Navarro L, Mallah NEZ, Nowak W
… +5 more, Pardo-Seco J, Gómez-Carballa A, Pischedda S, Martinón-Torres F, Salas A
Front Integr Neurosci
· 2025 · PMID 41230119
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INTRODUCTION: Several disciplines have explored the relationship between autism spectrum disorder (ASD) and music, though most insights derive from cognitive sciences. This systematic review and meta-analysis synthesize...INTRODUCTION: Several disciplines have explored the relationship between autism spectrum disorder (ASD) and music, though most insights derive from cognitive sciences. This systematic review and meta-analysis synthesize evidence on the therapeutic effects of music-based interventions (MI) on communication, behavior, social engagement, attention, and quality of life in autistic individuals. It also examines how participants perceive and process music, situating therapeutic findings within this perceptual framework. METHODS: From a total of 346 publications screened in PubMed, Cochrane Library, and WILEY Online Library databases, 120 were included, of which 15 met the criteria for quantitative evaluation and meta-analysis, to assess the state- of-the-art of research on music and autism in the fields of neuropsychology and cognitive sciences. The reviewed studies span a range of methodologies, including randomized controlled trials and qualitative research, and incorporate diverse MI strategies, such as active music-making, structured listening, and improvisational techniques. RESULTS: Despite methodological heterogeneity, the findings suggest a moderate overall beneficial effect of MI, particularly in enhancing social interaction (z = 1.89, -value = 0.06), verbal communication-especially vowel articulation (z = 2.93, -value = 0.01), behavior (z = 1.92, -value = 0.06; after outlier removal), and quality of life (z = 1.67, -value = 0.09). DISCUSSION: This study highlights music's potential as a non-invasive, engaging therapeutic medium that elicits emotional, cognitive, and social responses in individuals on the spectrum. Given evidence of context-sensitive and domain-specific strengths in musical abilities, music emerges as a promising therapeutic approach. Future studies should investigate individual variability in response to MI, aim to standardize outcome measures, and assess long-term effects. Such efforts will support more personalized, neurodiversity-affirming therapeutic models in autism care.
Front Integr Neurosci
· 2025 · PMID 41180981
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Context-sensitive behaviors are crucial for the adaptive success of many organisms. Investigating neural processes that facilitate context-sensitive behavior requires knowledge of the molecular signaling and anatomical b...Context-sensitive behaviors are crucial for the adaptive success of many organisms. Investigating neural processes that facilitate context-sensitive behavior requires knowledge of the molecular signaling and anatomical brain connectivity within and between relevant brain networks. Here, we outline the roles of oxytocin and dopamine signaling systems in context-sensitive singing in songbirds. Additionally, using the recently compiled songbird connectome, we review anatomical connectivity between vocal-motor and social brain networks that may facilitate context-sensitive singing. We present a model for context-sensitive adaptability of singing behavior in songbirds. We propose that the medial preoptic nucleus of the hypothalamus may serve as the output nucleus of the social behavior network, influencing oxytocin-mediated dopamine delivery to the vocal control network, in a context-sensitive manner. As many components of this model are conserved across species, we speculate that this proposed model can be generalized to facilitate context-sensitive motor behaviors across vertebrate species. Overall, we emphasize the importance of investigating each component of our proposed model, within a single species. This perspective aims to uncover how integrated neural mechanisms give rise to behavior.
Front Integr Neurosci
· 2025 · PMID 41133258
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OBJECTIVE: This study utilized resting-state functional magnetic resonance imaging (rs-fMRI) to investigate changes in the spontaneous activity of the default mode network (DMN) in patients with primary dysmenorrhea (PD)...OBJECTIVE: This study utilized resting-state functional magnetic resonance imaging (rs-fMRI) to investigate changes in the spontaneous activity of the default mode network (DMN) in patients with primary dysmenorrhea (PD) through amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses, aiming to explore their relationship with emotional regulation. METHODS: A total of 14 PD patients (the PD group) and 24 healthy controls matched by age, education, and gender (the HC group) underwent rs-fMRI scans. First, changes in ALFF were calculated for the PD group in comparison to the HC group, and brain regions with ALFF differences were used as regions of interest (ROIs). Subsequently, rs-fMRI was employed to detect differences in FC intensity between the two groups. Nine PD patients completed neuropsychological scale assessments, and correlations between their ALFF and FC values were analyzed. RESULTS: Compared to the HC group, the PD group exhibited decreased ALFF in the middle temporal gyrus, temporal pole, and superior temporal gyrus on the left side. Using the temporal pole as the ROI, the PD group also showed decreased connectivity between the temporal pole and the superior frontal gyrus (SFG), dorsolateral supplementary motor area (SMA), and precentral gyrus on the right side. A trend suggesting a positive correlation between ALFF values and anxiety was observed. CONCLUSION: PD patients exhibited multidimensional functional changes in the brain. ALFF and FC may serve as sensitive biomarkers for distinguishing PD patients from healthy individuals.
Front Integr Neurosci
· 2025 · PMID 40771880
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BACKGROUND: Anti-metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare autoimmune disease affecting cerebellar Purkinje cells. Only thirty-nine cases have been reported globally, with inconsistent documentati...BACKGROUND: Anti-metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare autoimmune disease affecting cerebellar Purkinje cells. Only thirty-nine cases have been reported globally, with inconsistent documentation of treatments and outcomes. A systematic review is needed to identify prognostic factors and expand clinical understanding and treatment options. METHODS: Observational follow-up data of anti-mGluR1 encephalitis cases were collected. All anti-mGluR1 encephalitis cases published in the PubMed and Google Scholar databases in English before November 1, 2024 were included. Clinical information and possible predictive factors from both current and previously reported cases were statistically analyzed. RESULTS: We present a case of anti-mGluR1 encephalitis successfully treated with ofatumumab. During the patient's initial episode, she partially recovered after first-line treatment. She experienced a relapse 6 months later and was treated with ofatumumab, resulting in complete recovery. Forty cases of anti-mGluR1 encephalitis, including our case, were summarized. The prevalence was similar between men and women, with 50% of patients aged 40-59 years. The most common clinical manifestations were ataxia and dysarthria. Cerebrospinal fluid analysis showed normal white blood cell count and IgG index in 37.1% of patients. Almost half of the patients (48.6%) exhibited cerebellar atrophy on cerebral MRI scans at initial presentation or during follow-up. Only 25% of patients recovered completely. According to the modified Rankin Scale (mRS) scores at the last follow-up, patients with poor outcome ( = 13, 32.5%) had a lower proportion of first-line immunotherapy (62%, = 0.017) and a longer follow-up time (median 36 months, = 0.038). CONCLUSION: The peak incidence of anti-mGluR1 encephalitis occurs between ages of 40-59 years. More than one-third of patients have normal cell counts and IgG index in the cerebrospinal fluid. Therefore, patients suspected of having this encephalitis should be tested for the presence of anti-mGluR1 antibodies in serum and cerebrospinal fluid. Notably, the first-line immunotherapy may be a critical factor influencing clinical outcomes.
Front Integr Neurosci
· 2025 · PMID 40761541
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BACKGROUND: Central vertigo and peripheral vertigo are common clinical conditions with different underlying pathophysiologies. The identification of reliable biomarkers for differential diagnosis remains a challenge. OBJ...BACKGROUND: Central vertigo and peripheral vertigo are common clinical conditions with different underlying pathophysiologies. The identification of reliable biomarkers for differential diagnosis remains a challenge. OBJECTIVES: This study aimed to explore the differential expression of CCL4L2 in the serum of patients with central and peripheral vertigo and assess its diagnostic potential. METHODS: A total of 180 patients (90 central vertigo, 90 peripheral vertigo) were enrolled. RNA sequencing was on serum samples to identify differentially expressed genes (DEGs). Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed relevant biological pathways. The expression of CCL4L2 was measured using RT-qPCR, and its diagnostic performance was evaluated by Receiver operating characteristic (ROC) curve analysis. The correlation between CCL4L2 expression and biomarkers NSE and S100β was also assessed. RESULTS: RNA sequencing revealed significant differences in gene expression between central vertigo and peripheral vertigo groups. The KEGG pathway analysis identified several enriched pathways, including NF-κB signaling, where CCL4L2 was a key gene. CCL4L2 expression was significantly higher in the CV group compared to the PV group ( < 0.001). ROC analysis demonstrated high diagnostic accuracy for CCL4L2 in distinguishing CV from PV (AUC = 0.909, < 0.001). Additionally, moderate positive correlations were observed between CCL4L2 and NSE (r = 0.475, < 0.001), and a weaker correlation with S100β (r = 0.364, < 0.001). CONCLUSION: CCL4L2 may serve as a potential biomarker for differentiating central from peripheral vertigo. Its expression is closely associated with inflammatory pathways, making it a promising target for further investigation in vertigo diagnostics.
Front Integr Neurosci
· 2025 · PMID 40672965
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Reward processing, which ensures survival, has evolved to also shape emotions, learning, and overall well-being. While traditional models of reward have focused predominantly on central neural circuits, emerging evidence...Reward processing, which ensures survival, has evolved to also shape emotions, learning, and overall well-being. While traditional models of reward have focused predominantly on central neural circuits, emerging evidence underscores the role of peripheral bodily signals. This represents a new opportunity by which we may understand neurological and neuropsychiatric health. In this review, we explore the gut-brain and heart-brain interfaces in reward processing, delineating their contributions across distinct phases of reward and offering insights into their bioenergetic significance. By framing this interplay within an adaptive and clinical context, we propose new avenues for understanding and treating neuropsychiatric disorders through a mind-body medicine lens.
Front Integr Neurosci
· 2025 · PMID 40552096
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There is increasing interest in the utility of electrophysiological measures such as resting EEG and evoked potential (EPs) to serve as biomarkers to facilitate therapeutic development for rare genetic neurodevelopmental...There is increasing interest in the utility of electrophysiological measures such as resting EEG and evoked potential (EPs) to serve as biomarkers to facilitate therapeutic development for rare genetic neurodevelopmental disorders (NDDs). Research on this topic thus far has been encouraging, but has also revealed the necessity for unique methods when acquiring EEG and EPs in children with genetic NDDs. Details of these methods are typically beyond the scope of research publications, yet are crucial to the quality and ultimately, usability of the data. In the current manuscript, we detail the methods that we have developed for acquiring EEG and EPs as part of multi-site studies with participants with Rett syndrome, CDKL5 deficiency disorder, MECP2 duplication syndrome, and FOXG1 syndrome. By making our methods accessible, we hope to support other groups interested in acquiring EEG and/or EPs as part of clinical trials or research studies with individuals with genetic NDDs, including groups without prior experience with EEG/EP acquisition. The paper is presented as step-by-step procedures followed by a discussion of issues that may arise during acquisition and ways to troubleshoot these issues. We then discuss considerations for choosing EEG equipment and study paradigms and briefly, considerations for data analysis.
Chen Y, Young L, Kim M
… +9 more, Watson S, Kaufman V, Beal B, Tuomi I, Wang B, McDonald-McGinn DM, Edgar JC, Kuschner ES, Roberts TPL
Front Integr Neurosci
· 2025 · PMID 40486008
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INTRODUCTION: We have shown that a delayed auditory cortex neural response is associated with language ability in school-age children with autism spectrum disorder and related syndromes, with this delay exacerbated in th...INTRODUCTION: We have shown that a delayed auditory cortex neural response is associated with language ability in school-age children with autism spectrum disorder and related syndromes, with this delay exacerbated in the context of co-occurring intellectual disability (ID). As a clinical diagnosis of ID is generally not made until school age, identification of neural measures that precede a behaviorally assessed ID diagnosis would help identify young children likely to benefit from early treatment. The present study evaluated if the speed of auditory cortex neural activity (M50 latency) would predict language ability in 3-year-old children who have an existing diagnosis that is a risk factor associated with a range of later functional outcomes, including ID or developmental delay (DD), irrespective of autism spectrum disorder diagnosis. METHODS: Thirty 3-year-old children with elevated likelihood for ID or DD (ID/DD-EL) were enrolled. Evaluable magnetoencephalography (MEG) data as well as language and cognitive ability measures were obtained from 23 participants. RESULTS: A longer time to encode auditory stimuli (i.e., a delayed M50 cortical evoked response) in the left hemisphere predicted lower language ability. Left M50 latency was not associated with cognitive ability. Right hemisphere M50 latency was not associated with language or cognitive ability. DISCUSSION: Present observations demonstrate that non-invasive brain imaging in conjunction with a passive auditory task (with early primary/secondary auditory cortex neural responses) can identify paths for variable language outcome in preschool children with ID/DD-EL. This lays the foundation for further investigation of these neural mechanisms as early indications for treatment as well as early signals of response to treatment.
Kim H, Kang D, Jang YH
… +4 more, Ahn JH, Won S, Lee HJ, Kim JI
Front Integr Neurosci
· 2025 · PMID 40469474
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INTRODUCTION: Symptoms of attention-deficit/hyperactivity disorder (ADHD) are closely associated with impaired executive function. Medication is the first-line treatment for ADHD, yet its effects on brain function and st...INTRODUCTION: Symptoms of attention-deficit/hyperactivity disorder (ADHD) are closely associated with impaired executive function. Medication is the first-line treatment for ADHD, yet its effects on brain function and structure remain unclear. To investigate medication-related brain alterations in children with ADHD, we used functional near-infrared spectroscopy, which captures cortical hemodynamic activity, and structural magnetic resonance imaging, which measures subcortical volume. METHODS: We investigated the differences in brain hemodynamic activity between 23 children with ADHD taking medication and 22 children who were not taking medication. RESULTS: Compared with the medicated ADHD group, the unmedicated ADHD group showed significantly reduced activation in the left rostrolateral prefrontal cortex (channel 9, = 0.01; channel 13, = 0.02) and dorsolateral prefrontal cortex (channel 14, = 0.01). The unmedicated group also exhibited a negative correlation between oxygenated hemoglobin and symptom severity, whereas the medicated group showed a positive correlation. Furthermore, abnormal asymmetry of the thalamic volume was reduced in the medicated group compared to the unmedicated group. DISCUSSION: These findings suggest that increased prefrontal activation and reduced thalamic asymmetry may reflect medication-related improvements in inhibitory control in children with ADHD.
Front Integr Neurosci
· 2025 · PMID 40416080
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Statistical learning (SL) is a fundamental cognitive ability enabling individuals to detect and exploit regularities in environmental input. It plays a crucial role in language acquisition, perceptual processing, and soc...Statistical learning (SL) is a fundamental cognitive ability enabling individuals to detect and exploit regularities in environmental input. It plays a crucial role in language acquisition, perceptual processing, and social learning, supporting development from infancy through adulthood. In this review, we adopt a multidimensional perspective to synthesize empirical and theoretical findings on SL, covering experimental paradigms, developmental trajectories, and neural mechanisms. Furthermore, we extend the discussion to the emerging intersection between SL and affective processes. Although emotional factors have recently been proposed to modulate SL performance, this area remains underexplored. We highlight current insights and theoretical frameworks addressing the SL-emotion interaction, such as predictive coding theory, and propose directions for future research. This review provides a comprehensive yet focused overview of SL across cognitive and affective domains, aiming to clarify the scope and future potential of this growing field.
Front Integr Neurosci
· 2025 · PMID 40297515
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While the autism diagnosis emphasizes "deficits" in social communication, the article advances that sensory-movement differences underpin autism through a review of the following sources of evidence. This account critica...While the autism diagnosis emphasizes "deficits" in social communication, the article advances that sensory-movement differences underpin autism through a review of the following sources of evidence. This account critically challenges "autistic regression", with evidence that sensory-movement features appear by birth as the earliest signs of autism and underlie the behavioral differences used for diagnosis, which may reflect adaptations to inherent differences and misunderstandings from others. Sensory and motor differences are salient to autistic people, but they often go underrecognized by others. They cause cascading effects in infancy on behavior and communication through differences in sensorimotor learning, automatic imitation, eye contact, sensory perception, and interests. The article then explains how sensory processing differences may influence reduced perceptual narrowing, which involves a bottom-up information processing style grounded in the surrounding environment. Furthermore, this bottom-up processing may grow from reduced sensory integration in feedback loops potentially involving the cerebellum of the brain. The article then moves into implications for the widespread consequences of these inherent differences on quality of life. The article closes with implications for autism as a construct (including underestimated empathy and pain), testing the theory, providing sensory-sensitive support and acceptance of autistic people, and applications to diverse autistic people. The theory may apply particularly well to autistic women and girls, autistic people with speech divergence, autistic people with ADHD, and autistic people with co-occurring sensory and motor-related neurodivergences. Throughout the article, the theory also provides clinical, neurological, and experiential evidence for sensory and motor differences as lifelong, challenging the notion of "losing" (an) autism (diagnosis) as instead reflecting (risky and not necessarily "successful") camouflaging.
Baniel A, Almagor E, Sharp N
… +2 more, Kolumbus O, Herbert MR
Front Integr Neurosci
· 2024 · PMID 40290839
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This article presents the theoretical foundation of two well established movement-based methods that represent a fundamental departure from most current interventions and are applied globally with children and adults exp...This article presents the theoretical foundation of two well established movement-based methods that represent a fundamental departure from most current interventions and are applied globally with children and adults experiencing diverse motoric, cognitive, and social challenges as well as with high functioning individuals: the Feldenkrais method and Anat Baniel Method NeuroMovement. These methods are based on leveraging neuroplasticity through the utilization of movement, not as "exercise" or externally imposed motor sequences, but as a means for effective, with the recipient and their brain. Through , we follow their , creating a dance-like dyadic process of self-discovery that mimics the spontaneous, organic way typically developing children play, learn, and grow. Practitioners in these methods, by joining and creating mutual connection with the recipient, help turn the subjective experience of the recipient into a reliable means of attaining spontaneous, mutually generated emergent learning in the recipient. In this process the autonomy of the recipient is respected and enhanced. Our work will be described through direct applications to autism seen as a neuro-motor-sensing disorder where those challenges can be transcended through the dyadic dance embodied in our techniques. Since 87% of children with autism spectrum disorder have significant movement challenges, we propose that movement, as a means for effective two-way communication with the child and their brain, needs to play a central role in autism intervention. In this article we outline how our interventions take place through case studies, vignettes and discussion, separately for each of the two methods. This article will also include recommendations for conducting investigations that characterize some of the basic components of these two methods, utilizing experimental designs and recently developed technologies and biometrics that generate unique individual profiles of both the receiver and the provider of the intervention, and of the interbrain synchrony, correlate them with changes in movement organization, cognitive functioning and coherence, and track changes in the signal-to-noise ratio. These methods should enable refinement and scalability of tracking and assessing the mechanisms and effectiveness of the interventions.
Front Integr Neurosci
· 2025 · PMID 40271199
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INTRODUCTION: Sex difference in latency for cervical vestibular-evoked myogenic potential (VEMP) has been reported in Brown Norway rats. Human investigations of sex difference in VEMP latency have shown inconsistent resu...INTRODUCTION: Sex difference in latency for cervical vestibular-evoked myogenic potential (VEMP) has been reported in Brown Norway rats. Human investigations of sex difference in VEMP latency have shown inconsistent results, although there are indicators of sexual dimorphism in vestibular function and a higher reporting rate for vestibular disorder in women than in men. METHODS: Sex effects in human VEMP were re-evaluated here using a procedure adapting clinical protocols for higher sensitivity. VEMP was compared between 24 women and 24 men using a novel procedure that (1) controlled neck tension with biofeedback and a padded head bar; (2) used body-conducted stimuli to eliminate sound exposure concerns and collect appreciably more data than is feasible with air-conducted stimuli; which in turn (3) increased statistical power because there were sufficient data for a linear mixed effects regression modelling analysis. RESULTS: Women had significantly shorter VEMP peak to trough latency than men. The sex difference of 2.4 ms (95% CI [-0.9, -3.9], p = 0.0020) was 21% of the mean 11.4 ms VEMP peak to trough latency measured across women and men. There was no significant sex difference in VEMP peak to trough amplitude. These findings are a reversal of several prior studies in humans, reviewed here with a simulation indicating the studies may have been underpowered. DISCUSSION: Findings are consistent with those in Brown Norway Rats, for which a study design featuring a custom rodent holder to control neck tension, extension of test sequences in comparison to those typically used in VEMP protocols for humans, and insertion of electrodes subcutaneously will have increased sensitivity compared to that achievable with clinical VEMP protocols for humans. Findings are interpreted as sex hormones affecting myelination or synaptic response; sexual dimorphism in neck/head size may also have contributed. The vestibular periphery and brainstem are highly conserved across vertebrates with similar findings in rat and human supporting use of VEMP as a reliable, non-invasive indicator of vestibular function. VEMP measures in humans may require higher sensitivity than is achievable using current clinical protocols in order to produce consistent results.
Li X, Gao J, Liu X
… +7 more, Guo J, Liu Y, Cui P, Yan D, Fei T, Chen M, Gao Y
Front Integr Neurosci
· 2025 · PMID 40271198
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Arecoline, a biologically active alkaloid extracted from the areca nut, serves as the primary psychoactive ingredient in betel quid, one of the most widely consumed psychoactive substances worldwide. Despite its extensiv...Arecoline, a biologically active alkaloid extracted from the areca nut, serves as the primary psychoactive ingredient in betel quid, one of the most widely consumed psychoactive substances worldwide. Despite its extensive use, the central nervous system (CNS) effects of arecoline remain inadequately understood. This study aims to investigate the central actions of arecoline through a comprehensive, multi-dimensional approach that integrates behavioral assays, neuroimaging techniques, calcium signaling analysis, and transcriptomic profiling. Our findings demonstrate dose-dependent addictive properties of arecoline, alongside distinct behavioral alterations that highlight its potential for addiction. Neuroimaging and calcium signaling data revealed region-specific alterations in neural activity, particularly in areas associated with learning, memory, and reward processing. Furthermore, transcriptomic analysis identified significant changes in gene expression, particularly in pathways related to synaptic plasticity, calcium signaling, and metal ion transport. These results provide valuable insights into the addictive potential of arecoline and its underlying neurobiological mechanisms, offering crucial information for understanding its broader impact on CNS function. The study's findings hold significant implications for informing public health strategies aimed at addressing arecoline misuse and its potential role in addiction-related disorders.
Front Integr Neurosci
· 2025 · PMID 40255474
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School mathematics mainly embraces algorithmic problem solving, pays less attention to strategic reasoning, and rarely contains insightful problem solving. Based on our previous research, we hypothesize that success in s...School mathematics mainly embraces algorithmic problem solving, pays less attention to strategic reasoning, and rarely contains insightful problem solving. Based on our previous research, we hypothesize that success in solving insight problems correlates strongly with general giftedness, while mathematical expertise is essential for strategy-based problem solving. Furthermore, we employ a phenomenon of greater ERP amplitudes in PO4/8 electrodes associated with insightful problem solving. In this study, 114 high school students (aged 16-18) with varying degrees of general giftedness and mathematical expertise were asked to solve mathematical problem of three distinct type: (1) function problems, whose solutions are memory-based; (2) area problems that necessitate strategic thinking; and (3) insight problems, that necessitate insight for their resolution. The problem solving process was accompanied by ERP recording. We demonstrate that variations in accuracy of solutions and reaction time for correct responses between tasks are influenced by students' general giftedness and mathematical expertise. Our ERP analyses partly supported our hypotheses regarding the relationship between PO electrode activation, insight-based problem solving processes, and participants' levels of giftedness and mathematical expertise.