Subcallosal Cingulate structural connectivity as a biomarker for chronic low back pain

Background Chronic low back pain (CLBP) poses a significant challenge, contributing significantly to the ongoing opioid crisis while also being a leading cause of disability. Although spinal cord stimulation (SCS) stands as the primary FDA-endorsed method for neuromodulatory therapy in CLBP, there remains a subset of patients unresponsive to SCS and others who experience insufficient pain relief over time. In view of the evidence suggesting the critical role of subgenual cingulate cortex (SCC) connectivity in pain processing, in the current study we investigated the role of the baseline SCC structural as a potential neuroimaging predictive biomarker to identify patients that are likely to benefit from SCS. Methods Diffusion magnetic resonance imaging scans were acquired in 8 patients with CLBP (mean (SD) age = 70 (10) years; 6 female/2 male, 6 UCLA site, 2 UTSW) before their initial SCS trial. Probabilistic tractography from subject-specific anatomically defined SCC seed regions to the ventral striatum (VS), anterior cingulate cortex (ACC), uncinate fasciculus (UCF) and bilateral medial prefrontal cortex (mPFC) was used to calculate FSL structural probabilistic connectivity in the target network. To explore cross-sectional variations in SCC connectivity related to SCS trial response, we employed a general linear model (GLM) using the SCC probability of connectivity as dependent variable, and the response to the SCS trial as independent variable. We used Pearson correlation to evaluate further the relationships between the critical SCC probability of connectivity and the change in VAS score after the SCS trial. Finally, the role of depression in the treatment outcome was evaluated. Results Responders to SCS had significantly lower ipsilateral SCC connectivity to mPFC (F1,8 =8.19, p = 0.03) and VS (F1,8 =17.48, p=0.01) on the left hemisphere compared to non-responders. Pearson correlation analysis showed that decreased ipsilateral SCC baseline connectivity to left mPFC (p=0.03) and VS (p=0.01) was correlated with higher improvement in VAS scores. The baseline depression severity did not significantly influence the change in VAS score following the SCS trial. On the other hand, baseline SCC-VS connectivity on the left hemisphere was a significant predictor of change in VAS score (p=0.02). Conclusions Our study highlights the important role of SCC connectivity that can serve as a potential biomarker for CLBP stratification and prediction to SCS treatment. These results can reshape our perspective on CLBP management and can serve as early indicator of response to the treatment providing a personalized approach based on the individual's underlying SCC connectivity.