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Abstract

Objectives The human brain is organized into large-scale networks that dynamically interact with each other. Extensive evidence has shown characteristic changes in certain large-scale networks during transitions from internally directed to externally directed attention. The aim of the present study was to compare these context-dependent network interactions during emotion regulation and to examine potential alterations in remitted unipolar and bipolar disorder patients. Methods We employed a multi-region generalized psychophysiological interactions analysis to quantify connectivity changes during distraction vs reappraisal pair-wise across 90 regions placed throughout the four networks of interest (default-mode, frontoparietal, salience, and dorsal attention networks). Using network contingency analysis and permutation testing, we estimated the likelihood that the number of significant condition-dependent connectivity changes in every pair of networks exceeds the number expected by chance. We first examined the pattern of functional connectivity in 42 healthy subjects (sample I) and then compared these connectivity patterns across healthy individuals (n=23) and remitted bipolar (n=21) and unipolar disorder patients (n=21) in an independent sample II. Results In sample I, distraction compared to reappraisal was characterized by reduced connectivity within the default-mode network and between the default-mode and two cognitive control networks and increased connectivity among the cognitive control networks. In sample II, both patient groups exhibited abnormally increased default-mode intra- and inter-network connectivity during distraction compared to reappraisal. Conclusions The present study highlights the role of large-scale network interactions in emotion regulation and provides preliminary evidence of default-mode inter- and intra-network connectivity impairments in remitted bipolar and unipolar patients during emotion regulation.