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.
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.
Restoration of proprioception with neurotechnology is critical to improve effectiveness of robotic neuro-prostheses. Unfortunately, after initial enthusiasm clinical results showed that unlike touch, proprioception could not be reliably induced. Here we show that concurrent activation of multiple sensory modalities may trigger unwanted sensory regulation mechanisms that disrupt proprioception. We recorded intra-spinal neural activity induced by stimulation of proprioceptive afferents from the radial nerve in three monkeys. Then, we superimposed stimulation of the radial nerve cutaneous branch and quantified its impact on spinal neural activity via population analysis. Proprioceptive pulses produced robust neural trajectories in the neural manifold that were disrupted by concurrent stimulation of cutaneous afferents. This disruption correlated with a reduction of afferent volleys and multi-unit activity both in the spinal cord and somatosensory cortex. Our results suggest that limited specificity not only impacts localization of artificial percepts, but also their nature to an extent that was never considered.
Restoration of proprioception with neurotechnology is critical to improve effectiveness of robotic neuro-prostheses. Unfortunately, after initial enthusiasm clinical results showed that unlike touch, proprioception could not be reliably induced. Here we show that concurrent activation of multiple sensory modalities may trigger unwanted sensory regulation mechanisms that disrupt proprioception. We recorded intra-spinal neural activity induced by stimulation of proprioceptive afferents from the radial nerve in three monkeys. Then, we superimposed stimulation of the radial nerve cutaneous branch and quantified its impact on spinal neural activity via population analysis. Proprioceptive pulses produced robust neural trajectories in the neural manifold that were disrupted by concurrent stimulation of cutaneous afferents. This disruption correlated with a reduction of afferent volleys and multi-unit activity both in the spinal cord and somatosensory cortex. Our results suggest that limited specificity not only impacts localization of artificial percepts, but also their nature to an extent that was never considered.
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