Date of Award

2022

Embargo Period

8-1-2022

Document Type

Thesis - MUSC Only

Degree Name

Doctor of Philosophy (PhD)

College

College of Graduate Studies

First Advisor

Brett Froeliger

Second Advisor

Michael Saladin

Third Advisor

Jane Joseph

Fourth Advisor

James Prisciandaro

Fifth Advisor

Christopher Cowan

Abstract

Background. Smoking maintenance is chiefly driven by negative affects, such as craving and aversion—and disrupted attentional control—mediated by the amygdala and insula in concert with the prefrontal cortex. Cognitive emotion regulation [CER] can modulate amygdala function and improve mood but may be compromised among individuals with TUD. This project aimed to identify corticolimbic negative CER task-state functional connectivity [tsFC] neurocircuits in TUD and abstinence, assess experiential CER effectiveness, and explore brain-behavior correlates of relapse vulnerability. Methods. On two fMRI visits, nonsmokers (n=23) and smokers (n=18) underwent fMRI during a negative CER task followed by an out-of-scanner Smoking-Relapse Task [SRT]. BOLD fMRI task data were preprocessed and denoised in CONN21.a, explicitly masked to isolate negative emotional information processing regions, and thresholded (negative > neutral) via t-contrast (p < 0.05 cluster-level FWE). Surviving regions’ data were then denoised for explicitly-masked tsFC analyses. Seed-to-voxel correlation maps were estimated using functionally-defined amygdala seeds, and tsFC neurocircuits were identified for each aim using F-contrast (p < 0.05 cluster-level FWE). Neurocircuits identified showing significant non-zero tsFC with an amygdala seed were characterized by extracting rZ values into SPSS. Results. In Aim 1, (nonsmokers vs. sated smokers), bilateral amygdala seeds showed positive tsFC with bilateral OFC/insula, vlPFC, and vmPFC. L.Amygdala—L.vlPFC evidenced an effect of negative reappraisal increasing tsFC. Smokers evidenced stronger tsFC between L.Amygdala—R.vlPFC across strategies, and between the R.Amygdala-vmPFC during negative view. Both groups significantly improved their self-reported mood by CER. No brain-behavioral associations were identified. In Aim 2, (abstinence vs. sated), positive tsFC was identified between bilateral amygdala seeds and bilateral OFC/insula, right vlPFC, and between right and left amygdala. Abstinence increased negative view tsFC between L.Amygdala—bilateral OFC/insula, and between L.Amygdala-R.vlPFC, where an interaction was additionally identified; abstinence also decreased L.Amygdala-R.vlPFC tsFC during negative reappraise. In R.Amygdala—L.Amygdala, negative reappraise decreased tsFC from negative view during satiety but not abstinence. Smokers improved mood by CER across states, with less aversive perturbation of mood from negative view while abstinent. No brain-behavior relations were identified between tsFC and relapse-factors, although abstinence increased withdrawal-indices of craving and negative affect. Discussion. Smokers did not evidence any specific CER deficits relative to nonsmokers, or during abstinence, although several patterns of hyperconnectivity related to negative view were identified. Future Directions. Relations between tsFC, BOLD, and dispositional ER, along with a priori investigation of these neurocircuits to predict relapse outcomes and relating neurocircuit dynamics to more nuanced probes of mood state (e.g., heart-rate variability) may be warranted.

Rights

All rights reserved. Copyright is held by the author.

Download

Share

COinS