Potentiation of Cortico-Spinal Output via Targeted Electrical Stimulation of the Motor Thalamus

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 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.

Intracranial Neuromodulation for Neurologic Recovery

“…15 Interestingly, these results were replicated in a human patient with chronic TBI with rightsided hemiparesis. 15 DBS of the motor thalamus led to significantly increased grip strength that persisted even after the DBS was turned off. 15 There is also evidence to suggest that DBS improves cognitive and psychological dysfunction in TBI patients.…”

“…15 DBS of the motor thalamus led to significantly increased grip strength that persisted even after the DBS was turned off. 15 There is also evidence to suggest that DBS improves cognitive and psychological dysfunction in TBI patients. Kuhn et al 16 report that DBS targeting the hypothalamus eliminated post-TBI self-mutilation behavior in a 22-year-old woman.…”

Intracranial Neuromodulation for Neurologic Recovery

“…It has been demonstrated that DBS of the motor thalamus leads to increased voluntary movement of the paretic limb in nonhuman primates. 15 Interestingly, these results were replicated in a human patient with chronic TBI with rightsided hemiparesis. 15 DBS of the motor thalamus led to significantly increased grip strength that persisted even after the DBS was turned off.…”

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation

“…We designed an experimental setup in anesthetized macaque monkeys (n=2; Mk-JC, Mk-Ka), who share with humans monosynaptic corticospinal innervations of spinal motoneurons 31,32 . Briefly, to replicate our simulations in a controlled fashion, we applied SCS at C6-C8 cervical spinal segments, while manipulating supraspinal input by means of deep-brain stimulation of the internal capsule 33 , which is a deep-brain structure hosting corticospinal fibers. In parallel, we measured motoneuron output directly, via intraspinal neural recordings, and indirectly, via evoked intramuscular electromyographic (EMG) in the hand muscles ( Fig.…”