POTENTIATION OF CORTICO-SPINAL OUTPUT VIA TARGETED ELECTRICAL STIMULATION OF THE MOTOR THALAMUS

Author:

Ho Jonathan C.,Grigsby Erinn M.,Damiani Arianna,Liang Lucy,Balaguer Josep-Maria,Kallakuri Sridula,Barrios-Martinez Jessica,Karapetyan Vahagn,Fields Daryl,Gerszten Peter C.,Hitchens T. Kevin,Constantine Theodora,Adams Gregory M.,Crammond Donald J.,Capogrosso MarcoORCID,Gonzalez-Martinez Jorge A.,Pirondini Elvira

Abstract

AbstractCerebral 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 new therapies aimed at improving volitional muscle activation. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby potentiating motor output. To test this hypothesis, we identified optimal thalamic targets and stimulation parameters that enhanced upper-limb motor evoked potentials and grip forces in anesthetized monkeys. This potentiation persisted after white matter lesions. We replicated these results in humans during intra-operative testing. We then designed a stimulation protocol that immediately improved voluntary grip 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.

Publisher

Cold Spring Harbor Laboratory

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