ABSTRACT
BACKGROUND AND OBJECTIVES: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. METHODS: A 27-year-old right-handed man with AIS-B (motor-complete, sensory-incomplete) C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of using a brain-machine interface to read from and write to the brain for restoring motor and sensory functions of the participant's own arm and hand. RESULTS: Multiunit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions, resulting in functional movements that the participant was able to command under brain control to perform virtual and actual arm and hand movements. The system was well tolerated with no operative complications. CONCLUSION: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to create bidirectional restoration of motor and sensory functions of the arm and hand after neurological injury.
Subject(s)
Arm , Brain-Computer Interfaces , Adult , Humans , Male , Arm/innervation , Brain , Electrodes, Implanted , Hand/physiology , Quadriplegia , Upper Extremity , Clinical Trials as TopicABSTRACT
Background: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. Objective: We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. Methods: A right-handed man with motor-complete C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of a bidirectional brain-machine interface to restore function of the participant's own arm and hand. Results: Multi-unit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions. The system was well tolerated with no operative complications. Conclusion: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to allow restoration of motor and sensory functions of the arm and hand after neurological injury.
ABSTRACT
Purkinje cells (PCs) in the cerebellar flocculus carry rate-coded information that ultimately drives eye movement. Floccular PCs lying nearby each other exhibit partial synchrony of their simple spikes (SS). Elsewhere in the cerebellum, PC SS synchrony has been demonstrated to influence activity of the PCs' synaptic targets, and some suggest it constitutes another vector for information transfer. We investigated in the cerebellar flocculus the extent to which the rate code and PC synchrony interact. One motivation for the study was to explain the cerebellar deficits in ataxic mice like tottering; we speculated that PC synchrony has a positive effect on rate code transmission that is lost in the mutants. Working in transgenic mice whose PCs express channelrhodopsin, we exploited a property of optogenetics to control PC synchrony: pulsed photostimulation engenders stimulus-locked spiking, whereas continuous photostimulation engenders spiking whose timing is unconstrained. We photoactivated flocculus PCs using pulsed stimuli with sinusoidally varying timing vs. continuous stimuli with sinusoidally varying intensity. Recordings of PC pairs confirmed that pulsed stimuli engendered greater PC synchrony. We quantified the efficiency of transmission of the evoked PC firing rate modulation from the amplitudes of firing rate modulation and eye movement. Rate code transmission was slightly poorer in the conditions that generated greater PC synchrony, arguing against our motivating speculation regarding the origin of ataxia in tottering. Floccular optogenetic stimulation prominently augmented a 250-300 Hz local field potential oscillation, and we demonstrate relationships between the oscillation power and the evoked PC synchrony.
