Resting State and Task Triple Network Connectivity Profiles in Remitted Depressed Patients Compared with Healthy Volunteers

Abstract

In addition to mood symptoms, major depressive disorder (MDD) is characterized by cognitive impairments that can have detrimental impacts on quality of life and daily function, and have been found to persist into remission. In particular, altered affective cognition (e.g. biased attention to negative stimuli) has been reported in MDD, and may continue into remission. Unfortunately, current pharmacotherapies do not adequately address cognitive dysfunction in acute or remitted MDD. Understanding the neurobiological underpinnings of affective cognitive dysfunction in remitted MDD may help inform the development of new interventions to address this lingering problem and the associated poorer functional outcomes. The triple network model posits that altered functioning of three key networks implicated in normal cognitive function – the default mode network (DMN), central executive network (CEN) and salience network (SN) – underlies cognitive dysfunction in a variety of psychiatric illnesses, including MDD. Though notable exceptions exist, work in acutely depressed MDD patients has found evidence of DMN hyperconnectivity, CEN hypoconnectivity and abberant SN connectivity both at rest and during the completion of various cognitive tasks. The evidence for triple network connectivity alterations persisting into remission is less robust, and warrants further investigation. Furthermore, there is a paucity of studies examining remitted MDD connectivity during affective tasks. As such, the primary objectives of this thesis were to: 1) compare resting-state and task triple network connectivity profiles in remitted MDD patients (rMDDs) and healthy volunteers (HVs) at rest, during an affective (emotional Stroop [eStroop]) task, and during rest vs. the task and, 2) assess the relationship between DMN and CEN connectivity and measures of daily functioning, quality of life and/or negative, self-relational rumination in the rMDD cohort. Behaviourally, there were findings of an affective attentional bias and impaired processing speed in the rMDD vs. HVs, as revealed by a computerized cognitive test battery. However, we found no evidence of DMN hyperconnectivity or CEN hyperconnectivity in the rMDD study sample. We did find evidence of altered intrinsic CEN and CEN-SN connectivity between the rest and task conditions that seemed driven by the rMDD sample, as well as positive CEN-DMN correlations across the entire sample both at rest and during the eStroop task. Suprisingly, we also found higher intrinsic DMN connectivity during the eStroop task vs. at rest across the whole sample. Finally, we found a positive relationship between task-based CEN connectivity and hopeless rumination, and a significant negative relationship between resting state and task-based DMN connectivity and psychosocial dysfunction in the rMDD sample. These findings contribute to our understanding of large-scale intrinsic network connectivity alterations during remitted depression, and their relationship to functional outcomes.