Disrupted brain network topology and structure-function coupling in non-specific low back pain
Lionel Butry, Frederick Junker, Sam Vickery, Daniel L. Belavy, Rebekka Döding, Katja Ehrenbrusthoff, Maia Angelova, Bjoern Buehring, Bernadette Fitzgibbon, Chandan Karmakar, Clint T. Miller, Patrick J. Owen, Tobias L. Schulte, Scott D. Tagliaferri, Guy Trudel, Jessica Van Oosterwijck, Hans-Joachim Wilke, Elena K. Enax-Krumova, Lara SchlaffkeAbstract
Central nervous system mechanisms contribute to non-specific low back pain (LBP), with widespread alterations in brain function and structure reported. It remains unclear how these alterations propagate to brain network topology and structure-function coupling. In this cross-sectional study, 282 participants with non-specific LBP (mean ± standard deviation, pain intensity 4.3±1.7 [0–10 numerical rating scale]; current pain duration 54±105 weeks) and 71 pain-free controls underwent resting-state functional and diffusion-weighted MRI to derive functional and structural connectomes. Subgroups were analysed by pain status during scanning and pain duration. The main graph-theory analysis revealed that participants with non-specific LBP had lower segregation (d=0.39–0.45, P=0.009–0.019) in the whole-brain functional network and higher integration (d=0.30–0.38, P=0.005–0.027) in the functional ventral attention network. Subgroup analysis showed that participants with chronic non-specific LBP had lower segregation (d=0.48, P=0.002) and higher integration (d=0.45, P=0.004) within the structural default mode network. By modelling functional connectivity using structural communication predictors in a multivariable linear regression, we identified structure-function decoupling in participants with non-specific LBP across the whole-brain (d=0.25–0.28, P=0.026–0.041), ventral attention (d=0.28–0.32, P=0.005–0.048), and default mode network (d=0.22–0.24, P=0.031–0.046), alongside complex regional patterns of both decoupling and hypercoupling. Explorative partial correlation analyses associated disability, rather than pain intensity, with differences in brain network topology and structure-function decoupling. These findings advance the mechanistic understanding of the severity and persistence of non-specific LBP, showing disrupted bottom-up attentional processing and self-referential circuitry, resulting in large-scale structure-function decoupling.