Annual Report 2019 Key Figures - 2019 Table of Contents

Annual Report 2019 Key Figures - 2019 Table of contents

1 Editorial ��page 4 CLINICAL INVESTIGATION Highlights ��page 6 CENTRE 4 RESEARCH A unique model �� page 11 FIELDS OUR SCIENTIFIC STRATEGY ��page 12 143 Paris Brain Institute teams ��page 14 CLINICAL TRIALS Cellular and molecular neurobiology ��page 16

Integrative neurophysiology �� page 18 10 CORE Cognitive neuroscience �� page 20 13 FACILITIES CLINICAL Clinical and translational neuroscience ��page 22

RESEARCH Neuroinformatics ��page 24

INFRASTRUCTURES Core facilities of the Paris Brain Institute ��page 26

Technological advances ��page 28

RESEARCH TEAMS 25 RESEARCH APPLICATIONS �� page 30 CLINICAL RESEARCH AND CARE : START-UPS 31 patients at the heart of our priorities �� page 34 INCUBATED

14 PRESTIGIOUS FUNDING FROM EDUCATION AND TRAINING ��page 40

THE EUROPEAN RESEARCH 686 PEOPLE AT THE The Paris Brain Institute, its national and international network �� page 44 COUNCIL (ERC), 3 IN 2019 PARIS BRAIN INSTITUTE

LIFE AT THE PARIS BRAIN INSTITUTE �� PAGE 46 6 MARIE SKLODOWSKA-CURIE 43 NATIONALITIES Sharing and passing along knowledge ��page 47 ACTIONS FELLOWSHIPS OF THE EU POST-DOCS 60 �� HORIZON 2020 PROGRAMME Patronage, donations and bequests page 50

Corporate social responsibility �� Page 52 MORE THAN 500 112 PHD STUDENTS Governance �� page 54 PUBLICATIONS IN INTERNATIONAL 102 ADMINISTRATIVE STAFF Financial report �� page 57 JOURNALS 48 MEDICAL AND Thank you ��page 61 96 GRANTS OBTAINED PARAMEDICAL STAFF COLLABORATIONS WITH MORE 134 RESEARCHERS THAN 1000 INSTITUTIONS AND TEACHER-RESEARCHERS 194 ENGINEERS AND TECHNICIANS 36 TRAINEES AND WORK-STUDY STUDENTS Editorial

Prof. Gérard Saillant, President of the Paris Brain Institute

t the Paris Brain Institute, we come together around shared values that are at the core of our daily activities. We share an innovative Prof. Alexis Brice, and ambitious project that bring women and men with different Chief Executive talentsA and backgrounds together, for whom sharing means progress and a “ of the Paris Brain Institute means of achieving our goal towards the greater good: searching, finding, and curing. As you will discover in this 2019 Annual Report, the past year was filled with advances on a scientific, clinical and societal level. This was made – what a year! Many possible by the many individuals involved in our project: researchers, donors, 2019 changes took place on and partners, who helped carry our Institute to the forefront of research in “ both a scientific and administrative level and neuroscience in Europe and abroad thanks to their work and dedication. thanks to the hard work of the Paris Brain As our Institute celebrates its 10-year anniversary, it is time to launch a new Institute’s teams as a whole, we can be very phase of our growth. We therefore decided on a change that reflects this: in proud of the results of this past year. The 2020, ICM becomes the Paris Brain Institute. A simple name that reflects the development of a new Mixed Research Unit clarity we are hoping to bring as we open to society and its neuroscience (UMR) with our public partners and a new research challenges. The ICM acronym will remain, in honor of our history administration, as well as the renewal of our and our important breakthroughs on the nervous system and its diseases in University-Hospital Institute accreditation the past 10 years. Our name may change, yet our research missions remain following an international assessment by the National Research Agency on course. (ANR), highlight our scientific credibility as well the financial credibility of I would like to extend my sincerest thanks once again. We have gotten to our public-private partnership model and its results. We acquired a building where we are together, and together, we will take the Paris Brain Institute located at rue du Chevaleret to grow further and improve research transfer, to new heights.” a sign of the Institute’s scientific, commercial, and financial growth. 2019 was also the year 13 iCRIN, neuroscience clinical research infrastructures, were designed. They are a testament to the Paris Brain Institute’s involvement in clinical research and illustrate the close proximity with the medical community at the Neuroscience Medical University Department of Pitié- Salpêtrière Hospital. Corinne Fortin, 2019 was also the year of the Open Brain School certified as “training Secretary General he Paris Brain Institute is a unique ecosystem at the organization” which brings together all our teaching and training programs. of the Paris Brain Institute heart of Paris. It is a prime example of a successful We have cause to celebrate the advances of our research teams, with an even partnership between a private foundation and a greater number of publications in high impact factor scientific journals, “T public research unit, located in the largest neurological hospital success in obtaining national and international awards and funding and in Europe. Since it was built, its excellence has been highlighted especially three new ERC (European Research Council) grants, highly on numerous occasions: with the IHU program, Carnot competitive grants that highlight the quality of our researchers’ work. accreditation, and more recently French Tech Seed certification, Now is the time for continued effort to reach even further. We must continue first of its kind for a research institute. This was made possible to recruit talented researchers to support our dynamic and cutting-edge thanks to the hard work of research teams and platforms on a ecosystem. We must focus on developing new technology to have the best daily basis and with administrative support. instruments at our disposal and achieve even greater breakthroughs. We must Administrative service and support staff help design a also look at nervous system functioning and diseases under novel angles, meticulous, simple, flexible and dynamic framework that frees which requires teaming up with experts in multiple fields. Our strength lies researchers from useless constraints and opens new funding in getting researchers to work together in an interdisciplinary manner to opportunities for ambitious projects. bring new concepts to life.” The Institute is experiencing continued growth both on a scientific level and in terms of resources, as you will discover in this 2019 Annual Report. To stay in line with this dynamic, we must focus on applying « rigorous flexibility » to our actions. We will continue to strive towards lightening the administrative load for our researchers and remaining firm in our respect of regulations and our standards of excellence for our organization.”

ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 5 Paris Brain Institute receives A Parkinson’s disease project wins the certification as part of the “French Health data hub call for projects! Tech Seed” The NS-Park project of the Paris Brain Institute is The Paris Brain Institute has just been selected and one of the winners of the “Health Data Hub” call certified by the State as part of the “French Tech for projects by the Ministry of Solidarity and Health, Seed” Fund managed by Bpifrance. This certifica- with the aim of facilitating interactions between tion confirms the dynamic strategy undertaken by producers of health data , users and citizens, with its iPEPS bio-incubator towards entrepreneurship, the utmost security for the development of re- Highlights with strong field-wide expertise in neurology and search innovations. It is coordinated by Professor psychiatry. Jean-Christophe Corvol (Sorbonne University / In 2019, the Paris Brain Institute welcomed two new team APHP), team leader at the Paris Brain Institute and neurologist at Pitié-Salpêtrière Hospital, in colla- leaders: Nathalie Cartier, head of the “Gene and cell therapy” boration with Stanley Durrleman (INRIA), team team and Jaime de Juan-Sanz, holder of the Diane Barrière Chair leader at the Paris Brain Institute and coordinator of the neuroinformatics center, Prof. Florence Tu- “Molecular physiology of synaptic bioenergetics”. bach, epidemiologist at Pitié-Salpêtrière Hospital, Prof. Olivier Rascol and Dr. Maryse Lapeyre-Mestre of Toulouse University Hospital. Its aim is to provide neurologists with an instrument that predicts individual trajectories of Parkinson’s patients in order to implement appropriate preventive measures. The data from this cohort of 20,000 individuals monitored in centers dedicated to Parkinson’s ne of the things I really enjoy about the Paris Brain disease will be linked to data from the National Institute is the concentration of forces and means on Healthcare Data System (SNDS) in order to im- neuroscience. The idea that all my colleagues are “ prove overall patient care. Oconducting very different research ranging from clinical trials Visit of Raymond G. Chambers, WHO to molecular biology, networks, and diseases is very exciting! ambassador for global strategy It is a great place to learn about all the aspects of neuroscience 2019 Philanthropy Award: Paris Brain I am not an expert in, but also to have the opportunity to help On April 4, 2019, the Brain Institute hosted Ray- Institute and Euryale AM are winners! others with my knowledge of molecular neurobiology, imaging mond G. Chambers, WHO ambassador for global and biosensors.” strategy and American philanthropist, for a visit The Paris Brain Institute and Euryale Asset Mana- Jaime de Juan-Sanz and meetings with Institute researchers. He res- gement were awarded the Grand Prize for Philan- ponded to an invitation from Jean Todt, vice-pre- thropy thanks to their joint initiative to finance and sident of the Paris Brain Institute. As WHO ambas- philanthropy together: the SCPI Pierval Santé Sha- sador, Raymond G. Chambers aims to help this ring Fund. international organization bring the international hy the Paris Brain Institute? Its environment, of community together to advance global health course. Collaborations with research teams and action within the framework of the sustainable The Paris Brain Institute receives the clinicians, access to clinical research, to patients, development goals set for 2030 by the United BFM RMC Organization Award at the Wthe Clinical Investigation Center and the iPEPS. This whole Nations. “ BFM AWARDS ecosystem fosters research and scientific and medical advances. This energy is also very important for establishing industrial For the 15th edition of the BFM Awards, the Paris partnerships. Pitié-Salpêtrière Hospital is an international Brain Institute, represented by its founders Profes- benchmark. I think the Paris Brain Institute can become an sor Gérard Saillant and Jean Todt, received the essential location in terms of neuroscience research and clinical RMC BFM association award. work.” Nathalie Cartier (Inserm)

6 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 7 Awards and distinctions obtained by our researchers in 2019

Lamia Bouslama Sinead Gaubert (AP-HP) (Sorbonne Université) Team “Aramis: algorithms, Team “Myelin plasticity and models and methods for CAP’CARNOT: The Paris Brain Institute plastic neurological syndromes regeneration” Stéphanie Baulac (Inserm) human brain imaging and Carnot annual summer partners with two university caused by autoimmune reactions”. — Marie-Ange Bouvet- Team “Genetics and signals” meeting at the Paris Brain hospital research projects Their aim is to develop diagnostic Labruyère Award physiopathology in epilepsy” — 2019 Philippe Chatrier Institute tools for these diseases and improve — Michael Foundation Award Two projects in which the Paris Brain patient care. International Epilepsy The association of Carnot institutes Institute is a partner are among the Research Award organizes Cap’Carnot, a meeting of 15 recipients of the fourth call for pro- — Robert Debré organization the Carnot institutes with innovation jects for University Hospital Research Launch of the Paris Brain for medical research Award leaders, on a yearly basis. This year, (RHU). The COZY project, led by Dr Institute’s first masterclass the event took place at the Paris Guillaume Canaud and involving Sté- on creativity Brain Institute, also a member of the phanie Baulac (Inserm), team leader Carnot network. The 2019 edition of at the Paris Brain Institute, aims at The Paris Brain Institute offers a wide this meeting showcased artificial in- developing new treatments for dis- range of training and education for telligence technologies applied to harmonious overgrowth syndrome, a neuro-experts and “neuro-curious”. healthcare including biomonitoring, rare disease. The BETPSY project, led Teaching benefits innovation and the neuroscience research, medical dia- by Jérôme Honnorat, with the colla- individual and at the Paris Brain Ins- Claire Wyart (Inserm) gnosis, machine learning and medical boration of Dr Agusti Alentorn of the titute, we believe it all starts with the Team “Spinal sensory signaling” Julia Sliwa (CNRS) imaging. Experimental Neuro-Oncology team, brain. Organized with scientists from — Voted in as member Team “MOV’IT: movement, is tackling “encephalitis and paraneo- the Paris Brain Institute and experts of EMBO, the European investigation, therapeutics, from the American Society for Neu- Molecular Biology normal and abnormal roscience, the aim of this masterclass Organization Catherine Lubetzki movement: physiopathology was to uncover the secrets of creati- (Sorbonne Université/AP-HP) and experimental therapy” vity and introduce participants to Team “Remyelination in — International Peter and their creative potentials and those of multiple sclerosis: from biology Patricia Gruber Award from their colleagues. to clinical translation” the Society for The Paris Brain Institute obtains renewal and — 2019 Charcot Award from Neuroscience additional funding for its IHU program the Mulstiple Sclerosis The Symbiosis Prize for International Federation short scientific film goes to The Paris Brain Institute obtained a 17-million-euro renewal of (MSIF) a Paris Brain Institute its IHU program. This renewal highlights the scientific, medical researcher and economic efficiency of the “IHU model” implemented in 2010 following a call for projects from the Ministry Nathalie Magne, post-doctoral fellow of Higher Education and Research and the Ministry in the “Genetics and Development of of Health, as part of the investments for the future Ninon Burgos (CNRS) Brain Tumors” team, won the Sym- program to strengthen the French attractiveness Team “Aramis: algorithms, biosis competition with director in the field of medical research. The goal is to pro- models and methods for Cyprien Bisot at the Pariscience In- vide France with several centers of excellence in human brain imaging and ternational Scientific Film Festival for research, care, training and technology transfer in signals” her short film “A glioma to healthcare. The Government confirms its support for — Cor Baayen Young Bassem Hassan (Inserm) Team demolish”. biomedical research, a major issue for the country’s com- Researcher Award “Brain development” petitiveness, development of knowledge, innovation, and the — 2019 Roger de Spoelberch improvement of scientific and medical practices. Award

8 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 9 2019 Marie Sklodowska-Curie Actions This year, 6 young researchers from the Paris Brain Institute were awarded a A unique model Marie Sklodowska-Curie Actions (MSCA) postdoctoral fellowship among 1,500 European laureates, with a total of 21 scholarships since the creation Tomorrow’s medical care is at the heart of today’s sion to the fight against nervous system diseases of the Institute. The Marie Sklodowska-Curie Actions (MSCA) scholarships research at Paris Brain Institute thanks to the incre- on a daily basis. A multicultural and multidiscipli- are part of Horizon 2020, the EU’s framework program for research and inno- dible synergy between 25 research teams, state- nary environment come together with a successful vation. They are awarded to excellent postdoctoral researchers as well as of-the-art platforms, the Clinical Investigation blend of private and public culture for optimal effi- exceptional doctoral and postdoctoral training programs. Center, the Medical University Neuroscience De- ciency! As a joint research unit (UMR) and with its partment and the entrepreneurial ecosystem public partners (INSERM, CNRS, Sorbonne Univer- enabled by its business incubator. sité, AP-HP), Paris Brain Institute’s governance is Three ERCs for the Paris Brain Institute in 2019 Paris Brain Institute is above all a human endeavor, founded on a strong partnership between public fueled by a community of experts who bring pas- and private stakeholders. Every year, the European Research Council (ERC) pro- In this ranking by scientific excellence, the Paris Brain motes the best scientific projects through competitive Institute is continuously positioned at the forefront. Since calls for projects open to all researchers from the Euro- 2012, our researchers have obtained 14 European grants pean economic community. These grants support high- for projects ranging from fundamental research to better Under level exploratory research. According to the President of understand the development and functioning of the heal- stan ding the ERC, Professor Jean-Pierre Bourguignon, “since 2007, thy brain to applied research for neurological and psy- the dge ne the European Research Council has funded the most chiatric pathologies. In 2019, three researchers from our le rvo ow us daring research projects and an independent evaluation Institute were among the best in Europe and recipients kn s on ys has shown that this strategy has paid off. Researchers of the ERC grant. These results highlight the quality of g 25 research teams in te in 22 000 m2 of laboratories. m from across Europe are able to develop their best ideas the research conducted at the Institute and the resear- ss A training school: a a nd P Open Brain School. i for tomorrow’s breakthrough discoveries. “ chers recruited. 700 top researchers and ts d physicians from around the world. is e a s e s A strong link with Sorbonne 10 technological st including University, 1 French platforms 1 • Jaime De Juan Sanz, a young re- • Fabrizio De Vico Fallani (INRIA), • Daniel Margulies (CNRS), resear- university in the Shanghai neuroimaging platform

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10 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 11 Scientific strategy that addresses the challenges of brain research

PROF BASSEM HASSAN, PARIS BRAIN INSTITUTE RENEWAL OF THE JOINT RESEARCH UNIT SCIENTIFIC DIRECTOR OF THE PARIS BRAIN INSTITUTE

On January 1, 2019, the Paris Brain Institute entered a new “The ambition of the Paris Brain mandate of its Joint Research Unit (UMR). The initial strategic Institute to become the world’s choices of the Paris Brain Institute were based on specific leading brain research institute research objectives and on a uniquely valuable environment to depends on two main pillars that we address challenges raised by neuroscience and its diseases. are currently building. The institute has succeeded in integrating basic neuroscience The first pillar is encouraging research that ques- research specialists and high-level clinical research expertise tions dogma, takes risks, research that is allowed to fail and try once more, and recruiting and rewar- in one place. The UMR renewal confirms the Paris Brain ding people who dare to challenge existing models. Institute’s ambitious scientific and medical strategy of The major discoveries that make a difference are by definition unexpected and unpredictable. Going we want to break down the traditional barriers of increasingly multidisciplinary approaches, a truly unique on charted paths with a step by step approach is “basic”, “translational” and “clinical” research. This positioning in its field. The Paris Brain Institute is organized still necessary to advance our understanding of a outdated vision slows progress and creates obs- problem, yet it is rarely, if ever, the source of new tacles to finding original and effective solutions to into 4 research domains: molecular and cellular, paradigms. The challenges of brain diseases and important problems. We also want to break down neurophysiology, cognition, clinical and translational. The their increasing cost for patients, their families and the barriers between idea-driven research and society in general show how essential it is for us technology-driven research. Technological pro- great flexibility between these fields is a cornerstone of our to challenge existing paradigms and to rework our gress almost always creates opportunities to ask scientific and medical growth. Many internal programs, models. and answer new questions, reach a deeper understanding, get a clearer picture of the situation and including Big Brain Theory, accelerate interactions between The second pillar is creating an open environment get things done faster. research areas. Strengthening the robust relationship between in which people who take an interest in the brain as a whole, from molecules to networks, cognition Today, the timespan between an initial discovery research teams, technological platforms, clinical research and disease, work together to create a virtuous and its benefit to society is around 30 years. Our through certified ICRIN centers is also a major ambition of our circle of knowledge from patients’ bedsides to a ambition is to cut this time in half and we stron- laboratory environment. At the Paris Brain Institute, gly believe that our vision is the best way to scientific and medical strategy. achieve it.

12 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 13 SCIENTIFIC STRATEGY

MOTIVATION, BRAIN AND BEHAVIOR Mathias Pessiglione (Inserm), Paris Brain Institute Sébastien Bouret (CNRS) and Jean Daunizeau (Inserm) Competitive grants received in Supporting research and its funding teams 2019: ANR-PRC, Région Ile-de- France, FRM Research institutes have developed a dynamic financial ALS : CAUSES AND MECHANISMS OF MOV’IT: MOVEMENT, REPAIR IN MULTIPLE SCLEROSIS: strategy to cope with the ever-changing regulations of public ARAMIS: ALGORITHMS, MODELS MOTOR NEURON DEGENERATION INVESTIGATION, THERAPEUTICS. FROM BIOLOGY TO CLINICAL financial support and to adapt to the industrial environment, AND METHODS FOR IMAGES AND Séverine Boillée (Inserm) NORMAL AND ABNORMAL MOTOR TRANSLATION where new trends and new needs arise close to daily. The SIGNALS OF THE HUMAN BRAIN Competitive grants received in CONTROL : MOVEMENT DISORDERS Catherine Lubetzki (Sorbonne Department of Medical and Scientific Affairs of the Paris Brain Olivier Colliot (CNRS) and Stanley 2019: ANR-PRC, ARLSA, SLA AND EXPERIMENTAL Université/AP-HP) and Bruno Institute (DAMS) is home to a grants office that offers Durrleman (Inria) association THERAPEUTICS Stankoff (Sorbonne Université/ numerous services to the Paris Brain Institute community. It is Competitive grants received in Marie Vidailhet (Sorbonne Univer- AP-HP) proactive to help build new external collaborations with the BASIC TO TRANSLATIONAL 2019: ERC Consolidator, ANR-JPND sité/AP-HP) and Stéphane Lehéricy Competitive grants received in Paris Brain Institute. With a wide range of skills, DAMS offers NEUROGENETICS (Sorbonne Université/AP-HP) 2019: FRM, ARSEP EXPERIMENTAL NEUROSURGERY sourcing and engineering assistance to obtain competitive Giovanni Stevanin (Inserm/EPHE) Competitive grants received in Brian Lau (CNRS) and Carine national, European and international research grants. and Alexandra Durr (Sorbonne MYELIN PLASTICITY AND 2019: ANR-FLASH, GIS-IBISA, Karachi (Sorbonne Université/ Université/AP-HP) REGENERATION APTES, ANR-PRC, ANR-JCJC, AP-HP) Competitive grants received in Brahim Nait-Oumesmar (Inserm) ANR-ERA NET E-RARE, France Competitive grants received in 2019: Ataxia UK, Fondation Agir and Violetta Zujovic (Inserm) Parkinson 2019: MSCA-IF/GF, ANR-PRC, pour l’Audition, ARSEP, AFAF, Competitive grants received in €18,40 million ANR-LABCOM, FRM, CHU de in external competitive grant revenue in 2019 ASL-HSP France, Association CSC, CELLULAR PHYSIOLOGY OF 2019: ANR-PRC, ARSEP Rouen CORTICAL MICROCIRCUITS MOLECULAR PATHOPHYSIOLOGY PICNIC- PHYSIOLOGICAL since 2012 Alberto Bacci (Inserm) BRAIN DEVELOPMENT €103 million OF PARKINSON’S DISEASE INVESTIGATION OF CLINICALLY Competitive grants received in Bassem Hassan (Inserm) 3 prestigious ERC grants Olga Corti (Inserm) and Jean- NORMAL AND IMPARIED COGNITION 2019: FRM Competitive grants received in obtained by our researchers in 2019, for a total of Christophe Corvol (Sorbonne Laurent Cohen (Sorbonne Univer- 2019: ANR-PRC, Idex Sorbonne 14 since the creation of the Institute Université/AP-HP) DYNAMICS OF EPILEPTIC sité/AP-HP), Lionel Naccache Université, Fondation Roger de Competitive grants received in NETWORKS AND NEURONAL (Sorbonne Université/AP-HP) and Spoelberch, ARSEP 2019: Idex Sorbonne Université, EXCITABILITY Paolo Bartolomeo (Inserm) France Parkinson Stéphane Charpier (Sorbonne Competitive grants received in STRUCTURAL DYNAMICS OF ACRONYMS ASL-HSP France : Association Université), Mario Chavez (CNRS) 2019: MSCA-IF/GF, ANR-MRSEI, NETWORKS ALZHEIMER’S DISEASE AND PRION AFAF : Association française de Strumpell-Lorrain / Hereditary and Vincent Navarro (Sorbonne ANR-ERAPerMed, FRM Nicolas Renier (Inserm) l’Ataxie de Friedreich Spastic Paraplegia-France DISEASES Université/AP-HP) Competitive grants received in ANR-ERANET E-RARE : Shared Association CSC : Connaître les Marie-Claude Potier (CNRS) and FRONTLAB: FRONTAL FUNCTIONS Competitive grants received in 2019: MSCA-IF/GF, ANR-PRC, DIM European Program on rare diseases syndromes cérébrelleux Stéphane Haïk (Sorbonne Univer- AND PATHOLOGY 2019: ANR-PRC, Idex Sorbonne Mathinnov, Action on hearing loss ANR-ERAPerMed : National ARC : Association pour la sité/AP-HP) Richard Lévy (Sorbonne Univer- Research Agency – Transnational recherche sur le cancer Université, LRTCA Competitive grants received in sité/AP-HP) CELLULAR MECHANISMS OF Medical Project ARSEP : Association pour la ANR-FLASH : National Research recherche sur la sclérose en 2019: H2020, Institut de Veille GENETICS AND PHYSIOPATHOLOGY Competitive grants received in SENSORY PROCESSING Agency – Research practices and plaques sanitaire, Fondation Jérôme 2019: ANR-PRC, CNRS, ERC (CNRS) OF EPILEPSY Nelson Rebola open data ARSLA : Association pour la Lejeune, France Parkinson, France Éric Leguern (Sorbonne Université/ Consolidator Grant, FRC, Fondation Competitive grants received in ANR-IA-RHU : National Research recherche sur la Sclérose Latérale Alzheimer AP-HP) and Stéphanie Baulac pour la recherche sur Alzheimer, 2019: FRM Agency – Hospital-University Amyotrophique (Inserm) FRM Research DIM Mathinnov : Domain d’intérêt EXPERIMENTAL THERAPEUTICS OF GENE AND CELL THERAPIES Competitive grants received in ANR-JCJC : National Research majeur Math Innov PARKINSON’S DISEASE CIA: CONTROL – INTEROCEPTION Nathalie Cartier (Inserm) Agency – Young Researcher ELA research foundation : 2019: ANR-IA-RHU, AXA, FRM, Étienne Hirsch (CNRS) and - ATTENTION Competitive grants received in ANR – JPND : National Research European leucodystrophy ARDRM, Agency – Joint program in organisation Stéphane Hunot (CNRS) Philippe Fossati (Sorbonne 2019: ELA research foundation, neurodegenerative diseases ERC : European Research Council Université/AP-HP) Fondation Jérôme Lejeune, FRM, SENSORY SPINAL SIGNALING and Liane ANR-MRSEI : National Research FRM : Fondation pour la recherche Claire Wyart (Inserm) Schmidt (Inserm) AFSR Agency – European and médicale Competitive grants received in International Scientific Network GIS-IBISA : Infrastructures en GENETICS AND DEVELOPMENT OF DIANE BARRIÈRE CHAIR: 2019: Fondation NRJ, FRC Development biologie santé et agronomie NERVOUS SYSTEM TUMOURS “MOLECULAR PHYSIOLOGY OF ANR – PRC : National Research H2020 : European Horizon 2020 Emmanuelle Huillard (CNRS) and NEUROPHYSIOLOGY OF REPETITIVE SYNAPTIC BIOENERGETICS” Agency – Collaborative Research Program Marc Sanson (Sorbonne Université/ BEHAVIORS Jaime De Juan-Sanz Projects LRTCA : Laboratoire de recherche Assistance publique - en technologies chirurgicales AP-HP) Éric Burguière (CNRS) Competitive grants received in APHP : hôpitaux de Paris avancées Competitive grants received in Competitive grants received in 2019: ERC Starting Grant APTES : Association des personnes MSCA-IF/GF : Marie Skłodowska- 2019: ANR-IA-RHU, ARTC, APHP, 2019: FRM, Fondation de France concernées par le tremblement Curie actions - Individual and Cancéropôle Ile-de France, APHP, essentiel Global Fellowships (Europe) Ligue contre le cancer, Idex ARDRM : Association Robert Debré Sorbonne Université, ARC, FRM pour la Recherche médicale

14 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 15 SCIENTIFIC STRATEGY

The role of lymphatic vessels in Anti-inflammatory effect of neurodegenerative diseases cannabidiol, a non-psychoactive Cellular and molecular compound found in cannabis The lymphatic vascular system is present in nearly all tissues. It acts as a complement to blood ves- Cannabidiol (CBD), a non-psychoactive compound sels, ensuring the evacuation of waste as well as in cannabis, has the ability to limit immune system neurobiology immune surveillance within organs and tissues. cell response in various pathological inflammatory However, the lymphatic vascular system is absent contexts. Mauricio dos-Santos-Pereira and Patrick The teams focused on this line of research aim at deciphering the influence of genetics, from the brain and spinal tissue. Laurent Jacob Michel, in partnership with a team in Brazil, have dissecting the molecular machinery, establishing the role of different types of cells and and Jean-Léon Thomas, in collaboration with Nico- identified a key mechanism by which cannabidiol understanding the complex cellular interactions in normal or pathological conditions. las Renier, characterized the anatomy and func- exerts its anti-inflammatory effects. tions of vertebral lymphatic vessels for the very Dos-Santos-Pereira M, et al. Glia. October 2019 first time. They play a role in the transportation of A repertoire of unexplored DNA An important mechanism in myelin immune cells to lymph nodes, to which they are regions repair within the central nervous connected on a regional basis. The researchers Identification of genetic mutations system developed 3D mapping of this system and its orga- present in brain malformations A study led by Philippe Ravassard and Hélène Che- nization. They also highlighted the crucial role of associated with epilepsy val identified the spectrum of long non-coding When myelin, the insulating and protective sheath these vessels in the immune response to spinal RNAs in dopaminergic neurons, a primary target surrounding neurons, is damaged in the context cord injury. Malformations of cortical development (MCDs) are for degeneration in Parkinson’s disease. This reper- of demyelinating diseases such as multiple sclero- Jacob L, et al. Nature Communications. October major causes of pediatric intractable epilepsy. Sur- toire from unexplored areas of our genome is sis or spinal cord injuries, Schwann cells, res- 2019 gical resection of the epileptic foci is often the only extremely specific to dopaminergic neurons. Cha- ponsible for producing myelin in the peripheral treatment option for these children with epilepsy. racterizing the non-coding repertoires makes it nervous system, participate in central nervous Stéphanie Baulac’s team conducted a genetic ana- possible to assess the existence of an increased system lesion repair. Beatriz Garcia-Diaz and Anne The regulation of single gene lysis using DNA extracted from the postoperative relationship between these risk factors and specific Baron-Van Evercooren highlighted the mechanism determines the balance between sight tissue of 80 patients with MCD (collaboration with lncRNAs of dopaminergic neurons. If this relation- allowing the migration of Schwann cells in the spi- and smell Fondation Rothschild Hospital). Results highlight ship is proven, it could be a significant clue to help nal cord. the presence of so-called somatic mutations in explain the specific vulnerability of dopaminergic Garcia-Diaz B, et al. Acta Neuropathologica. April Finding a compromise between the size of visual several genes of the mTOR signaling pathway, res- neurons in Parkinson’s disease. 2019 and olfactory organs is common in animal evolu- ponsible for regulating brain development, in a Gendron J, et al. Scientific Reports. February 2019 tion, but the underlying genetic and developmental large subset of the cohort. Using a laser microdis- mechanisms remain unclear. A study conducted section approach on pools of cells, the team found A new therapeutic target to treat by Ariane Ramaekers and Bassem Hassan reveals that these somatic mutations were only present in spinocerebellar ataxias? that a single genetic variant that affects the deve- a few brain cells located within the malformation lopment of sensory organs in Drosophila (fruit flies) and displayed abnormal morphology. These results Spinocerebellar ataxias are genetic neurodegene- could explain the trade-off between the size of the are part of the emerging concept that the brain is rative diseases of the cerebellum and brainstem eyes and antenna. It may provide a fast track for like a mosaic, with each brain cell having its own that cause many motor disorders. The most pre- behavioral change and adaptation. The gene, unique DNA. These discoveries offer a new genetic valent form is SCA3, also known as Machado-Jo- eyeless / Pax6, is also found in invertebrates and framework for MCD-associated epilepsy, streng- seph disease. In her recent research, Nathalie Car- vertebrates, including humans. This discovery may thening the relationship between neuropathology tier-Lacave and her team discovered the crucial highlight a general mechanism in the compromise and genetics and guiding towards a precision- role of an enzyme that improves disease symptoms between the sizes of sensory organs within the based medical approach targeting somatic brain in mice. A European program (Erare) is underway animal kingdom. mutations. and coordinated by Inserm at the Paris Brain Ins- Ramaekers A, et al. Developmental Cell. July 2019 Baldassari S, et al. Acta Neuropathologica. Decem- titute to confirm these results on other models of ber 2019 ataxia and to assess the feasibility and tolerance of a potential treatment application in patients suffering from these severe genetic pathologies. Nóbrega C, et al. Acta Neuropathologica. June 2019

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Inhibitory autapses, modulators of Beneficial effects of coffee in treating cortical neural network activity dyskinesia Integrative A study conducted by Alberto Bacci’s team found A team from the neurology department of Pitié- that Parvalbumin-expressing basket cells (PV cells), Salpêtrière hospital (AP-HP) and Paris Brain Insti- a major type of cortex-inhibiting neurons that play tute, directed by Emmanuel Flamand-Roze and a part in several major cognitive functions, form a Aurélie Méneret, found that coffee has beneficial neurophysiology large number of synapses with themselves, called effects in treating abnormal movements due to a autapses. This auto-inhibition (autaptic inhibition) mutation in the ADCY5 gene in an eleven year-old The aim of the teams in this field is to better understand the physiology of is much stronger than the inhibition that these cells child. neurons and their networks under normal and pathological conditions. The exert on other neurons in the cortical network. This Méneret A, et al. Annals of Internal Medicine. Sep- approaches shared by the Institute’s different teams include molecular, cellular, mechanism influences coupling between the acti- tember 2019 electrophysiological methods and optical recordings, optogenetics and the vity of these neurons and gamma oscillations, a manipulation of neuronal activity through transcranial magnetic stimulation, as brain rhythm essential to sensory perception, at- well as computer models that link physiological recordings amongst themselves. tention, memory and other cognitive functions. Autaptic self-inhibition could therefore be an im- Cerebral anoxia and brain resuscitation in real time from inside neurons portant mechanism that underlies the essential role of these cells during sensory and other major Stéphane Charpier’s team described, for the very phalogram referred to as a “Wave of death”. This cognitive functions, with possible crucial first time, the real-time electrical changes that is the first time this wave has been on a neuronal consequences on certain cortical actions under occur simultaneously in neurons and an elec- scale. The team also highlighted a correlation physiological and pathological conditions. troencephalogram during death (due to cerebral between the shutdown of brainstem functions Deleuze C, et al. PLOS Biology. September 2019 anoxia, for example during cardiopulmonary arrest) (where vital functions are controlled) and the neu- and during an attempt at resuscitation. ronal process of imminent death. Re-oxygenation The study found that oxygen deprivation in the can reverse this process leading to a new brain Quantifying brain changes in brain halts synaptic activity followed by a leak in wave, never previously described, called a “Resus- progressive supranuclear palsy electrical current from the inside of the neurons, citation Wave”. Its occurrence is accompanied by creating a brain wave recorded in the electroence- recovery of synaptic activities in the brain and Progressive supranuclear palsy (PSP) is a clinically electrical properties of neurons. heterogeneous neurodegenerative disease. It This wave could constitute a reliable and reprodu- causes damage to the brainstem, leading to pro- cible real-time marker of recovery of neuronal and gressive loss of balance, eyesight, speech and cerebral functions as it is only observed in the mobility. There is currently no treatment for this event of successful resuscitation. The results obtai- disease, and one challenge for considering new ned by this team open up new perspectives for treatment strategies is to improve detection and real-time assessment of the chances of successful quantification of the development of neurodege- resuscitation in the context of cerebral anoxia. neration in patients. A study conducted by Nadya Schramm AE, et al. Progress in Neurobiology. De- Pyatigorskaya, Marie Vidailhet and Stéphane Lehé- cember 2019 ricy highlighted the potential of using an imaging method called quantitative MRI to assess brain degeneration in PSP in a non-invasive and precise manner even in the smallest brain structures including in brainstem nuclei. This method also allows clinicians to differentiate degeneration present in PSP from that of Parkinson’s disease. Pyatigorskaya N, et al. Movement disorders. 2019

18 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 19 Cognitive Neuroscience

The teams in this field combine structural, electrophysiological and functional studies to understand the functioning of neural networks on a whole brain scale as well as their importance in the onset of specific behaviors and cognitive processes in healthy individuals and in patients with neurological and psychiatric disorders.

The dynamics of our brain activity First ever identification of neurons in determine our state of consciousness the visual cortex that respond to faces Jacobo Sitt and collaborators found that signal coordination of brain activity determines state of A study led by Dr. Vadim Axelrod, head of the consciousness. They highlighted the link between Conscience and Cognition Laboratory at Gonda communication dynamics among different areas (Goldschmied) Multidisciplinary Brain Research of the brain on the one hand, and the level of Center at Bar-Ilan University (Israel), in collabora- consciousness on the other. These results represent tion with Lionel Naccache (Sorbonne University- an important breakthrough in understanding the APHP) and team at the Paris Brain Institute and at various states of consciousness or unconsciousness Pitié-Salpêtrière Hospital, was the first to find in encountered in non-communicating patients, and humans, neurons of the visual cortex within the © Stéphane Lehéricy could pave the way for unique treatments based face fusiform area respond much more strongly to on stimulation of patients with real-time analysis faces than landscapes or objects. of fluctuations in brain activity. Axelrod V, et al. Neurology. January 2019 Is intensive sports training beneficial Our color categorisation is not Demertzi A, et al. Science Advances. February 2019 for our health? language-dependent When narcolepsy makes you more creative! Everyone hears that physical activity is good for We use language every day to express our thoughts The first complete mapping of your health, but up to what level of training can and the way we view the world. But to what extent functional brain lateralisation Could sleeping make us more creative? Studying we go without damaging our brain? A study carried does language influence our thinking? In this individuals with narcolepsy, who have specific out by Mathias Pessiglione’s team in collaboration context, the perception of colors raises an interes- Certain processes within the brain are carried out access to REM sleep, could provide key information with INSEP (National Institute of Sports, Expertise ting question. The colors we see form a continuous preferentially in the right or left hemisphere of the for understanding this phenomenon. Isabelle Ar- and Performance) and the French Anti-Doping spectrum from purple to red. However, we draw brain. But which functions for which hemisphere? nulf’s team, in collaboration with a team from the Agency (AFLD) found that overly intense physical boundaries between different colors: red, purple, A Franco-Italian research team led by Michel Thie- University of Bologna in Italy, highlighted the exis- training harms brain capabilities and especially etc. The fundamental cognitive process of cate- baut de Schotten answers this question by creating tence of greater creativity in patients with narco- cognitive control. These results highlight that cere- gorisation refers to our ability to classify these the first complete mapping of lateralisation of brain lepsy. The study results suggest a link between a bral fatigue must be taken into account to prevent different shades of color under nominal categories. functions. Their results are the first to show that specific sleep phase, REM sleep, and creative abi- poor decision-making in economic, political or A study by Katarzyna Siuda-Krzywicka and Paolo decision-making, perception, and action as well as lities. This important breakthrough paves the way even judicial contexts. On a clinical level, the fa- Bartolomeo shows that there is no correlation emotion, mostly involves the right hemisphere. for understanding the cognitive function of sleep tigue related to cognitive control may represent a between our ability to name colors and our ability Symbolic communication, on the contrary, is based and the mechanisms of creative thinking. first step in the development of burn-out, observed to categorize them. These results suggest a pre- predominantly in the left hemisphere. Lacaux C, et al. Brain. July 2019 in all types of professional fields. verbal notion of colors. This novel idea is in line Karolis VR, et al. Nature Communications. March Blain B, et al. Current Biology. September 2019 with experiments carried out on animals and child- 2019 ren from four to six months who demonstrate an ability to categorise colors without the vocabulary to qualify them. Siuda-Krzywicka, K, et al. Cell Reports. 2019

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Early spinal cord damage in A multimodal approach for brain- individuals at risk of developing FTD/ machine interface optimization ALS “Brain-machine interface” is a generic term that A collaborative study led by doctors Giorgia Quérin includes the ability to use brain activity for inte- and Pierre-François Pradat from the Biomedical ractions with the outside world without going Imaging Laboratory (Sorbonne Université), the through muscles. It includes technologies such as Neurology department of Pitié-Salpêtrière Hospital neurofeedback - techniques used in neuroscience - APHP and the Paris Brain Institute highlights the to relax, modify stress levels, or other tasks, as well existence of early spinal cord damage in subjects as the possibility of controlling external objects at risk of developing frontotemporal degeneration using our brain, to write with our thoughts, to (FTD) or amyotrophic lateral sclerosis (ALS) as control a cursor on a screen, or a robotic arm, for Clinical and they carry a specific genetic mutation. Early brain example. If these technologies seem so powerful, damage before the age of 40 was found in a pre- why aren’t brain-machine interfaces used on a vious study by the PREVDEMALS cohort. These regular basis? One simple reason: they don’t work Translational new spinal cord injuries, visible only after the age all the time. In fact, it is currently very complicated of 40, may suggest the existence of primary brain to use these interfaces routinely, especially in cli- damage with subsequent diffusion to spinal struc- nical practice. A study conducted by Marie- tures. These results provide important information Constance Corsi and Fabrizio De Vico Fallani shows Neuroscience on the pre-symptomatic phase of the disease and how a multimodal approach for brain-machine are one step further towards developing early interface optimization could be of interest. Opti- The aim of clinical and translational research is to enable the development treatments. mization of these brain-machine interfaces sug- of predictive or progression markers and treatments for neurological and psychiatric Querin G, et al. Annals of Neurology. June 2019 gests that they may be used in clinical practice in diseases, from identification in simple laboratory modelling to clinical trials at the the coming years, for example in motor imagina- Paris Brain Institute’s Clinical Investigation Center and throughout the entire tion for motor skills recovery after a stroke. Institute. Clinical and translational research increasingly involves computational Neurological consequences of the Corsi MC, et al. Int J Neural Syst. February 2019 neuroscience, the joint analysis of clinical and biological data, and therefore requires Zika virus finally revealed development of novel mathematical and statistical approaches, a field called Towards diagnosis of predisposition Neuroinformatics. to Alzheimer’s disease using a blood Zika viral infection remains a global public health test issue. The identified pathogen is the Zika virus, Diagnosing Alzheimer’s disease in the Doc feeling: caregiver expertise transmitted by Aedes mosquitoes. Since 2007, The diagnosis of a person at risk of developing preclinical phase using contributes to improving diagnosis of numerous epidemics have been recorded in Asia Alzheimer’s disease is a major challenge in view electroencephalography patients in an altered state of and Africa and more recently in Central America of the increase in the number of cases expected consciousness and South America. Researchers and doctors are in the coming years due to extended lifespans. Diagnosing Alzheimer’s disease as soon as possible very familiar with the virus yet frequency of occur- Currently, detection of amyloid plaques in the brain is essential in order to provide early treatment for Teams from the Pitié-Salpêtrière hospital (AP-HP), rence of neurological complications, their clinical using imaging (positron emission tomography) is patients. However, there is currently no easy-to-use Inserm and the Paris Brain Institute found that the description and prognosis remain enigmatic. Teams a first step towards this diagnosis given that the technique for diagnosing Alzheimer’s disease in assessment of caregivers (nurses and nursing assis- of French researchers including Annie Lannuzel presence of these lesions constitutes an increased the preclinical phase, before symptom onset. Si- tants) regarding the state of consciousness of and Emmanuel Flamand-Roze of the Paris Brain risk of developing Alzheimer’s disease. At the Paris nead Gaubert, Federico Raimondo and Stéphane patients represents a real added value to medical Institute discovered the long-term effects of the Brain Institute, the team led by Marie-Claude Potier Epelbaum discovered early electrical changes in diagnoses and to electrophysiology and traditional virus. Long-term sequelae are common in Neuro- in collaboration with clinician and neurometabo- the brain measured by electroencephalography brain imaging exams. This research is based on the Zika and the patient’s viral status upon admission lism researcher Fanny Mochel identified a biologi- (EEG) in subjects with preclinical Alzheimer’s di- notion of “collective intelligence”. The study, ini- may inform the prognosis. These elements must cal blood profile 99.4% correlated to the presence sease within the INSIGHT-preAD cohort followed tiated by Gwen Goudard and Karine Courcoux, two be taken into account to adapt diagnosis and of amyloid plaques in the brains of subjects in- by Professor Bruno Dubois’ clinical research team nurses from the neurological intensive care unit at management of patients with NeuroZika. cluded in the INSIGHT study led by Pr Bruno Du- at the Memory and Alzheimer’s disease Institute. Pitié-Salpêtrière Hospital, involved over 80 care- Lannuzel A, et al. Neurology. January 2019 bois at the Paris Brain Institute and IM2A. These highly promising results suggest that EEG givers over more than a year. It demonstrates the Xicota L, et al. EBioMedicine. September 2019 may be used in the coming years for early detec- extraordinary motivation and enormous potential tion of preclinical Alzheimer’s disease. of paramedical research in the unit. Gaubert S, et al. Brain. July 2019 Hermann B, et al. BMJ Open. February 2019

22 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 23 Neuroinformatics

Neuroinformatics for tomorrow’s Neuroinformatics center expertise research and medicine Data analysis Medical research generates billions of data and the The center for neuroinformatics offers expertise advancement of technologies only increases the in biostatistics, mathematical modeling, and ma- number and the complexity of the data collected, chine learning for the analysis of multimodal data be it genetic, imaging or biological. Faced with the for use by teams at the Paris Brain Institute. challenges of this growing increase in data, scientists must develop the tools and methods neces- Data management sary to analyze and make the most of it. Implementation of standardized processes for neuroscience data organization of various types: geno- The Center for Neuroinformatics at the Paris Brain mics, electrophysiology, imaging, clinical, etc Institute aims at developing shared instruments and methods to manage and analyze all types of Software development neuroscience data. It enables all scientists, whate- Software for structuring and indexing heteroge- ver their field, to contribute to and benefit from neous data sets as well as data processing and interoperable databases and a shared portfolio of analysis tools. methods and instruments for analysis. Scientific computing One of the main assets of the Paris Brain Institute Management of servers and computing clusters is the ability to collect large amounts of medical dedicated to scientific data and biological data of all types and to know how to “give them a voice” thanks to powerful statistical Training & communication calculation tools and the collaboration of many The center for neuroinformatics develops a full players: researchers, engineers, doctors, computer range of training programs on statistical analysis scientists and technicians. Several multidisciplinary and modeling methods and software for Paris Brain projects combining genomics, neuroimaging, cli- Institute teams. It also organizes events to bring nical observations and data science are underway the scientific community together around neuroin- and focus on the effective use of artificial intelli- formatics issues and promote its activities on a gence. They constitute a great hope in improving regular basis. our understanding of the brain and its diseases, diagnosis, and assistance in developing tailored treatment.

24 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 NOTRE STRATÉGIESCIENTIFIC SCIENTIFIQUE STRATEGY

Core facilities of the 10 CORE FACILITIES AND BIOBANKS Paris Brain Institute

The progress and quality of science depends as much on technological progress as it does on good ideas. At the Paris Brain Institute, researchers and core facility managers work together to continuously monitor technological advances to offer the most advanced equipment and iVector CELIS techniques operated by highly competent staff to move brain research forward. iGenSeq customized lenti, Screening, cell culture, adenovirus, Crispr iPSC, electrophysiology Next generation sequencing Beyond providing innovative equipment, the mis- cal functional exploration, functional exploration, of RNA and DNA sion of the core facilities at the Paris Brain Institute bioinformatics and banks. is to pool skills and provide services and expertise for the entire scientific community: Institute re- The main activities of the Paris Brain Institute are search teams, external scientific teams, incubated three-fold: companies and outside companies as well. - Supplying equipment and services from project design to results analysis; Basic equipment is distributed according to re- - Maintaining cutting-edge technological research search areas and their scale of analysis: molecular and development in each area of expertise; exploration, cellular exploration, imaging, preclini- - Training for equipment use or implementing PhenoPark techniques. Histomics Preclinical functional processing of histological ICMQuant exploration, behavioural animal and human material analyses, surgery, conventional fluorescence electrophysiology microscopy, microscopy confocal laser scanning, bi-photonic microscopy, confocal rotating disk microscopy or transmission electron microscope

PRISME cognitive and social evaluation CENIR in ecological conditions and Center for NeuroImaging virtual reality Research: 3T MRI, PET-MRI, TMS, MEG- EEG, Gait analysis

iCONICS Databases and Datawarehouse, Genomics, Bioinformatics and Biostatistics

Biobanks biological ressource collection, DNA, plasma, cells, brain tissue

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Technological advances essential to scientific research

Updates in the organization of our New cutting-edge equipment technological core facilities To remain at the forefront of what technology can A new organization has been implemented for the offer to scientific and medical research, a priority Paris Brain Institute’s technological core facilities. for the Paris Brain Institute is to acquire expert Expert committees of Paris Brain Institute resear- equipment to support work of its entire scientific A publication in Nature on the PRISME core facility involved chers have been set up for each core facility to community. development of the Coelacanth skull in a study conducted by Mathias ensure that we are always at the forefront of what In 2019, the Paris Brain Institute acquired the Nova- thanks to the 11.7T MRI core facility Pessiglione’s team on neurocognitive technology has to offer to science. We are also seq 6000 ILLUMINA, the world’s most powerful consequences of physical moving towards simplifying interactions between short fragment DNA sequencer, for the iGenSeq The Latimeria coelacanth is a deep-sea animal rela- overexertion published in Current core facilities and the other services of the Paris core facility. The DNA and cell bank has equipped ted to terrestrial vertebrates. Since its discovery Biology Brain Institute to reduce administrative burden on itself with two new nucleic acid extraction 80 years ago, the study of coelacanths has yielded core facility staff so that they can devote them- machines. important information about the evolutionary A study carried out by Mathias Pessiglione (In- selves even more to developing their core facility A collaborative project with Nikon has enabled a changes in vertebrates that led to the appearance serm), team leader at the Paris Brain Institute, in activities. three-year loan of a high-resolution imaging sys- of tetrapods. It is the only current vertebrate to collaboration with INSEP (National Institute of Throughout 2019, core facility managers worked tem for high-content analysis. This system allows share anatomical characteristics with the fossil Sports, Expertise and Performance) and the French to put new core facility websites online, always high-speed acquisitions using confocal or wide forms of the Devonian (-410 to -360 million years), Doping Control Agency (AFLD) found that overly with the aim of increasing visibility for the incre- field mode as well as tailored acquisition and ana- ancestors of terrestrial vertebrates, and especially intense physical training harms our brain capabi- dible activity of our core facilities and the expertise lysis protocols, for different 2D / 3D cell culture a skull divided into two portions by an intracranial lities, especially when it comes to cognitive control. of staff who work there. models. joint. Thanks to the work of Mathieu Santin on the The study is a good illustration of how PRISME can The Paris Brain Institute’s Neuroimaging Research ultra-high-field MRI core facility (11.7 Tesla) at the explore all facets of human behavior, in this case Center (CENIR) has acquired a high-intensity fo- Paris Brain Institute, 3D images of coelacanth by combining physical effort and cognitive perfor- cused ultrasound treatment system (HIFU) for heads were obtained. In addition to this unique mance, in coordination with CENIR to study the patients with essential tremor. The first treatments instrument, we also used our specific skill set for neurobiological correlates of these cognitive in France are set to begin in 2020. tha analysis of these types of samples. We were mechanisms. able to generate a 3D image, in their entirety, of Source : Blain B, et al. Current Biology. Septembre two of the six models of the study, in particular 2019 the juvenile stage of the coelacanth. These images were then integrated into a structure segmentation Launch of research protocols in model to analyze its anatomical characteristics. collaboration with manufacturers These results provide novel information on the origin of coelacanth skull features and create new The SPAST industrial protocol (Pathmaker Neuro- research perspectives on the evolution of the ver- modulation Inc, Boston) is a randomized, control- tebrate skull. led, double-blind study aimed at evaluating a new Source : Dutel H, et al. Nature. 2019 medical device for the treatment of lower limb spasticity after a stroke. The GAIN industrial protocol (MindMaze, Lau- sanne) aims at evaluating a virtual reality device in motor recovery of the upper limb after a stroke.

ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 29 Research Applications

FRENCH TECH SEED By creating the “Deeptech fund”, a public investment fund of BY ALEXIS GENIN, 400 million euros focused on the “seed” sector (i.e. the first RESEARCH AND TECHNOLOGY OFFICE DIRECTOR stage of entrepreneurship after exiting the research project 2018 marked the launch of “Made @ ICM” initiatives, namely the stage), the Public Investment Bank (BPI) aims to promote the development of health products produced by or enabled by the development of a greater number of entrepreneurial projects Paris Brain Institute. The following year, 2019, saw the development of the first innovative small treatment molecules with based on highly innovative science. These “deeptech” projects France’s best medicinal chemists. At the same time, the Institute are meant to allow the proliferation of breakthrough decided to invest in a new building to accelerate medical technology development --- this is a true change of scale, with soon innovation throughout France. In order to detect these young to be three separate sites for the iPEPS incubator. The Healthtech yet promising technologies in the most organized way, the BPI Hub will be organized around three sites: The initial incubator at the heart of the Paris Brain Institute building, mainly for young relies on a limited number of structures with experts both in companies developing drugs research-accelerating instruments; science and in the support of innovative companies. They a space dedicated to digital health, hosted at Station F; and by the end of 2020, a new building halfway between the Paris Brain carry “French Tech Seed” certification and are responsible for Institute and Station F, made possible by the support of the City detecting and qualifying innovations of very young companies, of Paris and Ile-de-France. This unique space will welcome entrepreneurs from all horizons in an environment that is both modern following which the BPI grants seed funding of up to 250,000 and green, built around a skylight in a large central agora. euros to build the project. The Paris Brain Institute is currently Beyond quality of life, essential to the creativity of researcher- entrepreneurs, an integrated service offer will strengthen the the only French organization certified for its expertise in the relationship with the hospital environment by allowing access field of neuroscience entrepreneurship and represents a sign to the Institute’s platforms - and especially to its LivingLab – and will support innovators towards clinical research with the help of recognition and a true asset for both the start-ups it of “Neurotrials” experts… while facilitating even greater access supports and its entrepreneur researchers. to financing and investments. We are counting on an extraordinary year and cannot wait to present the next output of this great idea machine!

ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 31 RESEARCH APPLICATIONS

NEUROTRIALS and manages the test procedure. The of this unprecedented partnership. Proof through clinical perfect integration of NeuroTrials wit- 2019 was also the year of renewed research hin the Paris Brain Institute ecosystem trust by the Ile de France Region with and its proximity to expert clinicians funding for the continued develop- 2018 was dedicated to creating and is a major asset in supporting the heal- ment of incubator services and par- structuring the NeuroTrials team. 2019 thcare industry for clinical develop- tnership between the Paris Brain Ins- then saw the development of interac- ment of neurology and psychiatry titute and STATION F. Several of the tions with industrial partners in the products. incubated companies have taken field of drugs and medical devices. In important steps in their development: this framework, NeuroTrials supported WeFight and its virtual companion Vik Research the clinical development of a French IPEPS SME that plans to use its technology Full-fledged for fine characterization of gait disor- entrepreneurship ders (observed in many neurodege- Applications in 2019 nerative illnesses). NeuroTrials also iPEPS, the Paris Brain Institute’s inno- advises another young European vative business incubator, is located company focused on researching a at the heart of the Institute as well as metabolic approach to Charcot’s di- at STATION F, the world’s largest star- BIOTECH cules have been identified, one of cation to help patients cook using sease to “reposition” a drug already tup campus. Since 2012, the incubator medical drug gardeners which is, very interestingly, highly the “kitchen” tool to stimulate me- used for other purposes. Discussions has supported roughly fifty young raised an investment of 1.8 million toxic for tumor cells and not for heal- mory and help them regain their are also underway to develop gene innovative companies in developing euros, and Neurallys accelerated the 2019 was marked by an increasing thy cells. In 2020, these molecules and independence. therapy for Huntington’s disease their technology. development of its connected implant number of partnerships with industrial many others will be protected by The LivingLab (collaborative innova- based on the research of a team lea- In 2019, the incubator operated the thanks to a new investment of healthcare players in France and patents and offered to various par- tion organization) and the Workshop der from the Institute. Finally, 2020 “Pfizer Innovation France” endow- 750,000 Euros. abroad. The Paris Brain Institute has tners to secure the funding to conti- (rapid prototyping platform) also will see the launch of a “phase II” cli- ment fund’s first acceleration pro- Bioserenity, formerly incubated at the established a collaboration with ma- nue their development. created a panel of services to facilitate nical study offering a new option to gram. Four startups in the digital Institute, is the only healthcare start- nufacturer Nikon to develop robotic the “user-centered” innovation pro- treat patients with acute optic neuri- health field benefited from the sup- up to join the Next 40, an index crea- microscopes allowing high-speed cess of start-ups and large groups. For tis. The drug candidate, developed by port and resources of the incubator, ted by the French government in Sep- “subcellular” imaging capable of rea- MEDTECH example, the LivingLab was able to another young European company, as well as the expertise of the leader tember 2019 to track 40 French ching the depths of neuron functio- Medical technologies support Roche group employees wit- presents interesting neurotrophic and in the pharmaceutical industry. Buil- start-ups with very high potential. ning. Another collaboration was ini- designed for patient needs hin the framework of an intrapreneu- neuroprotective properties. Neuro- ding on the success of this first edi- Finally, six new companies joined tiated with a French SME to assess the rial program in designing a professio- Trials brings these partnerships its tion, which allowed these start-ups to iPEPS, including HealthyMind (a vir- protective potential of novel small 2019 was an important year for the nal mediation solution for those ability to identify the best clinical trial project themselves more rapidly both tual reality solution for pain manage- molecules that may help fight Parkin- development of “user-centered” tech- suffering from invisible illnesses. On design to quickly demonstrate pro- towards their market and on an inter- ment) and Cairn Biosciences from San son’s disease. A new experimental nology products. Throughout the year, its end, the Workshop supported the duct effectiveness, ensures patient national level, a second edition will Francisco to develop new drugs model was developed by researchers and in interaction with the physical prototyping of a robot designed by a protection with regulatory authorities, take place in 2020 with the renewal against addiction. at the Institute for this project, using and rehabilitative medicine depart- start-up to facilitate interaction with a small worm called C. Elegans whose ment of Pitié-Salpêtrière hospital and those suffering from neurodegenera- neurons carry the alterations found in the support of Medtronic and Hap- tive diseases. the disease. pyNeuron by SBT Human(s) Matter, Several patents were also filed during engineers and designers reflected the year, one of which is to protect a with caregivers and patients on solu- drug with promising effects for trea- tions to improve care and self-suffi- ting neurological dysfunctions linked ciency of patients suffering from brain to strokes. injury, especially following a stroke. The “sleeping beauties” project to Various solutions were drawn up assess the treatment potential of small including: molecules was strengthened by the - DocFeeling (project led by Dr Ben- creation of new strategic partnerships jamin Rohaut): collaborative appli- with medicinal chemistry research cation to facilitate monitoring of the institutes. Several families of mole- state of consciousness of intensive cules were assessed using cellular care patients by medical teams; models of pathologies such as Parkin- - Au fil des mots (project led by Agnès son’s disease or multiple sclerosis. Weill Chounlamountry): rehabilita- Screening of over 2,000 compounds tion support application to facilitate was also carried out to assess the abi- improvements in pronunciation and lity of these compounds to kill glio- lexical memory of stroke patients; blastoma cells (a highly aggressive - BRO (project led by the physical and brain tumor). Several promising mole- rehabilitation medicine team): appli-

32 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 33 Clinical research and care Patients at the heart of our priorities This progress in our organization has led to significant results in 2019. These include the start of several industrial therapeutic trials testing innova- At the Paris Brain Institute, tive therapies in rare neurodegenerative diseases everything is implemented to such as anti-sense oligonucleotides in Huntington’s disease and amyotrophic lateral sclerosis, or anti- develop synergies between clinical tau antibodies in progressive supranuclear para- and scientific fields, supported by lysis (2 trials completed in 2019). In addition, NeuroTrials has signed its first contracts with com- our Institute, the clinical CIC 2019 BY THE NUMBERS: panies for the development of medical devices in investigation center, and Pitié- gait assessment, for the treatment of pain in virtual 143 CLINICAL TRIALS IN 2019 reality, and for an innovative drug in optic neuritis. Salpêtrière hospital group. For years, In terms of academic studies, the NS-PARK cohort SLEEP DISORDERS----- a major effort has been underway to coordinated by the Paris Brain Institute has been 1 selected as one of the 10 Health Data Hub pilot structure clinical research within EPILEPSY ------projects, also demonstrating the Brain Institute’s 1 hospital services by providing Paris commitment to data sharing in the spirit of “open BY PROF JEAN-CHRISTOPHE CORVOL, NEURO-VASCULAR----- science”. Brain Institute thanks to the IHU 2 DIRECTOR OF THE CLINICAL INVESTIGATION NEUROPSYCHIATRY ------program. We can now consider our The challenge ahead, and one in which we can CENTER AT THE PARIS BRAIN INSTITUTE AND 3 keep improving, is to increase our inclusions in Institute as the driving force of TRAUMATIC BRAIN INJURY ------PROF JEAN-YVES DELATTRE, PARIS BRAIN clinical trials. For each patient that enters our cli- 3 clinical neuroscience research on the nical services, we must be able to help them “here INSTITUTE MEDICAL DIRECTOR AND PSYCHIATRY ------and now”, using available treatments, as well as Pitié-Salpêtrière site. 6 DIRECTOR OF THE NEUROSCIENCE MEDICAL- offering participation in clinical trials for innovative COGNITIVE NEUROSCIENCE ------treatments to increase our understanding of di- UNIVERSITY DEPARTMENT AT THE PITIÉ- In 2019, we officially launched iCRIN, the clinical 6 seases and their treatment. research infrastructure of the Paris Brain Institute, ALS------SALPÊTRIÈRE HOSPITAL to further this structuring of clinical research. We 8 can now give clinical teams the means to work in NEUROGENETICS ------a better environment as well as establish the 16 culture of the Paris Brain Institute and its transla- DEMENTIA ------tional research in hospital departments. Other tools 19 have also been implemented or developed to pro- NEURO-ONCOLOGY ------mote clinical research: Neurotrials, now including 20 a support unit for clinical research development, MULTIPLE SCLEROSIS ------Neurocatalyst, and the Big Brain Theory program 23 that brings clinicians and researchers together on MOVMENT DISORDERS --- breakthrough research projects. 35

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The Neuroscience Medical-University The 13 Clinical Research Department (DMU) Infrastructures (iCRIN) The Nervous System Diseases Hub at Pitié-Salpêtrière hospital was recently renamed as the at Paris Brain Institute Neuroscience Medical-University Department (DMU) in line with a reorganization of AP-HP. Sorbonne Université hospital departments. The aim of iCRIN infrastructures is to develop interactions and knowledge-sharing between team members of the Neuroscience Medical-University Department and Paris Brain Institute The 13 new medical-university departments replace • “Adult Psychiatry - Addictology” (Saint Antoine, research teams. The winners of this call for projects received “Clinical research infrastructure the 24 old hubs of Pitié-Salpêtrière-Charles Foix Tenon, Salpêtrière, Charles Foix); of the Paris Brain Institute” certification paired with funding to develop their project within hospital group and the university hospitals of eas- • “Physical medicine rehabilitation, Follow-up reha- the hospital. A call for projects was launched in Spring 2018 in hospital units for medical and tern Paris (Saint Antoine, Tenon, Trousseau, Roth- bilitation care (MPR-SSR)” (Rothschild and paramedical teams. Projects were assessed by the Scientific Advisory Board of the Paris Brain schild), now united as a single hospital system: Salpêtrière); Institute on criteria including expertise, performance, quality, visibility of the structure. Sorbonne University / AP-HP. Beyond activity • « Neurophysiology-neuropathology “ (Saint An- 13 projects were selected with an official launch in 2019, backed by Paris Brain Institute’s management and human resources, that remain toine, Salpêtrière, Charles Foix). Clinical Investigation Center. under the help of the MUD, the development of these new departments aims at improving their The Neuroscience DMU has the considerable ad- services, optimizing healthcare channels and deve- vantage of having a very strong thematic consis- The launch of the iCRINs now makes it possible to ALZHEIMER’S DISEASE loping teaching and research. tency and backing by very large research institu- support numerous clinical research projects in the tions (Paris Brain Institute, Institute of Myology), clinical services of the Neuroscience Medical Uni- Coordinator: Richard LEVY (AP-HP/Sorbonne and of being part of the Paris Brain Institute, the versity Department directly or indirectly linked to Université) Organization of the Neuroscience only Neuroscience IHU in the country. The integra- the Paris Brain Institute. This adds to the Institute’s In collaboration with the Institute of Alzheimer’s Medical-University Department tion of new units is an opportunity. By strengthe- historical partner services new prospects for col- and Associated Diseases (IM2A), this project aims ning the adult psychiatry-addiction and MPR-SSR laboration with other services at the Pitié-Salpê- to: identify novel cognitive markers and bring toge- The Neuroscience Medical-University Department units, it becomes possible to develop a true “pillar- trière Hospital (sleep, neurosurgery) but also at ther specific populations of patients; develop cli- includes 13 services or departments, for a total of based strategy” for the fields of “adult psychiatry” Saint Antoine (psychiatry, neurology, addictology), nical applications by increasing preclinical and 34 functional units. It is made up of 4 pillars: and “MPR”, alongside the already-large “Neuro- Rothschild Hospital (rehabilitation) and Tenon Hos- clinical trials and proof of concept studies. To do • “Neurology” (Saint Antoine and Salpêtrière); logy” pillar. pital (outpatient psychiatry). The Paris Brain Ins- so, we group and monitor patient cohorts suffering titute’s Clinical Investigation Centre team coordi- from neurodegenerative diseases. Their clinical, The department has 541 beds and spots, 249 medi- nates this activity by organising monthly meetings biological and neuroimaging data will be organized cal staff and 1054 paramedical and administrative with the ICRIN referents for each theme to share in a database. staff. The DMU also takes part in 14 rare disease experience, set up common procedures and report reference centers (including 8 as coordinator or activity indicators. These meetings with iCRIN refe- constitutive center) and 2 rare cancer reference rents, mostly project managers or clinical study PARKINSON’S DISEASE AND centers (coordinators). technicians, are also intended for training sessions. MOVEMENT DISORDERS These meetings are also an opportunity to take “The main goal of the DMU is to bring “care” and stock of the different missions of the ICRIN refe- Coordinator: David GRABLI (AP-HP/Sorbonne “academics” (teaching and research) together rents and to exchange on their possible difficulties Université) within medical and nursing teams. They enrich in order to offer them adequate assistance. The iCRIN specialized in Parkinson’s disease and each other. A second goal is to extend the “patient movement disorders benefits from a partnership care” aspect to the period preceding and fol- between the team led by Olga Corti and Jean- lowing hospitalization, which explains the impor- Christophe Corvol and the team led by Marie Vi- tance granted to the “healthcare channels” dailhet and Stéphane Lehéricy. Its two main objec- group.” tives are to identify biomarkers of disease severity, Prof Jean-Yves Delattre, director of the Neuros- its progression and response to treatment, and to cience Medical-University Department and Paris decipher the pathophysiological mechanisms un- Brain Institute’s Medical Director. derlying behavioral and motor control disorders in rare movement disorders.

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AMYOTROPHIC LATERAL SCLEROSIS NEUROGENETICS STROKES TRAUMATIC BRAIN INJURY (ALS) Coordinator: Alexandra DURR (AP-HP/Sorbonne Coordinators: Yves SAMSON (AP-HP/Sorbonne Coordinator: Éléonore BAYEN (AP-HP/Sorbonne Coordinator: François SALACHAS (AP-HP) Université) Université) and Charlotte ROSSO (AP-HP/Sor- Université) The ALS center in Paris is one of the largest in The NEUROLOP clinical research center, including bonne Université) Novel approaches to integrate multimodal data Europe, both in terms of new patients and patients reference centers for rare diseases from the Gene- The Stroke iCRIN has the following objectives: par- are crucial for monitoring brain vulnerability, indi- treated. It collaborates with several members of tics department of the hospital and Paris Brain ticipation and coordination of randomized control- vidual pathways and the evolution of head trauma Séverine Boillée’s team at the Paris Brain Institute. Institute teams, aims at deciphering phenotypes led trials, use of Big data to build a dynamic pro- (TBI). This iCRIN aims to structure and develop a The ALS iCRIN is composed of four main pillars: associated with genes involved in neurogenetics gnosis model of stroke outcome; identification of large prospective cohort of individuals affected by elucidating ALS triggering and identifying biomar- pathologies such as spinocerebellar ataxia and novel structural and functional markers of stroke a head trauma, multimodally explored (clinic, radio- kers; understanding propagation of motor neuron Huntington’s disease; is involved in clinical, ima- sequelae; development of innovative treatment logy, physiology) and to develop modeling of mul- dysfunction; discovering why compensation me- ging, biological and genetic data research; inno- approaches in rehabilitation, such as non-invasive timodal results, including by using statistical lear- chanisms for innervation remain in some patients; vative treatment trials in small rare disease cohorts; brain stimulation techniques and playful and inno- ning techniques. and studying the effect of opening the blood-brain and the transition between neurodevelopmental vative rehabilitation strategies (serious games, barrier with focused ultrasound in ALS. defects and programmed neuron loss in adulthood neurofeedback) or drug treatments. in neurogenetic diseases in collaboration with basic MULTIPLE SCLEROSIS research. NEUROLOGICAL INTENSIVE CARE ORTHOPEDIC SURGERY Coordinatosr: Catherine LUBETZKI (AP-HP/Sor- bonne Université) and Bruno STANKOFF (AP-HP/ Coordinator: Sophie DEMERET (AP-HP) NEURO-ONCOLOGY Coordinator: Hugues PASCAL-MOUSSELARD (AP- Sorbonne Université) The neurological intensive care unit is a structure HP/Sorbonne Université) The Multiple Sclerosis iCRIN is focused on trans- with extensive experience in the management of Coordinator: Ahmed IDBAIH (AP-HP/Sorbonne The clinical project of the Pitié-Salpêtrière orthope- lational development of remyelination strategies patients with acute disorders of the peripheral Université) dics department focuses on three main topics: to prevent progression of disability; development nervous system and / or the central nervous sys- The partnership between the neuro-oncology genetic causes of idiopathic scoliosis in collabo- of new imaging tools to assess strategies for repair tem. Its activity focuses on four major pathologies: department and a dedicated research team, led ration with Claire Wyart’s team at Paris Brain Ins- in patients with MS; development of treatments categorization and monitoring of consciousness by Marc Sanson and Emmanuelle Huillard at the titute; establishing a systematic database of pre- targeting the immune system; detection and un- disorders in collaboration with Lionel Naccache’s Paris Brain Institute, as well as a tumor bank (Onco- and postoperative neurological state for all patients derstanding of multiple sclerosis symptom phy- team; diagnosis and treatment of status epilepticus neurotek), a preclinical treatment research group in the spinal unit; developing various prospective siopathology, and development of new connected with the team led by Stéphane Charpier and (GlioTex, led by Ahmed Idbaih) and National Can- analysis protocols that create a pathway between instruments for a more precise assessment of disa- Vincent Navarro; early diagnosis of encephalitis; cer Institute certification for early phase clinical neuroscience and sports surgeries or spinal cord bility progression. and the development of a large clinical database trials and innovative treatments makes it possible injuries. in myasthenia gravis. to reach for the following goals: accelerating transfer of laboratory innovations into clinical applica- ADULT PSYCHIATRY SLEEP tions by identifying novel biomarkers and testing NEUROSURGERY innovative treatments, including areas that have Coordinator: Bruno MILLET (AP-HP/Sorbonne Coordinator: Isabelle ARNULF (AP-HP/Sorbonne yet to be explored. Université) Université) Coordinators: Carine KARACHI (AP-HP/Sorbonne The Psychiatry iCRIN offers a multimodal approach In the rapidly evolving field of physiology and sleep Université) and Alexandre CARPENTIER (AP-HP/ combining brain stimulation with drug therapy or medicine, this iCRIN focuses on improving the des- Sorbonne Université) psychotherapy. It represents a strong interface cription of the semiology of these disorders, their Nearly all of the clinical activities of the neurosur- between clinical services and Paris Brain Institute genetics, neurophysiological and brain imaging gery department have research programs with and more specifically with the team led by Philippe markers and the best course of treatment. It also Paris Brain Institute teams and platforms. iCRIN Fossati and Liane Schmidt. Two lines of research aims to understand the mechanisms of normal aims to ensure the development of multimodal are currently under exploration: development of sleep and dreaming; to determine whether certain databases for future clinical trials. There are five pragmatic trials in stress dysregulation disorders brain functions (including memory and emotions) main lines of research: identification of morbidity such as post-traumatic stress; and exploring are related to REM sleep; to study preclinical neu- and mortality predictors in brain tumor and aneu- network neuromodulation in psychiatric and addic- rodegeneration and implement neuro-protective rysm patient cohorts; novel deep brain stimulation tion disorders. treatment trials in patients with the early signs of targets and brain-machine interfaces; opening of Parkinson’s disease and Lewy body disease. the blood-brain barrier in various neurological pathologies; novel treatment approaches for me- ningiomas; ex vivo human tissue for cellular electrophysiology.

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BY ALEXANDRA AUFFRET DIRECTOR OF MEDICAL AND SCIENTIFIC AFFAIRS programs in administration and business, in finance, and more. To seize this opportunity, the Institute began tea- This past year saw the official launch ching neuroscience to people outside of the research field this year, while developing training for of the Paris Brain Institute training highly qualified professionals in the clinical and school, known as the Open Brain research fields. In 2019, the first Master Class dedicated to creati- School. What we know about the vity for non-experts began and the Brain Bee pro- brain and how it works can be ap- gram created for high school students with an introduction to neuroscience and its pathologies plied to much more than the fight was launched. against neurological and psychiatric 2019 was the first “Open” year for this young training organization, a fantas- diseases. tic impulse to make Paris Brain Institute discoveries The brain is, in itself, the very essence of who we accessible to the public! EXECUTIVE MASTER CLASS: are. Nearly every aspect of our daily life is directly openbrainschool.com related to neuroscience. Much of the training that WHAT NEUROSCIENCE TEACHES US exists in the area of continuing education could benefit immensely from neuroscience-based ABOUT CREATIVITY knowledge and several Paris Brain Institute training Together with Paris Brain Institute scientists and guest experts programs have already been the subject of case from the American Society for Neuroscience of Creativity, we studies that highlight the beneficial pedagogical results of their innovative approaches. The need developed a tailor-made course aimed at demystifying for continuous training keeps growing. Business creativity and uncovering our own creative potentials and schools are among the key players that capitalize on this trend with innovative Master’s degree those of our colleagues. The program, designed by Dr. Emmanuelle Volle, welcomed ten participants. EDUCATION AND TRAINING

Potential for bringing neuroscience and the PILLAR 3: ENCOURAGING various educational INTERDISCIPLINARITY BRAIN TO MARKET SUMMER SCHOOL WHAT’S NEXT? The “Brain to Market” summer school is an annual fields together. program combining translational neuroscience and • Maintaining and developing Open Brain School entrepreneurial training through intensive training by integrating all of the institute’s programs and to encourage new projects, new initiatives and new initiatives, including clinical workshops, open approaches to neurological pathologies. 2019’s training in neuroscience and management To pass down and share knowledge at national and international level, fifth edition was focused on rehabilitation after a • Continue working towards program recognition the paris brain institute created a training school, the open brain school, stroke, with an innovation value chain in close col- by officially integrating them into training courses with the ambition of becoming a new international leader in laboration with the Living Lab and activities carried (STARE, currently on a voluntary basis, will be- neuroscience-based training. The open brain school is organized around out by iPEPS. come a teaching unit by 2020) and by obtaining 4 pillars with major advances in 2019: program certification. SELF CONFIDENCE & LEADERSHIP TRAINING • Developing pillar 4 intended to implement novel A leadership and self-confidence program imple- teaching methods (virtual reality programs) to mented in collaboration with XX initiative. This create new development opportunities with the PILLAR 1: PROMOTING SCIENTIFIC PILLAR 2: PROMOTING CLINICAL intensive program helps develop leadership skills world of EdTech. EXCELLENCE RESEARCH and mastery of communication tools. Since 2019, 46 women (doctoral students, post-doctoral PROGRAMME INTERNATIONAL BRAIN BEE THE MOVE students, researchers, clinicians, support staff) The program is an international neuroscience com- The Move is an innovative simulation-based trai- have benefited from the program. petition for high school students. Brain Bee’s mis- ning program that uses mime to teach medical sion is to help students learn more about the brain students neurological semiology, otherwise known MASTERCLASS FOR RESEARCHER CAREER and its basic functions, neuroscience research, and as the expression of neurological diseases. This DEVELOPMENT misconceptions about brain disorders. The Paris program is a remarkable example of educational Throughout the year, the Medical and Scientific Brain Institute hosted the French National Brain innovation, the pedagogical benefits of which have Affairs Department offers various training sessions Bee competition for the first time in April 2019. been the subject of several publications and is now to Paris Brain Institute researchers to improve Seung-Bin Joo, winner of Brain Bee France 2019, approved by the College of Teachers of Neurology transdisciplinary skills such as management, com- took part in the international competition (IBB) in (the highest authority for neurology education in munication, and grant-writing. Daegu, South Korea. France) for distribution to all French universities. The third edition was held in 2019 with the parti- CREATIVITY MASTERCLASS INTERNATIONAL iMIND MASTER cipation of teams from London, Dublin, Lisbon, Together with Paris Brain Institute scientists and The iMIND master’s program is an international Rennes, Lille, Bordeaux and Paris universities. guest experts from the American Society for and interdisciplinary two-year program. Designed Neuroscience of Creativity, we deve- in collaboration with Sorbonne Université and PARAMEDICAL PROGRAM loped a tailor-made course aimed at renowned foreign universities (University of A set of programs has been implemented to pro- demystifying creativity and uncove- Vienna, TUM, KU Leuven, Trinity College), this mas- mote paramedical research with article writing ring our own creative potentials and ter’s program is the first of its kind specially dedi- workshops, coursework in English, training in re- those of our colleagues. The pro- cated to neurodegenerative diseases, one of to- search reasoning, two thesis grants, and the orga- gram, designed by Dr. Emmanuelle day’s major societal challenges. nization of meetings between international peers. Volle, welcomed a dozen participants.

42 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 43 EDUCATION AND TRAINING

MIT, The Paris Brain MASSACHUSETTS INSTITUTE OF TECHNOLOGY (USA), STANFORD UNIVERSITY, St JOHN’S UNIVERSITY Institute and Every year, the Institute invites students from three major American universities, MIT, Stanford and St John’s. In 2019, we welcomed 5 of these its national and students as part of this program. BRAIN BEE INTERNATIONAL (Daegu, Corée du Sud)

The Institute is proud to host France international Brain Bee, a neuroscience competition for high school students, that will send the winning student to the final network competition in Daegu, South Korea. Our diversity and close ties with our collaborators around the world are a driving force to improve our work and make it more efficient. Our institute brings together individuals from 43 countries, committed to advancing brain research.

Each year, the Paris Brain Institute cooperates with hundreds of institutes in various ways. In 2019, we collaborated with institutions from 12 different countries to obtain national, European and international funding. Our researchers also published articles with collaborators from over 1,000 different institutions. The Paris Brain Institute Open Brain School welcomed more than 65 participants from abroad to participate in its various training programs and exchange opportunities. To foster debates and discussion, our scientific conferences continue to bring together the world’s best researchers. In 2019, the Institute proudly organized international conferences on an almost weekly basis! YALE UNIVERSITY (New Haven, USA)

As part of an ongoing clinician exchange program, the Paris Brain Institute sent two doctors to Yale to learn and share their knowledge with this high-level institution in the United DRI (Dementia Research Institute, UK), States. VIB Leuven (Belgium), DZNE (Germany)

These three institutes have launched a task force with the Paris Brain Institute to develop a new European network of excellence on neurodegenerative diseases.

44 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 45 Sharing and passing along knowledge about the brain and Life at the its pathologies

The Paris Brain Institute’s communication aims at developing the Institute’s notoriety, visibility, and attractiveness in France and Paris Brain abroad.

To do so, we build strong relationships with the In addition, as a high-level research and teaching media, set up partnerships, communication cam- institution, the Paris Brain Institute is committed paigns, events and joint actions with our academic to informing as many people as possible. That’s Institute partners (INSERM, CNRS, AP-HP, Sorbonne why every year, the Institute hosts creative and University, INRIA ...). educational events.

As we strive to take up the major challenges of The research carried out at the Paris Brain Institute better understanding the functioning of the brain benefits from resources from our donors, compa- and treating nervous system diseases, the Paris nies, partner organizations and foundations and Brain Institute communicates to: the events they host for the benefit of the Institute • Promote its experts and the results of their work year after year and with renewed passion. We so that they can benefit from international fun- extend our sincerest thanks. ding opportunities and support; • Encourage recruitment of the best research-wide experts in order to foster never-ending innovation and novel skills; • Share reports on scientific and medical advances at the Paris Brain Institute for donors and further engage them; • Share and pass along knowledge to as many individuals as possible.

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Our actions in 2019

Support from our partners Events and programs to inform and raise awareness of challenges TOUR DE FRANCE AUTO OPTIC 2000 surrounding brain research - PIERRE MOREL, from 29/04 to 04/05 FUTURE RESEARCHERS LES OPEN BRAIN BAR In partnership with INSERM and the Paris school THE TOMATO AGAINST The Paris Brain Institute has created a recurring district, the Paris Brain Institute research teams DYSTONIA, from 30/5 to 2/06 “meet-up”: Open Brain Bar, friendly meetings dedi- welcome students from middle school and high cated to medical innovation and the future of heal- BRAIN WEEK school every year. This initiative allows its young LE VENDOME 80 RALLY, on 7, 8 & 9/06 thcare (in partnership with Sciences & Avenir Each year in March, Brain Week is coordinated by participants to take a deep dive into research one Magazine and Le Figaro). These events reach au- the society for neuroscience. It is an opportunity Wednesday per month and to take part in HEROES RACE, on 23/06 diences outside of the Paris Brain Institute peri- for Paris Brain Institute to open its doors and to projects. meter and are aimed at concerned citizens who offer unique interactions with researchers, clini- ICM MX INTERNATIONAL, on 1/07 are curious about understanding the implication cians, engineers & technicians of the institute of science in their daily lives. The goal of these through workshops and conferences. An educa- SCIENCE, ART & CULTURE CONFERENCES CLASSIC DAYS, on 6 & 7 /07 evenings is to reach a younger audience and raise tional and fun itinerary gives visitors an opportu- • “Large Network Geometry” by Etienne Ghys their awareness of the major societal challenges nity to discover the brain and how it works. • “Researchers of the possible: Claude Bernard FÉE RARISSIME, on 13, 14 & 15/09 generated by neurological diseases. & Paul Bert” by William Rostene • “Prospects for Alzheimer’s and Parkinson’s RACE FOR DIVERSITY, on 19/09 OBB 2019 disease” by Yves Agid, Bruno Dubois and Jean- OPEN BRAIN BAR # 10: “What comes after a Christophe Corvol LES ECHOS GOLF TROPHY, on 26/09 stroke? Post stroke rehabilitation » • “Temporal mirror & innovation” by Mathias Fink OPEN BRAIN BAR # 11: “Technologies and neuros- • “Smartosphere meetings: Mental health in the PARIS 20K, on 13/10 cience: a marriage of reason” digital age” OPEN BRAIN BAR # 12 - in partnership with Groupe • “Why take an interest in the brain to understand UN CIRCUIT POUR LE CERVEAU, on 12/10 EDF Foundation and Sorbonne University: “When human psychology?” By Lionel Naccache emotions speak up ...” • “Is artificial intelligence more logical, geometric EVEN VIP PETANQUE OPEN BRAIN BAR # 13 - in partnership with inter- or empirical” by Stéphane Mallat COMPETITION, on 30/10 national scientific film festival PARISCIENCE: “Novel technologies in neuro-genetics: perspec- MUSIC PASSION PARKINSON, on 16/11 tives and limitations ...”

SOGNO DI CAVALLINO, on 12/11 S3ODEON The Paris Brain Institute has partnered with the SOLIDAIR’S, general public information initiative led by S3Odéon, intended to help citizens gain a better BCG CHARITY DAY BGC, on 09/11 understanding of the future of healthcare research. On the stage of the Odéon theater in Paris, the LION’S CLUBS best experts in their respective fields present the latest advances in healthcare science and medicine. ROTARY CLUBS DESTINATION RESEARCH LAB This, too, is the role of our Research Institute: pro- As part of the project led by Inserm, we hosted 2 moting better knowledge sharing between Science, UN PIED DEVANT L’AUTRE, on 23 & 24/11 primary school classes (CE2 and CM1) and opened Healthcare and Society. the doors to our laboratories. A one-of-a-kind BOURG LA RUN, on 9, 10 & 11/11 opportunity to approach the world of science and healthcare research.

ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 49 LIFE AT THE PARIS BRAIN INSTITUTE

better understanding of the work carried out by joined the ranks of the Institute’s patrons. Janssen our researchers. The end of the year remains the Horizon is committed to supporting a research fundraising highlight, notably with the Découvreurs project on gene therapy for neurodegenerative d’Espoir campaign in November. For the second diseases for a total of 3 years. AXA will contribute Patronage, donations year in a row, comedian Guillaume de Tonquédec to the funding of a program focusing on rare re- was the sponsor of this major event that brought fractory childhood epilepsies over 2 years. together over 10,000 donors, all driven by the hope Watchmaker Richard Mille offered, once again, to and bequests of quickly finding new treatments for brain sell a creation to benefit the Paris Brain Institute diseases. and made an exceptional contribution to suppor- As a Public Interest Foundation, Donations to the ting Institute researchers. The support of our donors, individuals, companies, foundations and organizations, is essential Paris Brain Institute, a Public Interest Foundation, to help the Paris Brain Institute strengthen its research programs, recruit the best scientists, are 66% income tax-deductible, 75% tax-deduc- Events in support of research attract young talent and make state-of-the-art equipment available to them. tible for Tax on Real Estate Fortune, and 60% corporate tax-deductible. On October 16th, 2019, thanks to FIAC and director The Donor Service can be reached at Jennifer Flay, the Paris Brain Institute organized Bequests, donations and life Fundraising +33(0)1 57 27 47 56 the 9th edition of its “Art and Science” breakfast insurance: powerful discovery or [email protected] honoring the work of Dr Benedetta Bodini and Prof accelerators for research. In 2019, fundraising efforts geared towards the Bruno Stankoff on multiple sclerosis. During this public at large was very important. With over € 7.7 Patronage: philanthropy to help matinee, hosted by Natacha Polony, dancers Alexia Thanks to the generosity of women and men who million raised and thanks to the support of its research Giordano and Mehdi Kerkouche and a jazz en- have chosen to pass along all or part of their estate donors, the Paris Brain Institute can count on semble led by singer Anne Ducros, actress Evelyne to the Institute, bequests, donations and life insu- growing financial resources to support the teams The Circle of Friends of the Paris Brain Institute Bouix and artist Georges-Pascal Ricordeau trans- rance amounted to 1.7 million euros in 2019, an working on a daily basis to advance our unders- brings together the institute’s patrons and major lated the hope created by the research carried out increase of 116% compared to 2018. This resource tanding of the brain, help finance the purchase of donors. Throughout the year, circle members may at the Paris Brain Institute on this disease through is strategic for our research work. It also highlights technological material and equipment that is es- take part in private laboratory visits, scientific and their performance. 120 guests, alongside the that an increasing number of individuals have per- sential to cutting-edge research, and cotribute to cultural conferences and meetings with Founding Members of the Institute, showed great ceived the high-quality research within our insti- the proper functioning of the building, the heart researchers. generosity during the matinee and generated an tute, a public interest foundation with an inheri- of the research ecosystem. To reduce its costs and The Circle’s Office can be reached at +33(0)1 important amount of donations. tance tax exemption, that places the Paris Brain allocate a larger share of donations to the Institute’s 57 27 40 32 or [email protected] The Paris Brain Institute was also fortunate to be Institute among the leading neuroscience institutes social missions, donors are welcome to make their one of the two beneficiaries of the President’s worldwide and put their trust in it. donations online or to switch to ongoing support Committed and generous patrons Barrel auction during Bequests to the Institute to us are varied in nature: by direct debit, thereby saving on postage and the prestigious life insurance contracts, real estate (houses, apart- printing costs. In 2019, the Paris Brain Institute is proud to have Hospices de Beaune ments), money, deeds .... Whatever its form, eve- Fundraising efforts take place throughout the year, been able to count on the support of particularly sale on November 17th, rything we receive is, above all, the transmission with mail and e-mail campaigns. These actions are generous patrons and a growing number of pa- 2019. Basketball player of a story that we know how to collect with the carried out with measure and remain essential to trons as well. The Janssen Horizon Fund and AXA Tony Parker agreed to utmost respect. the achievement of the Institute’s funding objec- sponsor the Paris Brain Faced with the considerable challenges of brain tives. Four times a year, the Donors Journal is Institute during this research, an increasing number of individuals published and sent to loyal donors. It is a true mee- CIRCLE OF FRIENDS OF THE PARIS BRAIN INSTITUTE event, during which contact us each year with the desire to include the ting place for those who wish to stay informed of € 130,000 were raised Paris Brain Institute in their will or as a beneficiary the latest advances in neuroscience and gain a Lily Safra, Jean Burelle, in support of the insti- of their life insurance contract. Carole Clément, Honorary President of the Sylvain Héfès, tute’s research. testator relationship manager, is available to ans- Circle of Friends of the Paris François Henrot, Brain Institute wer their question and in contact when necessary Jean-Philippe Hottinguer, Lindsay Owen-Jones, with our notary, an inheritance expert, with whom Eddie Misrahi, Honorary President of the Margaux Primat, an appointment can be arranged for tailored ad- Circle of Friends of the Paris vice. Visits to the Institute are also offered for tes- Brain Institute Christian Schmidt de la Brélie, tators who wish to learn more about how research Gérard Saillant, Sophie Seydoux, takes place there. This is a special time for those President of François Thomé, the Paris Brain Institute who decide to go forward with their plans for Serge Weinberg, Jean Todt, transmission. Vice-President of Members of the Campaign Please reach out to Carole Clément the Paris Brain Institute Committee on st for information on bequests, donations or life Maurice Lévy, December 31 , 2019 insurance (+33 (0)1 57 27 41 41 Co-President of the Paris Brain or [email protected]). Institute Campaign Committee AMBASSADORS David de Rothschild, Co-President of the Paris Brain Michèle Yeoh, Actress Institute Campaign Committee Jean Reno, Actor Jean-Luc Allavena, Cédric de Bailliencourt,

50 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 51 LIFE AT THE PARIS BRAIN INSTITUTE

facilitating reflection on their own practice and by Gender equality: contributing to general reflection based on pio- the contribution of neuroscience neering experiences. During its first year, it focused primarily on consulting with staff to define future Despite being a country internationally renowned priorities, the structuring of its response to queries for facilitating the career of women with the appro- and how to communicate on its missions. priate infrastructure and specific legislation, France is not any better in providing equal opportunities Ethics and professional conduct queries to women and men. In an article published in the The COMETH-ICM can respond to queries or ini- journal Nature Human Behavior, Violetta Zujovic, tiate discussion on problems requiring special and Christiane Schreiweis, members of the XX consideration to find the best course of action. Initiative committee of the Paris Brain Institute, When it examines a file, after having verified eligi- explain how a neuroscientific approach could more bility with regard to its missions, the committee effectively combat gender inequalities. The publi- works in compliance with the strictest conditions cation warns of the impact of cognitive biases, of impartiality and confidentiality. When the file beyond our control but deeply rooted in our men- requires specific expertise, independent experts tality. Unconscious prejudice and stereotypes have Corporate social are asked to provide their analysis. The experts a powerful influence on almost all of our choices. involved sign a form to verify the independence of their judgment as well as a confidentiality agree- The Paris Brain Institute’s XX initiative committee, ment. Based on their’ conclusions and the com- involving researchers and experts in neuroscience, responsibility: mittee’s own analysis, the COMETH-ICM issues an offers a roadmap in several stages. Their recom- opinion that is shared with the issuer of the mendations highlight an essential first step: the query. realization that implicit shortcuts, resulting from a major challenge COMETH issued 6 opinions in 2019. Three of the existing prejudices, impact our decision-making. queries came from general management or unit To facilitate this individual and collective aware- management at the Paris Brain Institute, and three ness, a quantified assessment of gender inequality came from research personnel. The issues submit- in terms of salary or level of responsibility is neces- for the Paris Brain ted by the management teams pertain to questions sary. The impact of this committee and its neuros- about the opportunity for industrial partnership cientific approach introduced a year and a half ago due to the nature of the company’s activity, and underscores the importance of combining concrete Institute the issue of multiple contracts per researcher. The action with national policy. The committee will 3 opinions were taken into account by the relevant organize a symposium on “gender bias: science departments. Two research teams contacted and actions” in 2020, open to all, and practical COMETH-ICM regarding tensions when research workshops presenting tools to revise our own pre- results were published. Another query was a judices and know how to assess our own values A sustainable approach at the Paris the ecological crisis as well as ways to deal with it request for an opinion from the ethics committee and skills. A neuroscience-based approach can Brain Institute and limit its impact as much as possible. It also of the coordinating institution, to meet the request now be a major driver to change the way we think hopes to set up concrete actions at the Paris Brain of partner institutions within the framework of a and our behaviors. We are all directly or indirectly affected by the Institute centered on the fight against waste, lowe- European project on a subject unconsidered by ecological crisis whether it is due to climate ring the use of disposable materials and limiting regulatory ethics committees (reuse of post-mor- change, pollution of natural areas, or the collapse CO2 emissions due to air transport. These actions tem biological samples). The COMETH-ICM opinion of biodiversity, and we will be even more greatly are at their starting point and the Green Team is allowed the project to start. affected in the future. In this context, the Paris in contact with several bodies of the Paris Brain Brain Institute has been involved in a sustainable Institute including the Social and Economic Communication and training approach since its opening. Several actions were Committee, the Ethics Committee and the Health, COMETH participated in two course units of the launched by Management including recycling, Safety and Environment (HSE) Unit to develop iMIND (international Master in Neurodegenerative which allowed us to recover nearly 32 tons of waste these actions further. Diseases) Master2 program at Sorbonne University: in 2018, or procedures to save energy, water, and “Brain to Market Summer School” (Regulatory and more. As part of a commitment to corporate social ethical aspects of data sharing) and “Novel tech- responsibility (CSR), Management encourages the The Paris Brain Institute ethics nologies applied to human pathologies” (Ethical Green Team initiative in its information, awareness committee in 2019 aspects in predictive genomics, iPS use and data and reflection process. sharing). The Ethics Committee of the Paris Brain Institute The Green Team brings together several dozen (COMETH-ICM) is responsible for fostering new From January 2020, COMETH will participate in individuals within the institute and hopes to get ideas on the ethical and deontological questions monthly training of new Paris Brain Institute mem- people thinking about sustainability and develop raised by scientific and medical research as it is bers, on the basis of the Institute code of ethics. practices to anticipate the inevitable changes to implemented within the Institute. Its mission is also come. The Green Team is preparing a series of to help all research staff at the Paris Brain Institute seminars that will address the multiple facets of act in accordance with ethical standards, by

52 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 53 LIFE AT THE PARIS BRAIN INSTITUTE

Paris Brain Institute’s governance

The Board of Directors regulates, through its deliberations, the affairs of the FOUNDERS Institute. It decides on the strategic orientations proposed by the Director General. He votes the budgets and approves the accounts. It is chaired by • Gérard Saillant, Professor of Orthopaedic and Professor Gérard Saillant, President of the Paris Brain Institute and composed of Traumatological Surgery, President of the Paris 15 members divided in 4 colleges: founders, qualified personalities, full members Brain Institute (INSERM, CNRS, Sorbonne University, AP-HP) and Friends of the Foundation. • Jean Todt, President of the FIA, Vice- President of the Paris Brain Institute • Yves Agid, Honorary Professor of Neurology THE BOARD OF DIRECTORS COMMITTEES OF THE BOARD and Neuroscience • Luc Besson, Film Director MEMBERS OF THE BOARD OF DIRECTORS SCIENTIFIC ADVISORY BOARD AUDIT COMMITTEE AND APPOINTMENTS AND • Louis Camilleri, CEO of Ferrari COLLEGE OF FOUNDERS The Scientific Advisory Board (SAB) assists the REMUNERATION COMMITTEE • Jean Glavany, Former Minister • Gérard Saillant, Professor of Orthopaedic and Board of Directors or the CEO on the main orien- • Serge Weinberg, Chairman of the Audit • Maurice Lévy, Chairman of the Executive Traumatological Surgery, President of the Paris tations, programmes or scientific approaches of Committee Board of Publicis Groupe, Co-Chair of the Paris Brain Institute the Institute. It is composed of the best interna- • Claire Giry, Chairwoman of the appointments Brain Institute Friends Committee • Jean Todt, President of the FIA, Vice-President tional experts in neuroscience. Every 5 years, the and remuneration committee, by delegation • Olivier Lyon-Caen, Professor of Neurology, of the Paris Brain Institute Paris Brain Institute, as a joint research unit (in from Gilles Bloch former Director of the Nervous System • Serge Weinberg, President of Weinberg French UMR), is assessed on the quality of its re- • Jean Glavany, Former Minister Diseases Centre of Pitié-Salpêtrière University Capital Partners, Treasurer of the Paris Brain search, its organization, its strategy and its five- • Jean-Pierre Martel, Lawyer Hospital Institute year scientific projects. The teams’ research pro- • Jean-Pierre Martel, Lawyer • Jean Glavany, Former Minister jects are evaluated by the SAB, whose mission is COORDINATION COMMITTEE OF THE • Max Mosley, Former President of the FIA • Jean-Pierre Martel, Lawyer to advise the Institute and assist it in defining its FOUNDATION WITH ITS PUBLIC PARTNERS • Lindsay Owen-Jones, Honorary President of general orientations. After exchanges and discus- • Gérard Saillant, President of the Paris Brain L’Oréal, Honorary President of the Paris Brain COLLEGE OF QUALIFIED PERSONALITIES sions, the SAB submits an opinion that is taken Institute Institute Friends Committee • Philippe Ménasché, Professor of Thoracic and into account to build the dossier submitted for • Gilles Bloch, Representative of the INSERM • David de Rothschild, President of the Cardiovascular Surgery evaluation by the High Council for the Evaluation • Bernard Poulain, Representative of the CNRS Executive Board of Rothschild Bank & Co., • Richard Frackowiak, Emeritus Professor at of Research and Higher Education (HCERES). • Bruno Riou, Representative of Sorbonne Co-Chair of the Paris Brain Institute Friends University College London Université Committee • Elisabeth Tournier-Lasserve, Professor of • Michael Shelanski - President of the CSI, • Erik Domain, Representative of AP-HP • Michael Schumacher, Formula 1 Driver medical genetics at Université Paris Diderot Columbia University, New York, USA • Serge Weinberg, President of Weinberg • Dimitri Kullman - ION, University College of THE ETHICS AND DEONTOLOGY COMMITTEE Capital Partners, Treasurer of the Paris Brain COLLEGE OF FULL MEMBERS London, UK The Paris Brain Institute Ethics and Deontology Institute • Gilles Bloch, representative of the Institut • Gabor Tamas - University of Szeged, Hungary Committee was established with the dual responsi- National de la Santé et de la Recherche - Peter Brown - University of Oxford, UK bility of contributing to the ethical conduct of Médicale (INSERM) • Brad Hyman - Massachusetts Alzheimer research and the compliance to the ethical rules THE PARIS BRAIN • Bernard Poulain, representative of the Centre Disease Research Center, USA of the trades that contribute to its production. It INSTITUTE ASSOCIATION National de la Recherche Scientifique (CNRS) • Stephen Hauser - UCSF Sandler Institute, San is composed of 12 members including 7 Paris Brain OF FRIENDS • Bruno Riou, representative of Sorbonne Fransisco, USA Institute collaborators and 5 qualified external Université • Bill Richardson - University College of London, personalities • Lily Safra, Honorary President, • Erik Domain, representative of the Assistance UK President of the Edmond J. Safra Publique – Hôpitaux de Paris (AP-HP) • Helen Mayberg - Center for Advanced Circuit Philanthropic Foundation Therapeutics, USA • Gérard Saillant COLLEGE OF THE FRIENDS OF THE • Christian Buchel, University Medical Centre • Jean Todt FOUNDATION Hamburg-Eppendorf - Department of Systems • Lindsay Owen-Jones • Maurice Lévy Neuroscience, Germany • Maurice Lévy • Christian Schmidt de la Brélie • Arnold Kriegstein - UCSF, San Fransisco, USA • David de Rothschild • David De Rothschild • Masud Husain - University of Oxford, UK • Jean-Pierre Martel • Michael Heneka - DZNE, University of Bonn, • Serge Weinberg PUBLIC COMMISSIONER Germany • Philippe Ritter

54 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 55 THE MANAGEMENT COMMITTEE • Pr Alexis Brice, Prof Alexis BRICE • Corinne FORTIN (CODIR) Chief executive of the Paris Brain Secretary General of the Paris Brain Decisions are taken by the Director Institute and the Mixed Research Institute and the Mixed Research General on the basis of the CODIR Unit (UMR) Unit (UMR) members’ recommendations. • Prof Jean-Yves DELATTRE • Jean-Louis DA COSTA Medical Director Director of Communications and • Prof Bassem HASSAN Development Financial report Scientific director and Deputy Director of the UMR In addition, the Support functions Rigor and transparency at the core of our actions management Committee (CODIS) pilots several institutional and The breakthroughs and actions of the Paris Brain Institute are carried out with the transversal projects utmost transparency. “Trusted donation” certification was granted to the Paris Brain Institute-ICM Foundation in November 2010 and renewed in October 2019. This accreditation certifies that the Institute’s activities are in line with the 4 ADVISORY COMMITTEES committee’s principles: statutory functioning and selfless management, rigorous management, quality of communication and fundraising actions and financial transparency. They issue opinions and recommendations in their area of expertise. Fundraising In-kind patronage and sponsorship THE SCIENTIFIC AND MEDICAL STEERING THE COMMITTEE ON GENDER EQUITY COMMITTEE (COPIL) The Paris Brain Institute, according to the recom- 2019 fundraising revenue stands at € 17 million. Many companies have given us their support by The Scientific and Medical COPIL enables resear- mendations of an internal collective, the XX initia- offering their expertise in their respective fields chers to participate in decision-making on scien- tive, approved by the Scientific Advisory Board In 2019, main new sponsorship agreements signed or by donating products free of charge. This sec- tific issues and financial issues that impact and the executive committee has formalized in were: tion also includes artists or collectors who have research. 2018 a new advisory committee: the Committee • Janssen Horizon donated works of art sold for to benefit the Paris for equity between men and women. • AXA SA - Axa Bank - Thellie Brain Institute. THE TEAMS’ COUNCIL Several missions and actions of this committee • Bolloré Group The teams’ council, made up of the Director have already been proposed and validated by the • UNIM The Paris Brain Institute-ICM Foundation has bene- General and all the team leaders (25 in 2019), Management. The first step is to inform as many • Fonds Saint Michel fited from in-kind patronage as part of its PR ac- meets once a month. It is consulted on the scien- people as possible about the existence and the • Roger de Spoelberch Foundation tions and at-large fundraising efforts, namely: tific policy, the budgetary aspects and the means effect of gender bias in decision-making, in the • media slots with: Air France, ReedExpo/FIAC, to be implemented in the UMR. behaviour adopted between colleagues but also The Circle of Friends of the Paris Brain Institute ZenithOptimedia, Richard Mille, TF1, Klesia in the way of approaching clinical research on brings together donors who have been involved • products and services free of charge: International THE LABORATORY COUNCIL mixed populations. These trainings will have for since the early days of the Paris Brain Institute Automobile Federation, Publicis Group, Orrick The mission of the Laboratory Council is to advise main goal a general awareness. Coordination with adventure with large donations (€ 10,000 + an- Rambaud Martel, IDEC, ANACOFI the UMR management on the life of the UMR, the human resources management will improve the nually). This Circle was created to specifically thank scientific policy, the budgetary and human rework environment and optimize research. major donors, individuals, companies and founda- sources policy, and all other questions related to • Key actions were or will be carried out for the tions, who have stepped up for Institute since the life of the UMR. The members of the laboratory career of women at the institute, juniors or se- 2008. Membership criteria for the Circle of Friends council are elected by their college (5 colleges in niors, so that a men/women ratio is respected: have changed and now include solely donors with 2018). The number of representatives is propor- A workshop on leadership for young women donations of a minimum of € 10,000 over a single tional to the number of members of the college scientists was set up with a first session in year and no longer over several years as was the (15 members in 2018). February 2018 and a second one in October 2018. case before. Following this change in criteria, the These trainings will be organized on a yearly Circle brings together 559 donors. In 2019, the basis. Circle was co-chaired by Mr. Maurice Lévy and Mr. • Management Committee recommendations have David de Rothschild, Founding Members of the been made to increase the number of women Paris Brain Institute. becoming team leaders as part of the Paris Brain Institute Joint Research Unit Renewal and for In order to increase its resources, the Paris Brain more new teams led by women to be recruited. Institute continued its fundraising campaigns in • The committee will ensure that more women are 2019. integrated into the various committees and The Paris Brain Institute is particularly grateful and councils of the institute. extends its sincerest thanks to loved ones who In addition, the committee for equity between men have organized in memoriam fundraisers for the and women coordinates its activities with other benefit of the Institute. national committees, participates in meetings on this subject and communicates its action plan to other universities (Bordeaux, Caen). FINANCIAL REPORT

2019 Financial situation Allocation of funding collected from the general public

2019 SOURCES OF FUNDS 2019 APPLICATIONS OF FUNDS Sources of funding collected from the general Reserve policy Research project funding is characterized by a Total 2018 applications of funds amounted to € public used in 2019 amounted to € 13.4 million. When it was created in 2006, the Paris Brain variety of funding sources with a long-term pers- 58.3 million: € 43.4 million used in 2019 and € 12.6 In summary, out of € 100 of resources collected Institute-ICM Foundation received an endowment pective in order to produce knowledge and major million to be used later with allocated resources. from the general public, € 72 were used to finance of € 11.7 million, of which € 1.2 million were nonex- neuroscience breakthroughs. The total dedicated to social missions amounted social missions and investments, € 22 were used pendable. Thanks to rigorous budget manage- to € 36.8 million, representing 85% of the total to cover fundraising and communication costs ment, the Paris Brain Institute-ICM Foundation has 2019 resources amounted to € 58.3 million, inclu- applications for the 2019 financial year. Social mis- and € 6 were used to cover Paris Brain Institute achieved an income-expense balance for 4 years, ding € 48.1 million in revenue for the year and € sions of the Paris Brain Institute include: operating costs. thereby avoiding drawing on its reserves. 10.2 million in the carry-over of resources allocated • Research programs; Furthermore, the policy of the members of the and not used in previous years. Revenues for the • Technological platforms; BILAN 2019 board of directors in terms of investment is extre- financial year mainly amount to revenue from fun- • Scientific leadership and implementation of inter- mely cautious. The Paris Brain Institute’s cash is ASSETS (M€) 2018 2019 draising (€ 17.3 million), either from the general national alliances; invested in marketable securities (capitalization public (€ 13.4 million), or from companies and pri- • Incubation of innovative companies. NET FIXED ASSETS 56 65 contract signed with leading banking institutions, vate foundations (€ 3.9 million). ACCOUNTS RECEIVABLE 65 67 guaranteed in capital and 100% in euro funds). Funding for research projects is mainly dedicated TOTAL ASSETS 121 132 They also include: to diseases of the nervous system and spinal cord Voluntary in-kind contributions • Revenue from technological platform activities injuries. Technological platforms (neuroimaging, Volunteering: (€ 5.3 million) and from research collaborations vectorology, genotyping sequencing, cell culture, LIABILITIES (M€) 2018 2019 The Paris Brain Institute benefited from hours of with industrial partners (€ 3.50 million), histology and bioinformatics) support these pro- ASSOCIATION FUNDS 57 51 volunteer work during the year, especially for com- • Public and private grants (€ 8.4 million) jects. Fundraising and communication costs cor- FINANCIAL YEAR INCOME - 0,2 1,7 munication activities and events. Estimated volume • Funding for the “IHU program” (€ 7.6 million). respond to the costs incurred to collect funds from is 1.2 FTE, or on the basis of an hourly minimum DEDICATED FUNDS 13 15 • Other revenue (leases, rebilled expenses, financial individuals (donations and legacies) and private wage, an amount of € 32k. products, etc.) (€ 6 million) companies and foundations (patronage and spon- DEBT 34 41 sorship actions), as well as PR actions. They repre- DEFERRED INCOME 18 24 In-kind sponsorship: sent 9% of applications. TOTAL LIABILITIES 121 132 The Paris Brain Institute Foundation-ICM has benefited from in-kind patronage as part of its PR ac- Operating costs represent support staff expenses tions and at-large fundraising efforts, namely: (general secretariat, finance, human resources, COMMENTS • media slots with: Air France, ReedExpo/FIAC, legal, IT and logistics) amounting to 6% of total Total investments made by the Paris Brain Institute ZenithOptimedia, Richard Mille, TF1, Klesia 18 % 23 % applications for the financial year. Commitments since its opening amount to € 46 million dedicated • products and services free of charge: International on allocated resources (€ 12.6 million) are dona- mainly to technological platforms that support Automobile Federation, Publicis Group, Orrick tions from companies or foundations received research. Investments for the year amounted to Rambaud Martel, IDEC, ANACOFI 10 % during the year that will be used later for specific €15.7 million. 7 % multi-year privately or publicly funded (ANR, etc.) The Paris Brain Institute is particularly committed research programs. They include: to maintaining its level of excellence and has 13 % 14 % • Scientific investments: Acquisition of a latest- implemented internal and external control to generation sequencer (€800K) and scientific guarantee its thorough and efficient manage- 15 % materials and equipment (€1 238K); ment, notably as a member of the Trusted 9 9 % 6 % • The acquisition of scientific computing storage Donations Charter Committee and by hiring an 6 capacity and computing clusters (€1 042K). independent auditor. Resources Funds collected from the general public Net fixed assets amounted to € 65.2 million. As of Funds collected from businesses and December 31, 2019, cash flow amounted to € 42.5 Trusted Donation private foundations million. Paris Brain Institute associative funds Public and private subsidies 85 % amount to € 56.1 million. They include equity for The breakthroughs and actions of Revenue from platform activity and Applications € 47.9 million supplemented by investment grants the Paris Brain Institute are carried industrial partnerships 85 Social missions of € 4.6 million. Nonexpendable endowment out with the utmost transparency. Funding of the “IHU Program” Fundraising and amounts to € 1.2 million. At the end of the financial “Trusted donation” certification was Other revenue (leases, rebilled expenses, communication costs year, dedicated funds (funds remaining to be com- granted to the Paris Brain Institute Foundation in financial products, etc.) Operating costs mitted to multi-year programs) amounted to € 15 November 2010 and renewed in October 2019. This Carry-over of previous resources million. accreditation certifies that the Institute’s activities are in line with the committee’s principles: statutory functioning and selfless management, rigorous management, quality of communication and fundraising actions and financial transparency.

58 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 59 2019 expenditure statement (in €)

2019 Allocation of Thank you resources raised 2019 Resources 2019 Resources 2019 Applications from the general APPLICATIONS RESOURCES collected collected and used public by • Claude Sfeir • Gérard Buffière • ERIC HOLDING application MAJOR PATRONS • Dominique Vizcaino • Jean et Anne-Marie • Claude Félix PATRONS Carryover of resources collected from general 0 • AIR FRANCE • Serge Weinberg Burelle • FERBLANC public not allocated/used at start of fiscal year • Elisabeth Badinter • Famille Jan Aron • 1 anonyme • Daniel Buren FUNDRAISING 1. Social Missions • Maria Rosa Bemberg • Luc Besson • Louis Camilleri • Roland Fernet 36 789 347 6 915 234 1. Resources collected from the general public 13 421 644 13 421 644 Actions directly carried out" • Dominique, • BOLLORÉ • CAMPENON • Emilio Ferré BENEFACTORS Alexandre et Joy • BOUYGUES BERNARD • FINETFO SA Research programs 24 579 082 2 551 114 Unallocated monetary donations 11 100 612 11 100 612 Desseigne • Olivier Carre • 2CRSI CONSTRUCTION • FONDATION Technological research platforms 8 670 672 2 385 582 Allocated monetary donations 640 644 640 644 • FIA FOUNDATION • Lucienne Collin • Benoit Abdelatif • CAPGEMINI ABEONA FOR THE • CRÉDIT MUTUEL - Classic Days • Marella Caracciolo • FONDATION AIR Research applications and incubator 2 141 065 974 409 Unallocated bequests and other gifts 1 680 388 1 680 388 AUTOMOBILE AND NORD EUROPE • ACCOR Agnelli LIQUIDE Other social missions 1 398 528 1 004 127 Allocated bequests and other gifts 0 0 SOCIETY • FÉDÉRATION • ACCURACY • P. et J.-P. Carle • FONDATION Other revenue from general public generosity 0 0 • FONDATION FRANÇAISE DU • AMAURY MEDIA • Patrick Charpentier PLENUM BETTENCOURT SPORT • Benoît André • Suzanne Charpentier • FONDATION 2. Fundraising costs 4 049 693 2 907 634 2. Other private funds 12 225 792 SCHUELLER AUTOMOBILE • Christine André • M. et Mme Léon MARIE-ANGE Cost of appeals to the generosity of the general • FONDATION • FONDATION AREVA • Yvon André et Cligman BOUVET- 3 686 834 2 647 105 Patronage 3 906 739 public GROUPE EDF • FONDATION ARPE Annette Gellé • Alberto Colussi LABRUYÈRE • FONDATION • FONDATION • Anne Bardinon • COMITE NATIONAL • FONDATION ROGER Costs related to private fund canvassing 362 699 260 414 Partnerships 4 490 303 EDMOND J. SAFRA COGNACQ-JAY • ARB CONSEIL SAS OLYMPIQUE ET DE SPOELBERCH Communication costs 160 115 Private subsidies 3 828 750 • FONDATION LILY • FONDATION • ASSOCIATION CLUB SPORTIF FRANCAIS • FONDS DE SAFRA D’ENTREPRISE DES 20 km DE • CRÉDIT AGRICOLE DOTATION 3. Subsidies and other public financial support 13 267 802 • FP JOURNE MICHELIN PARIS ILE DE FRANCE JANSSEN HORIZON 3. Institutional operational costs 2 608 348 802 857 4. Other products 9 200 655 - INVENIT ET FECIT • FONDS DE • ASSOCIATION • Jean-Patrice et • FONDS DE Financial products 517 319 • HSBC FRANCE DOTATION PIERRE DEMAIN DEBOUT Marie-Anne Dalem DOTATION LIONS Services rendered 5 324 739 Other products 3 358 597 • KLESIA - CARCEPT BERGÉ • ASSOCIATION RMC • M. et Mme Laurent CLUB LYON DOYEN PREV - IPRIAC • M. et Mme Garaialde BFM Dassault • FONDS PATRICK DE • Docteur Léone- • GROUPE IDEC • ASSOCIATION • DAVID HERRO BROU DE LAURIÈRE I. TOTAL APPLICATIONS 43 447 388 10 625 725 I. TOTAL RESOURCES 48 115 894 Noëlle Meyer • GROUPE PASTEUR SOGNO DI TRUST • FONDS SAINT • Richard Mille MUTUALITÉ CAVALLINO • Vicomte Olivier MICHEL II. PROVISIONS 555 076 II. CARRYOVER OF PROVISIONS • OCIRP • Sylvain et Michèle • M. et Mme Guy Davignon • Dimitri et Maryvonne III. CARRYOVER OF ALLOCATED RESOURCES • ORRICK RAMBAUD Héfès Autran • Jean-Charles et Fotiadi III. PLEDGES ON ALLOCATED RESOURCES 12 634 148 10 171 300 UNUSED IN PREVIOUS FISCAL YEARS MARTEL • François Henrot • AXA RESEARCH Natacha Decaux • Marie-Pierre

IV. VARIATION OF ALLOCATED FUNDS COLLECTED • Lindsay Owen-Jones • M. et Mme Alain Joly FUND • Jean-François Fournier - 14 940 FROM THE GENERAL PUBLIC • PUBLICIS • Serge Kampf • AXÉRIA Decaux • Jean-René Fourtou • RACE OF • MALAKOFF PRÉVOYANCE • Annette Decroix • GALORI TRUST IV. FISCAL YEAR SURPLUS 1 650 582 V. INSUFFICIENT FISCAL YEAR RESOURCES CHAMPIONS MÉDÉRIC HUMANIS • BANQUE PICTET Lavaur • GIULIANI S.p.A V. GRAND TOTAL 58 287 194 VI. GRAND TOTAL 58 287 194 13 406 704 • Édouard et Martine • Maurice Lévy • Jean-Paul • Ghislaine et Olivier • GLAXO SMITH de Royère • Christiane Laborie et Baudecroux Delattre KLINE Share of fixed assets acquired during the fiscal 3 041 300 year financed by collected funds • Michael Schumacher Roger Lionnet • Fernande Benveniste • Claude Demole • GROUPE • Jean Todt et • Alain Mallart • Gérard Bertinetti • Aline Derbesse ROUSSELET Neutralisation of provisions for depreciation of - 260 321 Michelle Yeoh - GROUPE • BGC PARTNERS • Jean-Louis et • Mina Gondler fixed assets financed by collected funds • 1 anonyme ENERGIPOLE • Christian et Marie-Cécile Dufloux • GROUPE EMERIGE TOTAL APPLICATIONS FINANCED BY FUNDS TOTAL APPLICATIONS FUNDED BY FUNDS • Dominique et Marie-Claire • Michel Duhoux • GROUPE G7 13 406 704 13 406 704 COLLECTED FROM THE GENERAL PUBLIC COLLECTED FROM THE GENERAL PUBLIC Danièle Mars Blanckaert • Jacques Dumas • GROUPE LUCIEN BALANCE OF FUNDS COLLECTED FROM THE GENERAL • ORACLE • M. et Mme Pascal • Jean-Christophe BARRIÈRE PUBLIC NOT ALLOCATED/USED BY END OF FISCAL 0 • PATHÉ Boileau Dumas • GROUPE PRÉVOIR YEAR • PHILIPPE • Tatiana et Adrien de • Rena et Jean-Louis • Paul Hermelin EVALUATION OF VOLUNTARY IN-KIND DONATIONS FOUNDATION, INC. Boisanger Dumas • Monique Guérinat et • Christian Poquet • Chantal Bolloré • Marcel Dupuis FISA "Social missions "Volunteering • RATP • Irène Bonnet • Henri Dura • Christian Haas Fundraising costs In-kind services 32 859 32 859 Operational costs In-kind donations • David de Rothschild • BOREL & BARBEY • Cécile et Christophe • Mireille et René Total" Total" • SCHNEIDER • Micheline Bridèle Durand-Ruel Hadjadje ELECTRIC • Famille Bucaille • ELIVIE • Pierre Hanriot

60 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019REPORT 2019 ANNUAL REPORT 2019 - PARIS BRAIN INSTITUTE — 61 • Bernard Hayot • Jean-Paul Ringeard • ASSOCIATION • M. et Mme Thierry • Jacques-Arthur • HUNTINGTON • Pierre Martinet • Jean-Jacques Rosa TESTATORS • Jean-Marie et • Richard Roth JEAN-CLAUDE Bourvis Essebag ESPOIR OUEST • Bruno Matheu • Martin Rosdy • Henriette B. Laurence Hennes • ROTHSCHILD & Cie DUSSE • Jean Bousquet • EVER PHARMA • Simone Huriot • Bernard Maurel • Jean Claude • Janine C. • Marie-Jeannine • Nelly Rouyrès • ASSOCIATION • Claude Bouygues France • IMPALA SAS • MEDTRONIC Rosenblum • Michel D. Jacobson • RSI, PROFESSIONS JÉROME GOLMARD • Renaud Bouygues • FONDATION • Pierre Jardinier • Jean-Claude Meyer • Pierre Rosenblum • Yves D. • Alain Kahn LIBÉRALES ET • ASSOCIATION PAUL • Jean-Jacques CHRISTINE GOUDOT • Anne Jousse • MILLE MERCIS • ROTARY CLUB • Jacqueline D. • kamel mennour ARTISANS ET PHILIPPE Branger • EXELGYN SA • Christophe Karvelis • Thierry et Natacha ORLÉANS • Jacqueline F. • KERIALIS • Jean Pierre Sabardu PERROT • François Buquet • FÉDÉRATION Senn Millemann VAL-DE-LOIRE • Christiane M. • LA FRANCAISE AM • Hubert Saltiel • ASSOCIATION • Daniel Buren FRANCAISE DE • Cyril Kongo • Claude et Isabelle • Elisabeth de • Françoise M. • M. et Mme François • Claire Sarti SPORTIVE ET • Marie-Noëlle TENNIS • Daniel Kouzo Montero Rothschild • Lucette P. Lafon • Guy Savoy CULTURELLE DE Canu-Duclert • FEDEX CORP • Sophie et Frédéric • Maÿlis de • Louise de Rothschild • Suzy S. • Bernard Lange • SOCIÉTÉ L’AIR • M. et Mme Arnaud • M. et Mme Fialip Krebs Montgolfier • Aurore et Stéphane • Bertrand Lavier FRANÇAISE DE • ASSOCIATION Caspar • Charles-Henri Filippi • LA LONGUE ROUTE • Charles Moore Rougeot • Martin Lebeuf MÉDECINE SPORTIVE • Henri et Michèle • FINANCIERE CADO DES MALADES DE Wilson • Thierry Roussel • Angélique Lenain et ESTHÉTIQUE GYMNIQUE NEUILLY Cassin • FINANCIÈRE DE LA SLA • Gérald Morand • Jean-François Fabrice de • SCLÉROSE EN • ASSOCIATION • CB RICHARD ELLIS L’ECHIQUIER • M. et Mme Patrice de • Daniel Moreau Roussely Gaudemar PANNE VIVRE À SAINT • CELIO • FINANCIÈRE POCH Laage de Meux • Hervé de La • M. et Mme Ruckstuhl PARIS BRAIN • Jean-Jacques • SLA FONDATION DAMIEN • CHAMPAGNE • Thierry Flecchia • M. et Mme Antoine Morinière • Igor Rybakow INSTITUTE Lestrade RECHERCHE • Jean-Pierre Aubin LAURENT-PERRIER • FONDATION Labbé • Yves Néron-Bancel • Angèle Sabardu VOLUNTEERS • LES AMIS DE (SLAFR) • AUREL BGC • Jean-Bernard RUMSEY-CARTIER • LABORATOIRE • NEUROLIGUE • M. et Mme Christian CAPUCINE • SOCAUSUD • AUTOMOBILE CLUB Champeau • FONDATION VENTE IPSEN PHARMA • NOVARTIS Schlumberger • Pascale Des Abbayes • LIGUE DE • SODEXO DE FRANCE • Jean-Paul Charmes PRIVÉE • LABORATOIRES • Nahed Ojjeh • SFR • Patricia Brault FOOTBALL • SoLidAir’s • AXA BANQUE • Amaury et Alix de • Philippe ECLAIR • Jacques Olivier • SICA2M • Ariane Bucaille PROFESSIONNEL • SOPAREXO • AXA SA Chaumont Quitry Foriel-Destezet • Jean-François • Jean-Claude Olivier • SORIN GROUP • Nicole Fourn • LILLY • Claudine Soubrié • Nicole Ayanian • Dominique Chedal • FRANCE GALOP Labrousse • ONDRA PARTNERS • SPB • Antonio Lopez • Georges Louviot • Jean-Cyril Spinetta Schneider • Dr André Chérot • Benoit Gallet • M. et Mme Michel • David Pastel • SPIFIN • Marie-Claude Theguel • Pascal Olivier et • SUCRE ET DENRÉES • Stéphanie et Martin • Brigitte Chichignoud • Florence Gombault Lacoste • Daniel Payan • Giuliana Spotorno • Annie Wilson Ilana Mantoux • Nicolas de Balas • Prince et Princesse • M. et Mme Gilles • Réjane et Michel • Valérie Pécresse • STADE DE FRANCE • M. et Mme Patrick Turckheim • BANQUE DE de Chimay Gantois Lacoste • Christophe Perchet • M. et Mme Vincent Martin-Michaud • Yannick Tarondeau LUXEMBOURG • Fabien Chone • Francis Thomas • Pauline Lamonica • Guy Percie du Sert Strauss • MAXI SEC • Jean-Philippe • Frédéric Banzet • Gérard Collet Gleeson • Christian • Jacques Pericchi • Hubert Taffin de • Florent Menegaux Thierry • M. et Mme Pierre- • Bertrand Collomb • GLG PARTNERS Langlois-Meurinne • Laurent Pétin Givenchy • M. et Mme Bertrand • François Thomé René Bardin • COMBATTRE LA • Christian Gloz • Philippe Lassus • M. et Mme Patrice • Claude Taittinger Meunier • Antoine et Enrica • Guy et Denise PARALYSIE • M. et Mme Gorriquer • Alain Lazimi Piccon • Astrid Therond • Renée Mullie Van Caloen Bechter • COTY INC. • Jean-François et • LE CHEVAL • Luciano Pietropoli • Alain Thinot This year again, the • NESTLÉ FRANCE SAS • Albert Uderzo • François Benais • M. et Mme Robert Dominique FRANCAIS • PMU • Nicole Toulouse • Eric et Hervé • UNIM • Robert Bensoussan Counoy Gouédard • Arlette Le Gall • M. et Mme Henri de • TRACE ONE Paris Brain Institute Neubauer • Thierry Varène • Claude Berda • Antoine et Ariane de • M. et Mme Pierre- • LES VOILES DE Ponnat • Nicolas de could count on the • Claude Pequart • Antoine Virgili • BIOCODEX Courcel Henri Gourgeon SAINT BARTHES • POTEL & CHABOT Turckheim • ORKYN • Yves Rocher • BIOGEN FRANCE • Charlie Coutouly • GRAND HÔTEL • Maurice Lesaffre SA • M. et Mme Guy precious support of the • Gilles et Sylvie • Famille Yoël Zaoui SAS • CRÉDIT AGRICOLE INTER • Nicolas Lescure • Philippe Pourchet Ullens actor Guillaume de Pélisson • 15 anonymes • Jean-Claude Biver CENTRE OUEST CONTINENTAL • Haim Leshanot • Margaux Primat • Patrick Vegeais • Luciano Pietropoli • Alain et Blandine • M. et Mme Cromback PARIS • LIONS CLUB DES • Pierre Pringuet • Jean Veil Tonquédec, as • John Persenda Bizot • Françoise Crouzet • Allan Green ESSARTS • PRODUCTION ET • VERTU MAJOR ambassador of the • Jean Peter • M. et Mme Jean de • Olivier Dassault • GROUPE BABILOU • Jacques et Irène MARCHÉS • Corinne et Ramon DONORS • Jean-Luc Blanquet du Chayla • Jean-Luc Davesne • GROUPE LHOIST Lombard • Bertrand Puech Villagrasa Découvreurs d’Espoir Petithuguenin • ADCY5.ORG • BLB SARL • Danielle Decaux • Caroline • L’ORÉAL • Paul Raingold • VINCI campaign. • PHILIP MORRIS • ALAIR & AVD • BMENERGIE • Blandine et Philippe Guerrand-Hermès • Francis • M. et Mme Patrick CONCESSIONS INTERNATIONAL • Marie-José Alfandari • M. et Mme André Delaunay • Jérôme Lotigie-Browaeys Rannou • Olimpia Weiller • Caroline et Olivier • Jean-Luc Allavena Bohm • Anne-Marie Depours Guerrand-Hermès • Daniel Louppe • Alain Ranval • Georges et Sophie Plantefève • ALTIUS TEMPORIS • Francis Boileau • Danielle Dubuit • Pierre Guichet • Bob Manoukian • Elisabeth Ratte Winter • Jacques Popper • Gabriel Roland • Charles de Boisriou • M. et Mme Claude • Vivien de Gunzburg • François Manset • Alain Rauscher • XO EDITIONS • Claude et Benoît Amare • Famille Eric Boizel Dumas Pilhou • Marc Haeberlin • Gilles de Margerie • M. et Mme Jean- • Gérard Zimmerlin Potier • Colette Amram • M. et Mme Michel • Paul Dupuy • Maria Halphen • M. et Mme Hervé Pierre Raynal • Vanessa Von • Colette Schumacher • Philippe André Yves Bolloré • M. et Mme Claude • Joseph Hamburger Margolis • Alain Recoules Zitzewitz • RELAIS & • Manuel et Marie- • Yves Boucheny Elmaleh • Bob Harifin • Monsieur • Simon Robertson • Anonymes CHÂTEAUX Thérèse Arango • BOURSE CATHY • EMERAUDE • Camille Henrot Marinopoulos • Bruno Roger • Jean Réno • ARTEMIS LEITUS INTERNATIONAL • Brigitte Hidden • Jean Pierre Martel • Patrick Roque

62 — PARIS BRAIN INSTITUTE - ANNUAL REPORT2019REPORT 2019 © : Bernard Simoni. Mathieu Génon. Jean-Philippe Parienté. Jean-Michel Wilmotte & associés. INRIA. CNRS. Glénat. Groupe Publicis. Nicolas Renier. Martin Carbo-Tano. Stéphane Lehéricy. Alexandre Bône. Conception : Guillaume Leynaert. Printing : BBCREATIONS