Pre-synaptic facilitation of corticospinal output improves dexterity and finemotor control after stroke

Abstract

The corticospinal tract (CST) is a neural pathway that supports skilled use of the arm and hand. Lesions of corticospinal axons result in muscle weakness, deficits of gross motor function, and loss of proximal and distal dexterous control for which effective treatments are still lacking. Here we exploited excitatory connections from motor thalamus to primary motor cortex to potentiate surviving descending signals and restore volitional arm and hand control in three monkeys with corticospinal tract lesion, using deep brain stimulation. Stimulation targeted to thalamocortical projections facilitated upper-limb movements, enabling monkeys with arm and hand paralysis to perform unconstrained 3D reach and fine dexterous tasks. Stimulation improved strength, hand gross motor function, and digits control. Electrophysiology suggested that effects were mediated by and more effective when targeting fibers with monosynaptic connection to the corticospinal motoneurons. Stimulation was delivered in continuous with FDA-clinically approved parameters holding realistic promises of clinical translation.