Where are effective electrodes localized in motor cortex stimulation? A large multicenter study

Epidural motor cortex stimulation (MCS) has been used for over 30 years to treat refractory chronic neuropathic pain¹. However, its efficacy remains controversial, its mechanisms of action unclear and the optimal electrode placement is debated. Our aim was to analyze a large series of patients to identify optimal lead localization.

We analyzed retrospectively 73 patients treated with MCS for chronic neuropathic refractory pain across six French and German centers. Postoperative CTs were normalized in the MNI template using ANTs to calculate the coordinates of the stimulating contacts. These coordinates were mapped onto several MNI space-registered atlases^2,3. The electrode-pia distance was computed. Patients were categorized in non-responders ("NR") and responders ("R" - >50% pain relief at 1 year). The latter were divided into sure-responders ("SR" - the analgesic effect ceased when the IPG was turned off) and doubtful responders ("DR"). Statistical comparisons were made for stimulation parameters, electrode coordinates and atlas values.

Statistical tests revealed a larger electrode-pia distance in NR compared to R (5.68 vs 4.78 mm, p< .005). Leads located on the right hemisphere, anteriorly and inferiorly were associated with higher response rates (p< .05). While effective electrodes were often localized on the premotor histo-functional areas in SR and R, the result was not significant. In SR, electrodes were effective regardless of motor cortex somatotopy (Fig. 1). Pain relief was associated with low electrical intensity and stimulation of 90-100 mm long streamlines.

These results challenge some traditional MCS assumptions. Precise targeting of somatotopic motor regions may not be critical for pain relief. Instead, duro-pial distance could predict MCS response. The association with medium length streamlines suggests MCS modulates distant pain centers. This study highlights the need for a more nuanced approach to MCS, moving away from motor somatotopy and integrating connectivity models to refine electrode placement and optimize clinical outcomes for chronic refractory neuropathic pain.

1. Lefaucheur, J.-P. Cortical neurostimulation for neuropathic pain: state of the art and perspectives. Pain (2016)
2. Glasser, M. F. et al. A multi-modal parcellation of human cerebral cortex. Nature (2016)
3. Bajada, C. J. et al. Fiber length profiling: A novel approach to structural brain organization. NeuroImage (2019)

Fig. 1 Lead localization in SR