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

Abstract

The spinal cord serves as a crucial relay for motor commands, yet the role of its local circuitry in sensorimotor integration remains poorly understood. Most non-invasive cortical stimulation studies, rely on electrophysiological readouts or inferred spinal function from corticospinal anatomy, leaving the downstream impact of cortical stimulation on spinal circuitry largely uncharted in vivo. Advances in spinal cord functional MRI (SC-fMRI) now enable spatially resolved imaging of segmental gray and white matter and their interactions with descending cortical inputs. Here, we introduce a multimodal framework that combines single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortex with SC-fMRI to probe TMS-evoked spinal activity in humans. Using graded TMS intensities, we examined blood oxygenation level-dependent (BOLD) responses in the cervical spinal cord and asked how spinal activation depends on effective engagement of the descending motor system. Our findings reveal robust, intensity-dependent spinal BOLD responses aligned with descending pathways, with activation concentrated in expected territories such as the lateral corticospinal tract and ventral horn at segments innervating the stimulated hand muscle. By linking peripheral output to segment- and pathway-resolved spinal signals, these results demonstrate that concurrent TMS–SCfMRI can capture, in vivo, how cortical drive is expressed within human spinal circuitry and provide a new framework to measure spinal contributions to sensorimotor control with spatial specificity beyond traditional peripheral readouts. Graphical Abstract