changes that occur after ovariectomy suggest estrogen involvement in the regulation of cognitive functions.