Potentiation of cortico-spinal output via targeted electrical stimulation of the motor thalamus
Jonathan Ho, Erinn M. Grigsby, Arianna Damiani, Lucy Liang, Josep-Maria Balaguer, Sridula Kallakuri, Lilly W. Tang, Jessica Barrios‐Martinez, Vahagn Karapetyan, Daryl P. Fields, Peter C. Gerszten, T. Kevin Hitchens, Theodora Constantine, Gregory M. Adams, Donald J. Crammond, Marco Capogrosso, Jorge González-Martínez, Elvira Pirondini
Abstract
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.