Background Approximately 20% of traumatic cervical spinal cord injuries result in tetraplegia. Neuroprosthetics are being developed to manage this condition and thus improve the lives of patients. We aimed to test the feasibility of a semi-invasive technique that uses brain signals to drive an exoskeleton. Methods We recruited two participants at Clinatec research centre, associated with Grenoble University Hospital, Grenoble, France, into our ongoing clinical trial. Inclusion criteria were age 18-45 years, stability of neurological deficits, a need for additional mobility expressed by the patient, ambulatory or hospitalised monitoring, registration in the French social security system, and signed informed consent. The exclusion criteria were previous brain surgery, anticoagulant treatments, neuropsychological sequelae, depression, substance dependence or misuse, and contraindications to magnetoencephalography (MEG), EEG, or MRI. One participant was excluded because of a technical problem with the implants. The remaining participant was a 28-year-old man, who had tetraplegia following a C4-C5 spinal cord injury. Two bilateral wireless epidural recorders, each with 64 electrodes, were implanted over the upper limb sensorimotor areas of the brain. Epidural electrocorticographic (ECoG) signals were processed online by an adaptive decoding algorithm to send commands to effectors (virtual avatar or exoskeleton). Throughout the 24 months of the study, the patient did various mental tasks to progressively increase the number of degrees of freedom. Findings Between June 12,2017, and July 21,2019, the patient cortically controlled a programme that simulated walking and made bimanual, multi-joint, upper-limb movements with eight degrees of freedom during various reach-andtouch tasks and wrist rotations, using a virtual avatar at home (64.0% [SD 5.1] success) or an exoskeleton in the laboratory (70.9% [11.6] success). Compared with rnicroelectrodes, epidural ECoG is semi-invasive and has similar efficiency. The decoding models were reusable for up to approximately 7 weeks without recalibration. Interpretation These results showed long-term (24-month) activation of a four-limb neuroprosthetic exoskeleton by a complete brain-machine interface system using continuous, online epidural ECoG to decode brain activity in a tetraplegic patient. Up to eight degrees of freedom could be simultaneously controlled using a unique model, which was reusable without recalibration for up to about 7 weeks. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Event Abstract Back to Event Brain Computer Interface human platform to control a 4-limb exoskeleton based on the ECoG-recording implant WIMAGINE®: preliminary results Corinne Mestais1*, Guillaume Charvet1, Fabien Sauter-Starace1, Neil Abroug1, N. Arizumi1, Serpil Cokgungor1, Thomas Costecalde1, Michael Foerster1, Boris Morinière1, Jeremy Pradal1, David Ratel1, Victor Rohu1, Marie Caroline Schaeffer1, Nicolas Tarrin1, Napoleon R. Torres Martinez1, Alexandre Verney1, Andriy Yelisyeyev1, Tatiana Aksenova1 and Alim L. Benabid1 1 CEA/LETI, MINATEC Campus, France The goal of CLINATEC® Brain Computer Interface Project is to improve tetraplegic subjects’ quality of life by allowing them to interact with their environment through the control of effectors with multiple degrees of freedom after training. Thanks to a long-term wireless 64-channel ECoG recording implant WIMAGINE® (Wireless Implantable Multi-channel Acquisition system for Generic Interface with NEurons) [1] and an innovative signal processing, the subject should be able to control a 4-limb exoskeleton EMY (Enhancing MobilitY) [2]. The ECoG signals from the subject’s brain will be recorded and wirelessly transmitted to a base station by the WIMAGINE® implant. This implant is composed of an array of 64 biocompatible electrodes, a hermetic titanium case which houses electronic boards, biocompatible antennas for wireless transmission of the data, and a remote power supply. The WIMAGINE implant complies with implantable medical device standards. Innovative ECoG signal decoding algorithms will allow self-paced control of the exoskeleton by decoding the subject’s brain activity [3] [4]. The neuronal signal processing approach is based on a tensor data analysis. It allows simultaneous treatment of the signal in several domains, (frequency, temporal, and spatial). Before applying the BCI platform to patients, a set of preclinical experiments are carried out on male Macaque Rhesus. Ethical approval was obtained from ComEth in accordance with the European Communities Council Directive of 1986 (86/609/EEC) for care of laboratory animals. High performance decoding of the continuous three-dimensional hand trajectory from epidural ECoG signals of the primate’s brain allows reproducing the arm movement by the exoskeleton arm (EMY) in real time. To ensure future clinical applications, algorithms were also tested in control human subjects, in noninvasive MEG acquisition system while they were executing real or imagined hand movements. Finally, the clinical research protocol submission to the French regulatory bodies is in progress. Applications of the BCI platform to post stroke patient rehabilitation are also investigated References [1] C. Mestais, G. Charvet, F. Sauter-Starace, M. Foerster, D. Ratel, and AL. Benabid, “WIMAGINE: Wireless 64-Channel ECoG Recording Implant for Long Term Clinical Applications”, IEEE Trans Neural Syst Rehabil Eng. 2015 Jan;23(1):10-21. [2] Y. Perrot, A. Verney, B. Morinière, and P. Garrec, "EMY: Full-body Exoskeleton," in ACM SIGGRAPH Emerging Technologies, Anaheim, USA, 2013. [3] A. Eliseyev and T. Aksenova, “Stable and artifact-resistant decoding of 3D hand trajectories from ECoG signals using the generalized additive model”, J. Neural Eng. 11 (2014) 066005 (13pp) [4] A. Eliseyev and T. Aksenova, "Recursive N-way partial least squares for brain-computer interface" PLoS One, vol. 8, p. e69962, 2013. The goal of CLINATEC® Brain Computer Interface Project is to improve tetraplegic subjects’ quality of life by allowing them to interact with their environment through the control of effectors with multiple degrees of freedom after training. Thanks to a long-term wireless 64-channel ECoG recording implant WIMAGINE® (Wireless Implantable Multi-channel Acquisition system for Generic Interface with NEurons) [1] and an innovative signal processing, the subject should be able to control a 4-limb exoskeleton EMY (Enhancing MobilitY) [2]. The ECoG signals from the subject’s brain will be recorded and wirelessly transmitted to a base station by the WIMAGINE® implant. This implant is composed of an array of 64 biocompatible electrodes, a hermetic titanium case which houses electronic boards, biocompatible antennas for wireless transmission of the data, and a remote power supply. The WIMAGINE implant complies with implantable medical device standards. Innovative ECoG signal decoding algorithms will allow self-paced control of the exoskeleton by decoding the subject’s brain activity [3] [4]. The neuronal signal processing approach is based on a tensor data analysis. It allows simultaneous treatment of the signal in several domains, (frequency, temporal, and spatial). Before applying the BCI platform to patients, a set of preclinical experiments are carried out on male Macaque Rhesus. Ethical approval was obtained from ComEth in accordance with the European Communities Council Directive of 1986 (86/609/EEC) for care of laboratory animals. High performance decoding of the continuous three-dimensional hand trajectory from epidural ECoG signals of the primate’s brain allows reproducing the arm movement by the exoskeleton arm (EMY) in real time. To ensure future clinical applications, algorithms were also tested in control human subjects, in noninvasive MEG acquisition system while they were executing real or imagined hand movements. Finally, the clinical research protocol submission to the French regulatory bodies is in progress. Applications of the BCI platform to post stroke patient rehabilitation are also investigated References [1] C. Mestais, G. Charvet, F. Sauter-Starace, M. Foerster, D. Ratel, and AL. Benabid, “WIMAGINE: Wireless 64-Channel ECoG Recording Implant for Long Term Clinical Applications”, IEEE Trans Neural Syst Rehabil Eng. 2015 Jan;23(1):10-21. [2] Y. Perrot, A. Verney, B. Morinière, and P. Garrec, "EMY: Full-body Exoskeleton," in ACM SIGGRAPH Emerging Technologies, Anaheim, USA, 2013. [3] A. Eliseyev and T. Aksenova, “Stable and artifact-resistant decoding of 3D hand trajectories from ECoG signals using the generalized additive model”, J. Neural Eng. 11 (2014) 066005 (13pp) [4] A. Eliseyev and T. Aksenova, "Recursive N-way partial least squares for brain-computer interface" PLoS One, vol. 8, p. e69962, 2013. The goal of CLINATEC® Brain Computer Interface Project is to improve tetraplegic subjects’ quality of life by allowing them to interact with their environment through the control of effectors with multiple degrees of freedom after training. Thanks to a long-term wireless 64-channel ECoG recording implant WIMAGINE® (Wireless Implantable Multi-channel Acquisition system for Generic Interface with NEurons) [1] and an innovative signal processing, the subject should be able to control a 4-limb exoskeleton EMY (Enhancing MobilitY) [2]. The ECoG signals from the subject’s brain will be recorded and wirelessly transmitted to a base station by the WIMAGINE® implant. This implant is composed of an array of 64 biocompatible electrodes, a hermetic titanium case which houses electronic boards, biocompatible antennas for wireless transmission of the data, and a remote power supply. The WIMAGINE implant complies with implantable medical device standards. Innovative ECoG signal decoding algorithms will allow self-paced control of the exoskeleton by decoding the subject’s brain activity [3] [4]. The neuronal signal processing approach is based on a tensor data analysis. It allows simultaneous treatment of the signal in several domains, (frequency, temporal, and spatial). Before applying the BCI platform to patients, a set of preclinical experiments are carried out on male Macaque Rhesus. Ethical approval was obtained from ComEth in accordance with the European Communities Council Directive of 1986 (86/609/EEC) for care of laboratory animals. High performance decoding of the continuous three-dimensional hand trajectory from epidural ECoG signals of the primate’s brain allows reproducing the arm movement by the exoskeleton arm (EMY) in real time. To ensure future clinical applications, algorithms were also tested in control human subjects, in noninvasive MEG acquisition system while they were executing real or imagined hand movements. Finally, the clinical research protocol submission to the French regulatory bodies is in progress. Applications of the BCI platform to post stroke patient rehabilitation are also investigated References [1] C. Mestais, G. Charvet, F. Sauter-Starace, M. Foerster, D. Ratel, and AL. Benabid, “WIMAGINE: Wireless 64-Channel ECoG Recording Implant for Long Term Clinical Applications”, IEEE Trans Neural Syst Rehabil Eng. 2015 Jan;23(1):10-21. [2] Y. Perrot, A. Verney, B. Morinière, and P. Garrec, "EMY: Full-body Exoskeleton," in ACM SIGGRAPH Emerging Technologies, Anaheim, USA, 2013. [3] A. Eliseyev and T. Aksenova, “Stable and artifact-resistant decoding of 3D hand trajectories from ECoG signals using the generalized additive model”, J. Neural Eng. 11 (2014) 066005 (13pp) [4] A. Eliseyev and T. Aksenova, "Recursive N-way partial least squares for brain-computer interface" PLoS One, vol. 8, p. e69962, 2013. Acknowledgements The BCI project was supported by French National Research Agency (ANR-Carnot Institute), Fondation Motrice, Fondation Nanosciences, Fondation de l’Avenir, and Fondation Philanthropique Edmond J. Safr Keywords: Brain computer interface (BCI), exoskeleton, ECoG-recording implant, WIMAGINE, Tetraplegic Conference: 2015 International Workshop on Clinical Brain-Machine Interfaces (CBMI2015), Tokyo, Japan, 13 Mar - 15 Mar, 2015. Presentation Type: Poster 4-5 Topic: Clinical Brain-Machine Interfaces Citation: Mestais C, Charvet G, Sauter-Starace F, Abroug N, Arizumi N, Cokgungor S, Costecalde T, Foerster M, Morinière B, Pradal J, Ratel D, Rohu V, Schaeffer M, Tarrin N, Torres Martinez NR, Verney A, Yelisyeyev A, Aksenova T and Benabid AL (2015). Brain Computer Interface human platform to control a 4-limb exoskeleton based on the ECoG-recording implant WIMAGINE®: preliminary results. Conference Abstract: 2015 International Workshop on Clinical Brain-Machine Interfaces (CBMI2015). doi: 10.3389/conf.fnhum.2015.218.00020 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Apr 2015; Published Online: 29 Apr 2015. * Correspondence: Dr. Corinne Mestais, CEA/LETI, MINATEC Campus, Grenoble, France, corinne.mestais@cea.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Corinne Mestais Guillaume Charvet Fabien Sauter-Starace Neil Abroug N. Arizumi Serpil Cokgungor Thomas Costecalde Michael Foerster Boris Morinière Jeremy Pradal David Ratel Victor Rohu Marie Caroline Schaeffer Nicolas Tarrin Napoleon R Torres Martinez Alexandre Verney Andriy Yelisyeyev Tatiana Aksenova Alim L Benabid Google Corinne Mestais Guillaume Charvet Fabien Sauter-Starace Neil Abroug N. Arizumi Serpil Cokgungor Thomas Costecalde Michael Foerster Boris Morinière Jeremy Pradal David Ratel Victor Rohu Marie Caroline Schaeffer Nicolas Tarrin Napoleon R Torres Martinez Alexandre Verney Andriy Yelisyeyev Tatiana Aksenova Alim L Benabid Google Scholar Corinne Mestais Guillaume Charvet Fabien Sauter-Starace Neil Abroug N. Arizumi Serpil Cokgungor Thomas Costecalde Michael Foerster Boris Morinière Jeremy Pradal David Ratel Victor Rohu Marie Caroline Schaeffer Nicolas Tarrin Napoleon R Torres Martinez Alexandre Verney Andriy Yelisyeyev Tatiana Aksenova Alim L Benabid PubMed Corinne Mestais Guillaume Charvet Fabien Sauter-Starace Neil Abroug N. Arizumi Serpil Cokgungor Thomas Costecalde Michael Foerster Boris Morinière Jeremy Pradal David Ratel Victor Rohu Marie Caroline Schaeffer Nicolas Tarrin Napoleon R Torres Martinez Alexandre Verney Andriy Yelisyeyev Tatiana Aksenova Alim L Benabid Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Event Abstract Back to Event A wireless fully implantable ECoG recording medical device WIMAGINE® for human Brain Computer Interface applications: toward a clinical trial Guillaume Charvet1*, Corinne Mestais1, Fabien Sauter-Starace1, Michael Foerster1, Aurelien Lambert1, Claude Chabrol1, Napoleon R. Torres Martinez1, Thomas Costecalde1, David Ratel1 and Alim L. Benabid1 1 CEA/LETI, MINATEC Campus, France The WIMAGINE® implant was developed to record ECoG (ElectroCorticoGram) signals for long term clinical applications in the context of a Brain Computer Interface project which goal is to allow a tetraplegic subject to control a 4-limb exoskeleton thanks to his brain activity [1]. This active implantable medical device [2] is composed of an array of 64 biocompatible electrodes, a hermetic titanium housing including the electronic boards and biocompatible antennae for wireless transmission of data and remote power supply. This implant is able to record ECoG on 64 electrodes with selectable gain and sampling frequency, with less than 0.7μV RMS input referred noise in the [0.5Hz – 300Hz] band thanks to a dedicated integrated circuit. It is powered remotely through an inductive link at 13.56MHz, communicates wirelessly on the MICS band at 402-405MHz with a custom designed base station connected to a PC and complies with the regulations applicable to class III AIMD. During the surgical procedure, the implant will be inserted into a 50 mm craniotomy so that the electrode array is in contact with the dura mater, and the implant recovered by the skin (Fig. 1). The design of the WIMAGINE® implant takes into account all the constraints of long term implantable medical devices. In particular, WIMAGINE® was designed to satisfy the Essential requirements of the European Medical Device Directives 93/42/CEE and 90/385/EEC. A risk analysis according to ISO 14971 standards has been carried out, and risk management actions were set up. The implant manufacturing was achieved according to a qualified industrial process under ISO certification 13485. In order to increase the reliability, all electronic boards undergo a burn-in procedure to avoid early in-use system failures, and functional tests. The electronic board is encapsulated into a dedicated titanium packaging with hermetic feedthrough. The hermeticity is achieved by laser welding and tested in terms of helium leakage and yield 10-9 bar.cm-3.s-1. Then, each implant is tested, cleaned and sterilized according to a validated process. The mechanical and electrical qualification tests of the implant according to the ISO 45502-1 standards were successfully achieved by certified bodies, such as resistance to mechanical forces, vibrations and shocks, electrodes leakage current less than 1μA, heating at the surface of the implant less than 2°C. Likewise, the electrical security tests and electromagnetic compatibility (EMC) tests according to the EN 60601-1 were performed on the WIMAGINE® platform. Finally, the long-term biocompatibility is evaluating according to the ISO 10993. The submission of the protocol for clinical trial authorization to the French authorities (ANSM and CPP) in the context of Brain Computer Interface for tetraplegia is in progress. Other neurological applications requiring wireless ECoG recording such as presurgical evaluation of epilepsy, or post stroke rehabilitation [3] can be addressed. References [1] A. Eliseyev, T. Aksenova, C. Mestais, A.-L. Benabid, et al., CLINATEC BCI platform based on the ECoG-recording implant WIMAGINE and the innovative signal-processing to control the exoskeleton EMY: preclinical results, EMBC, 36th Annual International Conference of the IEEE, 2014 [2] C. Mestais, G. Charvet, F. Sauter-Starace, M. Foerster, D. Ratel, and AL. Benabid, “WIMAGINE: Wireless 64-Channel ECoG Recording Implant for Long Term Clinical Applications”, IEEE Trans Neural Syst Rehabil Eng. 2015 Jan;23(1):10-21 [3] Silvoni, S., Ramos-Murguialday, A., Cavinato, M., Volpato, C., Cisotto, G., Turolla, A., ... & Birbaumer, N. (2011). Brain-computer interface in stroke: a review of progress. Clinical EEG and Neuroscience, 42(4), 245-252. Figure 1 Acknowledgements The development of WIMAGINE® Implant was supported by French National Research Agency (ANR-Carnot Institute), Fondation Motrice, Fondation Nanosciences, Fondation de l’Avenir, and Fondation Philanthropique Edmond J. Safra. Keywords: ECoG, WIMAGINE, Brain computer interface (BCI), AIMD, ANSM, CPP Conference: 2015 International Workshop on Clinical Brain-Machine Interfaces (CBMI2015), Tokyo, Japan, 13 Mar - 15 Mar, 2015. Presentation Type: Poster 3-2 Topic: Clinical Brain-Machine Interfaces Citation: Charvet G, Mestais C, Sauter-Starace F, Foerster M, Lambert A, Chabrol C, Torres Martinez NR, Costecalde T, Ratel D and Benabid AL (2015). A wireless fully implantable ECoG recording medical device WIMAGINE® for human Brain Computer Interface applications: toward a clinical trial. Conference Abstract: 2015 International Workshop on Clinical Brain-Machine Interfaces (CBMI2015). doi: 10.3389/conf.fnhum.2015.218.00028 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Apr 2015; Published Online: 29 Apr 2015. * Correspondence: Dr. Guillaume Charvet, CEA/LETI, MINATEC Campus, Grenoble, France, guillaume.charvet@cea.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Guillaume Charvet Corinne Mestais Fabien Sauter-Starace Michael Foerster Aurelien Lambert Claude Chabrol Napoleon R Torres Martinez Thomas Costecalde David Ratel Alim L Benabid Google Guillaume Charvet Corinne Mestais Fabien Sauter-Starace Michael Foerster Aurelien Lambert Claude Chabrol Napoleon R Torres Martinez Thomas Costecalde David Ratel Alim L Benabid Google Scholar Guillaume Charvet Corinne Mestais Fabien Sauter-Starace Michael Foerster Aurelien Lambert Claude Chabrol Napoleon R Torres Martinez Thomas Costecalde David Ratel Alim L Benabid PubMed Guillaume Charvet Corinne Mestais Fabien Sauter-Starace Michael Foerster Aurelien Lambert Claude Chabrol Napoleon R Torres Martinez Thomas Costecalde David Ratel Alim L Benabid Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A wireless 64-channel ElectroCorticoGram (ECoG) recording implant named WIMAGINE has been designed for various clinical applications. The device is aimed at interfacing a cortical electrode array to an external computer for neural recording and control applications. This active implantable medical device is able to record neural activity on 64 electrodes with selectable gain and sampling frequency, with less than 1 μV RMS input referred noise in the [0.5 Hz - 300 Hz] band. It is powered remotely through an inductive link at 13.56 MHz which provides up to 100 mW. The digitized data is transmitted wirelessly to a custom designed base station connected to a PC. The hermetic housing and the antennae have been designed and optimized to ease the surgery. The design of this implant takes into account all the requirements of a clinical trial, in particular safety, reliability, and compliance with the regulations applicable to class III AIMD. The main features of this WIMAGINE implantable device and its architecture are presented, as well as its functional performances and long-term biocompatibility results.

The goal of the CLINATEC® Brain Computer Interface (BCI) Project is to improve tetraplegic subjects' quality of life by allowing them to interact with their environment through the control of effectors, such as an exoskeleton. The BCI platform is based on a wireless 64-channel ElectroCorticoGram (ECoG) recording implant WIMAGINE®, designed for long-term clinical application, and a BCI software environment associated to a 4-limb exoskeleton EMY (Enhancing MobilitY). Innovative ECoG signal decoding algorithms will allow the control of the exoskeleton by the subject's brain activity. Currently, the whole BCI platform was tested in real-time in preclinical experiments carried out in nonhuman primates. In these experiments, the exoskeleton arm was controlled by means of the decoded neuronal activity.

The multi-way decoding algorithms are adapted to incomplete wirelessly transmitted data and integrated to CLINATEC ® BCI platform. The platform includes wireless 64channels ElectroCorticoGram (ECoG) recording implant WIMAGINE ® and BCI software environment associated to a 4-limbs exoskeleton EMY.