Frontiers in Neuroscience最新文献

Bainbridge-Ropers syndrome (BRPS, OMIM #615485) is a rare, heterogeneous autosomal dominant genetic disease that is mainly characterized by intellectual disability (ID) of varying degrees, developmental delay (DD), language impairments, failure to thrive, behavioral issues, hypotonia, feeding difficulties, and distinctive craniofacial features. It is caused by heterozygous pathogenic variants in the additional sex combs-like 3 (ASXL3, OMIM #615115) gene. In this study, four Chinese patients were diagnosed with BRPS caused by ASXL3 variants through whole exome sequencing. We detected two novel and two previously reported variants of the ASXL3 gene (NM_030632.3) in these 4 unrelated Chinese patients: two novel variants, namely, c.1276del (p.Val426^*) and c.3750del (p.Glu1251Asnfs^*5), and two recurrent variants, namely, c.4330C>T (p.Arg1444^*) and c.4336_4337delAG (p.Arg1446fs^*2). All four patients had a clinical profile similar to that associated with BRPS. Compared with previously reported cases of BRPS, these patients exhibited novel complications, including long eyelashes, congenital laryngeal cartilage hypoplasia and dextrocardia. These findings broaden our understanding of the mutational and clinical spectrum of BRPS, emphasizing the importance of long-term monitoring and vigilance regarding potential complications, such as cardiac abnormalities, in BRPS patients.

Background: Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders (NDDs) in offspring. While MIA-induced changes in the gut bacterial communities of offspring and their metabolites have been linked to behavioral abnormalities, the effects of MIA on the gut fungal communities and their mycotoxin-associated metabolites in offspring remain poorly characterized.

Methods: In this study, MIA was modeled in pregnant rats through intraperitoneal injection of 5 mg/kg Poly I:C on gestational day 15. The model's efficacy was validated using behavioral assessments, including the open-field test, elevated plus maze, and Morris water maze. Internal transcribed spacer (ITS) sequencing and untargeted metabolomics analysis were employed to detect the alterations of gut fungal microbiota and mycotoxin levels.

Results: Poly I:C-exposed offspring exhibited increased anxiety and cognitive deficits. Meanwhile, Poly I:C induces sex-related differences in gut fungal communities and mycotoxin levels in juvenile offspring rats. Several fungal genera and mycotoxins were significantly correlated with variations in anxiety-like behaviors and spatial learning performance.

Discussion: Our findings suggest that MIA-induced behavioral deficits in offspring are accompanied by sex-specific disruptions in gut fungal composition and mycotoxin metabolism, which highlights the need for further intervention studies to establish causality and elucidate the underlying mechanisms of gut fungi and mycotoxins in NDDs.

Background: Preclinical and clinical studies suggest that the multimodal antidepressant vortioxetine may offer a valuable therapeutic option in the treatment of depression associated with neurological disorders, including Parkinson's disease (PD).

Objectives: To compare the effect of vortioxetine and the SSRI sertraline in the treatment of PD and comorbid depression, placing emphasis on peripheral inflammation markers.

Methods: This is an observational longitudinal study. We have recruited 33 patients affected by PD with comorbid depression, evaluated for motor and non-motor symptoms, depression, and peripheral and soluble markers of inflammation at baseline and at the end of antidepressant treatment. Patients were divided into two groups treated with either vortioxetine (10-20 mg/day) or sertraline (50 mg/day) for 4 months. A group of 12 healthy controls was also used for comparative purposes.

Results: At baseline PD patients showed a higher number of "classical" monocytes and a lower number of "non-classical" monocytes and myeloid dendritic cells (mDCs). The number and activity of DCs generated from isolated monocytes were also lower in PD patients. While both sertraline and vortioxetine treatment further reduced the number of mDCs, only vortioxetine had a restorative effect on CD40- and CD54-expressing DCs and their function. Both drugs display an antidepressant activity, but vortioxetine was superior to sertraline in improving cognitive function, anxiety, anhedonia, and apathy.

Conclusion: These data evaluate for the first time the immunomodulatory effects of two different treatments in PD patients with comorbid depression, highlighting the greater immunomodulatory capacity of vortioxetine.

Background: Insomnia significantly impairs well-being, cognitive function, and social functioning, yet subjective psychological assessments often yield equivocal results regarding the extent of this impairment. Neural function may underlie this discrepancy and offer a more precise foundation for guiding treatment. This study therefore employed non-invasive transcranial magnetic stimulation (TMS) and functional near-infrared spectroscopy (fNIRS) to investigate cortical excitability and brain activity patterns in patients with short-term insomnia disorder (SID) and chronic insomnia disorder (CID), aiming to identify associated neural function changes.

Methods: We recruited 30 patients with SID and 30 with CID. For all participants, cortical excitability was assessed by measuring the resting motor threshold (RMT) via single-pulse TMS. fNIRS was utilized to measure the concentrations of oxy-hemoglobin (Oxy-Hb) and functional connectivity in the cerebral cortex during a verbal fluency task (VFT).

Results: Our study revealed that patients with SID had significantly lower RMT and higher cortical activation in the hemodynamic responses of Oxy-Hb in the bilateral dorsolateral prefrontal cortex (DLPFC), the left medial prefrontal cortex (mPFC), and the right temporal lobe (TL) than CID patients during the 60 s task period. The CID group showed significantly lower average inter-channel connectivity strength compared to the SID group. Moreover, the CID group exhibited significantly lower connectivity from the right DLPFC to the left DLPFC and the left mPFC compared to the SID group. For the SID patient group, we found that the RMT was negatively correlated with mean Oxy-Hb changes in the left mPFC. Conversely, functional connectivity between the left DLPFC and TL showed a positive correlation with RMT. Furthermore, diminished connectivity between the left TL and mPFC was associated with elevated cortical excitability.

Conclusion: Patients with CID demonstrated lower cortical excitability, decreased brain activity, and reduced task-related functional connectivity relative to the SID group. This finding indicates distinct neurological profiles between short-term and chronic insomnia, a distinction that will be critical for tailoring effective neuromodulatory interventions.

Background: Migraine is a prevalent neurological disorder that is frequently observed in clinical practice and is commonly comorbid with insomnia. Insomnia can exacerbate and precipitate migraine attacks, with both conditions exerting a reciprocal influence on one another. The cerebellar crus is significantly associated with the pathophysiology of migraine and insomnia. The relationship between cerebellar crus functional alterations and migraine-associated insomnia remains unclear. This study utilizes resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional alterations in the cerebellar crus of patients with migraine and concurrent insomnia.

Methods: Participants underwent resting-state functional magnetic resonance imaging. Subsequently, the disparity in amplitude of low-frequency fluctuations (ALFF) values among groups was analyzed, followed by functional connectivity (FC) investigations employing the cerebellum crus as seed regions.

Results: Migraine patients frequently experience neuropsychological disorders and insomnia, which are interconnected. Both migraine with insomnia (MwI) and migraine without insomnia (MwoI) groups demonstrated elevated amplitude of low-frequency fluctuations (ALFF) in the left Crus I and II compared to the healthy controls (HC) group, with the MwI group exhibiting more pronounced alterations. Additionally, both patient groups showed decreased FC between the left Crus I and the right middle temporal gyrus (MTG) and inferior temporal gyrus (ITG) relative to the HC group. The MwoI group showed significantly lower FC compared to both the HC and MwI groups. A significant negative correlation was observed between ALFF in the left Crus I/II and Pittsburgh Sleep Quality Index (PSQI) scores in the MwoI group. Conversely, in the combined migraine cohort, FC between the left Crus I and the right MTG/ITG showed a positive correlation with PSQI scores.

Conclusion: This study identified a correlation between aberrant functional activity in the left Crus I/II and migraine comorbidity with insomnia. These findings provide fresh perspectives on the neural mechanisms underlying the migraine-insomnia relationship, thereby facilitating the identification of potential neuroimaging biomarkers and the exploration of targeted interventions for this patient subgroup.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability (ID). However, its diagnostic rate needs to be improved by screening for specific populations. Here, we determined the genetic cause of three ID patients in the affected pedigree and derived diagnostic insights for FXS. Enrolled at Henan Provincial People's Hospital in April 2025, the family underwent multiple diagnostic tests. Whole-exome sequencing failed to detect causative variants-consistent with its inability to identify dynamic trinucleotide repeat expansions. Expanded pedigree analysis showed the inheritance did not fit typical autosomal dominant/recessive or X-linked models. This raised suspicion of FXS. Trinucleotide repeat primed PCR with capillary electrophoresis (TP-PCR/CE) confirmed proband III-1 as an FXS full-mutation individual, and comprehensive FXS analysis (CAFXS) validated this result while identifying counselee III-2 as a female pre-mutation carrier. All three ID cases harbored FMR1 full-mutation, with ID severity correlating with CGG repeat length. Notably, the maternal pre-mutation carrier (152 CGG repeats) had offspring with variable repeat dynamics: full-mutation (427 repeats) and reduced pre-mutation (71 repeats in III-2). These findings confirm FXS as the ID etiology and emphasize the clinical necessity of FXS-targeted screening in ID families with atypical inheritance patterns.

Background: Anorexia nervosa (AN) is a severe psychiatric disorder frequently marked by poor treatment response and chronic progression toward rigid, restrictive behaviors. These features highlight the need for innovative strategies targeting core mechanisms and symptoms of the disorder. This feasibility trial evaluates individualized intermittent theta-burst stimulation (iTBS) of the posterior parietal cortex (PPC) as an adjunct to treatment-as-usual, with the goal of identifying patient-specific targets and paving the way for personalized neuromodulation in AN.

Methods: Thirty-four adults with AN (≥18 years, illness ≥12 months, ≥1 prior unsuccessful treatment) will be randomized (1:1) to 20 sessions of real or sham iTBS over 4 weeks. Stimulation will be delivered with a MagPro system and a Cool B70 A/P active/sham coil; motor threshold will be estimated with the Stochastic Approximator (SAMT) and re-checked weekly. Individualized stimulation target will be defined based on resting state functional magnetic resonance imaging data to identify the cortical region within the PPC that is maximally functionally connected with the activity of two meta-analytically derived networks representing body representation and implicit behavioral tendencies. Coil placement will be neuronavigated on individual T1 magnetic resonance imaging (MRI). Assessments will take place at baseline (T0), post-treatment (T1), and 4-month follow-up (T2), covering clinical status (body mass index (BMI), psychopathology, and quality of life), experimental tasks (implicit body representation, peripersonal space, approach-avoidance tendencies toward food, interoceptive accuracy, and neurocognitive functioning), and MRI. Feasibility endpoints include recruitment, retention, completion, blinding, and tolerability. Ethics approval: 6168/EST/25; registration: NCT07106645.

Discussion: This trial emphasizes individualized PPC targeting and rigorous motor threshold (MT) estimation to advance personalized neuromodulation in AN. Feasibility and effect-size data will guide a confirmatory randomized clinical trial, while mechanistic analyses will test whether targeted iTBS strengthens body-schema circuits and aligns neural changes with clinical improvement, supporting a precision-psychiatry approach to eating disorders.

Trail registration: https://clinicaltrials.gov/study/NCT07106645, identifier NCT07106645.

The comparison of autism spectrum disorder (ASD) and Alzheimer's disease (AD) through shared pathophysiologic features offers intriguing insights into the similarities between the two disease states. The authors suggest diminished cerebrospinal fluid (CSF) drainage through the lymphatic system, perivascular system, and nasal turbinates may occur in ASD and AD, and be an important contributing factor in the occurrence of both disorders. Obstruction of the CSF's normal nasal lymphatic drainage results in abnormal processing of the waste proteins tau and amyloid in the brain in both of these disease states. Reproducible research has shown that ASD and AD patients, when compared to normal controls, exhibit increased extra-axial CSF, enlarged perivascular spaces, magnetic resonance imaging evidence of glymphatic dysfunction, and olfactory dysfunction. Some comparisons between the two disease states are robust while others remain speculative. However, the recognition of overlapping pathophysiologic and genetic features between the two disease states not only furthers understanding of these complex conditions, but could also pave the way for novel therapeutic avenues. The goal of this article is to demonstrate the empirically known similarities between ASD and AD and to stimulate research investigating CSF lymphatic drainage through the nasal turbinates. The authors suggest various ways to confirm their findings and provide suggestions for new therapeutic approaches for these disease states aimed at increasing the movement of CSF originating in the brain through the glymphatic system to meningeal and nasal turbinate lymphatics.

The role of the maternal microbiome in offspring neurodevelopment has become a prominent topic in neuroscience, yet its true causal status is under intense scrutiny. This critical review moves beyond conventional deconstructions of popular hypotheses in the field (e.g., "prenatal programming" "windows of opportunity") to challenge a more fundamental premise. We systematically argue that the currently observed associations along the "microbiota-gut-brain axis" may reflect complex confounding, with macroscopic social factors such as socioeconomic status (SES) being the true underlying drivers. The core thesis of this paper is that the maternal microbiome is, to a great extent, a "biological imprint" of the mother's living environment, diet, and stress levels-a highly sensitive "proxy" indicator acting as a biological mediator heavily shaped by the environment, rather than solely as an independent driver. By integrating evidence from social epidemiology, we contend that positioning the microbiome alongside factors like SES in a "flattened" network model is misleading. Instead, we propose a Hierarchical Causal Model where socioeconomic factors act as top-level "master regulators," systematically shaping all downstream biological processes, including the microbiome. Through a critical analysis of interventions such as Fecal Microbiota Transplantation (FMT) and vaginal seeding, this review further exposes the translational predicaments that arise from neglecting this hierarchical structure. Ultimately, this review advocates for a paradigm shift: from searching for a single "microbial panacea" to understanding the microbiome's true position within the socio-biological system, and proposes a conceptual framework for future research that is more aligned with real-world complexity and endowed with greater sociological imagination.

Laughter is a widespread social behavior that has been associated with increases in social connection. However, the mechanisms behind this link are not yet well understood. We hypothesized that laughter supports positive social outcomes by enhancing neural synchrony during social interactions. Neural synchrony is a process of mutual alignment of brain areas, which has been shown to positively affect social interactions. In a 2 × 2 design, participant pairs watched either funny or neutral videos (Laughter Manipulation: yes/no), either together or separately (Social Context: yes/no). Afterwards, they engaged in a 10-minute free interaction. Laughter behavior was annotated during both phases. Neural synchrony was measured using fNIRS hyperscanning for both phases and quantified across frontal and temporal regions using Wavelet Transform Coherence. As social outcomes, we measured Liking, Prosociality, and Bonding after the free conversation. We tested our hypotheses with Bayesian models that assessed the effects of Laughter and Social context on social outcomes, with synchrony modeled as a mediator. Parameter estimates for the effects of Laughter and Social Context on interpersonal neural synchrony were close to zero, with Bayes Factors indicating evidence for the null hypothesis. Similarly, the effects of Laughter and Social Context on Liking, Prosociality, and Bonding showed no effects. However, model comparisons provided evidence for annotated Laughter Behavior as a predictor of Liking, Prosociality, and Bonding. Mediation analyses revealed no overall effect, but some findings stood out. We observed a negative association between right IFG and right TPJ synchrony during the manipulation phase and later Liking, and a positive association between right and left IFG synchrony and subsequent Prosociality. Additionally, synchrony during the free interaction phase between the left IFG and right TPJ predicted Liking and synchrony between the left and right TPJ predicted Bonding. In total, our findings show no direct link between Laughter and neural synchrony. However, Laughter Behavior was associated with social outcomes. Additionally, neural synchrony was also linked to social outcomes, with distinct positive and negative associations depending on the brain regions involved. These results highlight the complexity of the relationship between laughter, neural synchrony, and social connection, suggesting the need for further research.