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.
