Neural Plasticity of Extinction: Relations with Anxiety and Extinction Retention

ABSTRACT NEURAL PLASTICITY OF EXTINCTION LEARNING: RELATIONS WITH ANXIETY AND EXTINCTION RETENTION by Emily L. Belleau The University of Wisconsin-Milwaukee, 2016 Under the Supervision of Associate Professor Christine Larson Anxiety is a significant public health problem characterized by substantial psychological, physical, and economic burden. A key feature of anxiety is the inability to regulate fear. Aberrant extinction of conditioned fear is one prominent model of the etiology of anxiety disorders. Previous studies have shown that the neural circuitry underlying anxiety pathology overlaps with that mediating fear extinction learning. Recently, more precise pathways supporting the expression (CMA-aMCC) and inhibition (BLA-vmPFC) of conditioned fear have been identified, and dysfunction in these pathways has been linked with anxiety. However, this work has focused on examining these pathways at one point in time, outside of the context of learning, and no one has examined plastic changes in functional activity before and after extinction learning. In addition, no one has applied this inquiry to individual differences in anxiety and extinction retention. This gap in knowledge is a problem because deficits in extinction-induced neural plasticity may be a substantial contributing factor to sustained fear responses in anxiety. The aim of this project was to examine changes in the strength of CMA-aMCC and BLA-vmPFC pathways from before to after extinction learning and how this is related to anxiety and retention of extinction. In a more exploratory fashion, I investigated the degree to which extinction-related plasticity varies as a function of white matter integrity within these pathways. Our results indicated that extinction learning is associated with enhanced plasticity in fear inhibition circuits (BLA-vmPFC and CMA-vmPFC). Plasticity in these circuits appears to be intact in high anxious individuals. However, trait anxiety was positively associated with strengthened connectivity in a fear expression pathway (BLA-aMCC). Enhanced plasticity within a fear expression circuit likely contributes to fear inhibition problems, a core feature of anxiety problems

Moderating Effects of Harm Avoidance on Resting State Functional Connectivity of the Anterior Insula

As an index of behavioral inhibition and an individual’s propensity to avoid, rather than seek, potentially dangerous situations, harm avoidance has been linked to internalizing psychopathology. Altered connectivity within intrinsic functional neural networks (i.e., default mode [DMN], central executive [CEN] and salience networks [SN]) has been related to internalizing psychopathology; however, less is known about the effects of harm avoidance on functional connectivity within and between these networks. Importantly, harm avoidance may be distinguishable from trait anxiety and have clinical relevance as a risk factor for internalizing psychopathology. A sample of young adults (n = 99) completed a resting state functional magnetic resonance imaging (fMRI) scan and self-report measures of harm avoidance and trait anxiety. Whole brain seed-to-voxel and seed-to-network connectivity analyses were conducted using anterior insula seeds to examine associations between harm avoidance/trait anxiety and connectivity. After adjusting for sex and age, there was a significant negative effect of harm avoidance on connectivity between the anterior insula and clusters in the precuneus/posterior cingulate cortex (PCC) left superior/middle frontal gyrus, dorsal anterior cingulate cortex (dACC) and bilateral inferior parietal lobule (IPL)/angular gyrus. Seed-to-network analyses indicated a negative effect of harm avoidance on connectivity between the right anterior insula and anterior and posterior DMN. There were no effects of trait anxiety on functional connectivity of the anterior insula. Overall, the results indicate that individual differences in harm avoidance relate to disruptions in internetwork connectivity that may contribute to deficits in appropriately modulating attentional focus