Subjective memory complaints in young people; their relationship withobjective cognitive performance and the role of neuroticism / Quejas subjetivas de memoria en jóvenes; su relación con el rendimiento cognitivo objetivo y el papel del neuroticismo

Las percepciones de olvidos recurrentes o episodios de distracción en la vida diaria se denominan quejas subjetivas de memoria (QSM). Su naturaleza se ha estudiado ampliamente en adultos mayores, pero su importancia y relación con el rendimiento neurocognitivo no se han abordado por completo en adultos más jóvenes. Se han sugerido algunos rasgos psicológicos como posibles moderadores de la asociación entre el rendimiento de la memoria objetiva y subjetiva. El primer objetivo de este estudio fue analizar la correspondencia entre la percepción objetiva y subjetiva de los fallos de memoria en jóvenes. En segundo lugar, estudiamos si el rasgo psicológico del neuroticismo podría estar influyendo en esta relación. Para ello, medimos QSM, diferentes dominios cognitivos (memoria episódica y de trabajo y funciones ejecutivas) y neuroticismo en 80 hombres y mujeres jóvenes. Los resultados mostraron que solo la memoria episódica inmediata estaba estadísticamente relacionada con los QSM. Curiosamente, las relaciones negativas entre el rendimiento de la memoria objetiva y subjetiva solo aparecieron en participantes con mayor neuroticismo. Por lo tanto, las quejas de memoria reportadas por los jóvenes podrían reflejar un peor rendimiento de la memoria episódica inmediata, mientras que el neuroticismo jugaría un papel principal en la asociación entre los déficits de memoria y las QSM. Este estudio proporciona datos que pueden ayudar a comprender mejor las QSM en los jóvenes.(AU)

Perceptions of recurrent forgetfulness or episodes of distraction in daily life are referred to as subjective memory complaints (SMCs). Their nature has been extensively studied in older adults, but their significance and relationship with neurocognitive performance have not been fully ad-dressed in younger adults. Some psychological traits have been suggested as possible moderators of the association between objective and subjective memory performance. The first aim of this study was to analyze the corre-spondence between the objective and subjective perception of memory failures in young people. Second, we studied whether the psychological trait of neuroticism could be influencing this relationship. Todo this, we measured SMCs, different cognitive domains (episodic and working memory and executive functions), and neuroticism in 80 young men and women. Results showed that only immediate episodic memory was statisti-cally related to SMCs. Interestingly, the negative relationships between ob-jective and subjective memory performance only appeared in participants with higher neuroticism. Thus, memory complaints reported by young people could reflect poorer immediate episodic memory performance, whereas neuroticism would play a main role in the association between memory deficits and SMCs. This study provides data that can help to bet-ter understand SMCs in young people.(AU)

An Exploration of the Memory Performance in Older Adult Hearing Aid Users on the Integrated Digit-in-Noise Test.

This study aimed to preliminarily investigate the associations between performance on the integrated Digit-in-Noise Test (iDIN) and performance on measures of general cognition and working memory (WM). The study recruited 81 older adult hearing aid users between 60 and 95 years of age with bilateral moderate to severe hearing loss. The Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) was used to screen older adults for mild cognitive impairment. Speech reception thresholds (SRTs) were measured using 2- to 5-digit sequences of the Mandarin iDIN. The differences in SRT between five-digit and two-digit sequences (SRT5-2), and between five-digit and three-digit sequences (SRT5-3), were used as indicators of memory performance. The results were compared to those from the Digit Span Test and Corsi Blocks Tapping Test, which evaluate WM and attention capacity. SRT5-2 and SRT5-3 demonstrated significant correlations with the three cognitive function tests (rs ranging from -.705 to -.528). Furthermore, SRT5-2 and SRT5-3 were significantly higher in participants who failed the MoCA-BC screening compared to those who passed. The findings show associations between performance on the iDIN and performance on memory tests. However, further validation and exploration are needed to fully establish its effectiveness and efficacy.

The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.

Virtual reality-based training may improve visual memory and some aspects of sustained attention among healthy older adults - preliminary results of a randomized controlled study.

BACKGROUND/AIMS: Older age and cognitive inactivity have been associated with cognitive impairment, which in turn is linked to economic and societal burdens due to the high costs of care, especially for care homes and informal care. Emerging non-pharmacological interventions using new technologies, such as virtual reality (VR) delivered on a head-mounted display (HMD), might offer an alternative to maintain or improve cognition. The study aimed to evaluate the efficacy and safety of a VR-based Digital Therapeutics application for improving cognitive functions among healthy older adults. METHODS: Seventy-two healthy seniors (experimental group N = 35, control group N = 37), aged 65-85 years, were recruited by the Medical University of Lodz (Poland). Participants were randomly allocated to the experimental group (a VR-based cognitive training which consists of a warm-up module and three tasks, including one-back and dual-N-back) or to the control group (a regular VR headset app only showing nature videos). The exercises are performed in different 360-degree natural environments while listening to a preferred music genre and delivered on a head-mounted display (HMD). The 12-week intervention of 12 min was delivered at least three times per week (36 sessions). Compliance and performance were followed through a web-based application. Primary outcomes included attention and working memory (CNS-Vital Signs computerized cognitive battery). Secondary outcomes comprised other cognitive domains. Mixed linear models were constructed to elucidate the difference in pre- and post-intervention measures between the experimental and control groups. RESULTS: The users performed, on average, 39.8 sessions (range 1-100), and 60% performed more than 36 sessions. The experimental group achieved higher scores in the visual memory module (B = 7.767, p = 0.011) and in the one-back continuous performance test (in terms of correct responses: B = 2.057, p = 0.003 and omission errors: B = -1.950, p = 0.007) than the control group in the post-test assessment. The results were independent of participants' sex, age, and years of education. The differences in CNS Vital Signs' global score, working memory, executive function, reaction time, processing speed, simple and complex attention, verbal memory, cognitive flexibility, motor speed, and psychomotor speed were not statistically significant. CONCLUSIONS: VR-based cognitive training may prove to be a valuable, efficacious, and well-received tool in terms of improving visual memory and some aspect of sustainability of attention among healthy older adults. This is a preliminary analysis based on part of the obtained results to that point. Final conclusions will be drawn after the analysis of the target sample size. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT05369897.

Functional connectivity is linked to working memory differences in children with reading learning disability.

Reading learning disability (RLD) is characterized by a specific difficulty in learning to read that is not better explained by an intellectual disability, lack of instruction, psychosocial adversity, or a neurological disorder. According to the domain-general hypothesis, a working memory deficit is the primary problem. Working memory in this population has recently been linked to altered resting-state functional connectivity within the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) compared to that in typically developing individuals. The main purpose of the present study was to compare the within-network functional connectivity of the DMN, SN, FPN, and reading network in two groups of children with RLD: a group with lower-than-average working memory (LWM) and a group with average working memory (AWM). All subjects underwent resting-state functional magnetic resonance imaging (fMRI), and data were analyzed from a network perspective using the network brain statistics framework. The results showed that the LWM group had significantly weaker connectivity in a network that involved brain regions in the DMN, SN, and FPN than the AWM group. Although there was no significant difference between groups in reading network in the present study, other studies have shown relationship of the connectivity of the angular gyrus, supramarginal gyrus, and inferior parietal lobe with the phonological process of reading. The results suggest that although there are significant differences in functional connectivity in the associated networks between children with LWM and AWM, the distinctive cognitive profile has no specific effect on the reading network.

The effects of slow wave sleep characteristics on semantic, episodic, and procedural memory in people with epilepsy.

Slow wave sleep (SWS) is highly relevant for verbal and non-verbal/spatial memory in healthy individuals, but also in people with epilepsy. However, contradictory findings exist regarding the effect of seizures on overnight memory retention, particularly relating to procedural and non-verbal memory, and thorough examination of episodic memory retention with ecologically valid tests is missing. This research explores the interaction of SWS duration with epilepsy-relevant factors, as well as the relation of spectral characteristics of SWS on overnight retention of procedural, verbal, and episodic memory. In an epilepsy monitoring unit, epilepsy patients (N = 40) underwent learning, immediate and 12 h delayed testing of memory retention for a fingertapping task (procedural memory), a word-pair task (verbal memory), and an innovative virtual reality task (episodic memory). We used multiple linear regression to examine the impact of SWS duration, spectral characteristics of SWS, seizure occurrence, medication, depression, seizure type, gender, and epilepsy duration on overnight memory retention. Results indicated that none of the candidate variables significantly predicted overnight changes for procedural memory performance. For verbal memory, the occurrence of tonic-clonic seizures negatively impacted memory retention and higher psychoactive medication load showed a tendency for lower verbal memory retention. Episodic memory was significantly impacted by epilepsy duration, displaying a potential nonlinear impact with a longer duration than 10 years negatively affecting memory performance. Higher drug load of anti-seizure medication was by tendency related to better overnight retention of episodic memory. Contrary to expectations longer SWS duration showed a trend towards decreased episodic memory performance. Analyses on associations between memory types and EEG band power during SWS revealed lower alpha-band power in the frontal right region as significant predictor for better episodic memory retention. In conclusion, this research reveals that memory modalities are not equally affected by important epilepsy factors such as duration of epilepsy and medication, as well as SWS spectral characteristics.

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy.

Introduction: Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi. While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC). Methods: Here, we employed high-dimensional flow cytometry to analyze CD4+ T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms. Results: Effector CD27-CD4+ T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4+ T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4+ T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21-, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients. Discussion: Taken together, our results showed that T. cruzi infection triggers changes in CD4+ T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease. Conclusion: Overall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.

Not Everybody Has an Inner Voice: Behavioral Consequences of Anendophasia.

It is commonly assumed that inner speech-the experience of thought as occurring in a natural language-is a human universal. Recent evidence, however, suggests that the experience of inner speech in adults varies from near constant to nonexistent. We propose a name for a lack of the experience of inner speech-anendophasia-and report four studies examining some of its behavioral consequences. We found that adults who reported low levels of inner speech (N = 46) had lower performance on a verbal working memory task and more difficulty performing rhyme judgments compared with adults who reported high levels of inner speech (N = 47). Task-switching performance-previously linked to endogenous verbal cueing-and categorical effects on perceptual judgments were unrelated to differences in inner speech.

Perceptions and outcomes of an embedded Alzheimer Society First Link Coordinator in rural primary health care memory clinics.

BACKGROUND: Primary health care has a central role in dementia detection, diagnosis, and management, especially in low-resource rural areas. Care navigation is a strategy to improve integration and access to care, but little is known about how navigators can collaborate with rural primary care teams to support dementia care. In Saskatchewan, Canada, the RaDAR (Rural Dementia Action Research) team partnered with rural primary health care teams to implement interprofessional memory clinics that included an Alzheimer Society First Link Coordinator (FLC) in a navigator role. Study objectives were to examine FLC and clinic team member perspectives of the impact of FLC involvement, and analysis of Alzheimer Society data comparing outcomes associated with three types of navigator-client contacts. METHODS: This study used a mixed-method design. Individual semi-structured interviews were conducted with FLC (n = 3) and clinic team members (n = 6) involved in five clinics. Data were analyzed using thematic inductive analysis. A longitudinal retrospective analysis was conducted with previously collected Alzheimer Society First Link database records. Memory clinic clients were compared to self- and direct-referred clients in the geographic area of the clinics on time to first contact, duration, and number of contacts. RESULTS: Three key themes were identified in both FLC and team interviews: perceived benefits to patients and families of FLC involvement, benefits to memory clinic team members, and impact of rural location. Whereas other team members assessed the patient, only FLC focused on caregivers, providing emotional and psychological support, connection to services, and symptom management. Face-to-face contact helped FLC establish a relationship with caregivers that facilitated future contacts. Team members were relieved knowing caregiver needs were addressed and learned about dementia subtypes and available services they could recommend to non-clinic clients with dementia. Although challenges of rural location included fewer available services and travel challenges in winter, the FLC role was even more important because it may be the only support available. CONCLUSIONS: FLC and team members identified perceived benefits of an embedded FLC for patients, caregivers, and themselves, many of which were linked to the FLC being in person.

From "online brains" to "online lives": understanding the individualized impacts of Internet use across psychological, cognitive and social dimensions.

In response to the mass adoption and extensive usage of Internet-enabled devices across the world, a major review published in this journal in 2019 examined the impact of Internet on human cognition, discussing the concepts and ideas behind the "online brain". Since then, the online world has become further entwined with the fabric of society, and the extent to which we use such technologies has continued to grow. Furthermore, the research evidence on the ways in which Internet usage affects the human mind has advanced considerably. In this paper, we sought to draw upon the latest data from large-scale epidemiological studies and systematic reviews, along with randomized controlled trials and qualitative research recently emerging on this topic, in order to now provide a multi-dimensional overview of the impacts of Internet usage across psychological, cognitive and societal outcomes. Within this, we detail the empirical evidence on how effects differ according to various factors such as age, gender, and usage types. We also draw from new research examining more experiential aspects of individuals' online lives, to understand how the specifics of their interactions with the Internet, and the impact on their lifestyle, determine the benefits or drawbacks of online time. Additionally, we explore how the nascent but intriguing areas of culturomics, artificial intelligence, virtual reality, and augmented reality are changing our understanding of how the Internet can interact with brain and behavior. Overall, the importance of taking an individualized and multi-dimensional approach to how the Internet affects mental health, cognition and social functioning is clear. Furthermore, we emphasize the need for guidelines, policies and initiatives around Internet usage to make full use of the evidence available from neuroscientific, behavioral and societal levels of research presented herein.

Choline Metabolites Reverse Differentially the Habituation Deficit and Elevated Memory of Tau Null Drosophila.

Impaired neuronal plasticity and cognitive decline are cardinal features of Alzheimer's disease and related Tauopathies. Aberrantly modified Tau protein and neurotransmitter imbalance, predominantly involving acetylcholine, have been linked to these symptoms. In Drosophila, we have shown that dTau loss specifically enhances associative long-term olfactory memory, impairs foot shock habituation, and deregulates proteins involved in the regulation of neurotransmitter levels, particularly acetylcholine. Interestingly, upon choline treatment, the habituation and memory performance of mutants are restored to that of control flies. Based on these surprising results, we decided to use our well-established genetic model to understand how habituation deficits and memory performance correlate with different aspects of choline physiology as an essential component of the neurotransmitter acetylcholine, the lipid phosphatidylcholine, and the osmoregulator betaine. The results revealed that the two observed phenotypes are reversed by different choline metabolites, implying that they are governed by different underlying mechanisms. This work can contribute to a broader knowledge about the physiologic function of Tau, which may be translated into understanding the mechanisms of Tauopathies.

Multiscale Transfer Printing via Shape Memory Polymer with High Adhesion and Modulus Switchability.

Flexible electronics have gained significant attention as an innovative solution to meet the growing need for information collection from the human body and the environment. However, a critical challenge lies in the need for a transfer printing technique that can fabricate rigid and brittle devices on flexible organic substrates. Here, we develop a multiscale transfer printing technique using an ultraviolet-curable shape memory polymer (SMP) that serves as both the stamp and the receiver substrate. The SMP demonstrates exceptional mechanical performance with toughness at room temperature and remarkable flexibility near its glass transition temperature. The SMP material exhibits an impressive shape recovery ratio and remarkable adhesion switchability. We demonstrate robust transfer printing of diverse objects with different materials and morphologies and in situ transfer of multiscale metallic structures. In addition, the in situ fabricated transparent hyperthermia patches with embedded metal grids are demonstrated, offering potential application in the field of sensors, wearable devices, and electronic skin.

Cellular senescence is a double-edged sword in regulating aged immune responses to influenza.

Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance of p16-expressing cells upon administration of ganciclovir (GCV). While p16-expressing cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although clearance of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV-treated mice. Furthermore, GCV-treated mice were unable to mount an optimal memory response and demonstrated increased viral load following heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.

Q-Learning to navigate turbulence without a map.

We consider the problem of olfactory searches in a turbulent environment. We focus on agents that respond solely to odor stimuli, with no access to spatial perception nor prior information about the odor location. We ask whether navigation strategies to a target can be learned robustly within a sequential decision making framework. We develop a reinforcement learning algorithm using a small set of interpretable olfactory states and train it with realistic turbulent odor cues. By introducing a temporal memory, we demonstrate that two salient features of odor traces, discretized in few olfactory states, are sufficient to learn navigation in a realistic odor plume. Performance is dictated by the sparse nature of turbulent plumes. An optimal memory exists which ignores blanks within the plume and activates a recovery strategy outside the plume. We obtain the best performance by letting agents learn their recovery strategy and show that it is mostly casting cross wind, similar to behavior observed in flying insects. The optimal strategy is robust to substantial changes in the odor plumes, suggesting minor parameter tuning may be sufficient to adapt to different environments.

Long-term effects of Preweaning environmental impoverishment on neurobehavioral and neurocognitive outcomes in Sprague Dawley rats: An early environmental stress model.

Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.

Acquired amusia after a right middle cerebral artery infarction - a case study.

A 62-year-old musician-MM-developed amusia after a right middle-cerebral-artery infarction. Initially, MM showed melodic deficits while discriminating pitch-related differences in melodies, musical memory problems, and impaired sensitivity to tonal structures, but normal pitch discrimination and spectral resolution thresholds, and normal cognitive and language abilities. His rhythmic processing was intact when pitch variations were removed. After 3 months, MM showed a large improvement in his sensitivity to tonality, but persistent melodic deficits and a decline in perceiving the metric structure of rhythmic sequences. We also found visual cues aided melodic processing, which is novel and beneficial for future rehabilitation practice.

MAdCAM-1 Co-stimulation Combined with Retinoic Acid and TGF-ß Induces Blood CD8+ T cells to Adopt a Gut CD101+ TRM Phenotype.

Resident memory T cells (TRMs) help control local immune homeostasis and contribute to tissue protective immune responses. The local cues that guide their differentiation and localization are poorly defined. We demonstrate that MAdCAM-1, a ligand for the gut homing receptor α4ß7 integrin, in the presence of retinoic acid and TGF-ß provide a costimulatory signal that induces blood CD8+ T cells to adopt a TRM -like phenotype. These cells express CD103 (integrin αE) and CD69, the two major TRM cell surface markers, along with CD101. They also express CCR5, CCR9 and α4ß7, three receptors associated with gut homing. A subset also express E-cadherin, a ligand for αEß7. Fluorescent lifetime imaging indicated an αEß7 and E-cadherin cis interaction on the plasma membrane. This report advances our understanding of the signals that drive the differentiation of CD8+ T cells into TRMs and provides a means to expand these cells in vitro, thereby affording an avenue to generate more effective tissue specific immunotherapies.

The association between dynamic balance and executive function: Which dynamic balance test has the strongest association with executive function? A systematic review and meta-analysis.

AIM: The aging global population poses increasing challenges related to falls and dementia. Early identification of cognitive decline, particularly before noticeable symptoms manifest, is crucial for effective intervention. This review aims to determine the dynamic balance test most closely associated with executive function, potentially serving as a biomarker for cognitive decline. RECENT FINDINGS: Based on recent reviews, inhibitory control, a component of executive function, holds significance in influencing balance performance. Studies suggest that the strength of the correlation between cognition and balance tends to be domain-specific and task-specific. Despite these findings, inconclusive evidence remains regarding the connection between executive function and various dynamic balance assessments. Our review identifies a significant association between all dynamic balance tests and executive function, albeit with varying strengths. Notably, a medium effect size is observed for the Timed Up and Go and Functional Reach Test, a small effect size for balance scales, and a strong effect size for postural sway. This review underscores a clear relationship between dynamic balance task performance and executive function. Dynamic posturography holds potential as a clinical biomarker for early detection of cognitive decline, with a note of caution due to observed heterogeneity and limited studies.

Spike-induced cytoarchitectonic changes in epileptic human cortex are reduced via MAP2K inhibition.

Interictal spikes are electroencephalographic discharges that occur at or near brain regions that produce epileptic seizures. While their role in generating seizures is not well understood, spikes have profound effects on cognition and behaviour, depending on where and when they occur. We previously demonstrated that spiking areas of human neocortex show sustained MAPK activation in superficial cortical Layers I-III and are associated with microlesions in deeper cortical areas characterized by reduced neuronal nuclear protein staining and increased microglial infiltration. Based on these findings, we chose to investigate additional neuronal populations within microlesions, specifically inhibitory interneurons. Additionally, we hypothesized that spiking would be sufficient to induce similar cytoarchitectonic changes within the rat cortex and that inhibition of MAPK signalling, using a MAP2K inhibitor, would not only inhibit spike formation but also reduce these cytoarchitectonic changes and improve behavioural outcomes. To test these hypotheses, we analysed tissue samples from 16 patients with intractable epilepsy who required cortical resections. We also utilized a tetanus toxin-induced animal model of interictal spiking, designed to produce spikes without seizures in male Sprague-Dawley rats. Rats were fitted with epidural electrodes, to permit EEG recording for the duration of the study, and automated algorithms were implemented to quantify spikes. After 6 months, animals were sacrificed to assess the effects of chronic spiking on cortical cytoarchitecture. Here, we show that microlesions may promote excitability due to a significant reduction of inhibitory neurons that could be responsible for promoting interictal spikes in superficial layers. Similarly, we found that the induction of epileptic spikes in the rat model produced analogous changes, including reduced neuronal nuclear protein, calbindin and parvalbumin-positive neurons and increased microglia, suggesting that spikes are sufficient for inducing these cytoarchitectonic changes in humans. Finally, we implicated MAPK signalling as a driving force producing these pathological changes. Using CI-1040 to inhibit MAP2K, both acutely and after spikes developed, resulting in fewer interictal spikes, reduced microglial activation and less inhibitory neuron loss. Treated animals had significantly fewer high-amplitude, short-duration spikes, which correlated with improved spatial memory performance on the Barnes maze. Together, our results provide evidence for a cytoarchitectonic pathogenesis underlying epileptic cortex, which can be ameliorated through both early and delayed MAP2K inhibition. These findings highlight the potential role for CI-1040 as a pharmacological treatment that could prevent the development of epileptic activity and reduce cognitive impairment in both patients with epilepsy and those with non-epileptic spike-associated neurobehavioural disorders.

High mirror symmetry in mouse exploratory behavior.

The physicality of the world in which the animal acts-its anatomical structure, physiology, perception, emotional states, and cognitive capabilities-determines the boundaries of the behavioral space within which the animal can operate. Behavior, therefore, can be considered as the subspace that remains after secluding all actions that are not available to the animal due to constraints. The very signature of being a certain creature is reflected in these limitations that shape its behavior. A major goal of ethology is to expose those constraints that carve the intricate structure of animal behavior and reveal both uniqueness and commonalities between animals within and across taxa. Exploratory behavior in an empty arena seems to be stochastic; nevertheless, it does not mean that the moving animal is a random walker. In this study, we present how, by adding constraints to the animal's locomotion, one can gradually retain the 'mousiness' that characterizes the behaving mouse. We then introduce a novel phenomenon of high mirror symmetry along the locomotion of mice, which highlights another constraint that further compresses the complex nature of exploratory behavior in these animals. We link these findings to a known neural mechanism that could explain this phenomenon. Finally, we suggest our novel finding and derived methods to be used in the search for commonalities in the motion trajectories of various organisms across taxa.