Targeted Deep Brain Stimulation of the Motor Thalamus Facilitates Voluntary Motor Control After Cortico-spinal Tract Lesions

Abstract

Cerebral white matter tract lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to untreatable muscle paralysis. However, in most cases the damage to cortico-spinal axons is incomplete and the spared connections could be potentiated by neurotechnologies to restore motor function. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, deep brain stimulation (DBS) of the motor thalamus could facilitate activation of spared cortico-spinal fibers improving muscle activation of the paretic limb. We first identified, in monkeys, optimal stimulation targets and parameters that enhanced motor evoked potentials to arm, hand, and face muscles, as well as grip forces. This potentiation persisted after cerebral white matter lesions. We then translated these results to human subjects by identifying the corresponding optimal thalamic targets (VIM/VOP nuclei) and replicated the results obtained in monkeys. Finally, we designed a DBS protocol that immediately improved voluntary grip force control in a patient with a chronic traumatic brain injury. Our results suggest that targeted DBS of the motor thalamus may become an effective therapy for motor paralysis.

GABA Increases Sensory Transmission In Monkeys

“…Then, we extracted a window of 25 ms (5 ms pre-stimulation, 20 ms post-stimulation) for analysis. To identify volleys from dorsal rootlet stimulation in the thalamus and cortex, we calculated an approximated time of 2-5 ms based on conduction speed of antidromic volleys in the spinal cord from thalamic stimulation as reported in a previous publication [34]. We measured the thalamic and cortical volleys within the 2-5 ms window, and the evoked field potentials within the 5-20 ms window.…”

“…All procedures in this study were carried out in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals. As part of our effort to minimize the number of animals used, the current dataset is derived from experiments that were designed to answer multiple scientific questions [34]. The datasets presented here were collected from 4 macaque monkeys, consisting of • PAD evoked by nerve stimulation.…”

“…Prior to the terminal experiments, animals went through one survival procedure to determine trajectories and depth for electrodes that would be implanted in the thalamus during terminal experiments. The details of this procedure have been reported in a previous publication [34].…”