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• Female rats show faster and more effective trauma extinction than males. • Shock reminder reactivates fear memory only in male rats. • Ultrasonic vocalizations mirror fear behavior profiles in both sexes. • Study underscores the need for female inclusion in preclinical PTSD research. Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition arising from traumatic experiences, marked by abnormal fear memories. Despite women are twice as likely as men to develop PTSD, the biological mechanisms underlying this disparity remain inadequately explored, particularly in preclinical studies involving female subjects. Previous research shows that female rats exhibit active fear responses, while males display passive behaviors. Additionally, sex differences in ultrasonic vocalizations (USVs) during fear conditioning have been observed, indicating varying emotional responses. Here, we validated a traumatic stress model consisting of footshock exposure paired with social isolation − originally developed in male rats − on females for the first time, focusing on sex differences in fear memory expression, retention and extinction. Our findings reveal that only during trauma exposure, males predominantly exhibited passive responses, whereas females demonstrated more active responses, despite both sexes emitting similar numbers of alarm USVs. Females also showed lower levels of freezing and USV emissions throughout extinction sessions and displayed a higher extinction rate compared to males. Notably, only males displayed a conditioned fear response when triggered by a single mild stressor. These findings highlight sex differences in trauma responses and fear memory processes. The study emphasizes the importance of incorporating 22-kHz USV evaluations along with other behavioral metrics for a comprehensive understanding of fear memory. This research contributes to the existing literature on traumatic stress models as well as underscores the necessity of including female subjects in preclinical studies to better inform treatment and prevention strategies tailored to both sexes. [ABSTRACT FROM AUTHOR]

Memory impairment is a serious cognitive side effect of electroconvulsive therapy (ECT) in the treatment of major depressive episodes (MDEs) and has garnered widespread attention in clinical practice, but its underlying evolution pattern during the course of ECT remains rarely understood in detail. Associative memory (AM) is a core indicator that reflects memory impairment in ECT. This study aimed to identify the dynamic trajectory of AM impairment and explore associated predictive factors. 405 intensive longitudinal AM data from 81 patients with MDE were collected at the baseline, after the first, third, fifth, and eighth ECT using five sets of face-cued word memory paradigms. Changes in AM score over time were analyzed using a linear mixed effects model. Trajectory subgroups and predictive factors were investigated using growth mixture model and logistic regression. AM score during ECT were significantly lower than at baseline, with the lowest scores observed after the eighth ECT session. Two trajectories of rapid (N = 56, 69.14%) and slow (N = 25, 30.86%) AM impairment were differentiated. Older female with lower education level were significant predictors contributing to more rapid memory impairment for ECT. The evolving pattern of associative memory impairment during ECT appears to occur early and worsen with subsequent treatment. This study may provide the important evidence understanding of the number effect of ECT sessions on memory impairment and suggest individual factors for predicting ECT memory outcome. [ABSTRACT FROM AUTHOR]

The cerebellum is a key structure in working and procedural memory. The aim of the present prospective exploratory study was to investigate, the metabolic characteristics of the cerebellum in posterior fossa tumor (PFT) survivors using 3D proton magnetic resonance spectroscopy imaging (3D MRSI), to determine whether metabolites could be useful biomarkers of memory impairment. Sixty participants were included in the IMPALA study, divided into three groups: 22 irradiated PFT, 17 nonirradiated PFT, and 21 healthy controls matched with irradiated PFT for age, sex, and handedness. PFT survivors were treated at least 5 years ago, either by surgery or a combination of surgery, chemotherapy, and radiotherapy. All participants underwent working and procedural memory tests and multimodal MRI including a 3D MRSI sequence. N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) metabolite values were extracted from the cerebellum for comparisons between groups, correlations with neurocognitive test scores, and radiotherapy doses. Median (range) age at neurocognitive tests was 18 (7–26) years. Median Cho, Cr, NAA, and Lac values, and the ratio of NAA to the sum of metabolites were significantly lower for PFT survivors than for healthy controls (p < 0.05). Scores on working and procedural memory tests were significantly lower for PFT survivors (p < 0.004) and correlated with median and maximum Cho and NAA values (0.28 < r < 0.49, p < 0.04). Except for creatine, the other metabolites were not significantly different between irradiated and nonirradiated survivors. MRSI values in the cerebellum were not correlated with either total dose or doses received by this structure. Results revealed changes in cerebellar metabolic values in PFT survivors that were closely correlated with memory deficits, suggesting that some metabolites could be used as markers of cognitive decline, but this will require validation on a larger sample size. • 3D MRSI was used to assess metabolic profile of cerebellum in posterior fossa tumor (PFT) survivors. • Cerebellar metabolic values were lower in PFT survivors. • Metabolite values were closely correlated with memory deficits. • Some metabolites could be used as markers of memory impairment. [ABSTRACT FROM AUTHOR]

• Cognitive impairments may be developed post nerve injuries of upper limb. • There is no cognitive impairment post musculoskeletal injuries to upper limb without nerve damage. • Cognitive impairments appear within one month post traumatic upper limb injuries. The purpose of this study was to investigate the association between cognitive impairments and traumatic upper limb injuries of the acute phase. A cross-sectional observational study was conducted with three groups: a nerve-injury group, a without nerve injury group, and a control group (uninjured participants). Demographic characteristics (e.g. age, sex, body mass index, and education) and traumatic characteristics (duration since injury, injury side, pain, light touch sensation, hand motor function) were recorded. Short-term memory and executive functions were assessed using Rey Auditory and Verbal Learning Test (RAVLT) and Stroop Color and Word Test (SCWT, including SIECT and SIECN), respectively. The study comprised 43 participants in the nerve-injury group, 30 participants in the group without nerve injury, and 104 participants in the control group. Generalized linear model was applied to explore the difference of cognitive functions among three groups with impactors. Significantly poorer performance on the RAVLT was observed in the nerve-injury group compared to the other two groups, and lower score of SIECT in nerve-injury group was lower compared to the control group. However, there was no significant difference of SIECN among three groups. In addition, traumatic characteristics did not significantly impact RAVLT and SIECT (p > 0.05) in all injured participants. Traumatic nerve injury to the upper limb appears to be associated with both short-term memory and executive function impairment, whereas musculoskeletal injuries without nerve damage showed no cognitive impairment. Therefore, it is important to monitor cognitive function following upper limb nerve injuries. [ABSTRACT FROM AUTHOR]

Stereotyped brain asymmetry, also known as laterality, is widespread and multiscale, encompassing asymmetrical molecular function, left–right (LR) asymmetrical neurons or circuits, structural differences, and lateralized behaviors. Brain laterality can modulate a wide variety of behaviors and cognitive functions, including sleep, memory, food preference, fear, and anxiety. Long-term memory is among the most evolutionary conserved cognitive traits influenced by brain lateralization. The mechanisms and molecular pathways governing brain laterality vary widely among model organisms. The current limited understanding of the diversity of asymmetries hinders the definition of common principles and conserved symmetry-breaking mechanisms. The concordance between body and brain LR asymmetry can be strong, partial, or completely absent, raising questions about the emergence and coordination of asymmetry between the brain and body. Chirality is a fundamental trait of living organisms, encompassing the homochirality of biological molecules and the left–right (LR) asymmetry of visceral organs and the brain. The nervous system in bilaterian organisms displays a lateralized organization characterized by the presence of asymmetrical neuronal circuits and brain functions that are predominantly localized within one hemisphere. Although body asymmetry is relatively well understood, and exhibits robust phenotypic expression and regulation via conserved molecular mechanisms across phyla, current findings indicate that the asymmetry of the nervous system displays greater phenotypic, genetic, and evolutionary variability. In this review we explore the use of nematode, zebrafish, and Drosophila genetic models to investigate neuronal circuit asymmetry. We discuss recent discoveries in the context of body–brain concordance and highlight the distinct characteristics of nervous system asymmetry and its cognitive correlates. [ABSTRACT FROM AUTHOR]

Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory. Sixteen adult Sprague–Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated. Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane. Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently. [ABSTRACT FROM AUTHOR]

An alternating direction implicit (ADI) scheme is proposed to study the numerical solution of a three-dimensional integrodifferential equation (IDE) with multi-term tempered singular kernels. Firstly, we employ the Crank-Nicolson method and the product integral (PI) rule on a uniform grid to approximate the temporal derivative and the multi-term tempered-type integral terms, thus establishing a second-order temporal discrete scheme. Then, a second-order finite difference method is used for spatial discretization and combined with the ADI technique to improve computational efficiency. Based on regularity conditions, the stability and convergence analysis of the ADI scheme is given by the energy argument. Finally, numerical examples confirm the results of the theoretical analysis and show that the method is effective. [ABSTRACT FROM AUTHOR]

The "structural disconnection" hypothesis of cognitive aging suggests that deterioration of white matter (WM), especially myelin, results in cognitive decline, yet in vivo evidence is inconclusive. We examined age differences in WM microstructure using Myelin Water Imaging and Diffusion Tensor Imaging in 141 healthy participants (age 20–79). We used the Virginia Cognitive Aging Project and the NIH Toolbox® to generate composites for memory, processing speed, and executive function. Voxel-wise analyses showed that lower myelin water fraction (MWF), predominantly in prefrontal WM, genu of the corpus callosum, and posterior limb of the internal capsule was associated with reduced memory performance after controlling for age, sex, and education. In structural equation modeling, MWF in the prefrontal white matter and genu of the corpus callosum significantly mediated the effect of age on memory, whereas fractional anisotropy (FA) did not. Our findings support the disconnection hypothesis, showing that myelin decline contributes to age-related memory loss and opens avenues for interventions targeting myelin health. • Myelin in prefrontal areas predicts memory performance. • Myelin, but not fractional anisotropy, mediates the age-memory relationship. • Myelin-cognition associations persist after adjusting for age. • Fractional anisotropy does not predict memory beyond age. [ABSTRACT FROM AUTHOR]

La radiothérapie cérébrale peut entraîner des complications neurologiques à long terme, notamment des troubles mnésiques. L'objectif de cette étude prospective est d'évaluer l'impact de l'irradiation des tumeurs bénignes de la base du crâne situées à proximité des hippocampes sur la mémoire autobiographique. De 2016 à 2019, les patients atteints de méningiome du sinus caverneux ou d'un adénome hypophysaire et traités par irradiation normofractionnée, ont été inclus. Les patients ont eu une évaluation neuropsychologique complète initiale, à 1 an puis à 2 ans après le traitement. Les tests neuropsychologiques ont été convertis en Z-Score pour être comparables. Douze patients sur les 19 inclus ont eu une évaluation complète sur le plan neuropsychologique à 2 ans et ont fait l'objet de l'analyse. Sur le Test épisodique de mémoire du passé autobiographique (« TEMPau »), aucune différence significative à 2 ans de la mémoire autobiographique n'a été constatée, quelle que soit la période concernant cette mémoire. La dose moyenne hippocampique n'avait pas d'impact sur la variation de la mémoire autobiographique. Il n'existait pas de dégradation cognitive significative dans les autres domaines évalués comme l'attention, la mémoire antérograde, la mémoire de travail et les fonctions exécutives. La mémoire autobiographique était indépendante de ces autres domaines cognitifs, ce qui justifie de son étude spécifique. La radiothérapie de la base du crâne pour une pathologie bénigne n'entraîne pas de différence de mémoire autobiographique à 2 ans. Un suivi plus long serait nécessaire afin de conforter ces résultats. Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory. From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1 year and 2 years post-treatment. Neuropsychological tests were converted to Z-Score for comparability. Twelve of the 19 patients included had a complete neuropsychological evaluation at 2 years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2 years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study. Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results. [ABSTRACT FROM AUTHOR]

Extending on previous findings that computerized Memory Specificity Training (c-MeST) improves memory specificity and depressive symptoms in Major Depressive Disorder (MDD) in adults, this study aimed to assess the effects of c-MeST in youth with MDD on memory specificity and depression in addition to other treatment. Participants aged 15–25 (N = 359, 76 % female; M age = 19.2, SD = 3.1), receiving predominantly psychological therapy or counseling (85 %) and/or antidepressants (52 %) were randomized to usual care and c-MeST or usual care. Cognitive and clinical outcomes were assessed at baseline and at one, three, and six-month follow-ups. The usual care and c-MeST group reported higher memory specificity at one-month (d = 0.42, p =.022), but not at three or six months (d 's < 0.15, p 's > 0.05). The rate of MDE was numerically lower in the c-MeST group at each follow-up time-point, but group was not a statistically significant predictor at one month (64 % usual care and c-MeST vs. 68 % usual care, OR = 0.81, p =.606), three months (67 % usual care and c-MeST vs. 72 % usual care, OR = 0.64, p =.327) or six months (55 % usual care and c-MeST vs. 68 % usual care, OR = 0.56, p =.266). The usual care and c-MeST group did report lower depressive symptoms at one month (d = 0.42, p =.023) and six-months (d = 0.84, p =.001), but not three-months (d = 0.13, p >.05). c-MeST may reduce symptoms in youth with MDD when provided alongside other treatments. However, there are significant limitations to this inference, including high attrition in the study and a need for more data on the acceptability of the intervention. • Overgeneral memory appears to maintain depressive symptoms. • Computerized memory specificity training (c-MeST) improved memory specificity. • Depressive symptoms were reduced at one and six-month follow-up. • The effects occurred in addition to receiving other mental health support. • C-MeST may be a beneficial adjunct for youth with major depressive disorder. [ABSTRACT FROM AUTHOR]

Nonmedical use of psychostimulants as cognitive enhancers is increasingly common in young adults, despite studies showing mixed results and health risks, including sleep disturbance and addiction. Given the importance of sleep for complex cognitions, expected outcomes of stimulants for performance should be consider as a function of the reliance of each cognitive domain on 'offline' processes optimized during sleep. Thus, performance on attention and vigilance task may be sustained with stimulants, whereas executive functions, long-term memory, creativity and the like will show no enhancement or even worse performance. Nonmedical use of stimulants is a public health problem. More systematic investigations are needed that thoroughly account for the impact of stimulants on cognitive domains, stages of processing, and the mediating role of sleep disturbance, in the short and long term. Nonmedical use of psychostimulants for cognitive enhancement is widespread and growing in neurotypical individuals, despite mixed scientific evidence of their effectiveness. Sleep benefits cognition, yet the interaction between stimulants, sleep, and cognition in neurotypical adults has received little attention. We propose that one effect of psychostimulants, namely decreased sleep, may play an important and unconsidered role in the effect of stimulants on cognition. We discuss the role of sleep in cognition, the alerting effects of stimulants in the context of sleep loss, and the conflicting findings of stimulants for complex cognitive processes. Finally, we hypothesize that sleep may be one unconsidered factor in the mythology of stimulants as cognitive enhancers and propose a methodological approach to systematically assess this relation. [ABSTRACT FROM AUTHOR]

• Age-related cognitive decline was detected through rodent temporal order recognition. • Poor temporal order memory is rescued by D 1 dopamine agonists. • Optimal effective doses vary markedly among individual rats of different age groups. • Population effectiveness may be influenced by agonist functional selectivity. Dopamine D 1 receptor agonists improve spatial working memory, but their effects on temporal order memory, particularly prone to the effects of aging, have not been studied. Two D 1 agonists, PF6256142 (PF) and 2-methyldihydrexidine (2MDHX), were examined for their effects in a rodent temporal order recognition task. Our results are consistent with the hypothesis that there is an age-related decline in rodent temporal order memory. The data also show that either agonist rescues the poor memory performance with a large effective size. Interestingly, the optimal effective dose varied among individual rats of different age groups. PF showed greater potency for older rats, whereas 2MDHX showed better overall population effectiveness. Both PF and 2MDHX have high intrinsic activity at rodent D 1 -mediated cAMP synthesis. Conversely, at D 1 -mediated β-arrestin recruitment, PF has essentially no intrinsic activity, whereas 2MDHX is a super-agonist. These findings suggest that D 1 agonists have potential to treat age-related cognitive decline, and the pattern of functional selectivity may be useful for developing drugs with an improved therapeutic index. [ABSTRACT FROM AUTHOR]

[Display omitted] • Memory consolidation occurs primarily through a coordinated communication between hippocampus and neocortex. • Sharp-wave ripples represent the reactivation of neurons associated with recently acquired memories and play a crucial role in memory storage and use. • Abnormalities in neuronal reactivation are a common phenomenon in many kinds of neuropsychiatric diseases. • Impaired neural reactivation underlies the mechanism and symptoms of some neuropsychiatric diseases. Memory consolidation refers to a process by which labile newly formed memory traces are progressively strengthened into long term memories and become more resistant to interference. Recent work has revealed that spontaneous hippocampal activity during rest, commonly referred to as "offline" activity, plays a critical role in the process of memory consolidation. Hippocampal reactivation occurs during sharp-wave ripples (SWRs), which are events associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Memory consolidation occurs primarily through a coordinated communication between hippocampus and neocortex. Cortical slow oscillations drive the repeated reactivation of hippocampal memory representations together with SWRs and thalamo-cortical spindles, inducing long-lasting cellular and network modifications responsible for memory stabilization. In this review, we aim to comprehensively cover the field of "reactivation and memory consolidation" research by detailing the physiological mechanisms of neuronal reactivation and firing patterns during SWRs and providing a discussion of more recent key findings. Several mechanistic explanations of neuropsychiatric diseases propose that impaired neural replay may underlie some of the symptoms of the disorders. Abnormalities in neuronal reactivation are a common phenomenon and cause pathological impairment in several diseases, such as Alzheimer's disease (AD), epilepsy and schizophrenia. However, the specific pathological changes and mechanisms of reactivation in each disease are different. Recent work has also enlightened some of the underlying pathological mechanisms of neuronal reactivation in these diseases. In this review, we further describe how SWRs, ripples and slow oscillations are affected in Alzheimer's disease, epilepsy, and schizophrenia. We then compare the differences of neuronal reactivation and discuss how different reactivation abnormalities cause pathological changes in these diseases. Aberrant neural reactivation provides insights into disease pathogenesis and may even serve as biomarkers for early disease progression and treatment response. [ABSTRACT FROM AUTHOR]

The representational momentum for physical state changes refers to the fact that we remember objects as more changed in physical state than they actually were. It has been well documented that depressive disorder is associated with impairment of time perception. Thus, the present work was conducted with the aim to investigate the representational momentum for physical state changes in patients with depressive disorder, firstly. Forty patients with depressive disorder and forty-two healthy controls were administrated with the task of representational momentum for physical state changes and task of time perception. The stimulus comprises 10 videos showing object state changes (e.g., ice melting). During playing, the video would stop and immediately be obscured by mosaics at a specific point. Participants select from three detection images (the exact frame of the video just be masked, the frame after that, and the frame before that) to test representational momentum and estimate the duration of the video in seconds to test time perception. The depressive group showed diminished representational momentum (i.e., lower scores on the task of representational momentum) than normal controls (U = 215.00, Z = −5.83, p < 0.001). In addition, the scores on the task of representational momentum were significantly positively related with the scores on the task of time perception among depressive group (r = 0.446, p = 0.004). The findings indicate that patients with depressive disorder may exhibit diminished representational momentum for physical states, which may be correlated with their impairment of time perception. • The representational momentum in patients with depressive disorder has not been explored. • Impairment affects representational momentum and time perception. • Impaired representational momentum may be associated with impaired time perception. [ABSTRACT FROM AUTHOR]

Historically, economic models of memory have neglected a pivotal aspect: decay, the established notion that memories deteriorate over time, resulting in a loss of fidelity. In this paper we show that a framework of rational memory with decay can produce the recency effect and other intuitively appealing memory phenomena. We apply the framework to both finite time and dynamic programming settings, deriving a wide range of results with a focus on comparative statics and asymptotic behaviors. Many of our results can also be applied to multi-dimensional rational inattention settings where individuals have to split their attention across several information sources. [ABSTRACT FROM AUTHOR]

• Caregivers read to their child a book with opportunities to integrate facts. • The book either had or did not have embedded questions on the book's facts. • Questions increased dyads' integration of facts in talk while reading. • Children's memory integration performance was most predicted by integration talk. • Shared book reading promotes young children's factual memory integration. Young children rapidly learn facts about the world. One mechanism supporting knowledge acquisition is memory integration: derivation of new knowledge by combining separate, yet related facts accumulated over time. There are both developmental changes and individual differences in young children's learning through memory integration. However, there is little research on how everyday social interactions may promote memory integration and contribute to individual differences. Accordingly, we investigated how the everyday social interactions of caregiver-child shared book reading support 5- to 6-year-olds' memory integration (N = 82 parent-child dyads; 47 female children; M age 6.10; 56.5 % White non-Latinx, 15 % Black, 6 % White Latinx, 5.5 % Asian, 17 % more than one race). Caregivers read a narrative book that included opportunities to integrate facts. Half the dyads were assigned to an embedded questions condition (questions on facts included throughout the book) and half to a no embedded questions condition (statements only). We measured dyads' extratextual talk while reading for the extent to which they integrated the facts (integration talk). Children's learning was tested with both memory integration and fact recall questions. Dyads in the embedded questions condition had more integration talk. The extent to which the dyads integrated while reading predicted children's integration performance, above and beyond condition effects. This effect was specific to memory integration: integration talk nor condition accounted for fact recall. These results suggest that shared book reading can support young children's integration, especially when books engage dyads through embedded questions and dyads integrate facts while reading. [ABSTRACT FROM AUTHOR]

Rescuing memory deficits remains a major challenge in treating Alzheimer's disease (AD) and schizophrenia (SCZ). Parvalbumin interneurons (PVIs) mediate network activities relevant to memory functions. Current research suggests that the ability of PVIs to functionally adapt upon increased network activity underlies the generation of memories. The cell-type-specific interaction of neuronal plasticity on the cellular and network level (PVI cell-to-network plasticity) is a promising target in addressing memory deficits. Two clinically accessible strategies targeting PVI plasticity have emerged for the treatment of memory deficits in AD and SCZ: PVI-specific neuromodulation and high-frequency stimulation in the gamma frequency range (40 Hz). Research into clinically assessing PVI cell-to-network plasticity in humans will be essential to transfer current findings into clinical practice. Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance. Here we argue that deficits of PVI cell-to-network plasticity may underlie memory deficits in AD and SCZ, and we explore two therapeutic avenues: the targeting of PVI-specific neuromodulation, including by neuropeptides, and the recruitment of network synchrony in the gamma frequency range (40 Hz) by external stimulation. We finally propose that these approaches be merged under consideration of recent insights into human brain physiology. [ABSTRACT FROM AUTHOR]

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60–80 years) and 26 young participants (20–30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4–8 Hz) and synchronization in gamma (30–45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging. • Sequence memory, an important aspect of episodic memory, declines in healthy aging. • Lower theta and higher gamma activity in encoding of correct trials in young adults. • No subsequent memory effect in oscillatory brain activity in healthy older adults. • Theta phase modulates gamma amplitude to code for item position in older adults. [ABSTRACT FROM AUTHOR]

Dissociative identity disorder (DID) is characterised by, among others, subjectively reported inter-identity amnesia, reflecting compromised information transfer between dissociative identity states. Studies have found conflicting results regarding memory transfer between dissociative identity states. Here, we investigated inter-identity amnesia in individuals with DID using self-relevant, subject specific stimuli, and behavioural and neural measures. Data of 46 matched participants were included; 14 individuals with DID in a trauma-avoidant state, 16 trauma-avoiding DID simulators, and 16 healthy controls. Reaction times and neural activation patterns related to three types of subject specific words were acquired and statistically analysed, namely non-self-relevant trauma-related words (NSt), self-relevant trauma-related words from a trauma-avoidant identity state (St), and trauma-related words from a trauma-related identity state (XSt). We found no differences in reaction times between XSt and St words and faster reaction times for XSt over NSt. Reaction times of the diagnosed DID group were the longest. Increased brain activation to XSt words was found in the frontal and parietal regions, while decreased brain activity was found in the anterior cingulate cortex in the diagnosed DID group. The current study reproduces and amalgamates previous behavioural reports as well as brain activation patterns. Our finding of increased cognitive control over self-relevant trauma-related knowledge processing has important clinical implications and calls for the redefinition of "inter-identity amnesia" to "inter-identity avoidance". [ABSTRACT FROM AUTHOR]

Effective learning strategies are crucial to the development of academic skills and information retention, especially in post secondary education where increasingly complex subjects are explored. Active recall-based strategies have been identified as particularly effective for long-term learning. This systematic review investigates the effectiveness of various active recall-based learning strategies for improving academic performance and self-efficacy in higher education students. A systematic review of peer-reviewed articles was conducted with a priori criteria by searching PubMed, ScienceDirect, JSTOR, PsycInfo, and Web of Science databases. Search results were screened/extracted and reconciled by two independent authors with the use of a piloted screening tool. Included studies were assessed for quality and risk of bias using the GRADE Quality Assessment Tool for Quantitative Studies. Three overarching study strategies were extracted for further investigation including flashcards, practice testing or retrieval practice, and concept mapping. Within each category, three additional unique search strings were searched, screened, and extracted. A qualitative analysis of the studies was provided. Among the appraised articles, flashcards were found to be popular and correlated with higher GPA and test scores. Self-testing, retrieval practice, and concept mapping were also effective but under-utilized. Concept mapping was found to boost student confidence. Active recall strategies exhibit promise for effective learning and additional research in these developing field can support academic pursuits. • There are a range of learning strategies that students can implement to achieve stronger information retention skills, that they can apply to different facets of their life. • Significant active recall strategies reflected potential in technology-associated interventions, gamified learning experiences, and edutainment-based learning intervention. • Heterogeneity in included studies allude to inconsistent reports for certain associations of academic outcomes and learning strategies [ABSTRACT FROM AUTHOR]

The retrieval–extinction paradigm based on memory reconsolidation can prevent fear memory recurrence more effectively than the extinction paradigm. High-intensity fear memories tend to resist reconsolidation. Novelty–retrieval–extinction can promote the reconsolidation of fear memory lacking neuroplasticity in rodents; however, whether it could effectively promote high-intensity fear memory reconsolidation in humans remains unclear. Using 120 human participants, we implemented the use of the environment (novel vs. familiar) with the help of virtual reality technology. Novelty environment exploration was combined with retrieval–extinction in fear memory of two intensity levels (normal vs. high) to examine whether novelty facilitates the reconsolidation of high-intensity fear memory and prevents recurrence. Skin conductance responses were used to clarify novelty–retrieval–extinction effects at the behavioral level across three experiments. Retrieval–extinction could prevent the reinstatement of normal-intensity fear memory; however, for high-intensity fear memory, only the novelty–retrieval–extinction could prevent recurrence; we further validated that novelty–retrieval–extinction may be effective only when the environment is novel. Although the high-intensity fear memory is higher than normal-intensity in this study, it may be insufficient relative to fear experienced in real-world contexts or by individuals with mental disorders. To some extent, these findings indicate that the novelty–retrieval–extinction paradigm could prevent the recurrence of high-intensity fear memory, and we infer that novelty of environment may play an important role in novelty–retrieval–extinction paradigm. The results of this study have positive implications for the existing retrieval extinction paradigm and the clinical treatment of phobia. • Retrieval-extinction could prevent reinstatement of normal-intensity fear. • Novelty-retrieval-extinction could prevent recurrence of high-intensity fear. • Novelty of environment may play an important role in novelty–retrieval–extinction paradigm. [ABSTRACT FROM AUTHOR]

Exercise training is among the main strategies that have been proposed to promote cognitive and brain health outcomes in older individuals with and without cognitive impairment. The effects of exercise on cognition are mediated, in part, by structural and functional adaptations in the brain, including changes in gray matter volumes and white matter microstructural integrity. Muscular contractions during exercise produce a category of cytokines referred to as myokines, which represent a potential molecular pathway mediating neuroplastic adaptations and associated cognitive improvements in response to exercise. Understanding the ideal combination of exercise training parameters across populations and life stages could lead to interventions that promote greater effects on cognitive and brain health outcomes. Exercise training is an important strategy to counteract cognitive and brain health decline during aging. Evidence from systematic reviews and meta-analyses supports the notion of beneficial effects of exercise in cognitively unimpaired and impaired older individuals. However, the effects are often modest, and likely influenced by moderators such as exercise training parameters, sample characteristics, outcome assessments, and control conditions. Here, we discuss evidence on the impact of exercise on cognitive and brain health outcomes in healthy aging and in individuals with or at risk for cognitive impairment and neurodegeneration. We also review neuroplastic adaptations in response to exercise and their potential neurobiological mechanisms. We conclude by highlighting goals for future studies, including addressing unexplored neurobiological mechanisms and the inclusion of under-represented populations. [ABSTRACT FROM AUTHOR]

Memories are sometimes best forgotten, but how do our brains weaken unwanted details of the past? We propose a theoretical framework in which memory reactivation during sleep supports adaptive forgetting. This mnemonic rebalancing underpins the affective benefits of sleep by ensuring that our memories remain aligned with our emotional goals. [ABSTRACT FROM AUTHOR]

Fish experiencing harvest mortality often evolve a fast life-history that prioritizes investment in current versus future reproduction, thereby potentially limiting energetic investment in the brain. Fisheries may also select for shy fish that are less willing to learn, or directly select fish with poor cognitive ability. The resulting evolutionary changes can alter the cognitive performance of individuals and affect fish populations and fisheries quality. [ABSTRACT FROM AUTHOR]

Decision making is often necessary before performing an action. Traditionally, it has been assumed that decision making and motor control are independent, sequential processes. Ogasa et al. challenge this view, and demonstrate that the decision-making process significantly impacts on the formation and retrieval of motor memory by tagging it with the level of confidence. [ABSTRACT FROM AUTHOR]

Sleep is crucial for memory, as it promotes its encoding, consolidation, storage, and retrieval. Sleep periods following learning enhance memory consolidation. Leptin, a hormone that regulates appetite and energy balance, also influences memory and neuroplasticity. It plays a neurotrophic role in the hippocampus, enhancing synaptic function and promoting memory processes. Given these associations between sleep, memory, and leptin, this study aimed to evaluate the interplay between sleep quality, memory complaints and leptin levels. Using data from the São Paulo Epidemiologic Sleep Study (EPISONO) 2007 edition, we analyzed data from 881 participants who underwent evaluations for subjective sleep quality (Pittsburgh Sleep Quality Index), memory function (Prospective and Retrospective Memory Questionnaire), body mass index and plasmatic leptin levels. After confirming that subjects with poor sleep quality had more memory complaints in our cohort, we observed that leptin levels were increased in individuals with more memory complaints, but there was no association between leptin levels and sleep quality. Mediation analysis reinforced the direct effect of sleep quality on memory function, but leptin had no indirect effect as mediator over the sleep-memory association. Moderation analysis revealed that leptin acted as a moderator in the relationship between sleep quality and memory, with increased leptin levels enhancing the effect of sleep quality over memory function. These findings underscore the intricate interplay between sleep, memory, and metabolic factors like leptin, shedding light on potential mechanisms through which sleep influences memory and cognitive functions. Further research is needed to elucidate the exact mechanisms underlying these relationships and their implications for overall health and well-being. • Poor sleep quality was associated with more memory complaints. • There was no significant difference in leptin levels between individuals with good and poor sleep quality. • Leptin acted as a moderator in the relationship between sleep quality and memory function. • Sleep, memory, and metabolic factors like leptin are probably interconnected, influencing each other's functions. [ABSTRACT FROM AUTHOR]

To establish the impact of a 3-minute computerized cognitive training program (START) on cognition in older adults with and without genetic risk of Alzheimer's disease. Two-arm randomized controlled trial of the START program. Remote online trial in adults older than 50 taking part from home. The trial compared the START program with placebo in 6544 people older than 50. Primary outcome was executive function measured through Trailmaking B, with other secondary cognitive measures. Genetic risk profile and ApoE4 status were determined by Illumina Array. START conferred benefit to executive function, attention, memory, and a composite measure, including in people with the ApoE4 genotype. The 3-minute START task offers a means of supporting cognitive health in older adults and could be used at scale and within a precision medicine approach to reduce risk of cognitive decline in a targeted way. [ABSTRACT FROM AUTHOR]

Stress modulates the activity of various memory systems and can thereby guide behavioral interaction with the environment in an adaptive or maladaptive manner. At the cellular level, a large body of evidence indicates that (nor)adrenaline and glucocorticoid release induced by acute stress exposure affects synapse function and synaptic plasticity, which are critical substrates for learning and memory. Recent evidence suggests that memories are supported in the brain by sparsely distributed neurons within networks, termed engram cell ensembles. While the physiological and molecular effects of stress on the synapse are increasingly well characterized, how these synaptic modifications shape the multiscale dynamics of engram cell ensembles is still poorly understood. In this review, we discuss and integrate recent information on how acute stress affects synapse function and how this may alter engram cell ensembles and their synaptic connectivity to shape memory strength and memory precision. We provide a mechanistic framework of a synaptic engram under stress and put forward outstanding questions that address knowledge gaps in our understanding of the mechanisms that underlie stress-induced memory modulation. [ABSTRACT FROM AUTHOR]

The ability to differentiate stimuli that predict fear is critical for survival; however, the underlying molecular and circuit mechanisms remain poorly understood. We combined transgenic mice, in vivo transsynaptic circuit-dissecting anatomical approaches, optogenetics, pharmacological methods, and electrophysiological recording to investigate the involvement of specific extended amygdala circuits in different fear memory. We identified the projections from central lateral amygdala (CeL) protein kinase C δ (PKCδ)–positive neurons and somatostatin (SST)-positive neurons to GABAergic (gamma-aminobutyric acidergic) and glutamatergic neurons in the ventral part of the bed nucleus of stria terminalis (vBNST). Prolonged optogenetic activation or inhibition of the PKCδCeL-vBNST pathway specifically reduced context fear memory, whereas the SSTCeL-vBNST pathway mainly reduced tone fear memory. Intriguingly, optogenetic manipulation of vBNST neurons that received the projection from PKCδCeL neurons exerted bidirectional regulation of context fear, whereas manipulation of vBNST neurons that received the projection from SSTCeL neurons could bidirectionally regulate both context and tone fear memory. We subsequently demonstrated the presence of δ and κ opioid receptor protein expression within the CeL-vBNST circuits, potentially accounting for the discrepancy between prolonged activation of GABAergic circuits and inhibition of downstream vBNST neurons. Finally, administration of an opioid receptor antagonist cocktail on the PKCδCeL-vBNST or SSTCeL-vBNST pathway successfully restored context or tone fear memory reduction induced by prolonged activation of the circuits. Together, these findings establish a functional role for distinct CeL-vBNST circuits in the differential regulation and appropriate maintenance of fear. [ABSTRACT FROM AUTHOR]

How well do we distinguish between different memory sources when the information from imagination and perception is similar? And how do metacognitive (confidence) judgments differ across different sources of experiences? To study these questions, we developed a reality monitoring task using semantically related words from the Deese-Roediger-McDermott (DRM) paradigm of false memories. In an orientation phase, participants either perceived word pairs or had to voluntarily imagine the second word of a word pair. In a test phase, participants viewed words and had to judge whether the paired word was previously perceived, imagined, or new. Results revealed an interaction between memory source and judgment type on both response rates and confidence judgments: reality monitoring was better for new and perceived (compared to imagined) sources, and participants often incorrectly reported imagined experiences to be perceived. Individuals exhibited similar confidence between correct imagined source judgments and incorrect imagined sources reported to be perceived. Modeling results indicated that the observed judgments were likely due to an externalizing bias (i.e., a bias to judge the memory source as perceived). Additionally, we found that overall metacognitive ability was best in the perceived source. Together, these results reveal a source-dependent effect on response rates and confidence ratings, and provide evidence that observers are surprisingly prone to externalizing biases when monitoring their own memories. • We developed a new reality monitoring paradigm using words from the DRM task. • Reality monitoring was better for new and perceived (compared to imagined) words. • Correct & incorrect imagined memories (reported as perceived) had similar confidence. • Modeling results suggest an "externalization bias" when judging memory sources. [ABSTRACT FROM AUTHOR]

Newly formed memories require strengthening and reorganisation (consolidation) after learning. The sleeping brain is hallmarked by slow oscillations (SOs), spindles, and ripples. These rhythms drive neuronal firing rates with increasing efficacy and spatiotemporal precision. While SOs set global windows of excitability and inhibition, nested spindles serve as relays that partially reactivate cortical learning networks, facilitate hippocampal ripples, and bias the content of associated memory reactivation. Ripples activate local memory circuits and drive hippocampal–cortical pattern completion to strengthen and reorganise memory traces. SO–spindle–ripple coupling thus governs consolidation processes at the neuronal (synaptic) and brain-wide (systems) level. How do passing moments turn into lasting memories? Sheltered from external tasks and distractions, sleep constitutes an optimal state for the brain to reprocess and consolidate previous experiences. Recent work suggests that consolidation is governed by the intricate interaction of slow oscillations (SOs), spindles, and ripples – electrophysiological sleep rhythms that orchestrate neuronal processing and communication within and across memory circuits. This review describes how sequential SO–spindle–ripple coupling provides a temporally and spatially fine-tuned mechanism to selectively strengthen target memories across hippocampal and cortical networks. Coupled sleep rhythms might be harnessed not only to enhance overnight memory retention, but also to combat memory decline associated with healthy ageing and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The Göttingen minipig is fast becoming the standard for assessing dermal chemical hazards because, like most swine, its skin is predictive of human skin response and because this strain's smaller size makes laboratory manipulations and husbandry easier. Unfortunately, standard behavioral tests and apparatus have not been developed for behavioral assessments of this swine strain. Indeed, computer-controlled automated behavioral testing procedures are much needed. The present research advanced this goal by producing a home-cage behavioral testing system that could accommodate minipigs of various sizes (ages). An aluminum frame housed three levers for recording operant responses, and LEDs above and below each lever served as discriminative stimuli. A commercially available food pellet dispenser was attached to a specialized pellet receptacle capable of measuring pellet retrieval. Two behavioral tests were selected and adapted from our commonly used non-human primate behavioral assessments: delayed match-to-sample (a memory test) and temporal response differentiation (a time-estimation test). Minipigs were capable of learning both tests and attaining stable performance. Next, scopolamine was used to validate the sensitivity of the behavioral tests for gauging behavioral perturbations in this swine strain. Scopolamine dose-effect functions were comparable to those observed in other species, including non-human primates, wherein 37.5 µg/kg of scopolamine (administered intramuscularly) reduced responding approximately 50%. Thus, we were successful in developing the apparatus and automated operant behavioral tests necessary to characterize drug safety in this swine strain. This capability will be valuable for characterizing chemical agent toxicity as well as the safety and efficacy of medical countermeasures. • Swine may provide a good large animal research alternative to canines and monkeys. • Standard, automated behavioral tests for swine are needed. • We developed an adaptable system for testing operant behavior in swine. • Methods were validated using scopolamine on memory and timing tests. • Results demonstrated the success of the methods and sensitivity of both tests. [ABSTRACT FROM AUTHOR]

Brain functional and structural changes lead to cognitive decline during aging, but a high level of cognitive stimulation during life can improve cognitive performances in the older adults, forming the cognitive reserve. Noradrenaline has been proposed as a molecular link between environmental stimulation and constitution of the cognitive reserve. Taking advantage of the ability of olfactory stimulation to activate noradrenergic neurons of the locus coeruleus, we used repeated olfactory enrichment sessions over the mouse lifespan to enable the cognitive reserve buildup. Mice submitted to olfactory enrichment, whether started in early or late adulthood, displayed improved olfactory discrimination at late ages and interestingly, improved spatial memory and cognitive flexibility. Moreover, olfactory and non-olfactory cognitive performances correlated with increased noradrenergic innervation in the olfactory bulb and dorsal hippocampus. Finally, c-Fos mapping and connectivity analysis revealed task-specific remodeling of functional neural networks in enriched older mice. Long-term olfactory enrichment thus triggers structural noradrenergic plasticity and network remodeling associated with better cognitive aging and thereby forms a promising mouse model of the cognitive reserve buildup. • Long-term olfactory enrichment broadly improves cognition in older mice. • Long-term olfactory enrichment induces local expansion of noradrenergic innervation. • Long-term olfactory enrichment drives task-specific brain network remodeling. • Olfactory stimulation along the life span allows the cognitive reserve build up. [ABSTRACT FROM AUTHOR]

Increasing evidence demonstrated that mitophagy and endoplasmic reticulum stress (ERS) was closely associated with memory decline in elderly type 2 diabetes mellitus (T2DM). Tea polyphenols (TP), an excellent natural antioxidant, has been reported to have neuroprotective properties in aging and diabetes, but the underlying mechanisms are still not fully understood. This study targets ERS-mitophagy in hippocampal neurons to investigate the improvement effect of memory in aged T2DM rats by TP. Rats were randomly divided into the control group, the aged group, the aged T2DM model group, the TP 75, 150, 300 mg/kg groups. TP 300 mg/kg ameliorated mitophagy by decreasing the levels of p-mTOR (S2448), P62 and HSP60 and increasing the levels of PINK1 and Parkin, the ratio of LC3Ⅱ/LC3Ⅰ, co-localization of LC3 and HSP60 and the number of autophagosomes and autolysosomes. TP 300 mg/kg attenuated ERS by downregulating the levels of p-PERK, p-eIF2α, ATF4, GRP78 and restoring the ER structure. To further verify epigallocatechin gallate (EGCG), which is the main active component of TP, enhanced mitophagy by inhibiting ERS, PC12 cells were pretreated with ERS activator tunicamycin (TM) or ERS inhibitor 4-phenylbutyric acid (4-PBA). The results showed that the improvement of mitophagy by EGCG was inhibited by TM and promoted by 4-PBA. Collectively, ERS-mitophagy in hippocampal neurons plays a key role in the improvement of memory by TP in aged T2DM rats. This study will provide a new perspective and strategy for the prevention of memory decline in elderly with T2DM. [Display omitted] • Tea polyphenols improves spatial memory and apoptosis in hippocampal neurons. • Mitophagy and endoplasmic reticulum stress involve in the apoptosis. • Endoplasmic reticulum stress mediated by PERK/eIF2α/ATF4 signaling pathway. • Mitophagy mediated by mTOR/PINK1/Parkin signaling pathway. • Tea polyphenols improves mitophagy by inhibiting endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Purposive decision-making, based on sensory input and memory, is a component of executive functioning. Evaluating executive functioning is crucial for understanding neuropsychiatric disorders and brain injuries. However, there's a lack of mouse tests for this purpose. To address this, we developed a novel touchscreen task to assess purposive decision-making in mice. In the present task, the mice had to touch the correct window (left or right), with a visual stimulus as a cue for decision-making. The mice gradually acquired a relationship between the visual stimuli and the action they should take. Each mouse made the correct choice more than 80% of the time based on the visual cue and memory and knowledge of themselves. We could clearly determine when the mice saw the visual cue. The present task offers a valuable tool for investigating the neural mechanisms behind decision-making. • Purposive decision-making task of mice was developed in touchscreen apparatus. • Mice can make a memory-dependent decision. • Provides a clear reference point for decision-making by touching a start cue. [ABSTRACT FROM AUTHOR]

While many people experience potentially threatening events during their life, only a minority develops posttraumatic stress disorder (PTSD). The identification of individuals at risk among those exposed to trauma is crucial for PTSD prevention in the future. Since re-experiencing trauma elements outside of the original trauma-context is a core feature of PTSD, we investigate if the ability to bind memories to their original encoding context (i.e. memory contextualization) predicts PTSD vulnerability. We hypothesize that pre-trauma neutral memory contextualization (under stress) negatively relates to PTSD-like behavior, in a prospective design using the cut-off behavioral criteria rat model for PTSD. 72 male Sprague Dawley rats were divided in two experimental groups to assess the predictive value of 1) memory contextualization without acute stress (NS-group) and 2) memory contextualization during the recovery phase of the acute stress-response (S-group) for susceptibility to PTSD-like behavior. A powerful extension to regression analysis -path analysis-was used to test this specific hypothesis, together with secondary research questions. Following traumatic predator scent stress, 19.4% of the rats displayed PTSD-like behavior. Results showed a negative relation between pre-trauma memory contextualization and PTSD-like behavior, but only in the NS-group. Pre-trauma memory contextualization was positively related to fear association in the trauma environment, again only in the NS group. If the predictive value of pre-trauma contextualization of neutral information under non-stressful conditions for PTSD susceptibility is replicated in prospective studies in humans, this factor would supplement already known vulnerability factors for PTSD and improve the identification of individuals at risk among the trauma exposed, especially those at high trauma risk such as soldiers deployed on a mission. • Only a minority of trauma-exposed individual develop posttraumatic stress disorder. • Pre-trauma neutral memory contextualization predicts PTSD-like behavior in rats. • This vulnerability factor needs replication in prospective human studies. [ABSTRACT FROM AUTHOR]

Schizophrenia is characterized by persistent cognitive deficits that significantly impact functional outcomes. Despite the current available treatments, these deficits remain inadequately addressed, highlighting the need to explore the effect of more novel treatments on cognition. The current study examined the effect of intranasal oxytocin on cognitive functioning in people with schizophrenia by utilizing data from a 12-week, randomized controlled trial. Sixty-seven participants with schizophrenia or schizoaffective disorder were randomized to receive placebo or intranasal oxytocin. Participants completed a comprehensive neuropsychological battery at baseline and 12 weeks. The results demonstrated that intranasal oxytocin did not significantly improve cognition in people with schizophrenia compared to placebo. These findings suggest that oxytocin does not worsen or enhance cognition in people with schizophrenia. Yet, the current intervention did not standardize the timing of cognitive assessments relative to the timing of oxytocin administration, which may explain our findings. Future studies attempting to clarify this relationship would benefit from employing a more controlled approach to the timing of treatment and assessments. [ABSTRACT FROM AUTHOR]

Recent papers have emphasized the primary role of cellular information management in biological and evolutionary development. In this framework, intelligent cells collectively measure environmental cues to improve informational validity to support natural cellular engineering as collaborative decision-making and problem-solving in confrontation with environmental stresses. These collective actions are crucially dependent on cell-based memories as acquired patterns of response to environmental stressors. Notably, in a cellular self-referential framework, all biological information is ambiguous. This conditional requirement imposes a previously unexplored derivative. All cellular memories are imperfect. From this atypical background, a novel theory of aging and death is proposed. Since cellular decision-making is memory-dependent and biology is a continuous natural learning system, the accumulation of previously acquired imperfect memories eventually overwhelms the flexibility cells require to react adroitly to contemporaneous stresses to support continued cellular homeorhetic balance. The result is a gradual breakdown of the critical ability to efficiently measure environmental information and effect cell-cell communication. This age-dependent accretion governs senescence, ultimately ending in death as an organism-wide failure of cellular networking. This approach to aging and death is compatible with all prior theories. Each earlier approach illuminates different pertinent cellular signatures of this ongoing, obliged, living process. [ABSTRACT FROM AUTHOR]

While depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. One hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. The time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = −0.20, p = 0.043; Fishers r-to-z = −3.19). Longitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. Older participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations. • Older adults with depressive symptoms demonstrate delayed sleep onset • Less SWS was associated with poorer memory in the depression group but not in the control group • Hippocampal volume and prefrontal cortex thickness were not related to slow wave sleep outcomes in older adults with depression symptoms [ABSTRACT FROM AUTHOR]

The hippocampus (HPC) plays a pivotal role in fear learning and memory. Our two recent studies suggest that rapid eye movement (REM) sleep via the HPC downregulates fear memory consolidation and promotes fear extinction. However, it is not clear whether and how the dorsal and the ventral HPC regulates fear memory differently; and how the HPC in wake regulates fear memory. By chemogenetic stimulating in the HPC directly and its afferent entorhinal cortex that selectively activated the HPC in REM sleep for 3-6 h post-fear-acquisition, we found that HPC activation in REM sleep consolidated fear extinction memory. In particular, dorsal HPC (dHPC) stimulation in REM sleep virtually eliminated fear memory by enhancing fear extinction and reducing fear memory consolidation. By contrast, chemogenetic stimulating HPC afferent the supramammillary nucleus (SUM) induced 3-hr wake with HPC activation impaired fear extinction. Finally, desipramine (DMI) injection that selectively eliminated REM sleep for >6 h impaired fear extinction. Our results demonstrate that the HPC is critical for fear memory regulation; and wake HPC and REM sleep HPC have an opposite role in fear extinction of respective impairment and consolidation. • HPC activation in REM sleep consolidated fear extinction memory. • The dorsal HPC stimulation in REM sleep eliminated fear memory by enhancing fear extinction and reducing fear memory consolidation. • Wake HPC and REM HPC have an opposite role in fear extinction of respective impairment and consolidation. [ABSTRACT FROM AUTHOR]

Contiguity in the perception of space and time is a crucial prerequisite for the formation of interpretable sensory experiences and impressions. As proposed by Wilhelm Wundt, the 'fusion' of spatial and temporal events relies on associative processes (i.e., the detection and learning of associative relationships). The role of associations in elementary sensory processes demonstrates the importance of the 'associativity motif' in brain function and has indeed been suggested as a basis of cognitive functions as well. Capacities for the processing of associative information are not only present in the cortex, but also in non-cortical brain areas, in particular the cerebellum. Input-specific calcium transients and calcium sensor proteins linked to plasticity pathways provide essential components of a cell's associativity detection machinery. Our brains are good at detecting and learning associative structures; according to some linguistic theories, this capacity even constitutes a prerequisite for the development of syntax and compositionality in language and verbalized thought. I will argue that the search for associative motifs in input patterns is an evolutionary old brain function that enables contiguity in sensory perception and orientation in time and space. It has its origins in an elementary material property of cells that is particularly evident at chemical synapses: input-assigned calcium influx that activates calcium sensor proteins involved in memory storage. This machinery for the detection and learning of associative motifs generates knowledge about input relationships and integrates this knowledge into existing networks through updates in connectivity patterns. [ABSTRACT FROM AUTHOR]

Fluctuations in temperature severely impact crop yield and trigger various plant response mechanisms. In a recent study, Zhou et al. discovered a non-canonical role of autophagy in mediating Golgi apparatus restoration after short-term heat stress (HS). Their results further suggest a critical, yet previously unknown, mechanism of autophagy-related (ATG)-8 in Golgi reassembly after HS. [ABSTRACT FROM AUTHOR]

• Swimming training and caffeine revert the increase of NF-kB phosphorylation in rat hippocampus induced by chronic fructose intake. • Swimming training decreases anxiety-like behavior in rats with metabolic syndrome. • Swimming and caffeine improve lipid profile and blood glucose clearance. Metabolic syndrome (MS) is a disorder that increasingly affects the world population, mainly because of changes in lifestyle and dietary habits. In this regard, both physical exercise and caffeine are low-cost and easily accessible therapies that separately have shown positive effects against metabolic disorders. Therefore, we hypothesized that physical exercise combined with caffeine could have a synergistic effect in the treatment of MS, risk factors, and cognitive deficits. Animals were divided into 8 groups and received fructose (15% w/v) or vehicle for 10 weeks. Swimming training and caffeine (6 mg/kg) started 4 weeks after fructose administration. Trained animals presented decreased body weight and visceral fat mass and increased soleus weight compared with untrained fructose-treated animals. Caffeine supplementation also prevented the gain of visceral fat mass induced by fructose. Furthermore, both treatments reversed fructose-induced decrease in glucose clearance over time and fructose-induced increase in 4-hydroxynonenal and nuclear factor-κB immunoreactivity. Physical training also improved the lipidic profile in fructose-treated animals (high-density lipoprotein, low-density lipoprotein, and triglycerides), improved short-term, long-term, and localization memory, and reversed the fructose-induced deficit in short-term memory. Physical training also increased nuclear factor erythroid 2-related factor 2 immunoreactivity per se. Considering that physical training and caffeine reversed some of the damages induced by fructose it is plausible to consider these treatments as alternative, nonpharmacological, and low-cost therapies to help reduce MS-associated risk factors; however, combined treatments did not show additive effects as hypothesized. Over 10 weeks, rats consumed water containing 15% fructose. During the last 6 weeks, animals underwent caffeine intake and swimming training. These treatments reduced fructose-induced anxiety-like behavior, hyperglycemia, body fat mass, 4-HNE and NF-κB immunoreactivity, and improved lipid profile impairments. Additionally, swimming training increased muscle mass and NRF2. Abbreviations: 4-HNE, 4-hydroxynonenal; NF-κB, nuclear factor κB); NRF2, nuclear factor erythroid 2-related factor 2). [Display omitted] [ABSTRACT FROM AUTHOR]

Episodic memory performance declines with increasing age, and older adults typically show reduced activation of inferior temporo-parietal cortices in functional magnetic resonance imaging (fMRI) studies of episodic memory formation. Given the age-related cortical volume loss, it is conceivable that age-related reduction of memory-related fMRI activity may be partially attributable to reduced grey matter volume (GMV). We performed a voxel-wise multimodal neuroimaging analysis of fMRI correlates of successful memory encoding, using regional GMV as covariate. In a large cohort of healthy adults (106 young, 111 older), older adults showed reduced GMV across the entire neocortex and reduced encoding-related activation of inferior temporal and parieto-occipital cortices compared to young adults. Importantly, these reduced fMRI activations during successful encoding could in part be attributed to lower regional GMV. Our results highlight the importance of controlling for structural MRI differences in fMRI studies in older adults but also demonstrate that age-related differences in memory-related fMRI activity cannot be attributed to structural variability alone. [Display omitted] • Structural differences in distinct age groups may in part explain fMRI differences. • We included voxel-wise GMV into models of the fMRI subsequent memory effect. • Reduced encoding-related activations could in part be attributed to lower local GMV. • Care is advised when modelling fMRI effects for groups with structural differences. • Structural modalities may in part explain alleged differences in function. [ABSTRACT FROM AUTHOR]

Healthy aging is typically accompanied by cognitive decline. Previous work has shown that engaging in multiple, non-work activities during midlife can have a protective effect on cognition several decades later, rendering it less dependent on brain structural health; the definition of "cognitive reserve". Other work has shown that increasing age is associated with reduced segregation of large-scale brain functional networks. Here we tested the hypothesis that functional segregation (SyS) mediates this effect of middle-aged lifestyle on late-life cognition. We used fMRI data from three tasks in the CamCAN dataset, together with cognitive data on fluid intelligence, episodic memory, and retrospective lifestyle data from the Lifetime of Experiences Questionnaire (LEQ). In all three tasks, we showed that SyS related to fluid intelligence even after adjusting for the (nonlinear) age effects. However, we found no evidence that SyS in late-life mediated the relationship between non-specific (non-occupation) midlife activities and either measure of cognition in late-life. Thus, the brain correlates of cognitive reserve arising from mid-life activities remain to be discovered. • System segregation (SyS) is stable across different brain states. • SyS is negatively associated with age. • Fluid intelligence, but not episodic memory, was robustly predicted by SyS. • Late life SyS was not associated with midlife outside of work activities. [ABSTRACT FROM AUTHOR]

[Display omitted] Efficient immune responses rely on the proper differentiation of CD8+ T cells into effector and memory cells. Here, we show a critical requirement of N6-Methyladenosine (m6A) methyltransferase Mettl3 during CD8+ T cell responses upon acute viral infection. Conditional deletion of Mettl3 in CD8+ T cells impairs effector expansion and terminal differentiation in an m6A-dependent manner, subsequently affecting memory formation and the secondary response of CD8+ T cells. Our combined RNA-seq and m6A-miCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators. Remarkably, Mettl3 binds to the Tbx21 transcript and stabilizes it, promoting effector differentiation of CD8+ T cells. Moreover, ectopic expression of T-bet partially restores the defects in CD8+ T cell differentiation in the absence of Mettl3. Thus, our study highlights the role of Mettl3 in regulating multiple target genes in an m6A-dependent manner and underscores the importance of m6A modification during CD8+ T cell response. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a debilitating neurological disorder caused by an impact to the head by an outside force. TBI results in persistent cognitive impairments, including fear generalization and the inability to distinguish between aversive and neutral stimuli. The mechanisms underlying fear generalization have not been fully elucidated, and there are no targeted therapeutics to alleviate this symptom of TBI. To identify the neural ensembles mediating fear generalization, we utilized ArcCreERT2 × enhanced yellow fluorescent protein (EYFP) mice, which allow for activity-dependent labeling and quantification of memory traces. Mice were administered a sham surgery or the controlled cortical impact model of TBI. Mice were then administered a contextual fear discrimination paradigm and memory traces were quantified in numerous brain regions. In a separate group of mice, we tested if (R , S)-ketamine could decrease fear generalization and alter the corresponding memory traces in TBI mice. TBI mice exhibited increased fear generalization when compared with sham mice. This behavioral phenotype was paralleled by altered memory traces in the dentate gyrus, CA3, and amygdala, but not by alterations in inflammation or sleep. In TBI mice, (R,S)-ketamine facilitated fear discrimination, and this behavioral improvement was reflected in dentate gyrus memory trace activity. These data show that TBI induces fear generalization by altering fear memory traces and that this deficit can be improved with a single injection of (R,S)-ketamine. This work enhances our understanding of the neural basis of TBI-induced fear generalization and reveals potential therapeutic avenues for alleviating this symptom. [ABSTRACT FROM AUTHOR]

Posterior fossa tumours (PFTs), which account for two-thirds of paediatric brain tumours, are successfully treated in about 70% of patients, but most survivors experience long-term cognitive impairment. We evaluated arterial spin labelling (ASL), a common, non-invasive magnetic resonance imaging (MRI) technique, as a biomarker of cognitive impairment in a paediatric PFT survivor population. Sixty participants were prospectively analysed. PFT survivors were at least 5 years post-treatment and had been treated as appropriate for their age and type of tumour. Group 1 had received radiotherapy and Group 2 had not. Group 3 were healthy controls matched to Group 1 for age, sex and handedness. All participants underwent cognitive assessment and multimodal MRI, including an ASL perfusion sequence. We used semi-quantitative ASL methods to assess differences in mean perfusion in the thalamus, caudate, putamen and hippocampus. Statistically, no significant associations between cognitive data and radiation doses were identified. Compared with healthy controls, Group 1 patients had significantly lower overall mean perfusion values (20–30% lower, depending on the cerebral structure) and Group 2 had slightly lower mean perfusion values (5–10% lower). Perfusion values did not correlate with total prescribed irradiation doses nor with doses received by different cerebral structures. Episodic and semantic memory test scores were significantly lower in Group 1 and correlated with lower mean absolute perfusion values in the hippocampus (P < 0.04). These preliminary results indicate that radiotherapy affects the perfusion of specific cerebral structures and identify perfusion as a potential biomarker of hippocampus-dependent memory deficit. • A semi-quantitative ASL method was used to quantify cognitive loss in PFT survivors. • Radiotherapy induced long-term overall cerebral semi-quantitative hypoperfusion in a paediatric PFT population. • Perfusion values tend to correlate significantly with the mean radiation dose received by the left hippocampus but not other brain structures examined. • A decrease in hippocampal perfusion is therefore a potential marker of memory impairment in irradiated children. [ABSTRACT FROM AUTHOR]