Predictive signature of static and dynamic functional connectivity for ECT clinical outcomes

Introduction: Electroconvulsive therapy (ECT) remains one of the most effective approaches for treatment-resistant depressive episodes, despite the potential cognitive impairment associated with this treatment. As a potent stimulator of neuroplasticity, ECT might normalize aberrant depression-related brain function via the brain's reconstruction by forming new neural connections. Multiple lines of evidence have demonstrated that functional connectivity (FC) changes are reliable indicators of antidepressant efficacy and cognitive changes from static and dynamic perspectives. However, no previous studies have directly ascertained whether and how different aspects of FC provide complementary information in terms of neuroimaging-based prediction of clinical outcomes. Methods: In this study, we implemented a fully automated independent component analysis framework to an ECT dataset with subjects (n = 50, age = 65.54 ± 8.92) randomized to three treatment amplitudes (600, 700, or 800 milliamperes [mA]). We extracted the static functional network connectivity (sFNC) and dynamic FNC (dFNC) features and employed a partial least square regression to build predictive models for antidepressant outcomes and cognitive changes. Results: We found that both antidepressant outcomes and memory changes can be robustly predicted by the changes in sFNC (permutation test p < 5.0 × 10^-3). More interestingly, by adding dFNC information, the model achieved higher accuracy for predicting changes in the Hamilton Depression Rating Scale 24-item (HDRS₂₄, t = 9.6434, p = 1.5 × 10^-21). The predictive maps of clinical outcomes show a weakly negative correlation, indicating that the ECT-induced antidepressant outcomes and cognitive changes might be associated with different functional brain neuroplasticity. Discussion: The overall results reveal that dynamic FC is not redundant but reflects mechanisms of ECT that cannot be captured by its static counterpart, especially for the prediction of antidepressant efficacy. Tracking the predictive signatures of static and dynamic FC will help maximize antidepressant outcomes and cognitive safety with individualized ECT dosing.