Identification of Deep Brain Stimulation Targets for Neuropathic Pain After Spinal Cord Injury Using Localized Increases in White Matter Fiber Cross-Section

Objectives The spinal cord injury (SCI) patient population is overwhelmingly affected by neuropathic pain (NP), a secondary condition for which therapeutic options are limited and have a low degree of efficacy. The objective of this study was to identify novel deep brain stimulation (DBS) targets that may theoretically benefit those with NP in the SCI patient population. We hypothesize that localized changes in white matter identified in SCI subjects with NP compared to those without NP could be used to develop an evidence-based approach to DBS target identification. Materials and Methods To classify localized neurostructural changes associated with NP in the SCI population, we compared white matter fiber density (FD) and cross-section (FC) between SCI subjects with NP (N = 17) and SCI subjects without NP (N = 15) using diffusion-weighted magnetic resonance imaging (MRI). We then identified theoretical target locations for DBS using fiber bundles connected to significantly altered regions of white matter. Finally, we used computational models of DBS to determine if our theoretical target locations could be used to feasibly activate our fiber bundles of interest. Results We identified significant increases in FC in the splenium of the corpus callosum in pain subjects when compared to controls. We then isolated five fiber bundles that were directly connected to the affected region of white matter. Our models were able to predict that our fiber bundles of interest can be feasibly activated with DBS at reasonable stimulation amplitudes and with clinically relevant implantation approaches. Conclusions Altogether, we identified neuroarchitectural changes associated with NP in the SCI cohort and implemented a novel, evidence-driven target selection approach for DBS to guide future research in neuromodulation treatment of NP after SCI.