Improved clinical outcome prediction in depression using neurodynamics in an emotional face-matching functional MRI task

Introduction: Approximately one in six people will experience an episode of major depressive disorder (MDD) in their lifetime. Effective treatment is hindered by subjective clinical decision-making and a lack of objective prognostic biomarkers. Functional MRI (fMRI) could provide such an objective measure but the majority of MDD studies has focused on static approaches, disregarding the rapidly changing nature of the brain. In this study, we aim to predict depression severity changes at 3 and 6 months using dynamic fMRI features.

Methods: For our research, we acquired a longitudinal dataset of 32 MDD patients with fMRI scans acquired at baseline and clinical follow-ups 3 and 6 months later. Several measures were derived from an emotion face-matching fMRI dataset: activity in brain regions, static and dynamic functional connectivity between functional brain networks (FBNs) and two measures from a wavelet coherence analysis approach. All fMRI features were evaluated independently, with and without demographic and clinical parameters. Patients were divided into two classes based on changes in depression severity at both follow-ups.

Results: The number of coherence clusters (nCC) between FBNs, reflecting the total number of interactions (either synchronous, anti-synchronous or causal), resulted in the highest predictive performance. The nCC-based classifier achieved 87.5% and 77.4% accuracy for the 3- and 6-months change in severity, respectively. Furthermore, regression analyses supported the potential of nCC for predicting depression severity on a continuous scale. The posterior default mode network (DMN), dorsal attention network (DAN) and two visual networks were the most important networks in the optimal nCC models. Reduced nCC was associated with a poorer depression course, suggesting deficits in sustained attention to and coping with emotion-related faces. An ensemble of classifiers with demographic, clinical and lead coherence features, a measure of dynamic causality, resulted in a 3-months clinical outcome prediction accuracy of 81.2%.

Discussion: The dynamic wavelet features demonstrated high accuracy in predicting individual depression severity change. Features describing brain dynamics could enhance understanding of depression and support clinical decision-making. Further studies are required to evaluate their robustness and replicability in larger cohorts.