Frontiers in Neuroscience最新文献

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.

Mitochondrial dysfunction is a central contributor to neurodegenerative disorders affecting both the central nervous system and the retina, where impaired energy metabolism, oxidative stress, and defective cellular resilience converge to drive progressive neuronal loss. Environmental enrichment (EE), a multimodal non-pharmacological paradigm, has emerged as a powerful modulator of brain and retinal plasticity in preclinical models, promoting adaptive responses that support mitochondrial function and neurotrophic signaling. This review synthesizes evidence indicating that EE influences mitochondrial quality control, redox homeostasis, synaptic resilience, and neuroimmune balance across a range of experimental models of neurodegeneration and retinal dystrophy. While these effects converge on shared downstream pathways, important disease-, cell-type-, and context-specific differences exist, and mechanistic generalization across systems requires caution. Human studies remain limited, heterogeneous, and often focused on functional outcomes rather than direct biological endpoints, resulting in modest and variable effect sizes. Rather than proposing EE as a stand-alone therapy, we frame it as a system-level, disease-modifying context that may enhance endogenous protective capacity and potentially complement pharmacological, genetic, or rehabilitative interventions, pending disease-specific validation. Forward-looking perspectives, including digitally mediated and AI-supported EE-inspired approaches, are discussed as conceptual strategies whose biological relevance will depend on future studies integrating functional outcomes with validated molecular and metabolic biomarkers. Together, the available evidence positions EE as a biologically grounded, non-invasive framework for promoting neuro- and retino-protective resilience, while underscoring the need for rigorously designed translational and clinical studies to define its therapeutic boundaries and mechanisms of action.

[This corrects the article DOI: 10.3389/fnins.2024.1237245.].

Introduction: Sleep-related hypermotor epilepsy (SHE) is a rare epileptic syndrome characterized by nocturnal seizures that predominantly arise during sleep, featuring complex motor behaviors. Pathogenic variants in the nitrogen permease regulator-like 3 (NPRL3) gene and other regulators of the mTOR pathway have been linked to diverse epilepsy phenotypes, including SHE. SHE is challenging to diagnose due to its diverse presentations, overlap with non-epileptic sleep disorders, and semiological similarities to functional/dissociative seizures (FDS).

Case report: We present the case of a 61-year-old woman with a lifelong history of nocturnal paroxysmal events and focal epilepsy. She experienced stereotyped nocturnal episodes of focal motor seizures with retained consciousness, characterized by hyperkinetic activity and asymmetric posturing. Despite multiple antiseizure medications (ASMs), only carbamazepine (CBZ) provided long-term seizure freedom. Genetic testing revealed a novel heterozygous mutation in the NPRL3 gene.

Discussion: This case highlights the diagnostic challenges of SHE and the importance of genetic testing in drug-resistant epilepsy. The identified NPRL3 mutation shows the genetic complexity of SHE and its implications for treatment.

Introduction: The rapid spread of misinformation during the COVID-19 pandemic has raised important questions about how individuals evaluate false information, particularly when it conflicts with strongly held prior attitudes. Understanding the neural mechanisms underlying the processing of vaccine-related misinformation may clarify why such beliefs persist despite corrective information.

Methods: Using functional magnetic resonance imaging (fMRI), we examined neural responses to COVID-19 vaccine misinformation and factual information in vaccine-receptive participants (N = 29). During scanning, participants were presented with a series of vaccine-related statements-both accurate and false-and indicated their level of agreement. Analyses focused on the influence of prior beliefs and attitude congruence on neural activation.

Results: Contrary to our hypotheses, exposure to attitude-incongruent misinformation did not elicit significant activation in emotional processing regions such as the amygdala or precuneus. However, when participants made attitude-incongruent responses-endorsing misinformation or rejecting accurate information-we observed increased activation in the left dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), intraparietal sulcus (IPS), and middle frontal gyrus (MFG), regions associated with decision-making, moral reasoning, memory integration, and cognitive control.

Discussion: These findings suggest that conflicts between incoming information and prior attitudes engage effortful, higher-order cognitive systems rather than affective processing. Resolving such conflicts appears to rely on decision-making and control mechanisms that manage uncertainty and cognitive dissonance. Due to recruitment limitations, the present study focused exclusively on vaccine-receptive individuals. Future research should investigate whether vaccine-resistant individuals exhibit similar or distinct neural patterns, which may provide further insight into the persistence of misinformation in the context of negative prior attitudes.