The amygdala is critically involved in processing emotion. Through bidirectional connections, the prefrontal cortex (PFC) is hypothesized to influence amygdala reactivity. However, research that elucidates the nature of amygdala-PFC interactions -through mapping amygdala-prefrontal tracts, quantifying variability among tracts, and linking this variability to amygdala activation -is lacking. Using probabilistic tractography to map amygdala-prefrontal white matter connectivity in 142 adolescents, the present study found that white matter connectivity was greater between the amygdala and the subgenual cingulate, orbitofrontal (OFC), and dorsomedial (dmPFC) prefrontal regions than with the dorsal cingulate and dorsolateral regions. Then, using a machine-learning regression, we found that greater amygdala-PFC white matter connectivity related to attenuated amygdala reactivity. This effect was driven by amygdala white matter connectivity with the dmPFC and OFC, supporting implicit emotion processing theories which highlight the critical role of these regions in amygdala regulation. This study is among the first to map and compare specific

Key Points Question Are violence exposure and social deprivation associated with person-specific patterns (heterogeneity) of adolescent resting-state functional connectivity? Findings In this cohort study of 175 adolescents, childhood violence exposure, but not social deprivation, was associated with reduced adolescent resting-state density of the salience and default mode networks. A data-driven algorithm, blinded to childhood adversity, identified youth with heightened violence exposure based on resting-state connectivity patterns. Meaning Childhood violence exposure appears to be associated with adolescent functional connectivity heterogeneity, which may reflect person-specific neural plasticity and should be considered in neuroscience-based interventions.

Background Childhood adversity is, unfortunately, highly prevalent and strongly associated with later psychopathology. Recent theories posit that two dimensions of early adversity, threat and deprivation, have distinct effects on brain development. The current study evaluated whether violence exposure (threat) and social deprivation (deprivation) were associated with adolescent amygdala and ventral striatum activation, respectively, in a prospective, well-sampled, longitudinal cohort using a pre-registered, open science approach. Methods 167 adolescents from the Fragile Families and Child Wellbeing Study completed fMRI scanning. Prospective longitudinal data from ages 3, 5 and 9 were used to create indices of childhood violence exposure and social deprivation. We evaluated whether these dimensions were associated with adolescent brain function in response to threatening and rewarding faces. Results Childhood violence exposure was associated with decreased amygdala habituation (i.e., more sustained activation) and activation to angry faces in adolescence, whereas childhood social deprivation was associated with decreased ventral striatum activation to happy faces in adolescence. These associations held when controlling for the other dimension of adversity and their interaction, gender, internalizing psychopathology, and current life stress. Conclusions Consistent with recent theories, different forms of early adversity were associated with region-specific differences in brain activation.

Ecological stress during adolescent development may increase the sensitivity to negative emotional processes that can contribute to the onset and progression of internalizing behaviors during preadolescence. Although a small number of studies have considered the link among the complex relations in ecological stress, amygdala reactivity and internalizing symptoms in childhood and adolescence, these studies have largely been small, cross-sectional, and often do not consider unique roles of parenting or sex. In the current study, we evaluated the interrelations among ecological stress, amygdala functioning, subsequent internalizing symptoms, and the moderating roles of parenting and sex, 9-and 10-year old preadolescents from the Adolescent Brain Cognitive Development study (ABCD). A subset of participants who met a priori quality control criteria for bilateral amygdala during the N-back faces versus places contrast (N = 7,385;Mean Age = 120 months, SD = 7.52; 49.5% Female) were included in the study. A Confirmatory Factor Analysis (CFA) was performed to create a latent variable of ecological stress, and multiple Structural Equation Model (SEM) models were conducted to evaluate the association among baseline ecological stress and internalizing symptoms one year later, the mediating role of amygdala activity, and moderating effects of parental acceptance and sex. The results revealed a significant association among ecological stress and subsequent internalizing symptoms, which was greater in males than females. There was no association between amygdala activity and ecological stress or subsequent internalizing symptoms, and no mediating role of amygdala, or moderating effect of parental acceptance, on the association between ecological stress and internalizing symptoms. An alternative mediation model was tested and revealed that parental acceptance mediated the association between ecological stress and internalizing symptoms, demonstrating lower internalizing symptoms among preadolescents one year later. Given the 4 Ecological stress, amygdala reactivity, and internalizing problems lack of association in brain function, ecological stress and internalizing symptoms in this registered report, effects from small studies should be reconsidered in larger samples.

Childhood adversity is heterogeneous with potentially distinct dimensions of violence exposure and social deprivation. These dimensions may differentially shape emotion-based neural circuitry, such as amygdala–PFC white matter connectivity. Amygdala–orbitofrontal cortex (OFC) white matter connectivity has been linked to regulation of the amygdala’s response to emotional stimuli. Using a preregistered analysis plan, we prospectively examined the effects of childhood exposure to two dimensions of adversity, violence exposure and social deprivation, on the adolescent amygdala–PFC white matter connectivity. We also reproduced the negative correlation between amygdala–PFC white matter connectivity and amygdala activation to threat faces. 183 15−17-year-olds were recruited from the Fragile Families and Child Wellbeing Study — a longitudinal, birth cohort, sample of predominantly low-income youth. Probabilistic tractography revealed that childhood violence exposure and social deprivation interacted to predict the probability of adolescent right hemisphere amygdala–OFC white matter connectivity. High violence exposure with high social deprivation related to less amygdala–OFC white matter connectivity. Violence exposure was not associated with white matter connectivity when social deprivation was at mean or low levels (i.e., relatively socially supportive contexts). Therefore, social deprivation may exacerbate the effects of childhood violence exposure on the development of white matter connections involved in emotion processing and regulation. Conversely, social support may buffer against them.