Whole-Brain Functional Connectivity Dynamics Associated with Electroconvulsive Therapy Treatment Response

Background: Major depressive disorder characterized by abnormalities of cognitive functions and mood is one of the leading causes of disability. Electroconvulsive therapy (ECT), which involves a brief electrical stimulation of the anesthesia brain, is the most potent treatment used in patients with depressive episodes (DEP) due to its rapid efficacy. Methods: In this work, we investigated how the human brain dynamically responds to ECT and whether the dynamic responses are associated with treatment outcomes and side-effects in 110 patients with DEP and 60 healthy controls (HCs) via a combination of a fully automated independent component analysis (ICA)-based pipeline and the clustering analysis. Findings: Five reoccurring connectivity states were identified, among which DEP had fewer occurrences in one antagonism state (state 1) with strong positive and negative connectivity. DEP patients increased the occupancy of two states (states 3 and 4) after ECT, resulting in significantly different occurrences of one additional state (state 3) compared to HC. We further found that DEP patients had diminished global meta-state dynamism, two of which recovered to normal after ECT. Interestingly, the changes in dynamic connectivity characteristics were associated with the changes in memory recall and Hamilton Depression Rating Scale of DEP after ECT. Interpretation: These converging results extend current findings on subcortical-cortical dysfunction and dysrhythmia in DEP and demonstrate that ECT might cause a remodeling of brain functional dynamics that underlies antidepressant symptom response and memory function of patients. Funding Statement: This work was supported National Institutes of Health (No. R01MH118695, R01EB020407 and R01MH117107), and China Natural Science Foundation (No. 61773380), Beijing Municipal Science and Technology Commission (No. Z181100001518005). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Written informed consent was obtained from all participants under protocols approved by the Institutional Review Board (IRB) of UNM and UCLA.