Neural Network Dynamics Over the Course of Aversive Conditioning: The Influence of Visuocortical and Attentional Network Activity in Predicting Extinction Learning

项目总结/文摘

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.