BackgroundMild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understanding of genetic contributions, particularly the role of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, remains limited. This study aimed to characterize acute effects of repetitive mTBI (rmTBI) in rats with the Val68Met SNP, the rodent equivalent of the human Val66Met, focusing on behavioral, fluid biomarker, and histological changes.MethodsUsing a closed-head injury model, rats underwent five mTBIs over consecutive days. Behavioral assessments included sensorimotor function, anxiety-like behavior, spatial learning and memory, and nociceptive response. Plasma neurofilament light (NfL) levels served as a biomarker of axonal injury and immunohistochemistry evaluated microglial activation.ResultsSensorimotor deficits and increased anxiety-like behavior were found in rats with rmTBI, but these changes were not affected by sex or genotype. Plasma NfL levels were higher in rmTBI compared with sham rats, with levels greater in female rmTBI when compared with male rmTBI rats. Microglial activation was observed in the hypothalamus of injured rats, but was not influenced by genotype or sex.ConclusionsWhile the Val68Met SNP did not significantly influence acute responses to rmTBI in this study, further investigation into alternative functional and pathophysiological outcomes, as well as long-term effects, is required.

Reward cues have long been considered to enhance creative performance; however, little is known about whether rewards can affect creative problem solving by manipulating states of flexibility and persistence. This study sought to elucidate the differential impacts of real versus hypothetical rewards on the creative process utilizing the Chinese compound remote association task. Behavioral analysis revealed a significantly enhanced solution rate and response times in scenarios involving real rewards, in contrast to those observed with hypothetical rewards. Electrophysiological findings indicated that hypothetical rewards led to more positive P200-600 amplitudes, in stark contrast to the amplitudes observed in the context of real rewards. These findings indicate a positive impact of real rewards on creative remote associations and contribute new insights into the relationship between rewards and creative problem solving, highlighting the crucial role of persistence/flexibility in the formation of creativity.

The large-conductance calcium- and voltage-activated potassium (BK) channels, encoded by the KCNMA1 gene, play important roles in neuronal function. Mutations in KCNMA1 have been found in patients with various neurodevelopmental features, including intellectual disability, autism spectrum disorder (ASD), or attention deficit hyperactivity disorder (ADHD). Previous studies of KCNMA1 knockout mice have suggested altered activity patterns and behavioral flexibility, but it remained unclear whether these changes primarily affect immediate behavioral adaptation or longer-term learning processes. Using a 5-armed bandit task (5-ABT) and a novel Δrepeat rate analysis method that considers individual baseline choice tendencies, we investigated immediate trial-by-trial Win-Stay-Lose-Shift (WSLS) strategies and learning rates across multiple trials in KCNMA1 knockout (KCNMA1−/−) mice. Three key findings emerged: (1) Unlike wildtype mice, which showed increased Δrepeat rates after rewards and decreased rates after losses, KCNMA1−/− mice exhibited impaired WSLS behavior, (2) KCNMA1−/− mice displayed shortened response intervals after unrewarded trials, and (3) despite these short-term behavioral impairments, their learning rates and task accuracy remained comparable to wildtype mice, with significantly shorter task completion times. These results suggest that BK channel dysfunction primarily alters immediate behavioral responses to outcomes in the next trial rather than affecting long-term learning capabilities. These findings and our analytical method may help identify behavioral phenotypes in animal models of both BK channel-related and other neurodevelopmental disorders.

Playing video games, especially games with action-based mechanics, is correlated with better cognitive performance, yet these performance advantages may originate from intrinsic factors such as earlier life cognitive differences. We investigated whether gaming-cognition associations in a sample past young adulthood remain robust after accounting for adolescent cognitive functioning. Using data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; N = 1241, Mage = 33.3, %, age range = 28–51, Female = 52.9%), we compared cognitive performance of adult recreational gamers (40.6%) to non-gamers (59.4%) and between different types of gamers. Measures included processing speed, spatial reasoning, and working memory cognitive tasks, gaming status, and gameplay type engagement. The majority of gamer participants reported exclusively playing puzzle/strategy/life simulation games (53.0%) or action type games (33.1%); a smaller proportion reported playing both types of games (10.3%). Overall, gamers significantly outperformed non-gamers across most cognitive tasks (Cohen’s d = 0.17–0.25), with limited evidence of a differential gameplay mechanic effect across tasks. Selection effects were evident whereby after adolescent IQ adjustment, gamer cognitive effects diminished by over 35% but persisted for spatial performance. Adolescent IQ predicted puzzle/strategy/life simulation preference but not action-type games, suggesting a selection effect. Our study replicates prior gaming findings and reveals that earlier life functioning contributes to adult gaming-cognition associations. Gamer-spatial associations are not fully attributable to intrinsic factors, and playing video games, regardless of a specific gameplay mechanic or genre, may represent a cognitively engaging lifestyle behavior that may benefit cognitive functioning, with implications for preserved cognition.

BackgroundEarly life stress (ELS) during the stress hypo-responsive period (SHRP) alters the curiosity-like behavior later during adolescence. Previous studies have shown maternal separation (MS) stress-induced heightened curiosity and associated risk-taking behavior in the object retrieval task (ORT). However, the neural correlates of curiosity in adolescent rats predisposed to early life stress remain unexplored. Hence, the present study aimed to investigate the neural oscillatory patterns and network characteristics in the regions implicated in curiosity behavior, such as the Prelimbic cortex (PL), Nucleus Accumbens (NAc), and CA1 of the Hippocampus. The local field potentials data were analysed to understand the neural activity patterns in these areas during the risky zone crossing and object retrieval phase of the ORT in MS rats and compared with the normal control (NC) group.ResultsIn comparison to NC, MS rats showed a reduction in the theta power at 8–12 Hz, beta power at 12–20 Hz, and gamma power at 20–40 Hz range in the PL during risky zone crossing time. MS rats also showed reduced cross-correlation between PL-CA1 and reduced theta coherence between NAc-CA1 during risky zone crossing. During the object retrieval phase, the MS rats showed reduced peak cross-correlation between PL-CA1 and PL-NAc. Behaviourally, MS rats displayed an increased preference for the curiosity platform and retrieved more hidden objects, thus accounting for a higher curiosity index than controls.ConclusionIn summary, a reduced synchronization between the PL, NAc, and CA1 during the object retrieval task indicates how early MS stress during a critical developmental period impacts the limbic circuit connectivity. This corresponded with enhanced curiosity index in adolescent MS rats, predicting an altered intrinsic motivation and hence a higher susceptibility to substance use disorders during adolescence.

BackgroundCutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer’s disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons.MethodsIn this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ1–42) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated.ResultsC. acnes-infected rats displayed memory deficits and Aβ1–42 deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals.ConclusionBased on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites.Graphical

BackgroundNeuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE.ResultsOptogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels.ConclusionOur data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case–control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways.

BackgroundAction semantics have been investigated in relation to context violation but remain less examined in relation to the meaning of gestures. In the present study, we examined tool–gesture incongruity by event-related potentials (ERPs) and hypothesized that the component N400, a neural index which has been widely used in both linguistic and action semantic congruence, is significant for conditions of incongruence.MethodsTwenty participants performed a tool–gesture judgment task, in which they were asked to judge whether the tool–gesture pairs were correct or incorrect, for the purpose of conveying functional expression of the tools. Online electroencephalograms and behavioral performances (the accuracy rate and reaction time) were recorded.ResultsThe ERP analysis showed a left centro-parieto-temporal N300 effect (220–360 ms) for the correct condition. However, the expected N400 (400–550 ms) could not be differentiated between correct/incorrect conditions. After 700 ms, a prominent late negative complex for the correct condition was also found in the left centro-parieto-temporal area.ConclusionsThe neurophysiological findings indicated that the left centro-parieto-temporal area is the predominant region contributing to neural processing for tool–gesture incongruity in right-handers. The temporal dynamics of tool–gesture incongruity are: (1) firstly enhanced for recognizable tool–gesture using patterns, (2) and require a secondary reanalysis for further examination of the highly complicated visual structures of gestures and tools. The evidence from the tool–gesture incongruity indicated altered brain activities attributable to the N400 in relation to lexical and action semantics. The online interaction between gesture and tool processing provided minimal context violation or anticipation effect, which may explain the missing N400.

Background Parsley was employed as an experimental probe to prevent the behavioral, biochemical and morphological changes in the brain tissue of the albino mice following chronic cadmium (Cd) administration.Methods Non-anesthetized adult male mice were given parsley juice (Petroselinum crispum, Apiaceae) daily by gastric intubation at doses of 10 and 20 g/kg/day. The animals were divided into six groups: Group A, mice were exposed to saline; Groups B and C, were given low and high doses of parsley juice, respectively; Group D, mice were exposed to Cd; Groups E and F, were exposed to Cd and concomitantly given low and high doses of parsley, respectively.ResultsCd intoxication can cause behavioral abnormalities, biochemical and histopathological disturbances in treated mice. Parsley juice has significantly improved the Cd-associated behavioral changes, reduced the elevation of lipid peroxidation and normalized the Cd effect on reduced glutathione and peroxidase activities in the brain of treated mice. Histological data have supported these foundations whereas Cd treatment has induced neuronal degeneration, chromatolysis and pyknosis in the cerebrum, cerebellum and medulla oblongata.ConclusionThe low dose (5 g/kg/day) of parsley exhibited beneficial effects in reducing the deleterious changes associated with Cd treatment on the behavior, neurotransmitters level, oxidative stress and brain neurons of the Cd-treated mice.