Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Dr. Ruth Lanius

Abstract

The amygdala and insula are highly implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in PTSD and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity of individual amygdala and insula subregions have not previously been compared in PTSD, PTSD+DS and healthy controls. In two separate studies, we examined amygdala complex (chapter 2) and insula subregion (chapter 3) functional connectivity patterns using resting-state fMRI. Patients with PTSD and PTSD+DS were found to display unique amygdala complex functional connectivity patterns to prefrontal cortex (PFC) regions involved in emotion regulation, in addition to regions involved in consciousness, awareness, and proprioception. Furthermore, PTSD patients displayed increased insula subregion connectivity to the basolateral amygdala. Differences in amygdala complex and insula subregion connectivity were found to parallel the unique symptom profiles of PTSD and PTSD+DS (hyper- vs. hypo-emotionality and arousal, respectively) and point towards specific biological markers. Similarly, we investigated how amygdala complex functional connectivity may change in response to treatment intervention (Chapter 4). Here, alpha desynchronizing EEG neurofeedback was associated with a shift in amygdala complex connectivity from areas implicated in defense and fear processing/memory retrieval, towards PFC areas implicated in emotion regulation/modulation. Additionally, we sought to observe the neurobiological effects of specifically downregulating the amygdala using real-time fMRI neurofeedback during symptom provocation (Chapter 5). It was found that downregulating the amygdala corresponded to increased activation in PFC regions related to emotion regulation, which was negatively correlated to PTSD symptoms. These findings have significant implications for developing targeted non-invasive treatment interventions for PTSD patients that utilize EEG and real-time fMRI neurofeedback, showing evidence of neuronal reconfiguration between areas highly implicated in the disorder. Finally, we investigated directed connectivity patterns of the amygdala with PFC and brainstem regions using resting-state fMRI dynamic causal modelling (Chapter 6). Here, our results suggest that the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality and arousal, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom-up defensive fear processing vs. enhanced top-down regulation.


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