Within-subject neural reactivity to reward and threat is inverted in young adolescents.

BACKGROUND: As children mature, they become increasingly independent and less reliant on caregiver support. Changes in brain systems are likely to stimulate and guide this process. One mechanistic hypothesis suggests that changes in neural systems that process reward and threat support the increase in exploratory behavior observed in the transition to adolescence. This study examines the basic tenets of this hypothesis by performing functional magnetic resonance imaging (fMRI) during well-established reward and threat processing tasks in 40 children and adolescents, aged 9-15 years. METHOD: fMRI responses in the striatum and amygdala are fit to a model predicting that striatal reward and amygdala threat-responses will be unrelated in younger participants (aged 9-12 years), while older participants (aged 13-15 years) will differentially engage these structures. RESULTS: Our data are consistent with this model. Activity in the striatum and amygdala are comparable in younger children, but in older children, they are inversely related; those more responsive to reward show a reduced threat-response. Analyses testing age as a continuous variable yield consistent results. In addition, the proportion of threat to reward-response relates to self-reported approach behavior in older but not younger youth, exposing behavioral relevance in the relative level of activity in these structures. CONCLUSIONS: Results are consistent with the notion that both individual and developmental differences drive reward-seeking behavior in adolescence. While these response patterns may serve adaptive functions in the shift to independence, skew in these systems may relate to increased rates of emotional psychopathology and risk-taking observed in adolescence.

Uncertain in the face of change: Lack of contingency shift awareness during extinction is associated with higher fear-potentiated startle and PTSD symptoms in children.

Intolerance of uncertainty is a transdiagnostic risk factor for fear-related disorders and is associated with higher levels of anxiety in children and adolescents. It is unclear how uncertainty relates to development of psychopathology in children who have experienced trauma in early life. The present study used a fear-potentiated startle paradigm in children to examine associations between uncertainty (assessed as unawareness of a change in reinforcement during fear extinction) and symptoms of anxiety and posttraumatic stress disorder (PTSD), as well as startle potentiation to threat and safety cues. Results showed that unaware children had strong positive associations between trauma exposure and PTSD symptoms, whereas aware children did not. Uncertainty interacted with anxiety in that children who were both unaware and had higher anxiety displayed higher fear-potentiated startle to safety cues and did not show discrimination between threat and safety during fear conditioning. These results suggest that anxious children who persist in associating a threat cue with an aversive event during extinction, after repeated presentations of the no longer reinforced conditioned stimulus, may express psychophysiological phenotypes related to PTSD.

Community Violence Exposure is Associated with Hippocampus-Insula Resting State Functional Connectivity in Urban Youth.

Our previous work has linked childhood violence exposure in Black youth to functional changes in the hippocampus, a brain region sensitive to stress. However, different contexts of violence exposure (e.g., community, home, school) may have differential effects on circuitry. We investigated the unique effect of community violence in predicting resting-state functional connectivity (rsFC) in the hippocampus. Fifty-two (26F) violence-exposed Black youth ages 8-15 performed resting-state functional neuroimaging scans while looking at a fixation cross for seven minutes with eyes open. Seed-based analyses were conducted to examine the association between total violence exposure and rsFC of the hippocampus to the whole brain. Follow-up hierarchical regression analysis were performed to specifically investigate community violence. Violence exposure was associated with higher hippocampus rsFC with a core node of the Default Mode Network (i.e., posterior cingulate cortex) and lower hippocampal rsFC with a core node of the Salience Network (i.e., insula). Community violence uniquely associated with lower hippocampus-insula rsFC, after controlling for home and school violence, sex and age. Age-related decreases in hippocampus-insula rsFC were also present in youth with lower violence exposure, but not in youth with higher violence exposure. This is one of the first studies to investigate the unique impact of community violence, above home and school violence, on threat circuitry. Our data suggest functional alterations in the hippocampus in violence-exposed youth, and that violence in the community may be a more salient form of threat exposure compared to other forms of violence experienced by youth.

You say 'prefrontal cortex' and I say 'anterior cingulate': meta-analysis of spatial overlap in amygdala-to-prefrontal connectivity and internalizing symptomology.

Connections between the amygdala and medial prefrontal cortex (mPFC) are considered critical for the expression and regulation of emotional behavior. Abnormalities in frontoamygdala circuitry are reported across several internalizing conditions and associated risk factors (for example, childhood trauma), which may underlie the strong phenotypic overlap and co-occurrence of internalizing conditions. However, it is unclear if these findings converge on the same localized areas of mPFC or adjacent anterior cingulate cortex (ACC). Examining 46 resting-state functional connectivity magnetic resonance imaging studies of internalizing conditions or risk factors (for example, early adversity and family history), we conducted an activation likelihood estimation meta-analysis of frontoamygdala circuitry. We included all reported amygdala to frontal coordinate locations that fell within a liberal anatomically defined frontal mask. Peak effects across studies were centered in two focal subareas of the ACC: pregenual (pgACC) and subgenual (sgACC). Using publicly available maps and databases of healthy individuals, we found that observed subareas have unique connectivity profiles, patterns of neural co-activation across a range of neuropsychological tasks, and distribution of tasks spanning various behavioral domains within peak regions, also known as 'functional fingerprints'. These results suggest disruptions in unique amygdala-ACC subcircuits across internalizing, genetic and environmental risk studies. Based on functional characterizations and the studies contributing to each peak, observed amygdala-ACC subcircuits may reflect separate transdiagnostic neural signatures. In particular, they may reflect common neurobiological substrates involved in developmental risk (sgACC), or the broad expression of emotional psychopathology (pgACC) across disease boundaries.