Increased Inhibition of the Amygdala by the mPFC may Reflect a Resilience Factor in Post-traumatic Stress Disorder: A Resting-State fMRI Granger Causality Analysis

Purpose: To determine whether effective connectivity of the amygdala is altered in traumatized subjects with and without post-traumatic stress disorder (PTSD). Materials and Methods: Resting-state functional MRI data were obtained for 27 patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC). Effective connectivity of the bilateral amygdala was examined with Granger causality analysis and then compared between groups by conducting an analysis of variance. Results: Compared to the HC group, both the PTSD group and the TEC group showed increased effective connectivity from the amygdala to the medial prefrontal cortex (mPFC). The TEC group showed increased effective connectivity from the mPFC to the amygdala relative to the HC group. Compared to the TEC group, the PTSD group showed increased effective connectivity from the amygdala to the supplementary motor area (SMA) whereas decreased effective connectivity was detected from the SMA to the amygdala. Both the PTSD group and the TEC group showed decreased effective connectivity from the superior temporal gyrus (STG) to the amygdala relative to the HC group. Compared to the HC group, the TEC group showed increased effective connectivity from the amygdala to the dorsolateral prefrontal cortex (dlPFC), while both the PTSD group and the TEC group showed decreased effective connectivity from the dlPFC to the amygdala. The PTSD group showed decreased effective connectivity from the precuneus to the amygdala relative to both control groups but increased effective connectivity from the amygdala to the precuneus relative to the HC group. Conclusion: Trauma leads to an increased down-top excitation from the amygdala to the mPFC and less regulation of the amygdala by the dlPFC. The results suggest that increased inhibition of the amygdala by the mPFC may reflect a resilience factor, altered amygdala-SMA and amygdala-STG effective connectivity may reflect compensatory mechanisms of brain function. These data raise the possibility that insufficient inhibition of the amygdala by the mPFC might lead to PTSD in those who have been exposed to traumatic incidents, and may inform future therapeutic interventions. Key words: post-traumatic stress disorder, amygdala, effective connectivity, medial prefrontal cortex, functional magnetic resonance imaging