Frontiers in Integrative Neuroscience

Differences in looking to and processing of audiovisual speech have been theorized to contribute to heterogeneity in language ability in autistic children. Differential audiovisual speech processing has been indexed by event-related potentials (ERPs), specifically via amplitude suppression in response to audiovisual versus auditory-only speech, and linked with vocabulary in school-aged children. This study used an intact-group comparison and concurrent correlational design in infant siblings of autistic children (Sibs-Autism) and non-autistic children (Sibs-NA) to determine whether amplitude suppression is (a) present in infancy, (b) different in Sibs-Autism versus Sibs-NA, and (c) related to looking to audiovisual speech and language abilities. We collected EEG data from 54 infants aged 12-18 months (29 Sibs-Autism; 25 Sibs-NA) while they viewed videos of audiovisual and auditory-only speech, as well as eye tracking and language data. We found significant amplitude differences at the N2 ERP component in response to audiovisual versus auditory-only speech but no significant group differences in ERP amplitudes. Associations between looking to audiovisual speech, amplitude effects, and language were moderated by group, chronological age, and biological sex. Our findings suggest that differential audiovisual speech processing is present in 12-18-month-olds and may explain heterogeneity in looking to audiovisual speech and emerging language ability.

Although HIV exposure has previously been found to affect brain white matter (WM) tract integrity and language development in infants and children, the impacts of HIV and antiretroviral therapy (ART) exposure on central auditory tracts remain unclear. Moreover, no research to date has investigated the relationship between auditory WM tract development and language outcomes in infants exposed to HIV but uninfected (iHEU). Brain images were acquired at the age of 0-5 weeks for 31 infants whose mothers began ART pre-conception (iHEU-pre), 29 infants whose mothers began ART post-conception (iHEU-post) and 25 infants who were HIV-unexposed (iHU). Full-probabilistic diffusion tensor imaging (DTI) tractography was used to assess WM integrity in tracts connected to central auditory structures. Language assessments were carried out at 9-14 months using the Griffiths Mental Development Scales (GMDS). Linear regression analysis was used to compare DTI tractography results between iHEU and iHU and to assess the relationship between DTI measures and language. Finally, the impacts of HIV and ART exposure on associations between language and DTI measures were visualised using groupwise language-DTI correlation plots. There were no results after multiple comparison correction. Unadjusted results show recurring patterns of reduced fractional anisotropy (FA), driven by iHEU-post, in auditory tracts of iHEU compared to iHU. Both iHEU-pre and iHEU-post contributed to the patterns of uncorrected elevations in mean diffusivity (MD) observed in the entire iHEU group, with the left medial geniculate nucleus being the auditory structure most frequently observed within the affected tracts. Effect sizes of uncorrected differences, which were small-to-moderate in size, were similar to other infant DTI tractography studies. Groupwise assessment of the data revealed moderately strong correlations between GMDS language scores and DTI measures in some affected tracts, only for iHU. Our findings indicate that HIV/ART exposure may have subtle effects on auditory WM tract development in infants. Delays in auditory tract maturation appear to occur irrespective of ART exposure duration and may be HIV exposure-specific effects. Tracts connected to the left auditory thalamus have notably been implicated in our unadjusted results. HIV and ART exposure may interfere with the way in which auditory WM tracts mature, potentially impacting the role of a small number of these tracts in language processing.

PurposePrevious research has demonstrated effects of head impact exposure on cortical neurophysiology, which may help with understanding variability in clinical sequelae. In separate lines of research, neurochemical and gene transcription markers of vulnerability to traumatic brain injury (TBI) have been established. The purpose of this study was to examine whether these cortical neurochemical and gene transcription gradients are spatially aligned with neurophysiological effects. Methods and MaterialsMagnetoencephalography (MEG) data was collected at a total of 278 pre- and post-season timepoints from 91 high school football players across up to four seasons of play. Of the 91 football players, 10 experienced a concussion, and of the remaining 81 non-concussed players, 71 met the criteria for complete imaging and kinematic data, with post-season evaluations less than six weeks after the end of the season. Head impacts were tracked over the course of the season with helmet-mounted sensors. MEG data underwent source-imaging, frequency-transformation, spectral parameterization, and linear modeling to examine the effects of concussive and non-concussive head impact exposure on pre-to-post-season changes in rhythmic and arrhythmic neurophysiological activity. To determine clinical effects, parent reported Post-Concussive Symptom Inventory scores related to cognitive symptoms were correlated with cortical neurophysiological changes. Multi-atlas data of neurochemical system densities from neuromaps and gene expression from the Allen Human Brain Atlas were examined for alignment with head impact-related alterations in neurophysiology via nonparametric spin-tests with autocorrelation-preserving null models (5,000 Hungarian spins; pFDR <.05). ResultsConcussion-related reductions in cortical excitability (i.e., aperiodic exponent slowing) were aligned with atlas-based norepinephrine transporter (NET) and alpha-4 beta-2 nicotinic receptor (4{beta}2) densities, and with apolipoprotein E (APOE) and brain-derived neurotrophic factor (BDNF) expression levels. More severe cognitive symptoms associated with concussion-related slowing of aperiodic neurophysiology were also aligned with atlas-based NET and 4{beta}2 receptor densities. Similar changes in cortical excitability related to non-concussive head impact exposure were colocalized with serotonin receptor (5-HT1A) density maps and APOE and BDNF expression. Rhythmic alpha activity was reduced by concussion and colocalized with histamine (H3) and mu-opioid (MOR) receptors, among others, as well as with gene transcription atlases of APOE and C-C chemokine receptor 5 (CCR5). ConclusionsThese findings extend our previous work to show that the effects of head impact exposure on neurophysiology are strongest in cortical areas with specific neurochemical and genetic profiles that are known to signal vulnerability to traumatic brain injury, and that these spatial alignments are also associated with self-reported symptom severity. Clinical Relevance / ApplicationChange in cortical excitability, as measured here by MEG, has potential value as a clinical tool for concussion diagnosis and prognosis. We provide genetic and neurochemical contextualization for these changes that may extend their clinical applications, for example to concussion risk assessment and pharmacotherapies.

PurposeNavigational ability develops throughout childhood alongside the maturation of brain regions supporting egocentric and allocentric processing. In Autism Spectrum Disorder (ASD), atypical hippocampal development may impact flexible spatial memory; however, findings on navigational ability in autistic children remain inconsistent. This study aimed to compare both objective and perceived navigation ability in children with ASD and typically developing (TD) peers. MethodTwenty-six children with high-functioning ASD and twenty-five age- and gender-matched TD children (M_age = 12.04 years, SD = 1.64) completed a battery of navigational tasks from the Spatial Performance Assessment for Cognitive Evaluation (SPACE), including Path Integration, Egocentric Pointing, Mapping, Associative Memory, and Perspective Taking. Perceived navigation ability was assessed using the Santa Barbara Sense of Direction (SBSOD) scale. ResultsNo significant group differences were observed across any objective navigation tasks. However, children with ASD reported significantly lower perceived navigation ability compared to TD peers. ConclusionThese findings suggest a dissociation between perceived and actual navigational ability in ASD. By early adolescence, objective navigation performance appears intact, potentially reflecting sufficient maturation of underlying neural systems or the presence of compensatory mechanisms. The results underscore the importance of incorporating objective, task-based measures when assessing cognitive abilities in autistic populations.

BackgroundHippocampal place cells (PCs) undergo representational drift, i.e., a gradual change in their place fields despite unaltered behavior. While Ca2+ imaging enables long-term tracking of PC populations, distinct PC detection methods have been shown to yield different subpopulations of PCs, with only a few systematic comparisons between methods, especially in open arenas. New MethodWe provide an analysis protocol for one-photon PC data obtained during free foraging in two-dimensional arenas that allows us to compare two widely used PC detection methods, significance of spatial information (SI), and split-half correlation (SHC), and their effect on representational drift. The analysis is demonstrated on previously published Ca2+ data from dorsal CA1 of freely foraging mice, with cells tracked for 10 consecutive days. ResultsBoth criteria, SI and SHC, yielded proportions of approx. 17% PCs with only 40% overlap. SI-identified PCs demonstrated higher stability, higher rate map correlations, and a slower rate of representational drift than SHC-PCs. Comparison with existing methodsPrevious studies comparing SI and SHC PC detection methods in Ca2+ data did not focus on either open field behavior or representational drift. ConclusionOur results indicate that the choice of PC detection method significantly affects the estimate of representational drift in Ca2+ imaging studies.

Visual processing undergoes rapid refinement in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a non-invasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-III). VEP components were characterized by P1 amplitude, latency, and trial-to-trial variability in latency. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both timepoints, showing age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both timepoints was significantly associated with higher cognitive and language scores at 24 months. Variability in visual cortical response timing was the strongest neural correlate of developmental skills in infancy. These findings suggest that temporal variability in early neural responses may reflect adaptive sensory circuit flexibility rather than inefficiency, potentially facilitating experience-dependent tuning of visual pathways. VEPs offer a mechanistic window into how developing sensory systems scaffold individual differences in early developmental trajectories. Research HighlightsO_LITrial-to-trial variability in visual cortical response timing predicts cognitive and language outcomes at 24 months in infants at familial likelihood for autism. C_LIO_LIMean P1 latency did not predict outcomes, suggesting variability is a more sensitive early neural marker than average response timing. C_LIO_LIGreater neural response variability in infancy may reflect adaptive sensory circuit flexibility rather than noise or inefficient processing. C_LIO_LIVEP-based biomarkers provide a scalable mechanistic window into how early sensory processing scaffolds cognitive and language development. C_LI

BackgroundNeurogenic bowel is a major cause of morbidity in patients affected by neural tube defects (NTDs) such as spina bifida, but the underlying reasons for bowel dysfunction are unknown. An absolute requirement for gastrointestinal (GI) motility is the enteric nervous system (ENS) located within the walls of the GI tract. Enteric neurons coalesce into circumferential stripes throughout embryonic and early postnatal development, and this gradual organization of the ENS into enteric neuronal stripes correlates with the emergence of neurogenic GI motility. We hypothesized that NTDs are associated with changes in ENS organization that correlate with specific GI motility defects. MethodsWe used prenatal valproic acid (VPA) exposure as a model for NTDs in embryonic mice. We used immunohistochemistry, high resolution confocal imaging, and ex vivo motility assays to assess enteric neuronal stripes and gastrointestinal motility in embryos with a VPA-induced neural tube defect. Key resultsGI tracts from embryos with a VPA-induced NTD contain blood. Structurally, the enteric neuronal stripes are thinner with a narrower interstripe distance, leading to an increased number of stripes. Functionally, GI motility is abnormal, with increased contraction frequency and increased length of contractile segments. Conclusions and inferencesENS organization and GI motility are disrupted in mouse embryos with a VPA-induced NTD. This has important implications for our understanding of neurogenic bowel in central nervous system diseases such as spina bifida. Key Points- VPA exposure is a reliable model of neural tube defects with variable intralitter susceptibility - Embryos with a VPA-induced neural tube defect have blood in the amniotic sac and within the lumen of the gastrointestinal tract - Enteric nervous system organization is abnormal in the duodenum and jejunum of embryos with a VPA-induced neural tube defect, with thinner enteric neuronal stripes and narrower interstripe distance - Ex vivo gastrointestinal motility is abnormal in the duodenum and jejunum of embryos with a VPA-induced neural tube defect, including increased contraction frequency and increased length of the contractile segment

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are influenced by both genetic abnormalities and environmental toxicants. Among environmental risk factors, endocrine-disrupting chemicals such as bisphenol A (BPA) and pharmaceutical drugs such as valproic acid (VPA) have been associated with an increased risk of autism. In this study, human induced pluripotent stem cell (iPSC)-derived forebrain organoids were used to model early neurodevelopmental disruptions induced by BPA and VPA exposure. On day 62 of differentiation, forebrain organoids were treated with physiologically relevant concentrations of BPA or VPA for 28 days. Following treatment, morphological, molecular, and electrophysiological changes were assessed across experimental conditions. Both compounds produced distinct alterations in organoid morphology, neurodevelopmental gene expression, and network electrical activity, with VPA inducing markedly stronger effects. Overall, these data suggest forebrain organoids as a robust, physiologically relevant in vitro model system for studying neurodevelopment. This platform enables systematic investigation of environmental and pharmacological risk factors implicated in the pathogenesis of neurodevelopmental disorders.

BackgroundEnriched environments support neurodevelopment. The pathways linking enrichment to cognitive processes such as episodic memory among youth remain unclear. This study examined whether brain function and structure in episodic memory-implicated neurocircuitry mediate the relationship between neighborhood enrichment and episodic memory performance. MethodsWe analyzed data from the Adolescent Brain Cognitive Development Study (n = 9,028) at two timepoints (baseline: 9-11-years-old and two-year follow-up: 11-13-years-old). Neighborhood enrichment was estimated at the childs primary residential address proxied by the Child Opportunity Index 2.0 (COI). Episodic memory was assessed using the Picture Sequence Memory Test (PSMT). A multimodal neuroimaging approach examined task-based working memory-related functional activity, brain volume, and resting-state intrinsic activity in 26 bilateral brain regions, segmented using the Desikan-Killiany atlas, implicated in episodic memory. Following FDR-corrected linear mixed effects models, controlling for sociodemographic, neuroimaging factors, and site-related variability, two sets of mediation analyses were conducted per time point. ResultsGreater neighborhood enrichment (i.e., higher COI scores) was directly associated with better episodic memory, prefrontal cortex (PFC) task-based functional activity, and larger PFC and medial temporal lobe volume across timepoints. PFC task-based functional activity, but not brain volume or intrinsic activity, partially mediated these relationships. Specifically, PFC task-activity in the left and right caudal and rostral middle frontal gyri, and left pars opercularis, accounted for [~]2-7% of the mediated effect. ConclusionOur findings contribute to a rapidly growing body of literature linking environmental influences on neurocognitive outcomes during development. Given childhood and adolescence represent sensitive periods for neurodevelopment, interventions aimed at increasing neighborhood access to enriching experiences such as educational opportunities, cognitively stimulating activities, and social support may have lasting benefits for neurocognitive development.

BackgroundAlpha oscillations are dominant rhythms in the human brain, supporting inhibitory control and coordination of neural activity. Altered alpha dynamics are observed across many neuropsychiatric and neurodevelopmental disorders, including Fragile X syndrome (FXS), the most common monogenic cause of autism and intellectual disability. FXS exhibits paradoxical alpha power: elevated absolute but reduced relative power. To resolve this incongruity, we considered that conventional power metrics, relying on averaging, may obscure the underlying critical temporal dynamics of such neural rhythms. MethodsHere, we investigate alpha oscillations in FXS as a model to decompose nonspecific alpha abnormalities into underlying temporal features. We used cycle-by-cycle (bycycle) alpha burst analysis from source-localized resting-state EEG of 70 individuals with FXS (20.5{+/-}10.0 years; 32 females, 38 males) and 71 age- and sex-matched typically developing controls (22.2{+/-}10.7 years; 30 females, 41 males). Statistical modeling examined group, sex, and regional differences in alpha burst features using generalized linear mixed-effects models. ResultsWe reveal that alpha bursts in FXS show reduced count only in males, prolonged periods across sexes, and elevated amplitudes, particularly in males. Spatial mapping identified differential circuit vulnerability: timing-associated dysregulation in cognitive-control regions and amplitude elevations in sensory cortices. Within the FXS group, global alpha burst amplitude correlated with hyperactivity symptoms and inversely with general intelligence scores, and burst count correlated with age. LimitationsThis study is limited by its resting-state design and cross-sectional nature. Future studies should explore task-based modulation of alpha burst features and longitudinal trajectories in FXS. Additionally, fragile X messenger ribonucleoprotein (FMRP) was not quantified for participants, limiting potential stratification by molecular severity. ConclusionsThese findings resolve paradoxical alpha power in FXS into features consistent with interneuron dysfunction, demonstrating the potential for burst-level decomposition in mechanistic hypothesis generation and biomarker development across neurodevelopmental and neuropsychiatric disorders.

ContextGrid cells in the medial entorhinal cortex (MEC) of head-fixed mice exhibit ultraslow (<0.01 Hz) oscillations (USO) during walking in a 1D running wheel in darkness. It was proposed that these oscillations may have a connection with navigational behavior. ProblemThere is no clear link between the functional role of these oscillations and path integration, a fundamental navigation strategy used by animals to calculate their current position and orientation by continuously summing self-motion cues. HypothesisGiven the synaptic projections from MEC to the hippocampus, we hypothesized that ultraslow oscillations have a role in linking spatiotemporal memories acquired during navigation. MethodologyA realistic computational model of entorhinal-grid with ultraslow oscillations and hippocampal-place cells is proposed using synaptic plasticity between cell types, sustaining path integration of a rodent-like simulated animal. ResultsUltraslow oscillations induced persistent changes in the grid cell dynamics, represented as a positional drift of grid fields. Such drift resulted in position estimation errors but generated new grid-place cell associations when combined with synaptic plasticity. >DiscussionsUltraslow entorhinal oscillations were found to shape spatial memory through grid cell drifting, which could serve as a mechanism for flexibly accessing different spatial memories during navigation. HIGHLIGHTSO_LIPath integration dynamics hide ultraslow oscillations despite coexistence. C_LIO_LIUltraslow oscillations significantly degrade position estimation in path integration. C_LIO_LIGrid and place fields drift after the effect of ultraslow oscillations. C_LIO_LINew spatial memories were created as a result of the ultraslow oscillation drift. C_LIO_LIUltraslow oscillations enable dynamic access of different spatial memories C_LI

Neural information flow describes the movement of activity between neurons or brain areas. Advances in experimental methods have allowed production of large amounts of observational data related to neuronal activity from the single-neuron to population level. Most current methods for analysing these data are based on pairwise comparison of activity, and fall short of reliably extracting neural information flow network structure. Dynamic Bayesian networks may overcome some of these limitations. Here we evaluate the performance of a range of Bayesian network scoring metrics against the performance of multivariate Granger causality and LASSO regression for their ability to learn the connectivity underlying simulated single-neuron and neuronal population data. We find that discrete dynamic Bayesian networks are the best performing method for single-neuron data, and perform consistently for neural-population data. Continuous dynamic Bayesian networks have a tenancy to learn overly dense structures for both data types, but may have utility in scoping studies on single-neuron data. Multivariate Granger causality is the most robust method for learning structure of neural information flow between neural-populations, but performs poorly on single-neuron data. Significance testing within multivariate Granger causality produces variable results between data types. Overall, this work highlights how the analysis of neural information flow can vary depending on they type and structure of underlying data, and promotes discrete dynamic Bayesian networks as a useful and consistent tool for neural information flow analysis.

BackgroundAutistic individuals experience higher rates of sleep problems throughout their lives, and there is considerable heterogeneity in manifestations of these issues that remains unexplained. Here, we examine associations over time of heterogenous sleep trajectories with autism diagnosis, and behavioural and genetic factors related to autism. MethodWe used data from the Avon Longitudinal Study of Parents and Children (N=13,886, autistic n=150). The primary outcome was parent and self-reported night-time sleep duration, measured on 10 occasions (between 0.5y and 15.5y). The independent variables were autism diagnosis, autism polygenic score (PGS) and four parent-reported autistic traits: repetitive behaviour, social communication, speech coherence, and sociability. Latent class growth analysis was conducted to identify heterogenous classes of sleep trajectories, and these trajectory classes were regressed onto the independent variables. ResultsFour night-time sleep duration trajectory subclasses were identified; shorter (n=512, 4.1%), longer (n=1654, 13.1%), intermediate-shorter (n=3630, 28.8%), and intermediate-longer (used as the reference class; n=6825, 54.1%). An autism diagnosis was associated with a shorter or intermediate-shorter sleep duration trajectory, compared to the reference class. Similarly, higher scores in domains of repetitive behaviour, speech coherence and social communication were associated with shorter sleep duration trajectories. The autism PGS and sociability were not associated with any sleep trajectories compared to the intermediate-longer sleep trajectory (reference group). ConclusionAn autism diagnosis and specific autistic traits were associated with poorer long-term sleep outcomes across childhood and adolescence, highlighting the need for early, sustained sleep interventions, and the potential of trait-specific mechanisms for sleep problems. HighlightsO_LIFour distinct night-time sleep duration trajectories were identified across development C_LIO_LIAutism diagnosis predicted shorter and intermediate-shorter sleep trajectories C_LIO_LISpecific (but not all) autistic traits were linked to shorter sleep trajectories C_LIO_LIAutism PGS did not predict sleep duration trajectories C_LI

Astyanax mexicanus consists of eyed, river-dwelling "surface" fish, and multiple, independently evolved cave populations, which have converged on troglobitic traits such as eye loss and reduced metabolism. However, considerably less is known about constructive adaptations, which include a larger olfactory epithelium in cavefish. It is unknown how this relates to the olfactory bulb (OB), which is the first stage of olfactory sensory processing in the brain. The goal of the present study is to begin to define the structure and functional organization of the OB in A. mexicanus, and to begin to understand how it was transformed via cave adaptation. We addressed these questions using whole-mount immunohistochemistry and in vivo Ca2+ imaging from the OB of developmentally matched surface and Pachon cavefish. The cavefish OB was significantly larger than surface fish by 14 days post fertilization (dpf), which was accompanied by a broad and proportional increase in synaptic input to most glomerular regions. Increases in the size of the OB were accompanied by increases in the number of neurons expressing tyrosine hydroxylase and calretinin, the latter of which occurred primarily in the medial OB and could not be explained as a compensatory response to a larger OB. In vivo Ca2+ imaging from the dorsal OB of surface and cavefish in response to a panel of chemical stimuli revealed odor-evoked responses that were spatially organized and highly conserved across the two populations. Surprisingly, the medial OB was consistently activated by any change in water flow in both populations, although the number of water-responsive neurons was significantly greater in cavefish when measurements were performed using either in vivo imaging or the neuronal activity marker phospho-ERK. Water-responding neurons were similarly present in the olfactory epithelium in both populations, along with neurons expressing the mechanosensitive ion channel Piezo2, with significantly more Piezo2-expressing neurons present in cavefish. Therefore, cavefish exhibit enhanced multisensory integration of olfactory and mechanosensory input in the earliest stage of olfactory sensory processing in the brain.

Noise pollution is an increasing threat to soniferous fishes, however, research on noise pollution impacts is limited to few species and rarely studied in situ. Red Drum (Sciaenops ocellatus) is an estuarine, fishery species that choruses during spawning. We tested predictions of the hypothesis that Red Drum alter sound production in response to vessel noise. We used passive acoustic monitoring in 2021 and 2022 at an estuarine inlet and Generalized Least Squares (GLS) models to assess vessel sound exposure levels over time (SEL) and other abiotic parameters on Red Drum chorus SELs. GLS models of daily crepuscular choruses indicated a >5% reduction in proportion to crepuscular vessel noise in 2021. GLS models testing influence of abiotic variables and prior vessel noise, predicted reduced chorus SELs proportional to prior noise SEL: ca. 5% and 3% of vessel SEL in 2021 and 2022, respectively. In some instances, SEL during vessel noise was lower than fish chorus SEL immediately prior, indicating instances when fish reduced chorus amplitude during vessel noise or fled the immediate area. In cases when SEL of vessel noise periods exceeded fish calling SEL immediately prior, it is not known if fish modulated calling amplitude because the portion of combined vessel noise and fish chorus amplitude from vessels is unknown. In peak spawning season (September-October) vessel noise was frequent, detected in >31% of recordings in both years and up to 100% of recordings on some dates. Observations of disrupted choruses and high vessel noise prevalence suggest spawning behavior may be impacted by abundant vessel noise.

Atypical sensory experiences are highly prevalent in autistic children and include both hyper- and hypo-responsivity, often accompanied by sensory overload. Alpha oscillations (7-13 Hz), which dynamically regulate cortical excitability, represent a plausible neural mechanism underlying these phenomena: reduced alpha activity is associated with enhanced sensory responsiveness, whereas increased alpha supports suppression of external input. Although decreased alpha power has been repeatedly reported in autism, it remains unclear whether this reduction reflects lower oscillatory amplitude or reduced temporal stability of alpha rhythms, two mechanisms with distinct neurophysiological implications. To better characterize alpha activity in autism, we examined resting-state alpha dynamics in non-autistic children (NA; n = 39), autistic children (AU; n = 52), and siblings of autistic children (SIB; n = 26), aged 8-14 years. We combined traditional broadband measures of relative alpha power, parametric separation of periodic and aperiodic activity, and single-event analyses that quantify the temporal structure of alpha oscillations. Both broadband relative alpha power and periodic alpha power were reduced in autism over parietal regions, replicating prior findings. Importantly, ordinal analyses revealed an intermediate profile in siblings, supporting a liability-related gradient of alpha alterations. However, single-event analyses demonstrated that the average amplitude of individual alpha bursts did not differ between groups. Instead, autistic children showed significantly shorter alpha burst duration and reduced alpha abundance (i.e., proportion of time occupied by rhythmic alpha episodes), with siblings again exhibiting intermediate values. Linear regression analyses confirmed that reductions in relative and periodic alpha power were primarily driven by decreased alpha abundance rather than diminished burst amplitude. These findings indicate that altered alpha activity in autism reflects reduced temporal stability and density of alpha events rather than weaker oscillatory amplitude per se. Reduced persistence of alpha rhythms may therefore represent a neural marker of altered cortical excitability and sensory regulation in autism. Lay summaryAutistic children often experience the world differently at the sensory level, including being more easily overwhelmed by sounds, lights, or other stimuli. In this study, we looked at a type of brain activity called alpha rhythms, which help regulate how strongly the brain responds to incoming information. We found that, in autistic children, these alpha rhythms were not weaker when they occurred, but they lasted for a shorter time and happened less often. Siblings of autistic children showed an intermediate pattern. These results suggest that sensory differences in autism may be linked to less stable brain rhythms that normally help control sensory input. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/716324v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1be733dorg.highwire.dtl.DTLVardef@7fea49org.highwire.dtl.DTLVardef@1ee9124org.highwire.dtl.DTLVardef@17af139_HPS_FORMAT_FIGEXP M_FIG C_FIG

Fragile X Syndrome (FXS) is a leading genetic cause of autism spectrum disorder (ASD) and results from a genetic mutation which silences the expression of Fragile X Messenger Ribonucleoprotein (FMRP). FMRP serves various roles regulating cellular protein synthesis and ion flux. However, a comprehensive comparison of multidimensional elemental balance (i.e., ionome) between FXS genotypes and tissues remains absent from the literature. Here, we measured the multivariate balance of 10 elements (i.e., ionome) in tissues of wild-type and Fmr1-knockout mice to compare ionomic composition of brain and somatic tissues within and across genotypes. We found that homogenized brain tissue including several regions (brain PMHTH; define at first use) differed in elemental balance between genotypes, according to MANOVA. We failed to observe differences between genotypes in the mean ratio of any individual element in PMHTH, but sodium displayed lower variance in knockout than wild-type PMHTH. Knockout striatum displayed lower variance in potassium than wild-type. Knockout olfactory bulbs contained higher mean iron and displayed higher variance in sodium and copper than wild-type. Wild-type feces contained higher mean magnesium and zinc than knockout. These results align with previous work showing FXS pathologies alter electrolytic and metal ion regulation, neuronal excitability, and gastrointestinal function. Further work is needed to identify the source of overall ionomic differences in heterogeneous brain tissue (PMHTH), which could be due to differences among regions. Future work should additionally test how elemental differences relate to function at the cellular level, as well as patterns of individual intake, digestion, assimilation, and/or excretion.

The early development of the prefrontal cortex is crucial for higher cognitive functions. However, current research presents inconsistent findings regarding whether intra-prefrontal connectivity increases or decreases in infants younger than six months. Do dynamic changes in connection strength across different states over time carry information about prefrontal maturation? This study used functional near-infrared spectroscopy (fNIRS) to record prefrontal brain activity in 48 healthy infants aged 1-8 months during natural sleep and auditory stimulation. By analyzing the fluctuations in frequency-domain characteristics of functional connectivity (FC) and various brain network properties, we found that: under auditory stimulation, the intensity of FC fluctuations in the ultra-low frequency range was positively correlated with age; while in the resting state, the fluctuation intensity of network properties in relatively higher frequency bands decreased with age. Furthermore, auditory stimulation reconfigured the energy distribution of network fluctuations, shifting it towards higher frequency bands. These results suggest that the early development of the infant prefrontal internal network is characterized by state-dependent optimization of its dynamic fluctuation properties, shedding light on the developmental tuning of functional network dynamics in infancy.

Identifying the location of a sound source in a complex environment and assessing its importance can be crucial for survival. The superior colliculus (SC), a midbrain structure involved in sensorimotor functions, contributes to sound localization and contains auditory responsive neurons that have spatially restricted receptive fields (RFs) that are organized into a topographic map along the azimuth. However, individual auditory SC neurons have large spatial RFs, are noisy, and do not respond to the same stimulus at each trial. Therefore, when an animal is presented with a "single trial" sound, and it needs to rely on a single neuron to locate the sound source direction, the location measurement may be erroneous, missing, or have poor spatial resolution. It is expected that a more reliable and accurate determination of the sound source location will come from a population of neurons. We therefore built a population pattern Maximum Likelihood Estimation (MLE) decoder to build a model that can accurately predict the location of a stimulus given the population response. We compared three models that use either strict firing rate (FR), weighting based on equal (EW) or mutual information (MIW) and show that the MIW model works best, needing only 92 neurons to localize a stimulus with behaviorally relevant precision. Furthermore, by comparing the models fit using the responses from non-RF and RF auditory neurons, we show that only RF neurons contain the information needed to localize a sound source. These results are consistent with the hypothesis that the SC uses a population of RF neurons to determine sound source location. Author SummaryBeing able to tell where a sound is coming from and how important it is can be critical for survival. The superior colliculus, a midbrain region involved in orienting behaviors, contains neurons that respond best to sounds coming from specific locations. This suggests that the combined activity of many neurons in the SC is used to determine sound location from a single sound event. To test this idea, we modeled responses from mouse SC neurons while sounds were played from different positions in space, both along the elevation and horizon. A model that weighted the most informative neurons performed best in both directions needing only 92 neurons to localize a stimulus with behaviorally relevant precision along the azimuth. Comparing the models fit using the responses from non-RF and RF auditory neurons, we show that only RF neurons contain the information needed to localize a sound source Overall, our findings show that the SC can accurately locate sounds in both horizontal and vertical space using a population-based strategy, providing a simple and effective solution for rapid sound localization.

Background Angelman syndrome (AS) is a rare neurodevelopmental disorder with characteristic electroencephalographic abnormalities caused by loss of function of the maternally inherited UBE3A gene. Converging evidence suggests a disrupted excitation-inhibition (E/I) balance towards hyperexcitability. However, noninvasive approaches capable of characterizing intrinsic cortical excitability and its relationship with large-scale brain dynamics in AS are still lacking. We used resting-state electroencephalography (EEG) to derive cortical excitability, testing the hypothesis that altered local E/I balance in AS is associated with instability of large-scale functional brain networks. Methods We recorded 7 minutes of task-free high-density EEG in 29 individuals with AS and 36 typically developing controls. Source-reconstructed cortical activity was used to compute the excitability index (EI), based on mean spatial phase synchronization in the gamma band. Dynamic functional connectivity was computed and summarized as fluidity index, which estimates temporal variability of network configurations. We assessed group differences and associations between EEG features, clinical variables and caregiver-reported questionnaires. Results AS participants showed increased EI in anterior cingulate, dorsolateral prefrontal, temporoparietal, and occipital regions. Fluidity was larger in AS across frequency bands, indicating greater network instability. EI positively predicted fluidity in widespread regions in AS, whereas the opposite pattern was observed in controls. Higher EI correlated with fewer antiseizure medications and with greater sensory-seeking behavior. Conclusions AS is characterized by cortical hyperexcitability coupled with unstable large-scale network dynamics. The EI provides a biologically meaningful marker linking intrinsic E/I imbalance to behavioral features and treatment-related variables