Preliminary examination of the effects of an early parenting intervention on amygdala-orbitofrontal cortex resting-state functional connectivity among high-risk children: A randomized clinical trial.

We examined the long-term causal effects of an evidence-based parenting program delivered in infancy on children's emotion regulation and resting-state functional connectivity (rs-fc) during middle childhood. Families were referred to the study by Child Protective Services (CPS) as part of a diversion from a foster care program. A low-risk group of families was also recruited. CPS-involved families were randomly assigned to receive the target (Attachment and Biobehavioral Catch-up, ABC) or a control intervention (Developmental Education for Families, DEF) before infants turned 2. Both interventions were home-based, manualized, and 10-sessions long. During middle childhood, children underwent a 6-min resting-state functional MRI scan. Amygdala seed-based rs-fc analysis was completed with intervention group as the group-level predictor of interest. Fifty-seven children (NABC = 21; NDEF = 17; NCOMP = 19; Mage = 10.02 years, range = 8.08-12.14) were scanned successfully. The DEF group evidenced negative left amygdala↔OFC connectivity, whereas connectivity was near zero in the ABC and comparison groups (ABCvsDEF: Cohen's d = 1.17). ABC may enhance high-risk children's regulatory neurobiology outcomes ∼8 years after the intervention was completed.

A Randomized Controlled Trial of a Parenting Intervention During Infancy Alters Amygdala-Prefrontal Circuitry in Middle Childhood.

OBJECTIVE: Early adverse parenting predicts various negative outcomes, including psychopathology and altered development. Animal work suggests that adverse parenting might change amygdala-prefrontal cortex (PFC) circuitry, but work in humans remains correlational. The present study leveraged data from a randomized controlled trial examining the efficacy of an early parenting intervention targeting parental nurturance and sensitivity (Attachment and Biobehavioral Catch-up [ABC]) to test whether early parenting quality causally affects amygdala-PFC connectivity later in life. METHOD: Participants (N = 60, mean age = 10.0 years) included 41 high-risk children whose parents were referred by Child Protective Services and randomly assigned to receive either ABC (n = 21) or a control intervention (n = 20) during the children's infancy and a comparison sample of low-risk children (n = 19). Amygdala-PFC connectivity was assessed via functional magnetic resonance imaging while children viewed fearful and neutral faces. RESULTS: Across facial expressions, ABC produced different changes than the control intervention in amygdala-PFC connectivity in response to faces. The ABC group also exhibited greater responses than the control intervention group to faces in areas classically associated with emotion regulation, including the orbitofrontal cortex and right insula. Mediation analysis suggested that the effect of ABC on PFC activation was mediated by the intervention's effect on amygdala-PFC connectivity. CONCLUSION: Results provide preliminary causal evidence for the effect of early parenting intervention on amygdala-PFC connectivity and on PFC responses to face viewing. Findings also highlight amygdala-PFC connectivity as a potential mediator of the effects of early parenting intervention on children's emotion regulation development. CLINICAL TRIAL REGISTRATION INFORMATION: Intervening Early With Neglected Children; https://clinicaltrials.gov/; NCT02093052. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

Development of Neural Mechanisms Underlying Threat Processing: Associations With Childhood Social Reticence and Adolescent Anxiety.

Background: Social reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety. Methods: In this 16-year longitudinal study, social reticence was assessed from 2 to 7 years of age; anxiety symptoms and neural mechanisms during the dot-probe task were assessed at 10, 13, and 16 years of age. The sample included 144 participants: 71 children provided data at age 10 (43 girls, meanage = 10.62), 85 at age 13 (46 girls, meanage = 13.25), and 74 at age 16 (36 girls, meanage = 16.27). Results: A significant interaction manifested among social reticence, anxiety symptoms, and time, on functional connectivity between the left amygdala and the left dorsolateral prefrontal cortex, voxelwise p < .001, clusterwise familywise error p < .05. Children with high social reticence showed a negative association between amygdala-dorsolateral prefrontal cortex connectivity and anxiety symptoms with age, compared to children with low social reticence, suggesting distinct neurodevelopmental pathways to anxiety. Conclusions: These findings were present across all conditions, suggesting task-general effects in potential threat processing. Additionally, the timing of these neurodevelopmental pathways differed for children with high versus low social reticence, which could affect the timing of effective preventive interventions.

Associations between cortical thickness and parasympathetic nervous system functioning during middle childhood.

Positive associations have been found between cortical thickness and measures of parasympathetic cardiac control (e.g., respiratory sinus arrhythmia, RSA) in adults, which may indicate mechanistic integration between neural and physiological indicators of stress regulation. However, it is unknown when in development this brain-body association arises and whether the direction of association and neuroanatomical localization vary across development. To investigate this, we collected structural magnetic resonance imaging and resting-state respiratory sinus arrhythmia data from children in middle childhood (N = 62, Mage = 10.09, range: 8.28-12.14 years). Whole-brain and exploratory ROI analyses revealed positive associations between RSA and cortical thickness in four frontal and parietal clusters in the left hemisphere and one cluster in the right. Exploratory ROI analyses revealed a similar positive association between cortical thickness and RSA, with two regions surviving multiple comparison correction, including the inferior frontal orbital gyrus and the Sylvian fissure. Prior work has identified these cortical areas as part of the central autonomic network that supports integrative regulation of stress response (e.g., autonomic, endocrine, and behavioral) and emotional expression. Our results suggest that the association between cortical thickness and resting RSA is present in middle childhood and is similar to the associations seen during adulthood. Future studies should investigate associations between RSA and cortical thickness among young children and adolescents.

A Comprehensive Multilevel Analysis of the Bucharest Early Intervention Project: Causal Effects on Recovery From Early Severe Deprivation.

OBJECTIVE: The Bucharest Early Intervention Project is the first randomized controlled trial of foster care as an alternative to institutional care. The authors synthesized data from nearly 20 years of assessments of the trial to determine the overall intervention effect size across time points and developmental domains. The goal was to quantify the overall effect of the foster care intervention on children's outcomes and examine sources of variation in this effect, including domain, age, and sex assigned at birth. METHODS: An intent-to-treat approach was used to examine the causal effects of the randomized controlled trial for 136 children residing in institutions in Bucharest, Romania (baseline age, 6-31 months) who were randomly assigned to either foster care (N=68) or care as usual (N=68). At ages 30, 42, and 54 months and 8, 12, and 16-18 years, children were assessed for IQ, physical growth, brain electrical activity (EEG), and symptoms of five types of psychopathology. RESULTS: Participants provided 7,088 observations across follow-up waves. Children assigned to foster care had better cognitive and physical outcomes and less severe psychopathology than did those who received care as usual. The magnitude of these effect sizes remained stable across development. The foster care intervention most influenced IQ and disorders of attachment/social relatedness. CONCLUSIONS: Young children benefit from placement in families after institutional care. The benefits of foster care for previously institutionalized children were remarkably stable across development.

Multimodal study of the neural sources of error monitoring in adolescents and adults.

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. As well, recent work has shown that individual differences in error monitoring moderate temperamental risk for anxiety and that this moderation changes with age. We investigated age differences in neural responses linked to performance monitoring using a multimodal approach. The approach combined functional MRI and source localization of event-related potentials (ERPs) in 12-year-old, 15-year-old, and adult participants. Neural generators of two components related to performance and error monitoring, the N2 and ERN, lay within specific areas of fMRI clusters. Whereas correlates of the N2 component appeared similar across age groups, age-related differences manifested in the location of the generators of the ERN component. The dorsal anterior cingulate cortex (dACC) was the predominant source location for the 12-year-old group; this area manifested posteriorly for the 15-year-old and adult groups. A fMRI-based ROI analysis confirmed this pattern of activity. These results suggest that changes in the underlying neural mechanisms are related to developmental changes in performance monitoring.

Age-related trends in aperiodic EEG activity and alpha oscillations during early- to middle-childhood.

Age-related structural and functional changes that occur during brain development are critical for cortical development and functioning. Previous electroencephalography (EEG) and magnetoencephalography (MEG) studies have highlighted the utility of power spectra analyses and have uncovered age-related trends that reflect perceptual, cognitive, and behavioural states as well as their underlying neurophysiology. The aim of the current study was to investigate age-related change in aperiodic and periodic alpha activity across a large sample of pre- and school-aged children (N = 502, age range 4 -11-years-of-age). Power spectra were extracted from baseline EEG recordings (eyes closed, eyes open) for each participant and parameterized into aperiodic activity to derive the offset and exponent parameters and periodic alpha oscillatory activity to derive the alpha peak frequency and the associated power estimates. Multilevel models were run to investigate age-related trends and condition-dependent changes for each of these measures. We found quadratic age-related effects for both the aperiodic offset and exponent. In addition, we observed increases in periodic alpha peak frequency as a function of age. Aperiodic measures and periodic alpha power were larger in magnitude during eyes closed compared to the eyes open baseline condition. Taken together, these results advance our understanding of the maturational patterns/trajectories of brain development during early- to middle-childhood.

Associations between cortical thickness and anxious/depressive symptoms differ by the quality of early care.

A variety of childhood experiences can lead to anxious/depressed (A/D) symptoms. The aim of the present study was to explore the brain morphological (cortical thickness and surface area) correlates of A/D symptoms and the extent to which these phenotypes vary depending on the quality of the parenting context in which children develop. Structural magnetic resonance imaging (MRI) scans were acquired on 45 children with Child Protective Services (CPS) involvement due to risk of not receiving adequate care (high-risk group) and 25 children without CPS involvement (low-risk group) (rangeage = 8.08-12.14; Mage = 10.05) to assess cortical thickness (CT) and cortical surface area (SA). A/D symptoms were measured using the Child Behavioral Checklist. The association between A/D symptoms and CT, but not SA, differed by risk status such that high-risk children showed decreasing CT as A/D scores increased, whereas low-risk children showed increasing CT as A/D scores increased. This interaction was specific to CT in prefrontal, frontal, temporal, and parietal cortical regions. The groups had marginally different A/D scores, in the direction of higher risk being associated with lower A/D scores. Results suggest that CT correlates of A/D symptoms are differentially shaped by the quality of early caregiving experiences and should be distinguished between high- and low-risk children.

Cross-sectional and Longitudinal Associations of Anxiety and Irritability With Adolescents' Neural Responses to Cognitive Conflict.

BACKGROUND: Psychiatric symptoms are commonly comorbid in childhood. The ability to disentangle unique and shared correlates of comorbid symptoms facilitates personalized medicine. Cognitive control is implicated broadly in psychopathology, including in pediatric disorders characterized by anxiety and irritability. To disentangle cognitive control correlates of anxiety versus irritability, the current study leveraged both cross-sectional and longitudinal data from early childhood into adolescence. METHODS: For this study, 89 participants were recruited from a large longitudinal research study on early-life temperament to investigate associations of developmental trajectories of anxiety and irritability symptoms (from ages 2 to 15) as well as associations of anxiety and irritability symptoms measured cross-sectionally at age 15 with neural substrates of conflict and error processing assessed at age 15 using the flanker task. RESULTS: Results of whole-brain multivariate linear models revealed that anxiety at age 15 was uniquely associated with decreased neural response to conflict across multiple regions implicated in attentional control and conflict adaptation. Conversely, irritability at age 15 was uniquely associated with increased neural response to conflict in regions implicated in response inhibition. Developmental trajectories of anxiety and irritability interacted in relation to neural responses to both error and conflict. CONCLUSIONS: Our findings suggest that neural correlates of conflict processing may relate uniquely to anxiety and irritability. Continued cross-symptom research on the neural correlates of cognitive control could stimulate advances in individualized treatment for anxiety and irritability during child and adolescent development.

Annual Research Review: Developmental pathways linking early behavioral inhibition to later anxiety.

Behavioral Inhibition is a temperament identified in the first years of life that enhances the risk for development of anxiety during late childhood and adolescence. Amongst children characterized with this temperament, only around 40 percent go on to develop anxiety disorders, meaning that more than half of these children do not. Over the past 20 years, research has documented within-child and socio-contextual factors that support differing developmental pathways. This review provides a historical perspective on the research documenting the origins of this temperament, its biological correlates, and the factors that enhance or mitigate risk for development of anxiety. We review as well, research findings from two longitudinal cohorts that have identified moderators of behavioral inhibition in understanding pathways to anxiety. Research on these moderators has led us to develop the Detection and Dual Control (DDC) framework to understand differing developmental trajectories among behaviorally inhibited children. In this review, we use this framework to explain why and how specific cognitive and socio-contextual factors influence differential pathways to anxiety versus resilience.

Attentional biases in human anxiety.

Across clinical and subclinical samples, anxiety has been associated with increased attentional capture by cues signaling danger. Various cognitive models attribute the onset and maintenance of anxiety symptoms to maladaptive selective information processing. In this brief review, we 1) describe the evidence for the relations between anxiety and attention bias toward threat, 2) discuss the neurobiology of anxiety-related differences in threat bias, 3) summarize work investigating the developmental origins of attention bias toward threat, and 4) examine efforts to translate threat bias research into clinical intervention. Future directions in each area are discussed, including the use of novel analytic approaches improving characterization of threat-processing-related brain networks, clarifying the role of cognitive control in the development of attention bias toward threat, and the need for larger, well-controlled randomized clinical trials examining moderators and mediators of treatment response. Ultimately, this work has important implications for understanding the etiology of and for intervening on anxiety difficulties among children and adults.

Development of Proactive Control and Anxiety Among Behaviorally Inhibited Adolescents.

OBJECTIVE: Behavioral inhibition (BI) is an infant temperament characterized by heightened reactivity and negative affect in response to novel people and situations. BI is among the earliest and strongest predictors of future anxiety problems. However, not all children with a history of BI will manifest anxiety problems. A growing body of evidence suggests that proactive control skills may help buffer youth with BI from future anxiety difficulties; yet, it remains unclear how temperament may interact with the development of cognitive control to influence anxiety risk. The present study tested whether enhancements in proactive control occurring during adolescence may reduce risk for anxiety among youth with a history of BI. METHOD: Participants included 185 adolescents (56% female) whose temperament was assessed during toddlerhood. In adolescence, participants completed anxiety assessments and an AX Continuous Performance Test (AX-CPT) to assess cognitive control strategy. Both assessments were administered at age 13 years and again at 15 years. RESULTS: Latent change score modeling revealed that, on average, participants increasingly used proactive control strategies and experienced worsening anxiety from age 13-15 years. Early BI was associated with a smaller anxiety increase from 13-15 years, but only among participants whose proactive control skills improved at mean or greater rates. CONCLUSION: The present findings suggest that greater proactive control development during adolescence protects youth with high BI from age-related increases in anxiety. Results support a framework that highlights cognitive control as a key moderator of anxiety risk among children with a history of high BI.

Temperamental risk for anxiety: emerging work on the infant brain and later neurocognitive development.

Behavioral inhibition (BI), an infant temperament characterized by distress to novelty, is amongst the strongest early risk markers for future anxiety. In this review, we highlight three ways that recent research elucidates key details about the pathophysiology of anxiety in individuals with BI. First, atypical amygdala connectivity during infancy may be related to BI. Second, developmental shifts in cognitive control may portend risk for anxiety for children with BI. Lastly, distinct cognitive control processes moderate the BI-anxiety relation in different ways. Studying the intersection of these three streams of work may inform prevention or intervention work.

Early exposure to parent-perpetrated intimate partner violence predicts hypervigilant error monitoring.

Early exposure to intimate partner violence (IPV) places children at risk for ongoing emotional difficulties, including problems with self-regulation and high levels of internalizing symptoms. However, the impact of IPV exposure on children's error monitoring remains unknown. The present study utilized electroencephalography (EEG) to examine the impact of exposure to IPV in infancy on error monitoring in middle childhood. Results indicated that parents' perpetration of IPV against their romantic partners when children were under 24 months of age predicted hypervigilant error monitoring in children at age 8 (N = 30, 16 female), as indexed by error-related neural activity (ERN and Pe difference amplitudes), above and beyond the effects of general adversity exposure and parental responsiveness. There was no association between partner perpetration of IPV and children's error monitoring. Results illustrate the harmful effects of early exposure to parent-perpetrated IPV on error monitoring and highlight the importance of targeting children's and parents' cognitive and emotional responses to error commission in psychotherapy.

Neurocognitive Profiles in Adolescence Predict Subsequent Anxiety Trajectories During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has created increased stress and anxiety for many; however, some individuals are particularly prone to heightened anxiety. It is unclear if and how prestress neurocognitive factors moderate risk for anxiety during high-stress situations. Enhanced error monitoring and a cognitive control strategy of more instantaneous (reactive) control have both been independently related to anxiety. We examined if a specific neurocognitive profile characterized by heightened error monitoring and a more reactive cognitive control strategy in adolescence predicts young adults' anxiety trajectories across 3 early months of the COVID-19 pandemic. METHODS: As part of a longitudinal study (N = 291), data were acquired in adolescence (13 years) on error monitoring (n = 124) and cognitive control strategy (n = 119). In young adulthood (18 years), anxiety was assessed three times during the COVID-19 pandemic (n = 162). RESULTS: On average, participants experienced greater anxiety in the first COVID-19 pandemic assessment, then anxiety decreased in the following months. Error monitoring and cognitive control strategy interacted to predict anxiety trajectories, such that among adolescents with an increased reliance on reactive control, error monitoring predicted greater anxiety in the first assessment but greater decreases the following months as stay-at-home orders were lifted and families adapted to the restrictions. CONCLUSIONS: Results suggest that neurocognitive profiles in adolescence predict young adults' anxiety responses during a highly stressful period, such as the initial months of the COVID-19 pandemic. Our findings have implications for the early identification of individuals at greater risk for anxiety.

Longitudinal age- and sex-related change in background aperiodic activity during early adolescence.

Aperiodic activity contains important and meaningful physiological information that has been shown to dynamically change with age. However, no longitudinal studies have examined its development during early-to-mid adolescence. The current study closes this gap by investigating age- and sex-related longitudinal change in aperiodic activity across early-to-mid adolescence (N = 186; 54.3% female). Participants completed a resting state task and a Flanker task while EEG was record at age 13 years and again at age 15 years. Across different tasks and two time points, we observed significant age-related reductions in aperiodic offset and exponent. In addition, we observed significant sex-related differences in the aperiodic offset and exponent over time. We did not find any significant correlation between aperiodic activity and behavioral measures, nor did we find any significant condition-dependent change in aperiodic activity during the Flanker task. However, we did observe significant correlations between aperiodic activity across tasks and over time, suggesting that aperiodic activity may demonstrate stable trait-like characteristics. Collectively, these results may suggest a developmental parallelism between decreases in aperiodic components alongside adolescent brain development during this period; changes to cortical and subcortical brain structure and organization during early adolescence may have been responsible for the observed sex-related effects.

Behavioral inhibition and dual mechanisms of anxiety risk: Disentangling neural correlates of proactive and reactive control.

BACKGROUND: Behavioral inhibition (BI) is a temperament style characterized by heightened reactivity and negative affect in response to novel people and situations, and it predicts anxiety problems later in life. However, not all BI children develop anxiety problems, and mounting evidence suggests that how one manages their cognitive resources (cognitive control) influences anxiety risk. The present study tests whether more (proactive control) or less (reactive control) planful cognitive strategies moderate relations between early BI and later anxiety. METHODS: Participants included 112 adolescents (55% female; M age = 15.4 years) whose temperament was assessed during toddlerhood. In adolescence, participants completed an AX Continuous Performance Test while electroencephalography was recorded to disentangle neural activity related to proactive (cue-locked P3b) and reactive (probe-locked N2) control. RESULTS: Greater BI was associated with greater total anxiety scores only among adolescents with smaller ΔP3bs and larger ΔN2s-a pattern consistent with decreased reliance on proactive strategies and increased reliance on reactive strategies. Additionally, a larger ΔP3b was associated with greater total anxiety scores; however, this effect was largely explained by the fact that females tended to have larger ΔP3bs and greater anxiety than males. CONCLUSIONS: Early BI relates to risk for later anxiety specifically among adolescents who rely less on proactive strategies and more on reactive control strategies. Thus, cognitive control strategy moderates the association between developmental context (i.e., temperament) and later anxiety. The present study is the first to characterize how proactive and reactive control uniquely relate to pathways toward anxiety risk.

Understanding the Emergence of Social Anxiety in Children With Behavioral Inhibition.

Behavioral inhibition (BI) is a temperament characterized in early childhood by distress to novelty and avoidance of unfamiliar people, and it is one of the best-known risk factors for the development of social anxiety. However, nearly 60% of children with BI do not go on to meet criteria for social anxiety disorder. In this review we present an approach to understanding differential developmental trajectories among children with BI. We review research using laboratory-based tasks that isolate specific attention processes that enhance versus mitigate risk for social anxiety among behaviorally inhibited children and studies that suggest that BI is associated with heightened detection of novelty or threat. Moreover, stimulus-driven control processes, which we term "automatic control," increase the probability that behaviorally inhibited children display socially reticent behavior and develop social anxiety. In contrast, goal-driven control processes, which we term "planful control," decrease risk for anxiety. We suggest that these three categories of processes (detection, automatic control, and planful control) function together to determine whether behaviorally inhibited children are able to flexibly regulate their initial reactions to novelty, and in turn, decrease risk for social anxiety. Although laboratory-based tasks have identified these processes underlying risk and resilience, the challenge is linking them to the emotions, thoughts, and behaviors of behaviorally inhibited children in real-world contexts.

Racial Disparities in Elementary School Disciplinary Actions: Findings From the ABCD Study.

OBJECTIVE: Detentions and suspensions are common practices of school discipline, despite evidence that they are largely ineffective and disproportionately affect children from racial and ethnic minority backgrounds, particularly Black children, and children of lower socioeconomic status. However, few studies have examined suspension and detention rates among race, ethnicity, and family structure (single parent versus secondary caregiver) when controlling for typical behaviors associated with detention and suspension such as externalizing symptoms, age, sex, family income, family education, family conflict, and special education needs. METHOD: Caregivers of 11,875 children between ages 9 and 10 years from the Adolescent Brain Cognitive Development (ABCD) study completed a questionnaire assessing their child's demographics, family information, emotions and behaviors, and past-year school discipline history. Data were analyzed with logistic regression, implemented with a generalized estimating equations model. RESULTS: 5.4% of children received a detention or suspension. Controlling for typical predictors of behaviors, Black and multiracial Black children had up to 3.5 times greater odds of receiving a detention or suspension than White children; there were no disciplinary differences for Hispanic or Asian children compared to White children. Children from single-parent households had 1.4 times the odds of receiving detentions or suspensions than children in homes with a secondary caregiver. CONCLUSION: Disciplinary actions that can impair typical childhood development, lead to academic failure and dropout, and cause significant emotional and psychological distress disproportionately affect Black children, multiracial Black children, and children from single-parent homes. Racism in elementary school discipline can perpetuate disparities in today's educational system.