White matter development and language abilities during infancy in autism spectrum disorder.

White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD.

Atypical functional connectivity between the amygdala and visual, salience regions in infants with genetic liability for autism.

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.

Quantifying latent social motivation and its associations with joint attention and language in infants at high and low likelihood for autism spectrum disorder.

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.

Early brain development in infants at high risk for autism spectrum disorder.

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

A cybernetic theory of autism: Autism as a consequence of low trait plasticity.

OBJECTIVE: According to Cybernetic Big Five Theory (CB5T), personality traits reflect variation in the parameters of evolved cybernetic mechanisms, and extreme manifestations of these traits correspond to a risk for psychopathology because they threaten the organism's ability to pursue its goals effectively. Our theory of autism as a consequence of low Plasticity extends CB5T to provide a cybernetic account of the origin of autistic traits. The theory argues that, because all psychological competencies are initially developed through exploration, typical development requires sensitivity to the incentive reward value of the unknown (i.e., the unpredicted). According to CB5T, motivation to explore the unknown is the core function underlying the metatrait Plasticity, the shared variance of Extraversion and Openness/Intellect. This theory makes predictions regarding the downstream developmental consequences of early low Plasticity, and each prediction maps well onto autistic symptomatology. METHOD: We surveyed 387 people. Measures included the Autism Quotient (AQ) scale and International Personality Item Pool items that are indicators of Plasticity and Stability. RESULTS: The association between AQ and Plasticity was ß = -.64. CONCLUSION: A strong negative correlation between Plasticity and AQ suggests ASD may be closely linked to a low sensitivity to the incentive reward value of the unknown.

Responding to joint attention as a developmental catalyst: Longitudinal associations with language and social responsiveness.

Joint attention (JA), infants' ability to engage in triadic attention with another person and a separate object or event, emerges in infancy. Responding to joint attention (RJA) develops earlier than initiating joint attention (IJA) and may benefit from a reconceptualization from a competence to a skill that varies in performance. Investigating associations between RJA performance and important skills of toddlerhood such as language, social responsiveness, and executive function (EF) in typically developing samples can better elucidate how RJA may serve as a developmental precursor to later dimensional skills, with implications for both typical and atypical development. Here, 210 (82% White) infants completed the Dimensional Joint Attention Assessment (DJAA), a naturalistic play-based assessment of RJA, at 8-15 months. At 16-38 months social responsiveness, verbal ability, and EF were assessed. Multilevel models showed that DJAA scores were associated with later verbal abilities and parent-reported social responsiveness. Exploratory analyses showed trend-level associations between RJA and EF. Results establish the content validity of the DJAA as a measure of RJA, and longitudinal associations with later verbal ability and social responsiveness. Future work should examine EF emergence and consolidation, and RJA and later EF associations.

Synthesizing pseudo-T2w images to recapture missing data in neonatal neuroimaging with applications in rs-fMRI.

T1- and T2-weighted (T1w and T2w) images are essential for tissue classification and anatomical localization in Magnetic Resonance Imaging (MRI) analyses. However, these anatomical data can be challenging to acquire in non-sedated neonatal cohorts, which are prone to high amplitude movement and display lower tissue contrast than adults. As a result, one of these modalities may be missing or of such poor quality that they cannot be used for accurate image processing, resulting in subject loss. While recent literature attempts to overcome these issues in adult populations using synthetic imaging approaches, evaluation of the efficacy of these methods in pediatric populations and the impact of these techniques in conventional MR analyses has not been performed. In this work, we present two novel methods to generate pseudo-T2w images: the first is based in deep learning and expands upon previous models to 3D imaging without the requirement of paired data, the second is based in nonlinear multi-atlas registration providing a computationally lightweight alternative. We demonstrate the anatomical accuracy of pseudo-T2w images and their efficacy in existing MR processing pipelines in two independent neonatal cohorts. Critically, we show that implementing these pseudo-T2w methods in resting-state functional MRI analyses produces virtually identical functional connectivity results when compared to those resulting from T2w images, confirming their utility in infant MRI studies for salvaging otherwise lost subject data.

Filtering respiratory motion artifact from resting state fMRI data in infant and toddler populations.

The importance of motion correction when processing resting state functional magnetic resonance imaging (rs-fMRI) data is well-established in adult cohorts. This includes adjustments based on self-limited, large amplitude subject head motion, as well as factitious rhythmic motion induced by respiration. In adults, such respiration artifact can be effectively removed by applying a notch filter to the motion trace, resulting in higher amounts of data retained after frame censoring (e.g., "scrubbing") and more reliable correlation values. Due to the unique physiological and behavioral characteristics of infants and toddlers, rs-fMRI processing pipelines, including methods to identify and remove colored noise due to subject motion, must be appropriately modified to accurately reflect true neuronal signal. These younger cohorts are characterized by higher respiration rates and lower-amplitude head movements than adults; thus, the presence and significance of comparable respiratory artifact and the subsequent necessity of applying similar techniques remain unknown. Herein, we identify and characterize the consistent presence of respiratory artifact in rs-fMRI data collected during natural sleep in infants and toddlers across two independent cohorts (aged 8-24 months) analyzed using different pipelines. We further demonstrate how removing this artifact using an age-specific notch filter allows for both improved data quality and data retention in measured results. Importantly, this work reveals the critical need to identify and address respiratory-driven head motion in fMRI data acquired in young populations through the use of age-specific motion filters as a mechanism to optimize the accuracy of measured results in this population.

Examining the factor structure and discriminative utility of the Infant Behavior Questionnaire-Revised in infant siblings of autistic children.

Using the Infant Behavior Questionnaire-Revised in a longitudinal sample of infant siblings of autistic children (HR; n = 427, 171 female, 83.4% White) and a comparison group of low-risk controls (LR, n = 200, 86 female, 81.5% White), collected between 2007 and 2017, this study identified an invariant factor structure of temperament traits across groups at 6 and 12 months. Second, after partitioning the groups by familial risk and diagnostic outcome at 24 months, results reveal an endophenotypic pattern of Positive Emotionality at both 6 and 12 months, (HR-autism spectrum disorder [ASD] < HR-no-ASD < LR). Third, increased 'Duration of Orienting' at 12 months was associated with lower scores on the 24-month developmental outcomes in HR infants. These findings may augment efforts for early identification of ASD.

Social motivation in infancy is associated with familial recurrence of ASD.

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.

Birthweight moderates the association between chronological age and infants' abilities to respond to cues for joint attention.

Infants born preterm are more likely than ever to survive, but relatively little is known about the factors that influence their subsequent sociocognitive development. Responding to joint attention (RJA) is a pivotal skill that is likely supported by biological preparedness at birth and ex-utero social experience. The goals of this study are to evaluate the relative roles of chronological age, gestation duration, and birthweight for early RJA and examine birthweight as a potential moderator of the associations between chronological age and RJA. This study leveraged a mixed longitudinal design of infants (N = 256, obs = 421) from 8 to 16 months of chronological age. Results show that chronological age and gestation duration both explain unique variation in RJA. Further, birthweight exhibits quadratic relations with RJA. Birthweight moderates the association between chronological age and RJA; infants born heavier demonstrate faster RJA growth compared to those born smaller. Findings suggest that birth weight, an index of nutrient sufficiency in utero and biological preparedness, may constrain or afford early RJA development, consistent with the Developmental Origins of Health and Disease (DoHAD) hypothesis. Findings inform our understanding of the roles of biological preparedness and experience in shaping RJA and help disaggregate potential mechanisms of prematurity-related challenges to social cognitive development.

A broadened estimate of syntactic and lexical ability from the MB-CDI.

A critical question in the study of language development is to understand lexical and syntactic acquisition, which play different roles in speech to the extent it would be natural to surmise they are acquired differently. As measured through the comprehension and production of closed-class words, syntactic ability emerges at roughly the 400-word mark. However, a significant proportion of the developmental work uses a coarse combination of function and content words on the MacArthur-Bates Communicative Development Inventory (MB-CDI). Using the MB-CDI Wordbank database, we implemented a factor analytic approach to distinguish between lexical and syntactic development from the Words and Sentences (WS) form that involves both function words and the explicit categorizations. Although the Words and Gestures (WG) form did not share the factor structure, common WG/WS elements recapitulate the expected age-related changes. This parsing of the MB-CDI may prove simple, yet fruitful in subsequent investigation.

Comparison of U.S. and Tajik infants' time in containment devices.

How infants are held or contained throughout the day shape infants' experiences, particularly around movement and exploration. In Tajikistan, caregivers use "gahvora" cradles, which severely restrict the body and limbs. The present study explored the variability and use of containment devices in U.S. and Tajik infants. Using time diaries, we compared 12-month-olds in the U.S. and Tajikistan on the types of containments used and time spent in them throughout the day. During the day, Tajik infants accumulated more time in gahvoras than infants in the U.S. spent in cribs, primarily used for sleep, suggesting gahvoras served other functions. Given the availability of other devices, U.S. infants' time was distributed in short yet frequent bouts across devices. Accumulated time in these containments matched accumulated time Tajik infants spent in gahvoras. Tajik infants accumulated more unrestricted time on the ground, which was distributed in prolonged bouts, than U.S. infants. Findings highlight differences in infants' everyday experiences during the developmental period when motor skills emerge. By embracing commonalities and exploring differences between cultures, this study offers insights into differences in infants' everyday experiences and opportunities for movement.

Emerging ethical issues raised by highly portable MRI research in remote and resource-limited international settings.

Smaller, more affordable, and more portable MRI brain scanners offer exciting opportunities to address unmet research needs and long-standing health inequities in remote and resource-limited international settings. Field-based neuroimaging research in low- and middle-income countries (LMICs) can improve local capacity to conduct both structural and functional neuroscience studies, expand knowledge of brain injury and neuropsychiatric and neurodevelopmental disorders, and ultimately improve the timeliness and quality of clinical diagnosis and treatment around the globe. Facilitating MRI research in remote settings can also diversify reference databases in neuroscience, improve understanding of brain development and degeneration across the lifespan in diverse populations, and help to create reliable measurements of infant and child development. These deeper understandings can lead to new strategies for collaborating with communities to mitigate and hopefully overcome challenges that negatively impact brain development and quality of life. Despite the potential importance of research using highly portable MRI in remote and resource-limited settings, there is little analysis of the attendant ethical, legal, and social issues (ELSI). To begin addressing this gap, this paper presents findings from the first phase of an envisioned multi-staged and iterative approach for creating ethical and legal guidance in a complex global landscape. Section 1 provides a brief introduction to the emerging technology for field-based MRI research. Section 2 presents our methodology for generating plausible use cases for MRI research in remote and resource-limited settings and identifying associated ELSI issues. Section 3 analyzes core ELSI issues in designing and conducting field-based MRI research in remote, resource-limited settings and offers recommendations. We argue that a guiding principle for field-based MRI research in these contexts should be including local communities and research participants throughout the research process in order to create sustained local value. Section 4 presents a recommended path for the next phase of work that could further adapt these use cases, address ethical and legal issues, and co-develop guidance in partnership with local communities.

Phenoscreening: a developmental approach to research domain criteria-motivated sampling.

BACKGROUND: To advance early identification efforts, we must detect and characterize neurodevelopmental sequelae of risk among population-based samples early in development. However, variability across the typical-to-atypical continuum and heterogeneity within and across early emerging psychiatric/neurodevelopmental disorders represent fundamental challenges to overcome. Identifying multidimensionally determined profiles of risk, agnostic to DSM categories, via data-driven computational approaches represents an avenue to improve early identification of risk. METHODS: Factor mixture modeling (FMM) was used to identify subgroups and characterize phenotypic risk profiles, derived from multiple parent-report measures of typical and atypical behaviors common to autism spectrum disorder, in a community-based sample of 17- to 25-month-old toddlers (n = 1,570). To examine the utility of risk profile classification, a subsample of toddlers (n = 107) was assessed on a distal, independent outcome examining internalizing, externalizing, and dysregulation at approximately 30 months. RESULTS: FMM results identified five asymmetrically sized subgroups. The putative high- and moderate-risk groups comprised 6% of the sample. Follow-up analyses corroborated the utility of the risk profile classification; the high-, moderate-, and low-risk groups were differentially stratified (i.e., HR > moderate-risk > LR) on outcome measures and comparison of high- and low-risk groups revealed large effect sizes for internalizing (d = 0.83), externalizing (d = 1.39), and dysregulation (d = 1.19). CONCLUSIONS: This data-driven approach yielded five subgroups of toddlers, the utility of which was corroborated by later outcomes. Data-driven approaches, leveraging multiple developmentally appropriate dimensional RDoC constructs, hold promise for future efforts aimed toward early identification of at-risk-phenotypes for a variety of early emerging neurodevelopmental disorders.

Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach.

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.

Visual input to the left versus right eye yields differences in face preferences in 3-month-old infants.

From birth, infants prefer looking at faces over scrambled faces. This face input is important for the development of face processing: individuals who experienced early visual deprivation due to congenital cataracts have long-lasting face processing deficits. Interestingly, the deficits are eye-specific such that left eye cataracts disrupt the development of face processing, whereas right eye cataracts do not. This raises the question of whether infant face preferences are driven primarily by faces observed through the left eye. To investigate this, we presented 3-month-old infants with intact faces paired with scrambled faces. Infants viewed the moving stimuli binocularly, only with their left eye, or only with their right eye. Infants viewing stimuli binocularly or with only the left eye spent significantly more time looking at intact faces than scrambled faces, but this effect was equivocal in infants viewing stimuli through only their right eye. Infants in the binocular group had the greatest preference for faces, and this preference was greater than the right eye group's preference for faces. The left eye group's preference for faces was not statistically different from the other two groups' preference for faces, but additional analyses revealed a correlation between preference for faces and age for the right eye group only, indicating that preference for faces seen with the right eye increase from 3 to 4 months of age. These results indicate that the left eye plays a special role in face processing at, or before 3 months of age, but a preference for faces through the right eye emerges soon after.

Infants' abilities to respond to cues for joint attention vary by family socioeconomic status.

The influence of socioeconomic variability on language and cognitive development is present from toddlerhood to adolescence and calls for investigating its earliest manifestation. Response to joint attention (RJA) abilities constitute a foundational developmental milestone that are associated with future language, cognitive, and social skills. How aspects of the family home environment shape RJA skills is relatively unknown. We investigated associations between family socioeconomic status (SES) -both parent education and family percentage of the federal poverty level (FPL)- parent depressive and anxiety symptoms and infant RJA performance in a cross-sectional sample of 173 infants aged 8-18 months and their parents from a variety of socioeconomic backgrounds. Results suggest that, correcting for age and receptive language, infants in families with greater economic resources respond to relatively less redundant, more sophisticated cues for joint attention. Although parent depressive and anxiety symptoms are negatively correlated with SES, parent depressive and anxiety symptoms were not associated with infant RJA. These findings provide evidence of SES-related differences in social cognitive development as early as infancy, calling on policymakers to address the inequities in the current socioeconomic landscape of the United States.

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study.

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.

Examining criterion-oriented validity of the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB).

Improved characterization of quantitative traits and dimensionally distributed complex behaviors during toddlerhood may improve early identification of autism spectrum disorder and related neurodevelopmental disorders. Parents of 205 community-ascertained toddlers (age: mean = 20.2, SD = 2.6 months) completed the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB), with longitudinal follow-up of behavioral assessments and/or another round of parent-report questionnaires. Criterion validity was examined both concurrently and longitudinally using the Infant Toddler Social Emotional Assessment (ITSEA) as a criterion anchor. Reciprocal social behavior as measured by the vrRSB was significantly associated with social competence as measured by the ITSEA, longitudinally and concurrently. Reciprocal social behavior was not associated with the externalizing subscale on the ITSEA, providing evidence of discriminant validity. Higher-order repetitive behaviors (restricted interests; rituals and routines) as measured by RBS-EC subscales were associated with the dysregulation and internalizing subscales of the ITSEA, longitudinally and concurrently. All RBS-EC subscales (excepting repetitive motor) were associated concurrently and longitudinally with the dysregulation subscale of the ITSEA. We report evidence of criterion-oriented and discriminant validity for the constructs/domains captured by the RBS-EC and vrRSB. These instruments may be particularly useful in characterizing dimensional variability across the typical-to-atypical continuum.