Dynamic Alterations in Neural Networks Supporting Aversive Learning in Children Exposed to Trauma: Neural Mechanisms Underlying Psychopathology

Abstract

Altered aversive learning represents a potential mechanism through which childhood trauma (CT) might influence risk for psychopathology. This study examines the temporal dynamics of neural activation and patterns of functional connectivity during aversive learning in children with and without CT, and evaluates whether these neural patterns mediate the association of CT with psychopathology in a longitudinal design. 147 children (aged 8-16 years, 77 with CT) completed a fear conditioning procedure during an fMRI scan. Dynamic patterns of neural activation were examined in whole-brain and region-of-interest analyses; functional connectivity was assessed with generalized psychophysiological interaction analyses. We evaluated whether the associations between CT and psychopathology symptoms at baseline and two-year follow-up were mediated by neural activation and connectivity during aversive learning. Children exposed to trauma displayed blunted patterns of neural activation over time during CS+>CS- in right amygdala and during CS->CS+ in right hippocampus and frontal pole. Additionally, during CS+>CS-, CT was associated with elevated functional connectivity of right amygdala with fronto-parietal regions and reduced connectivity with hippocampus, posterior parahippocampal gyrus, and posterior cingulate cortex. The longitudinal association between CT and later externalizing symptoms was mediated by blunted activation in right amygdala and insula. Reduced amygdala-hippocampal connectivity mediated the association of CT with transdiagnostic anxiety symptoms. CT is associated with poor threat-safety discrimination and altered functional coupling between salience and default mode network regions during aversive learning. These altered neural dynamics during learning may be key mechanisms linking CT with internalizing and externalizing psychopathology.

Why and how does early adversity influence development? Toward an integrated model of dimensions of environmental experience

“…Elevated emotional responses to stress and heightened responsivity to cues signaling the presence of threat in the environment are well-documented among children exposed to violence (Glaser et al, 2006;Heleniak et al, 2016;Hennessy et al, 1994;Kim & Cicchetti, 2010;Weissman et al, 2019). More recent evidence has documented altered patterns of aversive learning in children exposed to threat (DeCross et al, 2021;Machlin et al, 2019;. Critically, these patterns have been observed even in studies that control for co-occurring deprivation experiences.…”