Journal of Neurodevelopmental Disorders

Background: Sleep disruption is prevalent in people with neurodevelopmental disorders such as autism but is not clear whether it occurs as an endophenotype or secondary to other behaviours. The ABCD Study is a population-based longitudinal study that monitors the health, demography and lifestyle of over 11,000 children in the US. In this study we leverage these data to investigate whether traits consistent with autism (social responsiveness) are associated with sleep disruption independent of lifestyle and other behavioural measures. Methods: Autistic traits were assessed using the Social Responsiveness Scale at age 11, and sleep disruption and behavioural outcomes were assessed at ages 11 and 13 years using the Sleep Disturbance Scale, and the Child Behaviour Check List, respectively. Demographic, health and lifestyle-related variables were assessed by caregiver questionnaires. Regression models were applied to investigate associations between autistic traits and sleep outcomes. Results: There was a significant cross-sectional association between sleep disturbance and SRS at age 11 years old that was independent of sex, ethnicity, socioeconomic position, physical activity, sedentary behaviour and anxiety/depression ({beta} = 0.12, 95% CI (0.07, 0.17); p < 0.001), that persisted at age 13, and that was modulated by chronotype, with evening types showing a stronger association. Discussion: Social responsiveness assessed in early adolescence (age 11) were associated with sleep disruption independent of multiple confounding factors and were prospectively associated with sleep disruption at age 13 years. These findings contribute to the evidence that disruption of sleep and circadian timing may have a primary role in the neurobiological mechanisms that mediate autistic traits.

Autism development involves multiple genetic and early-life environmental factors. Studying the placenta's gene expression profile may reveal key mechanistic pathways in autism development. Here, using a nested case-cohort design within an Australian population-derived prebirth cohort study (n=1074), we identified 1,644 differentially expressed genes (DEGs; FDR<0.05) in the placenta of children with autism diagnosis (n=43), compared to those without (n=120). The top enriched pathways related to mitochondrial translation, oxidative stress, RNA processing and transcription regulation. CYP1A1, the most important xenobiotic-metabolising enzyme of the placenta, was the top downregulated DEG in the placenta of children with autism, while immuno-regulatory human leukocyte antigen (HLA)-related genes were among the top upregulated DEGs. A machine learning-based approach predicted autism from the transcriptomic data with a median sensitivity of 0.57 (2.5th-97.5th centiles: 0.29, 0.76) and median specificity of 0.92 (2.5th-97.5th centiles: 0.78, 0.98). Weighted Gene Correlation Network Analysis identified eight affected placental gene modules, with the largest five modules being enriched primarily for mitochondrial bioenergetics, oxidative phosphorylation and RNA processing pathways. This placental transcriptomic signature of impaired mitochondrial function and gene transcription regulation among infants subsequently diagnosed with autism has profound implications for understanding both risk factors and prediction, suggesting the possibility of identifying modifiable prenatal pathways to improve autism outcomes.

Differences in extracellular vesicles (EVs), bioactive nanoparticles involved in intercellular signaling, have been reported in those with autism. However, little is known about the association between maternal EVs during pregnancy and the likelihood of autism in offspring. This study evaluated the association of the concentration and cargo material of EVs in prenatal maternal plasma with childhood autism likelihood. Participants in the Nulliparous Pregnancy Outcomes Study provided maternal plasma at 15 to 23 weeks gestational age. EVs were isolated by ultracentrifugation, and concentration, mean size, CD63 levels, and RNA cargo were assessed by nanoparticle tracking analysis, ELISA, and small RNA sequencing. At 4.5 to 6 years of age, parents completed the Social Communication Questionnaire. Thirty-one children at high-risk for autism were matched to 31 low-risk children on sex, age, and gestational age. Differential RNA transcript analysis and over representation analysis were performed. There were no group differences in CD63 levels, mean particle size, or EV concentration (p>0.1). Nominal bin-level differences were observed at 280 to 290 nm and 430 to 440 nm before multiple-comparison correction. One hundred forty-five RNAs, including protein-coding RNAs, piRNAs, lncRNAs, miRNAs, snoRNAs, snRNAs, and tRNAs, were differentially contained, most of them downregulated in those at high risk of autism. These RNAs mapped to pathways involved in immune/inflammatory signaling, intracellular trafficking, protein turnover, and neurodevelopment. Six of the 62 (9.7%) differentially contained protein-coding RNAs overlapped with genes in the SFARI Gene database. These findings provide preliminary evidence that maternal prenatal EV RNA cargo is associated with childhood autism likelihood.

Sensory processing differences are a core feature of autism, affecting 60-95% of individuals, yet the associated neural mechanisms remain unclear. An excitation-inhibition (E/I) imbalance in brain circuits has been proposed, but in vivo evidence linking genetic variation in E/I pathways, regional neurochemistry, neural circuit function, and sensory behaviour has been lacking. Here we performed a multimodal investigation in 206 individuals (130 autistic), integrating gene-set polygenic scores for excitatory glutamatergic and inhibitory gamma-aminobutyric acid (GABA)-ergic pathways, magnetic resonance spectroscopy (MRS) measures of regional GABA and Glx (glutamate + glutamine) levels, vibrotactile psychophysical measures of tactile perception, and questionnaire measures of behavioural sensory reactivity. We found that glutamatergic polygenic scores predicted thalamic glutamate levels in neurotypical but not autistic individuals, suggesting altered genotype-neurochemistry coupling in autism. Thalamic Glx:GABA levels associated with tactile perception in both groups, but with opposing directions of effect, indicating that autistic and neurotypical individuals achieve similar perceptual outcomes with potentially differing thalamocortical circuit mechanisms. Within autistic individuals, tactile perceptual differences further related to behavioural sensory reactivity. Together, these findings suggest that autistic sensory processing potentially relies on distinct circuit mechanisms linking genetic variation, neurochemistry and perception. This work thus has important implications for how sensory differences are conceptualised, studied, and interpreted, and ultimately for how interventions and support are developed.

Autism is a heterogeneous neurodevelopmental condition, often accompanied by challenges in language and cognitive development. Although atypical functional connectivity (FC) has been reported in autism, the timing of when it first emerges and its relevance for later behavior remain poorly understood. In this study, we examined developmental trajectories of alpha-band FC and network organization across the first three years of life. We computed global alpha-band measures, including peak alpha connectivity frequency (PACF), mean FC, clustering coefficient, and modularity, to characterize nonlinear developmental trajectories from longitudinal EEGs collected from 238 children (3-to-36-month-olds) with (Autism; n=58) and without (LL-noAutism; n=180) autism. Network-based statistics (NBS-Predict) identified subnetworks contributing to group differences at each age. Exploratory graph analyses (EGA) examined associations among FC, network measures, and language outcomes. We observed that PACF increased linearly with age in both groups. Global alpha-band connectivity measures showed a similar developmental pattern, with mean global FC, clustering coefficient, and modularity all increasing rapidly during the first year in both groups. Thereafter, these measures declined in the Autism group but continued to gradually increase in the LL-noAutism group. Compared to LL-noAutism, NBS-Predict identified both hyper- and hypo-connectivity subnetworks in Autism at 3 months, followed by a hypo-connectivity subnetwork at 24 and 36 months. EGA indicated that early hyperconnectivity predicted later hypoconnectivity and was associated with subsequent network organization and language outcomes. These findings indicate that altered alpha-band connectivity trajectories are detectable in infancy in children later diagnosed with autism and may contribute to later differences in developmental outcomes.

Background The global prevalence of autism spectrum disorder (ASD) has significantly increased over the past two decades. Despite substantial research advances, critical aspects, including etiology, diagnostic biomarkers, and pharmacological interventions, remain incompletely elucidated. This persistent knowledge gap warrants systematic mapping of the field's evolution to inform future research priorities. Methods A bibliometric analysis of ASD-related publications indexed in Web of Science was conducted from January 2020 to May 2025. Following a systematic deduplication process, original articles, reviews, case reports, and clinical trials were included in the analysis. The analytical framework comprised co-authorship networks, institutional collaboration patterns, national research contributions, and keyword co-occurrence structures, all of which were examined using CiteSpace (version 5.8.R3) and VOSviewer. Results After deduplication, 8,162 publications (January 2020-May 2025) were analyzed. The annual output grew steadily, confirming ASD as a sustained priority in neuroscience. Research remains academia-driven, led by the United States, with China as the second-largest contributor. Chinese institutions place greater emphasis on mechanistic and developmental phenotyping, which aligns with national priorities. These studies maintain strong methodological rigor, and their growing volume underscores the central role of ASD in translational neuroscience. Conclusion Future research on ASD should focus on strengthening case identification, refining clinical phenotyping, and expanding large-scale cohort studies to advance our understanding of its etiology and identify reliable diagnostic biomarkers. It is equally important to develop and evaluate targeted interventions for core symptoms and integrate telemedicine into service delivery models. A critical yet understudied priority is improving the quality of life for autistic individuals and their families, an area in which research globally, including in China, requires greater depth and consistency. With China's growing investment in autism research, it is well-positioned to contribute to these pressing international challenges.

Purpose: Autism spectrum disorder (ASD) is genetically and phenotypically heterogeneous condition, complicating identification of causal variants. Current diagnostic approaches, have limited diagnostic yield, underscoring the need for new strategies. Methods: We developed a phenotype-driven framework to prioritize ASD-associated genetic variants using comprehensive phenotypic and exome sequencing (ES) data from 125 children with ASD. We used the Human Phenotype Ontology (HPO) nomenclature to prioritize candidate variants in each child based on the similarity between its observed phenotypes and variant-specific expected phenotypes. Results: We identified 228 HPO terms grouped into 41 phenotype categories. ASD-associated genes, according to HPO and SFARI Gene databases, were significantly enriched with these phenotypes compared to non-ASD genes (mean 16.1+/-5.7 vs. 6.5+/-5.4; p=1.1e-231; HPO, and 16.0+/-6.7 vs. 7.3+/-6.0; p=2.1e-57; SFARI) supporting the relevance of this phenotype battery to ASD genetics. In 36 genetically resolved participants, the phenotype-similarity approach ranked 58% of causal variants first and 89% within the top three. In the 89 unresolved cases, it highlighted six novel clinically relevant variants, thus increasing the diagnostic yield by 45%. Conclusions: Our novel ASD phenotype battery facilitates prioritization of clinically relevant ASD variants and hence may enhance diagnostic yield, gene discovery, and phenotype-guided precision medicine of ASD.

PurposeInterpersonal entrainment, defined as the tendency of interacting individuals to temporally align their behaviours, is considered a key mechanism supporting social interactions through predictive and multisensory processes. Autism Spectrum Disorder (ASD), characterized by social and communication difficulties, has been associated with atypical predictive and multisensory integration processes, which may affect spontaneous entrainment to others actions during rhythmic interactions. MethodsThe present study investigated spontaneous interpersonal entrainment in 24 autistic and 22 neurotypical young adults using a unidirectional adaptation of the drifting metronomes paradigm developed by Rosso et al. (2021). Participants synchronized their finger tapping with an auditory metronome while either seeing or not seeing a partners hand movements performing the same task at a slightly different tempo. Individual synchronization performance was assessed using asynchrony measures and computational modelling of sensorimotor synchronization, while interpersonal coordination dynamics were quantified using joint recurrence analysis. ResultsVisual exposure to the partners hand movements significantly increased tapping variability while simultaneously enhancing spontaneous interpersonal entrainment. Contrary to previous findings, these effects were comparable across groups, suggesting similar sensitivity to spontaneous low-level interpersonal coupling under stable and predictable conditions. ConclusionOverall, the findings support accounts proposing selective rather than generalized atypicalities in predictive processing and interpersonal entrainment in ASD.

Background: Social behavior is a core component of mental health, and its disruption characterizes many neuropsychiatric disorders such as autism. Social operant paradigms enable the quantification of volitional aspects of social motivation and interactions. While sex differences have been shown to influence social motivation, factors such as familiarity and social hierarchy are also likely to play a critical role that remain insufficiently explored. In addition, the subthalamic nucleus (STN), traditionally studied in motor circuits, has emerged as an important regulator of reward and motivational processes and may contribute to social behavior processes. Methods: In this study, we examined the influence of peer familiarity (cagemate vs. stranger) and social hierarchy (dominant vs. subordinate) 1) on operant volitional social interaction using a fixed ratio 1 (FR1) and 2) on social motivation using a progressive ratio (PR) schedule of reinforcement in non-isolated rats. To assess the causal contribution of the STN, we used optogenetic photo-inhibition during both tasks in male rats. Results: Male rats displayed a reduction of social interest and motivation toward familiar peers, mainly driven by the social hierarchy, while female did not. STN photoinhibition in males abolished the familiarity-driven reduction under FR1 but decreased motivation independently of familiarity or hierarchy in PR. Conclusions: These findings highlight sex, familiarity, and hierarchy as key modulators of volitional social behavior and demonstrate a direct role of the STN in regulating social motivation. Together, they provide mechanistic insights into processes that may be disrupted in neuropsychiatric disorders characterized by social dysfunction.

Background: Suicide attempts (SA) are elevated in individuals with autism spectrum disorder (ASD), but population-level data characterizing how SA prevalence varies across demographic and clinical subgroups - at the scale and granularity needed to inform evidence-based risk stratification - have been largely unavailable. This study examines SA prevalence across sex, age group, psychiatric comorbidity type, and substance use disorder subtype in the largest real-world ASD cohort to date. Methods: We conducted a retrospective cross-sectional analysis using Epic Cosmos electronic health record data from 2,311,171 individuals with ASD identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, spanning 2016-2025. SA prevalence was calculated with Wilson score 95% confidence intervals. Modified Poisson regression with robust variance estimation was used to estimate adjusted prevalence ratios (aPRs) for sex, age group, and psychiatric comorbidity. Unadjusted prevalence ratios (uPRs) were calculated separately for individual comorbidity types and substance use disorder subtypes. Results: Overall SA prevalence was 1.7% (38,160 individuals). Females showed higher SA prevalence than males (2.9% vs. 1.2%; aPR 1.61, 95% CI 1.35-1.92). SA prevalence peaked in the 15-24 age group overall (aPR 5.14, 95% CI 3.62-7.29), with sex-stratified analyses revealing that females peaked earlier (15-24 years; aPR 4.33, 95% CI 4.23-4.43) than males (25-34 years; aPR 6.08, 95% CI 5.05-7.31) - a sex-specific divergence in the timing of peak SA prevalence not previously documented in ASD. Having at least one psychiatric comorbidity was associated with a 30-fold higher SA prevalence (aPR 30.56, 95% CI 26.03-35.89), with the effect stronger in females (aPR 36.54, 95% CI 31.04-43.01) than males (aPR 27.77, 95% CI 22.65-34.06). Among comorbidity subtypes, substance-related disorders showed the highest crude SA prevalence (16.9%; uPR 134.20, 95% CI 67.68-266.10). Subtype-level characterization revealed SA prevalence ranging from 19.7% to 24.3% across all five substance use disorder subtypes examined, with stimulant use disorder showing the highest unadjusted prevalence ratio of any subtype (uPR 196.11, 95% CI 100.63-382.20). Conclusion: SA prevalence in ASD is markedly elevated relative to the general population and varies meaningfully by sex, age, and comorbidity profile in clinically important ways. Females carry a disproportionate SA burden relative to males, with peak vulnerability arriving earlier in adolescence; males peak later in young adulthood and remain at elevated risk into midlife. Psychiatric comorbidity - particularly substance use disorders - is associated with the largest relative elevations in SA prevalence. These population-level estimates are directly applicable to EHR-based risk stratification models and can inform the development of ASD-specific clinical decision support tools that concentrate surveillance and intervention on those at demonstrably elevated risk, rather than applying uniform approaches across a heterogeneous population.

Background: Previous large-scale structural MRI analyses of the brain in autism have identified gray matter (GM) differences when using region-of-interest analyses based on gross anatomical regions. However, such analyses have limited spatial specificity for localizing neuroanatomical alterations and may obscure subtle, spatially focal differences. Whole brain voxel-based morphometry (VBM) analyses enable greater spatial precision for localizing GM and white matter (WM) alterations in autism. Purpose: To rigorously identify voxel-wise GM and WM volume differences in autism in the largest VBM mega-analysis to date. Materials and Methods: This retrospective mega-analysis included structural 3D volumetric T1-weighted MRI brain scans from 3,051 participants (1,519 autism; 1,532 neurotypicals) collected across 51 sites/scanners. Voxel-wise GM and WM volumes were quantified using the ENIGMA CAT12 VBM pipeline. Linear mixed-effects regression was performed at each voxel to evaluate the association between diagnostic group and voxel-wise volume while adjusting for standard nuisance covariates Results: A total of 3,051 participants (15.0 {+/-} 8.2 yrs; 2,342 male) were included in the study. Autism was associated with widespread lower GM volume involving cortical, subcortical, and cerebellar regions. The most extensive alterations in autism were detected in the orbitofrontal cortex, amygdala, thalamus, and posterior lobes of the cerebellum. WM volume was lower in autism across major projection, commissural, association, and cerebellar/brainstem tracts, including the corona radiata, internal capsule, corpus callosum, and cerebellar peduncles. These findings remained consistent in sensitivity analyses, including the application of increasingly strict motion exclusion criteria. Conclusion: Autism is associated with smaller voxel-wise GM and WM volume involving widespread cortical, subcortical, and cerebellar regions. Our findings remained robust across supplementary analyses and provide high-resolution localization of structural brain differences in autism. These findings support the involvement of distributed neural systems underlying reward processing, sensory integration, and motor functioning in autism.

Introduction: Autism spectrum disorder, or autism, is a common neurodevelopmental condition characterized by socio-communicative problems together with restrictive and repetitive behaviors. Typically, the latter is manifested as deficits in behavioral flexibility, i.e. changing routine behaviors to adapt to environmental changes. Despite noticeable difficulties with flexible behavior in autism, there is to date not adequate knowledge about the intricacies of such challenges and neurobiological processes that may subserve them. This study aims to investigate both cognitive and motor flexibility in autistic compared with neurotypical adults using a novel combination of detailed methods for brain imaging and behavioral investigations in relation to probabilistic reversal learning (PRL) paradigms. In addition, the experiences of autistic adults on flexible behavior in education and everyday activities will be explored. Methods and analysis: Differences in cognitive flexibility between autistic (n[&ge;]20) and neurotypical (n[&ge;]20) adults (18-35 years) will be investigated in terms of brain activations, measured by functional magnetic resonance imaging (fMRI), during two-choice PRL performance (cognitive task). In addition, group differences in microcirculation as measured by arterial spin labelling (ASL) will be evaluated. Group differences in motor flexibility will be investigated as expressed in movement planning and execution (spatio-temporal parameters), measured by a robotic manipulandum platform (KinArm End-Point Robot), during two-choice PRL performance (motor task). Semi-structured interviews will be conducted individually with autistic participants (n=15). Questions concern own experiences of cognitive and motor behavior, and strategies used to support flexibility in these behaviors. Data from this qualitative approach will be analyzed by thematic analysis. Ethics and dissemination: Ethical approval has been obtained from the Swedish Ethical Review Authority (ref:2025-07939-01) and the study will be conducted in accordance with the Declaration of Helsinki, the European Union General Data Protection Regulation (GDPR) and national guidelines for the storing of personal data. The different investigations included are well-established, non-invasive and safe. Study outcomes will be published in peer-reviewed international scientific journals (open access), presented at national and international conferences, and to any interested audience/stakeholders.

Background: Children and young people (CYP) with intellectual disability (ID) frequently have co-occurring neurodevelopmental (ND) and mental health (MH) difficulties. While copy number variants (CNVs) are identified as an important aetiology of ID, it is unclear whether and how CNV risk scores predict ND and MH characteristics within the CNV-associated ID population. Methods: We analysed data from the UK-based IMAGINE-ID cohort of CYP (aged 4-19 years) with ID and clinically-reported CNVs (N = 1,640). CNVs were annotated with Gencode 19 in ENSEMBL to calculate CNV risk scores, including summed probability of loss-of-function intolerance (pLI) and dosage sensitivity. Multivariate regression models examined the prediction of CNV variables and inheritance on ND and MH characteristics, assessed via the Development and Well-Being Assessment (DAWBA). Post-hoc analyses explored CNV variable stratification (lower vs. higher range pLI). Results: Higher summed pLI scores (indexing CNV genes' intolerance to loss of function) unexpectedly predicted fewer MH difficulties and a lower likelihood of ND diagnoses, even after accounting for demographic factors and CNV inheritance. Post-hoc analyses identified a threshold effect. Within the lower pLI range, higher pLI scores were associated with greater MH difficulties, consistent with findings from population-based samples. In contrast, within the higher pLI range, higher pLI scores were associated with fewer MH difficulties (among individuals more likely to have severe ID). Conclusion: These findings challenge the assumption that CNV genomic "risk scores" universally predict ND and MH difficulties. Instead, within CNV-associated ID, complex relationships exist between CNV risk scores, inheritance and phenotypes. These insights emphasise the necessity of integrating genomic results with familial and developmental context to understand individual vulnerabilities and support needs.

Objective: Pediatric epilepsy patients undergoing stereo-electroencephalography (sEEG) for ictal onset evaluation provide a rare window to study the developing brain. While methodological frameworks for task-based sEEG research are well-established in adults, pediatric-specific guidance remains underdeveloped. Furthermore, many pediatric epilepsy patients have comorbidities that might typically exclude them from participating in research. We examine factors that influence research participation and discuss considerations for conducting sEEG research in children. Methods: Here, we present a retrospective analysis of task-based research participation patterns from an NIH-funded study of speech and language representations (1R01DC018579) in 66 patients (ages 4-24) undergoing sEEG monitoring at Texas Children's Hospital to determine whether specific comorbidities influenced research participation. Results: Eighty-nine percent (n=66) of patients approached for consent agreed to participate in the study. Despite high rates of comorbidities including neurocognitive disorder (66.67%), language delay (31.75%), global developmental delay (23.81%), mood disorders (33.33%), ADHD (46.03%), autism spectrum disorder (14.29%) or other cognitive/intellectual disabilities (36.51%), all participants engaged in at least one task. While the majority of these diagnoses did not appear to influence subject participation, global developmental delay was associated with a significant reduction in time spent on active tasks. Discussion: Despite high prevalence of neuropsychological comorbidities among participants, our evidence suggests that these participants contribute meaningfully to studies investigating important developmental questions. We suggest strategies for tailoring task-based research to accommodate the unique needs of individuals in this population. Such practices are important for ensuring that research studies reflect the true diversity of the population.

Autistic psychiatrists occupy a paradoxical position: trained to recognise and assess autism in others, yet navigating a professional culture in which their own autistic identity remains largely concealed. Despite growing visibility of autistic clinicians, the barriers autistic psychiatrists face to formal diagnosis and professional disclosure remain unexplored. This study used interpretive phenomenological analysis to examine the experiences of seven autistic psychiatrists in relation to diagnosis and disclosure. Data were generated through in-depth interviews and Retzinger's framework for identifying shame in discourse was applied as an analytical tool within the interpretive process. Shame emerged as the overarching theme across the dataset, operating through four group experiential themes. Its origins lay in childhood experiences of difference and perceived defectiveness, transmitted through family, peers, and the broader social environment. In professional life, shame was sustained and amplified by colleagues' misconceptions about autism, anticipated loss of credibility, and the deficit-based diagnostic criteria - which rendered self-recognition difficult and made formal diagnosis a perceived professional liability. Critically, shame did not only create barriers: it functioned as an override mechanism, rendering the known benefits of disclosure - to participants themselves, to colleagues, and to patients - insufficient to translate into action. This override function was not explained by fear of discrimination or rational career protection alone; it reflected shame's operation as an internal prohibition, dissociated from its original social source and persisting even where stigma had been intellectually processed and rejected. These findings reposition shame not as one barrier among many but as the organising force through which all barriers operate. Interventions aimed at increasing disclosure by raising awareness of its benefits misread the operative mechanism. Creating conditions in which autistic psychiatrists can make decisions about their identities freely requires naming and addressing shame - in research, in clinical training, and in the culture of psychiatry.

Objective: Studies assessing the validity of screening measures for avoidant/restrictive food intake disorder (ARFID) remain scarce. We evaluated the diagnostic performance and validity of an online, parent-reported screening approach for ARFID in a population-based sample of children. Methods: Participants were drawn from the ARFID Initiative Sweden (ARIES) cohort and included 65 children aged 6-14 years. Parents completed three screening questionnaires (Pica, ARFID, and Rumination Disorder Interview-ARFID Questionnaire [PARDI-AR-Q], Nine-Item ARFID Screen [NIAS], and Parent Eating Disorder Examination Questionnaire [PEDE-Q]), followed by a diagnostic interview (PARDI). Diagnostic performance indices (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) were calculated. Convergent validity was assessed via correlations between questionnaire and interview dimensions. Results: The combined screening algorithm demonstrated perfect sensitivity and NPV, indicating accurate detection of all ARFID cases and exclusion of non-cases. Specificity was high (0.83), and PPVs ranged from 0.91 to 0.95, decreasing to 0.78 under a more conservative operationalization of ARFID Criterion A4 (psychosocial impairment). Diagnostic performance varied across ARFID criteria: PPVs were low for medically anchored Criteria A1-A3 but high for Criterion A4 (psychosocial impairment; PPV=0.95). Correlations between screening measures and corresponding interview dimensions were generally moderate to strong, supporting convergent validity. Children meeting threshold ARFID criteria showed significantly greater symptom severity than subthreshold cases at screening. Discussion: These findings support the use of a multi-instrument, parent-reported screening approach for ARFID in large-scale pediatric research and highlight the centrality of psychosocial impairment, underscoring the need for standardized operationalization of this criterion.

Adolescence is a sensitive period during which unhealthy diets may shape metabolic health and cognition. Diets high in fat and sugar have been linked to obesity, impaired glucose regulation and hippocampus-dependent deficits, but the exposure duration required to affect cognition remains unclear. This study examined whether adolescent-onset exposure to a high-fat high-sucrose (HFHS) diet induces metabolic dysfunction and impairs object-based memory, spatial working memory and spatial pattern separation in male Long Evans rats. Rats were assigned to a control or HFHS diet at four weeks of age and remained on this diet into adulthood. Basal blood glucose was assessed monthly and home-cage behaviour using 48-hour LABORAS recordings. Cognitive testing started after 10 weeks of diet exposure, when basal glucose was elevated in HFHS-fed rats. Object displacement and novel object recognition were used in short open-field test settings, whereas touchscreen-based trial-unique nonmatching-to-location testing (TUNL) assessed spatial working memory and pattern separation across repeated operant sessions. Finally, glucose (in)tolerance and tissue weights were measured. HFHS diet exposure produced a metabolic phenotype, including increased body weight, elevated basal glucose, impaired glucose tolerance and increased liver and gonadal white adipose tissue weights. The diet also altered the general behavioural repertoire, with increased immobility and grooming and reduced rearing. HFHS-fed rats did not differ from controls in object displacement or novel object recognition performance. In the touchscreen task, both groups acquired the task at a comparable rate. Long-delay and spatial separation challenges reduced performance as expected, confirming task sensitivity, but did not reveal diet-related impairments. These findings show that adolescent-onset HFHS diet exposure induces metabolic dysfunction but does not necessarily produce detectable cognitive impairment when behavioural testing starts after 10 weeks of exposure. Longer exposure or advanced diet-induced inflammatory or neurobiological alterations may be required to reveal cognitive consequences.

Reported perceptual differences in autism may arise from reduced use of prior context to shape incoming sensory input. Speech perception provides a critical test of this account because stable perception requires listeners to integrate variable acoustic signals with contextual expectations. This study examined context-dependent modulation of speech encoding in autistic and non-autistic adults using the frequency-following response (FFR), a neurophysiological measure of phase-locked auditory encoding. Participants heard English intonational pitch contours presented in repetitive and variable contexts while EEG was recorded. Principal component analysis of FFR metrics yielded components indexing neural encoding fidelity and timing. Non-autistic participants showed enhanced encoding fidelity in more predictable contexts, whereas autistic participants showed reduced context-dependent modulation. Neural encoding timing also showed divergent context effects across groups, suggesting altered balance between feedback-based predictive mechanisms and locally driven adaptation processes. Within the autistic group, greater context-related modulation of encoding fidelity was associated with lower ADOS-2 Social Affect severity but poorer speech-in-noise perception, suggesting that the functional impact of contextual modulation depends on input reliability and task demands. These findings indicate that context-dependent modulation of speech encoding is altered in autism and may contribute to individual differences in auditory and social-communicative function.

Background: Rett syndrome (RTT), a rare neurodevelopmental disorder caused primarily by pathogenic variants in the MECP2 gene, is characterized by severe cognitive, motor, and autonomic impairments. Atypical sensory processing, including co-occurring hypo- and hyper-responsivity, is a core yet poorly understood feature. While evoked potentials (EPs) show delayed and attenuated sensory responses in RTT, the underlying mechanisms of these impairments remain unclear. Inter-trial phase coherence (ITPC), which quantifies trial-by-trial neural response consistency, offers a promising functional biomarker of variability in sensory processing. Methods: We characterized caregiver-reported sensory responsivity in 32 individuals with RTT (all female) and 28 typically developing controls (26 female, 2 male). EPs were then recorded during passive visual and auditory stimulation and ITPC was computed to assess whether variability in the timing of neural responses could account for reduced EP amplitudes and atypical sensory responsivity. Results: Hypo- and hyper-responsivity to sensory stimuli were both significantly elevated in RTT and were positively correlated, co-occurring within individuals. ITPC was significantly reduced in RTT across visual and auditory modalities and was associated with reduced EP amplitudes. Notably, reduced ITPC in visual-evoked potentials was further associated with elevated visual responsivity and greater behavioral symptom severity. Conclusions: Increased variability in neural response timing may contribute to both reduced EPs and atypical sensory responsivity in RTT, supporting ITPC as a functional biomarker. Decreased temporal precision of neural activity may explain the co-occurrence of hypo- and hyper-responsivity and provide a unifying framework for sensory dysfunction across neurodevelopmental disorders.

Objective: Working memory (WM) deficits are a co-occurring feature to numerous neuropsychiatric disorders, particularly attention-deficit/hyperactivity disorder (ADHD), and there remain no treatments that directly target WM. The coupling between the phase of theta band activity and amplitude of gamma band activity (i.e., TGC) is an established neural correlate of WM. However, no studies have examined WM-related TGC in ADHD or whether neuromodulation can modulate these oscillatory dynamics in youth. This set of studies examined the effects of intermittent theta burst stimulation (iTBS) to the left dorsolateral prefrontal cortex (DLPFC) and left posterior parietal cortex (PPC) on TGC in youth with ADHD. Methods: In two randomized, double-blind, sham-controlled crossover trials, adolescents with ADHD and clinically significant parent-reported WM symptoms first completed a single-session study comparing DLPFC versus PPC iTBS targeting (n = 47) and then a multi-session clinical trial comparing 10 sessions of active versus sham left DLPFC iTBS (n = 29). Participants completed a computerized visuospatial Sternberg WM task with concurrent electroencephalography (EEG) before and after the single sessions, as well as at baseline, midway through treatment, and approximately 24 hours after the final session within the multi-session trial. Phase-amplitude coupling between theta phase and gamma amplitude was quantified using the Kullback Leibler modulation index at frontoparietal electrodes. Linear mixed-effects models examined treatment effects and associations between change in TGC and WM status (including accuracy, reaction time, and clinical symptoms). Results: Across participants, lower TGC was associated with lower symptoms and better WM performance, including higher accuracy, faster and more consistent RT. Active iTBS increased frontoparietal TGC relative to sham stimulation, with effects observed both acutely after a single session and ~24 hours after multiple sessions. DLPFC-targeted iTBS increased TGC, whereas PPC-iTBS had no measurable effect. Change in TGC was associated with change in WM, such that a decrease in TGC was associated with faster RT and decreased RT variability. Higher baseline TGC was associated with greater improvement in WM. Active iTBS decoupled the TGC-WM association observed during sham iTBS, and greater electric field intensity of iTBS was associated with greater improvement in WM accuracy and greater decrease in TGC. Conclusions: Active iTBS to the left DLPFC modulated WM-related TGC in youth with ADHD. These findings provide preliminary evidence that neuromodulation may improve WW by modifying oscillatory dynamics within frontoparietal networks. Larger clinical trials with higher stimulation doses are needed to determine whether targeting oscillatory coupling represents a potential therapeutic strategy for WM deficits.