Institut du Cerveau et de la Moelle Epinière https://icm-institute.org Tue, 18 Sep 2018 14:30:36 +0000 https://wordpress.org/?v=4.8.2 hourly 1 https://wordpress.org/?v=4.8.2 Cerebrospinal fluid and spine development disorders https://icm-institute.org/en/actualite/cerebrospinal-fluid-and-spine-development-disorders/ https://icm-institute.org/en/actualite/cerebrospinal-fluid-and-spine-development-disorders/#respond Wed, 22 Aug 2018 10:14:00 +0000 Thomas Mariani https://icm-institute.org/?post_type=actualite&p=13943 Cerebrospinal fluid (CSF) is a fluid running through brain ventricles and spinal canal. It plays a role in the protection against shocks and infections, permits For more information ]]> Cerebrospinal fluid (CSF) is a fluid running through brain ventricles and spinal canal. It plays a role in the protection against shocks and infections, permits clearance of central nervous system’s wastes and also contains various signaling molecules which roles are still not clearly identified. The role of the CSF itself is still not entirely elucidated either but seems yet crucial to the normal development of vertebrates.

One of the main characteristics of brain ventricles and spinal canal’s surface is the presence of cilia, allowing circulation of CSF. Dysfunction of these cilia can prevent natural flow of CSF, causing excessive pressure on the brain or spinal cord, eventually leading to pathologies such as hydrocephalus.

Using a zebrafish model, which has the characteristic of being transparent, Claire Wyart’s team highlighted a new role for cilia in the CSF. Researchers showed that motility of those cilia is essential to the formation of Reissner fiber, composed of SCO-Spondin protein aggregates, described more than one century ago but which functions were little-studied.

The study of a model carrying a mutation on the gene coding for SCO-Spondin, causing either a complete loss of the protein or a modification in its structure, showed a disruption in the formation of Reissner fibers. In both cases, absence of motile cilia and/or absence of SCO-Spondin protein leads to deformation of posterior axis, appearing very early during development and increasing with age.

These results, published in Current biology, highlight « the essential role of Reissner fibers during embryonic development and opens promising avenues to discover new signals in the CSF influencing the development of body axis” concludes Pierre-Luc Bardet, associate professor at Sorbonne Université.
Recent studies showed a role of CSF flow/composition in animal models of juvenile idiopathic scoliosis. In humans, this pathology is characterized by unexplained, sudden and progressive development of spine deformations and affects 0.2% of the population in France.
A signal in the CSF could be an avenue of research towards a better understanding of juvenile scoliosis.

Source
The Reissner Fiber in the Cerebrospinal Fluid Controls Morphogenesis of the Body Axis. Cantaut-Belarif Y, Sternberg JR, Thouvenin O, Wyart C, Bardet PL. Curr Biol. 2018 Aug 6

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Testosterone increases men’s preference for status goods https://icm-institute.org/en/actualite/testosterone-increases-mens-preference-for-status-goods/ https://icm-institute.org/en/actualite/testosterone-increases-mens-preference-for-status-goods/#respond Thu, 12 Jul 2018 12:40:08 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13845 A recent study conducted by a research team around Hilke Plassmann, the INSEAD Chaired Professor of Decision Neuroscience & Brain and Spine Institute (ICM – For more information ]]> A recent study conducted by a research team around Hilke Plassmann, the INSEAD Chaired Professor of Decision Neuroscience & Brain and Spine Institute (ICM – Inserm/CNRS/Sorbonne Université), a principal investigator in the Social Affective Neuroscience Team at the ICM, David Dubois, Associate Professor of Marketing at INSEAD and Gideon Nave, Assistant Professor of Marketing at The Wharton School & the Wharton Neuroscience Initiative shows that testosterone, the male sex hormone, increased men’s preference for status goods compared to goods of similar perceived quality but seen as lower in status. The paper and its findings are published in Nature Communications.

The research reveals that consumption of status goods (e.g., luxury products or experiences) is partly driven by biological motives. The results are the first to demonstrate that testosterone causally influences rank-related consumer preferences and that the effect is driven by consumers’ aspiration to gain status rather than power or a general inclination for high quality goods.

The team investigated whether and when consumers’ desire for status goods is biologically rooted with a focus on the effect of testosterone on men’s desire for goods conveying status benefits such as luxury products. Basic research shows there is a fundamental need to signal one’s rank across species. Higher social rank brings individuals several significant advantages such as mating opportunities or access to resources or social influence. In human society, individuals often show their rank in the social hierarchy through economic consumption, in particular through possessing and displaying expensive, luxury brands. To what extent is consumers’ preference for such goods biologically motivated?

“In the non-human species literature, some evidence highlights the link between testosterone, and rank-related behaviour. In humans, testosterone levels can situationally increase in contexts related to social rank, during competitions and after winning them or in the presence of an attractive mate,” says Hilke Plassmann.

To gain more insights on the role of testosterone on social rank and status associated behaviour, Hilke Plassmann and her co-authors Gideon Nave of The Wharton School, Amos Nadler of Ivey Business School, David Dubois of INSEAD, David Zava, and Colin Camerer of California Institute of Technology, conducted a study involving 243 men of similar age and socio-economic background. Randomly, half of them received a single dose of testosterone that mimicked a testosterone spike that could occur in an everyday situation causing an increased testosterone level; the other half received a placebo treatment. All subjects then participated in two tasks.

In the first one, they were asked to choose between pairs of brands. The pairs were composed of brands that were all pretested to have polarised social rank associations but did not differ in perceived quality. That is, one brand was seen to lift its owner much higher in the social hierarchy (e.g., Calvin Klein) than the other (e.g., Levi’s). For each pair, participants were asked “which brand do you prefer and to what extent?” on 10-point scale anchored with each brand. The findings reveal that men who received the testosterone doses showed a higher preference for the status (positional) goods associated with higher social rank (such as a luxury brand). This suggests a causal link between testosterone and rank-related consumer preferences.

The second task meant to investigate the effect of testosterone on the two distinct routes to high social rank – status and power. While status refers to the respect in the eyes of others, power comes from one’s control of a valued resources. The research team used six different product categories from coffee machines to luxury cars and created three different framings for each product category, with a similar wording but emphasising the target product in terms of its status benefits, power benefits or high quality.

“For example, the mock ads variously described a Mont Blanc pen as “the internationally recognised symbol among the influential” (status), “mightier than the sword” (power) “an instrument of persistence and durability” (quality)” says David Dubois.

The researchers then asked participants how much they liked the product description and the product itself. Here testosterone did not increase liking when the product was perceived as a quality product or a power enhancing one but only when it was described as conveying status. These results establish a causal link between testosterone and increase of preference for status-enhancing goods.

The findings may be useful for generating new hypotheses regarding contexts where positional (status) consumption occurs. As men experience situational elevation in testosterone during and following competitions such as sporting events or in the presence of attractive mates, male consumers may be more likely to engage in status consumption and find status-related communications more appealing at certain times.

According to Gideon Nave, “While the study shows that consumption of positional goods is partly driven by biological motives, it is important not to forget that cultural differences might play a role in the biological underpinnings of status behaviour and that status signals are not universal. These results bring the first theoretical insights on the biological basis of preference for high status goods that need to be replicated and generalised in other populations.”

The findings also have broad implications for luxury brands and policy makers alike.

“I’ve always been struck by the variations in consumers’ appetite for luxury, with some markets or periods encouraging a “luxury fever” (e.g., urban areas, fast-developing markets such as China etc.) and others less so. Our findings are exciting because they show that consumers’ drive for luxury may stem directly from differences in testosterone levels varying with the amount of social competition, population density, or male/female imbalance,” says Amos Nadler.

Source : Single-dose testosterone administration increases men’s preference for status goods. Nave G, Nadler A, Dubois D, Zava D, Camerer C, Plassmann H. Nat Commun. 2018 Jul 3

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A new immune mechanism in Alzheimer’s disease! https://icm-institute.org/en/actualite/a-new-immune-mechanism-in-alzheimers-disease/ https://icm-institute.org/en/actualite/a-new-immune-mechanism-in-alzheimers-disease/#respond Tue, 10 Jul 2018 09:20:03 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13817 A study conducted by Cecile Delarasse and colleagues at ICM shows the deleterious role of P2X7 receptor and the positive effect of its inactivation in a mice model For more information ]]> A study conducted by Cecile Delarasse and colleagues at ICM shows the deleterious role of P2X7 receptor and the positive effect of its inactivation in a mice model of amyloid plaques, one of the main lesions in Alzheimer’s disease. The results, published in Molecular Psychiatry, open new avenues of research on the potential of this receptor as a therapeutic target.

Alzheimer’s disease is characterized by two types of lesions: amyloid lesions caused by aggregates of Aβ peptides and neurofibrillary tangles linked with the accumulation of aggregated Tau proteins. Their presence leads to chronic inflammatory response in the brain. In case of damages, cells release large quantities of ATP. High concentration of ATP is detected as a danger signal by specific receptors called P2X7.

A dual role for this receptor, both pro-inflammatory and neuroprotective, was reported in Alzheimer’s disease. A study conducted by Cecile Delarasse’s team at the ICM sought to better understand its role in this pathology. To this purpose, they studied the consequences of the inactivation of P2X7 receptor in a mouse model of amyloid lesions.

Through multiple behavioral, electrophysiological, biochemical and histological tests, they showed that the absence of P2X7 receptor was associated with decrease of amyloid lesions and an improvement of cognitive functions and synaptic plasticity, confirming the deleterious effect of the receptor activation during the course of the disease.
« The next step was to understand the underlying mechanisms. What’s going on with this receptor from a cellular and molecular point of view? Why does its absence have a beneficial effect? »

P2X7 receptor is activated in an inflammatory context or in case of lesions, so the researchers looked at the immune consequences of its inactivation.

They did not show any effect on specific activation of innate immune system: microglial cells of the central nervous system or recruitment of macrophages. However, they did show the involvement of the adaptive immune system through T cells.

In absence of P2X7 receptor, they observed a decrease in chemokines, which attract the immune system cells to the inflammatory site, and in consequence a smaller recruitment of T cells in the brain, which have a deleterious effect on the symptoms of the disease.

« These results bring new important elements on the pathological role of P2X7 receptor and the positive effect of its inactivation on amyloid pathology, characteristic of Alzheimer’s disease. They open new avenues of research on the potential of this receptor as a therapeutic target. » concludes Cécile Delarasse

Source : New role of P2X7 receptor in an Alzheimer’s disease mouse model. Elodie Martin, Majid Amar, Carine Dalle, Ihsen Youssef, Céline Boucher, Caroline Le Duigou, Matthias Brückner, Annick Prigent, Véronique Sazdovitch, Annett Halle, Jean M. Kanellopoulos, Bertrand Fontaine, Benoît Delatour, Cécile Delarasse. Molecular Pyschiatry. 2018

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GEoPD Annual Meeting and following Workshop in 2018 at ICM, Paris https://icm-institute.org/en/actualite/geopd-annual-meeting-and-following-workshop-in-2018-at-icm-paris/ https://icm-institute.org/en/actualite/geopd-annual-meeting-and-following-workshop-in-2018-at-icm-paris/#respond Tue, 10 Jul 2018 08:54:08 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13812 The 13th Annual Meeting of GEoPD (13-14 December 2018), is hosted by GEoPD French partners: Alexis Brice, Alexis Elbaz, Jean-Christophe Corvol, and Suzanne For more information ]]> The 13th Annual Meeting of GEoPD (13-14 December 2018), is hosted by GEoPD French partners: Alexis Brice, Alexis Elbaz, Jean-Christophe Corvol, and Suzanne Lesage.

GEoPD is a global consortium of researchers dedicated to promoting education, scientific research and translational development in PD. The consortium founded in 2003 by Michael J Fox Foundation has been operating since 2004, and has an active membership from more than 60 sites on 6 continents. The consortium includes most international leaders in Genetics and Epidemiology of PD (N Hattori, M Farrer, O Ross, EM Valente, A Elbaz, C Klein, T Gasser, K Markopoulo, etc). The GEoPD facilitates epidemiologic, clinical and genetic research in PD and provides a mechanism whereby active global site investigators may share their expertise, resources (41,988 PD patients and 41,505 controls) and reagents. More than 10 peer reviewed papers have been published based on the consortium’s work. The consortium’s mission is to promote multi-investigator research projects throughout the year. Annual Meetings since 2005 offer a valuable forum for consortium members to discuss unpublished data and ideas, highlight research questions or needs and identify global opportunities for partnership. These meetings are organized each year in a different country by one of the members; the first meeting was organized in Paris in 2005, and subsequent meetings took place in Greece, Norway, Germany, Japan, Korea, USA, Luxembourg, Canada… and in 2017, in Australia.
In 2018, the French partners, Alexis Brice, Alexis Elbaz, Jean-Christophe Corvol, and Suzanne Lesage wish to host the 13th Annual Meeting, on December 13th to 14th, at the Brain and Spinal Cord Institute (ICM), Paris, France.

We are organizing a 2-day scientific event, including the 13th Annual Meeting of the GEoPD consortium & a satellite Parkinson’s disease symposium. The first day will be a closed meeting dedicated to about 80 GEoPD members in order to review ongoing and future projects. The second day will be a symposium to discuss hot topics in PD research open to the scientific community.

 

More information will follow shortly regarding all aspects of the meeting.

 

REGISTER

 

Genetic Epidemiology of Parkinson’s disease – GEoPD : https://geopd.lcsb.uni.lu

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Brain anatomy predicts our food choices! https://icm-institute.org/en/actualite/brain-anatomy-predicts-our-food-choices/ https://icm-institute.org/en/actualite/brain-anatomy-predicts-our-food-choices/#respond Thu, 07 Jun 2018 08:28:53 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13743 Would you rather have a piece of chocolate cake or steamed veggies? Making healthy food choices isn’t always easy! A study conducted by a team of researchers For more information ]]> Would you rather have a piece of chocolate cake or steamed veggies? Making healthy food choices isn’t always easy! A study conducted by a team of researchers around Liane Schmidt (Inserm) and Hilke Plassmann (INSEAD) at the Brain and Spine Institute (ICM – Inserm/CNRS/Sorbonne University) found a link between the anatomy of several areas of the brain and the ability to exert self-control when making food choices. Results were published in The Journal of Neuroscience.

For many individuals, having a healthy diet is challenging. The ability to maintain a balanced diet and make healthy food choices varies greatly from one individual to another.

According to models in the nascent field of Neuroeconomics, choosing between several options involves two main mechanisms: the first step is attributing a value to each option by considering its different attributes and their value. For food choices, attributes include, for example, a food’s tastiness and healthiness. The second step, for our brain, is analyzing the weight given to each attribute to select the most adequate option that is the food with the highest overall subjective value.

Are there brain structures that predict an individual’s ability to make healthy food choices? If yes, which ones? To answer these questions, Liane Schmidt, Hilke Plassmann and their co-authors Anita Tusche of the California Institute of Technology (USA), Cendri Hutcherson of the University of Toronto (Canada) and Todd Hare of the University of Zurich (Switzerland) compiled structural brain imaging data and participants’ food choices from 4 studies.

In three of these studies, participants performed the same task in which they were asked how much they wanted to eat a specific food at the end of the experiment in three different conditions: their normal preference, when focussing on the food’s taste, and on its health benefits. Participants could base their choice solely on taste, or be more reasonable and show more self-control by concentrating on the food’s health.

In the fourth study, participants performed a different task. Using a method of their choice, they were asked to distance themselves from the food or decrease their desire for the tasty food.

According to Liane Schmidt, the study’s first author, « This is a more flexible control strategy that does not specifically zero in on taste or healthy attributes, but instead allows individuals to distance themselves from a certain food or desire. »

Based on structural imaging data from the first three studies, researchers studied how grey matter levels varied in participants’ brains compared with their ability to make healthy choices.

They found that grey matter in the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) predicted healthy food choices. In other words, individuals with more grey matter in these two areas showed more self-control in their food choices by focussing on health more and attributing a higher weight to health than taste attributes of the foods for choice.

To confirm these results, the research team used these structural markers of dietary self-control to predict food choices in the fourth study. “The idea here was to see whether predictions established in a context with very clear self-control strategies – focusing less on taste or more on health – could be expanded to a situation where control strategies remain vague”, added Hilke Plassmann.

The research team confirmed their results, showing for the first time that interpersonal differences in the neuroanatomy of the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) play a role in the ability to make healthy food choices. These results pave the way for better assessment and, with time, treatment, of food-related disorders such as bulimia and anorexia and also for helping to fight the obesity epidemic.

Source : Neuroanatomy of the vmPFC and dlPFC predicts individual differences in cognitive regulation during dietary self-control across regulation strategies. Liane Schmidt, Anita Tusche, Nicolas Manoharan, Cendri Hutcherson, Todd Hare, and Hilke Plassmann. The Journal of Neuroscience. June 2018

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A new pathway in axonal growth: first step to their regeneration after injury https://icm-institute.org/en/actualite/a-new-pathway-in-axonal-growth-first-step-to-their-regeneration-after-injury/ https://icm-institute.org/en/actualite/a-new-pathway-in-axonal-growth-first-step-to-their-regeneration-after-injury/#respond Thu, 19 Apr 2018 08:40:15 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13634 A study led by Bassem Hassan, team leader at ICM, and carried out with the VIB Leuven, identified a new pathway enhancing axonal growth during development and after For more information ]]> A study led by Bassem Hassan, team leader at ICM, and carried out with the VIB Leuven, identified a new pathway enhancing axonal growth during development and after injury in drosophila. Results just came out in Frontiers in Cellular Neuroscience.

Central nervous system (CNS) injury, such as spine lesion or neurodegeneration, have long-term consequences with more or less severe disabilities. The principal issue is that severed connections fail to regenerate after trauma. Understanding the fundamental mechanisms of axons development and growth is a major challenge and a first step in the hope of restoring lost functions.

A study conducted by Bassem Hassan addressed this problem by performing a genetic screen in Drosophila to identify genes involved in axonal growth after injury. The Drosophila central nervous system shows strong similarities to mammals in all the key morphological, genetic and molecular aspects. Thus it is a relevant and powerful model to study CNS axonal regeneration.

Researchers studied more than 300 genes and identified 13 promoting axonal growth in CNS neurons. Then they tested the effects of those genes in Drosophila with CNS injury. 3 of them were strongly involved as axonal growth regulators: Dscam1, Faf and JNK.

To understand how these regulators are actually involved at the molecular and cellular levels, the scientists, led by frst author Dr. Marta Koch, carried out further analysis and found that the 3 genes actually interacted with each other in a novel axonal growth and regeneration signaling pathway. In this pathway, Fat facets (Faf) promotes axonal regrowth after injury via the Down syndrome cell adhesion molecule (Dscam1) and JNK signaling. Previous data suggest that this mechanism is conserved in mammals. These results open novel perspectives in the study of axonal development and regeneration after injury.

Reference : A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury. Koch M, Nicolas M, Zschaetzsch M, de Geest N, Claeys A, Yan J, Morgan MJ, Erfurth ML, Holt M, Schmucker D, Hassan BA. Front Cell Neurosci. 2018 Feb 8

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A major international grant for Claire Wyart https://icm-institute.org/en/actualite/a-major-international-grant-for-claire-wyart/ https://icm-institute.org/en/actualite/a-major-international-grant-for-claire-wyart/#respond Wed, 04 Apr 2018 10:24:10 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13592 Claire Wyart, head of the team ”Optogenetic dissection of spinal circuits underlying locomotion“ at ICM, obtained an important Research Grant from the For more information ]]> Claire Wyart, head of the team ”Optogenetic dissection of spinal circuits underlying locomotion“ at ICM, obtained an important Research Grant from the International Human Frontier Science Program Organization (HFSPO) to support her research on flow of the cerebrospinal fluid and link to development.

The Human Frontier Science Program is an international program of research support implemented by the HFSPO. Its aims are to promote intercontinental collaboration and training in cutting-edge, interdisciplinary research focused on the life sciences. HFSPO receives financial support from the governments or research councils of many countries as well as from the European Union.

In 2018, 31 research teams are awarded among more than 750 applications. Claire Wyart’s team is selected for her project “How cerebrospinal fluid physico-chemical properties impact body axis formation and scoliosis”, in collaboration with Prof. François Gallaire’s team at Ecole Polytechnique Fédérale de Lausanne (Switzerland) and Prof. Maria Lehtinen’s at Boston Children’s Hospital (USA), also among the winning teams.

HFSP Program Grants appeal to the innovative and creative potential of the applicants under the general theme “Complex mechanisms of living organisms”. It is the only international program that funds teams of scientists globally “without borders”.

 

Claire Wyart’s team works on locomotion and the way sensory circuits in the spinal cord modulate movement and posture. Her preferred model is the zebrafish larva, a small transparent fish in the early stages of development, for which she has developed optical methods to remote control neuronal activity in vivo. Through such advanced technologies, Claire’s team identified a new sensorimotor loop in the spinal cord, which affects locomotion and posture. These results raise hopes that one day, we will be able to learn how to stimulate circuits to modulate posture and movement in humans.
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INSIGHT study highlights compensation mechanisms in patients with Alzheimer’s disease lesions https://icm-institute.org/en/actualite/insight-study-highlights-compensation-mechanisms-in-patients-with-alzheimers-disease-lesions/ https://icm-institute.org/en/actualite/insight-study-highlights-compensation-mechanisms-in-patients-with-alzheimers-disease-lesions/#respond Sat, 24 Mar 2018 14:19:55 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13448 INSIGHT study highlights compensation mechanisms in patients with Alzheimer’s disease lesions used to maintain intellectual and memory capabilities.

The For more information ]]> INSIGHT study highlights compensation mechanisms in patients with Alzheimer’s disease lesions used to maintain intellectual and memory capabilities.

The INSIGHT-preAD study, directed by Professor Bruno Dubois, was carried out by teams at ICM (Brain and Spine Institute – Inserm/CNRS/Sorbonne University) and the Memory and Alzheimer’s Disease Institute (IM2A) at AP-HP Pitié-Salpêtrière Hospital in Paris, in collaboration with the MEMENTO cohort. It aims at identifying factors underlying Alzheimer’s Disease development in healthy subjects over 70 with no current cognitive disorders.

The INSERM-sponsored study shows that at a 30-month follow-up, amyloid lesions (also called Alzheimer’s lesions) did not impact cognition or behaviour in affected subjects.

Results of the study were published on February 27th, 2018 in Lancet neurology and suggest that subjects with amyloid lesions may implement compensatory mechanisms.

Drugs currently under development to treat Alzheimer’s Disease demonstrate significant efficacy on brain lesions without a joint decrease in symptoms. Drug trials may be undertaken too late, with patients who are at an advanced stage of the disease. This led to the idea of testing treatment efficacy at an earlier stage, right at the start or even before onset of symptoms in patients with Alzheimer’s disease lesions. This implies extensive knowledge of disease progression markers at pre-clinical stage.

The INSIGHT-preAD study, short for “INveStIGation of AlzHeimer’s PredicTors in subjective memory complainers – Pre Alzheimer’s disease” was supervised by Professor Bruno Dubois and aimed at identifying these progression factors. Professor Dubois is Director of the Cognitive and Behavioural Diseases Center at AP-HP Pitié-Salpêtrière Hospital and Professor of Neurology at Sorbonne University.

The study is based on longitudinal monitoring of an active cohort launched in May 2013 at AP-HP Pitié-Salpêtrière of 318 volunteer patients over 70 years of age, with perceived memory problems despite normal cognitive and memory performance during testing.

Participants agreed to imaging examinations to determine whether or not their brain presented Alzheimer’s disease lesions (also called “amyloid” lesions). 28% of participants were found to have lesions although no factors were identified at this stage.

Amyloid-positive and amyloid-negative patients did not present any differences in cognitive (memory, language, orientation), functional, and behavioural testing when they entered the cohort. Additionally, sub-groups based on severity of perceived memory problems did not present any differences, whether in structural neuro-imaging (MRI) or metabolic neuro-imaging (PET-FDG).

As part of the INSIGHT-preAD study, patients passed a neuropsychological assessment, an electroencephalogram and actigraphy testing on a yearly basis as well as undergoing blood testing (to test for biomarkers) and neuro-imaging exams (MRI, PET-FDG and PET-amyloid) every two years.

The teams involved in the study analysed the data collected at its launch and two years later, as well as a 30-month follow-up clinical assessment of volunteer subjects. They did not find any significant evolution between amyloid-positive and amyloid-negative patients either for the full set of markers monitored (behavioural, cognitive, functional) or in in neuro-imaging testing. Electroencephalogram data, however, highlighted that patients with lesions displayed modified electrical activity in anterior regions of the brain, especially frontal areas, to maintain intellectual and memory performance.

At a 2.5-year follow-up, only four patients have developed Alzheimer’s Disease. When they entered the study, they displayed predictive factors including older age, higher concentration of amyloid lesions, and decreased hippocampal volume.

Results show that amyloid lesions in the brain do not translate into cognitive, morphological, metabolic or functional modifications in affected patients. Results of the study pertaining to electroencephalographic variations also suggest that a compensation mechanism may exist.

Progression towards Alzheimer’s Disease in these patients, with an average age of 76, is low, highlighting the existence of significant cognitive reserve in this type of population. Ongoing monitoring if necessary to determine whether these findings are verified over a longer time span.

The next INSIGHT-preAD study update will take place in 2022.

This research has received financial support from the French Ministry of Research (Investment for the Future), the Plan-Alzheimer Foundation, and Pfizer.

Reference: Cognitive and neuroimaging parameters and brain amyloidosis in individuals at risk of Alzheimer’s disease (INSIGHT-preAD): a longitudinal observational study. Prof Bruno Dubois MD, Stephane Epelbaum MD, Francis Nyasse, Hovagim Bakardjian PhD, Geoffroy Gagliardi, Olga Uspenskaya MD, Marion Houot PhD, Simone Lista PhD, Federica Cacciamani, Marie-Claude Potier PhD, Anne Bertrand MD, Foudil Lamari PhD, Habib Benali PhD, Jean-François Mangin PhD, Olivier Colliot PhD, Remy Genthon MD, Marie-Odile Habert MD, Prof Harald Hampel MD for the INSIGHT-preAD study group

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A new mechanism to control neural stem cell function during brain development https://icm-institute.org/en/actualite/a-new-mechanism-to-control-neural-stem-cell-function-during-brain-development/ https://icm-institute.org/en/actualite/a-new-mechanism-to-control-neural-stem-cell-function-during-brain-development/#respond Fri, 23 Mar 2018 09:40:47 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13533 Bassem Hassan’s team at ICM discovered a specific type of neural stem cell and deciphered a highly precise temporal control mechanism for their function during For more information ]]> Bassem Hassan’s team at ICM discovered a specific type of neural stem cell and deciphered a highly precise temporal control mechanism for their function during brain development in Drosophila (fruit flies). The results were published in the leading journal Developmental Cell and pave the way for advanced molecular and genetic studies focused on understanding the biology of these cells.

The development of our brain relies on a set of extremely complex mechanisms, many of which remain unexplored. One of these mechanisms enables production of the correct number of neurons, and relies on perfect spatiotemporal coordination of neural stem cells during development. This precise control of cell division and cellular differentiation into the various types of cells that make up an organ is still relatively unknown.

Over the course of development, neuronal and glial cell production originates from a series of cell divisions that start with neural stem cells:

  • Asymmetric divisions create a new stem cell and a daughter cell that will become a specific type of neuron. This enables stem cell self-regeneration and a stable stem cell reserve.
  • Symmetric divisions create either two cells that will differentiate, or two new stem cells. Therefore, depending on the developmental stage of the brain, these divisions enable either stem cell self-amplification to create a larger reserve, or the production of differentiated cells, such as the neurons that will form the basis of the brain.

A phase of symmetrical self-amplifying division in neural stem cells has been identified in human brain development. The mechanisms underlying and regulating this phase, however, have yet to be fully understood.

Drosophila models are a cornerstone of research into the molecular, cellular, and genetic mechanisms underlying brain development. According to current models, Drosophila neural stem cells were only undergo asymmetric divisions during brain development.

Bassem Hassan’s* team successfully identified the first example of self-amplifying neural stem cells in fruit flies that use symmetric division as well as their role in neuron increase.

«These cells can self-amplify, meaning that they can increase stem cell reserves during brain development. They may be partly responsible for the massive cortical increase observed in species with a larger brain. » explained Bassem Hassan.

« We welcome this important discovery. The work of Bassem Hassan’s team will shed valuable light on the regulation of stem cell during brain development, with significant impact on the way we think about the brain and development” Professor Alexis Brice, General Director of the ICM.

The research team then studied the mechanisms surrounding cell function.

Neurogenesis is regulated by a small and highly preserved set of “proneural proteins” during evolution: their role in asymmetrical division and initiation of cell differentiation is well-known.

The researchers, led by postdoctoral fellow Natalia Mora, the first author of the study, found that these stem cells are generated by temporal conversion of certain neural stem cells from an asymmetric division mode to a symmetric division mode. This conversion goes hand in hand with a change in how certain proneural proteins are expressed, and is a necessary and sufficient condition to modify division type and to generate the right number of neurons during development.

« Beyond identifying a new type of neural stem cell, our results suggest that differential, quantitative, and tightly controlled regulation of proneural proteins and their targets may act as a molecular clock that controls a series of events during development. » adds Bassem Hassan.

“This pioneering work from Bassem and his team to uncover this powerful biological switch is an important scientific discovery,” said Tom Skalak, executive director of The Paul G. Allen Frontiers Group. “It tells us that this critical timing of stem cell switches is critical in this complex system’s function, much as switches are key to complex human-designed systems like cell phones and computers. Perhaps it’s not so surprising that evolution makes use of switches for growing a big brain also.”

*Bassem Hassan, leader of the « Brain Development » team at ICM, is a Research Director at Inserm, Einstein Visiting Fellow at Free University of Berlin and at the Berlin Institute of Health, and an Allen Distinguished Investigator.

Reference: A Temporal transcriptional switch governs stem cell division, neuronal numbers and maintenance of differentiation. Natalia Mora, Carlos Oliva, Mark Fiers, Radoslaw Ejsmont, Alessia Soldano, Ting-Ting Zhang, Jiekun Yan, Annelies Claeys, Natalie De Geest, Bassem A. Hassan. Developmental Cell. March 22, 2018.

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ICM AND FONDATION ABEONA PARTNER ON TWO ARTIFICIAL INTELLIGENCE PROJECTS THAT WILL ADVANCE GENDER EQUALITY https://icm-institute.org/en/actualite/icm-and-fondation-abeona-partner-on-two-artificial-intelligence-projects-that-will-advance-gender-equality/ https://icm-institute.org/en/actualite/icm-and-fondation-abeona-partner-on-two-artificial-intelligence-projects-that-will-advance-gender-equality/#respond Tue, 30 Jan 2018 09:06:52 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13287 Men and women face different chronic disease risks. Women, for example, are 1.5 times more likely to develop Alzheimer's disease. Although biological differences, For more information ]]> Men and women face different chronic disease risks. Women, for example, are 1.5 times more likely to develop Alzheimer’s disease. Although biological differences, cultural and social factors play a role, we do not fully understand the causes. Data science and artificial intelligence have the potential to improve knowledge and diagnosis on such diseases and enable individualized treatments.

Fondation Abeona and ICM are joining forces to support two ground-breaking research projects on Multiple Sclerosis and neurodegenerative diseases such as Alzheimer’s. This two-year partnership comes into effect as Cédric Villani, a mathematician and member of the French Parliament, is preparing to submit a special report on France’s AI strategy in the next few weeks.

The “two infinities” of medical data: neuro-imaging and genomics

A million pixels in a medical image, a billion codes in a genome: high dimension is a major challenge to data science in medical research.

The second cause of severe disability after traffic accidents, Multiple Sclerosis manifests itself around the age of 30 and affects more than 80 000 people in France (source AP-HP). Three times as many women as men are afflicted. Different factors influence the onset of the disease and its progression.

The MSBioProgress project uses sophisticated statistical techniques to analyze high-dimensional data sets, such as genomic biomarkers and brain images to predict the individual evolution of the disease and propose personalized treatments.

Neurodegenerative disorders, such as Alzheimer’s disease, affect millions of people around the world. They progress over several decades before first symptoms appear. The Brain@Scale project develops a new algorithm to better diagnose neurodegenerative diseases from medical images. These two projects are led by researchers at the ICM’s Neuroinformatics Center, which incorporates innovative data science techniques into brain research.

“Medical data poses new challenges to data science. Algorithmic innovation is thus essential to building effective and useful tools for medical research. We particularly appreciate the stimulating support of the Abeona Foundation.” Olivier Colliot, research scientist at the ICM (CNRS) and co-leader of the ARAMIS team (Inria / ICM), and Violetta Zujovic, researcher at the ICM in the molecular and cellular approach team of myelin repair.

“We are excited to work with the ICM researchers and support these two multi-disciplinary projects at the crossroads of genomics, neuro-imaging and data science, as they demonstrate ethical applications of artificial intelligence” Anne Bouverot, President of the Abeona Foundation.

“We are delighted to partner with Fondation Abeona, a young and innovative foundation that has detected these two projects among our most promising ones in this area, and in doing so to promote gender equality, in full alignment with our values.” Professor Alexis Brice, Director General of the ICM.

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Optimization of an imaging technique for glioma analysis https://icm-institute.org/en/actualite/optimization-of-an-imaging-technique-for-glioma-analysis/ https://icm-institute.org/en/actualite/optimization-of-an-imaging-technique-for-glioma-analysis/#respond Mon, 29 Jan 2018 10:13:02 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13283 By optimizing an imaging technique, the edited magnetic resonance spectroscopy, ICM researchers managed to detect very precisely a certain type of brain tumors For more information ]]> By optimizing an imaging technique, the edited magnetic resonance spectroscopy, ICM researchers managed to detect very precisely a certain type of brain tumors non-invasively. A key step for diagnosis, prognosis and treatment of patients with glioma.

40% of gliomas, the most frequent brain tumor, have a mutation in the IDH gene. This mutation is associated with an intracellular accumulation of a molecule called 2HG. The detection of 2HG levels makes possible to diagnose those tumors and is of major interest for patient care. Is the tumor a glioma or not? Does it have the specific IDH gene mutation? This information will have several consequences, on surgery, treatment, and prognosis of the patient.

Until recently, the detection of IDH mutation and 2HG accumulation could only be quantified by analyzing tumor biopsies, an invasive procedure. Recent studies have shown that it is possible to detect this molecule non-invasively with magnetic resonance spectroscopy (MRS).

Several methods can be used with this imaging technique but the specificity and the sensitivity can be unsatisfying. A high specificity and sensitivity are needed to avoid getting false positive results.
In the present study, the researchers managed to optimize the acquisition technique and the post processing methods of MRS. They tested it on 24 subjects with suspected diagnosis of low grade glioma and compared it with the most commonly used method nowadays.

“Our method shows better results than those currently used in other research centers worldwide. We demonstrate a specificity and a sensitivity for detecting the 2HG metabolite of 100%.“ Francesca Branzoli, research engineer at ICM

The researchers now want to use their method for the follow-up of patients who undergo radiotherapy or chemotherapy, to monitor their reaction to therapies. This technique could also be used to follow the effect of new drugs in clinical trials, in particular new drugs in development which target specifically the 2HG oncometabolite.

“Overall the edited MRS represents one of the most reliable tool to predict IDH mutation. In clinical practice it could be highly beneficial for noninvasive diagnosis of gliomas, prognosis determination and patients’ follow-up.” Marc Sanson, neuro-oncologist and team leader at ICM.

 

Did you know: Magnetic resonance spectroscopy (MRS)

Magnetic resonance spectroscopy is an imaging technique which allows to measure the concentration of several metabolites in the body.

It is based on the principle that different metabolites have specific chemical properties and molecular composition which can be detected noninvasively with MRS. Thus, each metabolite is characterized by its own magnetic signal. An MRS recording consists of a spectrum composed of several peaks, each corresponding to a different metabolite.

This technique can be used in clinic as the concentration of metabolites may vary in different diseases. For example neuronal dysfunction or atrophy in neurodegenerative diseases can be measured through the altered concentration of specific metabolites present specifically in neurons.

 

Référence : Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy. Branzoli F, Di Stefano AL, Capelle L, Ottolenghi C, Valabrègue R, Deelchand DK, Bielle F, Villa C, Baussart B, Lehéricy S, Sanson M, Marjanska M. Neuro Oncol. 2017 Nov 6.

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In partnership with ICM, A joint FIA & EMOTIV tech experience leveraging Virtual Reality and real-time neuroinformatics to improve road safety will premiere in Davos next week https://icm-institute.org/en/actualite/in-partnership-with-icm-a-joint-fia-emotiv-tech-experience-leveraging-virtual-reality-and-real-time-neuroinformatics-to-improve-road-safety-will-premiere-in-davos-next-week/ https://icm-institute.org/en/actualite/in-partnership-with-icm-a-joint-fia-emotiv-tech-experience-leveraging-virtual-reality-and-real-time-neuroinformatics-to-improve-road-safety-will-premiere-in-davos-next-week/#respond Tue, 23 Jan 2018 17:13:02 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13251 The World Economic Forum is held from January 23 to 26. Some 70 heads of state and government are expected to participate in this popular meeting of bosses from For more information ]]> The World Economic Forum is held from January 23 to 26. Some 70 heads of state and government are expected to participate in this popular meeting of bosses from around the world.

With distracted driving a rapidly growing problem across the world, the Fédération Internationale de l’Automobile (FIA), in collaboration with personalised neuroinformatics global leader EMOTIV, will be introducing the #Tech4RoadSafety experience at the 2018 Annual Meeting of the World Economic Forum, to be held in Davos, Switzerland from January 22 to 26.

 

The FIA and EMOTIV will be showcasing new innovation that can help keep drivers’ minds on the road thanks to the unique combination of Virtual Reality (VR) and real-time mobile neuroinformatics. In Davos, attendees will be offered the opportunity to experience a VR simulator while their brainwaves will be monitored and displayed in real-time to better understand how distractions and altered perception can put people’s life at risk while they drive.

 

“Technological innovations need to be informed by neuroscientific insights in order to make the driving experience safer. Some of the world’s best researchers on the neural mechanisms of perception and action are working at our institute. Their findings will play a key role in our joint research project with the FIA and EMOTIV to improve road safety” says Prof. Gérard Saillant, President of the ICM.

 

 

 

 

 

 

 

 

 

 

 

“Distracted driving is a significant and rising cause of death on the road. By joining forces with EMOTIV and the Institut du Cerveau et de la Moelle épinière we are taking action to promote ground-breaking technology to reduce traffic fatalities.” says FIA President and Vice-President of ICM, Jean Todt. Todt also serves as the UN Secretary-General’s Special Envoy for Road Safety, and launched an FIA High-Level Panel for Road Safety in 2015, composed of global leaders in the public, private and development sectors. He is one of the Founders and the Vice-President of the Institut du Cerveau et de la Moelle épinière (ICM) in Paris, a world leading institute devoted to medical research for brain and spinal cord disorders.

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The Brain to Market Summer School 2018 : light on Parkinson’s disease https://icm-institute.org/en/actualite/the-brain-to-market-summer-school-2018-light-on-parkinsons-disease/ https://icm-institute.org/en/actualite/the-brain-to-market-summer-school-2018-light-on-parkinsons-disease/#respond Tue, 23 Jan 2018 14:01:07 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13241 The Brain to Market Summer School will take place from 3rd to 7th September 2018, at Institut du Cerveau et de la Moelle épinière (ICM), in Paris, on topic of For more information ]]> The Brain to Market Summer School will take place from 3rd to 7th September 2018, at Institut du Cerveau et de la Moelle épinière (ICM), in Paris, on topic of Parkinson’s disease.

The Brain to Market Summer School is a program combining translational neuroscience and entrepreneurship training in a boot-camp format. At the Institut du Cerveau et de la Moëlle épinière (Paris, France), a 5 days meeting with neuroscience and entrepreneurship courses (all in English) are offered to researchers and engineers from both national and international origins. The Brain to Market Summer School is an executive education program that will leave participants with a new mind-set and the skills needed to innovate and make a real difference for patients, research, development and health care systems.

This summer school is addressed to scientists (PhD, Post-doc, MD), Engineers, and Executives. Note that there is a selection process for admission based on motivation and background.

The first day, the scientific topic is introduced through lectures about the disease by all the care workflow (researchers, clinicians, paramedical staff). The goal of this day is to highlight the main disease challenges and pave the way for the project thinking.

The second and third day, the basis of marketing, business, health economy, ethic and regulatory aspects are provided by actors of the Health and Wellbeing Business Community examples (companies, patients, regulators professionals).

During three days, the participants work in teams of five on projects, while a coach works with participants to help them pitch their ideas. The projects are presented and reviewed by a panel of experts.

Working in multidisciplinary teams, the aim of the working groups is to develop a valuable proposal and improve their knowledge transferable from research to business and vice versa.

Find all informations (program, registration…) about Summer School 2018.

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NeoNeuro presents a new approach to the diagnosis of neurological disorders https://icm-institute.org/en/actualite/neoneuro-presents-a-new-approach-to-the-diagnosis-of-neurological-disorders/ https://icm-institute.org/en/actualite/neoneuro-presents-a-new-approach-to-the-diagnosis-of-neurological-disorders/#respond Mon, 22 Jan 2018 09:42:39 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=13225 Alzheimer’s disease represents one of the largest remaining unsolved threats to our health. This disease in common with other neurological disorders has been For more information ]]> Alzheimer’s disease represents one of the largest remaining unsolved threats to our health. This disease in common with other neurological disorders has been elusive because it is hard to diagnose. Our current ability to diagnose Alzheimer’s disease is equivalent to diagnosing cancer once the disease has metastasized, or equivalent to diagnosing people at risk for heart failures after heart attacks. To develop better treatments of the disease it is first necessary to diagnose it before it is too late, and the symptoms are recognizable as cognitive decline.

To date it has not proven possible to diagnose Alzheimer’s disease from blood analysis. This is the type of low-cost, simple, biological diagnosis that is necessary for the development of early treatment. Attempts to identify differences in the blood of Alzheimer’s patients from blood of healthy subjects has been frustrated by high levels of individual variability, and because the disease occurs in the brain. The brain is separated from the blood by the Brain-Blood-Barrier (BBB), a barrier that limits the flow of intact proteins from the brain into blood. Short fragments of proteins (peptides) are passed through, but these are difficult to detect with current analytical tools. This means that there is a fundamental technical difficulty associated with using our present tools to diagnose Alzheimer’s disease.

To date diagnostic approaches have been based on the identification of a biomarker, usually a protein, that is associated with the disease. Then an antibody is developed to quantify the biomarker. A new and exciting alternative approach is developing with the use of aptamers instead of antibodies as diagnostic tools. Aptamers are short single stranded fragments of DNA that mimic antibodies in their ability to bind to other molecules. A key difference though is that aptamers are identified by working with large random libraries of sequences in test tubes. These large libraries are characterized by the same advances in DNA sequencing that have enabled the sequencing of the human genome.
We can now characterize how a library of aptamer sequences is responding to all of the differences in blood between a pool of individuals with Alzheimer’s disease and healthy individuals. This publication in Plos One marks the first time that aptamers have been used in this way and thus serves as a benchmark for a whole new approach to the diagnosis of neurological disorders.

This new approach came about as a result of a collaboration between a globally leading aptamer development company, NeoVentures Biotechnology Inc. (Canada) and leading researchers on Alzheimer’s disease at ICM in Paris including Professor’s Bruno Dubois (Scientific director of “Fondation pour la recherche sur Alzheimer”), Charles Duyckaerts (head of the Laboratoire de Neuropathologie Escourolle at Hopital Pitié salpêtrière and head of the Alzheimer Prion team at Inserm), Harald Hampel (holder of the AXA Research Fund & Sorbonne Université Chair ‘Anticiper la Maladie d’Alzheimer’) ), Dr. Marie Claude Potier (head of the Alzheimer and Prions team at ICM) and Magali Dumont (head of the Phenoparc platform at ICM). This collaboration led to the formation of a French private company, NeoNeuro which has been conducting research for over two years within the ICM incubator. The company is currently validating the discoveries reported in this paper in human subjects in collaboration with the AIBL cohort (Australia) and the INSIGHT cohort (France).

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ICM PHD CANDIDATES AND POSTDOCS WORKSHOP https://icm-institute.org/en/actualite/workshop-docs-postdocs-2017/ https://icm-institute.org/en/actualite/workshop-docs-postdocs-2017/#respond Tue, 31 Oct 2017 10:09:59 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=12790 This year, the workshop of ICM PhD students and postdocs, organized by the Ajités, gathered students from our institute and the UCL Institute of Neurology in For more information ]]> This year, the workshop of ICM PhD students and postdocs, organized by the Ajités, gathered students from our institute and the UCL Institute of Neurology in London.

During those 3 days of hard work, they exchanged on their respective scientific work through oral presentations and posters and attented high-level presentations by senior researchers from both institutes. This first exchange will be followed by a visit from PhD students and postdocs from IoN in 2018 to continue and strengthen the close partnership between the two institutes.

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CALL FOR APPLICATIONS : GROUP LEADER POSITIONS AT THE ICM https://icm-institute.org/en/actualite/call-for-applications-group-leader-positions-at-the-icm/ https://icm-institute.org/en/actualite/call-for-applications-group-leader-positions-at-the-icm/#respond Thu, 05 Oct 2017 08:55:11 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=12584 ICM is seeking to recruit group leaders to reinforce its research in Neurophysiology, and welcomes applications for recruit highly talented individuals with the For more information ]]> ICM is seeking to recruit group leaders to reinforce its research in Neurophysiology, and welcomes applications for recruit highly talented individuals with the ambition to establish an internationally competitive research group in a stimulating environment. ICM invites applications from exceptionally talented neurophysiologists working on or interested in expanding into epilepsy research in close interaction with clinicians at the Hopital Pitié-Salpêtrière. Applications must be sent by January 15th 2018.

ICM welcomes applications from starting, junior and mid-career investigators with a strong scientific track record in fundamental and/or translational neurophysiology research. Women are strongly encouraged to apply. The successful candidate is expected to be appointed as early as 2019.

ICM is home to 28 research teams bringing together more than 700 personnel, including 150 researchers, 200 technical staff and 300 students and post-docs. ICM laboratories use multiscale approaches from cellular and molecular neurobiology, neurophysiology, systems to cognitive neuroscience. ICM offers state-of the-art core facilities that support fundamental, preclinical and clinical research, including access to human tissue.

The ICM is a private foundation working in synergy with French public bodies, and affiliated with Sorbonne Université, CNRS and INSERM. Importantly, ICM is associated with the Pole for the Diseases of the Nervous System of the Pitié-Salpêtrière hospital (APHP), as well as with a large network of public and industrial partners. ICM is dedicated to fundamental, translational and clinical research in Neuroscience, and fosters improved quality of care and education. Moreover, it hosts an in-house neuroscience clinical research center, spinoff, start-ups companies. The ICM is located alongside 13 National Reference Centers at the Pitié-Salpêtrière for rare neurological diseases.

Successful candidates will benefit from a competitive start-up package, recurrent core funding and will work in a stimulating and collaborative international environment. Group leaders at the ICM are affiliated with the Neuroscience Ph.D. program of Sorbonne Université. Skilled assistance for applications to national and international funding programs will be also provided (e.g. ERC, CNRS, Inserm, ANR, ATIP-Avenir, Equipes FRM).

Applications must be sent by January 15th 2018. Find here all informations for applications.

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Better definition of the state of consciousness by measuring brain–heart interactions? https://icm-institute.org/en/actualite/better-definition-of-the-state-of-consciousness-by-measuring-brain-heart-interactions/ https://icm-institute.org/en/actualite/better-definition-of-the-state-of-consciousness-by-measuring-brain-heart-interactions/#respond Thu, 28 Sep 2017 09:44:14 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=12549 How can we know if a patient is conscious if he or she is unable to communicate? Disorders of consciousness can be differentiated in two types: the “vegetative” For more information ]]> How can we know if a patient is conscious if he or she is unable to communicate? Disorders of consciousness can be differentiated in two types: the “vegetative” state, with no awareness from the patient and the “minimally conscious” state, with a certain degree of awareness. The distinction between these two states is very important to provide a prognosis on the patient’s neurological outcome, to choose the more adapted treatment and to inform patient’s relatives. All the tools that have been developed to determine consciousness until now, like EEG, f-MRI or PET scan are naturally “neurocentric” (focused on the brain activity). These tools require either heavy equipment or complex analysis. Can the rest of the body, however, contribute with extra information about the state of consciousness in noncommunicating patients?

The present study, conducted by Federico Raimondo and supervised by Dr. Jacobo Sitt, all part of the team of Lionel Naccache at the ICM, attempted to answer this question. The work builds on previous studies showing that “unconscious” functions of the autonomic nervous system, such as respiration or heartbeats are in fact modulated by conscious processes. Therefore, the researchers hypothesized that if patients are conscious the way their brains process external stimulation, for instance auditory clicks, will affect their heart activity.

By analyzing the data of 127 patients in vegetative or minimally conscious state, the team found that the heart cycle was indeed modulated by auditory stimulation only in minimally conscious patients: their cardiac activity “accelerated” when the auditory stimulation induced a “surprise” effect, suggesting that patients in MCS might have been able to predict this surprise more efficiently as compared to unconscious patients. The authors also showed that these results were complementary to previous investigations obtained using EEG. When these two tests (cardiac and EEG) were combined, the authors found that the prediction about the patients’ state of consciousness dramatically enhanced.

These results open new perspectives on a brain-body approach to evaluate consciousness in patients. The scientists now want to extend the framework to other physiological signals modulated by conscious processes, such as respiration or modulation of the pupil size, to develop a complete tool for evaluating consciousness at the bedside.

Référence : Brain-heart interactions reveal consciousness in non-communicating patients. Raimondo F, Rohaut B, Demertzi A, Valente M, Engemann D, Salti M, Fernandez Slezak D, Naccache L, Sitt JD. Ann Neurol. 2017 Sep 11

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The « Brain to Market » summer school is launched! https://icm-institute.org/en/actualite/the-brain-to-market-summer-school-is-launched/ https://icm-institute.org/en/actualite/the-brain-to-market-summer-school-is-launched/#respond Tue, 05 Sep 2017 14:25:05 +0000 Antoine Bonvoisin https://icm-institute.org/?post_type=actualite&p=12352 The 2017 « Brain to Market » summer school, takes place from the 4th to the 8th of September, at the Institut du Cerveau et de la Moelle Epinière (ICM), in Paris, For more information ]]> The 2017 « Brain to Market » summer school, takes place from the 4th to the 8th of September, at the Institut du Cerveau et de la Moelle Epinière (ICM), in Paris, with the depression for theme.

As every year, national and international researchers (Master and PhD students, post-doctorant), clinicians, engineers, and executives participate in the event 2017 « Brain to Market » summer school. This novel and innovative week of training combine both translational neuroscience and entrepreunarial formation providing to participants a comprehensive overview of reality and issues of the economic and industrial sphere.

During a 5 days period, through an intensive training, participants are challenged on research issues, on the depression concern for this year, with a final aim to imagine together medicine for tomorrow.

Find here the training program.

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THE ICM, DRIVING ECONOMIC GROWTH AND ACCELERATING MEDICINE IN FRANCE AND BEYOND! https://icm-institute.org/en/actualite/the-icm-driving-economic-growth-and-accelerating-medicine-in-france-and-beyond/ https://icm-institute.org/en/actualite/the-icm-driving-economic-growth-and-accelerating-medicine-in-france-and-beyond/#respond Thu, 31 Aug 2017 09:18:02 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=12326 French Prime Minister Edouard Philippe made an official visit to Station F during Ambassador Week.

“Our digital transformation must be a success, and we will For more information ]]> French Prime Minister Edouard Philippe made an official visit to Station F during Ambassador Week.

“Our digital transformation must be a success, and we will dedicate 10 billion euros to a major research and innovation investment project” Edouard Philippe

 

Alexis Génin, Directeur des Applications de la Recherche à l’ICM, Jean-Yves Le Drian, Ministre des Affaires Etrangères, Edouard Philippe, Premier ministre, et Mounir Mahjoubi, Secrétaire chargé du Numérique.

 

As a part of Ambassador Week, the ICM welcomed French Prime Minister Edouard Philippe along with Jean-Yves Le Drian, Minister of International Affairs, Mounir Mahjoubi, French Secretary of State for Digital Affairs, and Xavier Niel to get an overview of high-level digital innovation in France. During Ambassador Week, French government leaders and ambassadors discuss the upcoming year’s roadmap and meet with elected officials, experts and representatives from the general public and the business world.

 

Alexis Brice, Directeur Général de l’ICM, Alexis Génin, Directeur des Applications de la Recherche à l’ICM, et Edouard Philippe, Premier ministre

 

The ICM is one of the key players on the French digital scene: an Institute at the heart of medical, technological, and digital innovation for the benefit of patients.

The delegation met with the ICM’s spokesperson, learned about the iPEPS incubator, and met with the managers of BioSerenity, an ICM startup incubated in situ. This was a fantastic opportunity for our Institute to highlight its specificities in research, in the digital world, as well as its international outlook.

The ICM, home to over twenty startups in its iPEPS incubator, chose to grow further in the place where future standards and trends will be developed: Station F, a huge Campus that brings together high-level digital startups including HEC, Microsoft, and the ICM (with IHU and Carnot Institute certification).

 

 

The Institute is world-renowned owing to numerous collaborations with top-of-class industrial and academic institutions, giving startups incubated at Station F the motivation to aim to international markets.

 

 

BioSerenity, as an example, is a rapidly-growing company that combines high-tech engineering, medical development and big data. It has received over 12 national and international awards as well as the support from doctors and patient organizations throughout the world. The company currently has over 50 employees throughout Europe, Asia, and North America. It is headquartered at the Brain and Spine Institute (ICM) at the heart of the largest teaching hospital in France: La Pitié-Salpêtrière, in Paris.

 

 

Ad Scientiam, yet another incubated startup, has been in the United States since early 2017 and recently took part in the “European Healthcare Startup Investment Mission” program organized by the United States Department of Commerce and SelectUSA. Ad Scientiam will leverage the program results to accelerate its growth: key priorities are the implementation of a distribution partnership for DAMS (medical device for patients with multiple sclerosis) and the creation of a network of research partners (universities, healthcare professionals and patient organizations).

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https://icm-institute.org/en/actualite/the-icm-driving-economic-growth-and-accelerating-medicine-in-france-and-beyond/feed/ 0 NEW GENES INVOLVED IN BRAIN TUMORS https://icm-institute.org/en/actualite/new-genes-involved-in-brain-tumors/ https://icm-institute.org/en/actualite/new-genes-involved-in-brain-tumors/#respond Fri, 28 Jul 2017 09:31:44 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=12328 A large-scale genetic study that ICM researchers took part in, within an international consortium, highlights the relationship between genetic profiles of patients For more information ]]> A large-scale genetic study that ICM researchers took part in, within an international consortium, highlights the relationship between genetic profiles of patients and varying susceptibility to different types of brain tumors.

Gliomas represent roughly 27% of primitive brain tumors, meaning tumors that originate directly within the brain. They are split up into two main categories: glioblastomas, the most aggressive (high-grade gliomas), and low-grade gliomas. Despite current treatment options including chemotherapy, radiotherapy and surgery, glioma prognosis is generally poor. A better understanding of tumor development is crucial.

Currently, no link between environmental factors and tumor development has been found. Research on genetic predisposition and familial risk in glioma development, however, has recently accelerated in part owing to pangenome assembly studies. These studies analyze genetic variations in many individuals with the same illness in order to study correlation with the illness.

Recent research on gliomas identified 13 new DNA areas involved in brain tumor predisposition. To continue these efforts in understanding glioma development, a multicenter study combined former pangenome assembly studies with 2 more recent studies with the participation of ICM researchers. Researchers analyzed a total of 12,496 cases and 18,190 control subjects.

In addition to the previously identified areas, researchers highlighted DNA areas that are “at risk” for glioma development. A specific DNA mutation in these areas may be linked to higher risk of developing a glioma-type brain tumor. 5 new areas were identified for glioblastomas, and 8 for low-grade gliomas.

This study is the largest pangenome assembly study on gliomas to date. On the whole, results highlight crucial data on specific assemblies for different subtypes of glioma and highlight the polygenic (linked to a set of genes) aspect of glioma predisposition.

Further research on pangenome assembly as well as functional analyses are necessary to gain a deeper understanding of the biological and developmental aspects of the various types of glioma. Studies may help acquire highly useful information for the implementation of new therapy and tailored treatment.

Source : Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Melin BS, Barnholtz-Sloan JS, Wrensch MR, Johansen C, Il’yasova D, Kinnersley B, Ostrom QT, Labreche K, Chen Y, Armstrong G, Liu Y, Eckel-Passow JE, Decker PA, Labussière M, Idbaih A, Hoang-Xuan K, Di Stefano AL, Mokhtari K, Delattre JY, Broderick P, Galan P, Gousias K, Schramm J, Schoemaker MJ, Fleming SJ, Herms S, Heilmann S, Nöthen MM, Wichmann HE, Schreiber S, Swerdlow A, Lathrop M, Simon M, Sanson M, Andersson U, Rajaraman P, Chanock S, Linet M, Wang Z, Yeager M; GliomaScan Consortium, Wiencke JK, Hansen H, McCoy L, Rice T, Kosel ML, Sicotte H, Amos CI, Bernstein JL, Davis F, Lachance D, Lau C, Merrell RT, Shildkraut J, Ali-Osman F, Sadetzki S, Scheurer M, Shete S, Lai RK, Claus EB, Olson SH, Jenkins RB, Houlston RS, Bondy ML. Nat Genet. 2017 May;49(5):789-794.

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GUEST RESEARCHER: PROF. CORI BARGMANN “SIMPLE ORGANISMS TO UNDERSTAND GENETICS. “ https://icm-institute.org/en/actualite/guest-researcher-prof-cori-bargmann-simple-organisms-to-understand-genetics/ https://icm-institute.org/en/actualite/guest-researcher-prof-cori-bargmann-simple-organisms-to-understand-genetics/#respond Thu, 27 Jul 2017 09:28:59 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=12327 Prof. Cori Bargmann from Rockefeller University was at the Brain and Spine Institute – ICM on June 6th 2017 to give a conference on « Neuromodulatory regulation For more information ]]> Prof. Cori Bargmann from Rockefeller University was at the Brain and Spine Institute – ICM on June 6th 2017 to give a conference on « Neuromodulatory regulation through timescales in C. Elegans nematodes ».


All our latest «Invited Researcher» videos’ on YouTube..

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SLEEPWALKING AND BEHAVIORAL DISORDERS IN REM SLEEP: SHARED CHARACTERISTICS? https://icm-institute.org/en/actualite/sleepwalking-and-behavioral-disorders-in-rem-sleep-shared-characteristics/ https://icm-institute.org/en/actualite/sleepwalking-and-behavioral-disorders-in-rem-sleep-shared-characteristics/#respond Wed, 26 Jul 2017 09:38:13 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=12329 Restlessness in sleep is common, however it may be a symptom of two illnesses that seem to be complete opposites: sleepwalking and behavioral disorders in REM sleep. For more information ]]> Restlessness in sleep is common, however it may be a symptom of two illnesses that seem to be complete opposites: sleepwalking and behavioral disorders in REM sleep. The first affects a younger population and takes place during deep sleep, whereas the second mainly affects older patients and is often linked to neurodegenerative illness. However, a recent study carried out by ICM and APHP doctors and researchers found that certain characteristics of sleepwalking and behavioral disorders in REM sleep converge. These results could have an impact on diagnosis and patient care.

Sleepwalking and night terrors are considered abnormal behavior in deep sleep. Patients with low levels of consciousness are able to open their eyes, sit, scream, run, walk, hold onto objects, speak, or answer questions, for example – but often in an inappropriate fashion. Sleepwalking and night terrors mostly affect children and young adults, with high familial predisposition.

Conversely, behavioral disorders in REM sleep mainly affect individuals over 50. They are often associated with Parkinson’s disease or various types of dementia, as a precursor or associated disorder. Many studies have highlighted the link between Parkinson’s disease and sleep. Behavioral disorders are characterized by gesticulation, sudden arm and leg movement, laughs, speaking and screams. This type of behavior usually takes place in the patient’s bed and is not associated with walking. Patients describe the behavior as an attempt to act during dreams or nightmares.

These two disorders shouldn’t have any shared characteristics. However, previous studies found that in rare cases, some elderly patients had both behavioral disorders in REM sleep and experienced sleepwalking. Could this mean that the two illnesses share common characteristics?

To gain a deeper understanding of the question, doctors and researchers from the ICM and the sleep pathologies unit at Pitié-Salpêtrière Hospital examined 62 patients with sleepwalking or night terror disorders, 64 patients with behavioral disorders in REM sleep, 66 healthy elderly patients and 59 healthy young patients.

Participants answered a series of questions aiming at analyzing mental content and dreams during pathological episodes as well as their behavior, and took a video-polysomnography test in that records various physiological datasets including an encephalogram, heartrate, and muscular activity during sleep along with video recording.
Results show that typical characteristics of behavioral disorders in REM sleep such as intense dreams or nightmares and a feeling of physically “experiencing” them through gesticulation are often seen in sleepwalking patients. This observation has an impact on the specificity of questionnaires used in general population epidemiology to detect behavioral disorder in REM sleep, with possible false positives.

In addition to abnormal behavior in deep slow-wave sleep, patients with sleepwalking disorders or night terrors display muscle tremors and excessive jolts in REM sleep without exhibiting abnormal behavior in REM sleep. The origin of these tremors has yet to be found. They may be linked to greater REM sleep dreaming in sleepwalkers (explaining an increase in short tremors) or a lack of motor inhibition during both deep and REM sleep.

While the networks involved in sleepwalking have yet to be detailed (those at play in behavioral disorders have been clearly identified with damage to the locus subcoeruleus, that usually locks movement down in REM sleep), these results highlight that an individual complaining of intense nightmares or dream activity is not necessarily affected by behavioral disorders in REM sleep nor are they at risk for Parkinson’s disease. They may simply be affected by night terrors in deep slow-wave sleep. This makes it all the more important to record sleep activity and behavior of individuals that scream, are agitated, and gesticulate during sleep. Risk associated with self-harm or harming others may justify recommending a light course of treatment to reinstate true muscular relaxation during sleep.

Source : Is there a common motor dysregulation in sleepwalking and REM sleep behaviour disorder? Haridi M, Weyn Banningh S, Clé M, Leu-Semenescu S, Vidailhet M, Arnulf I. J Sleep Res. 2017 May 17

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The first WIRED Workshop https://icm-institute.org/en/actualite/the-first-wired-workshop/ https://icm-institute.org/en/actualite/the-first-wired-workshop/#respond Mon, 17 Jul 2017 14:17:27 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=12095 The first WIRED (Workshop on Intracranial Recordings in humans : Epilepsy, DBS) will be held at the ICM on October 3 and 4. Conferences, technical discussions, For more information ]]> The first WIRED (Workshop on Intracranial Recordings in humans : Epilepsy, DBS) will be held at the ICM on October 3 and 4. Conferences, technical discussions, poster session, commercial solutions, wine and cheese… all information and registration to this free event are on the website.

Intracranial electrophysiological recordings in human takes advantage of clinical investigations performed in the context of epileptic focus localization and deep brain stimulation (DBS) implants in movement disorder diseases. These recordings have proven to be of tremendous help to understand the physiopathology of these diseases, to validate results obtained with non-invasive approaches, and to study the general physiology of the human brain. Numerous technical developments have been recently made in the field, including the introduction of microelectrodes that allow investigators to obtain the level of spatial precision reached in animal models – down to single unit activity.

The first WIRED (Workshop on Intracranial Recordings in humans : Epilepsy, DBS) meeting will gather French and international participants, and invite leading speakers in the field. Featured talks will illustrate how intracranial recordings can be used for state of the art research projects, highlighting similarities and differences in DBS and epileptic investigation. All participants will have a chance to present their work at a poster session, with a prize worth 800€ to be awarded to the best poster. Since technical developments are key to scientific investigations, half a day will be dedicated to presentations and discussions on technical aspects. During the event, our partners will exhibit their latest commercial solutions.

The WIRED meeting will be held at the ICM on October 3 and 4, all information and registration to this free event are on the website.

Organisation : Katia Lehongre, Adrien Schramm.

Comité scientifique : Vincent Navarro, Brian Lau, Nathalie George, Michel Le Van Quyen, Marie Laure Welter, Lionel Naccache.

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How do emotions evolve over time ? https://icm-institute.org/en/actualite/how-do-emotions-evolve-over-time/ https://icm-institute.org/en/actualite/how-do-emotions-evolve-over-time/#respond Mon, 03 Jul 2017 13:01:56 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=11974 A collaborative study involving Philippe Fossati's team at the ICM, a team from KU Leuven and a team from Maastricht University has shown that neural bases of For more information ]]> A collaborative study involving Philippe Fossati’s team at the ICM, a team from KU Leuven and a team from Maastricht University has shown that neural bases of emotions vary with time.

Our emotions evolve over time. This can seem obvious, but understanding the variations, dynamics and areas of the brain involved in the process is key for future therapy. Emotional variations are a key component in several mental health disorders, such as depression post-traumatic stress disorder and borderline personality.

What happens when we experience an emotion? How does it evolve over time? Research on emotional dynamics is fairly recent. The various methods developed have highlighted two main phases in emotional dynamics. First is the start of the emotion, either brutal or progressive, referred to as the degree of explosiveness. Next comes the emotional compensation phase, meaning a deepening or mitigation of the emotion with time, assessed with a degree of accumulation.

Neural bases of these two phases and their possible variations over time remain unclear. Recent studies have identified certain areas of the brain involved in the establishment of emotions such as the medial prefrontal cortex, the amygdala and the insula.

HOW DOES THE ACTIVITY OF THE VARIOUS AREAS OF THE BRAIN VARY THROUGHOUT THE DIFFERENT PHASES OF AN EMOTIONAL EXPERIENCE?

To find out, researchers from the ICM, KU Leuven and Maastricht University conducted an experiment on 31 participants.
They asked them to write several short texts on personal topics such as their dreams and aspirations. The texts were then read by a jury who inferred the personality of participants. All participants actually received the same negative or neutral responses regarding their personality independently from their texts. Researchers then asked participants to read and think about the responses during 90 seconds and indicate emotional changes felt over time. Meanwhile, brain activity was recorded using functional MRI for real-time observation brain area activity.

Researchers were therefore able to study brain areas involved in explosiveness and accumulation of emotional response following negative social experiences, known to generate long-lasting emotional response enabling
differentiation of both phases.

Results show that emotional trigger and compensation phases are the two main components of emotional change over time and are associated with distinct areas of the brain. Differences in emotional trigger explosiveness are linked to medial prefrontal cortex activity. This area is supposedly involved in self-perception. In this case, activation may reflect the difference between the jury’s evaluation and the self-perception of participants.

Differences in accumulation are linked to activation of the posterior insula, an area known to play a key role in integration of emotional signals.

This is the first study to show the varying activity in areas of the brain that orchestrate emotional response. It underlines how important it is to take the time component into account to understand underlying neural bases in the evolution of emotions, from initiation to intensification or mitigation, following social exclusion.

These results could have an impact on treatments for mental health disorders.

Source : The neural basis of emotions varies over time: Different regions go with onset- and offset-bound processes underlying emotion intensity. Résibois M, Verduyn P, Delaveau P, Rotgé JY, Kuppens P, Van Mechelen I, Fossati P. Soc Cogn Affect Neurosci. 2017 Apr 11.

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Towards european healthcare https://icm-institute.org/en/actualite/towards-european-healthcare/ https://icm-institute.org/en/actualite/towards-european-healthcare/#respond Mon, 03 Jul 2017 13:01:45 +0000 Armance Gelaude https://icm-institute.org/?post_type=actualite&p=11973 The ICM belongs to a European reference center on rare neurological diseases. The launch seminar for the European Reference Network, or ERN, dedicated to rare For more information ]]> The ICM belongs to a European reference center on rare neurological diseases. The launch seminar for the European Reference Network, or ERN, dedicated to rare neurological diseases took place on May 15th and 16th and the ICM is a member.

This initiative brings together members from 13 European countries and aims at encouraging interaction, discussions, sharing of expertise and data transfer between European Reference Centers to benefit patients.
Ségolène Aymé, Rare Diseases Project Manager at the ICM and founder of Orphanet, tells us more about the Network’s goals.

HOW IS HEALTHCARE MANAGED AT THE EUROPEAN LEVEL?

Every European country is independent in its healthcare policy. Healthcare is not a European Community competency as it is out of treaty and cannot be managed on a European level. The only possible European action is helping countries cooperate.

Currently and for the past couple of years, an increasing number of travelers visit Europe and receive care in countries other than theirs. Countries must therefore agree on various points such as medical fee reimbursement or patient rights. In this context, a guideline on cross-border medical care was implemented two years ago. It aims at opening healthcare to all European citizens in every member country as well as allowing collaboration and resource-sharing among countries.

HOW WERE EUROPEAN REFERENCE NETWORKS CREATED AND WHAT IS THEIR OBJECTIVE?

A very important aspect of the guideline was the creation of European Reference Networks (ERN), especially focused on rare illnesses. The goal is to identify expertise and cutting-edge platform technology in each country so that every European citizen can access these resources, even if they are located outside of their home country. These ERN are a way of improving overall quality of healthcare.

Expertise travels, not the patient. The ERN’s main mission is patient care: organizing teleconsultations, meetings among experts to solve difficult cases, involving a larger number of patients in clinical trials, as well as homogenizing clinical methods and collecting comparable data.

WHAT WAS THE GOAL OF THE RARE NEUROLOGICAL DISEASES NETWORK LAUNCH SEMINAR?

The goal of the seminar was to agree on a work package and define a roadmap for the 5 coming years.

ICM clinicians are very proactive within the network. Alexandra Durr, leader of the task force dedicated to clinical diagnosis, presented a roadmap on European organization of rare neurological disease diagnosis. The goal of the work package is to advise on the best way of setting a clinical and molecular diagnosis on a European level. Isabelle Leber is coordinator for the task force dedicated to fronto-temporal dementia and Marie Vidailhet is coordinator for the task force dedicated to dystonia, paroxysmal disorders and neurodegeneration with brain iron accumulation.

WHAT IS THE FOCUS FOR THE NEXT 5 YEARS?

Nearly one half of patients affected by a rare neurological disease cannot be classified as a specific pathology. The network will enable the design of a shared database to help make a precise diagnosis for as many patients as possible and in hopes of identifying new neurological illnesses. 50% of rare neurological diseases currently remain unidentified.

This cooperation will also facilitate clinical trials and patient recruitment when new therapy options are made available. Healthcare and research inseparable!

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