Behavioral And Brain Functions[JOURNAL]
Sun
200 papers
Next generation preventive neurology: how artificial intelligence and machine learning are reshaping Alzheimer's disease research.
Singh S, Sharma Y, Bhardwaj P … +6 more , Kothari D, Chhikara A, Gupta V, Kumar D, Choudhary N, Kondaveeti SB
Behav Brain Funct · 2026 Mar · PMID 41918005 · Full text
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 f...
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% for early AD and mild cognitive impairment using multimodal MRI and PET data. However, most reported performance metrics are derived from retrospective analyses and internal validation cohorts, with limited external validation across diverse populations. These methods include multimodal data integration from neuroimaging, genetics, and clinical records. Years before symptoms appear, AI-based frameworks can predict disease progression, identify modifiable risk factors, and guide individualized treatment plans. Future developments in federated learning and explainable AI (XAI) are promising, although data privacy, algorithmic bias, and ethical ramifications are concerns. Overall, AI and ML have a great deal of promise to transform the prevention of AD, enabling precision therapy and enhancing the lives of those who are at risk.
The impact of paternal PTSD-like stress on cognitive behavior and hippocampal BDNF expression in adolescent male and female rat offspring: modulatory effects of lithium.
Ebrahimkhani Z, Behnoud H, Kazemi AS … +1 more , Yekta BG
Behav Brain Funct · 2026 Mar · PMID 41906149 · Full text
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...
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.
The neural, neurotransmitter, and transcriptomic mechanisms underlying dispositional greed: exploring its link to negative psychopathology.
Feng L, Hu Y, Li X … +6 more , Liu C, Ge Y, Wang P, Jin W, Chang H, Wang Q
Behav Brain Funct · 2026 Mar · PMID 41904537 · Full text
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Impact of high-fat diet and feeding time on daily anxious-like behaviors in aged male rats.
Rivera A, Thorstenson E, Ghasemzadeh MB … +1 more , Arble DM
Behav Brain Funct · 2026 Mar · PMID 41888918 · Full text
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...
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.
A brainstem-thalamocortical circuit mediates postoperative pain duration induced by sleep deprivation.
Li L, Zhang H, Gao Y … +9 more , Khan S, Wu F, Ren X, Zhang J, Bedane KH, Jian L, Zang W, Bai Q, Cao J
Behav Brain Funct · 2026 Mar · PMID 41851744 · Full text
BACKGROUND: Postoperative sleep disturbances are common and have been shown to exacerbate incisional pain by enhancing the central nervous system's excitability. However, the specific neural circuit mechanisms underlying...
BACKGROUND: Postoperative sleep disturbances are common and have been shown to exacerbate incisional pain by enhancing the central nervous system's excitability. However, the specific neural circuit mechanisms underlying the pain chronification induced by postoperative sleep deprivation remain largely elusive. METHODS: We established a model of postoperative pain by plantar incision with perioperative sleep deprivation 6 h/day for 3 consecutive days in male mice. The activity of the neurons in the paraventricular thalamus nucleus (PVT) and the locus coeruleus (LC) was assessed using immunofluorescence and fiber photometry. Viral tracing, immunofluorescence staining, chemogenetics, optogenetics, and fiber photometry were utilized to investigate the anatomical and functional connections of the neural circuit. Furthermore, chemogenetic and optogenetic manipulations, combined with behavioral tests, were employed to investigate the roles of various nuclei or neural circuits in the perioperative sleep deprivation-induced prolongation of postsurgical pain. RESULTS: Sleep deprivation prolonged the duration of postsurgical pain and increased the excitability of glutamatergic neurons in the PVT (PVT) and tyrosine hydroxylase-positive neurons in the LC (LC). Viral tracing revealed a direct projection from LC neurons to PVT neurons. Selective chemogenetic activation of the LC-PVT pathway reduced sleep duration and replicated the pain-prolonging effects of sleep deprivation. Furthermore, viral tracing and morphology indicate that GABAergic neurons in the medial prefrontal cortex (mPFC) receive projections from the LC-PVT pathway. We found that hypersensitivity was sustained by the activation of the LC-PVT-mPFC after incision, while its chemogenetic inhibition reversed sleep deprivation mediated pain prolongation. CONCLUSION: These findings indicate that brainstem-thalamocortical pathway mediates the sleep deprivation-induced prolongation of postoperative pain. This circuit may serve as a mechanistic link between disrupted arousal states and pain duration, representing a potential therapeutic target for managing postsurgical pain.
The role of the kynurenine pathway in conditioned place aversion induced by synthetic cannabinoid CP-55940.
Cong J, Zhang H, Li N … +5 more , Yang J, Liu M, Ma Q, Zhang C, Yan G
Behav Brain Funct · 2026 Mar · PMID 41845411 · Full text
BACKGROUND: The therapeutic potential of cannabinoids is increasingly recognized; however, their use is often associated with adverse effects, such as conditioned place aversion (CPA). The molecular mechanisms underlying...
BACKGROUND: The therapeutic potential of cannabinoids is increasingly recognized; however, their use is often associated with adverse effects, such as conditioned place aversion (CPA). The molecular mechanisms underlying CPA remain poorly understood, particularly the role of the kynurenine pathway (KP) and its interaction with cannabinoid receptors. This study aimed to elucidate these mechanisms, focusing on the synthetic. METHODS: We employed a mouse conditioned place preference behavioral model to assess CPA following the administration of CP-55940 at a dosage of 1 mg/kg via intraperitoneal injection. We conducted a comprehensive analysis of key metabolites in the kynurenine pathway, specifically measuring levels of kynurenic acid (KYNA) in the hippocampus, while also monitoring quinolinic acid levels for comparison. Additionally, we utilized pharmacological inhibition of KATII with PF-04859989 to further explore KYNA’s role in mediating CPA. RESULTS: Our findings revealed significant increases in tryptophan, kynurenine, and KYNA levels in the hippocampus following administration of CP-55940, whereas quinolinic acid levels remained unchanged. Notably, pharmacological inhibition of KATII effectively reduced CPA, thereby affirming the critical role of KYNA in the aversive response. Furthermore, we observed that KYNA downregulated CB1 receptor (CB1R) expression, which was restored upon inhibition of KYNA synthesis. Additionally, G protein-coupled receptor 35 (GPR35) expression was significantly reduced in the CPA model, and its levels were positively correlated with KYNA, suggesting intricate molecular interactions. CONCLUSION: This study elucidates the complex interplay between KYNA, CB1R, and GPR35 in the context of cannabinoid-induced CPA, highlighting the pivotal role of the TRP–KYN pathway in mediating adverse behavioral effects associated with cannabinoids. These findings open avenues for the development of therapeutic targets aimed at mitigating such effects. Future research should focus on validating these results through gene knockout models and further exploring the clinical implications of KYNA modulation in cannabinoid pharmacology and neuropsychiatric disorders.
Cognitive training in neurological disorders: meta-analytic evidence for behavioral gains and neural correlates.
Li G, Liu Y, Liu C … +1 more , Zhang Y
Behav Brain Funct · 2026 Mar · PMID 41772608 · Full text
BACKGROUND: 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 behavio...
BACKGROUND: 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. METHODS: 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. RESULTS: Cognitive training produced a significant, moderate improvement in cognitive task performance (Hedges’ g = 0.451, 95% CI 0.207–0.696; p < .001). Neuroimaging meta-analysis showed increased task-evoked activation after training in the bilateral precuneus and the left precentral gyrus (L. PreCG) relative to controls. Only precuneus activation increases were associated with behavioral gains. Moderator analyses indicated reduced precuneus activation but increased L. PreCG activation during transfer relative to trained tasks, and reduced L. PreCG activation for adaptive versus fixed-difficulty training. Passive controls also showed stronger L. PreCG activation changes than active controls, whereas participant characteristics and training dose showed no significant effects. CONCLUSIONS: Cognitive training improved cognitive task performance and was accompanied by a convergent activation signature centered on the bilateral precuneus and the L. PreCG in neurological disorders. Precuneus engagement tracked cognitive gains, highlighting it as a candidate neural marker of training-related plasticity in this population.
The impact of predator stress on electroshock seizure threshold: insights into GABAergic, glutamatergic, and serotonergic pathways in mice.
Vafaei A, Kharaghani MA, Shahsavand A … +4 more , Mohammad Jafari R, Shafaroodi H, Ghasemi M, Dehpour AR
Behav Brain Funct · 2026 Feb · PMID 41691280 · Full text
BACKGROUND: Post-traumatic stress disorder (PTSD) disrupts neural pathways, increasing susceptibility to neurological disorders, including epilepsy. Stress-induced alterations in glutamatergic, GABAergic, and serotonergi...
BACKGROUND: Post-traumatic stress disorder (PTSD) disrupts neural pathways, increasing susceptibility to neurological disorders, including epilepsy. Stress-induced alterations in glutamatergic, GABAergic, and serotonergic systems influence seizure susceptibility. This study investigates seizure thresholds within a PTSD-relevant mouse model, evaluating the roles of these neurotransmitters. METHODS: Male NMRI mice were exposed to predator stress using Wistar rats. Seizure thresholds were assessed via electroshock tests at multiple post-stress intervals. Pharmacological interventions, diazepam, MK-801, and fluoxetine, were administered seven days post-stress. Hippocampal tissues were analyzed for GABA receptor α subunit, NMDAR1, and 5-HT receptor expression, as well as nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) protein levels, utilizing Western blot techniques. RESULTS: Predator stress significantly decreased seizure thresholds in a time-dependent manner, with the highest effect on day 7 (P < 0.0001). Treatment with diazepam (P < 0.05), MK-801 (P < 0.0001), and fluoxetine (P < 0.0001) reversed these effects, increasing seizure thresholds. Western blot analysis revealed reduced expression of GABAα, NMDAR1, and 5-HT receptors (P < 0.001). Additionally, NF-κB levels were elevated while ERK levels were reduced (P < 0.001). CONCLUSION: This study shows that predator stress is associated with increased seizure susceptibility and with downregulation of hippocampal GABAAα1R and 5-HT1AR expression, together with enhanced NF-κB activation and reduced ERK signaling. Pharmacological modulation of GABAergic, glutamatergic, and serotonergic pathways reversed the stress-induced reduction in seizure threshold in this model, suggesting that these systems may contribute to stress-related seizure susceptibility.
Investigating interbrain synchrony under teamwork disruption: an fNIRS hyperscanning study.
Réveillé C, Vergotte G, Dray G … +5 more , Jean PA, Jean P, Pla S, Perrey S, Bosselut G
Behav Brain Funct · 2026 Feb · PMID 41656247 · Full text
BACKGROUND: Teams are inherently adaptive entities that continuously adapt to changes or disruptions in their tasks or environments. During collaboration, interbrain synchrony (IBS) emerges, reflecting the temporal align...
BACKGROUND: Teams are inherently adaptive entities that continuously adapt to changes or disruptions in their tasks or environments. During collaboration, interbrain synchrony (IBS) emerges, reflecting the temporal alignment of neural activity between team members. Building on this, IBS has been proposed as a potential marker of teamwork, suggesting that IBS should be sensitive to changes in teamwork. PURPOSE: The present study investigated whether IBS is sensitive to changes in teamwork. We hypothesized that disruptions in teamwork would be accompanied by alterations in IBS dynamics. METHODS: Ninety-eight healthy adults (mean age = 22.5 ± 3.22 years; 69 females, 65.1%) were assigned to forty-nine dyads. Each pair completed a 20-minute computer-based navigation task while their brain activity was simultaneously recorded using fNIRS hyperscanning. Dyads in the experimental group encountered an unexpected increase in task difficulty midway through the task, whereas those in the control group completed the task without disruption. We examined three features of IBS - its overall level, temporal slope trajectory, and the temporal recurrence patterns. RESULTS: Control analyses confirmed that IBS reliably emerged during the task (χ²(1) = 50.24, p < .001) and that the experimental manipulation successfully disrupted teamwork, as reflected in altered team behavioral responses in communication (χ²(1) = 8.48, p = 0.004) and performance (χ²(1) = 24.99, p < .001). Nevertheless, no evidence was found for disruption-related changes in IBS across the three features examined (all Time x Group interactions p > .05. CONCLUSION: These findings raise the possibility that IBS may reflect a stable collective state rather than a reactive one, thereby challenging its interpretation as a direct marker of teamwork. Methodological considerations, including the operationalization of IBS, are also discussed as potential explanations for the lack of observed change in IBS.
Effects of electroacupuncture at Zusanli on pain-perception-related brain nuclei in KOA mice: a study on cortical and subcortical c-fos expression.
Chen A, Zhao T, Gao X … +3 more , Liang H, Xiong L, Shen W
Behav Brain Funct · 2026 Feb · PMID 41656233 · Full text
BACKGROUND: Electroacupuncture is widely accepted to treat pain related conditions, but detailed mechanisms remain unknown. OBJECTIVE: To explore cortical and subcortical subnuclei involved in electroacupuncture stimulat...
BACKGROUND: Electroacupuncture is widely accepted to treat pain related conditions, but detailed mechanisms remain unknown. OBJECTIVE: To explore cortical and subcortical subnuclei involved in electroacupuncture stimulation (EAS) analgesia by observing EAS's analgesic efficacy and c-fos expression changes, providing a basis for neural circuit research and clinical transcranial magnetic stimulation (TMS) therapy. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A chronic inflammatory pain model was established using knee osteoarthritis (KOA). Bilateral Zusanli was selected for electroacupuncture intervention. Von Frey test, open field test, elevated plus maze, and tail suspension test, and immunohistochemical staining were performed. MAIN OUTCOMES MEASURES: Changes in mechanical pain threshold and pain-related emotional behaviors and distribution of c-fos positive cells in cortical and subcortical nuclei. RESULTS: Electroacupuncture significantly increased mechanical pain thresholds in KOA model mice. KOA modeling caused c-fos downregulation in the motor cortex, insular cortex, secondary auditory cortex, dorsal peduncular cortex, temporal association cortex, caudate putamen, lateral septal nucleus, accumbens nucleus, and the anterior cortical amygdaloid area. Electroacupuncture at Zusanli reversed these changes, upregulating c-fos in abovementioned brain regions, and additionally upregulated c-fos expression in the granular insular cortex, extended amydala. CONCLUSION: Inflammatory pain induces widespread inhibition of neuronal activity in cortical and subcortical nuclei. The core mechanisms of electroacupuncture analgesia may involve direct reversal of abnormal inhibition in the lateral septal nucleus, caudate putamen, accumbens nucleus, and the anterior cortical amygdaloid area and activation of the granular insular cortex, medial septal nucleus and the extended amygdala for pain information integration.
Overexpression of FoxO3a in the dentate gyrus alleviates CUS-induced anxiety- and depression-like behaviors and cognitive impairment.
Yi S, Yang B, Zhang X … +4 more , Zhao B, Wei L, Yao Z, Zhang R
Behav Brain Funct · 2026 Feb · PMID 41622191 · Full text
BACKGROUND: Excessive stress leads to injury and dysfunction, but the underlying mechanism remains unclear. As a human longevity gene, forkhead box O3a (FoxO3a) is a transcription factor that regulates various cellular p...
BACKGROUND: Excessive stress leads to injury and dysfunction, but the underlying mechanism remains unclear. As a human longevity gene, forkhead box O3a (FoxO3a) is a transcription factor that regulates various cellular processes, including the response to oxidative stress, apoptosis, and autophagy. This study aims to explore whether FoxO3a in the dentate gyrus (DG) of the hippocampus is involved in the formation of anxiety- and depressive-like behavior and cognitive impairment in stressed rats and to investigate the detailed mechanism. METHODS: This study was conducted using the 6-week chronic unpredictable stress (CUS) model. Before the stress treatment, we injected an adeno-associated virus (AAV) vector to overexpress FoxO3a specifically in the DG. Following the 6-week CUS treatment, a series of behavioral tests was conducted. Depression-like behavior was assessed using the sucrose preference test (SPT) and the open field test (OFT). The state of desperation was assessed with the forced swim test (FST) and tail suspension test (TST). Anxiety-like behavior was measured in the elevated plus maze (EPM) and OFT. Cognitive function was examined using the Y-maze test (Y-maze), novel object recognition test (NORT), and Morris water maze test (MWM). The level of reactive oxygen species (ROS) and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. The levels of inflammatory factors were detected by ELISA. Pathological injury in DG was observed using thionine staining. The expression levels of FoxO3a, brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), and proliferation marker Ki67 (Ki67) were determined using western blot. RESULTS: CUS leads to various abnormal changes, including anxiety- and depressive-like behavior, cognitive impairment, oxidative stress, neuroinflammation, neuropathological alterations in the DG, and decreased expression of FoxO3a, BDNF, PSD95, SYN, and Ki67. All these abnormal changes were significantly alleviated by targeted AAV-FoxO3a injection in the DG. CONCLUSIONS: In conclusion, our study demonstrates that the downregulation of FoxO3a induced by CUS in the DG triggers oxidative stress and inflammatory response, inhibits cell proliferation, and induces abnormal synaptic plasticity, ultimately leading to anxiety- and depressive-like behaviors and cognitive impairment.
Effect of low frequency stimulation of olfactory bulb and olfactory epithelium on epileptiform activity and synaptic plasticity following pentylenetetrazol administration in rats.
Choupankareh S, Zare M, Rezaei M … +5 more , Barkley V, Shojaei A, Raoufy MR, Fathollahi Y, Mirnajafi-Zadeh J
Behav Brain Funct · 2026 Jan · PMID 41618379 · Full text
BACKGROUND: The effect of olfactory bulb (OB) and olfactory epithelium (OE) electrical stimulation on epileptiform activity and seizure-induced impairment on synaptic plasticity and memory was investigated in anesthetize...
BACKGROUND: The effect of olfactory bulb (OB) and olfactory epithelium (OE) electrical stimulation on epileptiform activity and seizure-induced impairment on synaptic plasticity and memory was investigated in anesthetized and freely-moving animals. METHODS: Male Wistar rats were anesthetized with urethane (1.5 g/kg). Stimulating electrodes were bilaterally placed in either the OB or the OE. Another electrode was placed in the CA1 area for recording epileptiform discharges (EDs) following a pentylenetetrazol (PTZ, i.v.) injection and evoked field potentials following Schaffer collateral stimulation. Subjects were divided into PTZ and control groups. Each group received a 1 Hz stimulation either in the OB (OBS) or the OE (OES). ED threshold and duration, and the ability to generate long-term potentiation (LTP) were assessed. Finally, the effect of OBS on acute PTZ-induced seizures and working memory was investigated in freely-moving animals. OBS significantly increased the ED threshold when applied at 250 µA and decreased ED duration when applied at 125 and 250 µA. RESULTS: Applying OES had a small effect on the ED threshold but significantly decreased ED duration when applied at 125 and 250 µA. Both OBS and OES mitigated the PTZ-induced increase in basal synaptic transmission. Meanwhile, OBS and OES significantly restored the LTP generation following PTZ injection in anesthetized rats. In addition, applying OBS in freely-moving animals reduced the seizure severity and restored working memory impairment. CONCLUSIONS: OB and OE may be considered effective stimulation targets for the attenuation of epileptiform activity and seizure severity. In addition, both OBS and OES decreased the seizure-induced impairment in LTP generation.
A two-week period of detraining reduces hippocampal volume in regularly active young adults: a structural MRI study.
Cherednichenko A, Baena-Pérez M, Beltran-Valls MR … +2 more , Moliner-Urdiales D, Ávila C
Behav Brain Funct · 2026 Jan · PMID 41580862 · Full text
BACKGROUND: Regular physical activity (PA) confers numerous benefits to both peripheral and cerebral health, including enhanced cardiovascular and muscular function, as well as improved cognitive performance and neuropla...
BACKGROUND: Regular physical activity (PA) confers numerous benefits to both peripheral and cerebral health, including enhanced cardiovascular and muscular function, as well as improved cognitive performance and neuroplasticity. The hippocampus, a brain region highly sensitive to the effects of PA, has been consistently shown to undergo structural enhancements with sustained exercise. However, the impact of physical detraining-the cessation or significant reduction of regular PA-on hippocampal structure remains largely unexplored, particularly in humans. This study aimed to investigate whether a 14-day period of voluntary exercise reduction leads to measurable structural changes in the hippocampus, and whether these changes are associated with anxiety symptomatology. RESULTS: Paired t-tests analyses did not reveal significant changes in hippocampal volume for the whole sample. However, multiple regression analyses on volume change including physical fitness index and degree of moderate and vigorous PA reduction as independent variables, revealed a significant decrease in hippocampal gray matter volume following detraining in individuals with greater MVPA reduction. Notably, pre and post-detraining state anxiety levels were lower in participants who showed larger reductions in hippocampal volume. CONCLUSIONS: These findings suggest that even short-term interruptions in regular physical activity may prompt rapid structural changes in the hippocampus, modulated by the extent of detraining. The observed relationship between hippocampal volume reduction and decreased state anxiety points to stress regulation as a potential mechanism. Further research is warranted to explore the functional significance and potential reversibility of these neuroplastic changes.
Conserved NT5C2 links context-specific behaviors with psychiatric and metabolic risk.
Moulin TC, Aldavero-Muñoz I, Williams MJ … +1 more , Schiöth HB
Behav Brain Funct · 2026 Jan · PMID 41495857 · Full text
BACKGROUND: The cytosolic 5'-nucleotidase II (NT5C2) enzyme has been implicated in both psychiatric disorders and metabolic traits, but whether these associations reflect a shared biological basis remains unclear. Here w...
BACKGROUND: The cytosolic 5'-nucleotidase II (NT5C2) enzyme has been implicated in both psychiatric disorders and metabolic traits, but whether these associations reflect a shared biological basis remains unclear. Here we combined cross-species approaches to investigate how reduced NT5C2 function shapes behavior. RESULTS: In Drosophila melanogaster, neuronal knockdown of the ortholog dNT5B increased activity around light-dark transitions, reduced sleep fragmentation, and selectively suppressed food intake under satiated conditions. Moreover, analysis of mouse phenotyping data revealed that whole-body Nt5c2 knockout alters locomotor activity, sensorimotor gating, and anxiety-related behaviors. Finally, human variant-trait associations showed reproducible enrichment in both metabolic domains, including body composition and BMI, and neuro-psychiatric outcomes such as schizophrenia, smoking, and anxiety. CONCLUSIONS: Together, these phenotypic findings indicate that NT5C2 is a conserved neuro-metabolic regulator, linking energy-related pathways to specific behavioral dimensions that may underlie its pleiotropic impact on psychiatric and metabolic risk.
Correlation of prefrontal-based resting state functional connectivity with the degree of cognitive impairment in Alzheimer's disease: a functional near-infrared spectroscopy study.
Chen M, Zhang W, Yan M … +7 more , Zhong F, Song J, Guo Y, Chen Y, Tian Q, Yu W, Lü Y
Behav Brain Funct · 2025 Dec · PMID 41454385 · Full text
BACKGROUND: This study aims to investigate the differences in neural network connectivity within the prefrontal cortex (PFC) among elderly individuals with normal cognition (NC), mild cognitive impairment (MCI), and Alzh...
BACKGROUND: This study aims to investigate the differences in neural network connectivity within the prefrontal cortex (PFC) among elderly individuals with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) using functional near-infrared spectroscopy (fNIRS). RESULTS: Significant differences in functional connectivity (FC) strength were observed between the NC, MCI, and AD groups in several Brodmann areas (BA) pairs, including BA46.L-BA45.R and BA9.L-BA1.L. The most pronounced FC strength differences between the NC and MCI groups occurred at the 2nd -minute mark in BA45.R, while differences between the MCI and AD groups peaked at the 5th-minute mark in BA1.L. Additionally, the NC and MCI groups displayed FC strength differences during the first 2 minutes and first 3 minutes, again with BA45.R being central. FC strength between BA46.L-BA45.R was negatively correlated with Neuropsychiatric Inventory and Clinical Dementia Rating scores. CONCLUSIONS: FC strength in the left dorsolateral PFC, where BA46.L and BA9.L are located, emerged as a key region for cortical dysfunction in cognitive impairment. Moreover, there were differences in FC across levels of cognitive impairment, and significant correlations between differences in FC strength in BA brain regions and cognitive level.
Brain network efficiency during social interaction is associated with real-world social network size.
Han M, Liu X, Shao Y … +8 more , Ge H, Chen F, Li J, Wang L, Zhong X, Hu Y, Zhu Y, Yang L
Behav Brain Funct · 2025 Dec · PMID 41408556 · Full text
Social ties critically influence individual health and well-being, raising important questions about why some individuals occupy advantageous social network positions. While social cognition is known to play a key role,...
Social ties critically influence individual health and well-being, raising important questions about why some individuals occupy advantageous social network positions. While social cognition is known to play a key role, it remains unclear whether neural differences during social information processing is associated with variability in the social network structure. Using the Prisoner's Dilemma Game (PDG) combined with multilayered social network analysis, brain network analysis, and machine learning, we investigated how neural activation patterns relate to individual social network structures. The results revealed that individuals with a larger social network size were associated with (1) heightened nodal efficiency in the midcingulate cortex (MCC), (2) reduced efficiency in the inferior occipital gyrus (IOG), (3) enhanced functional connectivity between the anterior cingulate cortex-supplementary motor area (ACC-SMA) and olfactory-somatosensory regions, and (4) significantly negative predictive effects of nodal efficiency in both the IOG and hippocampus (as identified through machine learning). These findings demonstrate that efficient brain network organization, characterized by optimized integration in the cingulate cortex with a conflict monitoring function and selective suppression of visual attention and memory processing, is related to real-world social adaptation. Our study offers novel neurobiological insights into social networks, highlighting the crucial role of neural efficiency in social resource acquisition.
Regulation of glial markers expression in the rat basolateral amygdala and hippocampus during morphine aversive memory retrieval and its extinction.
Franco-García A, Gómez-Murcia V, Núñez C
Behav Brain Funct · 2025 Dec · PMID 41392136 · Full text
BACKGROUND: Opioid use disorder is driven by neurobehavioral adaptations where environmental cues trigger relapse. Consequently, extinction therapy (ET) aims to modify drug-associated memories but has limited long-term e...
BACKGROUND: Opioid use disorder is driven by neurobehavioral adaptations where environmental cues trigger relapse. Consequently, extinction therapy (ET) aims to modify drug-associated memories but has limited long-term efficacy. Recently, evidence suggested that glial cells may contribute to neuroplasticity phenomena in addiction. In this sense, this study examined whether aversive memories of morphine withdrawal and their extinction induce transcriptional changes in glial markers (gfap, aif1, itgam, klf4) in key memory-related regions: the basolateral amygdala (BLA) and hippocampus (dentate gyrus [DG] and CA1). RESULTS: Using the conditioned place aversion (CPA) paradigm in rats, we assessed avoidance behavior after naloxone-precipitated withdrawal and its extinction. Transcriptional analyses did not reveal major changes in the BLA. However, in CA1, downregulation of microglial markers cooccurred with aversive memory retrieval and restored after extinction. Moreover, one of the microglial markers, klf4, was reduced concomitantly with extinction memory retrieval in the DG. Correlation analyses showed negative associations between microglial markers and aversive memory strength, suggesting glial involvement in withdrawal-related learning. CONCLUSIONS: These findings might indicate that microglial activity in CA1 plays a role in opioid withdrawal-associated memories, and extinction training might be returning these effects to basal levels. Therefore, targeting glial responses could provide new therapeutic strategies to prevent relapse.
Space and time in words: exploring neural overlap and specificity.
Conca F, Mattavelli G, Gianelli C … +2 more , Canessa N, Catricalà E
Behav Brain Funct · 2025 Dec · PMID 41392133 · Full text
BACKGROUND: A common magnitude system-consistently involving the right intraparietal sulcus (IPS)-has been proposed to support the representation of space, time and numerosity. While shared mechanisms are acknowledged, d...
BACKGROUND: A common magnitude system-consistently involving the right intraparietal sulcus (IPS)-has been proposed to support the representation of space, time and numerosity. While shared mechanisms are acknowledged, domain-specific contributions have also been suggested. Among these, the role of the right precuneus remains debated, with inconclusive evidence regarding its involvement in spatial and temporal processing. Translating this question into the language domain and within a grounded cognition framework, we investigated the causal contribution of the IPS and precuneus to the processing of spatial and temporal concepts (e.g., circuit, eternity) using a state-dependent Transcranial Magnetic Stimulation (TMS) priming paradigm. Twenty healthy participants received stimulation over the IPS and precuneus, and a sham stimulation over the control site (vertex). RESULTS: Results showed that stimulation of the IPS abolished the priming effect observed under the sham control condition for both spatial and temporal concepts, whereas stimulation of the precuneus selectively disrupted priming for temporal concepts only. CONCLUSIONS: These findings support the role of the right IPS as a key area for magnitude processing in language, while also highlighting a more specific contribution of the precuneus-particularly its ventral portion-to temporal concepts.
Cognitive training shapes brain plasticity and schematic representations.
Chen W, Hao Y
Behav Brain Funct · 2025 Dec · PMID 41388423 · Full text
Cognitive functions are critical to everyday life, and enhancing cognitive abilities has significant implications for both individual development and societal advancement. However, there remains no consensus on whether c...
Cognitive functions are critical to everyday life, and enhancing cognitive abilities has significant implications for both individual development and societal advancement. However, there remains no consensus on whether cognitive capacities can be systematically improved through behavioral interventions, commonly known as cognitive training. Recent advancements in large-scale neural recordings offer unprecedented insights into the brain's cognitive mechanisms, presenting new opportunities to rigorously assess the effectiveness of cognitive training. In this review, we examine the core neural substrates underlying cognitive processes and explore generalized mechanisms of neuroplasticity associated with cognitive training. Integrating findings from animal models and human research, we emphasize the role of emerging schematic neural representations as potential mediators of cognitive transfer. Finally, we discuss future directions that could shed light on the mechanistic foundations of transfer after training, aiming to bridge the gap between experimental findings and real-world cognitive enhancement.
Sex-dependent effects of tamoxifen on mouse behavior.
Xu RX, Liao SH, Wang N … +5 more , Jiang WY, Wang X, Li XW, Gao TM, Yang JM
Behav Brain Funct · 2025 Dec · PMID 41366492 · Full text
This study aimed to investigate the sex-dependent behavioral effects of tamoxifen, commonly used to induce Cre recombination in transgenic systems, across three developmental stages (adult, adolescent, and neonatal) and...
This study aimed to investigate the sex-dependent behavioral effects of tamoxifen, commonly used to induce Cre recombination in transgenic systems, across three developmental stages (adult, adolescent, and neonatal) and two CreERT2 mouse lines (CaMKIIα-CreERT2 and Aldh1l1-CreERT2). Both male and female mice, including wild-type C57BL/6J and CreERT2 transgenic lines, were subjected to tamoxifen treatment followed by behavioral tests assessing locomotion, anxiety-like behavior (open field test and elevated plus maze), social interaction, recognition memory (new object recognition), sucrose preference, and depression-like behavior (forced swimming test) at least 4 weeks post-treatment. We found that adult tamoxifen treatment increased depression-like behavior specifically in males, while adolescent treatment increased sucrose preference only in males, yet impaired recognition memory and increased depression-like behavior in both sexes. Neonatal treatment caused pervasive impairments, reducing locomotion and increasing anxiety- and depression-like behavior in both sexes, while enhancing social interaction only in males. Furthermore, effects differed in adult CaMKIIα-CreERT2 and Aldh1l1-CreERT2 mice. In the former, tamoxifen treatment impaired locomotion, increased anxiety-like behavior, and reduced recognition memory specifically in females, while increasing sucrose preference in males. In the latter, tamoxifen treatment impaired recognition memory in both sexes but increased sucrose preference only in males. These results demonstrate that tamoxifen alone induced long-lasting, sex-specific behavioral alterations dependent on developmental exposure. Furthermore, interactions of tamoxifen with CreERT2 expression introduced additional complexity, potentially confounding genetic studies. These findings emphasize the necessity of including appropriate controls (vehicle, tamoxifen-only, Cre-only) and both sexes in studies using the tamoxifen-inducible CreERT2-loxP system.
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