Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for FMRI

Social anxiety disorder (SAD) is characterized by over-reactivity of fear-related circuits in social or performance situations and associated with marked social impairment. We used dynamic causal modeling (DCM), a method to evaluate effective connectivity, to test our hypothesis that SAD patients would exhibit dysfunctions in the amygdala-prefrontal emotion regulation network. Thirteen unmedicated SAD patients and 13 matched healthy controls performed a series of facial emotion and object discrimination tasks while undergoing fMRI. The emotion-processing network was identified by a task-related contrast and motivated the selection of the right amygdala, OFC, and DLPFC for DCM analysis. Bayesian model averaging for DCM revealed abnormal connectivity between the OFC and the amygdala in SAD patients. In healthy controls, this network represents a negative feedback loop. In patients, however, positive connectivity from OFC to amygdala was observed, indicating an excitatory connection. As we did not observe a group difference of the modulatory influence of the FACE condition on the OFC to amygdala connection, we assume a context-independent reduction of prefrontal control over amygdalar activation in SAD patients. Using DCM, it was possible to highlight not only the neuronal dysfunction of isolated brain regions, but also the dysbalance of a distributed functional network.