bioRxiv Science⌕ Search
Home/Archive/bioRxiv

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.
View original source ↗Export metadata ↓

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.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

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

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗
bioRxiv2026

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗
bioRxiv2026

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗