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BACKGROUND: Emerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life. We investigated the perspectives of parents about the anticipated utility and impact of predicting later autism diagnosis from a biomarker-based test in infancy. METHODS: Parents of infants were interviewed to ascertain receptiveness and perspectives on early (6-12 months) prediction of autism using emerging biomarker technologies. One group had experience parenting an older autistic child (n=30), and the other had no prior autism parenting experience (n=25). Parent responses were analyzed using inductive qualitative coding methods. RESULTS: Almost all parents in both groups were interested in predictive testing for autism, with some stating they would seek testing only if concerned about their infant's development. The primary anticipated advantage of testing was to enable access to earlier intervention. Parents also described the anticipated emotions they would feel in response to test results, actions they might take upon learning their infant was likely to develop autism, attitudes towards predicting a child's future support needs, and the potential impacts of inaccurate prediction. CONCLUSION: In qualitative interviews, parents of infants with and without prior autism experience shared their anticipated motivations and concerns about predictive testing for autism in the first year of life. The primary reported motivators for testing-to have more time to prepare and intervene early-could be constrained by familial resources and service availability. Implications for ethical communication of results, equitable early intervention, and future research are discussed.
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Transtorno Autístico , Pais , Humanos , Lactente , Masculino , Feminino , Transtorno Autístico/diagnóstico , Adulto , Biomarcadores , Pesquisa Qualitativa , Transtorno do Espectro Autista/diagnósticoRESUMO
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 4.16â¯% and quality control loss rates at 11.66â¯%. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16â¯%, 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.
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OBJECTIVE: Naturalistic developmental behavioral interventions for children with autism spectrum disorder show evidence for effectiveness for specific social communication targets such as joint attention or engagement. However, combining evidence from different studies and comparing intervention effects across those studies have not been feasible due to lack of a standardized outcome measure of broader social communication skills that can be applied uniformly across trials. This investigation examined the usefulness of the Brief Observation of Social Communication Change (BOSCC) as a common outcome measure of general social communication skills based on secondary analyses of data obtained from previously conducted randomized controlled trials of 3 intervention models, Early Social Intervention (ESI), Early Start Denver Model (ESDM) and Joint Attention Symbolic Play Engagement and Regulation (JASPER). METHOD: The subset of datasets from the 3 randomized controlled trials was created to examine differences in the BOSCC scores between intervention and control groups over the course of the interventions. RESULTS: Based on 582 videos from 207 caregiver-child dyads, the BOSCC noted significant differences between intervention vs control groups in broad social communication skills within 2 of the 3 intervention models, which were longer in duration and focused on a broad range of developmental skills. CONCLUSION: The BOSCC offers the potential to take a uniform measurement approach across different intervention models to capture the effect of intervention on general social communication skills but may not pick up the effects of some brief interventions targeting proximal outcomes. CLINICAL TRIAL REGISTRATION INFORMATION: Comparing Parent-Implemented Interventions for Toddlers With Autism Spectrum Disorders; https://www. CLINICALTRIALS: gov/; NCT00760812. Intensive Intervention for Toddlers With Autism (EARLY STEPS); https://www. CLINICALTRIALS: gov/; NCT00698997. Social and Communication Outcomes for Young Children With Autism; https://www. CLINICALTRIALS: gov/; NCT00953095.
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BACKGROUND: Naturalistic Developmental Behavioral Interventions (NDBIs) for young children with autism spectrum disorder commonly involve caregiver-mediated approaches. However, to date, there is limited research on how caregivers' skills change, and, in turn, impact child outcomes. METHODS: We evaluated the NDBI strategy use of 191 caregivers prior to participation in NDBIs (or control groups) across multiple randomized controlled trials, using the Measure of NDBI Strategy Implementation, Caregiver Change (MONSI-CC). Clustering analyses were used to examine caregiver variability in NDBI strategy use at intervention entry. Generalized Linear Mixed Models were used to examine changes in caregiver strategy use over the course of intervention and its impact on changes in children's social communication. RESULTS: Using clustering analysis, we found that caregivers' baseline skills fit four profiles: limited, emerging, variable, and consistent/high, with few demographic factors distinguishing these groups. Caregivers starting with limited or emerging skills improved in their strategy use with intervention. Caregivers starting with more skills (consistent/high or variable) maintained higher skills over intervention. Children of caregivers in these groups who received target NDBIs improved in their social communication skills. CONCLUSIONS: Results suggested that caregiver skills improve through participation in NDBIs and may directly contribute to their children's outcomes, although more research on mediating factors is needed. Individualized approaches for caregivers and their children starting with differing skill profiles at intervention entry may be warranted.
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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.
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Tonsila do Cerebelo , Imageamento por Ressonância Magnética , Córtex Visual , Humanos , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Masculino , Feminino , Lactente , Córtex Visual/diagnóstico por imagem , Córtex Visual/fisiopatologia , Córtex Visual/crescimento & desenvolvimento , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Transtorno Autístico/diagnóstico por imagem , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/diagnóstico por imagem , Predisposição Genética para Doença/genéticaRESUMO
Autism spectrum disorder is associated with a high rate of sleep problems, affecting over 80% of autistic individuals. Sleep problems have pervasive negative effects on health, behavior, mood, and cognition but are underrecognized in autistic children. Problems initiating and maintaining sleep-hallmarks of insomnia-are common. Sleep-disordered breathing and restless legs syndrome have also been described in autism at a higher prevalence than in community populations. The authors describe current research on sleep in autistic children and potential pathophysiologic mechanisms. They describe practical approaches to sleep assessment and synthesize approaches to addressing sleep problems in autistic children.
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BACKGROUND: Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants. METHODS: The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls. RESULTS: Infants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD. CONCLUSIONS: Our results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.
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Transtorno do Espectro Autista , Transtorno Autístico , Síndrome do Cromossomo X Frágil , Lactente , Humanos , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/psicologia , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Idioma , CogniçãoRESUMO
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.
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Gestures are an important social communication skill that infants and toddlers use to convey their thoughts, ideas, and intentions. Research suggests that early gesture use has important downstream impacts on developmental processes, such as language learning. However, autistic children are more likely to have challenges in their gestural development. The current study expands upon previous literature on the differences in gesture use between young autistic and non-autistic toddlers by collecting data using a parent-report questionnaire called the MCDI-Words and Gestures at three time points, 12, 18, and 24 months of age. Results (N = 467) showed that high-likelihood infants who later met diagnostic criteria for ASD (n = 73 HL-ASD) have attenuated gesture growth from 12 to 24 months for both deictic gestures and symbolic gestures when compared to high-likelihood infants who later did not meet criteria for ASD (n = 249 HL-Neg) and low-likelihood infants who did not meet criteria for ASD (n = 145 LL-Neg). Other social communicative skills, like play behaviors and imitation, were also found to be impacted in young autistic children when compared to their non-autistic peers. Understanding early differences in social communication growth before a formal autism diagnosis can provide important insights for early intervention.
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Transtorno do Espectro Autista , Transtorno Autístico , Lactente , Humanos , Transtorno Autístico/diagnóstico , Gestos , Transtorno do Espectro Autista/diagnóstico , Desenvolvimento da LinguagemRESUMO
BACKGROUND: Narrative discourse, or storytelling, is used in daily conversation and requires higher-level language and social communication skills that are not always captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) have difficulties with both social communication and language skills, and narrative discourse analysis offers an ecologically relevant approach to assessing those challenges. AIMS: This study investigated narrative discourse in individuals with autism and FASD, as well as an age- and sex-matched comparison group. METHODS AND PROCEDURES: Narratives from 45 adolescents and adults, 11 with autism, 11 with FASD and 23 age- and sex-matched comparison participants were elicited using a wordless storybook. They were then transcribed orthographically, formatted to the Systematic Analyses of Language Transcript (SALT) convention and scored based on the SALT Narrative Scoring Scheme (NSS), a standardised language analysis protocol. In addition to the NSS total score, which assesses the overall structure and cohesion of the narratives produced, local and global measures of language ability were also employed. The local language measures included the number of mental state and temporal relation terms produced, while the global language measures included mean length of utterance, total different words, total words, total utterances, rate of speech, the number of mazes (e.g., repetitions, 'um', 'uh' or self-corrections) per total word and the NSS total score. OUTCOMES AND RESULTS: Using the SALT Language Sample Analysis tool, our results revealed that on global language measures, group differences were found on rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. The autism group produced significantly more mazes per total word and scored higher on the NSS conflict/resolution category score compared to the FASD and comparison groups. Both the autism and FASD groups spoke at a lower rate than the comparison group. On local language measures of narrative production, all groups were comparable, on average. CONCLUSIONS AND IMPLICATIONS: While many aspects of narrative discourse in the autism and FASD groups were similar to each other and to the comparison group, we observed group differences on global measures of narrative production and significant individual variability within groups, suggesting that narrative abilities considered at an individual level may provide important clinical information for intervention planning. Future research should also consider additional variables that influence narrative discourse, such as motivation, distractibility or decision-making of individual participants. WHAT THIS PAPER ADDS: What is already known on the subject Narrative discourse, or storytelling, is used in daily conversational interactions and reveals higher-level language skills that may not be well captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) show difficulty with pragmatic and expressive language skills. What this paper adds to existing knowledge We found that many aspects of the narratives produced by the adolescents/young adults in the autism and FASD groups were comparable to each other and to the neurotypical group. However, the groups differed on three global measures of narrative production: rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. Also, significant variability was observed within groups, suggesting that narrative abilities should be considered at an individual level as opposed to their clinical groups. What are the potential or actual clinical implications of this work? This study showed that narrative discourse is an appropriate task that can be added to routine clinical assessments of language abilities in autistic adolescents/young adults as well as those with FASD or typical development and has the potential to reveal higher-level, real-world language skills. An important clinical implication of this study is that narrative language abilities should be considered at an individual level and individual-tailored interventions based on ability level due to the variability observed across individuals.
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Transtorno do Espectro Autista , Transtorno Autístico , Transtornos do Espectro Alcoólico Fetal , Feminino , Adolescente , Gravidez , Adulto Jovem , Humanos , Comunicação , Idioma , NarraçãoRESUMO
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.
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Transtorno do Espectro Autista , Criança , Lactente , Recém-Nascido , Humanos , Ansiedade , Transtornos de Ansiedade , Encéfalo , Imageamento por Ressonância Magnética/métodos , Tonsila do CerebeloRESUMO
Importance: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume. Objective: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep problems in later childhood. Design, Setting, and Participants: This prospective, longitudinal cohort study used data from the Infant Brain Imaging Study. Magnetic resonance images were acquired at ages 6, 12, and 24 months (2007-2017), with sleep questionnaires performed between ages 7 and 12 years (starting in 2018). Data were collected at 4 sites in North Carolina, Missouri, Pennsylvania, and Washington. Data were analyzed from March 2021 through August 2022. Exposure: PVS (ie, fluid-filled channels that surround blood vessels in the brain) that are enlarged (ie, visible on magnetic resonance imaging). Main Outcomes and Measures: Outcomes of interest were enlarged PVS and EA-CSF volume from 6 to 24 months, autism diagnosis at 24 months, sleep problems between ages 7 and 12 years. Results: A total of 311 infants (197 [63.3%] male) were included: 47 infants at high familial likelihood for autism (ie, having an older sibling with autism) who were diagnosed with autism at age 24 months, 180 high likelihood infants not diagnosed with autism, and 84 low likelihood control infants not diagnosed with autism. Sleep measures at school-age were available for 109 participants. Of infants who developed autism, 21 (44.7%) had enlarged PVS at 24 months compared with 48 infants (26.7%) in the high likelihood but no autism diagnosis group (P = .02) and 22 infants in the control group (26.2%) (P = .03). Across all groups, enlarged PVS at 24 months was associated with greater EA-CSF volume from ages 6 to 24 months (ß = 4.64; 95% CI, 0.58-8.72; P = .002) and more frequent night wakings at school-age (F = 7.76; η2 = 0.08; P = .006). Conclusions and Relevance: These findings suggest that enlarged PVS emerged between ages 12 and 24 months in infants who developed autism. These results add to a growing body of evidence that, along with excessive CSF volume and sleep dysfunction, the glymphatic system could be dysregulated in infants who develop autism.
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Transtorno Autístico , Lactente , Humanos , Masculino , Criança , Pré-Escolar , Feminino , Transtorno Autístico/diagnóstico por imagem , Estudos Longitudinais , Estudos Prospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , SonoRESUMO
Theories of altered inhibitory/excitatory signaling in autism spectrum disorder (ASD) suggest that gamma amino butyric acid (GABA) and glutamate (Glu) abnormalities may underlie social and sensory challenges in ASD. Magnetic resonance spectroscopy was used to measure Glu and GABA+ levels in the amygdala-hippocampus region and cerebellum in autistic children (n = 30), a clinical control group with sensory abnormalities (SA) but not ASD (n = 30), and children with typical development (n = 37). All participants were clinically assessed using the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Scale-2, and the Child Sensory Profile-2. The Social Responsiveness Scale-2, Sniffin Sticks Threshold Test, and the University of Pennsylvania Smell Identification Test were administered to assess social impairment and olfactory processing. Overall, autistic children showed increased cerebellar Glu levels compared to TYP children. Evidence for altered excitatory/inhibitory signaling in the cerebellum was more clear-cut when analyses were restricted to male participants. Further, lower cerebellar GABA+/Glu ratios were correlated to more severe social impairment in both autistic and SA males, suggesting that the cerebellum may play a transdiagnostic role in social impairment. Future studies of inhibitory/excitatory neural markers, powered to investigate the role of sex, may aid in parsing out disorder-specific neurochemical profiles.
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Transtorno do Espectro Autista , Ácido Glutâmico , Humanos , Masculino , Criança , Transtorno do Espectro Autista/diagnóstico por imagem , Olfato , Espectroscopia de Ressonância Magnética/métodos , Ácido gama-AminobutíricoRESUMO
Existing research suggests that self-injurious behavior (SIB) is a relatively common interfering behavior that can occur across the lifespan of individuals with autism spectrum disorder (ASD). We previously reported that SIB or proto-injurious SIB at 12 months was related to increased risk of SIB at 24 months among a preschool sample of children with a high familial likelihood for ASD (Dimian et al., 2017). In the present study, we extend these findings, examine SIB occurrence, and associated potential risk factors at 36 months. The present sample included 149 infants with an older sibling with ASD (65.8% male) who completed assessments at ages 12, 24, and 36 months. Descriptive analyses and binary logistic regression models were utilized. SIB was more prevalent among those children who received a diagnosis of ASD. Logistic regression indicated that presence of SIB, stereotypy, hyper- and hypo- sensory responsivity, and lower intellectual functioning at age 12 months significantly predicted the occurrence of SIB at 36 months. These findings have implications for understanding developmental processes culminating in persistent SIB and may inform prevention programming.
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Transtorno do Espectro Autista , Transtorno Autístico , Comportamento Autodestrutivo , Humanos , Masculino , Pré-Escolar , Criança , Lactente , Feminino , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/diagnóstico , Irmãos , Fatores de Risco , Comportamento Autodestrutivo/epidemiologiaRESUMO
Debates about the ethics of human brain organoids have proceeded without the input of individuals whose brains are being modeled. Interviews with donors of biospecimens for brain organoid research revealed overall enthusiasm for brain organoids as a tool for biomedical discovery, alongside a desire for ongoing engagement with research teams to learn the results of the research, to allow transfer of decision-making authority over time, and to ensure ethical boundaries are not crossed. Future work is needed to determine the most feasible and resource-efficient way to longitudinally engage donors participating in brain organoid research.
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Bancos de Espécimes Biológicos , Pesquisa Biomédica , Humanos , Doadores de Tecidos , Encéfalo , Organoides , Consentimento Livre e EsclarecidoRESUMO
Auditory processing differences, including hyper- or hyposensitivity to sound, aversions to sound, and difficulty listening under noisy, real-world conditions, are commonly reported in autistic individuals. However, the developmental course and functional impact of these auditory processing differences are unclear. In this study, we investigate the prevalence, developmental trajectory, and functional impact of auditory processing differences in autistic children throughout childhood using a longitudinal study design. Auditory processing differences were measured using the Short Sensory Profile, a caregiver questionnaire, in addition to adaptive behaviors and disruptive/concerning behaviors at 3, 6, and 9 years of age. Our results showed that auditory processing differences were reported in greater than 70% of the autistic children in our sample at all three timepoints, maintained a high prevalence through 9 years of age, and were associated with increased disruptive/concerning behaviors and difficulty with adaptive behaviors. Furthermore, in our sample of children, auditory processing differences at age 3 years predicted disruptive/concerning behaviors and difficulty with adaptive behaviors at age 9 years. These findings warrant further investigations of the potential benefit of incorporating measures of auditory processing during routine clinical evaluations as well as interventions targeting auditory processing differences in autistic children.
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Importance: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored. Objective: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives. Design, Setting, and Participants: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL (n = 55) of autism at 4 university-based research centers. Data were collected from January 1, 2007, to December 31, 2013, and analyzed between August 2021 and June 2022 as part of the Infant Brain Imaging Study. Main Outcomes and Measures: Direct assessments of EF and acquired structural magnetic resonance imaging were performed to determine frontal lobe, parietal lobe, and total cerebral brain volume. Results: A total of 165 toddlers (mean [SD] age, 24.61 [0.95] months; 90 [54%] male, 137 [83%] White) at HL for autism (n = 110; 17 diagnosed with ASD) and LL for autism (n = 55) were studied. The toddlers at HL for autism scored lower than the toddlers at LL for autism on EF tests regardless of sex (mean [SE] B = -8.77 [4.21]; 95% CI, -17.09 to -0.45; η2p = 0.03). With the exclusion of toddlers with autism, no group (HL vs LL) difference in EF was found in boys (mean [SE] difference, -7.18 [4.26]; 95% CI, 1.24-15.59), but EF was lower in HL girls than LL girls (mean [SE] difference, -9.75 [4.34]; 95% CI, -18.32 to -1.18). Brain-behavior associations were examined, controlling for overall cerebral volume and developmental level. Sex differences in EF-frontal (B [SE] = 16.51 [7.43]; 95% CI, 1.36-31.67; η2p = 0.14) and EF-parietal (B [SE] = 17.68 [6.99]; 95% CI, 3.43-31.94; η2p = 0.17) associations were found in the LL group but not the HL group (EF-frontal: B [SE] = -1.36 [3.87]; 95% CI, -9.07 to 6.35; η2p = 0.00; EF-parietal: B [SE] = -2.81 [4.09]; 95% CI, -10.96 to 5.34; η2p = 0.01). Autism likelihood group differences in EF-frontal (B [SE] = -9.93 [4.88]; 95% CI, -19.73 to -0.12; η2p = 0.08) and EF-parietal (B [SE] = -15.44 [5.18]; 95% CI, -25.86 to -5.02; η2p = 0.16) associations were found in girls not boys (EF-frontal: B [SE] = 6.51 [5.88]; 95% CI, -5.26 to 18.27; η2p = 0.02; EF-parietal: B [SE] = 4.18 [5.48]; 95% CI, -6.78 to 15.15; η2p = 0.01). Conclusions and Relevance: This cohort study of toddlers at HL and LL of autism suggests that there is an association between sex and EF and that brain-behavior associations in EF may be altered in children at HL of autism. Furthermore, EF deficits may aggregate in families, particularly in girls.
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Transtorno do Espectro Autista , Transtorno Autístico , Lactente , Humanos , Masculino , Feminino , Pré-Escolar , Adulto Jovem , Adulto , Função Executiva , Transtorno Autístico/diagnóstico por imagem , Estudos de Coortes , Transtorno do Espectro Autista/epidemiologia , Estudos ProspectivosRESUMO
This study investigated the extent to which sensory responsivity in infancy contributes to adaptive behavior development among toddlers at high-familial likelihood for autism. Prospective, longitudinal data were analyzed for 218 children, 58 of whom received an autism diagnosis. Results indicated that sensory profiles at age one year (hyperresponsivity, sensory seeking) were negatively associated with later adaptive behavior, particularly for socialization, at age 3 years regardless of diagnostic status. These results suggest that early differences in sensory responsivity may have downstream developmental consequences related to social development among young children with high-familial likelihood for autism.
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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.