Associations of Childhood Trauma With Dynamic Fear Conditioning and Psychopathology

• In Event: 2-067 - Childhood Adversity and Fear Learning Mechanisms

Integrative Statement

Alterations in the way the brain learns to detect, interpret, and respond to threatening stimuli in the environment is one potential mechanism linking childhood trauma (CT) with risk for multiple forms of psychopathology. Fear conditioning is the primary mechanism through which specific stimuli become associated with threat. While the neural networks underlying fear conditioning in adults are well understood, few studies have examined neural correlates of fear conditioning in children and adolescents. Whether exposure to CT alters fear conditioning processes in ways that contribute to psychopathology also remains unknown.

To investigate these questions, we recruited a community sample of 161 children (ages 8-16 years) with and without exposure to CT, defined as exposure to physical abuse, sexual abuse, or domestic violence. Participants completed a Pavlovian fear conditioning paradigm while completing an fMRI scan. The unconditioned stimulus was a loud aversive noise, and the conditioned stimuli were colored shapes that appeared in four block types: reinforced CS+ (CS+R), non-reinforced CS+ (CS+), CS-, and ITI. Whole-brain analyses were conducted to identify regions more active during CS+ vs. CS- (and vice versa) across the entire task. Dynamic patterns of learning were examined across the four blocks in voxel-wise parametric modulation analyses and region-of-interest analyses, and multiple regression was used to examine associations with psychopathology symptoms.

Significant activation for CS+ > CS- was observed throughout the salience network, including anterior insula (aINS), anterior cingulate cortex (ACC), and amygdala; for CS- > CS+, the hippocampus and areas within the ventral visual stream were active. Parametric modulation analyses revealed dynamic learning, such that activation to the CS+ vs. CS- decreased linearly across blocks in aINS, ACC, and amygdala, while activation increased linearly to the CS- vs. CS+ in the subgenual cingulate, frontal pole, posterior cingulate, precuneus, angular gyrus, hippocampus, and parahippocampal gyrus.

Significant group differences in neural response to the CS+ vs. CS- as a function of CT were observed as stimulus x block x group interactions in aINS, ACC, right amygdala, right hippocampus, posterior parahippocampal gyrus, and frontal pole. In these regions, children with CT displayed delayed acquisition of differential learning and lack of habituation, as well as blunted initial responses to the CS+ in right amygdala and hippocampus. Dynamic neural responses in several regions were associated with symptoms of depression (amygdala, hippocampus, aINS, frontal pole), anxiety (amygdala, hippocampus, frontal pole), and PTSD (amygdala, ACC), such that steeper habituation slopes were associated with fewer symptoms.

Canonical networks involved in fear and safety learning were activated in children during a fear conditioning task. Exposure to CT was associated with altered patterns of learning, and several patterns of activation during learning were associated with multiple psychopathology outcomes. Alterations in fear learning processes and the dynamic communication between regions of the fear and safety networks may be a key mechanism underlying the link between CT and psychopathology.

Authors

• Stephanie N. DeCross, Harvard University
  Presenting Author

• Katie McLaughlin, Harvard University
  Non-Presenting Author