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INTRODUCTION: For decades, predicting response to the antidepressant medication has been a critical unmet need in depression treatment in clinic, and a technical challenge in depression research. METHODS: In this study, a recently developed functional brain network controllability (fBNC) analysis approach was employed to identify the antidepressant treatment responders and non-responders from depression patients at pre-treatment period. The fBNC, which captures the ability of brain regions to guide the brain's behavior from an initial state to a desired state with suitable choice of inputs, may provide valuable features for antidepressant response prediction. The performance of prediction was evaluated using resting-state functional magnetic resonance imaging data collected from a six-week longitudinal clinical trial with escitalopram in treating unmedicated depression patients (n = 20). Treatment outcomes were assessed using the Hamilton Depression Rating Scale (HAMD) scores. Patients were considered as the treatment responders if their post-treatment HAMD scores were decreased by 50% or more at 6-week post-treatment. RESULTS: Results showed significantly larger global average controllability and lower global modal controllability, greater regional average controllability, and smaller regional modal controllability of default mode network in treatment responders compared to the treatment non-responders at pre-treatment period. By performing optimal control analysis, our results showed that no significant difference of the neuromodulation effects between the treatment responders and non-responders. DISCUSSION: Our results suggest that the functional brain network controllability measures may be utilized as novel biomarkers to predict antidepressant response on depression and provide theoretical support to employ neuromodulation for treating antidepressant non-responders.

Original publication




Journal article


Brain Connect

Publication Date



Brain connectivity, Cognitive control, Depression, Transcranial magnetic stimulation (TMS)