Performances of whole-brain dynamic and static functional connectivity fingerprinting in machine learning-based classification of major depressive disorder

Abstract

Background: Alterations in static and dynamic functional connectivity during resting state have been widely reported in major depressive disorder (MDD). The objective of this study was to compare the performances of whole-brain dynamic and static functional connectivity combined with machine learning approach in differentiating MDD patients from healthy controls at the individual subject level. Given the dynamic nature of brain activity, we hypothesized that dynamic connectivity would outperform static connectivity in the classification.

Methods: Seventy-one MDD patients and seventy-one well-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Whole-brain dynamic and static functional connectivity patterns were calculated and utilized as classification features. Linear kernel support vector machine was employed to design the classifier and a leave-one-out cross-validation strategy was used to assess classifier performance.

Results: Experimental results of dynamic functional connectivity-based classification showed that MDD patients could be discriminated from healthy controls with an excellent accuracy of 100% irrespective of whether or not global signal regression (GSR) was performed (permutation test with P < 0.0002). Brain regions with the most discriminating dynamic connectivity were mainly and reliably located within the default mode network, cerebellum, and subcortical network. In contrast, the static functional connectivity-based classifiers exhibited unstable classification performances, i.e., a low accuracy of 38.0% without GSR (P = 0.9926) while a high accuracy of 96.5% with GSR (P < 0.0002); moreover, there was a considerable variability in the distribution of brain regions with static connectivity most informative for classification.

Conclusion: These findings suggest the superiority of dynamic functional connectivity in machine learning-based classification of depression, which may be helpful for a better understanding of the neural basis of MDD as well as for the development of effective computer-aided diagnosis tools in clinical settings.

Keywords: dynamic functional connectivity; machine learning; major depressive disorder; resting-state functional magnetic resonance imaging; static functional connectivity.