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bioRxiv · 10.1101/2025.09.17.675603

Task-Based Spinal fMRI using a Median Nerve Stimulation Reveals Functional Alterations in Degenerative Cervical Myelopathy

Haynes, G.·Muhammad, F.·Weber, K. A.·Khan, A. F.·Hameed, S.·Shakir, H. J.·Rohan, M.·Ding, L.·Smith, Z. A.
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Abstract

Functional spinal cord MRI (fMRI) is an emerging technique for evaluating sensorimotor responses in both healthy and disease states. However, degenerative cervical myelopathy (DCM), a non-traumatic, age-related pathology characterized by spinal cord compression, often leads to motor and sensory impairments that make standard task-based fMRI paradigms challenging to perform or execute. To overcome this, we implemented an fMRI paradigm using direct electrical stimulation to the median nerve to evoke neural responses in both motor and sub-motor spinal cord pathways. In this study, 23 DCM and 23 aged-matched healthy controls (HC) underwent two task-based spinal cord fMRI sessions with direct, median nerve stimulation to the right upper limb. Motor thresholds were determined on an individual basis by a thumb/finger twitching, and sub-motor thresholds were set to be 15% underneath motor with no visible twitching. Blood Oxygenation Level Depended (BOLD) signals were analyzed across the C5-C8 cervical spinal cord segments. HCs demonstrated increased activation during motor vs sub-motor stimulation (1155 vs 496 voxels; +7.1%), whereas DCM patients showed reduction in activation with higher stimulation (1028 vs 1220 voxels; -2.2%). This activation pattern was consistent across the cervical spinal segments, with HCs peaking at C7 (sub-motor: 328 voxels, motor: 608 voxels), which is consistent with median nerve input for forearm and hand. While DCM responses were altered, with sub-motor differentially maximized at C6 (406 voxels) and abnormal recruitment at C5 (112 voxels) and C8 (198 voxels). Spatially, HC responses were focused in the gray matter (GM) and bilateral, whereas DCM responses showed reduced GM localization and were more ipsilateral. Furthermore, we saw spikes in sub-motor DCM deactivation at the overall (3032 voxels) and C6 root level (1500 voxels) that were greater than the other conditions. This study demonstrates the feasibility and effectiveness of median nerve stimulation as a task-based paradigm for assessing spinal cord function in those with spinal cord compression. Group level differences between DCM patients and age-matched HCs showed spatial and quantitatively distinct patterns across stimulation thresholds and spinal segments. Our findings suggest disrupted sub-motor and motor activation in the DCM group, highlighting the use of this approach as a functional biomarker to capture disease specific alterations.

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Haynes, G., Muhammad, F., Weber, K. A., Khan, A. F., Hameed, S., Shakir, H. J., Rohan, M., Ding, L., Smith, Z. A.. 2025-09-19. Task-Based Spinal fMRI using a Median Nerve Stimulation Reveals Functional Alterations in Degenerative Cervical Myelopathy. https://doi.org/10.1101/2025.09.17.675603

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