The role of prefrontal cortex in chronic low back pain with comorbid depression: A resting-state fMRI study

Patients with chronic low back pain (CLBP) experience comorbid depression. However, the central neural processing profile of CLBP with comorbid depression remains unclear. Therefore, this study aimed to investigate specific brain abnormalities in CLBP with comorbid depression by functional magnetic resonance imaging. Fourteen CLBP patients with depression, 25 CLBP patients without depression, and 24 matched controls were included. Alterations in spontaneous brain activity and connectivity were examined through regional homogeneity (ReHo) and functional connectivity (FC). Analysis of variance and post hoc analyses among groups were conducted. Correlational analyses were performed between neuroplasticity and clinical variables. Mediation analysis was conducted to elucidate the interrelationships among brain alterations, pain, and depression. Significant between-group differences in ReHo values were found across extensive brain regions, particularly the right dorsolateral prefrontal cortex (DLPFC). Altered FC between the DLPFC and cerebellum as well as the orbitofrontal cortex was noted. ReHo and FC were associated with depression, pain catastrophizing, and back pain-related disability. ReHo values of superior frontal gyrus and its FC to cerebellum mediated the correlation between BDI and variables such as pain intensity and pain catastrophizing. CLBP patients with comorbid depression exhibit abnormal regional homogeneity in regions involving the DLPFC, and altered functional networks are observed between the DLPFC and other areas. Central changes are correlated with back pain-related outcomes and mediate the relationship between pain and depression. Our findings contribute additional insights for identifying potential biomarkers of refractory CLBP with depression comorbidity, potentially aiding in pain phenotype stratification and optimizing pain management strategies.