Institut du Cerveau https://institutducerveau-icm.org Fri, 22 Oct 2021 08:45:32 +0000 https://wordpress.org/?v=4.9.13 hourly 1 https://wordpress.org/?v=4.9.13 Thinking collectively to understand the social intelligence of animals https://institutducerveau-icm.org/en/actualite/thinking-collectively/ https://institutducerveau-icm.org/en/actualite/thinking-collectively/#respond Fri, 22 Oct 2021 08:45:32 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=22163 What if, in order to understand the social intelligence of animals, including humans, we had to study the brain at the group level and not only at rather than the For more information ]]> What if, in order to understand the social intelligence of animals, including humans, we had to study the brain at the group level and not only at rather than the individual level? This is a perspective put forward by Julia Sliwa, a CNRS researcher at the Paris Brain Institute, in the journal Science.

All animals evolving in social groups, from ants to humans, birds and monkeys, adapt their behaviour to the group. The group represents a considerable evolutionary advantage for many species. It allows them to find solutions or accomplish tasks that are impossible to achieve alone: from reducing predation to building habitats, from ant hills to human cities. These behaviours arise from social interaction, be it verbal or non-verbal communication, mimicry, memorisation, or other signalling processes.

 

From ethology to social neuroscience

Research in ethology has already revealed collective decision-making within social groups of animals. These decisions are made by individuals without them realising that it is a collective effort, but simply by having one-to-one interactions that gradually guide the whole group in the same direction. This is for example the case with some birds such as starlings when they fly. By computer modelling interactions, it is even possible to simulate what type of collective behaviour would emerge from these interactions, by varying the skills of the individuals in the group, such as memory and the ability to signal information to others.

But what happens in the brains of these individuals when they interact and make individual decisions within groups? Until now, neuroscience has mainly studied animal intelligence at the level of an individual brain in isolation. However, it is quite possible that the brain of this animal changes its functioning when it evolves within a group. Technological advances in brain imaging now make it possible to make electroencephalographic recordings, i.e. of the brain’s electrical activity, using portable machines. The study of social cognition has thus been able to move out of the laboratory and into ‘real life’. We now know that in humans, within a group, the electrical activity of the brains of the individuals that make up the group can be synchronised during various social interactions, from communication to learning.

 

Towards a collective approach of social intelligence

Two recent publications in the journal Science focus not only on how animals perceive the social interactions of others but also on how they experience them, i.e. how they interact with others. The other major novelty of their approach is that they look not only at two-to-two interactions but also at all interactions within the group, potentially a very large number of interactions at the same time. The synchronisation phenomenon already observed in humans also exists in other primates and bats, suggesting a mechanism that is conserved at least in mammals. Moreover, while humans and several primates are individually able to represent group decisions, many other animals, especially insects, are not. How this ability is encoded in the brain is a new field of research that these publications started to uncover.

Finally, could the key to social intelligence lie in the synchronisation of the brains, allowing group interactions to be made? If so, should social neuroscience now focus on the group rather than the individual? Above all, this work suggests the importance of studying social intelligence at both scales. Another perspective would be to extend group interaction from the real to the virtual, to explore the new collective dynamics resulting from the use of social networks on the internet.

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New data on inflammation in multiple sclerosis using PET-MRI https://institutducerveau-icm.org/en/actualite/news-data-sclerosis/ https://institutducerveau-icm.org/en/actualite/news-data-sclerosis/#respond Wed, 20 Oct 2021 18:00:54 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=22117
Several studies by Prof. Bruno Stankoff's team "Remyelination in multiple sclerosis: from biology to clinical translation", highlight new mechanisms of brain For more information ]]>

Several studies by Prof. Bruno Stankoff’s team “Remyelination in multiple sclerosis: from biology to clinical translation”, highlight new mechanisms of brain inflammation in multiple sclerosis, thanks to new imaging tools based on the combination of magnetic resonance imaging (MRI) and positron emission tomography (PET).

Using PET-MRI, Prof. Stankoff’s team has just published in the journal Radiology the results of a study of 97 MS patients and 44 healthy controls showing abnormalities (increased volume and inflammation) in the choroid plexuses of the patients. The choroid plexuses are structures located in the cerebral ventricles responsible for the production of cerebrospinal fluid, and act as a barrier between the nervous system and the immune system.

These choroidal plexus abnormalities were correlated with brain inflammation, indicating disease activity. These results open a new avenue for the application of imaging of this structure as a marker of the immune response in the brain and point to the choroid plexus as an important player in the pathophysiology of the disease.

The choroïd plexuses (circled in red) of MS patients with a remitting form are larger (on the right) than healthy controls’ (on the left)

 

Work by the same team published in the journal Neurology, shows activation of innate immune cells associated with white matter micro-lesions in MS patients with worsening disability, and that this immune activation follows a gradient centered around the cerebral ventricles, which contain cerebrospinal fluid.

 

These results obtained thanks to the combination of PET targeting innate immune cells and MRI confirm the existence of a correlation between the activation of these cells around the ventricles, privileged areas of MS lesions in contact with cerebrospinal fluid (CSF), and the worsening of the disability in patients. This suggests that molecules contained in the CSF could worsen the inflammation present in the white matter of patients and thus promote a deleterious evolution of the disease, making these molecules candidates for future research into treatments.

Activated innate immune cells in a patient with MS using PET-scan around ventricles.

 

Source

Structural and Clinical Correlates of a Periventricular Gradient of Neuroinflammation in Multiple Sclerosis. Poirion E, Tonietto M, Lejeune FX, Ricigliano VAG, Boudot de la Motte M, Benoit C, Bera G, Kuhnast B, Bottlaender M, Bodini B, Stankoff B. Neurology. 2021 Apr 6;96(14):e1865-e1875.

 

Choroid Plexus Enlargement in Inflammatory Multiple Sclerosis: 3.0-T MRI and Translocator Protein PET Evaluation. Ricigliano VAG, Morena E, Colombi A, Tonietto M, Hamzaoui M, Poirion E, Bottlaender M, Gervais P, Louapre C, Bodini B, Stankoff B. Radiology. 2021 Oct;301(1):166-177.

 

Positron emission tomogramphy in multiple sclerosis – straight to the target. Bodini B, Tonietto M, Airas L, Stankoff B. Nat Rev Neurol. 2021 Sep 20.

 

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Discover the Paris Brain Institute https://institutducerveau-icm.org/en/actualite/discover/ https://institutducerveau-icm.org/en/actualite/discover/#respond Tue, 19 Oct 2021 09:51:46 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=22110 Paris Brain Institute (ICM) is a research center of international dimension,  innovative in its conception as in its organization. By bringing together patients, For more information ]]> Paris Brain Institute (ICM) is a research center of international dimension,  innovative in its conception as in its organization. By bringing together patients, doctors and researchers in the same place, the objective is to enable the rapid development of treatments for nervous system injuries in order to apply them to patients as quickly as possible. Coming from all horizons and all countries, the best scientists develop the most advanced research in this field.

 

Discover our institute in this video :

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World Mental Health Day https://institutducerveau-icm.org/en/actualite/world-mental-health-day/ https://institutducerveau-icm.org/en/actualite/world-mental-health-day/#respond Sun, 10 Oct 2021 08:06:23 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=22059 If we need to take care of our mental health every day, World Mental Health Day, held every October 10, is an opportunity to bring this essential component of our For more information ]]> If we need to take care of our mental health every day, World Mental Health Day, held every October 10, is an opportunity to bring this essential component of our lives back into focus. The events of the Covid-19 pandemic have also had a heavy impact on our mental health. It is essential to talk about it!

 

Mental health is an essential component of our health, defined by the WHO as “a state of well-being in which a person can achieve personal fulfillment, cope with the normal stresses of life, do productive work, and contribute to his or her community. In this positive sense, mental health is the foundation for an individual’s well-being and for the proper functioning of a community.

 

This definition covers many aspects, from the development of the individual to the protection of his or her psychological balance. Mental health therefore goes far beyond the pathological dimension, but since more than one adult in four is or will be affected by a psychiatric disorder during his or her lifetime, it is important to shed light on what these conditions are and their impact on the lives of the people they affect.

 

Psychiatric disorders represent a major public health issue today. Although their therapeutic management has progressed considerably thanks to research, societal prejudices persist. These distorted views of reality, fueled by media coverage of violent but “rare” events (less than 1% of patients being potentially dangerous to others), still lead to discrimination and a significant delay in the diagnosis of patients. The association between psychiatry and madness is unfortunately still widespread in society’s beliefs. Nowadays, psychiatric disorders benefit from appropriate care and effective treatments that allow patients to continue their social, family and professional life.

 

Innovative targeted and personalized therapies

 

The treatment of patients with psychiatric disorders is multidisciplinary and must combine psychotherapy, drug treatments, and new therapeutic technologies. Clinicians and researchers at the Paris Brain Institute, in close collaboration with the adult psychiatry department of the Pitié-Salpêtrière Hospital (AP-HP), have as their main objective to develop the use of existing and effective technologies in more pathologies, but also to allow therapies to be adapted to each patient.

 

New ways to treat psychiatric disorders

 

These “new generation” therapies are generally associated with psychotherapy and drug treatments specific to each psychiatric disorder.

 

Virtual reality

The objective of this therapy is to allow the patient to gradually tame anxiety-provoking situations and to desensitize himself. Equipped with a 3D headset projecting a scene that usually provokes his disorder, the patient can progress without risk since he knows that he is only facing virtual dangers.

 

Transcranial magnetic stimulation

Transcranial magnetic stimulation consists of using a magnetic field to modify the electrical activity in the cerebral cortex. This technology has shown its effectiveness in cases of severe depressive syndromes, but also in cases of auditory hallucinations in schizophrenic patients. It is currently being evaluated for OCD and addictions.

 

Deep brain stimulation

In cases of severe depression or OCD, resistant to other therapies, deep brain stimulation is indicated. These stimulations are performed with electrodes implanted in specific regions of the brain. They deliver permanent electrical stimulation to the neurons in very specific areas of the brain. Researchers at the Paris Brain Institute are pioneers in the use of deep brain stimulation in many neurological and psychiatric pathologies, such as Parkinson’s disease or Tourette’s syndrome, for example.

 

E-psychiatry

The development of “connected” devices allowing access to clinical information in real time in the patient’s natural environment is beginning to change the way psychiatric disorders are managed. In the case of suicidal tendencies, for example, variables such as appetite and sleep appear to be very informative for the clinician in predicting and preventing a possible act.

The Covid-19 pandemic: a heavy impact on our mental health

 

The Covid-19 pandemic, the successive confinements and the multiple changes of sanitary rules, more globally the uncertainty that this crisis has generated in our lives, have had a heavy impact on our psychic well-being and repercussions on our mental health. Cases of anxiety and depression have increased in the last year and a half in the general population. Psychiatrists have identified several reasons for these disorders: anxiety about being contaminated, about contaminating one’s loved ones, uncertainty about the future, and the many constraints in daily life imposed by the health situation.

 

 

 

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Our checking behaviours deciphered by experimental psychology! https://institutducerveau-icm.org/en/actualite/our-checking-behaviours-deciphered-by-experimental-psychology/ https://institutducerveau-icm.org/en/actualite/our-checking-behaviours-deciphered-by-experimental-psychology/#respond Fri, 24 Sep 2021 12:51:43 +0000 Nicolas BRARD https://institutducerveau-icm.org/?post_type=actualite&p=21891 We engage in checking behaviours on a daily basis. In certain pathologies such as OCD, these behaviours can be exacerbated and greatly disturb the quality of life of For more information ]]> We engage in checking behaviours on a daily basis. In certain pathologies such as OCD, these behaviours can be exacerbated and greatly disturb the quality of life of patients. A study conducted by Axel Baptista (AP-HP/Sorbonne University), Maxime Maheu (UKE Hamburg), Luc Mallet (AP-HP/Université Paris-Est Créteil) and Karim N’Diaye (CNRS) at the Paris Brain Institute shows that these checking behaviours are modulated by two cognitive mechanisms: metacognition and self-beliefs. The results are published in Scientific Reports.

 

The decisions we make every day include an element of uncertainty. To reduce this uncertainty and thus facilitate our choices, we carry out verification behaviours, such as listening several times to a message on the answering machine when the sound quality is poor. In some psychiatric conditions, such as obsessive-compulsive disorder (OCD), these checks are exacerbated and greatly handicap patients in their daily lives. While we experience these behaviours all the time, their brain mechanisms and disruptions in OCD are poorly understood.

“This spontaneous behaviour is not easy to explore in the laboratory, particularly in healthy participants. To do this, we had to set up a specific computer test in which the participants would be inclined to view the same stimulus several times,” explains Karim N’Diaye, head of the PRISME core facility dedicated to behavioural studies at the Paris Brain Institute, the last author of the study.

The task in question consisted of participants giving the direction of the global movement of a cloud of animated dots. The degree of difficulty was also adapted individually. In parallel, the researchers measured obsessive-compulsive tendencies, such as the propensity to check that the gas is turned off, as well as metacognitive beliefs, such as the extent to which the participants trust their memory, using standardised questionnaires.

 

“We put a lot of effort into the methodological rigour and then the statistical analysis of the data to show that the subjective evaluation of our degree of uncertainty does modulate the tendency to check, but that this seems to be relatively limited to the uncertainty that we apprehend explicitly, i.e. the uncertainty that we become aware of when we are asked to evaluate our confidence in a decision,” explains Axel Baptista, first author of the publication.

 

The link between subjective uncertainty and verification behaviour is also modulated by negative metacognitive beliefs – the fact of not trusting one’s “cognitive abilities”. These beliefs tend to decouple verification behaviour from the degree of uncertainty. Finally, the researchers show in this study that obsessive-compulsive tendencies, in these healthy participants, exacerbate the link between uncertainty and checking. This may seem paradoxical insofar as OCD patients spontaneously report suffering from feeling compelled to check, while being aware that it is probably unnecessary.

This study will allow further work to confirm these mechanisms, and to study them in populations of patients with neuropsychiatric disorders like OCD. Indeed, it is suspected that these mechanisms are altered in this condition. Overall, this work could lead to a better understanding of the link between uncertainty, metacognition and OCD.

 

 

Source

Baptista A, Maheu M, Mallet L, N’Diaye K (2021). Joint contributions of metacognition and self-beliefs to uncertainty-guided checking behaviorSci Rep, 2021. doi: 10.1038/s41598-021-97958-1

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ECOCAPTURE@HOME: assessing apathy and its consequences in everyday life https://institutducerveau-icm.org/en/actualite/ecocapturehome-assessing-apathy-and-its-consequences-in-everyday-life/ https://institutducerveau-icm.org/en/actualite/ecocapturehome-assessing-apathy-and-its-consequences-in-everyday-life/#respond Thu, 23 Sep 2021 11:16:46 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21824 Apathy, a pathological absence of motivation and emotion, is a common symptom of many neurological and psychiatric diseases, such as dementia or depression. The For more information ]]> Apathy, a pathological absence of motivation and emotion, is a common symptom of many neurological and psychiatric diseases, such as dementia or depression. The ECOCAPTURE@HOME program, developed by researchers and clinicians at the Paris Brain Institute, aims to establish a precise diagnosis of apathy and to set up personalised care for patients.

 

Apathy is the most common neuropsychiatric symptom in neurodegenerative diseases such as Alzheimer’s, Parkinson’s or fronto-temporal degeneration. It is associated with greater cognitive impairment and an overall deterioration in the quality of life of patients and their carers. Indeed, this pathological loss of motivation makes daily activities a real challenge.

Drug treatments for apathy, mainly antidepressants, show only moderate effects. Non-medicinal approaches such as psychotherapy require a very precise assessment of the degree of apathy in each patient in order to propose personalised treatment and hope for an improvement in symptoms.

“Define and assess apathy is far from obvious. Apathy can take many different forms and clinical assessment scales are biased by the subjectivity of the evaluator, usually the patient themselves or their carer“ explains Valérie Godefroy, first author of the study and post-doctoral fellow under the supervision of Bénédicte Batrancourt (Inserm) and Richard Lévy (AP-HP/Sorbonne University) at the Paris Brain Institute’s Frontlab.

The ECOCAPTURE programme, led at the Paris Brain Institute by Bénédicte Batrancourt (Inserm) and Richard Lévy (AP-HP/Sorbonne University), aims to develop new approaches to measuring apathy. It has recently defined several forms of the behavioural variant of frontotemporal dementia (FTD), through evaluation in the functional exploration room of the PRISME core facility.

In order to be as close as possible to the real-life conditions of patients, one of the objectives of ECOCAPTURE is to bring its assessment tools directly to their homes. This study, ECOCAPTURE@HOME, has been set up to validate a method for monitoring apathy at a distance. To do this, the researchers and clinicians at the Brain Institute wish to recruit 40 patient-caregiver pairs, 20 for Alzheimer’s disease, 20 for the behavioural variant of FTD, and 20 control subjects without pathology. The data will be acquired using a connected watch and questionnaires on a smartphone application.

“Our objective is to validate the relevance of our measurement method based on three behavioural markers of apathy: daytime activity, sleep quality and the emergence of emotions. If the results are positive, ECOCAPTURE@HOME could enable a better diagnosis of apathy in order to implement personalised management in the daily lives of patients,” concludes Bénédicte Batrancourt, the study’s last author.

 

The Paris Brain Institute thanks the Malakoff Humanis group for its support of the Ecocapture project.

Source

ECOCAPTURE@HOME: Protocol for the Remote Assessment of Apathy and Its Everyday-Life Consequences. Godefroy V, Levy R, Bouzigues A, Rametti-Lacroux A, Migliaccio R, Batrancourt B. Int J Environ Res Public Health. 2021 Jul 2

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Discovery of the association between two key cellular mechanisms of Alzheimer’s disease https://institutducerveau-icm.org/en/actualite/discovery-of-the-association-between-two-key-cellular-mechanisms-of-alzheimers-disease/ https://institutducerveau-icm.org/en/actualite/discovery-of-the-association-between-two-key-cellular-mechanisms-of-alzheimers-disease/#respond Wed, 15 Sep 2021 15:18:48 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21864 A study by Bassem Hassan's team (Inserm) at the Paris Brain Institute shows for the first time the direct link between two key mechanisms of Alzheimer's disease: the For more information ]]> A study by Bassem Hassan’s team (Inserm) at the Paris Brain Institute shows for the first time the direct link between two key mechanisms of Alzheimer’s disease: the amyloid precursor protein (APP) defect and the Wnt signalling defect. In collaboration with Marie Claude Potier’s team (CNRS), they also show a direct effect of this interaction on the production of amyloid, one of the proteins that becomes pathological in the disease. The results are published in eLife.

 

 

Mutations in the APP gene, which produces the amyloid precursor protein, are one of the main familial causes of Alzheimer’s disease. These share most of their clinical features with the sporadic forms of the disease, which account for 95% of cases. The biological mechanisms between the two forms should also share a number of similarities between the two forms. The study of the genetic forms is therefore essential for a better understanding of this pathology as a whole.

Results have been accumulating for years, in Alzheimer’s disease models and in patients, on another cell signalling pathway that is very important in brain development and physiology, the Wnt pathway. This pathway has been shown to be associated with both more severe and milder forms of the disease.

A study conducted by Bassem Hassan’s team (Inserm) looked at the link between these two pathways and how they interact in normal and pathological conditions in the case of Alzheimer’s disease.

Using the fruit fly (Drosophila melanogaster) and mouse neurons, the researchers show that APP is in fact a receptor for the Wnt pathway, and that there is therefore a direct link between these two mechanisms. Wnt regulates APP levels and the way APP is processed in neurons.

APP is the precursor of the amyloid-beta peptide, known to be one of the major pathological proteins in Alzheimer’s disease. In collaboration with Marie-Claude Potier’s team (CNRS), the researchers wanted to evaluate the impact of the interaction between Wnt and APP on the production of beta-amyloid. They thus confirmed that the regulation of APP levels by the Wnt pathway affects amyloid production.

Taken together, these results provide important insights into the pathological mechanisms of Alzheimer’s disease at the molecular level, and their consequences for the production of beta amyloid.

Source The amyloid precursor protein is a conserved Wnt receptor. Liu T, Zhang T, Nicolas M, Boussicault L, Rice H, Soldano A, Claeys A, Petrova I, Fradkin L, De Strooper B, Potier MC, Hassan BA.Elife. 2021 Sep 9;10:e69199.

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Inter-subject heart rate synchronization: a new sign for monitoring consciousness https://institutducerveau-icm.org/en/actualite/inter-subject-heart-rate-synchronization/ https://institutducerveau-icm.org/en/actualite/inter-subject-heart-rate-synchronization/#respond Tue, 14 Sep 2021 15:38:31 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21844 When we listen to a story being told, our attention might be reflected in the inter-subject synchronisation of our heart rate. This is shown by a study carried by For more information ]]> When we listen to a story being told, our attention might be reflected in the inter-subject synchronisation of our heart rate. This is shown by a study carried by Pauline Perez (co-first author) from Jacobo Sitt’s group (Inserm) in the “PICNIC – physiological investigation of clinically normal and impaired cognition” team at Paris Brain Institute, which also reports that this synchronisation could constitute a new biomarker of states of consciousness. The results are published in Cell Reports.

 

Our heart rate fluctuates greatly depending on the information we receive. Physical activity causes it to speed up, but just thinking about it could also change our heartbeat. Meditation, on the other hand, can slow it down. Mental processes could therefore play an important role in our body rhythms. Jacobo Sitt’s group at the Paris Brain Institute sought to understand whether and how awareness of a stimulus could synchronize our body rhythms across individuals (EEG, heart rate, etc.) and in particular cardiac activity, which has the advantage of being easily measured. To do this, they used a new type of stimulus, the narration of a story, audio or audiovisual. They show that when subjects listen to a story, their cardiac activity synchronizes, i.e. it increases and decreases at the same moments.

The study was conducted in collaboration with British and American teams on four groups of subjects. The first group recorded in Birmingham, UK (lead by Damian Cruse) measured only heart timing while listening to a story.

A second group in New York (Lucas Parra – co-senior author – and Jens Madsen – co-first author of the study) tested two conditions: in one they attentively watch educational videos, in the other they watch the same video while doing a simultaneous task (counting backwards in steps of 7) in order to disrupt their attention. In this case, there was a significant difference between subjects who were attentive to the story, who were synchronized in their heart activity, and those who were distracted and did not synchronize.

The third group was evaluated by the Paris Brain Institute team. The stories presented to them were audio only. This was necessary in order to be able to carry out this experiment with patients with impaired consciousness, who are not able to watch a video. He followed a similar test pattern to the New York group. At the end of the story, the subjects were also asked to fill in a questionnaire about the story in question. The results obtained were identical to those of New York. The addition of the questionnaire also allowed the team to show that the subjects’ levels of synchronization with the group were predictive of their ability to memorise the story. Thus, subjects with very high levels of synchronization remembered the story much better than subjects with low levels of heart synchronization.

Finally, the last group consisted of subjects with impaired consciousness. The researchers show that the synchronization levels between patients and healthy subjects are still very low. However, some patients showed a higher synchronization with the healthy subjects. This was associated with a better recovery of consciousness.

“While we don’t know for sure if these patients are fully conscious, they can react in the same way as healthy subjects. This response appears to be predictive of recovery of consciousness. This result suggests a new approach to assessing consciousness, easy to implement in the clinic and complementary to other methods of measuring consciousness” explains Jacobo SITT (Inserm)

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A major role for PIK3CA gene mutations in sporadic cavernoma https://institutducerveau-icm.org/en/actualite/a-major-role-for-pik3ca-gene-mutations-in-sporadic-cavernoma/ https://institutducerveau-icm.org/en/actualite/a-major-role-for-pik3ca-gene-mutations-in-sporadic-cavernoma/#respond Fri, 10 Sep 2021 15:49:34 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21837 Teams from the Paris Brain Institute and Pitié-Salpêtrière Hospital AP-HP, coordinated by Dr Matthieu Peyre and Prof Michel Kalamarides, have studied the presence For more information ]]> Teams from the Paris Brain Institute and Pitié-Salpêtrière Hospital AP-HP, coordinated by Dr Matthieu Peyre and Prof Michel Kalamarides, have studied the presence of mutations in the PIK3CA gene in cavernomas. This work is published in the New England Journal of Medicine.

Cavernomas are low-flow cerebral vascular malformations consisting of abnormally enlarged capillary cavities without intervening brain parenchyma; the condition affects 1 in 200 to 250 people. Although mainly characterised by subclinical bleeding, cavernomas can lead to epileptic seizures and haemorrhagic strokes with significant neurological complications, particularly when they are located in the brainstem.

Cavernomas can occur in isolation or as part of a familial genetic disease. Mutations occurring in a familial context concern in 80% of cases the CCM genes. The genetics of sporadic cavernomas, which account for up to 90% of cases, is poorly understood.

In order to study meningeal tumorigenesis and meningiomas (the most frequent tumour of the central nervous system, of which they are experts), Dr Peyre and Prof Kalamarides have generated two new genetically modified mouse models of meningiomas by activating mutation of the PIK3CA and AKT1 genes in the PI3K-AKT-mTOR pathway.

The unexpected observation of typical cavernomas identical to human lesions prompted them to investigate the possible involvement of PIK3CA and AKT1 mutations in sporadic human cavernomas. They identified 39% PIK3CA mutations in a series of 88 sporadic cavernomas. Furthermore, their results shed new light on the potential cell of origin of cerebral cavernous malformations that was previously considered to be of endothelial lineage. They have shown that it is in fact PGDS-positive pericytes that cause cavernomas in their models by disorganisation of the neurovascular unit.

Their results may provide a better understanding of the biology of sporadic cerebral cavernous malformations by highlighting the major role of PIK3CA mutations in them, rather than that of the CCM genes, initially considered to be predominant.

This result, which was corroborated by a preclinical model, opens new perspectives, still to be validated, for the development of targeted therapies for the treatment of sporadic human PIK3CA-mutated cavernomas that are refractory to surgery and radiotherapy or radiosurgery and lead to frequent complications. PIK3CA inhibitors have indeed shown promising results in patients with CLOVES syndrome (PIK3CA-related hypergrowth syndrome) as well as in patients with a wide range of tumours.

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Discovery of a new way for our brain cells to communicate https://institutducerveau-icm.org/en/actualite/discovery-of-a-new-way-for-our-brain-cells-to-communicate/ https://institutducerveau-icm.org/en/actualite/discovery-of-a-new-way-for-our-brain-cells-to-communicate/#respond Thu, 09 Sep 2021 09:31:43 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21815 A study conducted by Anne Desmazières, Rémi Ronzano and Thomas Roux in Catherine Lubetzki’s team at Paris Brain Institute, shows for the first time a new For more information ]]> A study conducted by Anne Desmazières, Rémi Ronzano and Thomas Roux in Catherine Lubetzki’s team at Paris Brain Institute, shows for the first time a new interaction between neurons and microglia, immune cells present in the brain. This hitherto unknown mode of communication could be key to a better understanding of brain repair mechanisms and pathologies such as multiple sclerosis. The results are published in Nature Communications.

In our nervous system, the transmission of nerve impulses (nerve messages) takes place via the extensions of neurons, the axons, surrounded by an insulating sheath called myelin. The nodes of Ranvier, small domains interspersed between the myelin segments, are essential for the rapid diffusion of information, but they are also a hub of cellular interactions in the brain.

 

 

Previous studies have already shown that certain types of brain cells, such as oligodendrocytes and astrocytes, form contacts with neurons at these nodes of Ranvier. However, interactions with another essential brain cell type, microglia, had not been explored. These immune cells play a key role in protecting the brain and in regenerative processes such as remyelination, the reformation of the myelin sheath, which is affected in diseases such as multiple sclerosis.

A study conducted at the Paris Brain Institute by Anne Desmazières and her colleagues Rémi Ronzano and Thomas Roux in Catherine Lubetzki’s team shows for the first time that contacts and communication exist between neurons and microglial cells at the level of the nodes of Ranvier.

Thanks to studies carried out on ex-vivo (tissue culture) and in-vivo mouse models, in particular using real-time imaging approaches to observe the dynamics of these contacts, but also on human tissue, the researchers revealed a particularly stable interaction between these two types of cells, and a reinforced dialogue in a context of myelin regeneration. They also identified the mechanisms underlying this dialogue. Neuronal activity mediates and reinforces the interaction. Microglia are able to ‘read’ the information arriving at the nodes of Ranvier in the form of an ionic signal, thus modulating their state and their interaction with the neuron. Alteration of this ionic signal can keep microglia in a pro-inflammatory state, preventing them from playing their pro-regenerative and pro-remyelinating role.

In the case of multiple sclerosis, this discovery opens up several avenues of research to better understand the disease, in particular the impact of inflammatory signals in this disease on the neuron-microglia dialogue and the pro-remyelinating potential of microglia. The discovery of this dialogue is all the more interesting as therapies being tested in multiple sclerosis are now trying to act on the physiology of these microglia in order to promote their pro-regenerative character.

This new mode of communication also raises the question of the impact of neuronal activity on the behaviour of microglia. Indeed, many neurological pathologies, including epilepsy, are associated with alterations in neuronal activity, and the consequences of this alteration on microglial cells are still unknown.

Source

Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination. Ronzano R, Roux T, Thetiot M, Aigrot MS, Richard L, Lejeune FX, Mazuir E, Vallat JM, Lubetzki C, Desmazières A.Nat Commun. 2021 Se

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A Proposal to Make Biomedical Research into Alzheimer’s Disease More Democratic Following an International Survey with Researchers https://institutducerveau-icm.org/en/actualite/a-proposal-to-make-biomedical-research-into-alzheimers-disease-more-democratic-following-an-international-survey-with-researchers/ https://institutducerveau-icm.org/en/actualite/a-proposal-to-make-biomedical-research-into-alzheimers-disease-more-democratic-following-an-international-survey-with-researchers/#respond Fri, 13 Aug 2021 12:57:15 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21739 Background: Therapeutic research into Alzheimer’s disease (AD) has been dominated by the amyloid cascade hypothesis (ACH) since the 1990s. However, targeting For more information ]]> Background: Therapeutic research into Alzheimer’s disease (AD) has been dominated by the amyloid cascade hypothesis (ACH) since the 1990s. However, targeting amyloid in AD patients has not yet resulted in highly significant disease-modifying effects. Furthermore, other promising theories of AD etiology exist.

Objective: We sought to directly investigate whether the ACH still dominates the opinions of researchers working on AD and explore the implications of this question for future directions of research.

Methods: During 2019, we undertook an international survey promoted with the help of the Alzheimer’s Association with questions on theories and treatments of AD. Further efforts to promote a similar study in 2021 did not recruit a significant number of participants.

Results: 173 researchers took part in the 2019 survey, 22% of which held “pro-ACH” opinions, tended to have more publications, were more likely to be male, and over 60. Thus, pro-ACH may now be a minority opinion in the field but is nevertheless the hypothesis on which the most clinical trials are based, suggestive of a representation bias. Popular vote of all 173 participants suggested that lifestyle treatments and anti-tau drugs were a source of more therapeutic optimism than anti-amyloid treatments.

Conclusion: We propose a more democratic research structure which increases the likelihood that promising theories are published and funded fairly, promotes a broader scientific view of AD, and reduces the larger community’s dependence on a fragile economic model.

Source: https://content.iospress.com/articles/journal-of-alzheimers-disease-reports/adr210030

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Primary Progressive Aphasia Associated With GRN Mutations: New Insights Into the Nonamyloid Logopenic Variant https://institutducerveau-icm.org/en/actualite/primary-progressive-aphasia-mutations-nonamyloid-logopenic/ https://institutducerveau-icm.org/en/actualite/primary-progressive-aphasia-mutations-nonamyloid-logopenic/#respond Tue, 20 Jul 2021 13:40:25 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21678 Objective: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with GRN (progranulin) mutations and to For more information ]]> Objective: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with GRN (progranulin) mutations and to study their neuroanatomic correlates.

Methods: Patients with PPA carrying GRN mutations (PPA-GRN) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and gray matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls and patients with sporadic PPA.

Results: Among the 235 patients with PPA, 45 (19%) carried GRN mutations, and we studied 32 of these. We showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (n = 13, 41%), followed by nonfluent/agrammatic (nfvPPA; n = 9, 28%) and mixed forms (n = 8, 25%). Semantic variant was rather rare (n = 2, 6%). Patients with lvPPA, qualified as nonamyloid lvPPA, presented canonical logopenic deficit. Seven of 13 had a pure form; 6 showed subtle additional linguistic deficits not fitting criteria for mixed PPA and hence were labeled as logopenic-spectrum variant. GM atrophy involved primarily left posterior temporal gyrus, mirroring neuroanatomic changes of amyloid-positive-lvPPA. Patients with nfvPPA presented agrammatism (89%) rather than apraxia of speech (11%).

Conclusions: This study shows that the most frequent PPA variant associated with GRN mutations is nonamyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that the language network may be affected at different levels. GRN testing is indicated for patients with PPA, whether familial or sporadic. This finding is important for upcoming GRN gene-specific therapies.

Source

Primary Progressive Aphasia Associated With GRN Mutations: New Insights Into the Nonamyloid Logopenic Variant. Saracino D, Ferrieux S, Noguès-Lassiaille M, Houot M, Funkiewiez A, Sellami L, Deramecourt V, Pasquier F, Couratier P, Pariente J, Géraudie A, Epelbaum S, Wallon D, Hannequin D, Martinaud O, Clot F, Camuzat A, Bottani S, Rinaldi D, Auriacombe S, Sarazin M, Didic M, Boutoleau-Bretonnière C, Thauvin-Robinet C, Lagarde J, Roué-Jagot C, Sellal F, Gabelle A, Etcharry-Bouyx F, Morin A, Coppola C, Levy R, Dubois B, Brice A, Colliot O, Gorno-Tempini ML, Teichmann M, Migliaccio R, Le Ber I; French Research Network on FTD/FTD-ALS.Neurology. 2021 Jul 6;97(1):e88-e102.

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CALL FOR APPLICATIONS : GROUP LEADER POSITIONS AT THE PARIS BRAIN INSTITUTE https://institutducerveau-icm.org/en/actualite/call-for-applications/ https://institutducerveau-icm.org/en/actualite/call-for-applications/#respond Thu, 01 Jul 2021 10:09:52 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21560 The Institut du Cerveau - Paris Brain Institute (ICM) is an internationally renowned neuroscience research institute located in Paris, France, on the campus of the For more information ]]> The Institut du Cerveau – Paris Brain Institute (ICM) is an internationally renowned neuroscience research institute located in Paris, France, on the campus of the Pitié-Salpêtrière hospital, providing world class expertise in basic and clinical neuroscience.

Paris Brain Institute is seeking to recruit up to 3 team leaders at the starting, junior or mid-career levels working in any area of molecular, cellular, circuit, cognitive, computational or theoretical neuroscience. Paris Brain Institute welcomes applications from talented individuals with the ambition to establish an internationally competitive research group. Successful candidates will be expected to develop an independent research program addressing challenging fundamental, translational or clinical problems in a stimulating and collaborative international environment. The new team leaders will benefit from a competitive start-up package, recurrent core funding and access to state of the art core facilities. Team leaders at the Paris Brain Institute are affiliated with the neuroscience Ph.D. program of Sorbonne University. Onboarding and skilled assistance for applications to national and international funding programs will also be provided. Successful candidates are expected to be appointed in 2023. Women and minorities are strongly encouraged to apply. Paris Brain Institute is a member of the Alba Network and endorses values of equity and diversity among all its research and support activities. ICM is committed to ensuring a safe, welcoming, and inclusive workplace, with a gender equity committee, and actively supports the local gender equity movement, the XX initiative.

Paris Brain Institute is home to 25 research teams bringing together over 700 personnel, including 150 researchers, 200 technical staff and 300 students and post-docs. Paris Brain Institute laboratories use multiscale approaches from different domains. Applicants are encouraged to consult the Paris Brain Institute description booklet available here. Paris Brain Institute is supported by a private foundation working in synergy with French public bodies, and affiliated with Sorbonne Université, CNRS and Inserm. For candidates in computational or theoretical neuroscience, neuroinformatics or digital sciences for neuroscience, partnership with Inria, the National Institute for Research in Digital Science and Technology, will provide opportunities to create a joint research team. Importantly, Paris Brain Institute is associated with clinical neuroscience departments (neurology, psychiatry, rehabilitation, …) of the Pitié-Salpêtrière hospital (APHP), as well as with a large network of public and industrial partners. Paris Brain Institute is dedicated to fundamental, translational and clinical research in Neuroscience, and fosters improved quality of care and education. Moreover, it hosts an in-house clinical neuroscience research center as well as a start-up incubator. The Paris Brain Institute is located alongside 13 National Reference Centers for rare neurological diseases at the Pitié-Salpêtrière.

Expression of interest must include a short CV, a complete list of publications highlighting up to five significant papers, and a brief description of achievements and future research (2 pages). Applications must be sent by November 15th, 2021 to: scientific.affairs@icm-institute.org

Short-listed applicants will be invited to submit a full application proposal including:

– Project/title and summary and a list of up to five of the candidate’s most significant publications (limited to 2 pages)

– CV including list of publications and invited presentations to conferences

– Description of the research project (no more than 10 pages)

– Names and contacts of three references

Full applications must be sent by February 15th, 2022 to: scientific.affairs@icm-institute.org. All applications will be reviewed by the International Scientific Advisory Board of the Institute. Shortlisted applicants will be invited for an interview and oral presentation in Paris in April 2022.

You can access to the application form here 

Expression of interest

Deadline

(2 pages maximum)

Invitation to submit full application Full application proposal Deadline Finalists’ oral presentation & Site visit
November 15th, 2021 December 15th , 2021 February 15th, 2022 April 2022
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Predicting lapses of attention with sleep-like slow waves https://institutducerveau-icm.org/en/actualite/predicting-lapses-attention-sleep-slow-waves/ https://institutducerveau-icm.org/en/actualite/predicting-lapses-attention-sleep-slow-waves/#respond Tue, 29 Jun 2021 15:17:04 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21574 Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or For more information ]]> Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants performing a task. Random interruptions prompted participants to indicate their mental states as task-focused, mind-wandering or mind-blanking. Using high-density electroencephalography, we report here that spatially and temporally localized slow waves, a pattern of neural activity characteristic of the transition toward sleep, accompany behavioural markers of lapses and preceded reports of mind wandering and mind blanking. The location of slow waves could distinguish between sluggish and impulsive behaviours, and between mind wandering and mind blanking. Our results suggest attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain.

Source : https://www.nature.com/articles/s41467-021-23890-7

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Alpine F1 Team proud to shine light on Paris Brain Institute at French Grand Prix https://institutducerveau-icm.org/en/actualite/alpine-f1-paris-brain-institute/ https://institutducerveau-icm.org/en/actualite/alpine-f1-paris-brain-institute/#respond Sun, 20 Jun 2021 09:00:03 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21520 As part of initial discussions aimed at establishing a close collaboration, Alpine F1 Team is proud to display the logo of the Paris Brain Institute on the A521 cars For more information ]]> As part of initial discussions aimed at establishing a close collaboration, Alpine F1 Team is proud to display the logo of the Paris Brain Institute on the A521 cars of Fernando Alonso and Esteban Ocon and mechanics’ helmets at the 2021 Formula 1 Emirates French Grand Prix this weekend. Through the vector of human performance, this association unites the scientific excellence of an established and internationally-respected medical research organisation with the technical excellence of Alpine F1 Team.

The Paris Brain Institute, also known as the Institut du Cerveau, ICM, is embedded into the Pitié Salpêtrière Hospital in Paris, France. The Paris Brain Institute was founded in 2010 by the highly-respected Professor Gérard Saillant, President of the Institute, and Jean Todt, current FIA President and Vice President of the Paris Brain Institute.

The Institute is revolutionary in the development of innovative research programs in multiple pioneering areas of neurosciences: molecular and cellular neurobiology, neurophysiology, cognition, computational, but also clinical and translational neurosciences to enhance the understanding of the nervous system and fight the illnesses affecting it.

Alpine F1 Team mechanics’ helmets. French Grand Prix, Saturday 19th June 2021. Paul Ricard, France.

As well as bringing recognition to the brilliant and pioneering work of the Institute, this is a first step towards a collaboration between Alpine F1 Team and the Paris Brain Institute to analyse, thanks to cognitive neurosciences, decision-making and human performance involved in the relentless pursuit of performance.

Alpine F1 Team has consistently collaborated with medical organisations over the past year, through Project Pitlane to develop ventilators in response to the COVID-19 pandemic, most recently with the University of Leicester to contribute to the design of a throat-operated voice microphone to be used by medics wearing full PPE.

Laurent Rossi, Chief Executive Officer, Alpine: “The work Gérard and his teams have done to further our understanding of neurology and cognition is inspiring and their research has helped thousands of people. This ever-increasing knowledge of the mind is not only rehabilitating but also opens up new possibilities for high-level functioning in a multitude of areas. We are proud to bring attention to their revolutionary work and look forward to contributing to their ongoing research in understanding the brain and benefit from their work in our F1 team’s ongoing drive for individual and collective performance.”

Professor Gérard Saillant, President of the Paris Brain Institute: “This alliance with Alpine F1 Team is a reflection of the values that unite us: fighting spirit, collaboration and excellence. The commitment of Alpine F1 Team to our cause is a great asset as it allows us to go even further into our research, with an aim to better understand the brain’s functioning.”

Jean Todt, President of the FIA: “I am delighted with this partnership between the teams of Alpine F1 Team and the Paris Brain Institute, which will combine their talents in technical and medical innovation for further research and understanding into decision-making to help performance and health. “

 

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GAB1, a good biomarker for Hedgehog-activated anterior skull base meningiomas https://institutducerveau-icm.org/en/actualite/gab1-biomarker-meningiomas/ https://institutducerveau-icm.org/en/actualite/gab1-biomarker-meningiomas/#respond Mon, 14 Jun 2021 14:57:02 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21487 A study conducted by Julien Boetto and Franck Bielle (Sorbonne University. AP-HP) of the "Genetics and Development of Nervous System Tumours" team at the Paris Brain For more information ]]> A study conducted by Julien Boetto and Franck Bielle (Sorbonne University. AP-HP) of the “Genetics and Development of Nervous System Tumours” team at the Paris Brain Institute highlights the potential of GAB1 as a new biomarker for Hedgehog-activated anterior skull base meningiomas. This discovery, published in Neuropathology and Applied Neurobiology opens the way to a better diagnosis of these tumours and the development of targeted therapeutic strategies.

 Mutations activating the Hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh-activated tumours is hampered by the lack of a reliable immunohistochemical marker. Researchers report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh-activated meningiomas.

GAB1 staining was compared to SMO mutation detection with Sanger and NGS techniques as well as Hh pathway activation study through mRNA expression level analyses in a discovery set of 110 anterior skull base meningiomas and in a prospective validation set of 21 meningiomas.

Using an expression score ranging from 0 to 400, they show that a cut-off score of 250 lead to excellent detection of Hh pathway mutations (sensitivity 100%, specificity 86%). The prospective validation set confirmed the excellent negative predictive value of GAB1 to exclude Hedgehog independent meningiomas. The team describe a large series of 32 SMO-mutant meningiomas and define multiple ways of Hh activation, either through somatic mutations or associated with mutually co-exclusive SHH (Sonic Hedgehog) or IHH (Indian Hedgehog) overexpression independent of the mutations.

The assessment of GAB1 expression by an immunohistochemical score is a fast and cost-efficient tool to screen anterior skull base meningiomas for activation of the Hedgehog pathway. It could facilitate the identification of selected cases amenable to sequencing for hedgehog pathway genes as predictive markers for targeted therapy.

Source

GAB1 overexpression identifies Hedgehog-activated anterior skull base meningiomas. Boetto J, Lerond J, Peyre M, Tran S, Marijon P, Kalamarides M, Bielle F. Neuropathol Appl Neurobiol. 2021 May 31

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Generation of excitatory and inhibitory neurons from common progenitors via Notchsignaling in the cerebellum https://institutducerveau-icm.org/en/actualite/generation-neurons-notchsignaling-cerebellum/ https://institutducerveau-icm.org/en/actualite/generation-neurons-notchsignaling-cerebellum/#respond Tue, 08 Jun 2021 15:11:17 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21464 Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain For more information ]]> Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated, progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated is unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, with intermediate levels of Notch activity generate inhibitory neurons, while daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.

SourceGeneration of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum: Cell Reports

 

 

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iMIND international Master In Neurodegenerative Diseases https://institutducerveau-icm.org/en/actualite/imind-international-master-neurodegenerative-diseases-2/ https://institutducerveau-icm.org/en/actualite/imind-international-master-neurodegenerative-diseases-2/#respond Fri, 07 May 2021 13:44:05 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21315 Interested in Neurosciences and neurodegenerative diseases?

The call for applications to the iMIND - International Master in Neurodegenerative Diseases - Master 2 For more information ]]> Interested in Neurosciences and neurodegenerative diseases?

The call for applications to the iMIND – International Master in Neurodegenerative Diseases – Master 2 programme, will be open from May 10 to June 30th!

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

iMIND brings together expert researchers from the Paris Brain Institute and other Sorbonne Université neuroscience centers, providing students with an immersive experience in up-to-date innovative research into normal and pathological brain function.

This year, the Paris Brain Institute will offer up to 4 scholarships (600€/month during the first semester) for international students interested in iMIND (upon selection).

Information regarding the application process is detailed here:

http://master.bip.sorbonne-universite.fr/en/apply-forms.html

Download the iMind leaflet

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Stepwise target controllability identifies dysregulations of macrophage networks in multiple sclerosis https://institutducerveau-icm.org/en/actualite/stepwise-target-controllability-identifies-dysregulations-of-macrophage-networks-in-multiple-sclerosis/ https://institutducerveau-icm.org/en/actualite/stepwise-target-controllability-identifies-dysregulations-of-macrophage-networks-in-multiple-sclerosis/#respond Thu, 06 May 2021 15:42:08 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21290 Violetta ZUJOVIC, INSERM researcher and Team Leader and Fabrizio De VICO FALLANI, INRIA researcher at the Paris Brain Institute just published in Network For more information ]]> Violetta ZUJOVIC, INSERM researcher and Team Leader and Fabrizio De VICO FALLANI, INRIA researcher at the Paris Brain Institute just published in Network Neuroscience.
Identifying the nodes able to drive the state of a network is crucial to understand, and eventually control, biological systems. Despite recent advances, such identification remains difficult because of the huge number of equivalent controllable configurations, even in relatively simple networks.

Based on the evidence that in many applications it is essential to test the ability of individual nodes to control a specific target subset, we develop a fast and principled method to identify controllable driver-target configurations in sparse and directed networks. We demonstrate our approach on simulated networks and experimental gene networks to characterize macrophage dysregulation in human subjects with multiple sclerosis.
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Definition of new forms of the behavioural variant of frontotemporal degenerations (FTD) https://institutducerveau-icm.org/en/actualite/definition-of-new-forms-of-the-behavioural-variant-of-frontotemporal-degenerations-ftd/ https://institutducerveau-icm.org/en/actualite/definition-of-new-forms-of-the-behavioural-variant-of-frontotemporal-degenerations-ftd/#respond Wed, 05 May 2021 09:20:02 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21258 Frontotemporal degeneration (FTD) is a complex neurodegenerative disorder that can manifest itself through a wide range of symptoms. Valérie Godefroy, postdoctoral For more information ]]> Frontotemporal degeneration (FTD) is a complex neurodegenerative disorder that can manifest itself through a wide range of symptoms. Valérie Godefroy, postdoctoral researcher in the Frontlab, under the supervision of Lara Migliaccio, and her colleagues at the Paris Brain Institute and the Pitié-Salpêtrière Hospital are enriching the clinical picture of this pathology by identifying new subtypes of its behavioural variant. This more precise definition of the different forms of the disease is essential for more personalised management of patients. The results are published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.

Frontotemporal degeneration (FTD) is a neurodegenerative disease that can manifest itself through a wide range of clinical signs, making its diagnosis complex. A major objective for clinicians working on this disease is to better characterise this diversity of forms of the disease and to identify subgroups with common characteristics. The challenge is to better understand every aspect of the disease and its progression in order to provide personalised care for patients.

One of the main symptoms of the behavioural variant of FTD is inhibition deficits, i.e. a generalised difficulty in controlling behaviour. This manifests itself in socially maladaptive behaviour (inappropriate thinking, disregard for social conventions, etc.), impulsivity and compulsive actions (repeating the same action or gesture several times automatically, for example). Based specifically on these behavioural manifestations of inhibition deficits, the study conducted by Valérie Godefroy and her colleagues at the Paris Brain Institute sought to identify subtypes of FTD patients.

Disinhibition behaviours are particularly difficult to assess and objectify, and do not necessarily present themselves in an obvious way during consultations with the doctor. One of the challenges of the study was therefore to measure these symptoms in detail, by observing them in a context close to real life, using what is called an “ecological approach”.

We took advantage of a protocol already in place at the Brain Institute as part of the ECOCAPTURE project, led by Bénédicte Batrancourt and Richard Levy, which includes time in the functional exploration room of the Institute’s PRISME platform. “explains Valérie Godefroy. This room was set up as a comfortable waiting room and presented as such to the 15 FTD patients and 15 control subjects included in the study. The participants spent about 45 minutes in the room, which was filmed and included time for discussion with an investigator. “This seemed to us to be an interesting situation for measuring uninhibited behaviour because it could generate impatience or even frustration in the participants, who did not know how long this waiting situation would last,” continues the researcher.
By analysing the behaviours observed in the video recordings, the researchers identified two main types of inhibition deficit: automatic compulsive behaviour and socially maladaptive behaviour. They then highlighted three behavioural groups of FTD patients, whose specificities (notably in terms of atrophied brain regions) were explored. The first group, very different from the other two, showed a lot of compulsive behaviour and very severe atrophy in the orbitofrontal regions and the ventromedial prefrontal cortex. “These data suggest that strong compulsive behaviours may be indicative of high disease severity. “says Valérie Godefroy.

The other two groups were less affected in their behaviour and differed from each other in socially inappropriate behaviour. Unexpectedly, the group with the most socially inappropriate behaviour was the group with the least atrophy in the brain. It was also characterised by more anxiety and depressive symptoms, potentially related to more awareness of the disease.

Taken together, these results allow us to enrich the clinical picture of FTD. We identify two main subtypes of the behavioural variant of this disease, associated with different brain damage. These data need to be supported by other studies, particularly longitudinal studies, i.e. with follow-up of patients over time, but they should make it possible to better stratify patients on the basis of their behaviour in order to offer them appropriate treatments. “concludes the researcher.

https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/dad2.12178

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Jaime DE JUAN-SANZ, team leader at the Paris Brain Institute, selected for the FENS-Kavli Scholars https://institutducerveau-icm.org/en/actualite/jaime-de-juan-sanz-team-leader-at-the-paris-brain-institute-selected-for-the-fens-kavli-scholars/ https://institutducerveau-icm.org/en/actualite/jaime-de-juan-sanz-team-leader-at-the-paris-brain-institute-selected-for-the-fens-kavli-scholars/#respond Wed, 21 Apr 2021 12:31:45 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21200 The FENS-Kavli Network (FKNE) is pleased to announce the recruitment of the new 2021 cohort of FENS-Kavli Scholars. In 2014, FENS and the Kavli Foundation announced For more information ]]> The FENS-Kavli Network (FKNE) is pleased to announce the recruitment of the new 2021 cohort of FENS-Kavli Scholars. In 2014, FENS and the Kavli Foundation announced the FENS-Kavli Network of Excellence: a group of early career, independent neuroscience investigators based in Europe, and chosen for their scientific excellence, originality, and leadership. A new cohort of 15 FENS-Kavli Scholars representing 10 different European countries have now been selected. The new Scholars will join the 2018 cohort, forming am active network of 30 Scholars based representing13 different countries. FKNE Scholars are selected for 2 X 2-year terms, after which they become members of the growing FKNE Alumni.The multidisciplinary, international network of FENS-Kavli Scholars is self-organised and aims to improve neuroscience in Europe and beyond through scientific exchange, advocacy, and outreach. FKNE Scholars participate in several meetings per year that allow for lively discussion of a range of topics across Neuroscience as well as challenges and opportunities for European neuroscientists. They then put their ideas into action, for example through opinion articles and white-paper recommendations to European stakeholders on funding schemes and other key issues, public engagement, establishing conference childcare grants, and through the delivery of special prizes that are awarded during the FENS Forum for exceptional individuals. These prizes are aimed to shine a light on senior investigators who have shown outstanding examples mentorship, younger scientists who have delivered excellent PhD theses, and for role models who have substantially delivered the advancement of diversity in neuroscience.

“The world is changing –not only has the pandemic altered how we go about research, scientific collaboration, and dissemination; but the importance of neuroscience for the future of brain health is being increasingly underscored across society. At the same time, European neuroscience faces significant challenges in maintaining sufficient investment into blue skies fundamental research, mentoring trainee researchers and students, and empowering early career group leaders to do their best work as autonomously and creatively as possible.“

To help meet these challenges, the FENS-Kavli Network provides a powerful platform for amplifying the voices and reach of a diverse group of early career investigators in support of the wider European neuroscience community.“ -saysDr. Tomás Ryan, Associate Professor at Trinity College Dublin, Ireland; and Chair of the FENS Kavli Network.“The FENS-Kavli Network of Excellence is running since 2014 thanks to the generous support of the Kavli Foundation and in collaboration with FENS. This group of exceptional junior and mid-career neuroscientists from across Europe plays a key role to shape the future of neuroscience as the voice of the next-generation scientists. We are proud of what they accomplished. I am also glad that their vision includes not only the development of excellent science and basic research, the key to progress, but also concerns for the impact of the current crisis and the place of science in the society. I congratulate the new scholars and I am convinced they will enthusiastically be at the front place in research, outreach and advocacy,” says Professor Jean-Antoine Girault, President of FENS.

The names and profiles of all FKNE Scholars are available on the FENS-Kavli Scholars webpage at www.fenskavlinetwork.org  

Contact FENS-Kavli Network of Excellence (FKNE): excellence_network@fens.org 

Jaime de Juan Sanz  website : http://www.dejuansanzlab.org/

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A New Non-Invasive Therapy for the Treatment of Primary Orthostatic Tremor (POT): Trans-Spinal Electrical Stimulation https://institutducerveau-icm.org/en/actualite/a-new-non-invasive-therapy-for-the-treatment-of-primary-orthostatic-tremor-pot-trans-spinal-electrical-stimulation/ https://institutducerveau-icm.org/en/actualite/a-new-non-invasive-therapy-for-the-treatment-of-primary-orthostatic-tremor-pot-trans-spinal-electrical-stimulation/#respond Mon, 19 Apr 2021 09:58:25 +0000 Ines Haddad https://institutducerveau-icm.org/?post_type=actualite&p=21174 Primary orthostatic tremor (POT) is a rare and poorly understood neurological disorder. It presents as a very rapid tremor (not visible to the naked eye) of the legs For more information ]]> Primary orthostatic tremor (POT) is a rare and poorly understood neurological disorder. It presents as a very rapid tremor (not visible to the naked eye) of the legs and trunk, causing a feeling of instability and fear of falling. The symptoms appear when standing still (orthostatism) and disappear when walking or leaning on a support. This disorder has an important impact on daily life activities done in a standing position (shower, in line, kitchen, etc…) with a strong impact on the quality of life of patients.

The disorder generally appears between the ages of 50 and 60 and affects women more often than men. To date, drug treatments have had little or no effect on the symptoms of POT. A few patients have been treated with deep brain stimulation, a technique that involves implanting electrodes in the brain, as in essential tremor, but the effects have been minimal or inconclusive (Aptes | Association of people affected by essential tremor). At Paris Brain Institute, the “Mov’it” team (normal and abnormal motor control: movement disorders and experimental therapeutics) co-directed by Profs. Vidailhet and Lehéricy, is interested in movement disorders and, in particular, POT.

A study led by Jean-Charles Lamy, member of the Mov’it team and operational manager of PANAM the platform for the exploration of movement at Paris Brain Institute has just shown, thanks to research, that trans-spinal electrical stimulation improves both the time in a standing position and reduces the amplitude as well as the frequency of tremor. This study is published in the journal “Movement Disorders”.

The causes of POT are still unknown. But the mechanisms are beginning to be better understood. Our teams have identified a “communication” disorder between neurons in the brainstem (contributing to the control of body position), the cerebellum (controlling balance and coordination of movements) and the cerebral cortex (directing voluntary gestures). In addition, shaking muscles send altered sensory messages (proprioception) via the spinal cord to the cerebral cortex, distorting the perception of body posture when standing. This has led to the implantation of electrodes in the spinal cord of some patients, but this neurosurgical technique is very invasive.

The study conducted on 16 patients suffering from POT at Paris Brain Institute uses a non-invasive technique of electrical stimulation of the spinal cord, through the skin, thanks to localized stimulation (device dedicated to research not yet available for patient care).

The results show that after a single stimulation, tremors are reduced and the time patients spend standing without support is increased.

This study constitutes a proof of concept of the effect of trans-spinal electrical stimulation for future clinical trials and opens the way to the prospects of an effective non-invasive treatment of POT.

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Pierre Nectoux, co-founder of Wefight, named to the “30 Under 30” ranking by Forbes France magazine https://institutducerveau-icm.org/en/actualite/pierre-nectoux-co-founder-of-wefight-named-to-the-30-under-30-ranking-by-forbes-france-magazine/ https://institutducerveau-icm.org/en/actualite/pierre-nectoux-co-founder-of-wefight-named-to-the-30-under-30-ranking-by-forbes-france-magazine/#respond Tue, 13 Apr 2021 15:13:39 +0000 amélie mondoloni https://institutducerveau-icm.org/?post_type=actualite&p=21162 Forbes France magazine unveiled in its latest issue the ranking of its fifth edition "30 Under 30". This ranking is dedicated to a new generation of entrepreneurs For more information ]]> Forbes France magazine unveiled in its latest issue the ranking of its fifth edition “30 Under 30”. This ranking is dedicated to a new generation of entrepreneurs who disrupt the codes of their field: sports, finance, art, entertainment, environment or health.

The 2021 edition honors Pierre Nectoux, CTO and co-founder of the startup Wefight incubated within iPEPS – The Healthtech Hub.

Created in 2017 by Benoit Brouard, a hospital pharmacist, and Pierre Nectoux, and engineer,  Wefight aims to develop virtual assistants for patients with cancer or chronic diseases. In 2019, the company launched, in collaboration with the teams of the Paris Brain Institute and the adult psychiatry department of the Pitié-Salpêtrière Hospital, “Vik Dépression”, a virtual companion whose objective is to support and inform people affected by depression.

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SPECIFIC PATTERNS IDENTIFIED BY ELECTROENCEPHALOGRAPHY IN PATIENTS INFECTED WITH SARS-COV-2 https://institutducerveau-icm.org/en/actualite/patterns-identified-electroencephalography/ https://institutducerveau-icm.org/en/actualite/patterns-identified-electroencephalography/#respond Thu, 08 Apr 2021 13:35:39 +0000 Ignacio Colmenero https://institutducerveau-icm.org/?post_type=actualite&p=21512 Neurological disorders have been reported in patients with Covid-19. Researchers and clinicians from the Paris Brain Institute and the Hôpital Pitié-Salpêtrière For more information ]]> Neurological disorders have been reported in patients with Covid-19. Researchers and clinicians from the Paris Brain Institute and the Hôpital Pitié-Salpêtrière AP-HP have shown the interest of combining different examinations with electroencephalography (EEG), to better identify brain damage, including encephalopathy, in these patients and adapt their management.

SARS-CoV-2 infection is associated in some patients with various neurological symptoms, from loss of smell to consciousness disorders. It is a major challenge to better characterise the brain damage during Covid-19 infection in order to identify the causes and treat patients specifically.

In patients with a neurological form of Covid-19, imaging or biological data (following a lumbar puncture) may suggest a diagnosis of encephalitis. These test results may also be heterogeneous and lack specificity. The combination of these data with EEG, which records the electrical activity of the brain, and clinical evaluation, would make it possible to improve the characterisation of these encephalopathies and better manage patients.

As part of the Covid Neurosciences Cohort project (CoCo Neurosciences), conducted at the Paris Brain Institute (ICM) and the Department of Neurosciences at the Pitié-Salpêtrière Hospital (AP-HP), researchers and clinicians analysed EEG data from 78 patients hospitalised with a Covid-19 infection. The EEG was indicated following significant neurological symptoms such as confusion, epileptic seizures or delayed recovery in intensive care.

In 69 of these patients, the EEG showed pathological brain electrical activity, such as slow waves, especially in the frontal lobe, periodic repetition activities and epileptic activities. The majority of these patients also had abnormalities on neurological examination, biological tests and brain imaging. Clinicians and researchers sought to explain the causes of these neurological findings for each individual patient using clinical, treatment, biological and imaging data.

Nine patients presented with neurological symptoms, consistent with encephalopathy, with no evidence of any cause or comorbidity other than Covid-19. Compared to the overall cohort, these patients had more frequent abnormal movements, frontal syndrome or brainstem involvement, periodic repetition abnormalities on EEG and white matter involvement on MRI. Their condition was then defined as a Covid-19-associated encephalopathy.

Taken together, these results highlight the value of combining EEG with clinical, biological and imaging data in Covid-19 patients with neurological symptoms. EEG is a valuable tool to distinguish different types of brain damage, including encephalopathies, and thus allow better management of patients.

Source

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.

Lambrecq V*, Hanin A*, Munoz-Musat E, Chougar L, Gassama S, Delorme C, Cousyn L, Borden A, Damiano M, Frazzini V, Huberfeld G, Landgraf F, Nguyen-Michel VH, Pichit P, Sangare A, Chavez M, Morélot-Panzini C, Morawiec E, Raux M, Luyt CE, Rufat P, Galanaud D, Corvol JC, Lubetzki C, Rohaut B, Demeret S, Pyatigorskaya N, Naccache L, Navarro V; Cohort COVID-19 Neurosciences (CoCo Neurosciences) Study Group. JAMA Netw Open. 2021 Mar 1

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OPENING OF A NEW DOMAIN: COMPUTATIONAL MODELLING IN NEUROSCIENCE https://institutducerveau-icm.org/en/actualite/opening-of-a-new-domain-computational-modelling-in-neuroscience/ https://institutducerveau-icm.org/en/actualite/opening-of-a-new-domain-computational-modelling-in-neuroscience/#respond Mon, 29 Mar 2021 09:37:12 +0000 Thomas Mariani https://institutducerveau-icm.org/?post_type=actualite&p=21072 The objective of the new scientific domain (Computational modelling in neuroscience) is to recognise the particular interdisciplinary experience of some researchers For more information ]]> The objective of the new scientific domain (Computational modelling in neuroscience) is to recognise the particular interdisciplinary experience of some researchers at Paris Brain Institute. Up to now people using a computational neuroscience approach were included in the other domains and applied their expertise in their host team. This new domain will give them the opportunity to share their vision – complementary with the vision of the other domains – to the institute scientific and medical COPIL. 

The major aims of the PIs in the new domain are:

 – Mathematical and computational modelling of multi-scale brain mechanisms ranging from molecular/cellular processeslarge-scale integrated structure and dynamics (eg, anatomo-functional interactions), to cognition and behavior.

 – Development of data-mining methods including network sciencesignal/image processingmachine learning and AI, for data interpretation and analysis and for better diagnosis and prognosis in neurological and psychiatric diseases;

–  Development of scientific software and engineering tools for neuroscience applications.

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