Sleep problems are common in Autism Spectrum Disorder (ASD), affecting up to 80% of this population. Previous studies have shown associations between sensory hypersensitivity and sleep disturbances in ASD but the potential mechanisms underlying this link are not well defined. Our study tests the hypothesis that altered auditory cortex excitation/inhibition (E/I) balance can explain sleep disturbances in children with ASD. Typically developing (TD) children and those with ASD were enrolled in a multi-modal neuroimaging study assessing sleep and neurobehavior. The Hurst Exponent was derived from functional magnetic resonance imaging (fMRI; 12 minutes, TR=1125ms) as a proxy of E/I ratio for the bilateral primary auditory cortex. Sleep quality was assessed using actigraphy in the two weeks preceding the MRI scan. ANCOVA was used to analyze relationships between sleep measures and Hurst exponent, controlling for fMRI quality (in-scanner motion) and age. The results are preliminary as enrollment is ongoing. Data from 42 participants was included (TD n=25, ASD n=17; 6-11 years, mean=8, SD=1.7). The ASD and TD groups did not significantly differ on age, sex, actigraphy adherence (mean=11±2.8 days) or fMRI quality. Compared to TD participants, actigraphy in children with ASD showed increased sleep onset latency, decreased total sleep time and decreased sleep efficiency (all p< 0.05). The Hurst Exponent was lower in ASD participants, in comparison to TD children, in both left and right auditory cortices (p< 0.05), suggestive of increased excitability. Lower Hurst Exponent in right auditory cortex was associated with lower sleep efficiency (p< 0.05) and increased wake after sleep onset (WASO, p=0.051), in all children, independent of their diagnosis. A similar trend was observed in the left auditory cortex in association with sleep efficiency (p=0.054). Using objective measures, our data shows correlation between altered excitability of auditory cortex with sleep efficiency and WASO. While this relationship appears to be independent of an ASD diagnosis, we note that children with ASD are disproportionately affected by hypersensitivity to sounds. Our results suggest that this may contribute to disrupted sleep in children with autism. DOD W81XWH-22-1-0220, NIH R01MH107802

Symptoms of attention-deficit/hyperactivity disorder (ADHD) are common in children with autism spectrum disorder (ASD), and are associated with greater developmental challenges, poorer clinical outcomes, and alterations in functional connectivity (FC) of the brain. However, despite the consensus that ASD and other neurodevelopmental conditions emerge early in life, little is known about the trajectories of brain and behavioral development during the first years of life in children with ASD and co-occurring attention problems (AP). In a sample of 122 young children (ages 1.5–5 years) with and without ASD, we examined whether toddlers and preschoolers with ASD and co-occurring AP already differ from peers with ASD without co-occurring AP on adaptive and developmental skills, ASD symptoms, and FC of the frontoparietal and salience networks, which have been previously linked to ADHD symptoms in older children with ASD and ADHD. Results of general linear model analyses revealed lower developmental and adaptive skills across multiple domains in children with ASD and elevated AP compared with their peers with lower AP, despite equivalent levels of ASD symptoms. Further, children with ASD and elevated AP showed reduced FC within the frontoparietal network (p = .027), between the frontoparietal and language networks (p = .004), and the frontoparietal and default mode networks (p = .046) in comparison to their peers with lower AP. No group differences in FC of the salience network were observed (all p > .05). These findings provide evidence that neurodevelopmental and behavioral differences in children with ASD and co-occurring AP emerge very early in life, before a reliable diagnosis of ADHD is typically made. Specifically, these results demonstrate that early inattention symptoms are associated with unique connectivity patterns in executive circuitry as early as the first years of life in toddlers and preschoolers with ASD, likely contributing to the phenotypic and neural heterogeneity recognized in autism. Thus, our results underscore the importance of considering co-occurring conditions early in developmental research and clinical care, as further understanding these trajectories can inform early interventions during the critical time period when they have the greatest potential for positive impact.

Sleep disturbances affect up to 80% of children with autism spectrum disorder (ASD). Previous studies have used either subjective surveys and/or objective data (actigraphy) to characterize sleep disturbances. In this study, we aim to elucidate the congruence between subjective and objective measures of sleep in ASD. Children aged 6-11 years were enrolled in an ongoing study to assess sleep and neurobehavior. Sleep was assessed objectively using actigraphy and subjectively using a 2-week sleep diary and the Children’s Sleep Habits Questionnaire (CHSQ). The primary outcomes of interest were total sleep time (TST) and number of awakenings (NOA). Data from 24 typically developed children (TD) (age:8±1.7 years) and 16 with ASD (8.7±1.6 years) were included. Actigraphy was well tolerated, with no difference in days collected (ASD:11.7±2.4 days; TD:11.1±3.0, p=0.492). Actigraphy revealed that children with ASD had reduced TST (478 vs 503 minutes, p=0.027) but no significant difference in NOA. CSHQ showed no significant difference in NOA but did show differences among groups in reported TST (ASD:551 vs TD:598 minutes, p=0.044) and total CSHQ scores (ASD:49 vs TD:39, p< 0.001), with higher scores indicating greater sleep disturbances in children with ASD. Subjective reporting from sleep diary showed no differences between groups in TST or average NOA. In children with ASD, actigraphy measured TST correlated weakly with CSHQ data (r=0.496, p=0.051) and did not correlate with sleep diary (r=0.334, p=0.206) data. For NOA, actigraphy showed no correlation with either sleep diary (r=–0.063, p=0.816) or CSHQ (r=–0.368, p=0.178) data. Interestingly, in TD participants, there was a strong correlation between actigraphy TST and TST reported on sleep diary data (r=0.524, p=0.010). Objective measures like actigraphy effectively differentiated TST patterns between children with ASD and TD, aligning with differences observed in total CSHQ scores. However, among children with ASD, we found limited agreement between CSHQ, sleep diaries and actigraphy in estimating TST and NOA. These findings highlight the importance of incorporating both subjective and objective measures for a comprehensive assessment of sleep in autism. DOD-W81XWH-22-1-0220, NIH-R01MH107802

BACKGROUND: Atypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorder (ASD). E/I ratio can be estimated from resting-state functional magnetic resonance imaging (fMRI) using the Hurst exponent, H. A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), the vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in individuals with autism. METHODS: The current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity and emotional control in toddlers and preschoolers with ASD. A total of 83 children (45 with ASD), ages 1.5-5 years, underwent natural sleep fMRI as part of a longitudinal study. RESULTS: In a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired 2 years apart on average. Lower vmPFC H was also associated with reduced functional connectivity within the DMN as well as with higher emotional control deficits (although only significant transdiagnostically). CONCLUSIONS: These results suggest an early onset of E/I imbalances in the vmPFC in ASD, with likely consequences for the maturation of the DMN.

AbstractIntroductionIn vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age‐related trajectories differ between middle aged to older adults with ASD and age‐matched typical comparison participants.MethodsData from 30 individuals with ASD and 36 age‐matched typical comparison participants aged 40–70 years were analyzed. Given substantial heterogeneity in both etiology and outcomes in ASD, we utilized both group‐level and subject‐level analysis approaches to test for signs of atypical intracortical MC as estimated by T1w/T2w ratio.ResultsGroup‐level analyses showed no significant differences in average T1w/T2w ratio or its associations with age between groups, but revealed significant positive main effects of age bilaterally, with T1w/T2w ratio increasing with age across much of the cortex. In subject‐level analyses, participants were classified into subgroups based on presence or absence of clusters of aberrant T1w/T2w ratio, and lower neuropsychological function was observed in the ASD subgroup with atypically high T1w/T2w ratio in spatially heterogeneous cortical regions. These differences were observed across several neuropsychological domains, including overall intellectual functioning, processing speed, and aspects of executive function.ConclusionsThe group‐level and subject‐level approaches employed here demonstrate the value of examining inter‐individual variability and provide important preliminary insights into relationships between brain structure and cognition in the second half of the lifespan in ASD, suggesting shared factors contributing to atypical intracortical myelin content and poorer cognitive outcomes for a subset of middle aged to older autistic adults. These atypicalities likely reflect diverse histories of neurodevelopmental deficits, and possible compensatory changes, compounded by processes of aging, and may serve as useful markers of vulnerability to further cognitive decline in older adults with ASD.

Background Atypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorders (ASD). E/I ratio can be estimated from resting state functional magnetic resonance imaging (fMRI) using the Hurst Exponent (H). A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in autistic individuals. Methods The current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity (FC) and emotional control in toddlers and preschoolers with ASD. 83 children (n=45 ASD), ages 1½ - 5 years, underwent natural sleep fMRI as part of a longitudinal study. Results In a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired two years apart on average. Lower vmPFC H was further associated with reduced FC within the DMN as well as with higher emotional control deficits (though only significant transdiagnostically). Conclusions These results suggest an early onset of E/I imbalances in vmPFC in ASD with likely consequences for the maturation of the DMN.

Middle-aged and older adults with autism spectrum disorder may be susceptible to accelerated neurobiological changes in striato- and thalamo-cortical tracts due to combined effects of typical aging and existing disparities present from early neurodevelopment. Using magnetic resonance imaging, we employed diffusion-weighted imaging and automated tract-segmentation to explore striato- and thalamo-cortical tract microstructure and volume differences between autistic (n = 29) and typical comparison (n = 33) adults (40 to 70 years old). Fractional anisotropy, mean diffusivity, and tract volumes were measured for 14 striato-cortical and 12 thalamo-cortical tract bundles. Data were examined using linear regressions for group by age effects and group plus age effects, and false discovery rate correction was applied. Following false discovery rate correction, volumes of thalamocortical tracts to premotor, pericentral, and parietal regions were significantly reduced in autism spectrum disorder compared to thalamo-cortical groups, but no group by age interactions were found. Uncorrected results suggested additional main effects of group and age might be present for both tract volume and mean diffusivity across multiple subcortico-cortical tracts. Results indicate parallel rather than accelerated changes during adulthood in striato-cortical and thalamo-cortical tract volume and microstructure in those with autism spectrum disorder relative to thalamo-cortical peers though thalamo-cortical tract volume effects are the most reliable.

While disruptions in brain maturation in the first years of life in ASD are well documented, little is known about how the brain structure and function are related in young children with ASD compared to typically developing peers. We applied a multivariate pattern analysis to examine the covariation patterns between brain morphometry and local brain spontaneous activity in 38 toddlers and preschoolers with ASD and 31 typically developing children using T1-weighted structural MRI and resting-state fMRI data acquired during natural sleep. The results revealed significantly reduced brain structure-function correlations in ASD. The resultant brain structure and function composite indices were associated with age among typically developing children, but not among those with ASD, suggesting mistiming of typical brain maturational trajectories early in life in autism. Additionally, the brain function composite indices were associated with the overall developmental and adaptive behavior skills in the ASD group, highlighting the neurodevelopmental significance of early local brain activity in autism.

Projections between the thalamus and sensory cortices are established early in development and play an important role in sleep regulation as well as in relaying sensory information to cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorders (ASD) might therefore be linked to sensory and sleep problems common in ASD. Here we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep fMRI, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5 to 5-year-olds) with ASD compared to a matched group of 46 typically developing (TD) children. In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high quality MRI data (n=29). Additionally, auditory cortex BOLD signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep. These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.

Accumulation of iron in the striatum is observed in aging and is thought to contribute to cognitive deficits and reduced motor function. In adults with ASD, increased frequency of motor impairments and parkinsonism have been reported. However, the cause of potentially accelerated decline in motor function with age is unknown. Here we assessed iron levels in striatal nuclei in middle-aged and older adults with ASD and its association with motor skills.

Co-occurring neurodevelopmental disorders (NDDs) are common in children with autism spectrum disorders (ASD), with attention-deficit/hyperactivity disorder (ADHD) or subthreshold symptoms present in the majority of children with ASD. Co-occurring NDDs pose serious challenges for the differential diagnosis of ASD (delaying its detection), are associated with greater impairments and worse outcomes than autism alone, and impede response to interventions. Despite the consensus that ASD and most other NDDs emerge early in life, little is known about the trajectories of brain and behavioral development during the first years of life in children with ASD and co-occurring NDDs. The current study aimed to examine brain functional connectivity in young children with ASD with and without co-occurring ADHD symptoms.

Objective:Concerns that exposure to more than one language in the home might negatively impact language development in young children with autism spectrum disorder (ASD) are common among caregivers. Although research directly examining the impact of a multilingual home environment in ASD is scarce, emerging evidence shows that language outcomes might be equivalent or better in children with ASD exposed to more than one language (Romero & Uddin, 2021). However, no evidence to date exists on whether exposure to more than one language affects early brain functional development in children with ASD. The current study aims to examine the (1) cross-sectional and (2) longitudinal associations between home language environment (exposure to one v. multiple languages at home, H1l vs. H>1l) and receptive and expressive language skills in young children with and without ASD, and (3) to investigate links between home language environment and brain functional network organization.Participants and Methods:Participants included young children with ASD (n=67, mean age: 35±13 months, H>1l n=43) and typically developing (TD) children (n=39, mean age: 32±16 months, H>1l n=17) enrolled in a longitudinal study of early brain markers of autism. A subset of children with ASD for whom longitudinal behavioral data from two study visits were available (n=21, H>1l n=11) were used for exploratory analysis. Receptive language (RL) and expressive language (EL) skills were assessed by the Mullen Scales of Early Learning at each study visit. Data from 42 children with ASD (H>1l n=27) and 38 TD children (H>1l n= 15) for whom functional MRI data were acquired during natural sleep were included in functional connectivity (FC) analysis. ANCOVAs were employed to examine the effect of diagnosis, home language environment (H1l vs. H>1l) and its interaction on RL and EL skills while controlling for socioeconomic variables (i.e., maternal education level, income-to-needs ratio) and gestational age at birth. Linear mixed models were applied to explore the longitudinal effect of home language environment on RL and EL skills across two study visits in the ASD group. Lastly, FC analysis was conducted to compare functional connectivity across 7 canonical brain networks in children with and without ASD who were raised in H1l and H>1l.Results:We found significant diagnosis by home language environment interaction effect on EL skills, with children with ASD and H1l exhibiting the lowest EL skills. Longitudinal analysis identified a significant home language environment by study visit interaction effect on EL skills in children with ASD. Specifically, children with ASD and H1l showed lower EL skills at study visit 1 but equivalent EL skills at study visit 2 compared to children with ASD and H>1l. FC analysis revealed that children with ASD and H>1l displayed more typical brain network organization (similar to TD children) compared to those with H1l, specifically for FC between language, frontoparietal, and default mode networks.Conclusions:These results suggest that early exposure to more than one language in the home may be linked with better expressive language skills in young children with ASD. Results of functional connectivity analysis also suggest that exposure to more than one language may be associated with more neurotypical functional network organization, particularly involving language and high-order networks.

Parents of children diagnosed with autism spectrum disorder (ASD) report higher levels of stress than parents of typically developing children. Few studies have examined factors associated with parental stress in early childhood. Even fewer have investigated the simultaneous influence of sociodemographic, clinical, and developmental variables on parental stress. We examined factors associated with stress in parents of young children with ASD. Multiple regression models were used to test for associations between socioeconomic indices, developmental measures, and parental stress. Externalizing behaviors, communication, and socialization skills accounted for variance in parental stress, controlling for ASD diagnosis. Results highlight the importance of interventions aimed at reducing externalizing behaviors in young children as well as addressing stress in caregivers of children with ASD.

Intracortical myelin is thought to play a significant role in the development of neural circuits and functional networks, with consistent evidence of atypical network connectivity in children with autism spectrum disorder (ASD). However, little is known about the development of intracortical myelin in the first years of life in ASD, during the critical neurodevelopmental period when autism symptoms first emerge. Using T1‐weighted (T1w) and T2w structural magnetic resonance imaging (MRI) in 21 young children with ASD and 16 typically developing (TD) children, ages 1.5–5.5 years, we demonstrate the feasibility of estimating intracortical myelin in vivo using the T1w/T2w ratio as a proxy. The resultant T1w/T2w maps were largely comparable with those reported in prior T1w/T2w studies in TD children and adults, and revealed no group differences between TD children and those with ASD. However, differential associations between T1w/T2w and age were identified in several early myelinated regions (e.g., visual, posterior cingulate, precuneus cortices) in the ASD and TD groups, with age‐related increase in estimated myelin content across the toddler and preschool years detected in TD children, but not in children with ASD. The atypical age‐related effects in intracortical myelin, suggesting a disrupted myelination in the first years of life in ASD, may be related to the aberrant brain network connectivity reported in young children with ASD in some of the same cortical regions and circuits.

Symptoms of autism spectrum disorder (ASD) emerge in the first years of life. Yet, little is known about the organization and development of functional brain networks in ASD proximally to the symptom onset. Further, the relationship between brain network connectivity and emerging ASD symptoms and overall functioning in early childhood is not well understood. Resting-state fMRI data were acquired during natural sleep from 24 young children with ASD and 23 typically developing (TD) children, aged 17–45 months. Intrinsic functional connectivity (iFC) within and between resting-state functional networks was derived with independent component analysis (ICA). Increased iFC between visual and sensorimotor networks was found in young children with ASD compared to TD participants. Within the ASD group, the degree of overconnectivity between visual and sensorimotor networks was associated with greater autism symptoms. Age-related weakening of the visual–auditory between-network connectivity was observed in the ASD but not the TD group. Taken together, these results provide evidence for disrupted functional network maturation and differentiation, particularly involving visual and sensorimotor networks, during the first years of life in ASD. The observed pattern of greater visual–sensorimotor between-network connectivity associated with poorer clinical outcomes suggests that disruptions in multisensory brain circuitry may play a critical role for early development of behavioral skills and autism symptomatology in young children with ASD.

It is now established that socioeconomic variables are associated with cognitive, academic achievement, and psychiatric outcomes. Recent years have shown the advance in our understanding of how socioeconomic status (SES) relates to brain development in the first years of life (ages 0-5 years). However, it remains unknown which neural structures and functions are most sensitive to the environmental experiences associated with SES. Pubmed, PsycInfo, and Google Scholar databases from January 1, 2000, to December 31, 2019, were systematically searched using terms "Neural" OR "Neuroimaging" OR "Brain" OR "Brain development," AND "Socioeconomic" OR "SES" OR "Income" OR "Disadvantage" OR "Education," AND "Early childhood" OR "Early development". Nineteen studies were included in the full review after applying all exclusion criteria. Studies revealed associations between socioeconomic and neural measures and indicated that, in the first years of life, certain neural functions and structures (e.g., those implicated in language and executive function) may be more sensitive to socioeconomic context than others. Findings broadly support the hypothesis that SES associations with neural structure and function operate on a gradient. Socioeconomic status is reflected in neural architecture and function of very young children, as early as shortly after birth, with its effects possibly growing throughout early childhood as a result of postnatal experiences. Although socioeconomic associations with neural measures were relatively consistent across studies, results from this review are not conclusive enough to supply a neural phenotype of low SES. Further work is necessary to understand causal mechanisms underlying SES-brain associations.

Background. Skin infections due to Staphylococcus aureus have recently become a public concern, mainly because of emerging resistance against widely used antibiotics and specific virulence determinants. Strains harboring the lukS-lukF gene (which codes for Panton-Valentine leukocidin) are frequently associated with severe furunculosis. Generally applicable strategies for the control of community outbreaks of furunculosis have not been defined.Methods. We report the investigation and successful termination of an outbreak of furunculosis due to lukS-lukF-positive S. aureus in a German village (n = 144). Nasal swab specimens were obtained from village residents. A retrospective cohort study was conducted. Nasally colonized persons, persons who had current furuncles or who had experienced relapsing furuncles since 2002, and their family members underwent stringent decolonization measures using mupirocin nasal ointment and disinfecting wash solution. Multiple nasal swab specimens were obtained to monitor the long-term outcome of decolonization measures.Results. From January 1998 through December 2004, 42 cases and 59 relapses of furunculosis were identified by active case finding. Of 140 participants tested, 51 (36%) were found to be nasally colonized with S. aureus. In 9 participants, the strain was positive for lukS-lukF. No methicillin resistance was detected. Risk of furunculosis was associated with contact with case patients (relative risk, 6.8; 95% confidence interval, 3.2-14.3) and nasal colonization with a lukS-lukF-positive strain of S. aureus (relative risk, 3.6; 95% confidence interval, 2.3-5.9). Passive surveillance implemented in January 2005 did not detect any case of lukS-lukF-positive, S.aureus-associated furuncles in this village.Conclusion. This report describes a successful strategy for terminating the transmission of epidemic strains of S. aureus among a nonhospitalized population.