Altered Amygdala-prefrontal Connectivity in Chronic Nonspecific Low Back Pain: Resting-state fMRI and Dynamic Causal Modelling Study

Chronic nonspecific low back pain (cNLBP) is a leading contributor to disease burden worldwide that is difficult to treat due to its nonspecific aetiology and complexity. The amygdala is a complex of structurally and functionally heterogeneous nuclei that serve as a key neural substrate for the interactions between pain and negative affective states. However, whether the functions of amygdalar subcomponents are differentially altered in cNLBP remains unknown. Little attention has focused on effective connectivity of the amygdala with the cortex in cNLBP. In this study, thirty-three patients with cNLBP and 33 healthy controls (HCs) were included. Resting-state functional connectivity (rsFC) and effective connectivity of the amygdala and its subregions were examined. Our results showed that the patient group exhibited significantly greater rsFC between the left amygdala and left dorsal medial prefrontal cortex (mPFC), which was negatively correlated with pain intensity ratings. Subregional analyses suggested a difference located at the superficial nuclei of the amygdala. Dynamic causal modelling revealed significantly lower effective connectivity from the left amygdala to the dorsal mPFC in patients with cNLBP than in HCs. Both groups exhibited stronger effective connectivity from the left amygdala to the right amygdala. In summary, these findings not only suggested altered rsFC of the amygdala-mPFC pathway in cNLBP but also implicated an abnormal direction of information processing between the amygdala and mPFC in these patients. Our results further highlight the involvement of the amygdala in the neuropathology of cNLBP.