Objective: In generalized anxiety disorder (GAD), abnormal top-down control from prefrontal cortex (PFC) to amygdala is a widely accepted hypothesis through which "emotional dysregulation model" may be explained. However, whether and how the PFC directly exerted abnormal top-down control on amygdala remained largely unknown. We aim to investigate the amygdala-based effective connectivity by using Granger causality analysis (GCA). Methods: Thirty-five drug-naive patients with GAD and thirty-six

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... ealthy controls (HC) underwent resting-state functional MR imaging. We used seed-based Granger causality analysis to examine the effective connectivity between the bilateral amygdala and the whole brain. The amygdala-based effective connectivity was compared between the two groups. Results: In HC, the left middle frontal gyrus exerted inhibitory influence on the right amygdala, while in GAD group, this influence was disrupted (single voxel P < 0.001, Gaussian random field corrected with P < 0.01). Conclusion: Our finding might provide new insight into the "insufficient top-down control" hypothesis in GAD.