Electronic Thesis and Dissertation Repository


Doctor of Philosophy


Anatomy and Cell Biology


Derek Mitchell


The ability of emotionally significant stimuli to bias our behaviour is an evolutionarily adaptive phenomenon. However, sometimes emotions become excessive, inappropriate, and even pathological, like in major depressive disorder (MDD). Emotional flexibility includes both the neural processes involved in reacting to, or representing, emotional significance, and those involved in controlling emotional reactivity. MDD represents a potentially distinct form of emotion (in)flexibility, and therefore offers a unique perspective for understanding both the integration of conflicting emotional cues and the neural regions involved in actively controlling emotional systems.

The present investigation of emotional flexibility began by considering the functional neural correlates of competing socio-emotional cues and effortful emotion regulation in MDD using both negative and positive emotions. Study 1 revealed greater amygdala activity in MDD relative to control participants when negative cues were centrally presented and task-relevant. No significant between-group differences were observed in the amygdala for peripheral task-irrelevant negative distracters. However, controls demonstrated greater recruitment of the ventrolateral (vlPFC) and dorsomedial prefrontal cortices (dmPFC) implicated in emotion control. Conversely, attenuated amygdala activity for task-relevant and irrelevant positive cues was observed in depressed participants. In Study 2, effortful emotion regulation using strategies adapted from cognitive behaviour therapy (CBT) revealed greater activity in regions of the dorsal and lateral prefrontal cortices in both MDD and control participants when attempting to either down-regulate negative or up-regulate positive emotions. During the down-regulation of negative cues, only controls displayed a significant reduction of amygdala activity. In Study 3, an individual differences approach using multiple regression revealed that while greater amygdala-vmPFC structural connectivity was associated with low trait-anxiety, greater connectivity between amygdala and regions of occipitotemporal and parietal cortices was associated with high trait-anxiety.

These findings are discussed with respect to current models of emotional reactivity and emotion control derived from studies of both healthy individuals and those with emotional disorders, particularly depression. The focus is on amygdala variability in differing contexts, the role of the vmPFC in the modulation of amygdala activity via learning processes, and the modulation of emotion by attention or cognitive control mechanisms initiated by regions of frontoparietal cortices.