Restoring walking after spinal cord injury remains a major clinical challenge, and deep brain stimulation (DBS) of brainstem locomotor centers is emerging as a promising approach. A new study by Anna-Sophie Hofer, Martin Schwab and colleagues at UZH and collaborating institutions provides a roadmap for targeting the human cuneiform nucleus, a key region for gait control. By combining rodent experiments with human imaging, the researchers derive anatomical coordinates to guide future DBS interventions.
Locomotion is modulated by a small but critical region in the brainstem known as the mesencephalic locomotor region, which includes the cuneiform nucleus. While stimulation of this region can restore walking in animal models and is now being explored in humans, precisely locating the target in the human brain has remained a major obstacle. To address this, the researchers combined functional mapping in rodents with detailed anatomical analyses and translated these findings to the human brain.
Bridging across species, the study identified a consistent “hotspot” within the rodent cuneiform nucleus that reliably triggered coordinated stepping. This functional region closely matched the distribution of specific molecular markers, providing an anatomical anchor for translation. Using these relationships, the researchers derived landmarks and approximate coordinates for the human brainstem and tested them against imaging data and electrode placements from early clinical cases. The resulting maps suggest that optimal stimulation sites lie slightly more lateral and dorsal than previously used targets, and highlight how even millimetre-scale deviations can influence which neural pathways are activated.
Together, these findings provide practical guidance for improving the precision of DBS targeting in a region that is both small and densely packed with critical structures. More broadly, the work illustrates how combining animal models with human imaging can bridge the gap between basic neuroscience and clinical application. While the proposed coordinates remain approximate and will need refinement through clinical experience, they represent an important step toward more reliable and effective neuromodulation therapies for restoring gait after neurological injury.
Reference: Hofer AS, Scheuber MI, Sartori AM, Skorup I, Gascho D, Colacicco G, Kiseleva A, Curt A, Stieglitz LH, Schwab ME. Stereotactic rodent-to-human approximation of the mesencephalic cuneiform nucleus to guide deep brain stimulation. Brain Stimulation. 2026. https://doi.org/10.1016/j.brs.2026.103066
Useful Links:
First human study that investigates the therapeutic potential of cuneiform nucleus stimulation in patients with incomplete spinal cord injury (DBS-SCI trial):
- DBS Study | Spinal Cord Injury Center, Research | UZH
- Deep Brain Stimulation in Patients With Incomplete Spi | SCI Trials Finder
Publication on the first two individuals with spinal cord injury who received cuneiform nucleus stimulation:
Hofer AS, Stieglitz LH, Bolliger M, Filli L, Cathomen A, Willi R, Lerch I, Krüsi I, Giagiozis M, Meyer C, Schubert M, Hubli M, Kessler TM, Demkó L, Baumann CR, Imbach L, Oertel MF, Prusse A, Kiseleva A, Regli L, Schwab ME, Curt A. Cuneiform Nucleus Stimulation Can Assist Gait Training to Promote Locomotor Recovery in Individuals With Incomplete Tetraplegia. Annals of Neurology. 2026. https://doi.org/10.1002/ana.78026.
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