Cognitive Vulnerability to Major Depression: View from the Intrinsic Network and Cross-network Interactions

Abstract

Although it is generally accepted that cognitive factors contribute to the pathogenesis of major depressive disorder (MDD), there are missing links between behavioral and biological models of depression. Nevertheless, research employing neuroimaging technologies has elucidated some of the neurobiological mechanisms related to cognitive-vulnerability factors, especially from a whole-brain, dynamic perspective. In this review, we integrate well-established cognitive-vulnerability factors for MDD and corresponding neural mechanisms in intrinsic networks using a dual-process framework. We propose that the dynamic alteration and imbalance among the intrinsic networks, both in the resting-state and the rest-task transition stages, contribute to the development of cognitive vulnerability and MDD. Specifically, we propose that abnormally increased resting-state default mode network (DMN) activity and connectivity (mainly in anterior DMN regions) contribute to the development of cognitive vulnerability. Furthermore, when subjects confront negative stimuli in the period of rest-to-task transition, the following three kinds of aberrant network interactions have been identified as facilitators of vulnerability and dysphoric mood, each through a different cognitive mechanism: DMN dominance over the central executive network (CEN), an impaired salience network-mediated switching between the DMN and CEN, and ineffective CEN modulation of the DMN. This focus on interrelated networks and brain-activity changes between rest and task states provides a neural-system perspective for future research on cognitive vulnerability and resilience, and may potentially guide the development of new intervention strategies for MDD.

Figure 1

Aberrant intrinsic network interaction model that integrates the dual-process model of cognitive vulnerability, which has been adapted from Beevers (2005). The dual-process model includes two modes of information processing: (1) an associative mode involving quick, effortless processing, and (2) a reflective mode involving slow, effortful processing. We propose that abnormally increased resting-state DMN activity and connectivity, along with the corresponding biased associative processing (depressive rumination), contribute to the foundation of cognitive vulnerability. In the period of rest-to-task transition, aberrant network interactions contribute to three scenarios in which an associative bias cannot be corrected, thus promoting cognitive vulnerability. These three scenarios are (1) DMN dominance over the CEN (cognitive-resource depletion), (2) abnormal SN switching between the DMN and CEN (associative bias does not violate internal expectancies and trigger reflective processing), and (3) failure to activate the CEN effectively (reflective processing being triggered but failing to accurately adjust associative bias). As a result, a feedback loop between negative bias and dysphoria occurs, leading to a downward spiral. The solid lines in the triple-network model indicate enhanced interactions, while the dotted lines indicate attenuated interactions. CEN, central executive network; DMN, default mode network; SN, salience network.

Figure 2

Schematic figure of triple-network model showing the SN-induced coordination between the DMN and CEN. According to this model, the SN (I) mediates the “switching” between the DMN (II) and CEN (III) to guide appropriate responses to salient stimuli. Salience signals are integrated in the anterior insular cortex of the SN, and then causally influence signals in the DMN and CEN, which support internally directed and externally directed cognition, respectively.^, In light of recent work that suggests the existence of distinct functional subdivisions within the insular cortex,^, the right anterior insular cortex is now thought to be the specific brain region that assists in switching between networks. The large dots show the key nodes of each network in the triple-network model. AI, anterior insular cortex; CEN, central executive network; dACC, dorsal anterior cingulated cortex; DLPFC, dorsolateral prefrontal cortex; DMN, default mode network; mPFC, medial prefrontal cortex; PCC, posterior cingulate cortex; SN, salience network; PPC, posterior parietal cortex. Adapted from Uddin (2014) and Uddin & Menon (2009).