Developmental Trajectories of Irritability across the Transition to Toddlerhood: Associations with Effortful Control and Psychopathology.

Preschool-age irritability is a transdiagnostic marker of internalizing and externalizing problems. However, researchers have generally been reluctant to examine irritability within a clinically salient framework at younger ages due to some instability during the "terrible twos" period. Developmentally sensitive and dense measurements to capture intra- and inter-individual variability, as well as exploration of developmental processes that predict change, are needed. This study aimed to examine (1) the trajectories of irritability at the transition to toddlerhood (12-24 months of age) using repeated measures, (2) whether effortful control was associated with individual differences in level and growth rate of irritability, and (3) whether individual differences in the irritability trajectories were associated with later psychopathology. Families were recruited when the child was 12-18 months old (N = 333, 45.65% female). Mothers reported on their toddler's irritability at baseline and every two months until a follow-up laboratory assessment approximately one year later. Effortful control was measured at baseline. Clinical internalizing/externalizing symptoms were measured at the follow-up assessment. Hierarchical linear models revealed an increase in irritability over time, yet there was relatively little within-person variability. Effortful control was only associated with the level of irritability and not growth rate. Level of irritability was associated with internalizing, externalizing, and combined symptoms, but growth rate was not. Findings suggest intraindividual stability in irritability at the transition to toddlerhood and the possibility that screening for elevated irritability at toddler age is meaningful.

Behavioral and neural measures of infant responsivity increase with maternal multisensory input in non-irritable infants.

INTRODUCTION: Parents often use sensory stimulation during early-life interactions with infants. These interactions, including gazing, rocking, or singing, scaffold child development. Previous studies have examined infant neural processing during highly controlled sensory stimulus presentation paradigms. OBJECTIVE: In this study, we investigated infant behavioral and neural responsiveness during a mother-child social interaction during which the mother provided infant stimulation with a progressive increase in the number of sensory modalities. METHODS: We prospectively collected and analyzed video-coded behavioral interactions and electroencephalogram (EEG) frontal asymmetry (FAS) from infants (n = 60) at 2-4 months born at ≥ 34 weeks gestation. As the number of sensory modalities progressively increased during the interaction, infant behaviors of emotional connection in facial expressiveness, sensitivity to mother, and vocal communication increased significantly. Conversely, infant FAS for the entire cohort did not change significantly. However, when we accounted for infant irritability, both video-coded behaviors and EEG FAS markers of infant responsiveness increased across the interaction in the non-irritable infants. The non-irritable infants (49%) demonstrated positive FAS, indicating readiness to engage with, rather than to withdraw from, multisensory but not unisensory interactions with their mothers. RESULTS: These results suggest that multisensory input from mothers is associated with greater infant neural approach state and highlight the importance of infant behavioral state during neural measures of infant responsiveness.

A systematic review of interventions to ameliorate the impact of adversity on brain development.

Adversity, including abuse, neglect, and poverty, impacts child brain development. However, the developing brain is highly plastic, and some of the impacts of childhood adversity may be mitigated by psychosocial interventions. The purpose of this review is to synthesize literature on neural outcomes of childhood interventions among individuals exposed to adversity. A systematic literature search identified 36 reports of 13 interventions. Overall, these studies provide evidence for experience-dependent plasticity in the developing brain. We synthesize studies in light of three themes. First, there was mixed evidence for a benefit of a younger age at intervention. Second, interventions tended to accelerate functional brain development, but the impact of interventions on the pace of structural brain development was less clear. Third, individual differences in intervention response were difficult to predict, in part due to small samples. However, there was significant variability in intervention type and timing, neuroimaging outcomes, and follow-up timing. Together, the studies reviewed here hold promise for the role of psychosocial interventions in ameliorating the neurodevelopmental consequences of childhood adversity.

What the Evidence Does (and Does Not) Show for the Centers for Disease Control and Prevention Child Development Milestones: An Illustrative Example Using Expressive Vocabulary.

PURPOSE: Child development milestones are a critical tool for pediatricians and caregivers to use for developmental surveillance. Following review and selection by a panel of subject matter experts, the Centers for Disease Control and Prevention (CDC) published a revised list of milestones across multiple domains of development. Using expressive vocabulary, a key indicator of language development, as an illustrative example, the purpose of this brief review is to evaluate the evidence used to establish the CDC developmental milestones and determine whether the samples used to establish these milestones are representative of U.S. children. METHOD: Authors reviewed the methods and evidence cited to determine the CDC milestones. First, authors identified each language/communication milestone that measured expressive vocabulary as number of words, followed by review of the sources cited in support of each extracted milestone. Then, data related to both milestones and sample characteristics were extracted and compiled as well as compared with data from a validated parent report measure of expressive vocabulary, the MacArthur-Bates Communication Development Inventories. RESULTS: Results indicated that evidence was conflicting, misaligned, or missing for the selected CDC expressive vocabulary milestones. This review also indicated that the samples used to determine the selected CDC expressive vocabulary milestones are not representative of U.S. children. CONCLUSION: The striking paucity of evidence supporting the new CDC milestones for expressive vocabulary illustrates the critical need for future research in this area to establish more accurate milestones for U.S. children, with a focus on culturally inclusive large-scale data.

Neurodevelopmental vulnerability to psychosis: developmentally-based methods enable detection of early life inhibitory control deficits that predict psychotic-like experiences at the transition to adolescence.

BACKGROUND: Inhibitory control develops in early childhood, and atypical development may be a measurable marker of risk for the later development of psychosis. Additionally, inhibitory control may be a target for intervention. METHODS: Behavioral performance on a developmentally appropriate Go/No-Go task including a frustration manipulation completed by children ages 3-5 years (early childhood; n = 107) was examined in relation to psychotic-like experiences (PLEs; 'tween'; ages 9-12), internalizing symptoms, and externalizing symptoms self-reported at long-term follow-up (pre-adolescence; ages 8-11). ERP N200 amplitude for a subset of these children (n = 34) with electrophysiological data during the task was examined as an index of inhibitory control. RESULTS: Children with lower accuracy on No-Go trials compared to Go trials in early childhood (F(1,101) = 3.976, p = 0.049), evidenced higher PLEs at the transition to adolescence 4-9 years later, reflecting a specific deficit in inhibitory control. No association was observed with internalizing or externalizing symptoms. Decreased accuracy during the frustration manipulation predicted higher internalizing, F(2,202) = 5.618, p = 0.004, and externalizing symptoms, F(2,202) = 4.663, p = 0.010. Smaller N200 amplitudes were observed on No-Go trials for those with higher PLEs, F(1,101) = 6.075, p = 0.020; no relationship was observed for internalizing or externalizing symptoms. CONCLUSIONS: Long-term follow-up demonstrates for the first time a specific deficit in inhibitory control behaviorally and electrophysiology, for individuals who later report more PLEs. Decreases in task performance under frustration induction indicated risk for internalizing and externalizing symptoms. These findings suggest that pathophysiological mechanisms for psychosis are relevant and discriminable in early childhood, and further, suggest an identifiable and potentially modifiable target for early intervention.

How penalizing substance use in pregnancy affects treatment and research: a qualitative examination of researchers' perspectives.

Introduction: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood. Methods: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis. Results: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal impacts on research, (iii) proposals for legal reform, and (iv) activism over time. Discussion: Researchers view laws penalizing substance use during pregnancy as failing to treat addiction as a disease and harming pregnant people and families. Respondents routinely made scientific compromises to protect participants. While some have successfully advocated for legal reform, ongoing advocacy is needed. Conclusion: Adverse impacts from criminalizing substance use during pregnancy extend to research on this common and stigmatized problem. Rather than penalizing substance use in pregnancy, laws should approach addiction as a medical issue and support scientific efforts to improve outcomes for affected families.

Preliteracy Skills Mediate the Relation Between Early Speech Sound Production and Subsequent Reading Outcomes.

PURPOSE: Learning to read is a complex, multifaceted process that relies on several speech and language-related subskills. Individual differences in word reading outcomes are indicated among children with inaccurate speech sound productions, with some of these children developing later reading difficulties. There are inconsistent reports as to whether phonological deficits and/or weaknesses in oral language explain these subsequent reading difficulties. Thus, it remains unclear how variability in speech production accuracy in early childhood may impact reading development. Therefore, the present longitudinal study seeks to clarify the relation between speech sound production accuracy in kindergarten and subsequent reading outcomes with a focus on additional potential mediating factors. METHOD: Speech accuracy, core preliteracy skills (phonological awareness, rapid naming, and letter-name knowledge), and additional potential mediators (phonological memory and oral language abilities) were characterized at the start of formal reading instruction. Word reading, decoding, reading fluency, and comprehension were assessed at the end of second grade. Mediation analyses were conducted to examine factors that mediate the relation between speech accuracy in kindergarten and subsequent reading outcomes. RESULTS: Initial associations between early speech sound production accuracy and subsequent reading outcomes were indicated; however, mediation effects of preliteracy skills (phonological awareness and letter-name knowledge) were identified for word reading, decoding, and reading fluency outcomes. For reading comprehension, mediation effects of preliteracy and vocabulary skills were observed. CONCLUSIONS: The relation between speech sound production accuracy and subsequent word reading, decoding, reading fluency, and comprehension was observed to be mediated by preliteracy skills, specifically phonological awareness and letter-name knowledge. For reading comprehension only, vocabulary knowledge were of additional importance. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23671491.

Predictive Utility of Irritability "In Context": Proof-of-Principle for an Early Childhood Mental Health Risk Calculator.

OBJECTIVE: We provide proof-of-principle for a mental health risk calculator advancing clinical utility of the irritability construct for identification of young children at high risk for common, early onsetting syndromes. METHOD: Data were harmonized from two longitudinal early childhood subsamples (total N = 403; 50.1% Male; 66.7% Nonwhite; Mage = 4.3 years). The independent subsamples were clinically enriched via disruptive behavior and violence (Subsample 1) and depression (Subsample 2). In longitudinal models, epidemiologic risk prediction methods for risk calculators were applied to test the utility of the transdiagnostic indicator, early childhood irritability, in the context of other developmental and social-ecological indicators to predict risk of internalizing/externalizing disorders at preadolescence (Mage = 9.9 years). Predictors were retained when they improved model discrimination (area under the receiver operating characteristic curve [AUC] and integrated discrimination index [IDI]) beyond the base demographic model. RESULTS: Compared to the base model, the addition of early childhood irritability and adverse childhood experiences significantly improved the AUC (0.765) and IDI slope (0.192). Overall, 23% of preschoolers went on to develop a preadolescent internalizing/externalizing disorder. For preschoolers with both elevated irritability and adverse childhood experiences, the likelihood of an internalizing/externalizing disorder was 39-66%. CONCLUSIONS: Predictive analytic tools enable personalized prediction of psychopathological risk for irritable young children, holding transformative potential for clinical translation.

From Recognizing Known Words to Learning New Ones: Comparing Online Speech Processing in Typically Developing and Late-Talking 2-Year-Olds.

PURPOSE: This study examines online speech processing in typically developing and late-talking 2-year-old children, comparing both groups' word recognition, word prediction, and word learning. METHOD: English-acquiring U.S. children, from the "When to Worry" study of language and social-emotional development, were identified as typical talkers (n = 67, M age = 27.0 months, SD = 1.4; Study 1) or late talkers (n = 30, M age = 27.0 months, SD = 2.0; Study 2). Children completed an eye-tracking task assessing their ability to recognize both nouns and verbs, to use verbs to predict an upcoming noun's referent, and to use verbs to infer the meaning of novel nouns. RESULTS: Both typical and late talkers recognized nouns and verbs and used familiar verbs to predict the referents of upcoming nouns, whether the noun was familiar ("You can eat the apple") or novel ("You can eat the dax"). Late talkers were slower in using familiar nouns to orient to the target and were both slower and less accurate in using familiar verbs to identify the upcoming noun's referent. Notably, however, both groups learned and retained novel word meanings with similar success. CONCLUSIONS: Late talkers demonstrated slower lexical processing, especially for verbs. Yet, their success in using familiar verbs to learn novel nouns suggests that, as a group, their slower processing did not impair word learning in this task. This sets the foundation for future work investigating whether these measures predict later language outcomes and can differentiate late talkers with transient delays from those with language disorders.

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.

Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual's risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood.

Maturation of large-scale brain systems over the first month of life.

The period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child's earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain "growth curve" that could be used to identify atypical brain maturation in infancy.

Lability of prenatal stress during the COVID-19 pandemic links to negative affect in infancy.

The association between prenatal stress and children's socioemotional development is well established. The COVID-19 pandemic has been a particularly stressful period, which may impact the gestational environment. However, most studies to-date have examined prenatal stress at a single time point, potentially masking the natural variation in stress that occurs over time, especially during a time as uncertain as the pandemic. This study leveraged dense ecological momentary assessments from a prenatal randomized control trial to examine patterns of prenatal stress over a 14-week period (up to four assessments/day) in a U.S. sample of 72 mothers and infants. We first examined whether varied features of stress exposure (lability, mean, and baseline stress) differed depending on whether mothers reported on their stress before or during the pandemic. We next examined which features of stress were associated with 3-month-old infants' negative affect. We did not find differences in stress patterns before and during the pandemic. However, greater stress lability, accounting for baseline and mean stress, was associated with higher infant negative affect. These findings suggest that pathways from prenatal stress exposure to infant socioemotional development are complex, and close attention to stress patterns over time will be important for explicating these pathways.

Developmental patterning of irritability enhances prediction of psychopathology in preadolescence: Improving RDoC with developmental science.

The transdiagnostic importance of irritability in psychopathology has been demonstrated. However, the contribution of developmentally unfolding irritability patterns to specific clinical and neural outcomes remains an important and unanswered question. To address this gap in the literature, irritability patterns of 110 youth from a large, diverse cohort were assessed at preschool age and again at early school age (∼2.5 years later) with a dimensional irritability scale designed to capture the normal:abnormal spectrum. At preadolescence (∼6 years later), clinical outcomes (internalizing/externalizing symptoms) derived from a semistructured clinical interview and neural outcomes (characterized as gray-matter-volume abnormalities) were assessed. For clinical outcomes, preschool-age irritability alone was a transdiagnostic predictor of internalizing and externalizing symptoms at preadolescence. However, in a model including both preschool and early school age, irritability provided greater specificity, suggesting that higher irritability at early school age related to elevated preadolescent externalizing but not internalizing symptoms. In terms of neural outcomes, elevated preschool irritability did not predict preadolescent gray-matter-volume abnormality; however, irritability at early school age demonstrated an interactive effect among regions, with reduced volume in preadolescence emotional regions (e.g., amygdala, medial orbitofrontal cortex) and increased volume in other regions (e.g., cerebellum). These complex patterns highlight the contribution of a developmentally informed approach, the National Institute of Mental Health's Research Domain Criteria (RDoC) approach, to yield transdiagnostic phenotypes and multiple units of analysis. Capturing these individual differences and developmental heterogeneity can provide critical insight into the unfolding of mechanisms underlying emerging psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Joint Consideration of Inhibitory Control and Irritability in Young Children: Contributions to Emergent Psychopathology.

Deficits in self-regulation capacity have been linked to subsequent impairment and clinical symptomology across the lifespan. Prior work has identified difficulty regulating angry emotions (i.e., irritability) as a powerful transdiagnostic indicator of current and future clinical concerns. Less is known regarding how irritability intersects with cognitive features of self-regulation, in particular inhibitory control, despite its mental health relevance. A promising avenue for improving specificity of clinical predictions in early childhood is multi-method, joint consideration of irritability and inhibitory control capacities. To advance early identification of impairment and psychopathology risk, we contrast group- and variable-based models of neurodevelopmental vulnerability at the interface of irritability and inhibitory control in contexts of varied motivational and emotional salience. This work was conducted in a longitudinal study of children recruited at well-child visits in Midwestern pediatric clinics at preschool age (N = 223, age range = 3-7 years). Group-based models (clustering and regression of clusters on clinical outcomes) indicated significant heterogeneity of self-regulation capacity in this sample. Meanwhile, variable-based models (continuous multiple regression) evidenced associations with concurrent clinical presentation, future symptoms, and impairment across the broad spectrum of psychopathology. Irritability transdiagnostically indicated internalizing and externalizing problems, concurrently and longitudinally. In contrast, inhibitory control was uniquely associated with attention-deficit/hyperactivity symptoms. We present these findings to advance a joint consideration approach to two promising indicators of neurodevelopmental vulnerability and mental health risk. Models suggest that both emotional and cognitive self-regulation capacities can address challenges in characterizing the developmental unfolding of psychopathology from preschool to early childhood age.

Social EEG: A novel neurodevelopmental approach to studying brain-behavior links and brain-to-brain synchrony during naturalistic toddler-parent interactions.

Despite increasing emphasis on emergent brain-behavior patterns supporting language, cognitive, and socioemotional development in toddlerhood, methodologic challenges impede their characterization. Toddlers are notoriously difficult to engage in brain research, leaving a developmental window in which neural processes are understudied. Further, electroencephalography (EEG) and event-related potential paradigms at this age typically employ structured, experimental tasks that rarely reflect formative naturalistic interactions with caregivers. Here, we introduce and provide proof of concept for a new "Social EEG" paradigm, in which parent-toddler dyads interact naturally during EEG recording. Parents and toddlers sit at a table together and engage in different activities, such as book sharing or watching a movie. EEG is time locked to the video recording of their interaction. Offline, behavioral data are microcoded with mutually exclusive engagement state codes. From 216 sessions to date with 2- and 3-year-old toddlers and their parents, 72% of dyads successfully completed the full Social EEG paradigm, suggesting that it is possible to collect dual EEG from parents and toddlers during naturalistic interactions. In addition to providing naturalistic information about child neural development within the caregiving context, this paradigm holds promise for examination of emerging constructs such as brain-to-brain synchrony in parents and children.

Nonrapid eye movement sleep characteristics and relations with motor, memory, and cognitive ability from infancy to preadolescence.

Sleep plays a critical role in neural neurodevelopment. Hallmarks of sleep reflected in the electroencephalogram during nonrapid eye movement (NREM) sleep are associated with learning processes, cognitive ability, memory, and motor functioning. Research in adults is well-established; however, the role of NREM sleep in childhood is less clear. Growing evidence suggests the importance of two NREM sleep features: slow-wave activity and sleep spindles. These features may be critical for understanding maturational change and the functional role of sleep during development. Here, we review the literature on NREM sleep from infancy to preadolescence to provide insight into the network dynamics of the developing brain. The reviewed findings show distinct relations between topographical and maturational aspects of slow waves and sleep spindles; however, the direction and consistency of these relationships vary, and associations with cognitive ability remain unclear. Future research investigating the role of NREM sleep and development would benefit from longitudinal approaches, increased control for circadian and homeostatic influences, and in early childhood, studies recording daytime naps and overnight sleep to yield increased precision for detecting age-related change. Such evidence could help explicate the role of NREM sleep and provide putative physiological markers of neurodevelopment.

ERP Mismatch Negativity Amplitude and Asymmetry Reflect Phonological and Rapid Automatized Naming Skills in English-Speaking Kindergartners.

The mismatch negativity (MMN), an electrophysiological response to an oddball auditory stimulus, is related to reading ability in many studies. There are conflicting findings regarding exactly how the MMN relates to risk or actual diagnosis of dyslexia/reading impairment, perhaps due to the heterogeneity of abilities in children with reading impairment. In this study, 166 English-speaking kindergarten children oversampled for dyslexia risk completed behavioral assessments and a speech-syllable MMN paradigm. We examined how early and late MMN mean amplitude and laterality were related to two established predictors of reading ability: phonological awareness (PA) and rapid automatized naming (RAN). In bootstrapped group analyses, late MMN amplitude was significantly greater in children with typical PA ability than low PA ability. In contrast, laterality of the early and late MMN was significantly different in children with low versus typical RAN ability. Continuous analyses controlling for child age, non-verbal IQ, and letter and word identification abilities showed the same associations between late MMN amplitude with PA and late MMN laterality with RAN. These findings suggest that amplitude of the MMN may relate to phonological representations and ability to manipulate them, whereas MMN laterality may reflect differences in brain processes that support automaticity needed for reading.

EEG/ERP as a pragmatic method to expand the reach of infant-toddler neuroimaging in HBCD: Promises and challenges.

Though electrophysiological measures (EEG and ERP) offer complementary information to MRI and a variety of advantages for studying infants and young children, these measures have not yet been included in large cohort studies of neurodevelopment. This review summarizes the types of EEG and ERP measures that could be used in the HEALthy Brain and Cognitive Development (HBCD) study, and the promises and challenges in doing so. First, we provide brief overview of the use of EEG/ERP for studying the developing brain and discuss exemplar findings, using resting or baseline EEG measures as well as the ERP mismatch negativity (MMN) as exemplars. We then discuss the promises of EEG/ERP such as feasibility, while balancing challenges such as ensuring good signal quality in diverse children with different hair types. We then describe an ongoing multi-site EEG data harmonization from our groups. We discuss the process of alignment and provide preliminary usability data for both resting state EEG data and auditory ERP MMN in diverse samples including over 300 infants and toddlers. Finally, we provide recommendations and considerations for the HBCD study and other studies of neurodevelopment.

Linking irritability and functional brain networks: A transdiagnostic case for expanding consideration of development and environment in RDoC.

The National Institute of Mental Health Research Domain Criteria (RDoC) framework promotes the dimensional and transdiagnostic operationalization of psychopathology, but consideration of the neurodevelopmental foundations of mental health problems requires deeper examination. Irritability, the dispositional tendency to angry emotion that has both mood and behavioral elements, is dimensional, transdiagnostic, and observable early in life-a promising target for the identification of early neural indicators or risk factors for psychopathology. Here, we examine functional brain networks linked to irritability from preschool to adulthood and discuss how development and early experience may influence these neural substrates. Functional connectivity measured with fMRI varies according to irritability and indicates the atypical coordination of several functional networks involved in emotion generation, emotion perception, attention, internalization, and cognitive control. We lay out an agenda to improve our understanding and detection of atypical brain:behavior patterns through advances in the characterization of both functional networks and irritability as well as the consideration and operationalization of developmental and early life environmental influences on this pathway.