Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment

We previously reported that effective treatment of chronic low back pain (CLBP) reversed abnormal brain structure and functional MRI (fMRI) activity during cognitive task performance, particularly in the left dorsolateral prefrontal cortex (DLPFC). Here, we used resting-state fMRI to examine how chronic pain affects connectivity of brain networks supporting cognitive functioning and the effect of treatment in 14 CLBP patients and 16 healthy, pain-free controls (scans were acquired at baseline for all subjects and at 6-months post-treatment for patients and a matched time-point for 10 controls). The main networks activated during cognitive task performance, task-positive network (TPN) and task-negative network (TNN) (aka default mode) network, were identified in subjects' task fMRI data and used to define matching networks in resting-state data. The connectivity of these cognitive resting-state networks was compared between groups, and before and after treatment. Our findings converged on the bilateral insula (INS) as the region of aberrant cognitive resting-state connectivity in patients pretreatment versus controls. These findings were complemented by an independent, data-driven approach showing altered global connectivity of the INS. Detailed investigation of the INS confirmed reduced connectivity to widespread TPN and TNN areas, which was partially restored post-treatment. Furthermore, analysis of diffusion-tensor imaging (DTI) data revealed structural changes in white matter supporting these findings. The left DLPFC also showed aberrant connectivity that was restored post-treatment. Altogether, our findings implicate the bilateral INS and left DLPFC as key nodes of disrupted cognition-related intrinsic connectivity in CLBP, and the resulting imbalance between TPN and TNN function is partially restored with treatment.