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.

White matter connectivity and social functioning in survivors of pediatric brain tumor.

OBJECTIVE: Survivors of pediatric brain tumors (SPBT) are at risk for social deficits, fewer friendships, and poor peer relations. SPBT also experience reduced brain connectivity via microstructural disruptions to white matter from neurological insults. Research with other populations implicates white matter connectivity as a key contributor to poor social functioning. This case-controlled diffusion-weighted imaging study evaluated structural connectivity in SPBT and typically developing controls (TDC) and associations between metrics of connectivity and social functioning. METHODS: Diffusion weighted-imaging results from 19 SPBT and 19 TDC were analyzed using probabilistic white matter tractography. Survivors were at least 5 years post-diagnosis and 2 years off treatment. Graph theory statistics measured group differences across several connectivity metrics, including average strength, global efficiency, assortativity, clustering coefficient, modularity, and betweenness centrality. Analyses also evaluated the effects of neurological risk on connectivity among SPBT. Correlational analyses evaluated associations between connectivity and indices of social behavior. RESULTS: SPBT demonstrated reduced global connectivity compared to TDC. Several medical factors (e.g., chemotherapy, recurrence, multimodal therapy) were related to decreased connectivity across metrics of integration (e.g., average strength, global efficiency) in SPBT. Connectivity metrics were related to peer relationship quality and social challenges in the SPBT group and to social challenges in the total sample. CONCLUSIONS: Microstructural white matter connectivity is diminished in SPBT and related to neurological risk and peer relationship quality. Additional neuroimaging research is needed to evaluate associations between brain connectivity metrics and social functioning in SPBT.

Social impairment in survivors of pediatric brain tumors via reduced social attention and emotion-specific facial expression recognition.

BACKGROUND/OBJECTIVES: Survivors of pediatric brain tumors (SPBT) experience significant social challenges, including fewer friends and greater isolation than peers. Difficulties in face processing and visual social attention have been implicated in these outcomes. This study evaluated facial expression recognition (FER), social attention, and their associations with social impairments in SPBT. METHODS: SPBT (N = 54; ages 7-16) at least 2 years post treatment completed a measure of FER, while parents completed measures of social impairment. A subset (N = 30) completed a social attention assessment that recorded eye gaze patterns while watching videos depicting pairs of children engaged in joint play. Social Prioritization scores were calculated, with higher scores indicating more face looking. Correlations and regression analyses evaluated associations between variables, while a path analysis modeling tool (PROCESS) evaluated the indirect effects of Social Prioritization on social impairments through emotion-specific FER. RESULTS: Poorer recognition of angry and sad facial expressions was significantly correlated with greater social impairment. Social Prioritization was positively correlated with angry FER but no other emotions. Social Prioritization had significant indirect effects on social impairments through angry FER. CONCLUSION: Findings suggest interventions aimed at improving recognition of specific emotions may mitigate social impairments in SPBT. Further, reduced social attention (i.e., diminished face looking) could be a factor in reduced face processing ability, which may result in social impairments. Longitudinal research is needed to elucidate temporal associations between social attention, face processing, and social impairments.

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.

Reduced Fusiform Gyrus Activation During Face Processing in Pediatric Brain Tumor Survivors.

OBJECTIVE: The neural mechanisms contributing to the social problems of pediatric brain tumor survivors (PBTS) are unknown. Face processing is important to social communication, social behavior, and peer acceptance. Research with other populations with social difficulties, namely autism spectrum disorder, suggests atypical brain activation in areas important for face processing. This case-controlled functional magnetic resonance imaging (fMRI) study compared brain activation during face processing in PBTS and typically developing (TD) youth. METHODS: Participants included 36 age-, gender-, and IQ-matched youth (N = 18 per group). PBTS were at least 5 years from diagnosis and 2 years from the completion of tumor therapy. fMRI data were acquired during a face identity task and a control condition. Groups were compared on activation magnitude within the fusiform gyrus for the faces condition compared to the control condition. Correlational analyses evaluated associations between neuroimaging metrics and indices of social behavior for PBTS participants. RESULTS: Both groups demonstrated face-specific activation within the social brain for the faces condition compared to the control condition. PBTS showed significantly decreased activation for faces in the medial portions of the fusiform gyrus bilaterally compared to TD youth, ps ≤ .004. Higher peak activity in the left fusiform gyrus was associated with better socialization (r = .53, p < .05). CONCLUSIONS: This study offers initial evidence of atypical activation in a key face processing area in PBTS. Such atypical activation may underlie some of the social difficulties of PBTS. Social cognitive neuroscience methodologies may elucidate the neurobiological bases for PBTS social behavior.

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.

Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years.

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.

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.

Natural language markers of social phenotype in girls with autism.

BACKGROUND: Girls with autism spectrum condition (ASC) are chronically underdiagnosed compared to boys, which may be due to poorly understood sex differences in a variety of domains, including social interest and motivation. In this study, we use natural language processing to identify objective markers of social phenotype that are easily obtained from a brief conversation with a nonexpert. METHODS: 87 school-aged children and adolescents with ASC (17 girls, 33 boys) or typical development (TD; 15 girls, 22 boys) were matched on age (mean = 11.35 years), IQ estimates (mean = 107), and - for ASC participants - level of social impairment. Participants engaged in an informal 5-min 'get to know you' conversation with a nonexpert conversation partner. To measure attention to social groups, we analyzed first-person plural pronoun variants (e.g., 'we' and 'us') and third-person plural pronoun variants (e.g., 'they' and 'them'). RESULTS: Consistent with prior research suggesting greater social motivation in autistic girls, autistic girls talked more about social groups than did ASC boys. Compared to TD girls, autistic girls demonstrated atypically heightened discussion of groups they were not a part of ('they', 'them'), indicating potential awareness of social exclusion. Pronoun use predicted individual differences in the social phenotypes of autistic girls. CONCLUSIONS: Relatively heightened but atypical social group focus is evident in autistic girls during spontaneous conversation, which contrasts with patterns observed in autistic boys and TD girls. Quantifying subtle linguistic differences in verbally fluent autistic girls is an important step toward improved identification and support for this understudied sector of the autism spectrum.

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.

Face Processing and Social Functioning in Pediatric Brain Tumor Survivors.

OBJECTIVE: Pediatric brain tumor survivors (PBTS) experience deficits in social functioning. Facial expression and identity recognition are key components of social information processing and are widely studied as an index of social difficulties in youth with autism spectrum disorder (ASD) and other neurodevelopmental conditions. This study evaluated facial expression and identity recognition among PBTS, youth with ASD, and typically developing (TD) youth, and the associations between these face processing skills and social impairments. METHODS: PBTS (N = 54; ages 7-16) who completed treatment at least 2 years prior were matched with TD (N = 43) youth and youth with ASD (N = 55) based on sex and IQ. Parents completed a measure of social impairments and youth completed a measure of facial expression and identity recognition. RESULTS: Groups significantly differed on social impairments (p < .001), with youth with ASD scoring highest followed by PBTS and lastly TD youth. Youth with ASD performed significantly worse on the two measures of facial processing, while TD youth and PBTS were not statistically different. The association of facial expression recognition and social impairments was moderated by group, such that PBTS with higher levels of social impairment performed worse on the expression task compared to TD and ASD groups (p < .01, η2 = 0.07). CONCLUSIONS: Variability in face processing may be uniquely important to the social challenges of PBTS compared to other neurodevelopmental populations. Future directions include prospectively examining associations between facial expression recognition and social difficulties in PBTS and face processing training as an intervention for PBTS.

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.

Bayesian regression-based developmental norms for the Benton Facial Recognition Test in males and females.

Face identity recognition is important for social interaction and is impaired in a range of clinical disorders, including several neurodevelopmental disorders. The Benton Facial Recognition Test (BFRT; Benton & Van Allen, 1968), a widely used assessment of identity recognition, is the only standardized test of face identity perception, as opposed to face memory, that has been normed on children and adolescents. However, the existing norms for the BFRT are suboptimal, with several ages not represented and no established time limit (which can lead to inflated scores by allowing individuals with prosopagnosia to use feature matching). Here we address these issues with a large normative dataset of children and adolescents (ages 5-17, N = 398) and adults (ages 18-55; N = 120) who completed a time-limited version of the BFRT. Using Bayesian regression, we demonstrate that face identity perception increases asymptotically from childhood through adulthood, and provide continuous norms based on age and sex that can be used to calculate standard scores. We show that our time limit of 16 seconds per item yields scores comparable to the existing norms without time limits from the non-prosopagnostic samples. We also find that females (N = 156) score significantly higher than males (N = 362), supporting the existence of a female superiority effect for face identification. Overall, these results provide more robust norms for the BFRT and promote future research on face identity perception in developmental populations.

Abnormal maturation of the resting-state peak alpha frequency in children with autism spectrum disorder.

Age-related changes in resting-state (RS) neural rhythms in typically developing children (TDC) but not children with autism spectrum disorder (ASD) suggest that RS measures may be of clinical use in ASD only for certain ages. The study examined this issue via assessing RS peak alpha frequency (PAF), a measure previous studies, have indicated as abnormal in ASD. RS magnetoencephalographic (MEG) data were obtained from 141 TDC (6.13-17.70 years) and 204 ASD (6.07-17.93 years). A source model with 15 regional sources projected the raw MEG surface data into brain source space. PAF was identified in each participant from the source showing the largest amplitude alpha activity (7-13 Hz). Given sex differences in PAF in TDC (females > males) and relatively few females in both groups, group comparisons were conducted examining only male TDC (N = 121) and ASD (N = 183). Regressions showed significant group slope differences, with an age-related increase in PAF in TDC (R2 = 0.32) but not ASD (R2 = 0.01). Analyses examining male children below or above 10-years-old (median split) indicated group effects only in the younger TDC (8.90 Hz) and ASD (9.84 Hz; Cohen's d = 1.05). In the older ASD, a higher nonverbal IQ was associated with a higher PAF. In the younger TDC, a faster speed of processing was associated with a higher PAF. PAF as a marker for ASD depends on age, with a RS alpha marker of more interest in younger versus older children with ASD. Associations between PAF and cognitive ability were also found to be age and group specific.

A longitudinal study of parent-reported sensory responsiveness in toddlers at-risk for autism.

BACKGROUND: Atypical sensory responsivity and sensory interests are now included in the DSM 5 diagnostic criteria for autism spectrum disorder (ASD) under the broad domain of restricted and repetitive behavior (RRB). However, relatively little is known about the emergence of sensory-related features and their relation to conventionally defined RRB in the first years of life. METHODS: Prospective, longitudinal parent-report data using the Sensory Experiences Questionnaire (SEQ) were collected for 331 high-risk toddlers (74 of whom met diagnostic criteria for ASD at age 2) and 135 low-risk controls. Longitudinal profiles for SEQ scores were compared between groups across ages 12-24 months. Associations between SEQ measures and measures of RRB subtypes (based on the Repetitive Behavior Scale, Revised) were also examined. RESULTS: Longitudinal profiles for all SEQ scores significantly differed between groups. SEQ scores were elevated for the ASD group from age 12 months, with differences becoming more pronounced across the 12-24 month interval. At both 12 and 24 months, most measures derived from the SEQ were significantly associated with all subtypes of RRB. CONCLUSIONS: These findings suggest that differences in sensory responsivity may be evident in high-risk infants later diagnosed with ASD in early toddlerhood, and that the magnitude of these differences increases over the second year of life. The high degree of association between SEQ scores and RRB supports the conceptual alignment of these features but also raises questions as to explanatory mechanisms.

Pre- and Paralinguistic Vocal Production in ASD: Birth Through School Age.

PURPOSE OF REVIEW: We review what is known about how pre-linguistic vocal differences in autism spectrum disorder (ASD) unfold across development and consider whether vocalization features can serve as useful diagnostic indicators. RECENT FINDINGS: Differences in the frequency and acoustic quality of several vocalization types (e.g., babbles and cries) during the first year of life are associated with later ASD diagnosis. Paralinguistic features (e.g., prosody) measured during early and middle childhood can accurately classify current ASD diagnosis using cross-validated machine learning approaches. Pre-linguistic vocalization differences in infants are promising behavioral markers of later ASD diagnosis. In older children, paralinguistic features hold promise as diagnostic indicators as well as clinical targets. Future research efforts should focus on (1) bridging the gap between basic research and practical implementations of early vocalization-based risk assessment tools, and (2) demonstrating the clinical impact of targeting atypical vocalization features during social skill interventions for older children.

Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers.

Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction.

Whole brain white matter connectivity analysis using machine learning: An application to autism.

In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.