Institut du Cerveau https://institutducerveau-icm.org Tue, 24 Nov 2020 15:30:14 +0000 https://wordpress.org/?v=4.9.13 hourly 1 https://wordpress.org/?v=4.9.13 Stanley Durrleman, winner of the Inria – Young researcher Prize of the French Academy of Sciences https://institutducerveau-icm.org/en/actualite/stanley-durrleman-inria-academy-sciences/ https://institutducerveau-icm.org/en/actualite/stanley-durrleman-inria-academy-sciences/#respond Tue, 24 Nov 2020 12:30:45 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20363 Stanley Durrleman, co-leader of the "ARAMIS - Algorithms, Models and Methods for Images and Signals of the Human Brain" team at the Paris Brain Institute, received For more information ]]> Stanley Durrleman, co-leader of the “ARAMIS – Algorithms, Models and Methods for Images and Signals of the Human Brain” team at the Paris Brain Institute, received the Inria Young researcher prize from the French Academy of Sciences for his work.

This €20,000 prize rewards the work of Stanley Durrleman and his team on the development of statistical learning methods and the design of predictive models of the evolution of neurodegenerative diseases such as Alzheimer’s or Parkinson’s. He has developed algorithms capable of predicting the progression of Alzheimer’s disease in patients over the next four years. This tool could play a key role in evaluating the effectiveness of therapeutics for neurodegenerative diseases.

I am very honoured to receive this prestigious award. It is recognition of work that has been built at the frontier between several disciplines: mathematics, computer science, neuroscience and medicine. We are now looking to use our tools to help demonstrate the effectiveness of promising treatments by administering them at the right time to the right patient. ”

Stanley Durrleman

 

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MAKING SENSE OF THE WORLD: THE CEREBRAL BASES OF ABSTRACTION https://institutducerveau-icm.org/en/actualite/cerebral-bases-abstraction/ https://institutducerveau-icm.org/en/actualite/cerebral-bases-abstraction/#respond Thu, 19 Nov 2020 13:40:40 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20340 A study conducted at the Zuckerman Institute of Columbia University (USA) by Jerome Munuera, co-first author and researcher at the Paris Brain Institute, and his For more information ]]> A study conducted at the Zuckerman Institute of Columbia University (USA) by Jerome Munuera, co-first author and researcher at the Paris Brain Institute, and his collaborators, led to the development of the first functional model of abstraction in the brain. The results are published in the prestigious journal Cell.

The curse of dimensionality plagues models of reinforcement learning and decision making. The process of abstraction solves this by constructing variables describing features shared by different instances, reducing dimensionality and enabling generalization in novel situations. Here, we characterized neural representations in monkeys performing a task described by different hidden and explicit variables. Abstraction was defined operationally using the generalization performance of neural decoders across task conditions not used for training, which requires a particular geometry of neural representations. Neural ensembles in prefrontal cortex, hippocampus, and simulated neural networks simultaneously represented multiple variables in a geometry reflecting abstraction but that still allowed a linear classifier to decode a large number of other variables (high shattering dimensionality). Furthermore, this geometry changed in relation to task events and performance. These findings elucidate how the brain and artificial systems represent variables in an abstract format while preserving the advantages conferred by high shattering dimensionality.

Source

The Geometry of Abstraction in the Hippocampus and Prefrontal Cortex. Bernardi S, Benna MK, Rigotti M, Munuera J, Fusi S, Salzman CD. Cell. 2020 Oct 9

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Healthy Mind and Uptale selected for STATION F’s Future 40 ranking https://institutducerveau-icm.org/en/actualite/healthy-mind-uptale-stationf/ https://institutducerveau-icm.org/en/actualite/healthy-mind-uptale-stationf/#respond Wed, 18 Nov 2020 16:00:20 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20350 On November 18, Station F unveiled the second edition of its Future 40 ranking. 2 startups hosted in our incubator iPEPS -The Healthtech Hub are included: Healthy For more information ]]> On November 18, Station F unveiled the second edition of its Future 40 ranking. 2 startups hosted in our incubator iPEPS -The Healthtech Hub are included: Healthy Mind and Uptale.

These start-ups were chosen among the 1.000 companies of STATION F according to different criteria such as their size and growth, their innovative technology, their expertise or their team.

Healthy Mind

Healthy Mind is a startup offering virtual therapies to relieve the pain and anxiety of hospitalized patients.

By combining neuroscience, psychology and virtual reality technologies, the company has developed and commercialized two products:

  • a virtual reality solution that uses the processing power of a computer to deliver real-time experiences while providing in-depth customization and personalized medical hypnosis features to healthcare professionals
  • a completely autonomous solution focused on on the friendliness, the user experience and the ergonomics.

Uptale

Uptale is developing a training solution for companies using immersive learning. The startup deploys a cloud platform using virtual reality at scale and neurotechnologies to create and deliver 360° training.

The different modules made available to companies allow reinforcing the skills of operational teams, improving the onboarding of new employees or creating empathy in different situations.

 

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A new custom-made multi-photon microscope at the Paris Brain Institute https://institutducerveau-icm.org/en/actualite/custom-made-multi-photon-microscope/ https://institutducerveau-icm.org/en/actualite/custom-made-multi-photon-microscope/#respond Wed, 04 Nov 2020 15:39:00 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20260 The Paris Brain Institute has acquired a new state-of-the-art multi-photon microscope thanks to the support of the Edmond J. Safra Foundation. This custom-built For more information ]]> The Paris Brain Institute has acquired a new state-of-the-art multi-photon microscope thanks to the support of the Edmond J. Safra Foundation. This custom-built microscope will enable several teams at the Institute to carry out highly advanced explorations on multiple scales.

For the past few weeks, the Paris Brain Institute has been equipped with a new multi-photon microscope, tailored to the needs of its researchers, thanks to the support of the Edmond J. Safra Foundation, which, along with its Chairwoman, Mrs. Lily Safra, is among the most significant donors to the Institute.

The multi-photon microscope is an instrument that allows scientists to acquire images deep inside the brain of a still developing animal, or while it is performing a behavioural task. This type of instrument is essential for establishing links between brain activity and behaviour.

Because each type of experience is unique, a multi-photon microscope must be versatile and customizable. By working with Bruker, a leading company specializing in the construction of these devices, the experts of the Paris Brain Institute have designed instruments that meet their needs.

Two pulsed infrared lasers, two very sensitive detectors, custom-made microscope stand, and the swivel objective allow a great freedom on the type of samples visualized and experimental conditions. This microscope is particularly well suited for studies in drosophila but can also be used in behavioral studies in zebrafish and mice, conducted by several teams at the Paris Brain Institute. » Basile Gurchenkov, operational manager of the ICM.quant cell imaging platform.

 

ICM.quant Biomimaging core facility : https://quant.institutducerveau-icm.org

 

 

Several teams at the Paris Brain Institute have developed new research projects, using mice and fruit flies, based on special behavioral tests of very high level. The multi-photon microscope represents a major and absolutely essential piece of equipment for the Brain Institute.

Developmental and behavioral imaging work involves long-term experiments, in which each manipulation can occupy the instrument for several hours and sometimes up to 24 hours at a time. The acquisition of this equipment, thanks to the support of the Edmond J. Safra Foundation, provides a real impetus for the advancement of research, in particular our project to understand the cerebral bases of our individuality.“Bassem Hassan, team leader and scientific director of the Paris Brain Institute

I am very proud to make this new contribution to the Paris Brain Institute. I am confident that this cutting-edge equipment, in the hands of the Institute’s remarkable researchers, will lead to important advances in the quest for a fuller understanding of brain diseases.” Mrs. Lily Safra, Chairwoman of the Edmond J. Safra Foundation and Honorary Chairwoman of the Association of Friends of the Paris Brain Institute.

EMERGENCE OF BEHAVIORAL INDIVIDUALITY IN THE FLY’S BRAIN: A GENERAL PRINCIPLE FOR THE NEURODEVELOPMENTAL ORIGIN OF AN ASPECT OF PERSONALITY?

https://institutducerveau-icm.org/en/actualite/emergence-of-behavioral-individuality/

 

 

About the Edmond J. Safra Foundation

Edmond J. Safra, one of the 20th century’s most accomplished bankers and a devoted philanthropist, established a major philanthropic foundation to ensure that individuals and organizations would continue to receive his assistance and encouragement for many years to come. Under the chairmanship of his beloved wife Lily, the Edmond J. Safra Foundation draws continuing inspiration from its founder’s life and values. It has supported hundreds of organizations in more than 40 countries around the world, largely in its three main areas of focus: education, science and medicine, and religious life. In 2005, it enabled the creation of the Paris Brain Institute by financing the construction of its research building. Even today, its generous loyalty allows researchers to continue their fight against diseases of the nervous system. www.edmondjsafra.org

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Alberto Bacci receives the Camille Woringer Award from the Fondation pour la Recherche médicale https://institutducerveau-icm.org/en/actualite/alberto-bacci-camille-woringer-award/ https://institutducerveau-icm.org/en/actualite/alberto-bacci-camille-woringer-award/#respond Tue, 03 Nov 2020 10:59:09 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20234 Alberto Bacci, head of the "Cellular Physiology of Cortical Microcircuits" team at the Paris Brain Institute, received the Camille Woringer Award from the Fondation For more information ]]> Alberto Bacci, head of the “Cellular Physiology of Cortical Microcircuits” team at the Paris Brain Institute, received the Camille Woringer Award from the Fondation pour la Recherche médicale.

The prize, worth €7,000, is intended to support research on brain diseases.

Alberto Bacci’s team is particularly interested in brain circuits of sensory perception. How is sensory information from the environment integrated at the level of the cerebral cortex to generate an adequate response? To answer this question, they study different populations of neurons in the cortex, their interactions and the connections they establish between them. The functioning of these networks requires as many neuron activation processes as inhibition processes in order to control the flow of information. Of particular importance for this are the interneurons. Structured interactions between these different types of cells in the cortex is essential to generate coherent representations of perceived information.

The study of brain circuits involved in the integration of sensory information is essential because several brain pathologies such as schizophrenia or autism are characterized by a disturbance of sensory perception and other cognitive functions. Studying the functioning of these networks is an essential step to better understand the alterations present in neurological and psychiatric diseases in order to provide therapeutic solutions.

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A promising therapeutic approach in amyotrophic lateral sclerosis (ALS) https://institutducerveau-icm.org/en/actualite/therapeutic-approach-amyotrophic-lateral-sclerosis-als/ https://institutducerveau-icm.org/en/actualite/therapeutic-approach-amyotrophic-lateral-sclerosis-als/#respond Tue, 20 Oct 2020 10:35:48 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20148 Paris, October 19th, 2020 - ALS is characterized by the degeneration of motor neurons resulting in a progressive and irreversible deficit in walking and speech, For more information ]]> Paris, October 19th, 2020 – ALS is characterized by the degeneration of motor neurons resulting in a progressive and irreversible deficit in walking and speech, until a complete paralysis of all muscles, including those controlling respiration. The team led by Séverine Boillée (Inserm researcher) at the Paris Brain Institute has just published work in the prestigious scientific journal Nature Neuroscience, paving the way to a new therapeutic approach for this still incurable disease.

Ten percent of ALS cases are familial, linked to mutations in genes, identified in 2/3 of cases. Experimental models (particularly in mice) in which the SOD1 gene is mutated,  reproduce the clinical phenotype of the disease in humans and are used to study biological mechanisms of the disease, but also give the opportunity to test the efficiency and harmlessness of new treatments before using them in patients for therapeutic trials.

Spinal motor neurons affected in ALS have the particularity of being surrounded both by microglial cells in the spinal cord and by peripheral macrophages in the nerve, which is the part of the motor neuron exiting from the spinal column to connect peripheral muscles.

Macrophages are the blood cells at the forefront of the immune response whose main role is to defend the body against infections but also to contribute to heal the injured tissue during damage. Microglial cells (or microglia) are a subgroup of macrophages located in the central nervous system (spinal cord and brain).

While the role of microglia in motor neuron degeneration in ALS is now recognized, the role of circulating macrophages in disease progression was still controversial mainly because previous studies focused on their infiltration into the central nervous system while their implication, from the periphery, in the nerves during the course of the disease had not been fully demonstrated.

The objective of the project led by Séverine Boillée’s team was to show the involvement of these immune cells from the periphery since they would be more accessible in patients, in order to identify new therapeutic targets.

Using experimental mouse models and tissues of 11 patients suffering from ALS, the researchers were able to show for the first time:

– The ability of peripheral macrophages to influence, from the periphery, microglial cell activation in the central nervous system and motor neurons degeneration, showing a delay in the symptomatic phase and an increase in lifespan in the mouse model.

– Molecular profiles (transcriptomes) of microglial cells (in the spinal cord) and peripheral macrophages (in the sciatic nerve) are very different. This reflects the distinct response of these two cell types although closely related and reacting to the same event, the motor neuron death, and gives the possibility to identify new mechanisms to target for future therapies.

The authors of this work conclude for the first time that peripheral macrophages have an important role in the progression of amyotrophic lateral sclerosis (ALS), thus paving the way to new therapeutic strategies for patients.

In longer term, the development of research aiming at treating neurotoxic macrophages outside the central nervous system, i.e. in a less invasive manner could lead to a significant decrease in motor neuron death in ALS patients.

These results now constitute a promising treatment approach to be explored.

Source:

Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival.

Aude Chiot, Sakina Zaïdi, Charlène Iltis, Matthieu Ribon, Félix Berriat, Lorenzo Schiaffino, Ariane Jolly, Pierre de la Grange, Michel Mallat, Delphine Bohl, Stéphanie Millecamps, Danielle Seilhean, Christian S. Lobsiger and Séverine Boillée

NATURE NEUROSCIENCE. DOI: 10.1038/s41593-020-00718-z.

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NEW DATA CONFIRM THE BENEFIT OF DEEP BRAIN STIMULATION TO TREAT OBSESSIVE-COMPULSIVE DISORDERS https://institutducerveau-icm.org/en/actualite/brain-stimulation-obsessive-compulsive-disorders/ https://institutducerveau-icm.org/en/actualite/brain-stimulation-obsessive-compulsive-disorders/#respond Tue, 13 Oct 2020 14:48:17 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20133 A study by researchers and clinicians from the Paris Brain Institute (Inserm/CNRS/Sorbonne University) and AP-HP (Henri Mondor and Pitié-Salpêtrière Hospitals) For more information ]]> A study by researchers and clinicians from the Paris Brain Institute (Inserm/CNRS/Sorbonne University) and AP-HP (Henri Mondor and Pitié-Salpêtrière Hospitals) confirms the beneficial effect of deep brain stimulation on several brain structures in severe obsessive-compulsive disorders that are resistant to drug treatment. The results are published in the journal Biological Psychiatry.

For more than 10 years, deep brain stimulation has been a source of hope for the treatment of obsessive compulsive disorders (OCD), considered one of the most disabling disorders by the WHO. OCD is associated with more years of lost years due to disability than multiple sclerosis and Parkinson’s disease combined. It manifests itself in 2 main categories of symptoms: obsessions in the form of thoughts, images with unpleasant content that are involuntarily imposed on the subject. These obsessions generate major anxiety and require the person to perform repeated behaviors and rituals to try to calm these distressing ideas.

Cognitive-behavioural psychotherapy (CBT) and/or serotonergic antidepressants prescribed in high doses to achieve an anti-OCD effect, improve the symptoms of two-thirds of patients. For the remaining third, therapeutic strategies involve complex combinations of treatments, and for a part of them, deep brain stimulation (DBS) represents a real therapeutic perspective.

In a new study, published in the journal Biological Psychiatry, researchers and clinicians from the Paris Brain Institute analyzed the effects of DBS on three brain structures, the subthalamic nucleus, the accumbens nucleus and the caudate nucleus, in 8 patients with severe OCD resistant to all available treatments. This is the first study comparing the effect of DBS on three distinct targets in the brain in the same patients.

Their results show an almost equivalent reduction in symptoms regardless of the structure stimulated after 3 months of stimulation, but the majority of patients expressed a subjective preference for the stimulation of a region of the subthalamic nucleus, without knowing that it was this structure that was targeted. They also highlight the possibility of identifying early predictors of response to long-term subthalamic nucleus stimulation.

“Consistent with our previous results*, we also observed a significant improvement of symptoms in longer-term in 3 patients responding to subthalamic nucleus stimulation and a partial response in another 3 patients. This suggests that the most beneficial effects of DBS may be delayed and that this should be taken into account in patient follow-up. The “blinded” choice of patients for this target also shows the interest in taking into account clinical dimensions that go beyond the usual quantitative clinical evaluations to assess a therapeutic effect. “explains Luc Mallet, Professor of Psychiatry at the University of Paris Est Créteil and researcher at the Paris Brain Institute.

The present study confirms the benefit of stimulating different deep brain structures in patients with severe obsessive-compulsive disorders that are resistant to other available treatments, underlining the interest of precisely identifying the neural networks underlying these disorders. Research is still needed to identify precise characteristics that predict whether or not patients will respond to deep brain stimulation.

* Mallet, L., Du Montcel, S. T., Clair, A.-H., Arbus, C., Bardinet, E., Baup, N., Chabardès, S., Chéreau, I., Czernecki, V., Fontaine, D., Harika-Germaneau, G., Haynes, W. I., Houeto, J.-L., Jaafari, N., Krack, P., Millet, B., Navarro, S., Polosan, M., Pelissolo, A. and Welter, M.-L. (2019) ‘Long-term effects of subthalamic stimulation in Obsessive-Compulsive Disorder: Follow-up of a randomized controlled trial’, Brain Stimulation, 12(4), 1080-1082.

Source
Deep Brain Stimulation of the Subthalamic, Accumbens, or Caudate Nuclei for Patients With Severe Obsessive-Compulsive Disorder: A Randomized Crossover Controlled Study.
 Welter ML, Alves Dos Santos JF, Clair AH, Lau B, Diallo HM, Fernandez-Vidal S, Belaid H, Pelissolo A, Domenech P, Karachi C, Mallet L. Biol Psychiatry. 2020 Oct 2

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Neural mechanisms resolving exploitation-exploration dilemmas in the medial prefrontal cortex https://institutducerveau-icm.org/en/actualite/neural-mechanisms/ https://institutducerveau-icm.org/en/actualite/neural-mechanisms/#respond Thu, 08 Oct 2020 10:12:18 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20105

Everyday life often requires arbitrating between pursuing an ongoing action plan by possibly adjusting it versus exploring a new action plan instead. Resolving For more information ]]>

Everyday life often requires arbitrating between pursuing an ongoing action plan by possibly adjusting it versus exploring a new action plan instead. Resolving this so-called exploitation-exploration dilemma involves the medial prefrontal cortex (mPFC). Using human intracranial electrophysiological recordings, we discovered that neural activity in the ventral mPFC infers and tracks the reliability of the ongoing plan to proactively encode upcoming action outcomes as either learning signals or potential triggers to explore new plans. By contrast, the dorsal mPFC exhibits neural responses to action outcomes, which results in either improving or abandoning the ongoing plan. Thus, the mPFC resolves the exploitation-exploration dilemma through a two-stage, predictive coding process: a proactive ventromedial stage that constructs the functional signification of upcoming action outcomes and a reactive dorsomedial stage that guides behavior in response to action outcomes.

Source

Neural mechanisms resolving exploitation-exploration dilemmas in the medial prefrontal cortex.

Domenech P, Rheims S, Koechlin E. Science. 2020 Aug 28

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WINDOW TO OUR DREAMS AND NIGHTMARES https://institutducerveau-icm.org/en/actualite/dreams-nightmares/ https://institutducerveau-icm.org/en/actualite/dreams-nightmares/#respond Thu, 01 Oct 2020 12:43:46 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20342 What could be more enigmatic than a dream? That experience we live every night, even if we don't remember it when we wake up. What can they teach us? The progress of For more information ]]> What could be more enigmatic than a dream? That experience we live every night, even if we don’t remember it when we wake up. What can they teach us? The progress of neurosciences allows us today to better understand this mysterious phenomenon. In a review published in Lancet Neurology, Francesca Sidari, Katja Valli and Isabelle Arnulf, head of the sleep pathology department at the Pitié-Salpêtrière Hospital and researcher at the Paris Brain Institute, explore the different aspects of our dreams and nightmares and the prospects for neurological diseases.

Dreams are experiences that occur during sleep, while we are disconnected from the environment. Thanks to recent progress in neuroimaging techniques, it is now becoming possible to relate dream features to specific patterns of brain activity. Some conditions occurring in patients with neurological disorders, such as lucid dreams and parasomnias, not only have diagnostic value, but also offer a window into the dream process. They show that dreaming is reflected in physiological signals, behaviours, and brain activity patterns, and that the body can enact dream content. Yet, the dream body can also be distinct from the real body; in their dreams, patients with congenital paraplegia can walk, those with sleep apnoea rarely suffocate, and phantom limb pain can disappear. These conditions provide valuable models for future studies investigating the mechanisms that underlie oneiric experiences.

Source
Dreams and nightmares in healthy adults and in patients with sleep and neurological disorders.
 Siclari F, Valli K, Arnulf I. Lancet Neurol. 2020.

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Cohort Covid Neuroscience project offers insight to COVID-19 risks and impacts https://institutducerveau-icm.org/en/actualite/neuroscience-covid-19-risks-impacts/ https://institutducerveau-icm.org/en/actualite/neuroscience-covid-19-risks-impacts/#respond Mon, 28 Sep 2020 10:18:50 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=20047 Paris Brain Institute's Cohort Covid Neuroscience project is studying the neurological and psychiatric consequences of SARS-CoV-2 infection over the course of one For more information ]]> Paris Brain Institute’s Cohort Covid Neuroscience project is studying the neurological and psychiatric consequences of SARS-CoV-2 infection over the course of one year. This unique study focuses on two aspects: the direct effects of Covid-19 on the central nervous system and the impact of the infection on patients suffering from neurological diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis.

The project’s initial results, six months after the start of the study, have already identified a notable range of impacts of the disease and factors that impact the severity of COVID-19.

Multiple Sclerosis (MS) can increase the risk of severe COVID-19, according to study findings published in JAMA Network. In the way that age and obesity are recognized factors, the severity of neurological disability as a result of MS (the scale of which is known as the EDSS score) is linked to increased COVID-19 risk (requiring at least one hospitalization), although no association was found between disease modifying therapy (DMTs) exposure to treat the neurological condition and COVID-19 severity.

Several types of brain abnormalities have been identified in patients with Covid-19, through brain imaging and the neuroradiology teams of the medical-university Neuroscience Department of the Pitié-Salpêtrière Hospital. Published in Radiology, these findings provide important brain imaging data in patients with COVID-19 and identifies several potential brain targets for CoV-2 SARS infection.

Other publications in the European journal of neurology describe common features of encephalopathy visible on PET-scan, following SARS CoV-2 infection, which may reflect an immune mechanism. Cases of movement disorders were also reported, such as upper limb postural and action tremor, orthostatic tremor and myoclonus. Appearing several weeks after intensive care unit discharge, several hypotheses will be addressed in the future on the mechanisms involved, from direct central nervous system damage by SARS-CoV-2 and immune-mediated mechanism to metabolic origin.

Initial findings are helping researchers and clinicians build a better understanding of the neurological and psychiatric manifestations of Covid-19 and to develop new treatments to help patients in the best possible way. The efforts of researchers and clinicians to better characterize the neurological symptoms of patients have led to the development of a new therapeutic approach in intensive care units.

In the early weeks of the pandemic, neurological symptoms were reported by physicians in patients affected by Covid-19, such as loss of smell or taste, but also more serious conditions such as seizures or stroke. Faced with this challenge, in April 2020, over just a few weeks, the project mobilized the entire forces of the Neuroscience medical-university department of the AP-HP Pitié-Salpêtrière Hospital and the Paris Brain Institute, supported by the International Automobile Federation (FIA), the FIA Foundation and the Institute’s donors. Researchers and clinicians have accomplished the feat of setting up the study programme in a short time-frame, from clinical and ethical authorizations to the establishment of the database and a steering committee.

More than 500 subjects are now enrolled in the study. Data collection, inclusion in a common database and analysis by the Paris Brain Institute’s biostatistics teams can be done in parallel with the entry of patients into the cohort. This is a considerable time saving in order to obtain information on the neurological consequences of Covid-19 and to be able to act almost in “real time” in patients.

Much more work is in the pipeline on stroke, brain tumor patients, and Parkinson’s disease. In addition, there is still much data already acquired to be analyzed, particularly biological data, which will provide a better understanding of the immune response to infection in patients suffering from immune-related pathologies such as multiple sclerosis. At the same time, long-term follow-up of patients on clinical, cognitive, biological and imaging aspects is underway to define the characteristics of the SARS-CoV-2 infection in the long term.

This study, which has mobilized the entire neurology and psychiatry community at the Pitié-Salpêtrière Hospital and many French centers, now goes beyond the national borders with collaborations with prestigious research centers such as Yale or Liverpool University and in international consortiums. They will be key to increasing our knowledge of the infection and its consequences on the central nervous system, always to the primary benefit of patients.

Sources: Publications resulting from research

  • Delorme et al. Covid-19-related encephalopathy: a case series with brain FDG-PET/CT findings. Eur J Neurol. 2020. DOI:1111/ene.14478
  • Chougar et al. Retrospective observational study of brain MRI findings in patients with acute SARS-CoV-2 infection and neurological manifestations. Radiology. 2020 DOI:1148/radiol.2020202422
  • Louapre et al. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol. 2020 DOI:1001/jamaneurol.2020.2581
  • Altmayer et al. Therapeutic plasma exchange in a critically ill Covid-19 patient. J Clin Apher. 2020DOI:1002/jca.21830
  • Cao et al. Severe Covid-19-related encephalitis can respond to immunotherapy. Brain. Accepted. (preprint: hal-02918661)
  • Cuhna et al. Movement disorders as a new neurological clinical picture in severe SARS-CoV2 infection. Eur J Neurol. 2020. DOI:1111/ene.14474

 

 

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RICHARD MILLE STRENGTHENS HIS COMMITMENT TO THE PARIS BRAIN INSTITUTE https://institutducerveau-icm.org/en/actualite/richard-mille-strengthens-his-commitment-to-the-paris-brain-institute/ https://institutducerveau-icm.org/en/actualite/richard-mille-strengthens-his-commitment-to-the-paris-brain-institute/#respond Thu, 17 Sep 2020 13:58:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19919 Richard Mille, new member of the Paris Brain Institute's Campaign Committee, mobilizes his company and supports actions to finance research programs and increase the For more information ]]> Richard Mille, new member of the Paris Brain Institute’s Campaign Committee, mobilizes his company and supports actions to finance research programs and increase the Institute’s visibility.

The first event that symbolizes this mobilization is the 24 Hours of Le Mans.

 

  •  1st 24 Hours of Le Mans for the Richard Mille Racing Team 
  • 100% Female crew composed of Tatiana Calderón, Sophia Floersch and Beitske Visser 
  • The race is dedicated to the Paris Brain Institute

Speed records may or may not be broken next weekend at Le Mans. Stereotypes, on the other hand, definitely will! The Richard Mille Racing Team, an all-female driver line-up is revving up this, the 88th edition of the world’s most famous motor race. 

[…]

‘Since the creation of this institute in Paris some 10 years ago it has grown to become one of the leading research centres for brain and spinal illnesses that can touch each and every one of us by the sheer magnitude of all those affected. This institute is the 2nd largest in the world dedicated to this cause and gathers very experienced researchers from all corners of the globe. My friendship towards Professor Gérard Saillant and Jean Todt only strengthens my commitment to this cause and to bring it to the attention of all those close to the brand so that as many people as possible are aware of this institute and its quest to cure the multiple diseases linked to the brain,’ explains Richard Mille.

 

 ‘I would like to warmly thank Richard Mille for his renewed support to the Paris Brain Institute through his first participation in the 24 Heures du Mans with an all-female team. This unique sporting competition embodies values of combativeness, perseverance and excellence that the Paris Brain Institute fully shares. Richard Mille’s commitment at our side represents a great strength for us, as it allows us to further develop the means of our ambitions, to increase the visibility of our commitment to an essential public health cause and gives our researchers the opportunity to go even further in their research work at the service of patients’. – Professor Gérard Saillant, President of the Paris Brain Institute.

Read Richard Mille’s Press Release in its entirety

Richard Mile

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Huntington’s disease: brain abnormalities detectable as early as the embryonic stage https://institutducerveau-icm.org/en/actualite/huntingtons-disease-alters-human-neurodevelopment/ https://institutducerveau-icm.org/en/actualite/huntingtons-disease-alters-human-neurodevelopment/#respond Fri, 17 Jul 2020 13:15:14 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=19551 Although Huntington’s disease is a late-manifesting neurodegenerative disorder, both mouse studies and neuroimaging studies of presymptomatic mutation carriers For more information ]]> Although Huntington’s disease is a late-manifesting neurodegenerative disorder, both mouse studies and neuroimaging studies of presymptomatic mutation carriers suggest that Huntington’s disease might affect neurodevelopment. To determine whether this is actually the case, we examined tissue from human fetuses (13 weeks gestation) that carry the Huntington’s disease mutation. These tissues showed clear abnormalities in the developing cortex, including mislocalization of mutant huntingtin and junctional complex proteins, defects in neuroprogenitor cell polarity and differentiation, abnormal ciliogenesis, and changes in mitosis and cell cycle progression. We observed the same phenomena in Huntington’s disease mouse embryos, where we linked these abnormalities to defects in interkinetic nuclear migration of progenitor cells. Huntington’s disease thus has a neurodevelopmental component and is not solely a degenerative disease.

Sources :

Huntington disease alters human neurodevelopment

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A LARGE-SCALE EXPLORATION OF GENETIC FORMS OF PARKINSON’S DISEASE https://institutducerveau-icm.org/en/actualite/a-large-scale-exploration-of-genetic-forms-of-parkinsons-disease/ https://institutducerveau-icm.org/en/actualite/a-large-scale-exploration-of-genetic-forms-of-parkinsons-disease/#respond Mon, 06 Jul 2020 08:19:27 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19450 Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson's disease For more information ]]> Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson’s disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ-1 mutations in a cohort of 1587 cases. Mutations were found in 14.1% of patients: 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians whereas PINK1 mutations predominated in Arab-Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa-induced motor complications, dysautonomia, and dementia than those without mutations.

 

Source :

Characterization of recessive Parkinson’s disease in a large multicenter study. Lesage S, et al. Ann Neurol. 2020 May 30.

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COVID-19: FIA FOUNDATION AND FIA SUPPORT THE BRAIN INSTITUTE https://institutducerveau-icm.org/en/actualite/covid-19-fia-foundation-and-fia-support-the-brain-institute/ https://institutducerveau-icm.org/en/actualite/covid-19-fia-foundation-and-fia-support-the-brain-institute/#respond Tue, 30 Jun 2020 12:18:17 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19429 LAUNCH OF AN UNPRECEDENTED STUDY TO FIND OUT THE IMPACT OF COVID-19 ON THE NERVOUS SYSTEM:

THE FIA FOUNDATION AND FIA PLEDGE SUPPORT FOR THE PARIS BRAIN For more information ]]> LAUNCH OF AN UNPRECEDENTED STUDY TO FIND OUT THE IMPACT OF COVID-19 ON THE NERVOUS SYSTEM:

THE FIA FOUNDATION AND FIA PLEDGE SUPPORT FOR THE PARIS BRAIN INSTITUTE

 

The Paris Brain Institute, in partnership with the AP-HP, Sorbonne-Université, Medico-University Department of Neurosciences at the Pitié-Salpêtrière Hospital, with grant of €400,000 from the FIA Foundation – historical patron of the Institute with a focus on public health – and support from FIA, is launching a major study to rapidly and accurately assess all the potential neurological and psychiatric impacts of Covid-19 on affected patients, with the aim of improving patient management, follow-up and rehabilitation.

 

Covid-19 is a multi-targeted viral disease whose disorders caused by the virus surprise by the diversity of symptoms, sometimes atypical. In addition to the lungs, many other organs can be affected by Covid-19 and lead to neurological complications such as loss of smell, loss of taste, headaches, dizziness, convulsions, stroke, altered consciousness and hemiplegia. In addition, the respiratory difficulties observed in patients with Covid-19 may be due to brain stem involvement in addition to the lungs. This region, located between the brain and the spinal cord, contains the centres that control breathing. However, experts know little about the overall impact of this coronavirus on the central nervous system, even though more than 10 million people worldwide are currently affected by the virus.

 

The data collected will be the subject of in-depth analysis, notably using artificial intelligence. The information obtained will be exploited in real time in order to draw practical consequences for patients as quickly as possible by May 2021.

 

 At the Paris Brain Institute, our mission is to find in order to cure. Therefore, the observations of our eminent specialists on this study will be decisive in helping people with Covid-19 to receive appropriate care. This ambitious project is led by the Neuroscience Medico-University Department at the Pitié-Salpêtrière hospital and the clinicians-researchers at the Paris Brain Institute, thanks to the FIA Foundation and the FIA, in favor of health for all. I would like to thank them very warmly. 

Gérard Saillant, President of the Paris Brain Institute and President of the FIA Medical Commission.

 The study will focus on:

– the neuropsychiatric manifestations of the affected individuals

– the psychiatric consequences for the patients themselves (due in particular to very long periods of resuscitation) as well as for their relatives

– the consequences for patients already suffering from neurological pathologies such as inflammatory diseases (including multiple sclerosis) and neurodegenerative diseases (such as Parkinson’s and Alzheimer’s). 

 

The long-term effects of the coronavirus on health are only beginning to be understood, so this important project will provide vital information to share with the world. We at the FIA Foundation are proud of our longstanding relationship with the Institute and its cutting-edge research.

Saul Billingsley, Executive Director of the FIA Foundation.

 

The Paris Brain Institute is probably one of the few centres in the world that is able to provide a comprehensive view of the neurology and psychiatry of Covid-19 infection. In the medium term, this will enable us as health professionals to be prepared to face a new pandemic and to have all the weapons at our disposal to better fight it. We can also think that this infection, when it strikes brains already damaged by a neurodegenerative or inflammatory disease, could have unknown effects. It is very important to know whether we are going to observe very atypical developments, for example in patients being monitored for Alzheimer’s disease or multiple sclerosis. There’s still a lot we don’t know. 

Prof. Jean-Yves Delattre, Medical Director of the Paris Brain Institute and Director of the AP-HP-Sorbonne University Neuroscience Medico-University Department at the Pitié-Salpêtrière Hospital, Prof. Jean-Christophe Corvol, Scientific Director of the project and Dr. Delorme, Principal Investigator.

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Two new fundamental discoveries for the diagnosis and treatment of patients suffering from disorders of consciousness https://institutducerveau-icm.org/en/actualite/two-new-fundamental-discoveries-for-the-diagnosis-and-treatment-of-patients-suffering-from-disorders-of-consciousness/ https://institutducerveau-icm.org/en/actualite/two-new-fundamental-discoveries-for-the-diagnosis-and-treatment-of-patients-suffering-from-disorders-of-consciousness/#respond Thu, 25 Jun 2020 13:57:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19401 Two new fundamental discoveries for the diagnosis and treatment of patients suffering from disorders of consciousness

The research team led by Prof. Lionel Naccache For more information ]]> Two new fundamental discoveries for the diagnosis and treatment of patients suffering from disorders of consciousness

The research team led by Prof. Lionel Naccache at the Paris Brain Institute (Sorbonne Université, APHP, INSERM, CNRS) has just published two important studies which concern patients suffering from a lasting disturbance of consciousness (e.g.: patients in ” vegetative state “or” minimally conscious state”). These two original studies correspond to part of the PhD work of Dr. Bertrand Hermann (INSERM, APHP, University of Paris) carried out under the supervision of Lionel Naccache.

 

A new clinical sign to probe the state of consciousness

The first work describes the discovery and validation of a new sign of clinical examination which makes it possible to identify among these non-communicating patients those whose brain function is the richest.  The researchers observed that the auditory startle reflex in response to noise (i.e.: blinking of the eyelids following a sudden sound) presented a habituation in patients capable of anticipating stimulus repetition. When the sounds were repeated, these patients were able to inhibit this behavioral response. Conversely, an inextinguishable startle response was present in patients whose detailed clinical examination and cerebral explorations (EEG with quantified high density, cognitive evoked potentials, diffusion tensor MRI, PET-scan with fluoro-deoxy- glucose) revealed very poor brain and cognitive activity. Beyond this precious diagnostic value, the presence of this clinical sign, – easy to find at patient’s bedside -, also made it possible to predict an improvement in their state of consciousness at six months. The invention of new clinical signs based on the use of the most recent structural and functional brain imaging techniques also demonstrates the contemporary vitality and renewal of neurological semiology. Published in the world’s largest neurology journal (Brain), this article was chosen by the editorial board as “Editor’s choice” because of its innovative nature and importance.

 

Reference : Hermann, B., A. Ben Salah, V. Perlbarg, M. Valente, N. Pyatigorskaia, M. O. Habert, F. Raimondo, J. Stender, D. Galanaud, A. Kas, L. Puybasset, P. Perez, S. J.D., B. Rohaut and L. Naccache (in press). “Habituation of auditory startle reflex is a new sign of minimally conscious state.” Brain

https://academic.oup.com/brain/article/doi/10.1093/brain/awaa159/5862031?searchresult=1

Improving consciousness with transcranial direct current stimulation of the prefrontal cortex

The second work reveals how transcranial direct current electrical stimulation (tDCS) of the frontal lobe can improve conscious state in some of these patients. By comparing patients who showed behavioral improvement after a single session of tDCS, to patients who did not show such an improvement, the researchers demonstrated that the clinical response to tDCS was associated with an increase in specific EEG markers of consciousness (long distance oscillations and communication between the prefrontal and parietal regions in the theta frequency band). The researchers also used a simulation model of the distribution of electric current based on the individual anatomy of the patients, to show that the clinical response to tDCS was correlated with the intensity of the electric field in the cortex next to the stimulation electrodes. These results are important both on the clinical level – by paving the way to the development of new therapeutic strategies for personalized patterns of tDCS stimulation – and on the level of basic research by confirming the importance of the prefrontal cortex and the fronto-parietal network in the physiology of consciousness, – as postulated by the theory of global neuronal space developed over the past twenty years by Stanislas Dehaene, Jean-Pierre Changeux and Lionel Naccache. This work was published in the journal Scientific Reports of the Nature group.

 

Reference : Hermann, B., Raimondo, F., Hirsch, L., Huang, Y., Denis-Valente M., Pérez P., Engemann, D., Faugeras, F., Weiss, N., Demeret, S., Rohaut, B., Parra, L.C., Sitt, J.D., Naccache, L. Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness. Sci Rep 10, 4323 (2020). https://doi.org/10.1038/s41598-020-61180-2

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APPLY NOW FOR THE IMIND – INTERNATIONAL MASTER IN NEURODEGENERATIVE DISEASES ! https://institutducerveau-icm.org/en/actualite/apply-now-for-the-imind-international-master-in-neurodegenerative-diseases/ https://institutducerveau-icm.org/en/actualite/apply-now-for-the-imind-international-master-in-neurodegenerative-diseases/#respond Wed, 03 Jun 2020 09:19:37 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19335 Interested in Neurosciences and neurodegeneratives diseases?

The application campaign for the iMIND - International Master in Neurodegenerative Diseases - Master 2 For more information ]]> Interested in Neurosciences and neurodegeneratives diseases?

The application campaign for the iMIND – International Master in Neurodegenerative Diseases – Master 2 program is now open! CLOSING DATE: JUNE 30, 2020.

iMIND is a selective programme built on the partnership between the Paris Brain Institute and Sorbonne University.

 

iMIND gathers expert researchers from the Paris Brain Institute and Neuroscience Paris Seine Institute, providing the students with an immersive experience in up-to-date innovative research topics in order to understand the functioning of the brain in normal and pathological conditions.

Details regarding iMIND can be found:

In the two following links:

Information regarding the application process are detailed here.

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MSCopilot, a new multiple sclerosis self-assessment digital solution, is clinically validated https://institutducerveau-icm.org/en/actualite/mscopilot-multiple-sclerosis-digital-solution/ https://institutducerveau-icm.org/en/actualite/mscopilot-multiple-sclerosis-digital-solution/#respond Tue, 02 Jun 2020 13:40:36 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18544 MSCopilot, a new multiple sclerosis self-assessment digital solution developed by AdScientiam a startup incubated at iPEPS, has been clinically validated in a For more information ]]> MSCopilot, a new multiple sclerosis self-assessment digital solution developed by AdScientiam a startup incubated at iPEPS, has been clinically validated in a clinical trial involving several French hospitals. The results are published in the European Journal of Neurology.

Assessing patients’ disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC).

This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores.

In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot.

This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.

The MSCopilot application has been presented to neurologists through a video that you can discover below:

 

 

Source

MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.

Maillart E, Labauge P, Cohen M, Maarouf A, Vukusic S, Donzé C, Gallien P, De Sèze J, Bourre B, Moreau T, Louapre C, Mayran P, Bieuvelet S, Vallée M, Bertillot F, Klaeylé L, Argoud AL, Zinaï S, Tourbah A. Eur J Neurol. 2019 Sep 20.

 

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Schizophrenia, a myelin deficiency ? https://institutducerveau-icm.org/en/actualite/schizophrenia-a-myelin-deficiency/ https://institutducerveau-icm.org/en/actualite/schizophrenia-a-myelin-deficiency/#respond Thu, 14 May 2020 09:45:10 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=19139 Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia, NATURE COMMUNICATIONS.

Dorien MAAS, PhD and Brahim For more information ]]> Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia, NATURE COMMUNICATIONS.

Dorien MAAS, PhD and Brahim NAIT-OUMESMAR, co-team leader at the Paris Brain Institute, just published in Nature Communications on the prefrontal cortex myelination as a key feature in schizophrenia aetiology.

 

Abstract

Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Here we report that in the apomorphine-susceptible (APO-SUS) rat model, which has schizophrenia-like features, a myelination defect occurred specifically in parvalbumin interneurons. The adult rats displayed medial PFC (mPFC)-dependent cognitive inflexibility, and a reduced number of mature oligodendrocytes and myelinated parvalbumin inhibitory axons in the mPFC. In the developing mPFC, we observed decreased myelin-related gene expression that persisted into adulthood. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility. Collectively, these findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits.

 

Source :

Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia , NATURE COMMUNICATIONS volume 11, Article number: 2329 (2020)

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ACTIVATION OF THE INNATE IMMUNE SYSTEM IN THE CENTRAL NERVOUS SYSTEM, A MARKER FOR THE DEVELOPMENT OF DISABILITY IN MULTIPLE SCLEROSIS? https://institutducerveau-icm.org/en/actualite/activation-of-the-innate-immune-system-in-the-central-nervous-system-a-marker-for-the-development-of-disability-in-multiple-sclerosis/ https://institutducerveau-icm.org/en/actualite/activation-of-the-innate-immune-system-in-the-central-nervous-system-a-marker-for-the-development-of-disability-in-multiple-sclerosis/#respond Wed, 06 May 2020 09:14:05 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18817

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) For more information ]]>

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS).

Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and 18F-DPA-714 PET. A threshold of significant activation of 18F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as “DPA-active”, “DPA-inactive” or “unclassified”.

Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS.

Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.

 

Source

Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of disability worsening in Multiple Sclerosis. Bodini B, et al. J Nucl Med 2020.

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Mechanisms and therapeutic implications of hypermutation in gliomas https://institutducerveau-icm.org/en/actualite/mechanisms-and-therapeutic-implications-of-hypermutation-in-gliomas/ https://institutducerveau-icm.org/en/actualite/mechanisms-and-therapeutic-implications-of-hypermutation-in-gliomas/#respond Tue, 28 Apr 2020 15:24:44 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18874 A high tumour mutational burden (hypermutation) is observed in some gliomas1,2,3,4,5; however, the mechanisms by which hypermutation develops and whether it predicts For more information ]]> A high tumour mutational burden (hypermutation) is observed in some gliomas1,2,3,4,5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood.

Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide.

Experimentally, the mutational signature of post-treatment hypermutated gliomas was recapitulated by temozolomide-induced damage in cells with MMR deficiency. MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade.

Moreover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, single-cell whole-genome sequencing analysis of post-treatment hypermutated glioma cells identified microsatellite mutations.

These results show that chemotherapy can drive the acquisition of hypermutated populations without promoting a response to PD-1 blockade and supports the diagnostic use of mutational burden and signatures in cancer.

 

Source :

Mechanisms and therapeutic implications of hypermutation in gliomas, Nature 2020.

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Four core properties of the human brain valuation system demonstrated in intracranial signals https://institutducerveau-icm.org/en/actualite/four-core-properties-of-the-human-brain-valuation-system-demonstrated-in-intracranial-signals/ https://institutducerveau-icm.org/en/actualite/four-core-properties-of-the-human-brain-valuation-system-demonstrated-in-intracranial-signals/#respond Thu, 16 Apr 2020 15:05:35 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18844 Estimating the value of alternative options is a key process in decision-making. Human functional magnetic resonance imaging and monkey electrophysiology studies For more information ]]> Estimating the value of alternative options is a key process in decision-making. Human functional magnetic resonance imaging and monkey electrophysiology studies have identified brain regions, such as the ventromedial prefrontal cortex (vmPFC) and lateral orbitofrontal cortex (lOFC), composing a value system.

In the present study, in an effort to bridge across species and techniques, we investigated the neural representation of value ratings in 36 people with epilepsy, using intracranial electroencephalography.

We found that subjective value was positively reflected in both vmPFC and lOFC high-frequency activity, plus several other brain regions, including the hippocampus. We then demonstrated that subjective value could be decoded (1) in pre-stimulus activity, (2) for various categories of items, (3) even during a distractive task and (4) as both linear and quadratic signals (encoding both value and confidence). Thus, our findings specify key functional properties of neural value signals (anticipation, generality, automaticity, quadraticity), which might provide insights into human irrational choice behaviors.

 

Source

Four core properties of the human brain valuation system demonstrated in intracranial signals, Nature Neurosciences 2020.

 

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Covid-19 pandemic: Paris Brain Institute mobilizes and carries on https://institutducerveau-icm.org/en/actualite/covid-19-pandemic-paris-brain-institute-mobilizes-and-carries-on/ https://institutducerveau-icm.org/en/actualite/covid-19-pandemic-paris-brain-institute-mobilizes-and-carries-on/#respond Sat, 21 Mar 2020 07:00:46 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=18793 In the context of the coronavirus pandemic, the Paris Brain Institute pursues its research activity in the best way possible and participates actively in the effort For more information ]]> In the context of the coronavirus pandemic, the Paris Brain Institute pursues its research activity in the best way possible and participates actively in the effort to fight the virus and help patients.

The Covid-19 pandemic has disrupted our activities and put on hold our lab-based work to a significant extent. All research teams have reduced their experiments to the minimum necessary, focusing on bringing their ongoing experiments to a successful conclusion. Almost all our staff now work from home and pursue their activities in the best way possible under the circumstances, analyzing data, writing papers and grants, and using virtual tools to communicate with one another. Research never stops!

Located in the heart of the Pitié-Salpêtrière Hospital, which receives many Covid-19 patients, the Paris Brain Institute is in close contact with the medical teams and has already offered access to its equipment and skills to participate in the screening and care of patients.

Furthermore, all our clinicians who are members of both the Paris Brain Institute and the Neuroscience Medico-University department of the hospital are mobilized to support the medical teams taking care of Covid-19 patients, as Pitié-Salpêtrière is now the reference center for the Covid-19 patient care.

In these difficult times, we need to reaffirm our values:

– For communication based on scientific and medical research facts, especially in the context of much fake news and false information being spread all over the internet.

– At the service of patients and knowledge, always.

– Openness and collaboration are the key to progress and we do our best to offer as much help as possible to the teams fighting the virus.

We cannot predict how the situation will evolve over coming weeks and months, but we are confident that the efforts of the physicians, nurses and all healthcare and research professionals involved will prevail. Our thoughts go out to all, and in particular to those for whom this crisis is adding to the burden of an affected brain. When the dust settles on this pandemic, the millions who suffer from disorders of the brain and mind will still need us. I can assure you that the Paris Brain Institute will be there to pursue its commitment to understand the brain and its pathologies, at the service of patients and the public.

Sincerely,

Prof Alexis Brice, Executive Director

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Emergence of behavioral individuality in the fly’s brain https://institutducerveau-icm.org/en/actualite/emergence-of-behavioral-individuality/ https://institutducerveau-icm.org/en/actualite/emergence-of-behavioral-individuality/#respond Fri, 20 Mar 2020 08:59:03 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18755  Where does our individuality come from? What makes us unique in our behavior? Could it all be in our brain? Prof. Bassem Hassan* and his team discovered a For more information ]]>  Where does our individuality come from? What makes us unique in our behavior? Could it all be in our brain? Prof. Bassem Hassan* and his team discovered a stochastic wiring mechanism of circuits in the fly’s brain at the origin of individual behavior, which might represent a general principle of how certain aspects of individuality emerge in the brain. Results are published in Science.

 

 The idea that brain circuits regulate behavior is pretty straightforward notion. If a circuit is different between individuals, then it might influence their behavior individually. This could explain some of the behavioral idiosyncrasy present in population. But how to demonstrate this idea in an experimental setting?

 

“The first problem we had to tackle was: how do you find a behavior that corresponds to the wiring of these particular neurons?” explains Prof Bassem Hassan. “The breakthrough came when a colleague of mine, Andrew Straw, contacted me, to tell me that while he was studying a specific behavior, he found that the specific circuit we were studying regulated that behavior. This is when the adventure took a leap” explains Bassem Hassan

 

Bassem Hassan and his team have been working on this specific circuit of the brain, a visual system circuit called Dorsal Cluster Neurons (DCN) for several years. They had identified a stochastic anatomical and developmental variability in this system meaning that the brain of one fly develop slightly differently from the brain of another fly and as soon as the development is finished, that pattern is stable throughout the fly’s life.

But what about behavior? Is it as stable and unique as the circuit? To delve that question, the team started to test this behavior in flies for several weeks checking and showed this behavior remained constant in an individual fly but differed between flies. Moreover, they observed that with every generation the entire variance of the behavior was reset, meaning that the behavioral individuality was more the result of the unique development of each brain, than the specific genome of each individual.

 

“Now we had the behavior and the circuit, both unique to an individual fly and stable over time, but what is the link between the two?”

 

To explore this question, they conducted a series of experiments, led by Dr. Gerit Linneweber the first author of the study, in close collaboration with the team of Prof. Peter Robin Hiesinger in Berlin. By modifying the wiring in the flies’ brain and silencing DCN, an expertise they gathered from more than 10 years working on that circuit, they showed that the strongest anatomical correlate was left-right asymmetry in the wiring of a specific area that correlate with narrow or wide a path a fly would take toward an object. Not only that, but also a causal link between the circuit and behavior when rewiring the circuit happened to shift the flies’ behavior while maintaining the correlation between the circuit and the behavior in individual flies. These results established that the way the circuit develops causally underlies to a certain significant extent, the way the animal behaves.

 

“The idea that there is something innate about certain aspects of idiosyncrasy, that we would call “personality” in human psychology, and that it originates in the brain, is a very old idea. For the first time we can pinpoint to a clear distinctive brain-based origin for a parameter of what we could call an animal’s personality. The fact that it is due to developmental mechanisms that cannot be predicted either by the environment alone or the genome alone but from the phenomenon of stochastic developmental noise is super exciting. We are lucky enough to begin to solve two mysteries at the same time.

Doing this very basic research for a long time, which had no other obvious goal than understanding how the brain develops, and being able to show that by taking those approach and slowly building a knowledge base about a certain question you are interested in simply by curiosity-driven science, is extremely satisfying and a real reward for the effort of so many people in the team.” Concludes Bassem Hassan


*Bassem Hassan is scientific director and team leader at Paris Brain Institute, Allen Distinguished Investigator and “Einstein Visiting Fellow” of the Berlin Institute of Health at the Free University of Berlin.

 

Source

A neurodevelopmental origin of behavioral individuality in the Drosophila visual system.Linneweber GA et al, Science. March 2020.

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TOURETTE SYNDROME : MOTOR IMPULSES DO NOT PREDICT PATIENTS’ TICS https://institutducerveau-icm.org/en/actualite/tourette-syndrome-motor-impulses-do-not-predict-patients-tics/ https://institutducerveau-icm.org/en/actualite/tourette-syndrome-motor-impulses-do-not-predict-patients-tics/#respond Fri, 20 Mar 2020 07:53:32 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18745 CYRIL ATKINSON-CLÉMENT (Institut du Cerveau - ICM) AND YULIA WORBE (SORBONNE UNIVERSITÉ/APHP) IN THE TEAM “NORMAL AND ABNORMAL MOTOR CONTROL: MOVEMENT DISORDERS For more information ]]> CYRIL ATKINSON-CLÉMENT (Institut du Cerveau – ICM) AND YULIA WORBE (SORBONNE UNIVERSITÉ/APHP) IN THE TEAM “NORMAL AND ABNORMAL MOTOR CONTROL: MOVEMENT DISORDERS AND EXPERIMENTAL THERAPEUTICS” AT PARIS BRAIN INSTITUTE, SHOW THAT THE CONTROL OF MOTOR IMPULSIVITY, THE TRAIT THAT CHARACTERIZES THE ABILITY TO INHIBIT A MOVEMENT OR ACTION ALREADY STARTED, IS NOT CORRELATED WITH TICS IN PATIENTS WITH TOURETTE’S GILLES SYNDROME. THESE RESULTS, PUBLISHED IN THE JOURNAL CORTEX, SHED NEW LIGHT ON THIS COMPLEX PATHOLOGY.

 

Abnormality of inhibitory control is considered to be a potential cognitive marker of tics in Tourette disorder (TD), attention deficit hyperactivity disorder (ADHD), and impulse control disorders. The results of the studies on inhibitory control in TD showed discrepant results. The aim of the present study was to assess reactive inhibitory control in adult TD patients with and without antipsychotic medication, and under emotional stimulation (visual images with positive, neutral and negative content).

 

We assessed 31 unmedicated and 19 medicated TD patients and 26 matched healthy controls using the stop signal task as an index of reactive motor impulsivity and emotional stimulation with the aim to increase impulsivity. We performed a multimodal neuroimaging analysis using a regions of interest approach on grey matter signal, resting-state spontaneous brain activity and functional connectivity analyses.

 

We found a higher reactive motor impulsivity in TD patients medicated with antipsychotics compared to unmedicated TD patients and controls. This propensity for reactive motor impulsivity in medicated TD patients was not influenced by ADHD or emotional stimulation. Neuroimaging results in medicated TD patients suggested that reactive motor impulsivity was underpinned by an increased grey matter signal from the right supplementary motor area and inferior frontal gyrus; decreased resting-state spontaneous activity of the left putamen; higher functional connectivity between the inferior frontal gyrus and the superior temporal gyri (bilaterally); lower functional connectivity between the cerebellum and the right subthalamic nucleus.

 

Taken together, our data suggested (i) a deficit in reactive motor impulsivity in TD patients medicated with atypical antipsychotics that was unrelated to ADHD and (ii) that motor impulsivity was underpinned by structures and by functional connectivity of the fronto-temporo-basal ganglia-cerebellar pathway.

 

Source

Neural correlates and role of medication in reactive motor impulsivity in Tourette disorder.

Atkinson-Clement C, et al. Cortex 2019.

 

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Scipio bioscience raises €6.0 M Series A financing  https://institutducerveau-icm.org/en/actualite/scipio-bioscience-raises-e6-0-m-series-a-financing/ https://institutducerveau-icm.org/en/actualite/scipio-bioscience-raises-e6-0-m-series-a-financing/#respond Fri, 20 Mar 2020 07:10:48 +0000 Margaux Orsini https://institutducerveau-icm.org/?post_type=actualite&p=18702 To develop and launch a kit dedicated to sample preparation for single-cell RNA-sequencing 

Paris, 25 February 2020 - Scipio bioscience, a Paris-based biotechnology For more information ]]> To develop and launch a kit dedicated to sample preparation for single-cell RNA-sequencing 

Paris, 25 February 2020 – Scipio bioscience, a Paris-based biotechnology company, developing a new generation of single-cell sequencing solutions, announces today that it has secured a €6.0 M Series A financing from an international syndicate led by M Ventures (Amsterdam, The Netherlands), the corporate venture capital arm of Merck. The initial shareholders Seventure Partners’ Quadrivum I (Paris, France) and High-Tech Gründerfonds (Bonn, Germany) participated in the capital increase, alongside additional investors Financière Arbevel (Paris, France) and investiere (Zürich, Switzerland). 

There is a substantial unmet need for cost-effective single-cell sequencing methods. The availability of such methods will drive single-cell market growth globally, both in the basic and clinical research fields. Scipio bioscience is pioneering affordable single-cell sample preparation for sequencing. We fully support the team to deliver a much-needed solution based on their disruptive technology and to grow Scipio bioscience into a major player in single-cell biology” says Arnaud Autret, Investment Principal at M Ventures. 

Philippe Tramoy, Partner at the Quadrivium 1 seed capital fund at Seventure Partners, adds: “We are thrilled that our seed investment in Scipio’s truly deep tech project was crucial to turn its disruptive technology into a potential game changer. We look forward to getting to the next phases of development.  

Prof Stuart Edelstein, President, says: “We are convinced that our user-friendly kit, requiring no specific equipment and accessible for any benchtop, will enable thousands of additional scientists to perform single-cell RNA-sequencing. This availability will change the way biological questions are addressed and ultimately benefit both basic research and clinical applications. We are delighted to initiate collaborations for beta-testing of our kit, initially with Institut du Cerveau – ICM (Brain & Spine Institute, Paris, France) laboratories, as the interactions so far with its world-class teams and cutting-edge core facilities have been extremely fruitful. Our goal is to extend collaborations to leading European research institutes.” 

The €6.0 M Series A funding will fuel the final development of its single-cell RNA-sequencing kit, as well as marketing and business development efforts to prepare for commercial launch in 2022. 

About Scipio bioscience 

Scipio bioscience develops a new generation of single-cell sequencing solutions, to answer the growing needs of clinical and basic research labs. The patented technology is based on an innovative chemical approach conceived by its President and Co-Founder, Prof Stuart Edelstein, a world-renowned biophysicist. Pierre Walrafen, PhD, CEO and Co-Founder of Scipio Bioscience, directs a team composed of scientists with expertise in molecular biology, chemistry, and bioinformatics. The company, hosted in the iPEPS-Institut du Cerveau – ICM incubator of the Brain & Spine Institute (Institut du Cerveau – ICM, Pitié-Salpêtrière Hospital, Paris), has developed the protocol from the initial proof-of-concept studies to a prototype kit ready for beta-testing by collaborating research teams. Scipio bioscience was supported by a grant from the Région Île-de-France and the Programme d’Investissement d’Avenir, operated by BPI France. 

For more information: www.scipio.bio 

About M Ventures 

M Ventures is the strategic, corporate venture capital arm of Merck. Its mandate is to invest in innovative technologies and products with the potential to significantly impact the company’s core business areas. From its headquarters in Amsterdam and offices in the US and Israel, M Ventures invests globally in transformational ideas driven by great entrepreneurs. M Ventures takes an active role in its portfolio companies and teams up with entrepreneurs and co-investors to translate innovation towards commercial success. For more information, visit www.m-ventures.com 

About Quadrivium 1 Seed Fund 

The Quadrivium 1 Seed Fund is one of the venture funds managed by Seventure Partners. This fund finances French companies in the seed round (FNA – Future Investment Program) in the areas of Life Sciences & Digital Technologies, which are related to or linked to the academic cluster federated around the UPMC, Paris II University, Paris IV University, National Museum of Natural History, IRCAM, ENSCI, Technological University of Compiègne, CNRS, Curie Institute , Pierre Gilles de Gennes Foundation, Voir et Entendre Foundation and Paris Sciences et Lettres (PSL). 

About Seventure Partners 

With €750 M net commitments under management as of the end of 2018, Seventure Partners is a leading venture capital firm in Europe. Since 1997, Seventure Partners has been investing in innovative businesses with high growth potential in two fields: Life sciences across Europe, Israel, Asia and North America and Digital technologies in France and Germany. Investments can range between €500 k and €10 M per round, or up to €20 M per company, from early to late stage. Seventure Partners is a subsidiary of Natixis Investment Managers. Natixis is a subsidiary of Groupe BPCE, the second-largest banking group in France. 

For more details: www.seventure.fr/en Twitter: @seventurep 

About the High-Tech Gründerfonds 

High-Tech Gründerfonds (HTGF) is a seed investor that finances high-potential, tech-driven start-ups. With €895.5 M in total investment volume across three funds and an international network of partners, HTGF has already helped forge more than 560 start-ups since 2005. Driven by their expertise, entrepreneurial spirit and passion, its team of experienced investment managers and start-up experts help guide the development of young companies. HTGF’s focus is on high-tech start-ups in a range of sectors, including software, hardware and life sciences/ chemistry. To date, external investors have injected over €2 B into the HTGF portfolio via about 1,400 follow-on financing rounds. HTGF has also successfully sold interests in more than 100 companies. 

Investors in the public-private partnership include the German Federal Ministry of Economics and Energy, KfW Capital, the Fraunhofer-Gesellschaft and the commercial enterprises ALTANA, BASF, Bayer, Boehringer Ingelheim, B. Braun, Robert Bosch, BÜFA, CEWE, Deutsche Post DHL, Dräger, Drillisch AG, EVONIK, EWE AG, FOND OF, Haniel, Hettich, Knauf, Körber, LANXESS, media + more venture Beteiligungs GmbH & Co. KG, PHOENIX CONTACT, Postbank, QIAGEN, RWE Generation SE, SAP, Schufa, Schwarz Gruppe, STIHL, Thüga, Vector Informatik, WACKER and Wilh. Werhahn KG. 

About Financière Arbevel 

Founded in 1997, Financière Arbevel, an entrepreneurial investment management company, has grown significantly since its takeover by the current owners in early 2009 – the AUM progressed from €25 M to €1.9 B as of today (of which €752 M under the umbrella SICAV “Pluvalca” comprising 9 sub-funds). The company currently employs a total of 34 staff, of which 13 are dedicated to fund management/investment research. Financière Arbevel is recognized for its expertise within the small & mid cap asset class. We are a research-driven organization with a strong emphasis on fundamental financial and strategic analysis, close relationships with top managements of listed companies (more than 1,000 company meetings last year) and a permanent quest for new investment themes offering structural growth opportunities. The digitalization, fintech, Industry 4.0, or the ageing of the world population are some of our favorite investment themes. We ensure we are following closely the latest developments within this universe, by participating in various conferences, trade fairs, sector-specific thematic events and by meeting regularly with managements of listed companies. Our small & mid cap DNA is spread across various strategies under the PLUVALCA family of funds with a cross-asset approach comprising our core equity funds, thematic equity funds, fixed income and diversified/flexible allocation funds). In 2015, the Norwegian sovereign wealth fund chose Financière Arbevel to manage its French equity mandate. In 2018, Financière Arbevel pursued its development by launching its first European private equity fund (FPCI form or “Professional private equity investment fund”) with a cross-over approach focused on the non-listed life-science universe, with the idea of accompanying a limited number of biotechnology start-ups in their development. www.arbevel.com 

About investiere 

investiere is the leading European startup investment platform for qualified and institutional investors. A team of investment professionals screens thousands of companies and presents the best investment opportunities on a digital platform after a rigorous due diligence process. investiere focuses on European high-tech startups. The investiere community consists of more than 4,000 qualified private investors, family offices and pension funds. Furthermore, numerous corporations rely on investiere’s expertise to screen, select and invest in promising startups. With CHF 100 M invested since inception in 2010, investiere is Switzerland’s most active startup investor. Switzerland’s third-largest bank, Zürcher Kantonalbank, is an anchor investor of investiere. To join investiere’s growing international investor community, visit www.investiere.ch. 

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