Combined Transcranial Magnetic Stimulation with Spinal Cord fMRI to Probe Spinal Motor Circuitry

1337 

Abstract Submission 

Ekansh Sareen^1,2, Nawal Kinany^1,2, Estelle Raffin¹, Rebecca Jones¹, Loan Mattera³, Roberto Martuzzi³, Friedhelm Hummel¹, Dimitri Van De Ville^1,2

¹École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland, ³Fondation Campus Biotech Geneva, Geneva

Ekansh Sareen  
École Polytechnique Fédérale de Lausanne|Department of Radiology and Medical Informatics, University of Geneva
Lausanne, Switzerland|Geneva, Switzerland

Nawal Kinany  
École Polytechnique Fédérale de Lausanne|Department of Radiology and Medical Informatics, University of Geneva
Lausanne, Switzerland|Geneva, Switzerland

Estelle Raffin  
École Polytechnique Fédérale de Lausanne
Lausanne, Switzerland

Rebecca Jones  
École Polytechnique Fédérale de Lausanne
Lausanne, Switzerland

Loan Mattera  
Fondation Campus Biotech Geneva
Geneva

Roberto Martuzzi  
Fondation Campus Biotech Geneva
Geneva

Friedhelm Hummel  
École Polytechnique Fédérale de Lausanne
Lausanne, Switzerland

Dimitri Van De Ville  
École Polytechnique Fédérale de Lausanne|Department of Radiology and Medical Informatics, University of Geneva
Lausanne, Switzerland|Geneva, Switzerland

The spinal cord, a pivotal neurological center within the central nervous system, houses intricate neural pathways facilitating and modulating sensorimotor activity for diverse human functions. Despite its significance, the exploration of its functional intricacies, particularly the independent characterization of underlying motor mechanisms, remains an evolving area of research. To tackle this challenge, our ongoing investigation employs a multimodal approach that combines transcranial magnetic stimulation (TMS) for targeted motor cortex stimulation with functional magnetic resonance imaging (fMRI) of subsequent spinal cord activity. This holds the potential for a systematic and comprehensive delineation of the motor aspect of spinal circuitry.

Ten healthy volunteers were included in this study. The experiments were performed on a Siemens 3T Prisma scanner using a concurrent TMS-fMRI acquisition protocol, previously used in [1]. 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, using the MagPro XP stimulator system. EMG electrodes were placed over the targeted muscle groups to record motor evoked potential (MEP) responses to the applied TMS. The study included two sessions of acquisitions (S1 and S2), with identical protocols separated by a week (Fig. 1A). The TMS pulse was applied with three varying intensities of pre-estimated subject-specific resting motor threshold (rMT), i.e., sub-threshold (0.8% rMT), threshold, (rMT), and supra-threshold (1.2% 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 C8 spinal levels. The acquired data were preprocessed using the pipeline introduced in [2] as implemented in the Spinal Cord Toolbox [3]. Preprocessed images were then analyzed using the GLM to extract spinal activation maps. We used an event-based design matrix with two explanatory variables: non-modulated (NM) and modulated (M, orthogonal to NM, derived from recorded MEP responses) (Fig. 1B). Average group-level activation maps were computed using fixed effects analysis (n=9 for S1, n=10 for S2).

Fig. 1C illustrates the average peak-to-peak MEP amplitude across subjects for three intensity modulation conditions. Fig. 1D illustrates the average group activation maps for S1 and S2 for NM and M regressors. In S1, activation maps for the NM condition present localized activity at C5 within descending white matter tracts and right ventral horns. For the M condition, a left-dominant bilateral activity was observed in the ventral horns at C7. In S2, NM condition activity localizes primarily at C7-C8 within descending white matter tracts, with additional activity observed in the right intermediate zone of ventral horn. For the M condition, no significant activity was found. Applied TMS (NM regressor) in both sessions predominantly induces activity in descending white matter tracts carrying motor information from the cortex. Conversely, TMS intensity modulation (M regressor) in S1 induces stimulation-side dominated bilateral activity in the ventral gray matter horns, housing motor neurons. We only observed the modulation effect in S1, which is coherent with our observation from the recorded MEP responses (Fig 1C).

This investigation demonstrates the viability of our proposed multimodal setup for simultaneous stimulation and imaging of corticospinal circuits, specifically the spinal motor circuitry. Our findings underscore the involvement of spinal motor neurons in response to modulating TMS intensity. Nevertheless, notable inter-subject and inter-session variability necessitates further exploration with an expanded subject pool.

Non-invasive Magnetic/TMS

TMS ²

Activation (eg. BOLD task-fMRI) ¹

BOLD fMRI

FUNCTIONAL MRI

Motor

Spinal Cord

Transcranial Magnetic Stimulation (TMS)