Search Results (401)

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex/anterior cingulate cortex (dmPFC/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 ± 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 ± 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann–Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD. Full article

Transcranial direct current stimulation (tDCS) modulates cortical excitability, thus inducing improvements in motor learning of simple tasks. In this study, we aimed to evaluate the effect of different tDCS conditions—anodal stimulation over the motor cortex (M1), anodal and cathodal stimulation over the prefrontal cortex (PFC), and sham—on the online and offline learning of a complex accuracy task (golf-putting) in novice golfers. Methods: A total of 40 young, healthy subjects (24 men, 16 women) without previous golf experience were randomly distributed in four groups receiving sham, anodal M1, anodal PFC or cathodal PFC tDCS. All subjects participated in two consecutive sessions. In the first session, they performed 15 blocks of 10 golf-putting along with tDCS stimulation. After 24 h, they performed the same task without tDCS. Results: Repeated measures ANOVA revealed a significant improvement in performance during the two consecutive golf-putting sessions regardless of the site and the stimulation conditions. Conclusion: Our findings suggest that tDCS over M1 or PFC does not confer additional benefits in the acquisition of complex, full-body motor skills such as golf-putting. Full article

Objective: Burning mouth syndrome (BMS) is a chronic and often debilitating orofacial pain condition characterized by a burning sensation in the oral mucosa without clear abnormal lesions. While its etiology is considered multifactorial, the underlying pathophysiology remains unclear. This narrative review aims to synthesize existing functional magnetic resonance imaging (fMRI) studies to shed light on the central neural mechanisms contributing to BMS. Methods: A focused electronic search was conducted across the PubMed and J-STAGE databases for relevant articles published in English from January 2000 to May 2025. The review prioritized studies investigating brain structure and function using fMRI in individuals with BMS. Results: Our synthesis of the literature consistently demonstrated that the brains of individuals with BMS exhibit augmented connectivity within the medial pain system and a diminished gray matter volume in the medial prefrontal cortex (mPFC). These findings suggest a crucial role for altered brain circuitry, particularly a reduction in the output of the basal ganglia dopamine system, in the experience of BMS pain. Conclusions: The consistent fMRI findings strongly indicate that BMS involves significant functional and structural brain alterations. The observed changes in the mPFC and its connections to the basal ganglia dopamine system highlight this pathway as a potential target for both pharmacological and non-pharmacological neurological interventions for individuals with BMS. Full article

Depression and obesity are comorbid conditions linked through shared neuroinflammatory and immune mechanisms. This study examined the effects of chronic cannabidiol (CBD) treatment on behavior and neuroinflammatory gene expression in female rats exposed to a combined model of high-fat diet (HFD) and unpredictable chronic mild stress (UCMS). Rats were subjected to an acute HFD for 2 weeks, followed by 4 weeks of UCMS. CBD (10 mg/kg, i.p.) or vehicle was administered during the final 2 weeks of UCMS. Specifically, mRNA levels of nuclear factor kappa B1 (NF-κB1), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were measured in the ventromedial prefrontal cortex (vmPFC) and CA1. CBD’s effects varied depending on the type of stressor. It promoted coping behavior, increased locomotion, reduced freezing, and restored UCMS-induced depressive-like behavior in a splash test. In the vmPFC, CBD normalized the HFD- and UCMS-induced increase in il1β, and downregulated nfkb1 and tnfa expression. In the CA1, it normalized stress-induced downregulation in nfkb1 expression. These findings suggest that the efficacy of CBD in modulating both behavior and neuroinflammation is contingent upon the nature of the stress exposure, highlighting its potential as a targeted treatment for stress-related neuropsychiatric disorders in females. Full article

Methamphetamine (METH) misuse-induced affective and cognitive dysfunctions cause severe global health and economic burdens. However, the mechanisms underlying METH withdrawal-induced negative emotions and cognitive deficits, as well as the treatment strategies for them, remain elusive. Previous findings suggest that METH use triggers neuroinflammation and neuronal apoptosis, and protein kinase B (AKT), forkhead box protein 1 (FOXO1), and heme-oxygenase-1 (HO-1) are implicated in these processes. In the present study, we aimed to reveal the role and potential mechanisms of luteolin, a flavonoid phytochemical with anti-inflammatory and antioxidative properties, in METH withdrawal-induced negative emotions and cognitive deficits. We found that prolonged METH withdrawal led to an increase in neuronal activity and a decrease in the protein expression of phosphorylated AKT (p-AKT) and HO-1 in the prefrontal cortex (PFC) and caudate putamen (CPu). Luteolin pretreatment partially mitigated these METH withdrawal-induced negative emotions and cognitive deficits, and prevented the abnormal activation of PFC and CPu as well as the downregulation of AKT/HO-1 expression. Notably, we further observed that luteolin inhibited the METH-induced nuclear translocation of FOXO1. Our findings suggest that luteolin may alleviate METH withdrawal-induced affective and cognitive dysfunctions by reducing oxidative injury in the brain through the AKT/FOXO1/HO-1 pathway, highlighting its potential for treating drug addiction-related health issues. Full article

Prenatal cannabis exposure (PCE) has been associated with altered prefrontal cortex (PFC) activity and connectivity in adulthood, potentially increasing the risk of psychopathology later in life. This risk is thought to involve a complex interplay between the endocannabinoid and dopaminergic systems. We investigated the transcriptional regulation of genes associated with these systems in an animal model of PCE during adolescence, focusing on DNA methylation and specific microRNAs (miRNAs). Our study revealed increased mRNA levels of dopamine D1 and D2 receptors (Drd1 and Drd2) in the PFC, with a notable effect on Drd2 in male offspring. Notably, we observed a consistent reduction in Drd2 DNA methylation levels in PCE male rats. Both Drd1 and Drd2 expressions were regulated by selective miRNAs. Accordingly, we found changes in the excitability of PFC pyramidal neurons in male adolescent PCE offspring, along with alterations in the Netrin-1/DCC guidance cue system. Our findings highlight PCE-induced modifications of the PFC dopaminergic system while maintaining stable gene expression of the endocannabinoid system in male offspring. Changes in this complex interaction during sensitive developmental periods like adolescence might lead to sex-dependent divergent behavioral outcomes induced by PCE. Full article

Emotional attunement, or emotional co-regulation in a relationship, can manifest as interpersonal neural synchrony, where partners exhibit similar anti-phase or phase-shifted brain activity. In adult romantic relationships, emotional attunement may differ according to relationship satisfaction. No study has examined how relationship satisfaction difference influences interpersonal neural synchrony. This exploratory pilot study on 17 couples (unmarried Chinese undergraduate couples in a Southeast Asian university) investigated whether relationship satisfaction difference influenced interpersonal neural synchrony during a shared emotive experience. Each couple wore an fNIRS cap to measure brain activity in their prefrontal cortex (PFC) while co-viewing seven videos intended to evoke positive, negative or neutral emotions. We found preliminary evidence that relationship satisfaction difference modulated interpersonal neural synchrony in the right ventral PFC regions, including the right ventromedial PFC (involved in the encoding of emotional values to stimuli and emotional regulation), right ventrolateral PFC (involved in voluntary emotional regulation) and the right orbitofrontal cortex (involved in processing of emotional experiences and regulation of emotions). This suggested that couples with mismatched relationship satisfaction displayed greater interpersonal neural synchrony, possibly due to mutual social cognitive processes when viewing emotive videos together. Further studies can replicate the findings with larger, diverse samples. Full article

Background/Objectives: Despite the growing recognition of cognitive disengagement syndrome (CDS), previously termed sluggish cognitive tempo, as a distinct dimension of psychopathology, the neural correlates of CDS remain largely unknown. We investigated the neural correlates of CDS in children using whole-head magnetoencephalography (MEG). Methods: A community-based sample of children (N = 43, ages 8–12 years) was recruited and completed self-report ratings of CDS. MEG was recorded while the children completed an adapted version of the attention network test (ANT). Results: The results indicated that higher levels of self-reported CDS symptoms were associated with larger changes in the root-mean square (ΔRMS) (incongruent—congruent trials) in M2 and M3, suggesting children with higher levels of CDS symptoms might require greater mental effort to overcome distractors during incongruent trials. The source localization analysis initially revealed a negative correlation between child self-reported CDS symptoms and ΔM2 power (incongruent—congruent trials) in the medial prefrontal cortex (mPFC), suggesting insufficient power allocation in a region critical for attentional processing. However, this association was no longer significant after controlling for ADHD status. No significant correlation was found between self-reported CDS symptoms and alerting or orienting. Conclusions: These findings provide initial evidence of the disrupted attentional processing associated with CDS in children. Further replication and extension with larger samples are warranted. Full article

Background/Objectives: Norepinephrine (NE) plays a crucial role in modulating cognitive processes via α2A-adrenoceptors (α2A-ARs) within the prefrontal cortex (PFC), an essential brain region responsible for higher cognitive functions. The α2A-ARs are found on both postsynaptic and presynaptic membranes in the PFC. Previous studies have shown that presynaptic α2A-ARs, predominantly located at NE terminals, function as autoreceptors that inhibit NE release. However, the expression of α2A-ARs at non-NE terminals, such as glutamate and GABA, remains ambiguous. To clarify the expression patterns and potential roles of α2A-ARs at non-NE terminals, we investigated their presence at the axon terminals of excitatory glutamate neurons and inhibitory GABA neurons in the rat PFC using immunofluorescence double-labeling, whole-cell patch-clamp recordings, and pharmacological approaches. Methods: To clarify the expression patterns and potential roles of α2A-ARs at non-NE terminals, we investigated their presence at the axon terminals of glutamate neurons and GABA neurons in the rat PFC using immunofluorescence double-labeling, whole-cell patch-clamp recordings, and pharmacological approaches. Results: Our findings delineated the distribution of α2A-ARs at the axon terminals of both glutamate and GABA neurons, and the expression of α2A-AR in the pyramidal neurons within the rat PFC as well. Furthermore, we employed the selective α2A-AR agonist guanfacine to assess the functional role of presynaptic α2A-ARs at these non-NE terminals. Following the application of the PKA inhibitor PKI_5–24 to block postsynaptic α2A-AR function, guanfacine still significantly decreased the frequency (not the amplitude) of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in layer 5–6 pyramidal neurons. Notably, the frequency reduction induced by guanfacine persisted even after the depletion of presynaptic NE vesicles. Conclusions: These findings offer a comprehensive analysis of presynaptic α2A-AR expression and function in the PFC, revealing for the first time their role as heteroreceptors that modulate the release of glutamate and GABA. Our results provide morphological and electrophysiological insights into a potential mechanism through which α2A-AR stimulation enhances cognitive functions. Full article

Background: Cognitive control (CC) underpins our ability to maintain task focus, update goals, and flexibly shift between strategies, and it is closely tied to prefrontal cortex (PFC) activity. Electronic gaming (e-gaming), such as the first-person shooter (FPS) genre, is a specialized domain that demands refined CC skills developed over years of practice. Although previous research has demonstrated that PFC hemodynamic activity can effectively evaluate CC in several skilled domains, the impact of prolonged FPS experience on CC and its underlying neural correlates remains unclear. Objectives: In this study, we examined differences in both behavioral performance and PFC hemodynamic responses between 70 novices and 50 experienced FPS gamers (n=120). Methods: We targeted three core CC subdomains—updating, shifting, and inhibition—by employing the Digit–Symbol Substitution Task, Dual Visual Search Task, and Stroop Task, respectively. Functional near-infrared spectroscopy (fNIRS)-based PFC activity was recorded as participants engaged in each task. Results: Experienced gamers showed higher levels of prefrontal neural efficiency for updating and shifting, but minimal differences for inhibitory control. Conclusions: These findings inform neuroergonomic approaches to performance evaluation and may be generalized to other complex, real-world environments that rely on extensive training for skill acquisition. Full article

Previous studies have largely overlooked cellular differential alterations across differentially affected brain regions in both disease mechanisms and therapeutic development of Alzheimer’s disease (AD). This study aimed to compare the differential cellular and transcriptional changes in the prefrontal cortex (PFC) and entorhinal cortex (EC) of AD patients through an integrated single-cell transcriptomic analysis. We integrated three single-cell RNA sequencing (scRNA-seq) datasets comprising PFC and EC samples from AD patients and age-matched healthy controls. A total of 124,658 nuclei and 31 cell clusters were obtained and classified into eight major cell types, with EC exhibiting much more pronounced transcriptional alterations than PFC. Through network analysis, we pinpointed hub regulatory genes that form interconnected networks driving AD pathogenesis, findings validated by RT-qPCR showing more pronounced expression changes in EC versus PFC of AD mice. Moreover, dysregulation of the LINC01099-associated regulatory networks in the PFC and EC, showing correlation with AD progression, may present new therapeutic targets for AD. Together, these results suggest that effective AD biomarkers and therapeutic strategies may require simultaneous, precise targeting of specific cell populations across multiple brain regions. Full article

Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels in the dorsolateral prefrontal cortex (dlPFC) and their correlations with clinical outcomes. Methods: In this randomized, sham-controlled, cross-over study, 33 adults with MDD received one session of t-PBM at low, medium, and high doses and a sham treatment. Proton magnetic resonance spectroscopy (1H-MRS) measured NAA, Cho, and Cr pre- and post-treatment. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ). Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for neurometabolite changes, and linear mixed-effects regression models for t-PBM dose, neurometabolites, and time effects. Results: NAA levels increased significantly (7.52 ± 0.777 to 8.12 ± 1.05 mmol/L for one session; 7.36 ± 0.85 to 7.85 ± 0.68 mmol/L across all sessions); however, these changes were not associated with specific t-PBM doses or sham. No significant changes were observed for Cho and Cr levels. Positive correlations were found between Cho levels and MADRS scores (r = 0.59, p = 0.017), and negative correlations between Cr levels and SDQ scores at the medium dose (r = −0.91, p = 0.011). Conclusions: While NAA levels increased, and correlations between neurometabolites and clinical outcomes were observed, these findings do not suggest a specific effect of t-PBM. Larger randomized controlled trials with optimized dosing protocols, extended follow-up, and advanced spectroscopy are needed to clarify the neurometabolic therapeutic potential of t-PBM in MDD. Full article

The dorsomedial caudate–putamen (dmCPu), a key input structure of the basal ganglia, plays a crucial role in goal-directed behaviors and the transition to habits. The functional specialization of the dmCPu along its anteroposterior axis suggests that distinct prefrontal cortex (PFC) subregions may differentially contribute to these processes. However, the precise topographical organization of PFC and adjacent areas projections to the anterior and posterior dmCPu remains poorly understood. We employed retrograde tracing using Fluoro-Gold to map the projections from PFC subregions and adjacent areas to the anterior and posterior dmCPu in male Sprague Dawley rats. Histological verification and immunohistochemical labeling were conducted to confirm injection sites and neuronal labeling. Quantitative analyses were performed to assess the effects of injection site placement (anterior vs. posterior dmCPu), laterality (ipsilateral vs. contralateral), and cortical subregion on projection density. The posterior dmCPu received significantly higher projection densities than the anterior dmCPu, with a pronounced ipsilateral dominance across all cortical subregions. Among the subregions examined, the cingulate cortex exhibited the highest number of labeled neurons projecting to the dmCPu, with distinct patterns of connectivity between anterior and posterior injection sites. Notably, motor and somatosensory cortical projections were more prominent in the posterior dmCPu, whereas cingulate projections demonstrated robust anteroposterior and lateralized differences. These findings provide a comprehensive map of the topographical organization of cortical inputs to the dmCPu, highlighting differential connectivity patterns that may underlie distinct functional roles in goal-directed and habitual behaviors. This work advances our understanding of corticostriatal circuits and their relevance to adaptive behaviors and neuropsychiatric disorders. Full article

This study investigates how the sound of a hair dryer influences users’ perceptions of its quality, using functional near-infrared spectroscopy (fNIRS) to measure prefrontal cortex (PFC) activation. Eighteen participants were involved in a within-subject evaluation experiment where they assessed the perceived quality of hair dryers with three different sound levels: no sound, low sound, and high sound. The results show that hair dryers with high sound levels were rated as having higher quality and caused greater increases in oxygenated hemoglobin (HbO) concentration in the dorsolateral prefrontal cortex (DLPFC) compared to soundless hair dryers. In contrast, when participants evaluated low-sound hair dryers, differential activation between the left and right hemispheres was observed, with increased left-brain activity. These findings highlight the significant role of multisensory factors, such as sound, in shaping product perception. Moreover, DLPFC activity, especially in the left hemisphere, emerges as a potential marker for evaluating product quality, contributing new insights to the understanding of sensory-driven decision-making in product evaluation. Full article