PROJECT SUMMARY/ABSTRACT
Visual cues predicting aversive outcomes facilitate low-level visual perception—often referred to as
attentional threat biases—and heighten defensive engagement at the behavioral, autonomic, and central
nervous system levels. However, as aversive conditioning proceeds over time, psychophysics and neuroimaging
work has found threat biases accompanied by reduced, instead of heightened, activity of the brain's defensive
network. Additional literature indicates that aversive conditioning is facilitated in females and individuals with
greater dispositional anxiety, implicating a critical role of biological sex and individual differences in trait-like
anxiety phenotypes. How these differences affect the acquisition and extinction of attentional threat biases is
currently unknown. Such knowledge is critical to identifying novel neural etiological and intervention targets for
clinical tools. The present training grant aims to establish the neural dynamics during visual threat bias acquisition
and extinction. Specifically, we test the overarching hypothesis that temporally extended aversive conditioning
increasingly relies on biased perception and attention, and less on defensive brain circuits including the
amygdala. This work will contribute to NIMH strategic priorities by defining the underlying neural mechanisms
contributing to complex behaviors. Thus, the proposed project aims to first (1) identify progressive changes in
visual, attentional, and limbic neural networks contributing to the representation of threat versus safe-related
visual cues over the course of acquisition by measuring trial-by-trial electrophysiological and hemodynamic
activity. Second, (2) determine the value of individual differences in visual and attentional frontoparietal network
changes during threat cue acquisition for predicting extinction and extinction recall. Third, (3) examine the extent
to which individual differences in biological sex and dispositional anxiety influence changes in cortical
representations of threat cues during acquisition and subsequent extinction. Participants will engage in a 2-day
aversive conditioning regimen in which they undergo differential aversive conditioning followed by an extinction
paradigm, and return on day 2 for a reinstatement test. Simultaneous electroencephalography (EEG) and
functional magnetic resonance (fMRI) imaging during these tasks will enable the identification of functional brain
alterations, fulfilling the aims of the proposed research. Pursuing these aims will aid in current efforts in improving
diagnostic assessment and treatment for anxiety disorders. The training goals of this fellowship will develop the
applicant's knowledge and research skills regarding theoretical components related to differential aversive
conditioning, EEG-fMRI acquisition, and advanced neuroimaging analytical techniques. This project is the first
to examine cortical network changes over the course of aversive conditioning, the influence these dynamics
have on extinction, and how individual differences moderate these effects.