Altered lateralization of dorsal language tracts in 6‐week‐old infants at risk for autism

Altered structural connectivity has been identified as a possible biomarker of autism spectrum disorder (ASD) risk in the developing brain. Core features of ASD include impaired social communication and early language delay. Thus, examining white matter tracts associated with language may lend further insight into early signs of ASD risk and the mechanisms that underlie language impairments associated with the disorder. Evidence of altered structural connectivity has previously been detected in 6‐month‐old infants at high familial risk for developing ASD. However, as language processing begins in utero, differences in structural connectivity between language regions may be present in the early infant brain shortly after birth. Here we investigated key white matter pathways of the dorsal language network in 6‐week‐old infants at high (HR) and low (LR) risk for ASD to identify atypicalities in structural connectivity that may predict altered developmental trajectories prior to overt language delays and the onset of ASD symptomatology. Compared to HR infants, LR infants showed higher fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF); in contrast, in the right SLF, HR infants showed higher FA than LR infants. Additionally, HR infants showed more rightward lateralization of the SLF. Across both groups, measures of FA and lateralization of these pathways at 6 weeks of age were related to later language development at 18 months of age as well as ASD symptomatology at 36 months of age. These findings indicate that early differences in the structure of language pathways may provide an early predictor of future language development and ASD risk.     

DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex

Caregivers play a critical role in scaffolding infant stress reactivity and regulation, but the mechanisms by which this scaffolding occurs is unclear. Animal models strongly suggest that epigenetic processes, such as DNA methylation, are sensitive to caregiving behaviors and, in turn, offspring stress reactivity. We examined the direct effects of caregiving behaviors on DNA methylation in infants and infant stress reactivity. Infants and mothers (N = 128) were assessed during a free play when infants were 5 months old. Maternal responsiveness and appropriate touch were coded. and infant buccal epithelial cells were sampled to assess for DNA methylation of the glucocorticoid receptor gene, NR3c1 exon 1F. Infant cortisol reactivity was assessed in response to the still-face paradigm. Greater levels of maternal responsiveness and appropriate touch were related to less DNA methylation of specific regions in NR3c1 exon 1F, but only for females. There was no association with maternal responsiveness and appropriate touch or DNA methylation of NR3c1 exon 1F on prestress cortisol or cortisol reactivity. Our results are discussed in relation to programming models that implicate maternal care as an important factor in programing infant stress reactivity.     

Imitation from 12 to 24 months in autism and typical development: a longitudinal Rasch analysis

The development of imitation during the second year of life plays an important role in domains of sociocognitive development such as language and social learning. Deficits in imitation ability in persons with autism spectrum disorder (ASD) from toddlerhood into adulthood have also been repeatedly documented, raising the possibility that early disruptions in imitation contribute to the onset of ASD and the deficits in language and social interaction that define the disorder. This study prospectively examined the development of imitation between 12 and 24 months of age in 154 infants at familial risk for ASD and 78 typically developing infants who were all later assessed at 36 months for ASD or other developmental delays. The study established a developmental measure of imitation ability and examined group differences over time, using an analytic Rasch measurement model. Results revealed a unidimensional latent construct of imitation and verified a reliable sequence of imitation skills that was invariant over time for all outcome groups. Results also showed that all groups displayed similar significant linear increases in imitation ability between 12 and 24 months and that these increases were related to individual growth in both expressive language and ratings of social engagement but not in fine motor development. The group of children who developed ASD by age 3 years exhibited delayed imitation development compared with the low-risk typical outcome group across all time-points, but were indistinguishable from other high-risk infants who showed other cognitive delays not related to ASD.     

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.

     

Parent-child interaction during the first year of life in infants at elevated likelihood of autism spectrum disorder

Autism spectrum disorder (ASD) likely emerges from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the environment. The interaction with parents forms a key aspect of an infant’s social environment, but few prospective studies of infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) have examined parent-child interactions in the first year of life. As part of a European multisite network, parent-child dyads of free play were observed at 5 months (62 EL infants, 47 infants at typical likelihood (TL)) and 10 months (101 EL siblings, 77 TL siblings). The newly-developed Parent-Infant/Toddler Coding of Interaction (PInTCI) scheme was used, focusing on global characteristics of infant and parent behaviors. Coders were blind to participant information. Linear mixed model analyses showed no significant group differences in infant or parent behaviors at 5 or 10 months of age (all ps≥0.09, d≤0.36), controlling for infant’s sex and age, and parental educational level. However, without adjustments, EL infants showed fewer and less clear initiations at 10 months than TL infants (p = 0.02, d = 0.44), but statistical significance was lost after controlling for parental education (p = 0.09, d = 0.36), which tended to be lower in the EL group. Consistent with previous literature focusing on parent-infant dyads, our findings suggest that differences between EL and TL dyads may only be subtle during the first year of life. We discuss possible explanations and implications for future developmental studies.     

How are social-emotional and behavioral competences and problems at age 1 year associated with infant motor development? A general population study

Based on limitations in previous research evidence, we concluded that more research is needed for deeper understanding of how social-emotional and behavioral (SEB) outcomes among infant-toddler-aged children in the general population are associated with early motor development. In this study, we investigated associations between early competencies and problems, as measured by the Brief Infant-Toddler Social and Emotional Assessment (BITSEA), and the timing of achievement of the main gross and fine motor milestones usually attained during the first year of life in a general population context. The study sample consisted of 515 infants (mean age 12.9 [SD 0.9] months) and their parents (514 mothers, 434 fathers), who were recruited in child health centers in Northern Finland. The infants were divided into two groups, based on their BITSEA screen status, and motor milestone achievement ages were compared across BITSEA screen status No Concern and Of-Concern infants. An Of-Concern screen status on the maternal and paternal Competence scale and Autism spectrum disorder (ASD) item cluster was associated with later infant achievement ages for gross motor milestones. By contrast, infants who were screened to be in the Of-Concern range on the maternal Problem scale achieved gross motor milestones earlier than infants with the corresponding No Concern screen status. No significant associations were found between the paternal Problem scale screen status and infant motor development. In further analyses, the strongest associations were found between an Of-Concern screen status on the paternal Competence scale and ASD item cluster and infant motor development. The findings indicate that the inclusion of infant motor developmental information may assist early identification and the clinical interpretation of parental reports of early SEB problems. Clinical implications of the current findings are discussed in the paper.     

The role of maternal responsiveness in predicting infant affect during the still face paradigm with infants born very low birth weight

There is limited empirical literature addressing infants' response to a standardized stressor with infants born very low birth weight (VLBW). The purpose of this study was to assess the relative strength of maternal responsiveness in predicting infant affect in response to the Still Face (SF) paradigm in a cross‐sectional cohort of ethnically diverse infants born VLBW and their mothers (N = 50; infants 6–8 months old). Infant affect and maternal responsiveness were coded in 1‐s intervals while dyads participated in the SF. In addition, perinatal medical status, developmental status, and infant temperament were assessed. Findings revealed that positive infant affect during and after the SF stressor were strongly associated with baseline infant positive affect and maternal responsiveness at the reunion episode, respectively. In contrast, when predicting negative infant affect during and after the SF stressor, prior infant negative affect was strongly and uniquely significant. Infant positive affect, negative affect, and maternal responsiveness were not significantly associated with gender, infant perinatal medical history, developmental status, or temperament. Future research is warranted to determine how these findings relate to infants' stress reactions in naturalistic settings and if relationship‐focused interventions may reverse infant negative emotionality, enhance positive emotionality, and thereby improve self‐regulation and longer term social and cognitive developmental outcomes in medically at‐risk infants.     

Infant motor skill predicts later expressive language and autism spectrum disorder diagnosis

Motor difficulties may be an early Autism Spectrum Disorder (ASD) risk indicator and may predict subsequent expressive language skills. Further understanding of motor functioning in the first year of life in children with ASD is needed. We examined motor skills in 6-month-olds (n = 140) at high and low familial risk for ASD using the Peabody Developmental Motor Scales (Grasping, Visual-Motor Integration, and Stationary subscales). In Study 1, motor skill at 6 months predicted ASD status at 24–36 months; ASD was associated with poorer infant motor skills. In Study 2, motor skill at 6 months predicted expressive language at 30 and 36 months. Findings provide evidence that vulnerability in motor function early in development is present in ASD. Findings highlight the importance of developmental monitoring in high-risk infants and possible cascading effects of early disruption in motor development.     

DNA methylation and behavioral changes induced by neonatal spinal transection

Although the importance of epigenetic mechanisms in behavioral development has been gaining attention in recent years, research has largely focused on the brain. To our knowledge, no studies to date have investigated epigenetic changes in the developing spinal cord to determine the dynamic manner in which the spinal epigenome may respond to environmental input during behavioral development. Animal studies demonstrate that spinal cord plasticity is heightened during early development, is somewhat preserved following neonatal transection, and that spinal injured animals are responsive to sensory feedback. Because epigenetic alterations have been implicated in brain plasticity and are highly responsive to experience, these alterations are promising candidates for molecular substrates of spinal plasticity as well. Thus, the current study investigated behavioral changes in the development of weight-bearing locomotion and epigenetic modifications in the spinal cord of infant rats following a neonatal low-thoracic spinal transection or sham surgery on postnatal day (P)1. Specifically, global levels of methylation and methylation status of the brain-derived neurotrophic factor (Bdnf) gene, a neurotrophin heavily involved in both CNS and behavioral plasticity, particularly in development, were examined in lumbar tissue harvested on P10 from sham and spinal-transected subjects. Behavioral results demonstrate that compared to shams, spinal-transected subjects exhibit significantly reduced partial-weight bearing hindlimb activity. Molecular data demonstrate group differences in global lumbar methylation levels as well as exon-specific group differences in Bdnf methylation. This study represents an initial step toward understanding the relationship between epigenetic mechanisms and plasticity associated with spinal cord and locomotor development.     

Increasing parenting self-efficacy: The Fussy Baby Network® intervention

High levels of infant crying place families at risk for disrupted relationships, parenting stress, and even for child maltreatment. We conducted an evaluation of the Fussy Baby Network^® (FBN), a program supporting families struggling with infant crying and related concerns. The study contrasted 29 families who sought help from FBN with 27 families with excessively crying infants who did not seek services. Researchers measured parenting self-efficacy, depression, and stress in each group before and after the intervention. Results from hierarchical multiple regression analysis indicated greater improvements over time in parenting self-efficacy for parents receiving FBN services. Furthermore, the greater improvements in parenting self-efficacy in the intervention group were not directly attributable to reductions in infant crying. These findings provide preliminary evidence that the FBN approach may be effective at boosting the confidence of parents struggling with caring for their infants. Future research with larger samples with baseline equivalence and stronger research designs should explore this intervention further. This study also suggests that interventions for families with excessively crying infants should move beyond the focus of reducing infant crying to a broader strategy of supporting parents and strengthening relationships between parents and their infants to build parenting capacity.     

Early and persistent motor difficulties in infants at-risk of developing autism spectrum disorder: A prospective study

Analyses were conducted in order to investigate motor development in younger siblings of children diagnosed with autism spectrum disorder (ASD). Infants at familial risk and low risk of developing ASD were tested longitudinally between the ages of 7 and 36 months. Data were analysed from motor scales on the Mullen Scales of Early Learning and the Vineland Adaptive Behaviour Scales at each age point. Significantly lower motor scores in at-risk infants were evident from the age of 7 months compared to the low-risk group. Infants who were later diagnosed with ASD demonstrated significantly poorer Fine Motor skills at 36 months than at-risk infants without any developmental difficulties. In addition, Gross Motor scores were highly correlated across the two measures for low-risk infants and infants who later developed ASD. Early motor difficulties may be an early indicator of a number of neurodevelopmental disorders, including ASD.     

The mediating role of maternal responsiveness in some longer term effects of postnatal depression on infant development

We hypothesized a mediating role for low maternal responsiveness in certain child developmental deficits found previously to be associated with postnatal depression. Forty depressed inpatients and 48 control (non-depressed) mothers and their infants were followed until 42 months postpartum. Mother–infant interactions were impaired at 6 months postpartum in the depressed group. Subsequent cognitive deficits were found in children's Full Scale IQ on the Wechsler Preschool Primary Scale of Intelligence (Revised) at 42 months of age. Statistical modeling of the mediation hypothesis confirmed that these effects were overwhelmingly explained by lowered maternal responsiveness at 6 months. Similarly, increased temperamental difficulties were apparent in children of depressed mothers but were not correlated with maternal responsiveness. Male infants of depressed mothers were disproportionately vulnerable (compared to females) to impaired cognitive abilities associated with maternal depression. The data concur with previous work and provide empirical support for the theoretical prediction that early disturbances of the mother–infant interaction will mediate some developmental deficits in the children of depressed mothers.     

Novelty responding and behavioral development in young,developmentally delayed children

This study examined whether or not a measure of information processing ability based on the discrimination of novel and familiar stimuli was related to behavioral development among developmentally-delayed infants. Two samples of handicapped infants were administered multiple measures of visual novelty discrimination and a battery of assessments which were representative of available measures of development in infancy. The results indicated that, as a group, the developmentally delayed infants were capable of discriminating novel and familiar stimuli. Also, correlational analyses indicated that responding to novelty was related to developmental accessment performance in both samples. This finding is consistent with previous data which indicates that novelty response measures are associated with important individual differences in young children.     

高风险婴儿前瞻性纵向研究与孤独症谱系障碍早期识别

孤独症谱系障碍(Autism Spectrum Disorder, ASD)早期识别有助于早期诊断和早期干预的实施, 对于改善ASD儿童发育结果至关重要。高风险前瞻性纵向研究以高风险婴儿(ASD儿童的年幼同胞, 入组年龄小于12个月)作为主要研究对象, 通过对ASD高风险婴儿(24至36个月之间诊断为ASD的高风险婴儿)的早期发育轨迹的描绘和核心症状早期表现的识别, 为ASD早期识别提供了重要依据。未来可以增加被试数量、延长观察时间并密集观察时间点、关注伴发障碍、综合考虑遗传、环境和文化因素影响, 并结合早期干预研究进行深入探索。未来在中国开展相关研究具有重要的科学价值和临床意义。     

Word comprehension mediates the link between gesture and word production: Examining language development in infant siblings of children with autism spectrum disorder

Children's gesture production precedes and predicts language development, but the pathways linking these domains are unclear. It is possible that gesture production assists in children's developing word comprehension, which in turn supports expressive vocabulary acquisition. The present study examines this mediation pathway in a population with variability in early communicative abilities—the younger siblings of children with autism spectrum disorder (ASD; high‐risk infants, HR). Participants included 92 HR infants and 28 infants at low risk (LR) for ASD. A primary caregiver completed the MacArthur‐Bates Communicative Development Inventory (Fenson, et al., 1993) at 12, 14, and 18 months, and HR infants received a diagnostic evaluation for ASD at 36 months. Word comprehension at 14 months mediated the relationship between 12‐month gesture and 18‐month word production in LR and HR infants (ab = 0.263; p < 0.01). For LR infants and HR infants with no diagnosis or language delay, gesture was strongly associated with word comprehension (as = 0.666; 0.646; 0.561; ps < 0.01). However, this relationship did not hold for infants later diagnosed with ASD (a = 0.073; p = 0.840). This finding adds to a growing literature suggesting that children with ASD learn language differently. Furthermore, this study provides an initial step toward testing the developmental pathways by which infants transition from early actions and gestures to expressive language.     

fNIRS在自闭症脑功能研究中的应用与展望

社会交往能力是人类生存的基本技能。社交能力的缺失会导致严重的行为障碍和精神疾病,如自闭症。由于自闭症儿童的特殊性,绝大多数的自闭症脑成像研究多集中在年龄较大的高功能自闭症儿童在静息态或简单的任务态下的脑激活模式或功能连接状态。自闭症的核心症状—社会交往障碍和语言交流障碍却较少有研究触及。近年来,近红外光学脑功能成像技术的发展为我们在真实的交流和互动中研究自闭症儿童的神经病理机制提供了新的工具和机遇。     

Facial Emotion Recognition in Autism Spectrum Disorders: A Review of Behavioral and Neuroimaging Studies

Behavioral studies of facial emotion recognition (FER) in autism spectrum disorders (ASD) have yielded mixed results. Here we address demographic and experiment-related factors that may account for these inconsistent findings. We also discuss the possibility that compensatory mechanisms might enable some individuals with ASD to perform well on certain types of FER tasks in spite of atypical processing of the stimuli, and difficulties with real-life emotion recognition. Evidence for such mechanisms comes in part from eye-tracking, electrophysiological, and brain imaging studies, which often show abnormal eye gaze patterns, delayed event-related-potential components in response to face stimuli, and anomalous activity in emotion-processing circuitry in ASD, in spite of intact behavioral performance during FER tasks. We suggest that future studies of FER in ASD: 1) incorporate longitudinal (or cross-sectional) designs to examine the developmental trajectory of (or age-related changes in) FER in ASD and 2) employ behavioral and brain imaging paradigms that can identify and characterize compensatory mechanisms or atypical processing styles in these individuals.     

Cerebral blood flow in 5‐ to 8‐month‐olds: Regional tissue maturity is associated with infant affect

Infancy is marked by rapid neural and emotional development. The relation between brain function and emotion in infancy, however, is not well understood. Methods for measuring brain function predominantly rely on the BOLD signal; however, interpretation of the BOLD signal in infancy is challenging because the neuronal‐hemodynamic relation is immature. Regional cerebral blood flow (rCBF) provides a context for the infant BOLD signal and can yield insight into the developmental maturity of brain regions that may support affective behaviors. This study aims to elucidate the relations among rCBF, age, and emotion in infancy. One hundred and seven mothers reported their infants' (infant age M ± SD = 6.14 ± 0.51 months) temperament. A subsample of infants completed MRI scans, 38 of whom produced usable perfusion MRI during natural sleep to quantify rCBF. Mother‐infant dyads completed the repeated Still‐Face Paradigm, from which infant affect reactivity and recovery to stress were quantified. We tested associations of infant age at scan, temperament factor scores, and observed affect reactivity and recovery with voxel‐wise rCBF. Infant age was positively associated with CBF in nearly all voxels, with peaks located in sensory cortices and the ventral prefrontal cortex, supporting the formulation that rCBF is an indicator of tissue maturity. Temperamental Negative Affect and recovery of positive affect following a stressor were positively associated with rCBF in several cortical and subcortical limbic regions, including the orbitofrontal cortex and inferior frontal gyrus. This finding yields insight into the nature of affective neurodevelopment during infancy. Specifically, infants with relatively increased prefrontal cortex maturity may evidence a disposition toward greater negative affect and negative reactivity in their daily lives yet show better recovery of positive affect following a social stressor.     

The effect of communication deficits on anxiety symptoms in infants and toddlers with autism spectrum disorders

Autism spectrum disorders (ASDs) are life-long developmental disorders characterized by impairments in the development of reciprocal social and communication skills, abnormal language development, and a restricted repertoire of behaviors and interests. While it has been known for some time that children with ASD can evince elevated rates of anxiety symptoms, little research has been conducted on whether deficits in communication skills affect the range of anxiety symptoms in infants and toddlers with ASD. This study represents a first attempt to determine whether deficits in communication skills have an effect on the expression of anxiety in infants and toddlers with autistic disorder and pervasive developmental disorder-not otherwise specified. Seven hundred thirty-five infants were evaluated with respect to the nature and extent of anxiety symptoms and developmental functioning. Both receptive and expressive communication skills appeared to play a significant role in the manifestation of anxiety symptoms.