Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.

Mature amygdala-prefrontal circuitry regulates affect in adulthood, but shows protracted development. In (semi-)altricial species, caregivers provide potent affect regulation when mature neurocircuitry is absent. This investigation examined a potential mechanism through which caregivers provide regulatory influences in childhood. Children, but not adolescents, showed evidence of maternal buffering, such that maternal stimuli suppressed amygdala reactivity. In the absence of maternal stimuli, children exhibited immature amygdala-prefrontal connectivity. However, in the presence of maternal stimuli, children displayed mature-like connectivity that resembled adolescents’ connectivity. Children showed improved affect-related regulation in the presence of their mother. Individual differences emerged, with maternal influence on amygdalaprefrontal circuitry associated with stronger mother-child relationships and maternal modulation of behavioral regulation. These findings suggest a neural mechanism through which caregivers modulate children's regulatory behavior by inducing mature-like connectivity and buffering against heightened reactivity. Maternal buffering in childhood, but not adolescence, suggests that childhood may be a sensitive period for amygdala-prefrontal development.

Background In altricial species, maternal stimuli have powerful effects on amygdala development and attachment-related behaviors. In humans, maternal deprivation has been associated with both “indiscriminate friendliness” towards non-caregiving adults and altered amygdala development. We hypothesized that maternal deprivation would be associated with reduced amygdala discrimination between mothers and strangers and increased parent report of indiscriminate friendliness behaviors. Methods 67 youths [33 previously-institutionalized (PI); 34 Comparison (Comp); age-at-scan 4-17 y] participated in an fMRI experiment designed to examine amygdala response to mother versus stranger faces. In-scanner behavior was measured. Indiscriminate friendliness was assessed using parental report. Results Comparison youth showed an amygdala response that clearly discriminated mother versus stranger stimuli. PI youths, by contrast, exhibited reduced amygdala discrimination between mothers and strangers. Reduced amygdala differentiation correlated with greater reports of indiscriminate friendliness. These effects correlated with age-at-adoption, with later adoptions being associated with reduced amygdala discrimination and more indiscriminate friendliness. Conclusions Our results suggest that early maternal deprivation is associated with reduced amygdala discrimination between mothers and strangers, and reduced amygdala discrimination was associated with greater reports of indiscriminate friendliness. Moreover, these effects increased with age-at-adoption. These data suggest that the amygdala, in part, is associated with indiscriminate friendliness, and that there may be a dose-response relationship between institutional rearing and indiscriminate friendliness.

Gastrointestinal and mental disorders are highly comorbid, and animal models have shown that both can be caused by early adversity (e.g., parental deprivation). Interactions between the brain and bacteria that live within the gastrointestinal system (the microbiome) underlie adversity–gastrointestinal–anxiety interactions, but these links have not been investigated during human development. In this study, we utilized data from a population of 344 youth (3–18 years old) who were raised with their biological parents or were exposed to early adverse caregiving experiences (i.e., institutional or foster care followed by international adoption) to explore adversity–gastrointestinal–anxiety associations. In Study 1, we demonstrated that previous adverse care experiences were associated with increased incidence of gastrointestinal symptoms in youth. Gastrointestinal symptoms were also associated with concurrent and future anxiety (measured across 5 years), and those gastrointestinal symptoms mediated the adversity–anxiety association at Time 1. In a subsample of children who provided both stool samples and functional magnetic resonance imaging of the brain (Study 2, which was a “proof-of-principle”), adversity was associated with changes in diversity (both alpha and beta) of microbial communities, and bacteria levels (adversity-associated and adversity-independent) were correlated with prefrontal cortex activation to emotional faces. Implications of these data for supporting youth mental health are discussed.

Background: The human brain remains highly plastic for a protracted developmental period. Thus, although early caregiving adversities that alter amygdala development can result in enduring emotion regulation difficulties, these trajectories should respond to subsequent enriched caregiving. Exposure to high quality parenting can regulate (e.g., decrease) children's amygdala reactivity, a process that, over the long-term, is hypothesized to enhance emotion regulation. We tested the hypothesis that, even following adversity, the parent-child relationship would be associated with amygdala decreases to parent cues, which would in turn predict lower future anxiety. Methods: Participants were 102 children (6-10 years old) and adolescents (11-17 years old), with one or two data points, that had experienced institutional care before adoption (PI; n=45) or lived with their biological parents (Comparison; n=57). We examined how amygdala reactivity to visual cues of the parent at Time 1 predicted longitudinal change (Time 1 to 2) in parent reported child anxiety across 3 years. Results: At Time 1, on average, amygdala reactivity decrements to parent cues were not seen in children that were PI but were seen in Comparison children. However, some children that were PI did show decreased amygdala to parent cues (~40%), which was associated with greater childreported feelings of security with their parent. Amygdala decreases at Time 1 were followed by steeper anxiety reductions from Time 1-2 (i.e., 3 years). Conclusions: These data provide a neurobiological mechanism by which the parent-child relationship can increase resilience, even in children at significant risk for anxiety symptoms.