Spatial Memory Research Articles

6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies

Abstract 6-Methoxyflavone (6-MOF) is a flavonoid that has been reported to be a GABA-A receptor agonist and reverses cisplatin-induced hyperalgesia and allodynia. Considering the varied neuropharmacological profile of 6-MOF, this study was intended to determine the pharmacological effects of 6-MOF on locomotion, anxiety, novel object recognition (NOR), depression, spatial memory, socialization behavior, nest-building behavior, and depression in various groups of mice. Selected groups of mice were injected with 25, 50, and 75 mg/kg 6-MOF. Using HPLC-UV, the frontal cortex, striatum, and hippocampus of the sacrificed mice were analyzed for the levels of vitamin C, dopamine, serotonin, noradrenaline, adenosine, and its metabolites. Statistical analysis showed significant results in socialization behavior and elevated plus maze with 75 mg/kg. In Y-maze, NOR 6-MOF showed significant results at all three doses, while in tail suspension test (TST), 50 and 75 mg/kg showed significant results; however, no statistical significance was observed in nest-building behavior; 50 and 75 mg/kg 6-MOF showed significant results in the Morris water maze. 6-MOF raised vitamin C levels in the frontal cortex and hippocampus. Serotonin, dopamine, and nor-adrenaline levels were raised in the hippocampus and striatum. It has also imparted region-specific neuroprotection by improving adenosine and its metabolite levels. In silico studies performed using PyRx have shown that the minimum binding energy of 6-MOF with antioxidant enzyme is −7.1 k/cal/mol. The binding energy showed that 6-MOF was successfully docked with an anti-oxidant enzyme. In conclusion, in silico and behavioral studies showed that 6-MOF can be a potential candidate for the treatment of cognitive decline, anxiety, and depression.

Cognitive Maps for a Non-Euclidean Environment: Path Integration and Spatial Memory on a Sphere

Humans build mental models of the world and utilize them for various cognitive tasks. The exact form of cognitive maps is not fully understood, especially for novel and complex environments beyond the flat Euclidean environment. To address this gap, we investigated path integration—a critical process underlying cognitive mapping—and spatial-memory capacity on the spherical (non-Euclidean) and planar (Euclidean) environments in young healthy adults (N = 20) using immersive virtual reality. We observed a strong Euclidean bias during the path-integration task on the spherical surface, even among participants who possessed knowledge of non-Euclidean geometry. Notably, despite this bias, participants demonstrated reasonable navigation ability on the sphere. This observation and simulation suggest that humans navigate nonflat surfaces by constructing locally confined Euclidean maps and flexibly combining them. This insight sheds light on potential neural mechanisms and behavioral strategies for solving complex cognitive tasks.

Modulation of memory by prism adaptation in healthy subjects

Recent findings suggest that prism adaptation can extend its effects beyond spatial attention, modulating the performance of different cognitive tasks by acting on cerebellar, parietal and temporal-frontal networks. We tested groups of healthy subjects to investigate the effects of rightward vs. leftward prism adaptation vs. neutral lenses exposure in a series of memory tasks, probing either short-term (Digit span, Corsi span) or long-term memory (Supraspan verbal and spatial learning). In the short-term memory tasks, leftward prism adaptation selectively increased verbal span, while rightward prism adaptation increased spatial span. In the long-term memory tasks, leftward prism adaptation selectively increased verbal supraspan, i.e., increased the number of digits in the correct sequence reproduced and reduced the number of repetitions needed to learn the supraspan sequence. On the other hand, rightward prism adaptation selectively increased spatial supraspan, i.e. it increased the number of spatial positions in the correct sequence reproduced and reduced the number of repetitions needed to learn the supraspan sequence. Moreover, rightward, but not leftward, prism adaptation selectively increased supraspan recall after a delay interval, regardless of the stimulus material, i.e., it increased the number of digits or spatial positions recalled after a delay interval. Neutral lenses exposure did not influence any memory task. These findings suggest that prism adaptation can induce both modality/hemispheric-specific and process-specific effects on short-term and long-term explicit memory.

The Wolf Spider Tigrosa helluo Uses Visual Associative and Beacon Landmarks During Water Maze Navigation Tasks

ABSTRACTWolf spiders can learn simple spatial navigation tasks. Previous studies have shown that the wolf spider Tigrosa helluo can use environmental edge features (reference frame landmarks) to learn the location of a dry target in flooded T‐mazes; however, the relative importance of different types or numbers of landmark cues to spatial learning remains unknown. We used a modified open arena water maze and recorded the ability of adult female T. helluo to find a target reward (a dark and dry cup) among cups that were identical to the target but flooded. We measured variation in spatial learning by measuring time to target with no landmark (control), with a beacon (a landmark that is part of the target), with an associative cue (a landmark associated with a specific navigational action), and with both a beacon and an associative cue (N = 92 subjects, n = 23 per landmark cue treatment). For each treatment, we tested females for five trials each on four consecutive days, with the last trial on the fourth day having an altered target location, totaling 19 training trials and one reversal trial (1840 trials). We found that spiders took significantly less time to find the target over subsequent trials within a day and learned more quickly when landmark cues were present, but we found no difference in the type or number of landmark features in the meantime to target entrance. After learning a target location, moving the landmark significantly increased the mean time to target entrance in the combined beacon and associative cue treatment relative to other treatments. Our results indicate that wolf spiders use visual beacons and associative cue landmarks alone or in combination and that performance improves across trials when landmarks are present and deteriorates more when multiple landmarks are moved.

Isolated theta waves originating from the midline thalamus trigger memory reactivation during NREM sleep in mice

During non-rapid eye movement (NREM) sleep, neural ensembles in the entorhinal-hippocampal circuit responsible for encoding recent memories undergo reactivation to facilitate the process of memory consolidation. This reactivation is widely acknowledged as pivotal for the formation of stable memory and its impairment is closely associated with memory dysfunction. To date, the neural mechanisms driving the reactivation of neural ensembles during NREM sleep remain poorly understood. Here, we show that the neural ensembles in the medial entorhinal cortex (MEC) that encode spatial experiences exhibit reactivation during NREM sleep. Notably, this reactivation consistently coincides with isolated theta waves. In addition, we found that the nucleus reuniens (RE) in the midline thalamus exhibits typical theta waves during NREM sleep, which are highly synchronized with those occurring in the MEC in male mice. Closed-loop optogenetic inhibition of the RE-MEC pathway specifically suppressed these isolated theta waves, resulting in impaired reactivation and compromised memory consolidation following a spatial memory task in male mice. The findings suggest that theta waves originating from the ventral midline thalamus play a role in initiating memory reactivation and consolidation during sleep.

Specific and Polyfunctional T Cell Response Against N-Methyl-d-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model

Background: Anti-N-Methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1359–378 peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment. Results: In this mouse model, we identified anti-GluN1-specific CD4+ but also CD8+ T cells in both spleen and meninges. T helper cells have a polyfunctional profile, arguing for a T and B cell crosstalk to generate anti-GluN1 pathogenic Abs. Interestingly, proteomic analysis of AE meninges showed enrichment of differentially expressed proteins in biological processes associated with B cell activation and cytokine signalling pathways. Conclusions: This study identified, for the first time, a potential contribution of T helper cells in the pathology of NMDAR AE and paved the way for the development of future tolerogenic approaches to treat relapses.

β-Amyloid impairs Proteasome structure and function. Proteasome activation mitigates amyloid induced toxicity and cognitive deficits.

Alzheimer's Disease (AD) is the leading cause of dementia globally, affecting around 50 million people and marked by cognitive decline and the accumulation of β-amyloid plaques and hyperphosphorylated tau. The limited treatment options and numerous failed clinical trials targeting β-amyloid (Aβ) highlight the need for novel approaches. Lowered proteasome activity is a consistent feature in AD, particularly in the hippocampus. Impaired proteasome function in AD is hypothesized to stem from direct inhibition by β-amyloid or hyperphosphorylated tau, disrupting critical neuronal processes such as memory formation and synaptic plasticity. This study tests the hypothesis that AD related deficits are driven in part by impaired proteasome function as a consequence of inhibition by Aβ. We evaluated how proteasome function is modulated by Aβ and the capacity of two proteasome-activating compounds, TAT1-8,9-TOD and TAT1-DEN to rescue Aβ-induced impairment in vitro, as well as survival deficits in cell culture and Aβ-induced cognitive deficits in Drosophila and mouse models. Our study demonstrates that oligomeric β-amyloid binds to the 20S proteasome and impairs its activity and conformational stability. The oligomers also destabilize the 26S proteasome to release the free 20S proteasome. Treatment with proteasome activators TAT1-8,9TOD and TAT1-DEN rescue the 20S proteasome function and reduces cell death caused by Aβ42 toxicity in SK-N-SH cells. In Drosophila models overexpressing Aβ42, oral administration of proteasome agonists delayed mortality and restored cognitive function. Chronic treatment with TAT1-DEN protected against deficits in working memory caused by Aβ42 in mice and in hAPP(J20) mice with established deficits, acute TAT1-DEN treatment significantly improved spatial learning, with treated mice performing comparably to controls. Aβ has dual impacts on 20S and 26S proteasome function and stability. Proteasome activation using TAT1-8,9TOD and TAT1-DEN shows promise in mitigating AD-like deficits by protecting against amyloid toxicity and enhancing proteasome function. These findings suggest that targeting proteasome activity could be a viable therapeutic approach for AD, warranting further investigation into the broader impacts of proteasome modulation on AD pathology.

Study While You Sleep: Using Targeted Memory Reactivation as an Independent Research Project for Undergraduates.

Newly acquired information is stabilized into long-term memory through the process of consolidation. Memories are not static; rather, they are constantly updated via reactivation, and this reactivation occurs preferentially during Slow-Wave Sleep (SWS, also referred to as N3 in humans). Here we present a scalable neuroscience research investigation of memory reactivation using low-cost electroencephalogram (EEG) recording hardware and open-source software, for students and educators across the K-12 and higher education spectrum. The investigation uses a method called targeted memory reactivation (TMR), whereby auditory cues that were previously associated with learning are re-presented during sleep, triggering the recall of stored memories and (through this) strengthening these memories. We demonstrated the efficacy of this technique on seven healthy human subjects (ages 19-35). The subjects learned to play a spatial memory game on an app where they associated pictures (e.g., a clock) with locations on a grid while they listened to picture-appropriate sounds (e.g., "tic-toc"); next, they took a nap while undergoing EEG recordings. During SWS, half of the sounds from the game were replayed by the app, while half were substituted with non-learned sounds. Subjects then played the memory game again after waking. Results showed that spatial recall was improved more for cued than uncued memories, demonstrating the benefits of memory replay during sleep and suggesting that one may intervene in this process to boost recall of specific memories. This research investigation takes advantage of the importance of sleep for memory consolidation and demonstrates improved memory performance by cueing sounds during SWS.

Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model.

Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone-3 lysine-9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic-AMP responsive element binding protein (p-CREB), c-fos, brain-derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety-related behavior significantly reduced in the treatment group compared to the VD group (p < 0.05). BIX01294 improved spatial and passive avoidance memory (p < 0.01 and p < 0.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p-CREB/CREB ratio (p < 0.05), cfos (p < 0.01), BDNF (p < 0.01), and suppressed H3K9me2 (p < 0.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (p < 0.05), and raised neural cell count in H&E staining (p < 0.01); amyloid beta accumulation significantly decreased in the treatment group (p < 0.05) compared to the VD group. In conclusion, long-term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.

Overcoming Catastrophic Forgetting in Continual Fine-Grained Urban Flow Inference

Citywide fine-grained urban flow inference (FUFI) problem aims to infer the high-resolution flow maps from the coarse-grained ones, which plays an important role in sustainable and economic urban computing and intelligent traffic management. Previous models tackle this problem from spatial constraint, external factors, and memory cost. However, utilizing the new urban flow maps to calibrate the learned model is very challenging due to the “catastrophic forgetting” problem and is still under-explored. In this article, we make the first step in FUFI and present CUFAR—Continual Urban Flow inference with augmented Adaptive knowledge Replay—a novel framework for inferring the fine-grained citywide traffic flows. Specifically, (1) we design a spatial-temporal inference network that can extract better flow map features from both local and global levels; (2) then, we present an augmented adaptive knowledge replay (AKR) training algorithm to selectively replay the learned knowledge to facilitate the learning process of the model on new knowledge without forgetting. We apply several data augmentation techniques to improve the generalization capability of the learning model, gaining additional performance improvements. We also propose a knowledge discriminator to avoid the “negative replaying” issue introduced by noisy urban flow maps. Extensive experiments on two large-scale real-world FUFI datasets demonstrate that our proposed model consistently outperforms strong baselines and effectively mitigates the forgetting problem.

The Importance of Gut Microbiota on Choline Metabolism in Neurodegenerative Diseases

The gut microbiota is a complex ecosystem that influences digestion, immune response, metabolism, and has been linked to health and well-being. Choline is essential for neurotransmitters, lipid transport, cell-membrane signaling, methyl-group metabolism and is believed to have neuroprotective properties. It is found in two forms, water-soluble and lipid-soluble, and its metabolism is different. Long-term choline deficiency is associated with many diseases, and supplements are prescribed for improved health. Choline supplements can improve cognitive function in adults but not significantly. Choline is a precursor of phospholipids and an acetylcholine neurotransmitter precursor and can be generated de novo from phosphatidylcholine via phosphatidylethanolamine-N-methyltransferase and choline oxidase. Choline supplementation has been found to have a beneficial effect on patients with neurodegenerative diseases, such as Alzheimer’s disease (AD), by increasing amyloid-β, thioflavin S, and tau hyper-phosphorylation. Choline supplementation has been shown to reduce amyloid-plaque load and develop spatial memory in an APP/PS1 mice model of AD. Choline is necessary for normative and improved function of brain pathways and can reduce amyloid-β deposition and microgliosis. Clinical research suggests that early neurodegenerative diseases (NDs) can benefit from a combination of choline supplements and the drugs currently used to treat NDs in order to improve memory performance and synaptic functioning.

Spatial memory in Alzheimer's disease 5XFAD mice is enhanced by XPO1 inhibitor KPT-330.

The proteostatic decline in Alzheimer's disease is well established and improvement in proteostasis could potentially delay cognitive impairment. One emerging entry point to modulate proteostasis is the regulation of nucleo-cytoplasmic partitioning of proteins across the nuclear pore via karyopherins. The nuclear exportin XPO1 is a key regulator of proteostasis by driving the assembly of ribosomes and by modulating the process of autophagy. We recently found that XPO1 inhibitor KPT-330 (Selinexor), an FDA approved drug against multiple myelomas, enhances proteostasis, leading to benefits in models of neurodegenerative diseases in C. elegans and Drosophila . Here, we find that KPT-330 increases autophagy in murine neuronal cells and improves spatial memory performance in a murine model of Alzheimer's disease (5XFAD). Unexpectedly, general amyloid deposition in several brain regions was significantly increased by KPT-330, but specific regions, especially the thalamus, displayed significantly lower deposition, suggesting that XPO1 inhibition has regional-specific effects on proteostasis and amyloid plaque formation. Altogether, we conclude that XPO1 inhibition can improve cognition via spatially-specific reductions in amyloid deposition.

Biopsychosocial Impact of Multiple Sclerosis in Omani Patients: A Multicenter Comparative Study.

Background/Objectives: Multiple sclerosis (MS) is a chronic neurological disorder characterized by various clinical presentations and manifestations that include biopsychosocial impediments. This study has three interrelated goals relevant to biopsychosocial functioning: (i) compare reasoning ability, neuropsychological functioning, affective range, and quality of life (QoL) between people with multiple sclerosis (PwMS) and healthy controls; (ii) explore gender differences in reasoning ability and neuropsychological functioning, affective symptoms, and QoL among PwMS; and (iii) examine the relationship between QoL and cognitive performance in PwMS, focusing on those with inadequate vs. adequate QoL. Methods: This multicenter study was carried out among clinically stable PwMS (no relapse in the last two months) at follow-up in two tertiary care units in urban Oman. Healthy controls, matched for age and sex, were also recruited as a comparison group. Data were collected using cognitive batteries sensitive to current reasoning ability and conventional neuropsychological batteries designed to measure verbal learning, visual-spatial ability, and processing speed. The affective range (anxiety and depressive symptoms) and quality of life (QoL) were also evaluated. Results: The PwMS group scored lower on current reasoning ability, verbal learning, visual-spatial ability, and processing speed compared to the control group. The incidence of anxiety was higher in the PwMS group, but there were no statistically significant differences in depressive symptoms. No significant differences were found in cognitive variables between the two sexes, except in visual-spatial ability, where women outperformed men. PwMS with low QoL scored lower on attention and concentration indices than those with adequate QoL. According to QoL, no significant differences were observed in reasoning, verbal learning, or visual-spatial ability. Conclusions: The present sentinel study suggests that the Omani cohort with MS tends to have lower indices of current reasoning ability, visual and spatial memory, and cognitive speed compared to control subjects. Gender differences are minimal, except for visual-spatial abilities, where women outperform men. Quality of life significantly affects cognitive functioning. In general, the biopsychosocial impediment appears to be significant, indicating the need for comprehensive evaluation and care in the management of MS.

Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia

The purpose of this research was to assess the impact of different doses of Daphnetin (DAP, a natural compound derived from coumarin) on hippocampus neuronal injury, neurobehavioral function, blood-brain barrier (BBB) integrity, expression of claudin-5, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), and inflammatory markers in a mouse model of cerebral ischemia. Cerebral ischemia was induced in mice through 30 minutes of bilateral common carotid occlusion (BCCAO), followed by 48 hours of reperfusion. The viability of hippocampal neurons was assessed using Cresyl violet staining and BBB function was determined by measuring Evans blue (E.B) dye leakage. Spatial memory was tested using the Radial Arm Water Maze (RAWM) task. Claudin-5 and BDNF were measured by immunofluorescence, while SOD, interleukin-1 beta (IL-1β), and nuclear factor-κB (NF-κB) expression were determined through western blotting. Administering DAP significantly increased neuron survival in the hippocampus CA1, CA3, and dentate gyrus (DG) regions and improved spatial memory dose-dependently (P<0.0001). Treatment with DAP (40 mg/kg IP) significantly reduced E.B leakage and brain water content (P<0.001). Furthermore, it increased the claudin-5, BDNF, and SOD levels and diminished NF-κB and IL-1β expression (P<0.0001). The research found that DAP protected neurons in the CA1, CA3, and DG areas of the hippocampus, enhanced behavioral functions, and preserved BBB integrity in a cerebral ischemia model. This positive impact is achieved by increasing the expression of claudin-5, BDNF, and SOD and diminishing neuroinflammation. Further research is required to clarify the mechanisms and possible clinical uses.

Hippocampal Leptin Resistance and Cognitive Decline: Mechanisms, Therapeutic Strategies and Clinical Implications

Background: Leptin, an adipokine essential for regulating energy balance, exerts important effects on brain function, notably within the hippocampus, a region integral to learning and memory. Leptin resistance, characterized by diminished responsiveness to elevated leptin levels, disrupts hippocampal function and exacerbates both obesity and cognitive impairments. Scope: This review critically examines how leptin resistance impairs hippocampal synaptic plasticity processes, specifically affecting long-term potentiation (LTP) and long-term depression (LTD), which are crucial for cognitive performance. Findings: Recent research highlights that leptin resistance disrupts N-methyl-D-aspartate (NMDA) receptor dynamics and hippocampal structure, leading to deficits in spatial learning and memory. Additionally, high-fat diets (HFDs), which contribute to leptin resistance, further deteriorate hippocampal function. Potential therapeutic strategies, including leptin sensitizers, show promise in mitigating brain disorders associated with leptin resistance. Complementary interventions such as caloric restriction and physical exercise also enhance leptin sensitivity and offer potential benefits to alleviating cognitive impairments. Aims of the review: This review synthesizes recent findings on the molecular pathways underlying leptin resistance and its impact on synaptic transmission and plasticity in the hippocampus. By identifying potential therapeutic targets, this work aims to provide an integrated approach for addressing cognitive deficits in obesity, ultimately improving the quality of life for affected individuals.

Harmful Effects on the Hippocampal Morpho-Histology and on Learning and Memory in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children.

Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice.

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the "K+ATP" channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral performance, neuropathology, and gene expression. Mortality was significantly higher for aged Grn-KO mice (particularly females), but there was a conspicuous improvement in survival for both sexes treated with nicorandil. Grn-KO mice performed worse on some cognitive tests than WT mice, but Morris Water Maze performance was improved with nicorandil treatment. Neuropathologically, Grn-KO mice had significantly increased levels of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytosis but not ionized calcium binding adaptor molecule 1 (IBA-1)-immunoreactive microgliosis, indicating cell-specific inflammation in the brain. Expression of several astrocyte-enriched genes, including Gfap, were also elevated in the Grn-KO brain. Nicorandil treatment was associated with a subtle shift in a subset of detected brain transcript levels, mostly related to attenuated inflammatory markers. Nicorandil treatment improved survival outcomes, cognition, and inflammation in aged Grn-KO mice.

Gender differences in operational and cognitive abilities.

Gender differences in cognitive and operational abilities have been identified. Yet, their interrelationship remains underexplored. This prevents tailored evidence-based selection, allowing discrimination to persist. Data from a test battery of operational and cognitive tests was analyzed. In total 2,743 aviation pilot candidates' test scores were analyzed. Males had a significantly higher score on mental spatial ability, memory retention, abstract problem solving, multitasking ability (MU), and manual spatial ability (MSA); and females on perceptual speed. Correlations between MU and MSA [difference = 0.269 (95% CI: 0.114; 0.405)] and between MSA and perceptual speed [difference = 0.186 (95% CI: 0.027; 0.332)] were significantly stronger among female applicants. A high MSA score was more predictive of a high score on MU, Perceptual speed, and Memory for female compared with male applicants (p < 0.002 for the MSA score × sex interaction effect in all three cases). Interpretation of test scores in between genders potentially may need to look different for final selection decisions for operational professions, as female test profiles were shown to exhibit greater homogeneity.

Theta-burst transcranial magnetic stimulation attenuates chronic ischemic demyelination and vascular cognitive impairment in mice

Vascular cognitive impairment and dementia (VCID) is mainly caused by chronic cerebral hypoperfusion and subsequent white matter lesions. Noninvasive transcranial magnetic stimulation has been utilized in treating various neurological disorders. However, the function of theta-burst transcranial magnetic stimulation on VCID remains to be defined. We utilized 4-week bilateral carotid artery stenosis model of male mice to mimic VCID. Intermittent theta-burst stimulation (iTBS) or consecutive theta-burst stimulation (cTBS) was administered for 14 consecutive days. Through luxol fast blue staining, electron microscopy and immunofluorescence, we found that iTBS, not cTBS, significantly improved demyelination, axonal damage and β-amyloid deposition, without affecting cerebral blood flow in VCID mice. At cellular levels, iTBS rescued the loss of mature oligodendrocytes, promoted precursor cell differentiation, and inhibited pro-inflammatory activation of astrocytes and microglia. Notably, iTBS attenuated cognitive deterioration in both short-term retention and long-term spatial memory of VCID mice as indicated by serial neurobehavioral tests. To explore the molecular involvement of iTBS, mRNA sequencing was carried out. By real-time PCR and combined RNA fluorescence in situ hybridization with immunofluorescence, iTBS was confirmed to increase Rxrg expression specifically in mature oligodendrocytes. Collectively, iTBS could ameliorate vascular cognitive dysfunction, probably via mitigating white matter lesions and neuroinflammation in the corpus callosum. Rxrg signaling in mature oligodendrocytes, which was increased by iTBS, might be a potential target for VCID treatment.

On prior visual experience in mental map navigation using allocentric and egocentric perspectives in the visually impaired.

Using new developments in the mental comparison task paradigm, this study addresses the question of the influence of prior visual experience in the natural use of mental perspective to achieve mental spatial tasks without any protocol-imposed perspective. During the experiment, 39 participants (11 early blind, 13 late blind, and 15 blindfolded-sighted) explored two corridor maps to memorise the spatial arrangement of 10 objects disposed along corridors. After the learning phase, several tasks addressing spatial memory and reasoning used in the mental spatial representation were performed. Blindfolded-sighted participants preferred an egocentric perspective, while the two visually impaired groups showed no overriding preference between egocentric and allocentric perspectives. Results showed a performance advantage for egocentric over allocentric perspectives, regardless of visual experience. Our results shed light on previous assumptions regarding cognitive mental map construction, suggesting the need to reflect on previous results and their dependence on imposed mental perspectives.