Distinct neural profiles during aversive learning mediate the longitudinal association of childhood trauma and symptoms of internalizing and externalizing psychopathology in youth

Oral presentation at the Association for Behavioral and Cognitive Therapies (ABCT) 2020 virtual conference as part of the symposium "Remembering (not) to fear: Understanding the development and treatment of anxiety and PTSD through translational research on fear memory and learning." Abstract One potential mechanism linking childhood trauma (CT) exposure with psychopathology is aversive learning. This study aims to describe the temporal dynamics of neural activation during aversive learning and patterns of task-based functional connectivity, as well as how CT may influence these neural correlates in ways that contribute to psychopathology. 147 children (aged 8-16 years) with and without exposure to CT completed a fear conditioning procedure during an fMRI scan, and measures of clinical symptoms were collected at baseline and two-year follow-up. Whole-brain and region-of-interest analyses were conducted to examine dynamic patterns of learning and connectivity, and nonparametric mediation models were run to test whether these neural measures mediated the relationship between CT and psychopathology at baseline and follow-up. In children, canonical salience network regions were active to the threat vs. safety cue, and exhibited habituation across blocks. Default mode network regions were active to the safety vs. threat cue, with activation increasing across blocks. Moreover, children with CT displayed blunted learning slopes over time in right amygdala, right hippocampus, and frontal pole, as well as elevated connectivity of amygdala with regions associated with attention direction and initiation of defensive responses and reduced amygdala-hippocampal connectivity. Patterns of neural response across blocks and task-based connectivity were associated with transdiagnostic psychopathology (depression, panic, generalized anxiety, externalizing, and PTSD) at baseline and follow-up. Critically, blunted learning slopes in right amygdala and insula mediated the pathway between CT and externalizing at two-year follow-up, controlling for baseline symptoms, and reduced amygdala-hippocampal connectivity mediated the pathway between CT and panic and generalized anxiety. This study provides evidence that alterations in aversive learning processes and the dynamic communication between salience network and default mode network regions may be a key mechanism underlying the link between CT and psychopathology. Disruptions in neural activation versus connectivity during learning may set some children on trajectories towards differentiable clinical symptom profiles