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 movements 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.

No 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.