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2. Polystyrene nanoplastics affect transcriptomic and epigenomic signatures of human fibroblasts and derived induced pluripotent stem cells: Implications for human health

Author

National Institutes of Health (US), Fondation Bertarelli, Remondi Family Foundation, Stojkovic, Miodrag, Ortuño, Francisco M., Han, Dongjun, Stojkovic, Petra, Dopazo, Joaquín, Stankovic, Konstantina M., National Institutes of Health (US), Fondation Bertarelli, Remondi Family Foundation, Stojkovic, Miodrag, Ortuño, Francisco M., Han, Dongjun, Stojkovic, Petra, Dopazo, Joaquín, and Stankovic, Konstantina M.

Abstract

Plastic pollution is increasing at an alarming rate yet the impact of this pollution on human health is poorly understood. Because human induced pluripotent stem cells (hiPSC) are frequently derived from dermal fibroblasts, these cells offer a powerful platform for the identification of molecular biomarkers of environmental pollution in human cells. Here, we describe a novel proof-of-concept for deriving hiPSC from human dermal fibroblasts deliberately exposed to polystyrene (PS) nanoplastic particles; unexposed hiPSC served as controls. In parallel, unexposed hiPSC were exposed to low and high concentrations of PS nanoparticles. Transcriptomic and epigenomic signatures of all fibroblasts and hiPSCs were defined using RNA-seq and whole genome methyl-seq, respectively. Both PS-treated fibroblasts and derived hiPSC showed alterations in expression of ESRRB and HNF1A genes and circuits involved in the pluripotency of stem cells, as well as in pathways involved in cancer, inflammatory disorders, gluconeogenesis, carbohydrate metabolism, innate immunity, and dopaminergic synapse. Similarly, the expression levels of identified key transcriptional and DNA methylation changes (DNMT3A, ESSRB, FAM133CP, HNF1A, SEPTIN7P8, and TTC34) were significantly affected in both PS-exposed fibroblasts and hiPSC. This study illustrates the power of human cellular models of environmental pollution to narrow down and prioritize the list of candidate molecular biomarkers of environmental pollution. This knowledge will facilitate the deciphering of the origins of environmental diseases.

Published
2023

3. Key issues in assessing threats to sea turtles: knowledge gaps and future directions

Author

Florida State University, Fondation Bertarelli, Ministerio de Ciencia e Innovación (España), National Science Foundation (US), American Geophysical Union, Agencia Estatal de Investigación (España), Fuentes, Mariana M. P. B., McMichael, Erin, Kot, Connie Y., Silver-Gorges, Ian, Wallace, Bryan P., Godley, Brendan J., Brooks, Annabelle, Ceriani, Simona A., Cortés-Gómez, Adriana A., Dawson, Tiffany M., Dodge, Kara L., Flint, Mark, Jensen, Michael P., Komoroske, Lisa M., Kophamel, Sara, Lettrich, Matthew D., Long, Christopher A., Nelms, Sarah E., Patrício, Ana R., Robinson, Nathan J., Seminoff, Jeffrey A., Ware, Mate, Whitman, Elizabeth R., Chevallier, Damien, Clyde-Brockway, Chelsea, Korgaonkar, Sumedha A., Mancini, Agnese, Mello-Fonseca, Juliana, Monsinjon, Jonathan R., Neves-Ferreira, Isabella, Ortega, Anna A., Patel, Samir H., Pfaller, Joseph B., Ramirez, Matthew D., Raposo, Cheila, Smith, Caitlin E., Abreu-Grobois, F. Alberto, Hays, Graeme C., Florida State University, Fondation Bertarelli, Ministerio de Ciencia e Innovación (España), National Science Foundation (US), American Geophysical Union, Agencia Estatal de Investigación (España), Fuentes, Mariana M. P. B., McMichael, Erin, Kot, Connie Y., Silver-Gorges, Ian, Wallace, Bryan P., Godley, Brendan J., Brooks, Annabelle, Ceriani, Simona A., Cortés-Gómez, Adriana A., Dawson, Tiffany M., Dodge, Kara L., Flint, Mark, Jensen, Michael P., Komoroske, Lisa M., Kophamel, Sara, Lettrich, Matthew D., Long, Christopher A., Nelms, Sarah E., Patrício, Ana R., Robinson, Nathan J., Seminoff, Jeffrey A., Ware, Mate, Whitman, Elizabeth R., Chevallier, Damien, Clyde-Brockway, Chelsea, Korgaonkar, Sumedha A., Mancini, Agnese, Mello-Fonseca, Juliana, Monsinjon, Jonathan R., Neves-Ferreira, Isabella, Ortega, Anna A., Patel, Samir H., Pfaller, Joseph B., Ramirez, Matthew D., Raposo, Cheila, Smith, Caitlin E., Abreu-Grobois, F. Alberto, and Hays, Graeme C.

Abstract

Sea turtles are an iconic group of marine megafauna that have been exposed to multiple anthropogenic threats across their different life stages, especially in the past decades. This has resulted in population declines, and consequently many sea turtle populations are now classified as threatened or endangered globally. Although some populations of sea turtles worldwide are showing early signs of recovery, many still face fundamental threats. This is problematic since sea turtles have important ecological roles. To encourage informed conservation planning and direct future research, we surveyed experts to identify the key contemporary threats (climate change, direct take, fisheries, pollution, disease, predation, and coastal and marine development) faced by sea turtles. Using the survey results and current literature, we also outline knowledge gaps in our understanding of the impact of these threats and how targeted future research, often involving emerging technologies, could close those gaps

Published
2023

4. Social networks and the conservation of fish

Author

European Commission, Consejo Superior de Investigaciones Científicas (España), Research England, Fondation Bertarelli, Villegas-Ríos, David, Jacoby, David M. P., Mourier, Johann, European Commission, Consejo Superior de Investigaciones Científicas (España), Research England, Fondation Bertarelli, Villegas-Ríos, David, Jacoby, David M. P., and Mourier, Johann

Abstract

Despite our critical dependence on aquatic wildlife, we lack a complete understanding of the drivers of population stability and structure for most fish species. Social network analysis has been increasingly used to investigate animal societies as it explicitly links individual decision-making to population-level processes and demography. While the study of social structure is of great ecological interest, it is also potentially important for species of economic value or of conservation concern. To date however, there has been little focus on how social processes are likely to influence the conservation of fish populations. Here we identify applications for how a social network approach can help address broad fish conservation themes such as population structure, biological invasions or fisheries management. We discuss the burgeoning opportunities offered and challenges still faced by current technologies to integrate social network approaches within fish conservation

Published
2022

5. Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance

Author

Pawel Maciejasz, David Andreu, Ken Yoshida, Xavier Navarro, Silvestro Micera, Stanisa Raspopovic, Paul Čvančara, Tim Boretius, Victor Lopezalvarez, Eduardo Fernandez, Giuseppe Granata, Thomas Stieglitz, Paolo Maria Rossini, David Guiraud, Jean-Louis Divoux, Winnie Jensen, Francesco Maria Petrini, Bernstein Center Freiburg (BCF), Albert-Ludwigs-Universität Freiburg, Department of Microsystems Engineering [Freiburg] (IMTEK), University of Freiburg [Freiburg], Universitat Autònoma de Barcelona (UAB), Otto Bock Healthcare GmbH, Contrôle Artificiel de Mouvements et de Neuroprothèses Intuitives (CAMIN), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Fondation Bertarelli Chair inTranslational Neuroscience and Neuroengineering [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL)-Fondation Bertarelli, Scuela Santa Anna (SSSA), Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Perdue University, Center for Sensory-Motor Interaction (SMI), Aalborg University [Denmark] (AAU), AXONIC - OBELIA dept, MXM-Laboratoires de Techologies Médicales, Center for Neuroprosthetics and Institute of Bioengineering, EPFL.-Fondation Bertarelli, and Fondazione 'Policlinico Universitario A. Gemelli' [Rome]

Subjects
Thin-film, Materials science, Electrode, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0206 medical engineering, Biomedical Engineering, 02 engineering and technology, polyimide, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Amputees, Electric Impedance, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Silicon carbide, Animals, Humans, neural interfaces, Thin film, Electrodes, Delamination, electrode, stability, thin-film, Prostheses and Implants, 020601 biomedical engineering, Electric Stimulation, Electrodes, Implanted, Microelectrode, chemistry, Implant, Neural interfaces, Polyimide, Stability, Microelectrodes, Failure mode and effects analysis, Layer (electronics), 030217 neurology & neurosurgery, Biomedical engineering
Abstract

Objective Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. Approach This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d. Main results About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Significance Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications., Journal of Neural Engineering, 17 (4), ISSN:1741-2560, ISSN:1741-2552

Published
2020

6. Enhancing functional abilities and cognitive integration of the lower limb prosthesis

Author

Marko Bumbasirevic, Bogdan Mijovic, Asgeir Alexandersson, Pavle Mijović, Arthur Hiairrassary, Giacomo Valle, Dario Bortolotti, Atli Örn Sverrisson, Alessandra Pedrocchi, Paul Čvančara, David Guiraud, Aleksandar Lesic, Thomas Stieglitz, Francesco Maria Petrini, Jean-Louis Divoux, Stanisa Raspopovic, Igor Popovic, Federica Barberi, Silvestro Micera, Knut Lechler, Center for Neuroprosthetics [Geneva] (CNP), Ecole Polytechnique Fédérale de Lausanne (EPFL), Fondation Bertarelli Chair inTranslational Neuroscience and Neuroengineering [Lausanne], Center for Neuroprosthetics and Institute of Bioengineering, EPFL.-Fondation Bertarelli, The BioRobotics Institute, Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), Department of Electronics, Information, and Bioengineering [Milano] (DEIB), Politecnico di Milano [Milan] (POLIMI), School of Medecine [Belgrade], University of Belgrade [Belgrade], University of Freiburg [Freiburg], Control of Artificial Movement and Intuitive Neuroprosthesis (CAMIN), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), mBrainTrain [Belgrade], Össur hf [Copenhagen], AXONIC - OBELIA dept, MXM-Laboratoires de Techologies Médicales, Special Hospital for Rehabilitation and Orthopaedic Prosthetics [Belgrade], Department of Microsystems Engineering [Freiburg] (IMTEK), Department of Health Sciences and Technology [ETH Zürich] (D-HEST), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Ecole Polytechnique Fédérale de Lausanne (EPFL)-Fondation Bertarelli, and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Inria Sophia Antipolis - Méditerranée (CRISAM)

Subjects
0301 basic medicine, leg, medicine.medical_specialty, sensory feedback, Neuroprosthetics, Knee Joint, medicine.medical_treatment, media_common.quotation_subject, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Sensory system, Artificial Limbs, system, Prosthesis Design, neuroprostheses, Prosthesis, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, walking, 0302 clinical medicine, Physical medicine and rehabilitation, Cognition, Amputees, discharge, Perception, amputation, Activities of Daily Living, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, knee-joint, media_common, Haptic technology, gait symmetry, Proprioception, Work (physics), General Medicine, 3. Good health, body regions, 030104 developmental biology, Lower Extremity, Psychology, 030217 neurology & neurosurgery, performance
Abstract

International audience; Lower limb amputation (LLA) destroys the sensory communication between the brain and the external world during standing and walking. Current prostheses do not restore sensory feedback to amputees, who, relying on very limited haptic information from the stump-socket interaction, are forced to deal with serious issues: the risk of falls, decreased mobility, prosthesis being perceived as an external object (low embodiment), and increased cognitive burden. Poor mobility is one of the causes of eventual device abandonment. Restoring sensory feedback from the missing leg of above-knee (transfemoral) amputees and integrating the sensory feedback into the sensorimotor loop would markedly improve the life of patients. In this study, we developed a leg neuroprosthesis, which provided real-time tactile and emulated proprioceptive feedback to three transfemoral amputees through nerve stimulation. The feedback was exploited in active tasks, which proved that our approach promoted improved mobility, fall prevention, and agility. We also showed increased embodiment of the lower limb prosthesis (LLP), through phantom leg displacement perception and questionnaires, and ease of the cognitive effort during a dual-task paradigm, through electroencephalographic recordings. Our results demonstrate that induced sensory feedback can be integrated at supraspinal levels to restore functional abilities of the missing leg. This work paves the way for further investigations about how the brain interprets different artificial feedback strategies and for the development of fully implantable sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability.

Published
2019

7. 'Comparison between Automatic and Human Subtitling: A Case Study with Game of Thrones'

Author

Sabrina Baldo de Brébisson, Université d'Évry-Val-d'Essonne (UEVE), Fondation Bertarelli Chair inTranslational Neuroscience and Neuroengineering [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL)-Fondation Bertarelli, COUTU, CECILE, and Center for Neuroprosthetics and Institute of Bioengineering, EPFL.-Fondation Bertarelli

Subjects
Multimedia, Computer science, business.industry, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Automatic translation, computer.software_genre, [SHS.LANGUE] Humanities and Social Sciences/Linguistics, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, [SHS]Humanities and Social Sciences, Software, Work (electrical), [SHS] Humanities and Social Sciences, [SHS.LANGUE]Humanities and Social Sciences/Linguistics, business, computer, ComputingMilieux_MISCELLANEOUS
Abstract

In this submission, I would like to share my experiences with the software DeepL and the comparison analysis I have made with human subtitling offered by the DVD version of the corpus I have chosen as the topic of my study – the eight Seasons of Game of Thrones. The idea is to study if the version proposed by an automatic translation program could be used as a first draft for the professional subtitler. It is expected that the latter would work on the form of the subtitles, that is to say mainly on their length, in a second step.

Published
2019

8. Six-months assessment of a hand prosthesis with intraneural tactile feedback

Author

Petrini, Francesco, Valle, Giacomo, Strauss, Ivo, Granata, Giuseppe, Di Iorio, Riccardo, d'Anna, Edoardo, Čvančara, Paul, Mueller, Matthias, Carpaneto, Jacopo, Clemente, Francesco, Controzzi, Marco, Bisoni, Lorenzo, Carboni, Caterina, Barbaro, Michael, Iodice, Francesco, Andreu, David, Hiairrassary, Arthur, Divoux, Jean-Louis, Cipriani, Christian, Guiraud, David, Raffo, Luigi, Fernandez, Eduardo, Stieglitz, Thomas, Raspopovic, Stanisa, Rossini, Paolo Maria, Micera, Silvestro, Fondation Bertarelli Chair inTranslational Neuroscience and Neuroengineering [Lausanne], Center for Neuroprosthetics and Institute of Bioengineering, EPFL.-Fondation Bertarelli, Università cattolica del Sacro Cuore [Roma] (Unicatt), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Bernstein Center Freiburg (BCF), Albert-Ludwigs-Universität Freiburg, Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), Department of Electrical and Electronic Engineering [University of Cagliari] (DIEE), University of Cagliari, Control of Artificial Movement and Intuitive Neuroprosthesis (CAMIN), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), MXM-AXONIC, University of Freiburg [Freiburg], Department of Health Sciences and Technology [ETH Zürich] (D-HEST), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), This work was supported by EU grant CP-FP-INFSO224012 (TIME project), the project NEMESIS (Neurocontrolled Mechatronic Hand Prosthesis) funded by the Italian Ministry of Health, EU grant FP7-611687 (NEBIAS, NEurocontrolled BIdirectional Artificial upperlimb and hand prosthesiS), EU grant FP7-HEALTH-1602547 (EPIONE, Natural Sensory Feedback for Phan-tom Limb Pain Modulation and Therapy), the SwissNational Science Foundation through the National Center of Competence in Research Robotics, and the Bertarelli Foundation., European Project: 602547,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,EPIONE(2013), European Project: 611687,EC:FP7:ICT,FP7-ICT-2013-10,NEBIAS(2013), Ecole Polytechnique Fédérale de Lausanne (EPFL)-Fondation Bertarelli, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Inria Sophia Antipolis - Méditerranée (CRISAM)

Subjects
Neuroprosthetics, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Neural stimulation, Sensory feedback, [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract

International audience; OBJECTIVE:Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated.METHODS:To this aim, we performed a six months clinical study with three trans-radial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks.RESULTS:All the subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state.INTERPRETATION:The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings.

Published
2019

9. Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain

Author

Francesco Maria Petrini, Federica Barberi, Marko Bumbasirevic, Stanisa Raspopovic, Natalija Katic, Pavle Mijović, David Andreu, Sanja Mazic, Silvestro Micera, Dario Bortolotti, Asgeir Alexandersson, Thomas Stieglitz, David Guiraud, Aleksandar Lesic, Bogdan Mijovic, Paul Čvančara, Knut Lechler, Giacomo Valle, Vladimir Ilić, Center for Neuroprosthetics [Geneva] (CNP), Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Medecine [Belgrade], University of Belgrade [Belgrade], Fondation Bertarelli Chair inTranslational Neuroscience and Neuroengineering [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL)-Fondation Bertarelli, mBrainTrain [Belgrade], Bernstein Center Freiburg (BCF), Albert-Ludwigs-Universität Freiburg, SensArs Neuroprosthetics [Lausanne], Institute Mihajlo Pupin [Belgrade], Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Össur hf [Copenhagen], Clinical Centre of Serbia, Control of Artificial Movement and Intuitive Neuroprosthesis (CAMIN), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Department of Microsystems Engineering [Freiburg] (IMTEK), University of Freiburg [Freiburg], Scuela Santa Anna (SSSA), Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), Department of Health Sciences and Technology [ETH Zürich] (D-HEST), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), The authors are deeply grateful to the study participants who freely donated months of their life for the advancement of knowledge and for a better future for traumatic leg amputees. Thanks are also due to T. Palibrk for helping during the surgical implantation/explantation of the TIMEs and M. Marazzi for helping during the data analysis. European Research Council grant no. 759998 (FeelAgain), European Commission grant no. 754497 (SensAgain) and Swiss National Science Foundation grant no. 176006 (SYMBIO-LEG) funded this research., Center for Neuroprosthetics and Institute of Bioengineering, EPFL.-Fondation Bertarelli, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Inria Sophia Antipolis - Méditerranée (CRISAM)

Subjects
0301 basic medicine, medicine.medical_specialty, prosthetic knee-joint, energy-cost, Stimulation neurale sélective, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, Population, Stimulation, Sensory system, General Biochemistry, Genetics and Molecular Biology, [SPI.AUTO]Engineering Sciences [physics]/Automatic, Neuroprothèses, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Sensation fantôme, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Amputation, Tibial nerve, education, time, gait symmetry, education.field_of_study, business.industry, lower-limb amputations, General Medicine, medicine.disease, Metabolic cost, 3. Good health, Preferred walking speed, 030104 developmental biology, efficiency, 030220 oncology & carcinogenesis, balance confidence, interface, business, Phantom pain, performance, Neuroprostheses
Abstract

Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue1–4. The lack of physiological feedback from the remaining extremity to the brain also contributes to the generation of phantom limb pain from the missing leg5,6. To determine whether neural sensory feedback restoration addresses these issues, we conducted a study with two transfemoral amputees, implanted with four intraneural stimulation electrodes7 in the remaining tibial nerve (ClinicalTrials.gov identifier NCT03350061). Participants were evaluated while using a neuroprosthetic device consisting of a prosthetic leg equipped with foot and knee sensors. These sensors drive neural stimulation, which elicits sensations of knee motion and the sole of the foot touching the ground. We found that walking speed and self-reported confidence increased while mental and physical fatigue decreased for both participants during neural sensory feedback compared to the no stimulation trials. Furthermore, participants exhibited reduced phantom limb pain with neural sensory feedback. The results from these proof-of-concept cases provide the rationale for larger population studies investigating the clinical utility of neuroprostheses that restore sensory feedback. A new prosthetic leg that can transmit sensory signals via implanted electrodes is shown to restore meaningful sensory feedback that improves walking performance and lowers phantom limb pain during use in two human lower-limb amputees.

Published
2019
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10. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

Author

Silvestro Micera, Stéphanie P. Lacour, Ivan R. Minev, Eduardo Martin Moraud, Jerome Gandar, Quentin Barraud, Peter Detemple, Rubia van den Brand, Jocelyne Bloch, Andrea Mortera, Julie Kreider, Felix Schmitz, Grégoire Courtine, Nadia Dominici, N. V. Pavlova, Erwan Bezard, Laetitia Baud, Camille G. Le Goff, Silvio Kraus, Arthur Hirsch, Marco Capogrosso, Jack DiGiovanna, Leonie Asboth, Oliver Haverbeck, Pavel Musienko, Simone Duis, Nikolaus Wenger, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], International Paraplegic Foundation Chair in Spinal Cord Repair, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Neurology with Experimental Neurology, Bertarelli Foundation Chair in Translational Neuroengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL)- Center for Neuroprosthetics and Institute of Bioengineering, Motor Physiology Laboratory, Pavlov Insitute of Physiology, Laboratory of Neuroprosthetics, St Petersburg State University (SPbU), Laboratory of Neurophysiology and Experimental Neurorehabilitation, Children's Surgery and Orthopedic Clinic, Department of Nonpulmonary Tuberculosis, Institute of Physiopulmonology, The BioRobotics Institute, Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), MOVE Research Insitute Amsterdam, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Fondation Bertarelli Chair inTranslational Neuroscience and Neuroengineering [Lausanne], Center for Neuroprosthetics and Institute of Bioengineering, EPFL.-Fondation Bertarelli, Micromotive GmbH, Mainz, Germany, Université Paris Diderot - Paris 7 (UPD7), Fraunhofer Institute for Chemical Technology (Fraunhofer ICT), Fraunhofer (Fraunhofer-Gesellschaft), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Motac Neuroscience, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Publica, VU University Amsterdam, Research Institute MOVE, and Coordination Dynamics

Subjects
Genetics and Molecular Biology (all), 0301 basic medicine, medicine.medical_specialty, Neurology, Time Factors, [SDV]Life Sciences [q-bio], Medicine (all), Biochemistry, Genetics and Molecular Biology (all), Biochemistry, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Gait (human), Lumbar, SDG 3 - Good Health and Well-being, Feedback, Sensory, medicine, Animals, Computer Simulation, Muscle, Skeletal, Spinal cord injury, Spinal Cord Injuries, Motor Neurons, Spinal Cord Stimulation, Proprioception, business.industry, Motor control, General Medicine, X-Ray Microtomography, Spinal cord, medicine.disease, Evoked Potentials, Motor, Neuromodulation (medicine), Biomechanical Phenomena, Hindlimb, Rats, Kinetics, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, Rats, Inbred Lew, Evoked Potentials, Motor/physiology, Feedback, Sensory/physiology, Female, Hindlimb/innervation, Hindlimb/physiopathology, Locomotion/physiology, Motor Neurons/physiology, Muscle, Skeletal/innervation, Muscle, Skeletal/physiopathology, Spinal Cord/physiology, Spinal Cord Injuries/pathology, Spinal Cord Injuries/physiopathology, Spinal Nerve Roots/physiopathology, business, Spinal Nerve Roots, 030217 neurology & neurosurgery, Locomotion
Abstract

International audience; Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

Published
2014

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