A brain-spine interface alleviating gait deficits after spinal cord injury in primates

被引：458

作者：

Capogrosso, Marco ^{[1
,2
,3
,4
]}

Milekovic, Tomislav ^{[1
,2
]}

Borton, David ^{[1
,2
,5
]}

Wagner, Fabien ^{[1
,2
]}

Moraud, Eduardo Martin ^{[3
,4
]}

Mignardot, Jean-Baptiste ^{[1
,2
]}

Buse, Nicolas ^{[6
]}

Gandar, Jerome ^{[1
,2
]}

Barraud, Quentin ^{[1
,2
]}

Xing, David ^{[5
]}

Rey, Elodie ^{[1
,2
]}

Duis, Simone ^{[1
,2
]}

Yang Jianzhong ^{[7
]}

Ko, Wai Kin D. ^{[7
]}

Li, Qin ^{[7
,8
]}

Detemple, Peter ^{[9
]}

Denison, Tim ^{[6
]}

Micera, Silvestro ^{[3
,4
,10
]}

Bezard, Erwan ^{[7
,8
,11
,12
]}

Bloch, Jocelyne ^{[13
]}

Courtine, Gregoire ^{[1
,2
,13
]}

机构：

[1] Swiss Fed Inst Technol EPFL, Ctr Neuroprosthet, Lausanne, Switzerland

[2] Swiss Fed Inst Technol EPFL, Brain Mind Inst, Sch Life Sci, Lausanne, Switzerland

[3] Ecole Polytech Fed Lausanne, Sch Bioengn, Ctr Neuroprosthet, Lausanne, Switzerland

[4] Ecole Polytech Fed Lausanne, Sch Bioengn, Inst Bioengn, Lausanne, Switzerland

[5] Brown Univ, Sch Engn, Providence, RI 02912 USA

[6] Medtronic, Minneapolis, MN USA

[7] Motac Neurosci Ltd, Manchester, Lancs, England

[8] China Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China

[9] Fraunhofer Inst Chem Technol ICT IMM, Mainz Inst Microtechnol, Mainz, Germany

[10] Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy

[11] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[12] CNRS, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[13] CHU Vaudois, Lausanne, Switzerland

来源：

NATURE | 2016年 / 539卷 / 7628期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

FUNCTIONAL ELECTRICAL-STIMULATION; MOTOR CONTROL; FREE BEHAVIOR; LOCOMOTION; PARALYSIS; NEUROMODULATION; TRANSLATION; PROSTHESIS; MECHANISMS; MOVEMENT;

D O I：

10.1038/nature20118

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces(1-3) have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis(1,4). Theoretically, this strategy could also restore control over leg muscle activity for walking(5). However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges(6,7). Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion(8-10). Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with realtime triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

引用

页码：284 / +

页数：23

共 37 条

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