Potentiation of cortico-spinal output via targeted electrical stimulation of the motor thalamus

• Published in: Nature communications 2024-10, Vol.15 (1), p.8461-21, Article 8461
• Main Authors: Ho, Jonathan C., Grigsby, Erinn M., Damiani, Arianna, Liang, Lucy, Balaguer, Josep-Maria, Kallakuri, Sridula, Tang, Lilly W., Barrios-Martinez, Jessica, Karapetyan, Vahagn, Fields, Daryl, Gerszten, Peter C., Hitchens, T. Kevin, Constantine, Theodora, Adams, Gregory M., Crammond, Donald J., Capogrosso, Marco, Gonzalez-Martinez, Jorge A., Pirondini, Elvira
• Format: Article
• Language: English
• Subjects: 631/378/2632/1663; 692/617/375/1345; 9/97; Animals; Arm; Axon guidance; Axons; Electric Stimulation - methods; Electrical stimuli; Evoked Potentials, Motor - physiology; Female; Fibers; Hand Strength - physiology; Human motion; Humanities and Social Sciences; Humans; Hypotheses; Lesions; Macaca mulatta; Male; Motor Cortex - physiology; Motor evoked potentials; Motor neurons; Motor Neurons - physiology; Motor task performance; multidisciplinary; Muscle contraction; Neurosciences; Parameter identification; Potentiation; Science; Science (multidisciplinary); Spinal Cord - physiology; Stimulation; Substantia alba; Thalamus; Thalamus - physiology; Traumatic brain injury; White Matter - physiology; White Matter - physiopathology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52477-1

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions. Cerebral lesions result in loss of upper-limb motor functions. Here, the authors show that electrical stimulation of the motor thalamus can immediately and significantly improve strength and volitional force control improving arm and hand functions.