The current study examined the link between temperamental reactivity in infancy and amygdala development in middle childhood. A sample (n = 291) of four-month-old infants was assessed for infant temperament, and two groups were identified: those exhibiting negative reactivity (n = 116) and those exhibiting positive reactivity (n = 106). At 10 and 12 years of age structural imaging was completed on a subset of these participants (n = 75). Results indicate that, between 10 and 12 years of age, left amygdala volume increased more slowly in those with negative compared to positive reactive temperament. These results provide novel evidence linking early temperament to distinct patterns of brain development over middle childhood.

Interacting with others by interpreting and responding to their facial expressions is an essential and early developing social skill in humans. We examined whether and how variation in catechol-O-methyltransferase (COMT) and serotonin transporter (5-HTTLPR) genes is associated with 7-month-old infants' electrocortical responses to facial expressions. The results revealed that COMT variants are associated with differences in infants' brain responses to fearful faces over centro-parietal regions, whereas 5-HTTLPR variants are associated with differences in infants' brain responses to happy faces over fronto-temporal regions. Further support for differential associations of these gene variants with emotional processing came from our analysis of infant behavioral temperament: variation in COMT was associated with differences in infants' recovery from distress, whereas variation in 5-HTTLPR was associated with infants' smiling and laughter. This pattern of findings indicates that, in infancy, these genetic variants influence distinct brain systems involved in the processing of either positive or negative emotions. This has wide reaching implications for our understanding of how genetic variation biases specific brain mechanisms, giving rise to individual differences in emotional sensitivity and temperament.

Development of communication and self-regulation skills is fundamental to psychosocial maturation in childhood. The Kia Tīmata Pai Best Start (KTP) longitudinal study aims to promote these skills through interventions delivered at early childcare centers across New Zealand. In addition to evaluating effects of the interventions on behavioral and cognitive outcomes, the study utilizes electroencephalography (EEG) to characterize cortical development in a subsample of participating children. Here, we present results of the baseline resting EEG assessment with 193 children aged 15 to 33 months. We identified EEG correlates of individual differences in demographics, communication abilities, and temperament. We obtained communication and behavior ratings from multiple informants, and we applied contemporary analytic methods to the EEG data. Periodic spectral power adjusted for aperiodic activity was most closely associated with demographic, language, and behavioral measures. As in previous studies, gamma power was positively associated with verbal language. Alpha power was positively associated with effortful control. Nonverbal and verbal language measures showed distinct associations with EEG indices, as did the three temperament domains. Our results identified a number of candidate EEG measurements for use as longitudinal markers of optimal cortical development and response to interventions in the KTP cohort.

Individual differences in temperament have been theorized to be supported by differential recruitment of key neural regions, resulting in the distinct patterns of behavior observed throughout life. Although a compelling model, its rigorous and systematic testing is lacking, particularly within the heightened neuroplasticity of early childhood. The current study tested a model of the link between temperament, the brain, and behavior for cognitive flexibility in a sample of 4-5-year-old children (N = 123) using functional near-infrared spectroscopy (fNIRS) to assess prefrontal cortex (PFC) activation. Structural Equation Modeling (SEM) was used to explore the link between survey reports of temperamental effortful control, and both performance-based and neuroimaging measures of cognitive flexibility. Results indicated that greater parent-reported temperamental effortful control was associated with better performance on a cognitive flexibility task, and less activation of the DLPFC in preschoolers. These findings support the theorized model of the interrelatedness between temperamental tendencies, behavior, and brain activation and suggest that better temperamentally regulated children use the DLPFC more efficiently for cognitive flexibility.

Neighborhood disadvantage has consistently been linked to alterations in brain structure; however, positive environmental (e.g., positive parenting) and psychological factors (e.g., temperament) may buffer these effects. We aimed to investigate associations between neighborhood disadvantage and deviations from typical neurodevelopmental trajectories during adolescence, and examine the moderating role of positive parenting and temperamental effortful control (EC). Using a large dataset (n = 1313), a normative model of brain morphology was established, which was then used to predict the age of youth from a longitudinal dataset (n = 166, three time-points at age 12, 16, and 19). Using linear mixed models, we investigated whether trajectories of the difference between brain-predicted-age and chronological age (brainAGE) were associated with neighborhood disadvantage, and whether positive parenting (positive behavior during a problem-solving task) and EC moderated these associations. We found that neighborhood disadvantage was associated with positive brainAGE during early adolescence and a deceleration (decreasing brainAGE) thereafter. EC moderated this association such that in disadvantaged adolescents, low EC was associated with delayed development (negative brainAGE) during late adolescence. Findings provide evidence for complex associations between environmental and psychological factors, and brain maturation. They suggest that neighborhood disadvantage may have long-term effects on neurodevelopment during adolescence, but high EC could buffer these effects.

During adolescence, increases in social sensitivity, such as heightened attentional processing of social feedback, may be supported by developmental changes in neural circuitry involved in emotion regulation and cognitive control, including fronto-amygdala circuitry. Less negative fronto-amygdala circuitry during social threat processing may contribute to heightened attention to social threat in the environment. However, "real-world" implications of altered fronto-amygdala circuitry remain largely unknown. In this study, we used multiple novel methods, including an in vivo attention bias task implemented using mobile eye-tracking glasses and socially interactive fMRI task, to examine how functional connectivity between the amygdala and prefrontal cortex (PFC) during rejection and acceptance feedback from peers is associated with heightened attention towards potentially critical social evaluation in a real-world environment. Participants were 77 early adolescent girls (ages 11-13) oversampled for shy/fearful temperament. Results support the reliability of this in vivo attention task. Further, girls with more positive functional connectivity between the right amygdala and anterior PFC during both rejection and acceptance feedback attended more to potentially critical social evaluation during the attention task. Findings could suggest that dysfunction in prefrontal regulation of the amygdala's response to salient social feedback supports heightened sensitivity to socially evaluative threat during adolescence.

Social Reticence (SR) is a temperament construct identified in early childhood that is expressed as shy, anxiously avoidant behavior and, particularly when stable, robustly associated with risk for anxiety disorders. Threat circuit function may develop differently for children high on SR than low on SR. We compared brain function and behavior during extinction recall in a sample of 11-to-15-year-old children characterized in early childhood on a continuum of SR. Three weeks after undergoing fear conditioning and extinction, participants completed a functional magnetic resonance imaging extinction recall task assessing memory and threat differentiation for conditioned stimuli. Whereas self-report and psychophysiological measures of differential conditioning, extinction, and extinction recall were largely similar across participants, SR-related differences in brain function emerged during extinction recall. Specifically, childhood SR was associated with a distinct pattern of hemodynamic-autonomic covariation in the brain when recalling extinguished threat and safety cues. SR and attention focus impacted associations between trial-by-trial variation in autonomic responding and in brain activation. These interactions occurred in three main brain areas: the anterior insular cortex (AIC), the anterior subdivision of the medial cingulate cortex (aMCC), and the dorsolateral prefrontal cortex (dlPFC). This pattern of SCR-BOLD coupling may reflect selective difficulty tracking safety in a temperamentally at-risk population.

High Temperamental Negative Affectivity in early childhood has been found to predict later emotion dysregulation. While much work has been conducted to separately probe bio-behavioral systems associated with Negative Affectivity, very little work has examined the relations among multiple systems across age. In this study, we use multi-modal methods to index neurobiological systems associated with Negative Affectivity in 53 4-7-year-old children. Prefrontal activation during emotion regulation was measured using functional near-infrared spectroscopy over the lateral prefrontal cortex (PFC) while children played a game designed to elicit frustration in Social (Happy and Angry faces) and Nonsocial contexts. Gaze behaviors while free-viewing Happy and Angry faces were also measured. Finally, Negative Affectivity was indexed using a score composite based on factor analysis of parent-reported temperament. Using mixed-effects linear models, we found an age-dependent association between Negative Affectivity and both PFC activation during frustration and fixation duration on the mouth area of Happy faces, such that older children high in Negative Affectivity spent less time looking at the mouths of Happy faces and had lower PFC activation in response to frustration (ps<0.034). These results provide further insight to how Negative Affectivity may be associated with changes in affective neurobiological systems across early childhood.

One potential obstacle limiting our ability to clarify ADHD etiology is the heterogeneity within the disorder, as well as in typical samples. In this study, we utilized a community detection approach on 106 children with and without ADHD (aged 7-12 years), in order to identify potential subgroups of participants based on the connectivity of the reward system. Children with ADHD were compared to typically developing children within each identified community, aiming to find the community-specific ADHD characteristics. Furthermore, to assess how the organization in subgroups relates to behavior, we evaluated delay-discounting gradient and impulsivity-related temperament traits within each community. We found that discrete subgroups were identified that characterized distinct connectivity profiles in the reward system. Importantly, which connections were atypical in ADHD relative to the control children were specific to the community membership. Our findings showed that children with ADHD and typically developing children could be classified into distinct subgroups according to brain functional connectivity. Results also suggested that the differentiation in "functional" subgroups is related to specific behavioral characteristics, in this case impulsivity. Thus, combining neuroimaging data and community detection might be a valuable approach to elucidate heterogeneity in ADHD etiology and examine ADHD neurobiology.

Irritability is an aspect of the negative affectivity domain of temperament, but in severe and dysregulated forms is a symptom of a range of psychopathologies. Better understanding of the neural underpinnings of irritability, outside the context of specific disorders, can help to understand normative variation but also characterize its clinical salience in psychopathology diagnosis. This study assessed brain activation during reward and frustration, domains of behavioral deficits in childhood irritability. Children (age 6-9) presenting in mental health clinics for extreme and impairing irritability (n = 26) were compared to healthy children (n = 28). Using developmentally sensitive methods, neural activation was measured via a negative mood induction paradigm during fMRI scanning. The clinical group displayed more activation of the anterior cingulate and middle frontal gyrus during reward, but less activation during frustration, than healthy comparison children. The opposite pattern was found in the posterior cingulate. Further, in clinical subjects, parent report of irritability was dimensionally related to decreased activation of the anterior cingulate and striatum during frustration. The results of this study indicate neural dysfunction within brain regions related to reward processing, error monitoring, and emotion regulation underlying clinically impairing irritability. Results are discussed in the context of a growing field of neuroimaging research investigating irritable children.

Behavioral inhibition (BI) is a biologically-based temperament characterized by vigilance toward threat. Over time, many children with BI increasingly fear social circumstances and display maladaptive social behavior. BI is also one of the strongest individual risk factors for developing social anxiety disorder. Although research has established a link between BI and anxiety, its causal mechanism remains unclear. Attention biases may underlie this relation. The current study examined neural markers of the BI-attention-anxiety link in children ages 9-12 years (N=99, Mean=9.97, SD=0.97). ERP measures were collected as children completed an attention-bias (dot-probe) task with neutral and angry faces. P2 and N2 amplitudes were associated with social anxiety and attention bias, respectively. Specifically, augmented P2 was related to decreased symptoms of social anxiety and moderated the relation between BI and social anxiety, suggesting that increasing attention mobilization may serve as a compensatory mechanism that attenuates social anxiety in individuals with high BI. The BI by N2 interaction found that larger N2 related to threat avoidance with increasing levels of BI, consistent with over-controlled socio-emotional functioning. Lastly, children without BI (BN) showed an augmented P1 to probes replacing angry faces, suggesting maintenance of attentional resources in threat-related contexts.

Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across childhood until age 9 years in Generation R and 11 years in MARS. Protective factors (temperament, cognition, self-esteem, maternal sensitivity, friendship quality) were assessed at various time-points during childhood. Global brain volumes and volumes of amygdala, hippocampus, and the anterior cingulate, medial orbitofrontal and rostral middle frontal cortices were assessed with anatomical scans at 10 years in Generation R and at 25 years in MARS. Childhood adversity was related to smaller cortical grey matter, cerebral white matter, and cerebellar volumes in children. Also, no buffering effects of protective factors on the association between adversity and the brain outcomes survived multiple testing correction. We found no robust evidence for an interaction between protective factors and childhood adversity on broad brain structural measures. Small interaction effects observed in one cohort only warrant further investigation.