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Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as part of the Infant Brain Imaging Study (IBIS) Network and reports interim feasibility and data quality results. We evaluated feasibility by measuring the percentage of infants from whom we successfully collected each EEG paradigm. The quality of task-free data was assessed based on the duration of EEG recordings remaining after artifact removal. Preliminary analyses revealed low data loss, with average in-session loss rates at 4.16 % and quality control loss rates at 11.66 %. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16 %, with high consistency across sites. The insights gained from this preliminary analysis highlight key sources of data attrition and provide practical considerations to guide similar research endeavors.

Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n = 257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n = 158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6–12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In the IBIS sample, children with higher anxiety showed accelerated amygdala growth from 6 to 24 months. ASD diagnosis and ASD familial likelihood were not significant predictors. In the EBDS sample, amygdala growth from birth to 24 months was associated with anxiety. More anxious children had smaller amygdala volume and slower rates of amygdala growth. We explore reasons for the contrasting results between high-familial likelihood for ASD and TD samples, grounding results in the broader literature of variable associations between early amygdala volume and later anxiety. Results have the potential to identify mechanisms linking early amygdala growth to later anxiety in certain groups.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection. Methods: Data from the Infant Brain Imaging Study (n = 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning–based predictive tests examined cerebellar–frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar–default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections. Results: Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections. Conclusions: We failed to identify cerebellar functional connectivity–based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

The corpus callosum (CC) is the largest connective pathway in the human brain, linking cerebral hemispheres. There is longstanding debate in the scientific literature whether sex differences are evident in this structure, with many studies indicating the structure is larger in females. However, there are few data pertaining to this issue in infancy, during which time the most rapid developmental changes to the CC occur. In this study, we examined longitudinal brain imaging data collected from 104 infants at ages 6, 12, and 24 months. We identified sex differences in brain-size adjusted CC area and thickness characterized by a steeper rate of growth in males versus females from ages 6–24 months. In contrast to studies of older children and adults, CC size was larger for male compared to female infants. Based on diffusion tensor imaging data, we found that CC thickness is significantly associated with underlying microstructural organization. However, we observed no sex differences in the association between microstructure and thickness, suggesting that the role of factors such as axon density and/or myelination in determining CC size is generally equivalent between sexes. Finally, we found that CC length was negatively associated with nonverbal ability among females.

Pre-diagnostic deficits in social motivation are hypothesized to contribute to autism spectrum disorder (ASD), a heritable neurodevelopmental condition. We evaluated psychometric properties of a social motivation index (SMI) using parent-report item-level data from 597 participants in a prospective cohort of infant siblings at high and low familial risk for ASD. We tested whether lower SMI scores at 6, 12, and 24 months were associated with a 24-month ASD diagnosis and whether social motivation's course differed relative to familial ASD liability. The SMI displayed good internal consistency and temporal stability. Children diagnosed with ASD displayed lower mean SMI T-scores at all ages and a decrease in mean T-scores across age. Lower group-level 6-month scores corresponded with higher familial ASD liability. Among high-risk infants, strong decline in SMI T-scores was associated with 10-fold odds of diagnosis. Infant social motivation is quantifiable by parental report, differentiates children with versus without later ASD by age 6 months, and tracks with familial ASD liability, consistent with a diagnostic and susceptibility marker of ASD. Early decrements and decline in social motivation indicate increased likelihood of ASD, highlighting social motivation's importance to risk assessment and clarification of the ontogeny of ASD. [ABSTRACT FROM AUTHOR]

Human large-scale functional brain networks are hypothesized to undergo significant changes over development. Little is known about these functional architectural changes, particularly during the second half of the first year of life. We used multivariate pattern classification of resting-state functional connectivity magnetic resonance imaging (fcMRI) data obtained in an on-going, multi-site, longitudinal study of brain and behavioral development to explore whether fcMRI data contained information sufficient to classify infant age. Analyses carefully account for the effects of fcMRI motion artifact. Support vector machines (SVMs) classified 6 versus 12 month-old infants (128 datasets) above chance based on fcMRI data alone. Results demonstrate significant changes in measures of brain functional organization that coincide with a special period of dramatic change in infant motor, cognitive, and social development. Explorations of the most different correlations used for SVM lead to two different interpretations about functional connections that support 6 versus 12-month age categorization.

Author(s): Heather Cody Hazlett (corresponding author) [1, 2]; Hongbin Gu [1]; Brent C. Munsell [3]; Sun Hyung Kim [1]; Martin Styner [1]; Jason J. Wolff [4]; Jed T. Elison [5]; [...]

This document is an abstract from the Journal of Clinical & Translational Science. The abstract discusses a study that aimed to understand the link between neonatal neuroimaging measures in very preterm infants and the emergence of strabismus (a visual disorder) later in life. The study found that specific changes in brain structure in the neonatal period were associated with strabismus in very preterm infants. The findings suggest that brain MRI in very preterm infants could be used to predict visual and ocular morbidity. [Extracted from the article]

Background: Restricted and repetitive behaviors are defining features of autism spectrum disorder (ASD). Under revised diagnostic criteria for ASD, this behavioral domain now includes atypical responses to sensory stimuli. To date, little is known about the neural circuitry underlying these features of ASD early in life. Methods: Longitudinal diffusion tensor imaging data were collected from 217 infants at high familial risk for ASD. Forty-four of these infants were diagnosed with ASD at age 2. Targeted cortical, cerebellar, and striatal white matter pathways were defined and measured at ages 6, 12, and 24 months. Dependent variables included the Repetitive Behavior Scale-Revised and the Sensory Experiences Questionnaire. Results: Among children diagnosed with ASD, repetitive behaviors and sensory response patterns were strongly correlated, even when accounting for developmental level or social impairment. Longitudinal analyses indicated that the genu and cerebellar pathways were significantly associated with both repetitive behaviors and sensory responsiveness but not social deficits. At age 6 months, fractional anisotropy in the genu significantly predicted repetitive behaviors and sensory responsiveness at age 2. Cerebellar pathways significantly predicted later sensory responsiveness. Exploratory analyses suggested a possible disordinal interaction based on diagnostic status for the association between fractional anisotropy and repetitive behavior. Conclusions: Our findings suggest that restricted and repetitive behaviors contributing to a diagnosis of ASD at age 2 years are associated with structural properties of callosal and cerebellar white matter pathways measured during infancy and toddlerhood. We further identified that repetitive behaviors and unusual sensory response patterns co-occur and share common brain-behavior relationships. These results were strikingly specific given the absence of association between targeted pathways and social deficits. [ABSTRACT FROM AUTHOR]

The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rs-fcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor "face" system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BG-cortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BG-cortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome). [ABSTRACT FROM AUTHOR]

To explore mechanisms underlying reduced fixation of eyes in autism, children with Autistic Spectrum Disorders (ASD) and typically developing children were tested in five visual search experiments: simple color feature; color-shape conjunction; face in non-face objects; mouth region; and eye region. No group differences were found for reaction time profile shapes in any of the five experiments, suggesting intact basic search mechanics in children with ASD. Contrary to early reports in the literature, but consistent with other more recent findings, we observed no superiority for conjunction search in children with ASD. Importantly, children with ASD did show reduced accuracy for eye region search (p = .005), suggesting that eyes contribute less to high-level face representations in ASD or that there is an eye region-specific disruption to attentional processes engaged by search in ASD. [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW: This review examines advances over the last year in the field of prepubertal mood disorders. RECENT FINDINGS: In bipolar affective disorder, general consensus has been established for a phenotype distinct from but co-morbid with attention deficit hyperactivity disorder. Pharmacological trials have provided some support for the safety and efficacy of combination pharmacotherapies. Debate has continued about the possible roles of selective serotonin reuptake inhibitors and stimulants in '''switching''' children from an episode of depression to mania. Work on the phenomenology of prepubertal major depressive disorder has identified a preschool phenotype. Double-blind placebo-controlled studies have increased the evidence base for use of fluoxetine in the treatment of major depressive disorder. Few controlled studies have explored the efficacy of psychotherapies. Results from general psychiatry underscore the developmental importance of identification of childhood mood disorders: providing evidence for gene-environment interactions in the pathogenesis of major depressive disorder, suggesting vulnerable periods for environmental insults, and raising the disturbing possibility that untreated major depressive disorder is detrimental to the brain. SUMMARY: Despite significant progress there remains a striking paucity of data to direct clinical practice in the treatment of prepubertal mood disorders. Data are badly needed to clarify the risk-benefit ratio in circumstances in which potential side effects are not fully understood and the consequences of not treating may, themselves, be detrimental. Further revisions of the early phenomenology of major depressive disorder and bipolar affective disorder will provide the basis for future treatment trials and further studies of etiology and neurobiology. [ABSTRACT FROM AUTHOR]

In January 1999, the Food Safety and Inspection Service (FSIS) finalized performance standards for the cooking and chilling of meat and poultry products in federally inspected establishments. More restrictive chilling (stabilization) requirements were adopted despite the lack of strong evidence of a public health risk posed by industry practices employing the original May 1988 guidelines (U.S. Department of Agriculture FSIS Directive 7110.3). Baseline data led the FSIS to estimate a "worst case" of 10[sup 4] Clostridium perfringens cells per g in raw meat products. The rationale for the FSIS performance standards was based on this estimate and the assumption that the numbers detected in the baseline study were spores that could survive cooking. The assumptions underlying the regulation stimulated work in our laboratory to help address why there have been so few documented outbreaks of C. perfringens illness associated with the consumption of commercially processed cooked meat and poultry products. Our research took into account the numbers of C. perfringens spores in both raw and cooked products. One hundred ninety-seven raw comminuted meat samples were cooked to 73.9°C and analyzed for C. perfringens levels. All but two samples had undetectable levels (<3 spores per g). Two ground pork samples contained 3.3 and 66 spores per g. Research was also conducted to determine the effect of chilling on the outgrowth of C. perfringens spores in cured and uncured turkey. Raw meat blends inoculated with C. perfringens spores, cooked to 73.9°C, and chilled according to current guidelines or under abuse conditions yielded increases of 2.25 and 2.44 log[sub 10] CFU/g for uncured turkey chilled for 6 h and an increase of 3.07 log[sub 10] CFU/g for cured turkey chilled for 24 h. No growth occurred in cured turkey during a 6-h cooling period. Furthermore, the fate of C. perfringens in cooked cured and uncured turkey held at refrigeration temperatures was investigated. C... [ABSTRACT FROM AUTHOR]

The article focuses on a study in the April 2014 issue of the "Journal of the American Academy of Child & Adolescent Psychiatry" which examined the broader autism phenotype (BAP) in infants. It cited some symptoms of BAP like language and communication problems, difficulties with social interaction, and repetitive behaviors and restricted interests. Also noted is the significance of conducting a research about BAP.

Objective: Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. Method: We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimpanzee SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees {n = 29) with the Chimpanzee SRS and typical and human children with autism spectrum disorder (ASD; n = 20) with the XSRS. Results: The Chimpanzee SRS demonstrated strong interrater reliability at the three sites (ranges for individual ICCs: 0.534 to 0.866; mean ICCs: 0.851 to 0.970). As has been observed in human beings, exploratory principal components analysis of Chimpanzee SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r = 0.976, p = .001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. Conclusion: Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) human beings and chimpanzees. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(5):508-518. Key Words: comparative cognition, autism, Social Responsiveness Scale, chimpanzee, nonhuman primate [ABSTRACT FROM AUTHOR]

Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcAARI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks. [ABSTRACT FROM AUTHOR]

Purpose: Children with autism spectrum disorder and intellectual disability often cannot tolerate wearing spectacles or contact lenses, which are the standard-of-care for treating ametropia. 1,2 We aimed to assess the impact of refractive surgery on social functioning and vision-specific quality-of-life (VSQOL) in this population., Design: Prospective, before-and-after case series., Methods: Setting: Single, academic tertiary care center., Study Population: 18 children with autism spectrum disorder and/or intellectual disability, ametropia, and spectacle nonadherence were included in the analysis., Procedure: Participants underwent refractive surgery with either intraocular lens implantation or keratectomy. Parents completed the Social Responsiveness Scale (SRS-2) and Pediatric Eye Questionnaire (PedEyeQ) at baseline and 1, 6, and 12 months postsurgery. 3,4 Main outcome measures: Median change in SRS-2 T-scores and PedEyeQ scores 12 months after surgery, compared to baseline. The minimum clinically important difference was set at 5 points for the SRS-2 and 10 points for the PedEyeQ., Results: At 12 months after surgery, statistically significant improvements were observed in the SRS-2 domains of Social Awareness (8 points, 95% CI 2-13, P = .03) and Social Motivation (7 points, 95% CI 2-15, P = .03). Total SRS-2 T-score improved in a clinically important manner for 56% (10/18) of patients, but the median change was not statistically significant (5 points, 95% CI -1 to 9, P = .10). VSQOL showed statistically significant improvements in the domains of Functional Vision (40 points, 95% CI 7-73, P = .02) and Bothered by Eyes/Vision (23 points, 95% CI 3-45, P = .02)., Conclusions: Refractive surgery led to clinically and statistically significant improvements in domains of social functioning and VSQOL at 12 months after surgery. A narrow majority of patients demonstrated a clinically important improvement in overall social functioning, but these changes were not statistically significant. The results suggest that refractive surgery in children with neurodevelopmental disorders, ametropia, and spectacle nonadherence may provide developmental and quality-of-life benefits. Larger, controlled studies are required to validate these findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits., Methods: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models., Results: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits., Limitations: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism., Conclusions: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits., (© 2024. The Author(s).)

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations 1,2 , despite evidence for concentric functional zones 3 and maps of complex actions 4 . Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action 5 and physiological control 6 , arousal 7 , errors 8 and pain 9 . This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions 4 and connectivity to internal organs 10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement., (© 2023. The Author(s).)

Social motivation-the psychobiological predisposition for social orienting, seeking social contact, and maintaining social interaction-manifests in early infancy and is hypothesized to be foundational for social communication development in typical and atypical populations. However, the lack of infant social-motivation measures has hindered delineation of associations between infant social motivation, other early-arising social abilities such as joint attention, and language outcomes. To investigate how infant social motivation contributes to joint attention and language, this study utilizes a mixed longitudinal sample of 741 infants at high (HL = 515) and low (LL = 226) likelihood for ASD. Using moderated nonlinear factor analysis (MNLFA), we incorporated items from parent-report measures to establish a novel latent factor model of infant social motivation that exhibits measurement invariance by age, sex, and familial ASD likelihood. We then examined developmental associations between 6- and 12-month social motivation, joint attention at 12-15 months, and language at 24 months of age. On average, greater social-motivation growth from 6-12 months was associated with greater initiating joint attention (IJA) and trend-level increases in sophistication of responding to joint attention (RJA). IJA and RJA were both positively associated with 24-month language abilities. There were no additional associations between social motivation and future language in our path model. These findings substantiate a novel, theoretically driven approach to modeling social motivation and suggest a developmental cascade through which social motivation impacts other foundational skills. These findings have implications for the timing and nature of intervention targets to support social communication development in infancy. HIGHLIGHTS: We describe a novel, theoretically based model of infant social motivation wherein multiple parent-reported indicators contribute to a unitary latent social-motivation factor. Analyses revealed social-motivation factor scores exhibited measurement invariance for a longitudinal sample of infants at high and low familial ASD likelihood. Social-motivation growth from ages 6-12 months is associated with better 12-15-month joint attention abilities, which in turn are associated with greater 24-month language skills. Findings inform timing and targets of potential interventions to support healthy social communication in the first year of life., (© 2022 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Background: Sex differences in the prevalence of neurodevelopmental disorders are particularly evident in autism spectrum disorder (ASD). Heterogeneous symptom presentation and the potential of measurement bias hinder early ASD detection in females and may contribute to discrepant prevalence estimates. We examined trajectories of social communication (SC) and restricted and repetitive behaviors (RRBs) in a sample of infant siblings of children with ASD, adjusting for age- and sex-based measurement bias. We hypothesized that leveraging a prospective elevated familial likelihood sample, deriving data-driven behavioral constructs, and accounting for measurement bias would reveal less discrepant sex ratios than are typically seen in ASD., Methods: We conducted direct assessments of ASD symptoms at 6 to 9, 12 to 15, 24, and 36 to 60 months of age (total n observations  = 1254) with infant siblings of children with ASD (n = 377) and a lower ASD-familial-likelihood comparison group (n = 168; n observations  = 527). We established measurement invariance across age and sex for separate models of SC and RRB. We then conducted latent class growth mixture modeling with the longitudinal data and evaluated for sex differences in trajectory membership., Results: We identified 2 latent classes in the SC and RRB models with equal sex ratios in the high-concern cluster for both SC and RRB. Sex differences were also observed in the SC high-concern cluster, indicating that girls classified as having elevated social concerns demonstrated milder symptoms than boys in this group., Conclusions: This novel approach for characterizing ASD symptom progression highlights the utility of assessing and adjusting for sex-related measurement bias and identifying sex-specific patterns of symptom emergence., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Autism spectrum disorder (ASD) is heritable, and younger siblings of ASD probands are at higher likelihood of developing ASD themselves. Prospective MRI studies of siblings report that atypical brain development precedes ASD diagnosis, although the link between brain maturation and genetic factors is unclear. Given that familial recurrence of ASD is predicted by higher levels of ASD traits in the proband, the authors investigated associations between proband ASD traits and brain development among younger siblings., Methods: In a sample of 384 proband-sibling pairs (89 pairs concordant for ASD), the authors examined associations between proband ASD traits and sibling brain development at 6, 12, and 24 months in key MRI phenotypes: total cerebral volume, cortical surface area, extra-axial cerebrospinal fluid, occipital cortical surface area, and splenium white matter microstructure. Results from primary analyses led the authors to implement a data-driven approach using functional connectivity MRI at 6 months., Results: Greater levels of proband ASD traits were associated with larger total cerebral volume and surface area and larger surface area and reduced white matter integrity in components of the visual system in siblings who developed ASD. This aligned with weaker functional connectivity between several networks and the visual system among all siblings during infancy., Conclusions: The findings provide evidence that specific early brain MRI phenotypes of ASD reflect quantitative variation in familial ASD traits. Multimodal anatomical and functional convergence on cortical regions, fiber pathways, and functional networks involved in visual processing suggest that inherited liability has a role in shaping the prodromal development of visual circuitry in ASD.

Objective: With development, infants become increasingly responsive to the many attention-sharing cues of adults; however, little work has examined how this ability emerges in typical development or in the context of early autism spectrum disorder (ASD). This study characterized variation in the type of cue needed to elicit a response to joint attention (RJA) using the Dimensional Joint Attention Assessment (DJAA) during naturalistic play., Method: We measured the average redundancy of cue type required for infants to follow RJA bids from an experimenter, as well as their response consistency, in 268 infants at high (HR, n = 68) and low (LR, N = 200) familial risk for ASD. Infants were assessed between 8 and 18 months of age and followed up with developmental and clinical assessments at 24 or 36 months. Our sample consisted of LR infants, as well as HR infants who did (HR-ASD) and did not (HR-neg) develop ASD at 24 months., Results: We found that HR and LR infants developed abilities to respond to less redundant (more sophisticated) RJA cues at different rates, and that HR-ASD infants displayed delayed abilities, identifiable as early as 9 months, compared to both HR-neg and LR infants. Interestingly, results suggest that HR-neg infants may exhibit a propensity to respond to less redundant (more sophisticated) RJA cues relative to both HR-ASD and LR infants., Conclusion: Using an approach to characterize variable performance of RJA cue-reading abilities, findings from this study enhance our understanding of both typical and ASD-related proficiencies and deficits in RJA development., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD., (© 2021 The Authors. Child Development © 2021 Society for Research in Child Development.)

Background: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis., Methods: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary., Results: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change., Conclusions: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses., (© 2021 Association for Child and Adolescent Mental Health.)

Intense interests are common in children with and without autism spectrum disorder (ASD), and little research has characterized aspects of interests that are unique to or shared among children with and without ASD. We aimed to characterize interests in a sample of infants at high-familial-risk (HR) and low-familial-risk (LR) for ASD using a novel interview. Participants included HR siblings who were diagnosed with ASD at 24 months (HR-ASD, n = 56), HR siblings who did not receive an ASD diagnosis at 24 months (HR-Neg, n = 187), and a LR comparison group (n = 109). We developed and collected data with the Intense Interests Inventory at 18- and 24-months of age, a semi-structured interview that measures intensity and peculiarity of interests in toddlers and preschool-aged children. Intensity of interests differed by familial risk at 24 months, with HR-ASD and HR-Neg groups demonstrating equivalent intensity of interests that were higher than the LR group. By contrast, peculiarity of interest differed by ASD diagnosis, with the HR-ASD group showing more peculiar interests than the HR-Neg and LR groups at 24 months. At 18 months the HR-ASD group had more peculiar interests than the LR group, though no differences emerged in intensity of interests. This measure may be useful in identifying clinically-relevant features of interests in young children with ASD. We also replicated previous findings of males showing more intense interests at 18 months in our non-ASD sample. These results reveal new information about the nature of interests and preoccupations in the early autism phenotype. LAY SUMMARY: Intense interests are common in young children with autism and their family members. Intense interests are also prevalent among typically-developing children, and especially boys. Here we catalog interests and features of these interests in a large sample of toddlers enriched for autism risk. Children who had family members with autism had more intense interests, and those who developed autism themselves had more unusual interests at 24 months. These results highlight the importance of different aspects of interest in autism., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Objective: Predictive testing for familial disorders can guide healthcare and reproductive decisions. Familial disorders with onset in childhood (e.g., autism spectrum disorder [ASD]) are promising targets for presymptomatic prediction; however, little is known about parent perceptions of risk to their children in the presymptomatic period. The current study examined risk perceptions in parents of infants at high familial risk for ASD enrolled in a longitudinal study of brain and behavior development., Methods: Semistructured interviews were conducted with 37 parents of high-risk infants during the presymptomatic window (3-15 months) that precedes an ASD diagnosis. Infants were identified as high familial risk due to having an older sibling with ASD. Parent interview responses were coded and interpreted to distill emerging themes., Results: The majority of parents were aware of the increased risk of ASD for their infants, and risk perceptions were influenced by comparisons to their older child with ASD. Parents reported a variety of negative emotions in response to perceived risk, including worry, fear, and sadness, and described impacts of perceived risk on their behavior: increased vigilance to emerging symptoms, altered reproductive and healthcare decisions, and seeking ongoing assessment through research., Conclusions: Parents of children at high familial risk for childhood-onset disorders like ASD face a period of challenging uncertainty during early development. In anticipation of a future in which presymptomatic testing for ASD is made available, it is important to understand how parents react to and cope with the elevated-but still highly uncertain-risk conveyed by family history., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)