Cognitive control is essential for goal-directed behavior and is often impaired in neurological conditions. Transcranial random noise stimulation (tRNS) has shown potential for cognitive enhancement, but its electrophysiological mechanisms remain unclear. This study examined whether bilateral parietal tRNS modulates paced auditory serial addition test (PASAT) performance (reaction time and accuracy) and event-related potential (ERP) indices of cognitive control. In a randomized, double-blind, sham-controlled crossover study, 40 healthy adults received active high-frequency tRNS (100–640 Hz, 2 mA, 20 min) or sham stimulation over bilateral posterior parietal regions. PASAT performance (reaction time, accuracy) and EEG were recorded pre- and post-stimulation. ERP analyses focused on N200, P300, and late slow wave (LSW). Active tRNS significantly reduced reaction times compared to sham, with no stimulation-specific effect on accuracy. Neurophysiologically, active tRNS reduced frontal N200 negativity and increased frontal P300 amplitude. Additionally, reductions in reaction time were significantly associated with increases in frontal P300 amplitude. The findings suggest that a single session of bilateral parietal tRNS reduced response latency and was associated with changes in frontal ERP markers during a demanding cognitive task. These results provide preliminary electrophysiological evidence that parietal tRNS may influence task-related neural activity expressed at frontal sites, with ERPs serving as potential markers of stimulation-related changes in performance.
The visual word form area (VWFA) has been proposed to function as a multiplex hub integrating both attentional and linguistic processing, yet how its functionally distinct subregions dynamically reconfigure their network connectivity across cognitive contexts remains unclear. This study examined resting-state and task-evoked functional connectivity of two VWFA subregions—posterior VWFA-1 and anterior VWFA-2—with predefined attention and language network regions of interest in 20 healthy adults performing a visuospatial flanker task and a Korean lexical decision task. We hypothesized that the posterior-to-anterior anatomical gradient corresponds to an attention-to-language functional role differentiation, observable both in intrinsic connectivity and in task-dependent reconfiguration. At rest, the VWFA exhibited a posterior-to-anterior intrinsic gradient, with VWFA-1 preferentially coupled to the attention network and VWFA-2 to language regions. Across both tasks, task context differentially shifted attention-network connectivity between VWFA-1 and VWFA-2, broadly following the intrinsic gradient. The alignment was only partial, however, as during lexical decision it was the posterior VWFA-1 rather than the anterior VWFA-2 that increased its coupling with the language network. Behaviorally, attention connectivity predicted accuracy across tasks from both subregions equivalently rather than from the gradient itself, suggesting a shared attention-based mechanism rather than gradient-specific contributions. Together, these findings provide preliminary support for the view that intrinsic VWFA organization shapes task-specific routing of attention network interactions, while behavioral performance converges on a shared attention-based mechanism.
This study aimed to investigate whether the probiotic Lactobacillus rhamnosus GG (LGG) (alone or combined with high-intensity interval training (HIIT)) could improve cognitive, electrophysiological changes, oxidative stress and metabolic parameters in HFD-fed rats. Rats were randomly divided into four groups (n = 8): HFD group, HFD + LGG group, HFD+ HIIT group, and HFD + LGG+ HIIT group. Rats were fed HFD daily for a period of 16 weeks, during which LGG (1 × 1010 colony forming unit (CFU)/ rats, orally), and HIIT protocol were administered four times a week on alternating days. At the end of study, assessment of social behavior, memory function, and Long-term potential (LTP) were performed using three-chambered apparatus, Y-maze task, and electrophysiology technique, respectively. Next, oxidative stress, lipid profiles, and liver enzymes were evaluated with routine kits. Both LGG and HIIT alone or in combination improved working memory, social memory, and LTP in HFD-fed rats. In addition, both LGG and HIIT alone or in combination increased the hippocampal levels of superoxide dismutase, catalase, and increased the serum levels of high-density lipoprotein (HDL), and decreased the serum levels of leptin, triglyceride, cholesterol, low-density lipoprotein (LDL), aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) in HFD-fed rats. The combination of LGG and HIIT provides a multi-pathway intervention that improves HFD-induced memory impairments by concurrently targeting oxidative stress, dyslipidemia, and hippocampal synaptic function. This supports the potential of combined lifestyle and microbiome-based therapies for preventing metabolic and cognitive disorders.
Hoxa5 encodes a transcription factor essential for embryonic patterning and organogenesis, with sustained expression in hindbrain precerebellar nuclei during postnatal development. Given prior evidence implicating HOXA5 in synaptogenesis and early postnatal circuit maturation, we investigated whether its inactivation during this critical developmental window contributes to neurodevelopmental disorder (NDD)–related phenotypes. Using previously generated transcriptomic data, we identified multiple deregulated genes classified as autism spectrum disorder (ASD) risk genes in the SFARI database, several of which are associated with a cerebellar phenotype in mice. We then performed a comprehensive behavioral assessment across motor, social, stereotypical, anxiety-related, and attentional domains in a postnatal inactivation mouse model (Hoxa5-cKO). Motor coordination, learning, gait, and sensorimotor functions were preserved. Social behavior assays yielded no consistent genotype-dependent effects, although results were sensitive to analytical methods and cohort variability. In contrast, Hoxa5-cKO mice exhibited increased stereotypical behaviors, including elevated scratching and marble burying, in the absence of anxiety- or locomotion-related confounds. Importantly, interpretation of social and cognitive phenotypes was impacted by well-known constraints of behavioral neuroscience. We discuss these downfalls and propose additional guidelines. Altogether, our findings indicate that postnatal Hoxa5 deficiency selectively enhances stereotyped behaviors without broadly affecting motor or social functions. The data support a model in which HOXA5 acts as a modulator of postnatal precerebellar circuit connectivity and/or function, with subtle behavioral consequences that require further research in specific genetic or environmental contexts.
Ketamine is an antagonist of the N-Methyl-D-aspartate (NMDA) receptor with the effect of inducing aberrant excitatory-inhibitory neurotransmission and oxidative neurotoxicity, which mimic the cognitive impairments found in schizophrenia. This study explored the potential of mangiferin, a strong antioxidant xanthone polyphenol, to normalize neurotransmitter levels and mitigate oxidative and glial changes in rats subjected to ketamine treatment. Male Wistar rats were anaesthetised with ketamine (50 mg/kg, i.p., for 7 days) to induce excitotoxicity and subsequently treated for 14 days with mangiferin (25, 50 or 75 mg/kg, p.o.) or risperidone (2 mg/kg, i.p.). Behavioral performance was assessed using the Morris Water Maze, Y-Maze, Open Field, and Novel Object Recognition tests. Neurochemical assays in the prefrontal, hippocampal and temporal cortices measured glutamate, γ-aminobutyric acid (GABA), dopamine, and acetylcholinesterase (AChE) activities. Cellular pathology was evaluated through histopathology (H E) and immunohistochemistry for glial fibrillary acidic protein (GFAP) and nuclear factor erythroid 2-related factor 2 (Nrf2). Ketamine induced severe cognitive deficits, hyperlocomotion, anxiety-like behavior, reduced cortical GABA and glutamate levels, increased dopamine, and elevated AChE activity—confirming excitatory-inhibitory imbalance and cholinergic disruption. Mangiferin enhanced spatial learning, working memory, recognition memory, and normalized locomotor activity in a dose-dependent manner, with higher doses restoring performance to near control levels. Neurochemically, mangiferin increased GABA and glutamate to baseline levels while decreasing dopamine and AChE hyperactivity. Histology showed preserved cortical cytoarchitecture and reduced neuronal loss and vacuolation. Notably, mangiferin reversed ketamine-induced astrogliosis (decreased GFAP immunoreactivity) and increased nuclear Nrf2 expression, indicating activated endogenous antioxidant defenses. Mangiferin exhibited significant neuroprotection against ketamine-induced excitotoxicity through restoration of neurotransmitter homeostasis, establishment of redox resilience, and regulation of astrocytic reactivity. These multifaceted actions underscore its therapeutic potential for neuropsychiatric diseases associated with oxidative stress and glial dysfunction.
Ketamine, a dissociative anesthetic, induces behavioral and molecular alterations associated with psychosis-like phenotypes. However, the epigenetic mechanisms bridging its cellular effects with behavioral outcomes are poorly defined. Here, we report that ketamine induces histone H3 Ser10 phosphorylation in both hippocampal neurons (HT22 cells) and the mouse hippocampus, an effect primarily driven by JNK activation. Critically, pharmacological inhibition of JNK with SP600125 not only reversed this epigenetic mark but also robustly attenuated ketamine-induced hyperlocomotion and cognitive deficits in mice. Integrated multi-omics analysis of the hippocampus 30 min post-ketamine revealed coordinated transcriptional and chromatin accessibility changes. We identified 262 differentially expressed genes (e.g., MAP3K9) enriched in MAPK signaling and neuroactive ligand-receptor pathways, alongside 165 differentially accessible regions, with motif analysis implicating CTCF as a key regulator. Our findings suggest that JNK-mediated H3S10 phosphorylation may play a critical role in linking ketamine exposure to psychosis-like phenotypes, providing a mechanistic framework that connects stress-sensitive signaling to rapid chromatin remodeling and sustained transcriptional reprogramming. This work unveils potential novel therapeutic targets for psychosis centered on the JNK–H3S10 phosphorylation axis.
Post-traumatic stress disorder (PTSD) is associated with cognitive impairments, anxiety, fear extinction deficits, and neurobiological alterations, particularly in the hippocampus. Oxidative stress, reduced brain-derived neurotrophic factor (BDNF), and dendritic remodeling are key contributors to these dysfunctions. This study investigated whether Ginkgo biloba extract, known for its antioxidant and neuroprotective properties, could ameliorate PTSD-like symptoms and hippocampal abnormalities in male rats exposed to the single prolonged stress (SPS) model. Adult male Wistar rats were exposed to SPS and treated with Ginkgo biloba extract (20 or 200 mg/kg) for 14 days. Behavioral assessments included anxiety-like behavior, fear extinction, spatial learning and memory, and working memory. Hippocampal tissue was analyzed for oxidative stress markers (MDA, SOD, TAC), BDNF expression (Western blot), and CA3 dendritic morphology (Golgi-Cox impregnation method). SPS exposure induced marked behavioral deficits, elevated oxidative stress, reduced BDNF expression, and dendritic atrophy in CA3 pyramidal neurons. Ginkgo biloba extract, particularly at a dose of 200 mg/kg, significantly attenuated anxiety-like behaviors, facilitated fear extinction, improved memory performance, reduced oxidative damage, restored BDNF levels, and reversed dendritic retraction and branching deficits in the CA3 region of the hippocampus. These findings demonstrate that Ginkgo biloba extract exerts neuroprotective effects against trauma-induced behavioral, molecular, and structural abnormalities in a validated animal model of PTSD. While promising, these results are based on preclinical data, and further studies are necessary to determine whether similar benefits can be translated to clinical populations.
Emotion is a complex psychological phenomenon involving both arousal and valence. emotional processing (EP) refers to the ability to perceive and interpret emotional stimuli, such as facial expressions or vocal cues. In this study, we investigated functional connectivity (FC), graph-theoretical network measures, and rich-club organization during EP using task-based functional magnetic resonance imaging (fMRI) data from 100 healthy participants from the Human Connectome Project (HCP). Mean time series were extracted from 264 regions of interest (ROIs) defined by the Power Atlas, encompassing 10 large-scale functional networks. Pairwise Pearson correlation coefficients were computed to generate FC matrices, which were then thresholded using the orthogonal minimal spanning tree (OMST) method to form adjacency matrices. These matrices served as the basis for calculating global and local network metrics and analyzing rich-club organization. Permutation-based paired t-tests (p < 0.05, 1000 permutations) and family wise error (FWE)-corrected were used to identify significant differences between face and shape conditions. Our findings indicate a significant modulation of neural activity between the face and shape conditions during facial EP. Significant differences in FC, network metrics, and rich-club organization were observed at both ROI and network levels. High-level cognitive networks exhibited stronger positive correlations, whereas low-level perceptual networks showed increased anticorrelations. Global network measures, including modularity, mean local efficiency, and clustering coefficient, were increased, indicating enhanced functional segregation. Simultaneously, selective rich-club connectivity among hubs in dorsal attention, frontoparietal, visual, somatomotor, and subcortical networks suggests preserved network integration at the mesoscale level. These findings uniquely combine rich-club organization with graph-theoretical measures across 10 large-scale networks, providing novel insights into hub coordination under emotional demands. EP induces reorganization of brain networks, enhancing functional specialization while selectively modulating hub regions to maintain efficient integration. These results offer deeper insight into neural mechanisms underlying emotional cognition and may help explain connectivity alterations in emotional and affective disorders.
BackgroundUnderstanding the neural maturation of emotional inhibitory control (IC) from adolescence to young adulthood is critical but remains incompletely characterized. The present study examined age-related differences in prefrontal activation during emotional conflict processing using functional near-infrared spectroscopy (fNIRS).MethodsTwenty-six adolescents (ages 13-16, 15 male) and thirty young adults (ages 18-22, 16 male) completed an emotional Flanker task while behavioral responses and prefrontal hemodynamic activity were recorded with fNIRS.ResultsBoth groups exhibited a significant emotional Flanker effect, with slower responses on incongruent than congruent trials. fNIRS results suggested age-related differences in prefrontal recruitment patterns. Adolescents showed relatively stronger O2Hb changes in the right dorsolateral prefrontal cortex (DLPFC), indicating a more right-lateralized response to emotional conflict. In contrast, young adults exhibited a more bilateral pattern of DLPFC activation.ConclusionsThese findings suggest a developmental shift from relatively focal, right-lateralized prefrontal engagement in adolescence to more distributed bilateral recruitment in young adulthood. Such age-related differences may reflect changes in cognitive strategies alongside ongoing maturation of prefrontal networks, with localized right-sided activation in adolescents supporting behavioral performance through compensatory engagement and bilateral recruitment in young adults reflecting greater network integration and neural efficiency.
Angiogenesis plays a vital role in cerebral tissue repair following ischemic stroke. Prior in vivo studies have identified astrocytic interleukin-17A (IL-17A) as a critical mediator of post-ischemic angiogenesis, associated with upregulation of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). However, the intracellular signaling mechanisms underlying these effects within astrocytes have not been fully elucidated. This study delineates a specific intracellular signaling mechanism through which astrocytic IL-17A promotes angiogenesis following an in vitro ischemia-like injury. Primary astrocytes were exposed to oxygen-glucose deprivation followed by reperfusion (OGD/R). Astrocyte viability was assessed using the Cell Counting Kit-8 assay. Brain microvascular endothelial cells (BMECs) were cultured with astrocyte-conditioned medium (ACM). Astrocytes were treated with recombinant IL-17A (rIL-17A), IL-17A-targeted small interfering RNA, a neutralizing antibody against IL-6, or the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor AG490. Protein levels were quantified, and angiogenic capacity was determined via tube formation assays and CD34 expression analysis. Exposure to OGD/R increased IL-17A secretion from astrocytes. Treatment with rIL-17A enhanced astrocyte viability and induced IL-6 production. Activation of the JAK2/STAT3 pathway by IL-6 was required for the subsequent VEGF upregulation. Consequently, ACM from rIL-17A-treated astrocytes significantly promoted angiogenic activity in BMECs, as evidenced by enhanced tube formation. These pro-angiogenic effects were significantly attenuated by IL-17A knockdown, IL-6 neutralization, or inhibition of JAK2/STAT3 signaling in astrocytes. This study delineates a specific intracellular signaling mechanism through which astrocytic IL-17A promotes angiogenesis following ischemia-like injury. The findings identify an IL-6-dependent activation of the STAT3-VEGF signaling axis as a key mediator of this process, underscoring the therapeutic potential of targeting astrocytic IL-17A signaling in post-stroke angiogenic repair.
Mammalian models are widely employed in the research of human diseases. Behavioral tests in animals is a critical evaluative approach in scientific research, offering insights into complex disease pathophysiology and facilitating the assessment of novel therapeutic interventions. Currently, behavioral testing paradigms are extensively applied in mammalian research, particularly in rodent models. Compared to rodents, the brains of large mammals exhibit closer anatomical and biochemical homology to the human brain, thereby endowing them with significant value in neuroscience. Numerous neurological disorders have been successfully used large mammals as models, with the widespread application of behavioral testing methods for these species. This review summarizes established behavioral testing methodologies developed for both small and large mammalian species, and discusses their applications, efficacy, and limitations.
An adaptive mechanism observed in virtually all living animals is the phenotypic plasticity, a phenomenon by which different phenotypes can develop from the same genotype depending on the environment experienced. Phenotypic plasticity can involve a range of life-history, physiology, morphology, and also behavioural and cognitive traits. For example, individuals exposed to complex and enriched environments generally show greater learning abilities compared to individuals raised in simpler or barren environments. Several studies suggest that brain-derived neurotrophic factor (BDNF) may be involved in this plasticity, as it is often differentially expressed in individuals exposed to different environments. We investigated this possibility in fish, taking advantage of a knockout zebrafish line lacking the gene coding for BDNF (bdnf). Zebrafish from both the knockout (bdnf -/-) and control (bdnf +/+) lines were raised in either barren or enriched environments, and their behavioural and cognitive phenotypes were analysed. bdnf -/- zebrafish exhibited higher behavioural and cognitive plasticity compared to bdnf +/+ controls, as evidenced by a pronounced increase in activity and learning scores following exposure to environmental enrichment. These results suggest that BDNF may play a modulatory role in phenotypic plasticity, although broader organisational alterations resulting from the absence of BDNF during development in knockout zebrafish cannot be ruled out. An additional exploratory analysis of the expression of other neuroplasticity-related genes identified potential pathways that may be involved in this effect.
BACKGROUND:In the last two decades, Neuropeptide S (NPS) has been identified as a key bioactive peptide in the mammalian brain, influencing fear, anxiety, wakefulness, reward, and learning. While some reviews have addressed its role in reward-seeking and anxiety, few have addressed its particular role in learning and memory. The neuropeptide S receptor 1 is highly expressed in key areas for learning processing, such as the hippocampus, cortex, thalamus, and amygdala. This review aims to examine evidence from human and animal studies that focused on the NPS system's role in modulating learning and memory. A special focus is given to experiments addressing the impact of NPS on associative learning leading to addiction and in fear conditioning, pointing to its potential therapeutic value in associated pathologies. MAIN BODY:An advanced search was conducted using the databases PubMed, Google Scholar, Web of Science, and Scopus, focusing on memory and Neuropeptide S. The reviewed data suggest that NPS modulation occurs at all memory phases, including acquisition, consolidation, and retrieval, and in extinction learning, whether motivated by appetitive or aversive stimuli. The summarized evidence shows that the NPS system interferes with working and short-term memory, mitigates learning impairments, enhances spatial and object memory consolidation, supports fear extinction learning and inhibitory avoidance consolidation, and reinstates drug-seeking behaviors. The NPS system closely interacts with key neuromodulators, including orexinergic, dopaminergic, and noradrenergic systems, in influencing memory. CONCLUSION:The Neuropeptide S system emerges as a critical modulator of memory processes. The NPS signaling may preferentially influence learning that involves emotionally or motivationally relevant stimuli. This highlights the NPS system's potential as a target for therapeutic interventions for particular memory impairments.
The Hypothalamic-pituitary-adrenal axis (HPA) and its single nucleotide polymorphisms (SNPs) potentially influence depressive symptoms and non-suicidal self-injury (NSSI) among adolescents. Adverse childhood experiences (ACEs) may dysregulate HPA axis functioning, with these complex gene-environment interactions showing significant heterogeneity across individuals. This study examined whether depressive symptoms mediate the relationship between ACEs and adolescent NSSI, and whether HPA axis genetic polymorphisms moderate this indirect pathway. For this study, 172 adolescents aged 12 to 18 years were recruited from Xuzhou Oriental Hospital affiliated with Xuzhou Medical University as the NSSI group. Additionally, 58 age-, sex-, residence-, and health-matched volunteers were recruited from the local area as the healthy control group. Demographic information was collected through questionnaires, and adverse childhood experiences, depressive symptoms, and non-suicidal self-injury behaviors were assessed using the Adverse Childhood Experiences Scale (ACEs Scale), the Beck Depression Inventory-II (BDI-II), and the Non-Suicidal Self-Injury Behavior Scale (NSSI-BS). Blood samples were collected for HPA axis genotyping targeting the following loci: SKA2 (rs7208505, rs9911583), SLC1A3 (rs2269272), FKBP5 (rs9470080), and AVPR1B (rs28373064), which were analyzed using TaqMan-PCR. All statistical analyses were performed in SPSS 27.0, including Hardy-Weinberg equilibrium (HWE), χ² test, and Pearson’s correlation coefficient, as well as PROCESS macro-model mediation analysis and simple slope analysis. Depressive symptoms were found to mediate the association between ACEs and NSSI. The SKA2-rs7208505 polymorphism significantly moderated the relationship between ACEs and depressive symptoms, influencing the indirect pathway from ACEs to depressive symptoms to NSSI. Adolescents with the AA genotype of the SKA2-rs7208505 polymorphism were more susceptible to ACEs and more likely to develop depressive symptoms compared to those with GA and GG genotypes. Timely identification and interventions targeting depressive symptoms, especially among individuals with AA genotypes of SKA2-rs7208505 who have experienced ACEs, may be crucial for preventing or reducing the risk of NSSI in adolescents.
Background Visual word recognition relies on a finely tuned interplay between the ventral and dorsal visual pathways. While the ventral stream is classically regarded as the primary substrate for orthographic processing, converging evidence suggests that the dorsal stream may provide compensatory support under increased perceptual demands. In particular, the degree of orthographic transparency influences the relative involvement of these pathways. We conducted a functional MRI study in Italian, a transparent orthography, to investigate supportive neural recruitment during reading under perceptual degradation. Participants performed a word recognition task in which visual real words were degraded through four types of visual manipulation (rotation, mirroring, reduced contrast, increased letter spacing) to increase processing difficulty. Both whole-brain and region-of-interest analyses were performed. Results Analyses revealed robust engagement of canonical ventral reading regions across conditions, alongside increased recruitment of dorsal stream areas during degraded word processing, and this dorsal involvement scaled with increasing level of visual degradation. This dorsal involvement was most prominent in the superior parietal and temporo-parietal cortices, consistent with their role in visuo-spatial attention Conclusion These findings suggest that, even in transparent languages where phonological decoding is relatively straightforward, the dorsal pathway can be part of a flexible reorganisation of the reading system. By demonstrating stimulus-driven adaptation of the reading network, our results provide novel insights into the neural flexibility underlying visual word recognition and highlight the importance of dorsal-ventral interactions in sustaining reading performance under suboptimal perceptual conditions.
A neurological condition that worsens over time, Alzheimer’s disease (AD) is typified by memory loss, cognitive decline, and functional degradation. Traditional diagnostic techniques such as neuroimaging, cerebrospinal fluid biomarkers, and neuropsychological testing are often intrusive, costly, or insensitive in the early stages. Recent years have seen the emergence of AI and ML as game-changing technologies for AD risk assessment, early detection, and customized prevention. Using sophisticated models such as deep learning, convolutional neural networks (CNNs), and graph-based algorithms, AI-driven methods achieve high performance: CNNs, for example, have reached diagnostic accuracies of 94–99
Abstract Prenatal stress may lead to cognitive and behavioral dysfunction in the offspring. Large evidence has shown the deleterious effects of maternal stress on cognitive and behavioral functions of the offspring; however, the effect of paternal stress has not been well documented. In the present study, we aimed to investigate the effect of paternal stress (chronic electrical footshocks, post-traumatic stress disorder or PTSD-like model) on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) hippocampal level in both male and female offspring during adolescence. The father rat (stress-exposed) was exposed to three consecutive shocks in a fear conditioning apparatus for ten times during four weeks, in an uncertain and unpredictable schedule. Saline (0.5 mL) or lithium chloride (50 mg/kg) was intraperitoneally injected to male and female offspring during 21–41 postnatal day (PND). The results showed that paternal stress decreased locomotor activity in female offspring, and increased anxiety-like behavior in both male and female offspring, with more effect on females. Paternal stress also decreased pain subthreshold only in female offspring and impaired passive avoidance and spatial memory in both male and female offspring. Paternal stress also decreased BDNF expression level only in female offspring. However, lithium reversed most of the behavioral dysfunctions in rats’ offspring with a history of paternal stress. We concluded that paternal stress significantly impairs cognitive and behavioral function in the offspring during adolescence, with more effect on females. Also, chronic lithium treatment may reverse the deleterious effects of paternal stress.
Anxiety symptoms exhibit day-night variation, often peaking in the late afternoon or evening. Despite clinical recognition of anxiety’s diurnal variation, time of day is rarely considered in the design or interpretation of anxiety research. In this study, we used aged (10–12 month) Long-Evans male rats to examine the extent in which time of day, chronic (> 15 weeks) high-fat diet feeding, and time-restricted feeding affect anxious-like behaviors in the elevated plus maze and the novelty box test. We find that anxious-like behaviors, such as closed-arm entries, are consistently higher during the animal’s inactive phase. This day-night variation was unaffected by high-fat diet feeding. Interestingly, restricting food to a 12-hour window did not invert the day-night variation in anxiety but reduced anxious-like behavior overall. These findings underscore the importance of multiple testing times when measuring anxiety and illustrate the relative resiliency of daily patterns in anxiety expression. Overall, we conclude that time of day modulates anxious-like behavior and should be considered in experimental designs and therapeutic interventions for anxiety.
Cognitive decline in neurological disorders substantially impairs daily functioning and quality of life, underscoring the need for effective non-pharmacological interventions. We aimed to quantify the behavioral benefits of cognitive training, characterize convergent patterns of task-related brain activation changes, and examine moderators of the neural responses underlying training effects. We conducted a meta-analysis of 21 task-based neuroimaging studies. Behavioral outcomes were synthesized using multivariate meta-analysis, while neural changes were examined with seed-based d mapping (SDM) to identify spatially consistent activation differences between training and control groups. Moderator analyses evaluated training parameters, study designs, and participant characteristics, and brain–behavior associations were assessed to link regional activation changes with cognitive improvements. Cognitive training produced a significant, moderate improvement in cognitive task performance (Hedges’ g = 0.451, 95
