Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

被引：276

作者：

Rowald, Andreas ^{[1
,2
,3
,4
,8
]}

Komi, Salif ^{[1
,2
,3
,4
,8
]}

Demesmaeker, Robin ^{[1
,2
,3
,4
,8
]}

Baaklini, Edeny ^{[1
,2
,3
,4
]}

Hernandez-Charpak, Sergio Daniel ^{[1
,2
,3
,4
]}

Paoles, Edoardo ^{[5
]}

Montanaro, Hazael ^{[6
,7
]}

Cassara, Antonino ^{[6
]}

Becce, Fabio ^{[8
]}

Lloyd, Bryn ^{[6
]}

Newton, Taylor ^{[6
]}

Ravier, Jimmy ^{[1
,2
,3
,4
]}

Kinany, Nawa ^{[1
,9
,10
]}

D'Ercole, Marina ^{[5
]}

Paley, Aurelie ^{[2
,3
,4
]}

Hankov, Nicolas ^{[1
,2
,3
,4
]}

Varescon, Camille ^{[1
,2
,3
,4
]}

McCracken, Laura ^{[1
,2
,3
,4
]}

Vat, Molywan ^{[2
,3
,4
]}

Caban, Miroslav ^{[5
,9
]}

Watrin, Anne ^{[5
]}

Jacquet, Charlotte ^{[5
]}

Bole-Feysot, Lea ^{[1
,2
,3
,4
]}

Harte, Cathal ^{[1
,2
,3
,4
]}

Lorach, Henri ^{[1
,2
,3
,4
]}

Galvez, Andrea ^{[1
,2
,3
,4
]}

Tschopp, Manon ^{[2
,3
]}

Herrmann, Natacha ^{[2
,3
]}

Wacker, Moira ^{[2
,3
]}

Geernaert, Lionel ^{[2
,3
]}

Fodor, Isabelle ^{[2
,3
]}

Radevich, Valentin ^{[2
,3
]}

van den Keybus, Katrien ^{[2
,3
]}

Eberle, Gregoire ^{[2
,3
]}

Pralong, Etienne ^{[11
]}

Roulet, Maxime ^{[4
,11
]}

Ledoux, Jean-Baptiste ^{[8
,12
]}

Fornari, Eleonora ^{[8
,12
]}

Mandija, Stefano ^{[13
]}

Mattera, Loan ^{[14
]}

Martuzzi, Roberto ^{[14
]}

Nazarian, Bruno ^{[15
]}

Benkler, Stefan ^{[6
]}

Callegari, Simone ^{[16
]}

Greiner, Nathan ^{[1
,2
,3
,4
]}

Fuhrer, Benjamin ^{[1
,2
,3
]}

Froeling, Martijn ^{[13
]}

Buse, Nik ^{[17
]}

Denison, Tim ^{[17
,18
]}

Buschman, Rik ^{[17
]}

机构：

[1] Swiss Fed Inst Technol EPFL, Sch Life Sci, Ctr Neuroprosthet & Brain Mind Inst, Lausanne, Switzerland

[2] Lausanne Univ Hosp CHUV, Dept Clin Neurosci, Lausanne, Switzerland

[3] Univ Lausanne UNIL, Lausanne, Switzerland

[4] EPFL CHUV UNIL, Defitech Ctr Intervent Neurotherapies NeuroRestor, Lausanne, Switzerland

[5] ONWARD Med, Lausanne, Switzerland

[6] Fdn Res Informat Technol Soc, Zurich, Switzerland

[7] Swiss Fed Inst Technol, Dept Informat Technol & Elect Engn, Zurich, Switzerland

[8] CHUV UNIL, Dept Diagnost & Intervent Radiol, Lausanne, Switzerland

[9] Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland

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

[11] CHU Vaudois, Dept Neurosurg, Lausanne, Switzerland

[12] CHU Vaudois, MR Sect, Biomed Imaging Ctr, Lausanne, Switzerland

[13] Univ Med Ctr Utrecht, Utrecht, Netherlands

[14] Fdn Campus Biotech Geneve, Geneva, Switzerland

[15] Aix Marseille Univ, CNRS, Inst Neurosci Timone, Marseille, France

[16] ZurichMedTech, Zurich, Switzerland

[17] Medtronic, Minneapolis, MN USA

[18] Univ Oxford, Dept Engn Sci, Oxford, England

[19] Tech Univ Munich, Med Mat & Implants, Munich, Germany

[20] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria

[21] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria

[22] Aix Marseille Univ, CNRS, Lab Neurosci Cognit, Marseille, France

[23] Ecole Polytech Fed Lausanne, Bertarelli Fdn, Translat Neuroengn, Ctr Neuroprosthet, Lausanne, Switzerland

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

[25] Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland

[26] Radboud Univ Nijmegen Med Ctr, Dept Neurosurg, Nijmegen, Netherlands

[27] Univ Fribourg, Dept Neurosci & Movement Sci, Fribourg, Switzerland

[28] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA

[29] Univ Bordeaux, CNRS, UMR 5293, Inst Malad Neurodegenerat, Bordeaux, France

来源：

NATURE MEDICINE | 2022年 / 28卷 / 02期

基金：

欧盟地平线“2020”; 瑞士国家科学基金会; 欧洲研究理事会;

关键词：

PHYSIOLOGICAL NOISE; ELECTRICAL-STIMULATION; EPIDURAL STIMULATION; TENDON VIBRATION; MUSCLE; ACTIVATION; MECHANISMS; LOCOMOTION; RECOVERY; DEFICITS;

D O I：

10.1038/s41591-021-01663-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial (www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

引用

页码：260 / +

页数：41

共 72 条

[1] Targeting recovery: Priorities of the spinal cord-injured population [J].

Anderson, KD .

JOURNAL OF NEUROTRAUMA, 2004, 21 (10) :1371-1383

[2] Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury [J].

Angeli, Claudia A. ;

Boakye, Maxwell ;

Morton, Rebekah A. ;

Vogt, Justin ;

Benton, Kristin ;

Chen, Yangshen ;

Ferreira, Christie K. ;

Harkema, Susan J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (13) :1244-1250

[3] Cortico-reticulo-spinal circuit reorganization enables functional recovery after severe spinal cord contusion [J].

Asboth, Leonie ;

Friedli, Lucia ;

Beauparlant, Janine ;

Martinez-Gonzalez, Cristina ;

Anil, Selin ;

Rey, Elodie ;

Baud, Laetitia ;

Pidpruzhnykova, Galyna ;

Anderson, Mark A. ;

Shkorbatova, Polina ;

Batti, Laura ;

Pages, Stephane ;

Kreider, Julie ;

Schneider, Bernard L. ;

Barraud, Quentin ;

Courtine, Gregoire .

NATURE NEUROSCIENCE, 2018, 21 (04) :576-+

[4]

BAROLAT G, 1986, APPL NEUROPHYSIOL, V49, P307

[5]

Barra B., EPIDURAL ELECT STIMU, DOI [10.1101/2020.11.13.379750(2021, DOI 10.1101/2020.11.13.379750(2021]

[6] A component based noise correction method (CompCor) for BOLD and perfusion based fMRI [J].

Behzadi, Yashar ;

Restom, Khaled ;

Liau, Joy ;

Liu, Thomas T. .

NEUROIMAGE, 2007, 37 (01) :90-101

[7] An exoskeleton controlled by an epidural wireless brain-machine interface in a tetraplegic patient: a proof-of-concept demonstration [J].

Benabid, Alim Louis ;

Costecalde, Thomas ;

Eliseyev, Andrey ;

Charvet, Guillaume ;

Verney, Alexandre ;

Karakas, Serpil ;

Foerster, Michael ;

Lambert, Aurelien ;

Moriniere, Boris ;

Abroug, Neil ;

Schaeffer, Marie-Caroline ;

Moly, Alexandre ;

Sauter-Starace, Fabien ;

Ratel, David ;

Moro, Cecile ;

Torres-Martinez, Napoleon ;

Langar, Lilia ;

Oddoux, Manuela ;

Polosan, Mircea ;

Pezzani, Stephane ;

Auboiroux, Vincent ;

Aksenova, Tetiana ;

Mestais, Corinne ;

Chabardes, Stephan .

LANCET NEUROLOGY, 2019, 18 (12) :1112-1122

[8] Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury [J].

Bonizzato, Marco ;

Pidpruzhnykova, Galyna ;

DiGiovanna, Jack ;

Shkorbatova, Polina ;

Pavlova, Natalia ;

Micera, Silvestro ;

Courtine, Gregoire .

NATURE COMMUNICATIONS, 2018, 9

[9] Physiological noise modelling for spinal functional magnetic resonance imaging studies [J].

Brooks, Jonathan C. W. ;

Beckmann, Christian F. ;

Miller, Karla L. ;

Wise, Richard G. ;

Porro, Carlo A. ;

Tracey, Irene ;

Jenkinson, Mark .

NEUROIMAGE, 2008, 39 (02) :680-692

[10] Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics [J].

Capogrosso, Marco ;

Wagner, Fabien B. ;

Gandar, Jerome ;

Moraud, Eduardo Martin ;

Wenger, Nikolaus ;

Milekovic, Tomislav ;

Shkorbatova, Polina ;

Pavlova, Natalia ;

Musienko, Pavel ;

Bezard, Erwan ;

Bloch, Jocelyne ;

Courtine, Gregoire .

NATURE PROTOCOLS, 2018, 13 (09) :2031-2061

← 1 2 3 4 5 6 7 8 →