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          Abstract

          Paralysis following spinal cord injury (SCI), brainstem stroke, amyotrophic lateral sclerosis (ALS) and other disorders can disconnect the brain from the body, eliminating the ability to carry out volitional movements. A neural interface system (NIS) 15 could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with longstanding tetraplegia can use an NIS to move and click a computer cursor and to control physical devices 68 . Able-bodied monkeys have used an NIS to control a robotic arm 9 , but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here, we demonstrate the ability of two people with long-standing tetraplegia to use NIS-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor five years earlier, also used a robotic arm to drink coffee from a bottle. While robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after CNS injury, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.

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          Most cited references28

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          Brain-controlled interfaces: movement restoration with neural prosthetics.

          Brain-controlled interfaces are devices that capture brain transmissions involved in a subject's intention to act, with the potential to restore communication and movement to those who are immobilized. Current devices record electrical activity from the scalp, on the surface of the brain, and within the cerebral cortex. These signals are being translated to command signals driving prosthetic limbs and computer displays. Somatosensory feedback is being added to this control as generated behaviors become more complex. New technology to engineer the tissue-electrode interface, electrode design, and extraction algorithms to transform the recorded signal to movement will help translate exciting laboratory demonstrations to patient practice in the near future.
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            Direct control of paralyzed muscles by cortical neurons

            A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury via artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralyzed limbs 1–3 . In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms 4–10 , and paralyzed muscles have been activated by functional electrical stimulation (FES) 11–13 . Here we show that monkeys can directly control stimulation of muscles using the activity of neurons in motor cortex, thereby restoring goal-directed movements to a transiently paralyzed arm. Moreover, neurons could control functional stimulation equally well regardless of any prior association to movement, a finding that significantly expands the source of control signals for brain-machine interfaces. Monkeys learned to utilize these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralyzed limbs.
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              Cognitive control signals for neural prosthetics.

              Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external devices. In this study, higher level signals related to the goals of movements were decoded from three monkeys and used to position cursors on a computer screen without the animals emitting any behavior. Their performance in this task improved over a period of weeks. Expected value signals related to fluid preference, the expected magnitude, or probability of reward were decoded simultaneously with the intended goal. For neural prosthetic applications, the goal signals can be used to operate computers, robots, and vehicles, whereas the expected value signals can be used to continuously monitor a paralyzed patient's preferences and motivation.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                10 April 2012
                16 May 2012
                01 May 2013
                : 485
                : 7398
                : 372-375
                Affiliations
                [1 ]Rehabilitation Research & Development Service, Department of Veterans Affairs, Providence, RI.
                [2 ]School of Engineering and Institute for Brain Science, Brown University, Providence, RI.
                [3 ]Department of Neuroscience and Institute for Brain Science, Brown University, Providence, RI.
                [4 ]Massachusetts General Hospital, Boston, MA.
                [5 ]Harvard Medical School, Boston, MA.
                [6 ]German Aerospace Center, Institute of Robotics and Mechatronics (DLR, Oberpfaffenhofen), Germany.
                Author notes
                Correspondence and requests for materials should be addressed to J.P.D. ( john_donoghue@ 123456brown.edu ) or L.R.H. ( leigh@ 123456brown.edu )
                Article
                NIHMS366580
                10.1038/nature11076
                3640850
                22596161
                4169d933-2ee6-4153-b5eb-0d6d4c842a40

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                History
                Funding
                Funded by: National Institute of Child Health & Human Development : NICHD
                Award ID: HHSN275201100018C || HD
                Funded by: National Institute of Child Health & Human Development : NICHD
                Award ID: RC1 HD063931-02 || HD
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R56 NS025074-23 || NS
                Funded by: National Institute of Biomedical Imaging and Bioengineering : NIBIB
                Award ID: R01 EB007401-05 || EB
                Funded by: National Institute on Deafness and Other Communication Disorders : NIDCD
                Award ID: R01 DC009899-02 || DC
                Funded by: National Institute of Child Health & Human Development : NICHD
                Award ID: N01 HD053403 || HD
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