Concurrent TMS and Spinal Cord fMRI Reveal Intensity-Dependent Modulation of Spinal Circuits

Presented During:

Wednesday, June 25, 2025: 5:57 PM - 6:09 PM
Brisbane Convention & Exhibition Centre  
Room: Great Hall  

Poster No:

64 

Submission Type:

Abstract Submission 

Authors:

Ekansh Sareen1,2, Rebecca Jones1, Estelle Raffin1, Friedhelm Hummel1, Dimitri Van De Ville1,2

Institutions:

1École polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland, 2Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland

First Author:

Ekansh Sareen  
École polytechnique fédérale de Lausanne (EPFL)|Department of Radiology and Medical Informatics, University of Geneva
Geneva, Switzerland|Geneva, Switzerland

Co-Author(s):

Rebecca Jones  
École polytechnique fédérale de Lausanne (EPFL)
Geneva, Switzerland
Estelle Raffin  
École polytechnique fédérale de Lausanne (EPFL)
Geneva, Switzerland
Friedhelm Hummel  
École polytechnique fédérale de Lausanne (EPFL)
Geneva, Switzerland
Dimitri Van De Ville  
École polytechnique fédérale de Lausanne (EPFL)|Department of Radiology and Medical Informatics, University of Geneva
Geneva, Switzerland|Geneva, Switzerland

Introduction:

The spinal cord, a vital component of the central nervous system, plays a critical role in regulating sensorimotor functions through complex neural networks. Despite its importance, the detailed characterization of its motor mechanisms is not yet fully understood and remains an area of active investigation. To address this gap, we utilize a multimodal approach integrating transcranial magnetic stimulation (TMS) for standardized and involuntary motor cortex activation with fMRI to map corresponding spinal cord activity. This method offers a robust framework for systematically elucidating the sensorimotor aspects of spinal circuitry.

Methods:

Nineteen healthy volunteers were included in this study. The experiments were performed on a Siemens 3T Prisma scanner using an MR-compatible TMS system (MagPro XP). Single-pulse TMS was applied over the right primary motor cortex, targeted over first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscle groups on the left hand. EMG electrodes were placed over the targeted muscle groups to record motor evoked potential (MEP) responses to the applied TMS. TMS pulses were applied at three different intensities relative to each participant's pre-determined resting motor threshold (rMT): low (rMT), medium (120% rMT), and high (140% rMT). The functional images of the spinal cord were acquired using a gradient-echo EPI sequence with inner field-of-view (TR = 2500 ms, TE = 34 ms, resolution = 1x1x3 mm3), spanning over C2 to T1 spinal levels. The acquired data were preprocessed using the pipeline introduced in [1, 2] as implemented in the Spinal Cord Toolbox [3]. Among the cohort, eleven participants were classified as responders, showing significant MEPs (> 0.5 μV) with a progressive increase in amplitude from low to high intensity, confirming the expected stimulation-intensity and motor-output relationship (Fig. 1D). The remaining eight were categorized as "non-responders. Using hemodynamic deconvolution based on the total activation (TA) framework [4], the preprocessed BOLD time courses were transformed into activity-inducing representations, enhancing the interpretability of spinal cord activity. The data was analyzed using a GLM to extract spinal activation maps for the effect of applied TMS and intensity modulation. An event-based design matrix with two explanatory variables-no-modulation (NM) and modulation (M, orthogonal to NM, based on recorded MEPs)-was applied. Group-level maps were computed using a one-sample t-test within a non-parametric permutation framework (p < 0.05, TFCE-corrected).

Results:

In responders, the effects of applied TMS were localized to the ipsilateral dorsal horn (left, C6), dorsal column (left), lateral corticospinal tract (left), and ventral horn (left, C5). Intensity modulation effects were found in the ipsilateral vestibulospinal (left), reticulospinal (left), ventral corticospinal (left) tracts, and contralateral ventral horn. In non-responders, TMS effects were limited to the ventral corticospinal tract, with no significant modulation effects. Fig. 1E shows the dice coefficient of activation maps with atlas regions (mean across levels ± standard deviation). The effect of applied TMS was primarily observed in sensory neuron sites within the ipsilateral dorsal horn and ascending somatosensory pathways, with some contralateral motor activation in the ventral horn. Modulation effects, however, were only observed in responders localized to contralateral descending motor tracts and the ventral horn housing motor neurons, consistent with anatomical knowledge [5-7].
Supporting Image: Fig1.png
 

Conclusions:

This study validates the feasibility of our proposed multimodal approach for simultaneous stimulation and imaging of spinal circuits. The findings indicate that TMS effects involve coordinated activation of ascending sensory pathways and descending motor commands, with the specific recruitment of descending motor tracts and spinal motoneurons playing a crucial role in mediating intensity-dependent responses.

Brain Stimulation:

TMS 1

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI) 2
Methods Development

Motor Behavior:

Motor Planning and Execution

Novel Imaging Acquisition Methods:

BOLD fMRI

Keywords:

FUNCTIONAL MRI
Modeling
Motor
Somatosensory
Spinal Cord
Transcranial Magnetic Stimulation (TMS)

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Task-activation

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI
TMS
Behavior
Other, Please specify  -   GLM

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

FSL
Other, Please list  -   SCT

Provide references using APA citation style.

[1] Kinany, N. (2023). Spinal cord fMRI: A new window into the central nervous system. The Neuroscientist, 29(6), 715–731.
[2] Kinany, N. (2019). Functional imaging of rostrocaudal spinal activity during upper limb motor tasks. NeuroImage, 200,590–600.
[3] De Leener, B. (2017). SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. NeuroImage, 145, 24–43.
[4] Karahanoğlu, F. I. (2013). Total activation: fMRI deconvolution through spatio-temporal regularization. NeuroImage, 73, 121–134.
[5] ten Donkelaar, H. J. (2011b). The somatosensory system. In Clinical Neuroanatomy (pp. 133–209). Springer, Berlin, Heidelberg.
[6] ten Donkelaar, H. J. (2011a). Motor systems. In Clinical Neuroanatomy (pp. 367–447). Springer, Berlin, Heidelberg.
[7] Landelle, C. (2021). Investigating the human spinal sensorimotor pathways through functional magnetic resonance imaging. NeuroImage, 245, 118684.
[8] Frostell, A. (2016). A review of the segmental diameter of the healthy human spinal cord. Frontiers in Neurology, 7, 238.

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