Institut du Cerveau https://institutducerveau-icm.org Fri, 01 Jul 2022 13:50:40 +0000 https://wordpress.org/?v=4.9.13 hourly 1 https://wordpress.org/?v=4.9.13 https://institutducerveau-icm.org/wp-content/uploads/2022/03/cropped-logo-tete-32x32.png En - Institut du Cerveau https://institutducerveau-icm.org 32 32 How do we explore our knowledge to be creative? https://institutducerveau-icm.org/en/actualite/how-do-we-explore-our-knowledge-to-be-creative/ https://institutducerveau-icm.org/en/actualite/how-do-we-explore-our-knowledge-to-be-creative/#respond Wed, 29 Jun 2022 11:34:50 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23934 Coming up with a creative idea requires us to draw on all our previous knowledge. But how does this happen in our mind and in our brain? Emmanuelle Volle's group For more information ]]> Coming up with a creative idea requires us to draw on all our previous knowledge. But how does this happen in our mind and in our brain? Emmanuelle Volle’s group (Inserm) at the Frontlab of the Paris Brain Institute, in collaboration with the Universities of Graz (Austria) and Warwick (UK), and the Israel Institute of Technology, has identified two semantic memory search processes involved in creativity.

 

Being creative does not come out of nowhere. Yet the birth of a creative idea in our brain is still an unknown phenomenon. Current theories suggest that it is based in part on the on the organization of our knowledge stored in semantic memory and how we search for concepts in it. “What actually happens when we look for a new idea? Until now, we didn’t have a clear idea about the processes that allow us to navigate our semantic memory and be creative,” explains Marcela Ovando-Tellez, a postdoctoral fellow at Frontlab and first author of the study.

 

Semantic memory and creativity

Semantic memory can be studied as a network of associations of objects and concepts that are linked together to a greater or lesser extent. For example, the word “apple” will be strongly connected to the broader set of “fruit” but will also be connected to the concepts of “sweet”, “vegetable” or even to more distant words such as “fairytale” (if you have read Snow White). It is all these concepts, stored in our semantic memory, that allow us to make sense of the world.

 

Creativity is intimately linked to the structure of this network and the way we navigate within it linked to executive control processes. If the semantic associations are organised in such a way that links between distant objects are easily established, it is easier to generate original ideas.

 

The components of the semantic memory search process: clustering and switching

In order to understand how we navigate along this network of semantic associations to unearth creative thoughts, Emmanuelle Volle’s group (Inserm) and their collaborators constructed a free semantic association task which consists of giving a cue word to a participant and asking them for all the associates that come to mind in relation to the proposed word. “The specificity here was that the cue words were polysemous, i.e., they had several possible meanings,” explains Emmanuelle Volle (Inserm), the study’s last author. “This ambiguity results in the activation of several meanings of the cue words, which allowed us to classify the responses according to the related meaning, and to distinguish two interacting components of the memory search process: clustering and switching.”

 

What are clustering and switching? Taking the example of a word generation task involving the category “Animals”, clustering would consist of listing successively number of names of a subcategory of animals such as birds, while switching would involve moving from one subcategory to another, from birds to amphibians or mammals.

 

The task developed by the group of scientists contained, for example, the French word “rayon”, which can have several meanings: the rays of the sun, the supermarket shelves, or the bicycle spokes. Thus, if a participant proposes words associated with “ray” in relation to the weather in a row, he or she adopts a clustering type of memory search, whereas if he or she alternates between words associated with the weather and the supermarket, his or her memory search now is of a switching type.

 

The researchers combined this association task with a whole series of other tests measuring creativity, the judgment of semantic associations, and executive control (i.e., inhibition, working memory, etc.). Thanks to these data, they were able to reconstruct the structure of the semantic network of each participant and relate the two components of memory search to creativity, semantic memory organization, and executive control abilities. Finally, functional imaging MRI acquisitions have enabled us to explore the underlying neural correlates.

 

 

Creativity, memory search and cognitive control

The first result obtained by the team is that clustering and switching are indeed related to creativity, but differently. Clustering is linked to divergent thinking, i.e., the free generation of ideas, while switching is related to the ability to combine distant associations between concepts. In addition, the switching component was also related to the organization of the concepts in memory and executive control abilities.

 

The researchers then were able to predict both clustering and switching from the participant’s brain functional connectivity and show that the two components have different brain correlates. Clustering was predicted by connectivity patterns between brain networks related to attention and executive control, suggesting that persisting on a semantic category – all the names of mammals that come to mind, for example – involves attentional processes and may be involved in creative idea generation. Switching, on the other hand, was predicted by connectivity patterns involving mainly the default network and the control network. This pattern of connectivity may support executive control processes interacting with semantic memory to explore and combine distant elements of memory.

 

Taken together, these results show how the alternations between exploratory search and focused attention support creativity, and provide new insights on the neurocognitive correlates of memory search related to creative cognition.

 

Source

An investigation of the cognitive and neural correlates of semantic memory search related to creative ability.Ovando-Tellez M, Benedek M, Kenett YN, Hills T, Bouanane S, Bernard M, Belo J, Bieth T, Volle E. Commun Biol. 2022 Jun 16

 

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Decision-making: a new distribution of tasks in our prefrontal cortex? https://institutducerveau-icm.org/en/actualite/decision-making-a-new-distribution-of-tasks-in-our-prefrontal-cortex/ https://institutducerveau-icm.org/en/actualite/decision-making-a-new-distribution-of-tasks-in-our-prefrontal-cortex/#respond Thu, 23 Jun 2022 14:11:19 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23897 The team "Motivation, Brain and Behavior", co-directed by Mathias Pessiglione (Inserm) at the Paris Brain Institute, proposes in a study published in the Journal of For more information ]]> The team “Motivation, Brain and Behavior”, co-directed by Mathias Pessiglione (Inserm) at the Paris Brain Institute, proposes in a study published in the Journal of Neuroscience a new approach to understand how our prefrontal cortex makes decisions.

 

Decision-making: costs and benefits

Making a decision is based on a fine balance between costs and benefits. In other words, when faced with several options, we must identify the one that will provide the greatest reward with the least effort. When we are faced with this situation, which is almost all the time in our lives, a series of operations take place in our brain to evaluate the different possibilities that are presented to us and choose the best one.

 

“If the role of the prefrontal cortex in the evaluation of effort and reward is well accepted, the functional role of each sub-region is subject to debate, because the results obtained in different studies are contradictory,” explains Nicolas Clairis, first author of the study, currently a post-doctoral fellow at the Ecole Polytechnique Fédéral de Lausanne (EPFL, Switzerland).

 

Deliberation and confidence in one’s own choices

In an attempt to answer this question, Mathias Pessiglione’s team at the Paris Brain Institute adopted another approach, in order to clarify the distribution of roles in the prefrontal cortex. To do this, they took into account the metacognitive part of the decision, i.e. the costs and benefits of the deliberation itself (spending time thinking to have more confidence in one’s decision). Thus, in a decision such as “Do I continue up to the pass to get the view of the other valley?”, one must evaluate not only the option under consideration, i.e., the effort to be made (you have to climb all the way up the scree and that seems difficult) and the reward to come (I’ve been told that the view is really nice from up there), but also the confidence in the choice under consideration (am I right in wanting to continue?) and the time of deliberation (do I need to think about it more?)

 

The researchers presented 39 participants with several preference tasks that ranged from ratings — do you like this option a little, a lot, or not at all? – as well as binary decisions — do you prefer option A or B? Are you willing to put in this much effort for this much reward? These tests were combined with functional imaging (fMRI).

 

A new distribution of tasks in our prefrontal cortex

Their results confirm the role of the ventromedial prefrontal cortex (vmPFC) in assigning a value to the different options presented during a choice. Thus, the activity of this region increases according to the value of the promised reward and decreases according to the cost of the effort required to obtain it. The more dorsal regions of the prefrontal cortex are more associated with the metacognitive variables proposed by the Paris Brain Institute’s team. Confidence in one’s own choices is represented in medial prefrontal cortex (mPFC) activity, while deliberation time is reflected active in dorsomedial prefrontal cortex (dmPFC).

 

“Here we confirm the value of distinguishing between variables that determine the decision (effort and reward) and those that determine the meta-decision (when to stop one’s choice) in understanding the functional architecture of the prefrontal cortex. The advantage of the new conceptual framework is that it can easily be generalized to other types of behavior than choices. For example, to make a judgment, there is also a metacognitive trade-off between confidence and deliberation: one must have confidence in one’s judgment, and at the same time one cannot take an infinite amount of time before stopping one’s judgment,” concludes Mathias Pessiglione, team leader at the Paris Brain Institute and last author of the study.

  

Source
Value, confidence, deliberation: a functional partition of the medial prefrontal cortex demonstrated across rating and choice tasks.
Clairis N, Pessiglione M.J Neurosci. 2022 Jun 1

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A better characterization of disinhibition in frontotemporal degeneration https://institutducerveau-icm.org/en/actualite/a-better-characterization-of-disinhibition-in-frontotemporal-degeneration/ https://institutducerveau-icm.org/en/actualite/a-better-characterization-of-disinhibition-in-frontotemporal-degeneration/#respond Mon, 20 Jun 2022 10:23:14 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23876 Thanks to an approach combining behavioral assessment and brain imaging, a study conducted by the Paris Brain Institute's FrontLAB has led to a better For more information ]]> Thanks to an approach combining behavioral assessment and brain imaging, a study conducted by the Paris Brain Institute’s FrontLAB has led to a better characterization of a major symptom of frontotemporal degeneration, disinhibition. These results, published in Neuroimage: Clinical, pave the way for a more adapted and personalized management of patients and support for their caregivers.

 

Disinhibition, a major symptom of frontotemporal degeneration 

Disinhibition is a symptom of many neurodegenerative diseases, in particular those affecting the frontal regions of the brain such as fronto-temporal degeneration (FTD). FTD is the second most common cause of dementia after Alzheimer’s disease. They can take different forms, including a variant called “behavioral”, characterized by cognitive and behavioral disorders. Disinhibition is at the heart of these behavioral changes and disorders.

 

Two main types of disinhibition are commonly distinguished: cognitive disinhibition, which corresponds to an inability to block (inhibit) inappropriate responses or to stop responses already underway, and behavioral disinhibition, which is manifested by the inability to repress behaviors in an environment, in social contexts or to adapt to changes in one’s environment.

 

“Despite these two relatively well-established definitions, there is still no way to accurately assess behavioral disinhibition in people with FTD other than through caregiver-completed questionnaires. Moreover, the neuroanatomical correlates of this symptom are not clearly defined,” said Delphine Tanguy, first author of the study.

 

The combination of a semi-ecological approach and brain imaging

For nearly 10 years, the Paris Brain Institute has been developing the ECOCAPTURE program, led by Bénédicte Batrancourt (Inserm) and Richard Lévy (AP-HP-Sorbonne University), which aims to objectively and quantitatively evaluate neuropsychiatric symptoms such as apathy and disinhibition under conditions close to real life (semi-ecological approach).

 

In order to better define disinhibition in FTD patients, the FrontLAB team of the Paris Brain Institute used the ECOCAPTURE approach to assess two components of disinhibition with new behavioral metrics: compulsivity and social disinhibition. They combined structural imaging (MRI) and classical cognitive assessment questionnaires such as the Hayling test (measures cognitive inhibition abilities during spontaneous verbal responses) and social cognition tests.

 

A better characterization of disinhibition in FTD patients

The researchers confirm that in patients with the behavioral variant of FTD, disinhibition is manifested on both components: compulsivity and social disinhibition. Moreover, the behavioral data collected through the semi-ecological approach are consistent with the results of the cognitive tests. Compulsivity observed in patients correlates with Hayling test scores. Furthermore, both compulsivity and social disinhibition are associated with the results of the social cognition and emotion recognition tests. Finally, the imaging data allow us to distinguish two different patterns of atrophy in the frontotemporal networks depending on the subtype of disinhibition: social disinhibition or compulsivity.

 

“These results confirm the interest of the semi-ecological approach for the assessment of disinhibition. By characterizing more precisely the type of disinhibition affecting a patient, we can set up better management strategies for the patient and also support his or her caregiver, whose quality of life can be heavily impacted by this type of symptom,” concludes Lara Migliaccio (Inserm), last author of the study.

 

 

Source

An ecological approach to identify distinct neural correlates of disinhibition in frontotemporal dementia. Tanguy D, Batrancourt B, Estudillo-Romero A, Baxter JSH, Le Ber I, Bouzigues A, Godefroy V, Funkiewiez A, Chamayou C, Volle E, Saracino D, Rametti-Lacroux A, Morandi X, Jannin P, Levy R, Migliaccio R; ECOCAPTURE study group. Neuroimage Clin. 2022 Jun 7

 

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Visual mental imagery: a patient case suggests a new key brain network https://institutducerveau-icm.org/en/actualite/visual-mental-imagery-a-patient-case-suggests-a-new-key-brain-network/ https://institutducerveau-icm.org/en/actualite/visual-mental-imagery-a-patient-case-suggests-a-new-key-brain-network/#respond Thu, 09 Jun 2022 11:36:48 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23824 Every day, we call upon a unique capacity of our brain, visual mental imagery, which allows us to visualise images, objects or people 'in our heads'. Based on the For more information ]]> Every day, we call upon a unique capacity of our brain, visual mental imagery, which allows us to visualise images, objects or people ‘in our heads’. Based on the recent case of a patient with a specific brain lesion, Paolo Bartolomeo’s group (Inserm) in the PICNIC Lab at the Paris Brain Institute has identified a region that may be key in mental visualisation.

 

A patient was admitted to the emergency room after a stroke that had spread to the occipitotemporal area of the left hemisphere. Although his life was saved, the patient woke up with multiple deficits: hemianopia – the loss of vision on the right side – alexia – an inability to read – and an inability to name colours.

 

These multiple impairments and the presence of the lesion in the left temporal lobe prompted clinicians and researchers at the Paris Brain Institute to evaluate another brain function: visual mental imagery.

 

The brain networks of mental imagery

At present, the predominant model of the brain basis of mental imagery proposes that it engages the primary visual area at the back of our brain, which is also involved in processing what we actually see with our eyes. However, evidence from patient cases has been accumulating over the last twenty years that contradicts this dogma. In a recent meta-analysis, Paolo Bartolomeo’s team suggested that mental imagery is instead encoded in the fronto-parietal networks of attention and working memory, as well as in a small region of the fusiform gyrus of the left temporal lobe. The case of this new patient with a left occipitotemporal lesion was therefore an opportunity for the researchers at the Paris Brain Institute to re-explore their hypothesis.

 

Intact visual mental imagery, despite the lesions

In order to test the patient’s mental imagery, the doctors gave him a battery of tests. These consisted of several questions about the visual appearance of objects: What is redder between a strawberry and a cherry? Which city is the furthest on the right of a map of France between Bordeaux and Strasbourg? To answer correctly, the patient had to use his mental imagery and visualise in his head a strawberry, a cherry, or a map of France. “To our great surprise, our patient’s visual mental imagery was well preserved,” explains Paolo Bartolomeo (Inserm), the study’s last author. “A new question then arose: why did he not have any difficulty, despite his lesion which should have affected important networks for exercising this function in our brain?”

 

Halfway between language and semantic networks

Thanks to MRI tractography, which makes it possible to visualise the tracts of neurons in the brain – the wiring, so to speak – the researchers were able to identify some key elements explaining why the patient’s mental imagery was intact despite his lesion. They found that the mental imagery node, located in the fusiform gyrus in the left temporal lobe, had been spared by the lesion.

 

The team of scientists then showed that two connectivity tracts passed through this node: the arcuate fasciculus, associated with the language system, and the inferior longitudinal fasciculus, linked to the semantic system, i.e. our knowledge of the world, objects and concepts.

 

Because of his lesion, the patient no longer received direct visual information in his left hemisphere. The fusiform imagery node therefore no longer received this type of information but continued to be fed by the semantic network.

 

These results support our hypothesis that visual mental imagery comes from a top-down activation from the language and semantic networks. This goes against the dominant model of mental imagery, according to which the primary visual areas are necessary for the implementation of this capacity” concludes Paolo Bartolomeo (Inserm).

 

Source

The connectional anatomy of visual mental imagery: evidence from a patient with left occipito-temporal damage. Hajhajate D, Kaufmann BC, Liu J, Siuda-Krzywicka K, Bartolomeo P. Brain Struct Funct. 2022 May 27

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Claire Wyart receives the Richard Lounsbery 2022 Prize for her work https://institutducerveau-icm.org/en/actualite/claire-wyart-receives-the-richard-lounsbery-2022-prize-for-her-work/ https://institutducerveau-icm.org/en/actualite/claire-wyart-receives-the-richard-lounsbery-2022-prize-for-her-work/#respond Wed, 08 Jun 2022 08:09:00 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23820 The Richard Lounsbery Prize 2022, awarded by the French Academy of Sciences and the American National Academy of Sciences (NAS), has been awarded to Claire Wyart For more information ]]> The Richard Lounsbery Prize 2022, awarded by the French Academy of Sciences and the American National Academy of Sciences (NAS), has been awarded to Claire Wyart (Inserm), head of the “Spinal Sensory Signaling” team at the Pris Brain Institute, for her work on the sensory interface between the nervous system and the cerebrospinal fluid (CSF), which modulates our posture and movements.

 

Sensory information and movement

The team led by Claire Wyart combines genetic, electrophysiological, behavioral and biophysical approaches to explore neuromodulatory networks originating in the brain or spinal cord and their effects on locomotion and posture. She recently discovered that ciliated neurons in contact with the cerebrospinal fluid detect the curvature of the spine and modulate locomotion and posture. One of the team’s goals is to understand how sensory information is integrated by the spinal cord throughout life, and how it impacts locomotion.

 

The Richard Lounsbery Award

The Richard Lounsbery Prize is awarded every other year to a French or American researcher. Created in 1979 by Vera Lounsbery in memory of her husband, this prize is supported by the Lounsbery Foundation in Washington. The prize is worth $75,000 and is awarded to a French or American researcher (under 45 years of age) for their achievements in biology and medicine.

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Predicting the risk of developing Alzheimer’s disease using genetic markers? https://institutducerveau-icm.org/en/actualite/predicting-the-risk-of-developing-alzheimers-disease-using-genetic-markers/ https://institutducerveau-icm.org/en/actualite/predicting-the-risk-of-developing-alzheimers-disease-using-genetic-markers/#respond Tue, 24 May 2022 10:23:23 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23789 Although Alzheimer's disease is not hereditary in 99% of cases, genetic factors can increase the risk of developing it. The "Alzheimer's disease, prion diseases" For more information ]]> Although Alzheimer’s disease is not hereditary in 99% of cases, genetic factors can increase the risk of developing it. The “Alzheimer’s disease, prion diseases” team, co-directed by Marie-Claude Potier (CNRS) at the Paris Brain Institute, has identified an association between the presence of cerebral amyloid plaques, one of the characteristic lesions of Alzheimer’s disease, and a combination of 17 genetic variants.

Today, in view of the increase in life expectancy and the consequent rise in the number of cases of Alzheimer’s disease, one major challenge is to predict the onset of the disease early in order to treat it before the first symptoms appear.

It has been shown that the presence of amyloid plaques (protein aggregates characteristic of the disease) in the brains of elderly people without cognitive decline significantly increases the risk of developing Alzheimer’s disease in later years.

However, to date, the detection of these plaques in the brain can only be done by an expensive imaging method, unusable in routine medicine, the PET-MRI (Positron Emission Tomography-Magnetic Resonance Imaging) or by an assay in the plasma or cerebrospinal fluid (lumbar puncture). On the other hand, detection is only possible at a late stage, when amyloid plaques are present in the brain, i.e. shortly before the onset of symptoms.

 

Genetic susceptibility factors in Alzheimer’s disease

Although Alzheimer’s disease is not hereditary (except in 1% of cases), it has been shown that there are genetic susceptibility factors that increase the risk of developing the disease. Previous studies have shown that people carrying a particular allele of the APOE gene, APOEe4, have a 3 to 15 times higher risk than non-carriers, but also that some patients with Alzheimer’s disease do not carry this allele.

Since then, other anonymous genome screening studies, i.e. the comparison of the frequencies of genetic variants between several thousand patients and control individuals, have identified more than 40 variants that predispose to the disease. As each of these variants is neither necessary nor sufficient, only a combination of several of them (multigene risk) gives an individual a greater risk of developing the disease.

A polygenic score associated with the presence of amyloid plaques

The “Alzheimer’s disease, prion diseases” team, co-led by Marie-Claude POTIER, a CNRS researcher at the Paris Brain Institute, hypothesised that a multigene score could be associated with the future appearance of amyloid plaques in the brain, thus allowing early targeting of people at greater risk of developing the disease.

The study began with the INSIGHT cohort of the Institute of Memory and Alzheimer’s Disease (IM2A) of 291 asymptomatic elderly people, 83 of whom had amyloid plaques in the brain. The team showed that an optimised polygenic score including 17 non-APOE Alzheimer’s disease susceptibility variants is associated with the presence of amyloid plaques in the INSIGHT cohort. This score was then validated in an independent cohort.

The results of this work show an association between the presence of cerebral amyloid plaques and a combination of 17 genetic variants, which are carried by the individuals studied. This score is valid for both APOE4 and non-APOE4 carriers, demonstrating that there are other genetic factors than APOE involved in amyloid plaque formation. Assessing the genetic load conferred by these 17 variants, prior to possible detection of amyloid plaques in the brain or plasma, would allow very early identification of patients most at risk of developing amyloid plaques and thus be able to prevent the onset of the disease through more interventional follow-up.

 

Source

Association of APOE-Independent Alzheimer Disease Polygenic Risk Score With Brain Amyloid Deposition in Asymptomatic Older Adults. Xicota L, Gyorgy B, Grenier-Boley B, Lecoeur A, Fontaine GL, Danjou F, Gonzalez JS, Colliot O, Amouyel P, Martin G, Levy M, Villain N, Habert MO, Dubois B, Lambert JC, Potier MC; INSIGHT pre-AD study group and for the Alzheimer’s Disease Neuroimaging Initiative*.Neurology. 2022 May 23. doi: 10.1212/WNL.0000000000200544.

 

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A new statistical method for improved brain mapping https://institutducerveau-icm.org/en/actualite/a-new-statistical-method-for-improved-brain-mapping/ https://institutducerveau-icm.org/en/actualite/a-new-statistical-method-for-improved-brain-mapping/#respond Mon, 23 May 2022 09:41:19 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23768 Brain mapping consists in finding the brain regions associated with different traits, such as diseases, cognitive functions, or behaviours, and is a major field of For more information ]]> Brain mapping consists in finding the brain regions associated with different traits, such as diseases, cognitive functions, or behaviours, and is a major field of research in neuroscience. This approach is based on statistical models and is subject to numerous biases. To try to counter them, researchers from the ARAMIS team, a joint team between the Paris Brain institute and Inria, and their collaborators at the University of Queensland (Australia) and Westlake University (China), propose a new statistical model for brain mapping. The results are published in the Journal of Medical Imaging.

 

Mapping the brain

 

Mapping the brain is a challenge that mobilises many neuroscience researchers around the world. The goal of this approach is to identify the brain regions associated with different traits, such as diseases, cognitive scores, or behaviours. This type of study is also known as “Brain-wide association study” and rely on an exhaustive screening of brain regions to identify those associated with the trait of interest.

 

The difficulty is that we are looking for a needle in a haystack, except that we don’t know how many needles there are, or in our case, how many brain regions there are to find,” explains Baptiste Couvy-Duchesne (Inria), first author of the study.

 

Meeting the challenges of signal redundancy

 

A first challenge lies in the number of brain measurements available per individual, which can quickly reach one million or more. In addition, brain regions are correlated with each other. Some regions are highly connected and associated with many others, like nodes in a network. Others, however, are more isolated, either because they are independent of other brain regions or because they contribute to very specific cognitive trait or brain function.

 

If a brain region associated with our trait of interest is part of a highly connected network, the analysis will tend to detect the whole network, because the signal propagates within regions that are correlated with each other,” continues the researcher, “This signal, which may seem very strong at first sight, is in fact redundant. How then can we find the region or regions that really contribute to the trait of interest within the network?

Modelling of the left hemisphere of the brain and the association between subject age and cortical thickness. Positively associated regions are in yellow/orange/red, negatively associated regions are in blue. Credit : Inria/Baptiste Couvy-Duchesne

To solve this problem, the researchers are proposing new statistical methods that are suited to the high dimensional image as well as for modelling the complex correlation structure within the brain.

 

Simulations to develop new statistical methods

 

In order to test the developed statistical methods, the researchers need very controlled data. “We cannot compare methods directly on real traits or diseases, since we do not know what we are supposed to find,” explains Baptiste Couvy-Duchesne, “one method could find 10 regions associated with a trait, another 20, although we cannot tell which one is giving the correct answer.”

 

The key to this solving problem is to use simulations. Researchers use real brain images, but study fake diseases or fake scores, which they have constructed to be associated with dozens or hundreds of predefined brain regions. This way, they are able to check whether the statistical methods detect the expected regions, but also whether they detect others (‘false positives’).

 

A more robust method and open questions

 

Once their method had been calibrated through these simulations (which revealed that the proposed approach was more accurate than existing ones) the researchers used real traits as validation.

 

Our new method finds fewer regions on average because it manages to remove some of the redundant associations. The next step is to apply it to study Alzheimer’s disease,” concludes the researcher.

 

A central result of the study it to demonstrate how pervasive are the redundant associations, using the current statistical methods. Thus, many associations identified to date may not be robust of directly pertinent for the trait studied. In addition, several factors that are difficult to control can affect the quality of MRIs, such as head movements or the type of machines used, which can exacerbate the problem and lead to false associations. Beyond the development of more refined analysis methods, the issue of data quality and homogeneity remains crucial.

 

Source

Baptiste Couvy-Duchesne, Futao Zhang, Kathryn E. Kemper, Julia Sidorenko, Naomi R. Wray, Peter M. Visscher, Olivier Colliot, Jian Yang, “A parsimonious model for mass-univariate vertex-wise analysis,” J. Med. Imag. 9(5), 052404 (2022), doi: 10.1117/1.JMI.9.5.052404.

 

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Paris Brain Institute announces a new research collaboration with Pfizer Inc. https://institutducerveau-icm.org/en/actualite/paris-brain-institute-announces-a-new-research-collaboration-with-pfizer-inc/ https://institutducerveau-icm.org/en/actualite/paris-brain-institute-announces-a-new-research-collaboration-with-pfizer-inc/#respond Mon, 16 May 2022 14:29:57 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23731 Paris Brain Institute announces a new research collaboration with Pfizer Inc. aimed at advancing the understanding of rare neurodegenerative diseases

The Paris Brain For more information ]]> Paris Brain Institute announces a new research collaboration with Pfizer Inc. aimed at advancing the understanding of rare neurodegenerative diseases

The Paris Brain Institute today announced an innovative research project to characterize the genetic mechanisms responsible for two rare neurodegenerative diseases with no currently known therapies. The project, conducted in collaboration with Pfizer Inc.’s Innovative Target Exploration Network (ITEN), is led by Dr. Isabelle Le Ber and Dr. Mathieu Barbier, members of the “Basic to Translational Neurogenetics” research team at the Institut du Cerveau (Paris). Their work aims to study so-called “expansion” diseases, caused by unstable repeats in the gene sequence, to understand the mechanisms by which certain regions of the genome can become unstable and generate these pathological expansions.

Dr. Mathieu Barbier and Dr. Isabelle Le Ber

This project will focus on the mechanisms of C9orf72 gene expansions, which are responsible for frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS). The characterization of these expansions will allow a better understanding of the molecular basis of these diseases and could lead to the discovery of biological targets aimed at preventing, slowing down, or stopping degenerative processes.

More broadly, this project will study the impact of the identified modifying factors on the clinical presentation of the disease. It also will be part of the search for predictive biomarkers of the age of onset and progression of these genetic diseases, which will be necessary for the development and monitoring of therapeutic trials.

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Conference Series: Conversations between the mind and body https://institutducerveau-icm.org/en/actualite/conference-series-conversations-between-the-mind-and-body/ https://institutducerveau-icm.org/en/actualite/conference-series-conversations-between-the-mind-and-body/#respond Wed, 11 May 2022 12:26:49 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23709 The mind, body and world interact in many fascinating ways. For example our emotions and thoughts influence bodily processes such as digestion, heart function and For more information ]]> The mind, body and world interact in many fascinating ways. For example our emotions and thoughts influence bodily processes such as digestion, heart function and breathing. In turn, bodily processes such as inflammation and disease also influence brain function and contribute to psychopathologies. 

In our new conference series “Conversations between the mind and body”, we explore interactions between the mind, body and our social and physical environments. These interdisciplinary explorations will take on various forms, including presentations, workshops and experiential explorations with scientists, clinicians, somatic practitioners, movement artists…

This first session Sense of self in health and psychopathology: Insights from brain-body interactions by speakers: Dr. Catherine Tallon-Baudry and Dr. Marion Plaze addresses links between the brain, visceral organs and our sense of self, and how those interactions contribute to consciousness and how they are altered in psychiatric conditions, such as depersonalization/derealization disorder. 

First Part: Brain, viscera & consciousness (in English)

Dr. Catherine Tallon-Baudry, CNRS Research Director, Laboratoire des Neurosciences Cognitives et Computationnelles, Ecole Normale Supérieure, Paris. 

Dr. Tallon-Baudry will present her recent research that demonstrates how the interplay between the human brain and visceral organs, such as the heart and stomach, contributes to brain dynamics and to consciousness.

Second Part: Depersonalization-Derealization Disorder (in French)

Par le Dr. Marion Plaze, Chef de service du SHU-S14, Pôle Hospitalo-Universitaire Paris 15, GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne

Depersonalization-derealization disorder is a common psychological disorder characterized by a chronic feeling of detachment from oneself and one’s environment. Dr. Plaze will present insights into the physiological mechanisms underlying this disorder and new therapeutic approaches.

Friday, May 13, 2022 17-19h

at the Paris Brain Institute / Institut du Cerveau, auditorium

Hôpital Pitié-Salpêtrière, 47 bd de l’Hôpital, 75013 Paris

https://institutducerveau-icm.org/fr/

and online: https://icm-institute.zoom.us/j/99182180783

Online streaming: https://icm-institute.zoom.us/j/99182180783

Contact: Dr. Claire Wyart (claire.wyart@icm-institute.org), Dr. Leonie Koban (leonie.koban@icm-institute.org), or Ann Moradian (shingaiayoga@gmail.com)

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How the first lockdown of the COVID-19 pandemic changed our creativity https://institutducerveau-icm.org/en/actualite/how-the-first-lockdown-of-the-covid-19-pandemic-changed-our-creativity/ https://institutducerveau-icm.org/en/actualite/how-the-first-lockdown-of-the-covid-19-pandemic-changed-our-creativity/#respond Tue, 10 May 2022 08:32:33 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23695 Covid-19 took us by surprise and the exceptional situation of the first lockdown required great capacities of adaptation, in particular for our brain. A study For more information ]]> Covid-19 took us by surprise and the exceptional situation of the first lockdown required great capacities of adaptation, in particular for our brain. A study conducted at the Paris Brain Institute (Inserm/CNRS/Sorbonne University/AP-HP) has just revealed how our creativity evolved during this period and the factors that may have influenced it. Thus, despite the lockdown, our creativity was increased, and focused on activities mainly related to the issues of the situation.

Creativity is one of the cognitive functions that allows us to be flexible in new environments and to find solutions in new situations. The unusual conditions of the first Covid-19 pandemic containment forced us to rethink our habits, imposed new constraints, and forced us to adapt… in short, to be creative.

A group of researchers from the Frontlab at the Paris Brain Institute conducted an online survey to assess the impact of lockdown on creativity, using a two-part questionnaire. The first part consisted of questions aimed at understanding the situation in which the participants found themselves in March-April 2020 (Were you confined alone or with others? Did you have more work or free time than before?), their mental states at that time (Did you feel more motivated? Did you feel a decrease or increase in your mood or stress?) and finally, whether they felt more or less creative than before. The second part asked participants about creative activities carried out during confinement, their frequency, their domain, their degree of success and valorisation, and the reasons that motivated or prevented these activities. The researchers collected almost 400 analysable responses.

Stressed but more creative

Our first observation is that the lockdown was psychologically distressing for the majority of participants, which other studies have shown, but that on average they felt more creative,” explains Théophile Bieth (AP-HP), co-first author of the study. “By correlating the two pieces of information, we showed that the better people felt, the more creative they thought they were.”

In contrast, when the researchers asked about the number of obstacles respondents had encountered, they observed a non-linear relationship. Whether the changes in creativity were positive or negative, participants felt they had encountered many obstacles. Indeed, many people encountered obstacles in their usual activities, which forced them to be creative in order to accomplish them, and conversely, some individuals felt that they were not creative because they faced too many problems to be creative.

More creative activities related to the issues of the situation

The second part of the questionnaire consisted of a list of 30 different activities, most of which are part of the international standards used in creativity research (Inventory Creativty Activities and Achievements). These included cooking, painting, sewing, gardening, decorating and music. Participants were asked whether they had engaged in these activities in the past five years, whether their practice had increased during the lockdown, why and how often, and if not, why it had decreased.

This section of the questionnaire tried to measure more objectively the quantitative and qualitative changes in creative behaviour, whereas the first part was based on a subjective report of the situation,” explains Emmanuelle Volle (Inserm), the last author of the study. “Our results show that this measure of creative behaviour is in line with the measure of subjective change reported by the subjects. In both cases, the changes observed were related to free time and emotional feelings.”

The five activities that increased the most during the lockdown were cooking, sports and dance programmes, self-help initiatives and gardening. On average, among the 28 activities investigated, which also included, for example, interior design, sewing, creating, or diverting objects, about 40% of those already practised in the five years prior to confinement increased their practice.

A positive correlation between mood and creativity

The results of this study highlight an overall increase in creativity during the first lockdown. This positive change could be linked to having more free time, feeling more motivated, the need to solve a problem, or the need to adapt to a new situation. However, when negative changes in creativity were experienced, they were related to negative emotions, such as stress or anxiety, feeling pressured, or a lack of material resources or opportunities.

The correlation between positive mood and creativity is quite debated.

“There is some evidence in the scientific literature that you need to feel good to be creative, while other evidence points the other way. Also, it is not known in which direction this process takes place: do we feel good because we are creative or does being creative make us happier?” concludes Alizée Lopez-Persem (Inserm), co-first author of the study, “Here, one of our analyses suggests that creative expression enabled individuals to better manage their negative emotions linked to confinement and therefore to feel better during this difficult period.

Source

Lopez-Persem A., Bieth T., et al. Through Thick and Thin: Changes in Creativity During the First Lockdown of the COVID-19 Pandemic. Frontiers in Psychology. May 10, 2022. DOI : 10.3389/fpsyg.2022.821550

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START-UP: A NEW MASTERCLASS FOR THE MGA PROGRAM https://institutducerveau-icm.org/en/actualite/start-up-a-new-masterclass-for-the-mga-program/ https://institutducerveau-icm.org/en/actualite/start-up-a-new-masterclass-for-the-mga-program/#respond Thu, 05 May 2022 14:51:09 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23680 As part of the Medtech Generator & Accelerator (MGA) program, supported by Bpifrance, the LivingLab of the Paris Brain Institute will host the second MasterClass For more information ]]> As part of the Medtech Generator & Accelerator (MGA) program, supported by Bpifrance, the LivingLab of the Paris Brain Institute will host the second MasterClass about the “Patient Journey”. 

The second one will take place on May 12th from 3pm to 5pm on the following topic: “Patient Journey: tips for building a complete Patient Journey”. It will be addressed to all start-ups involved in the development of a medical device, whatever their level of maturity and knowledge of the subject, as well as to researchers wishing to launch into entrepreneurship. (This MasterClass will be conducted in French). 

This MasterClass proposes to discover what a Patient Journey is, why it is an essential step at the beginning of the development phase and the mistakes to avoid. Indeed, this step is complex, but necessary to reinforce the relevance of a project to investors, by demonstrating its adequacy with the real needs of the patient experience. 

The program for this training session includes a presentation of the Patient Journey, the key steps in its construction, case studies and workshops, so that participants can benefit from a methodology that can be easily reproduced to meet their own needs. 

To participate, register at the following link before May 11: 

https://openbrainschool.com/programme/masterclass-tips-pour-construire-un-patient-journey-complet/

The Medtech Generator & Accelerator (MGA) program is coordinated by the Paris Brain Institute in partnership with Institut Imagine and Institut de la Vision. Focused on the use of medical technologies (Medtech) for neurological and genetic/rare diseases, this program will deploy tools ranging from initial training to accelerated clinical proof of concept. 

For more information about MGA program : https://www.mga-program.com/ 

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A new mathematical model of brain connectivity after stroke https://institutducerveau-icm.org/en/actualite/a-new-mathematical-model-of-brain-connectivity-after-stroke/ https://institutducerveau-icm.org/en/actualite/a-new-mathematical-model-of-brain-connectivity-after-stroke/#respond Fri, 22 Apr 2022 07:06:01 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23588 In a recent paper published in the Journal of Royal Society Interface, Catalina Obando, Charlotte Rosso (Sorbonne Université, AP-HP) Fabrizio de Vico Fallani For more information ]]> In a recent paper published in the Journal of Royal Society Interface, Catalina Obando, Charlotte Rosso (Sorbonne Université, AP-HP) Fabrizio de Vico Fallani (Inria) and their collaborators at the Brain Institute propose a new approach to mathematically model brain reconnection after a stroke.

After a stroke, the phenomenon of plasticity allows the brain to modify some connections to recover all or part of its capacities. Today, in many cases, it is difficult to predict how a patient will recover. A better understanding of connectivity mechanisms, how brain regions interact with one another, over time after a stroke is therefore essential to develop new therapeutic strategies.

Fabrizio de Vico Fallani’s group in the “ARAMIS – algorithms, models and methods for human brain images and signals” team collaborated with Maurizio Corbetta from the University of Padua (Italy), who gathered a unique database of stroke patients who underwent functional MRI at three time points – 2 weeks after the accident, 3 months after and at 1 year -. The researchers’ challenge was to find out whether it was possible, through mathematical modelling, to extract predictive information about the patient’s future condition.

For each subject, they modelled the functional networks of the brain to characterise their evolution over time and to correlate them with the clinical score of motor, visual, language, attention, and memory functions.

We addressed two main questions: what are the connectivity mechanisms over time after a stroke? Are we able to extract information from the first two MRIs to predict the patient’s behaviour at one year?” explains Fabrizio de Vico Fallani (Inria).

The group of researchers developed an approach based on two post-stroke mechanisms: the increase in connection intensity in the damaged brain hemisphere, and the increase in connections between the two hemispheres, and more particularly between the damaged system and its equivalent in the other half of the brain. In particular, the team equated these mechanisms in the form of temporal patterns, which represent basic patterns of connectivity building up or breaking down over time. To this, they combined a statistical model applicable at the individual level.

The model was then applied to 30 patients and control subjects. The results obtained show that these temporal connectivity mechanisms characterise the evolution of the brain network of stroke patients, whereas they are less present in healthy subjects. One question remains: does this dynamic connectivity revealed by the model have predictive potential for stroke recovery?

The temporal connection signatures are indeed associated with the evolution of the patients’ condition. There is a very strong correlation, especially for language. The formation of motifs reinforcing the interactions between brain areas close to the lesion and the formation of connections with the intact hemisphere are thus able to predict the recovery of language in patients,” explains Fabrizio de Vico Fallani.

The model developed by the researchers provides a new methodology, applicable on an individual scale, for identifying the temporal signatures of brain reorganisation after an injury. The results also demonstrate the fundamental dimension of temporality in this type of modelling and the predictive power of this model in the field of language.

Source
Temporal exponential random graph models of longitudinal brain networks after stroke.
Obando C, Rosso C, Siegel J, Corbetta M, De Vico Fallani F.J R Soc Interface. 2022 mars.

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Our pupil reveals elements of our imagination https://institutducerveau-icm.org/en/actualite/our-pupil-reveals-elements-of-our-imagination/ https://institutducerveau-icm.org/en/actualite/our-pupil-reveals-elements-of-our-imagination/#respond Wed, 20 Apr 2022 12:36:27 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23538 A collaboration between Australian (University of New South Wales and Macquarie University) and French (Paris Brain Institute) researchers has found that variations For more information ]]> A collaboration between Australian (University of New South Wales and Macquarie University) and French (Paris Brain Institute) researchers has found that variations in the diameter of our pupil reveal the sensory intensity of our mental imagination, such as the brightness of an imagined scene. These results, published in ELife, also provide the first physiological validation of aphantasia, the absence of mental visualisation.

Closing your eyes and visualising a landscape, a picture, a face in your head… this faculty, visual or mental imagery, may seem obvious to many of us.  However, it is not shared by everyone. It is estimated that around 3% of people are aphantasic, i.e. they do not possess this mental visualisation ability.

Today, visual imagery is often determined subjectively by asking a participant directly to describe their ability to visualise objects mentally. We lacked an objective tool to access an individual’s mental imagery capacity,” explains Dr. Thomas Andrillon (Inserm), one of the authors of the article.

When we see an object with our eyes, our pupils adapt to it. Their diameter varies according to the brightness outside, but studies have shown that it also adapts to the interpretation of an image. Thus, the pupil’s diameter is smaller for a black-and-white image depicting a sunny beach than for a moon-lit landscape, even when the images were manipulated to have the same luminance: the eye uses the context to approximate the expected level of luminance.

 “The pupillary reflex is an adaption that optimises the amount of light hitting the retina,” says Professor Joel Pearson from UNSW, senior author on the paper. “And while it was already known that imagined objects can evoke so-called ‘endogenous’ changes in pupil size, we were surprised to see more dramatic changes in those reporting more vivid imagery. This really is the first biological, objective test for imagery vividness.”

To explore this link between pupillary response and mental imagery, a group of Australian and French researchers set up two series of experiments. In the first, they presented participants with no visual imagery disorders with a series of geometric shapes varying in complexity and luminance, i.e. light intensity. The subjects were then asked to mentally visualise these shapes for 5 seconds. At the same time, their pupils were recorded using two cameras mounted on glasses. In a second phase, the researchers carried out the same study with aphantasic patients, who report no or limited mental imagery capacity.

The results show that the pupil diameter of the control subjects reacts both to the cognitive effort generated by the mental imagery and to the luminance of the visualised object. Furthermore, the pupil response to luminance was predictive of the subjective quality of the mental image reported by the subjects, i.e. how accurate they considered the image to be in their thoughts. In contrast, aphantasic subjects showed a smaller restriction of pupil diameter for more complex shapes but not for luminance.

“Our pupils are known to get larger when we are doing a more difficult task,” says Lachlan Kay, Phd candidate in the Future Minds Lab, UNSW. “Imagining four objects simultaneously is more difficult than imagining just one. The pupils of those with aphantasia dilated when they imagined four shapes compared to one, but did not change based on the whether the shapes were bright or dark. This indicated that the participants with aphantasia were indeed trying to imagine in this experiment, just not in a visual way”.

“These findings are also really interesting in regard to memory and aphantasia,” said Dr. Rebecca Keogh, Postdoctoral research fellow based at Macquarie University and another author of the study. “These findings further highlight the wide variability of the human mind that can often remain hidden until we ask someone about their internal experiences or invent new ways to measure the mind. It reminds us that just because I remember or visualise something one way, doesn’t mean everyone does.”

Our methodology provides the first objective and easy-to-use quantification of mental imagery. Thanks to it, it will be possible to test this capacity on a larger scale to identify the variability of mental imagery and the consequences on other cognitive functions such as attention or memory,” concludes Dr. Thomas Andrillon.

Source

The pupillary light response as a physiological index of aphantasia, sensory and phenomenological imagery strength. Kay L, Keogh R, Andrillon T, Pearson J. Elife. 2022 Mar 31

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Coffee to treat a form of dyskinesia https://institutducerveau-icm.org/en/actualite/coffee-to-treat-a-form-of-dyskinesia/ https://institutducerveau-icm.org/en/actualite/coffee-to-treat-a-form-of-dyskinesia/#respond Tue, 19 Apr 2022 11:29:35 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23578 Dyskinesias are rare diseases characterised by sudden, involuntary movements that can affect the whole body. Two years ago, the team of Prof. Flamand-Roze and Dr. For more information ]]> Dyskinesias are rare diseases characterised by sudden, involuntary movements that can affect the whole body. Two years ago, the team of Prof. Flamand-Roze and Dr. Méneret at the Paris Brain Institute and the neurology department of the Pitié-Salpêtrière Hospital AP-HP published the case of a child suffering from a form of the disease linked to the ADCY5 gene. This young patient was able to return to a normal life thanks to coffee. In a collaborative study, the same team has just confirmed this result by collating data from 30 patients worldwide who were also treated with coffee. 87% of them saw their symptoms improve significantly. This result could, according to the researchers, be explained by the fixation of coffee in the striatum, a deep region of the brain that is crucial for the control of movement. Their discovery, published in the journal Movement Disorders, could pave the way for the development of new treatments for movement disorders.

Dyskinesias are a group of rare disorders characterised by sudden, involuntary movements that can affect the whole body. One of the causes of this condition is a mutation in the ADCY5 gene, which starts mainly in childhood. These abnormal movements are often exacerbated in the form of paroxysmal movement disorders that can occur during the day, but also at night. Despite numerous explorations of the potential benefits of drug treatments, until recently no treatment has been confirmed to be effective in this condition.

Two years ago, a long-standing study by Prof. Emmanuel Flamand-Roze and Dr. Aurélie Méneret highlighted the benefit of caffeine on the symptoms of a child suffering from dyskinesia associated with the ADCY5 gene mutation. In order to confirm these results, the team from the Paris Brain Institute, the neurology department of the Pitié-Salpêtrière AP-HP hospital and Inserm conducted a retrospective study on a worldwide scale. The researchers were able to collect data from 30 patients affected by this rare condition who had consumed or were still consuming coffee for their dyskinesia.

Their results show that, in addition to a good tolerance of caffeine intake, including in children, 87% of patients reported a clear improvement in their motor symptoms. Coffee consumption not only reduced the frequency and duration of paroxysmal movement disorders, but also reduced their baseline movement disorders, as well as other symptoms such as gait, attention and concentration disorders, certain types of pain or hypotonia, with a notable improvement in the patients’ quality of life. This retrospective study thus confirms the potential of caffeine as a first-line treatment in this form of dyskinesia.

The efficacy of coffee can be explained by the fact that caffeine binds to adenosine receptors that modify the function of the dysfonctional protein (ADCY5). The latter is strongly located in the striatum of the brain, which is involved in motor control. Researchers and clinicians at the Paris Brain Institute are currently exploring the interest of the cyclic adenosine monophosphate (cAMP) pathway as a therapeutic target in this disease and more widely in pathologies associated with hyperkinetic movements.

Source
Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study.

Méneret A, Mohammad SS, Cif L, Doummar D, DeGusmao C, Anheim M, Barth M, Damier P, Demonceau N, Friedman J, Gallea C, Gras D, Gurgel-Giannetti J, Innes EA, Necpál J, Riant F, Sagnes S, Sarret C, Seliverstov Y, Paramanandam V, Shetty K, Tranchant C, Doulazmi M, Vidailhet M, Pringsheim T, Roze E.Mov Disord. 2022 Apr 5.

 

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Deciphering a direct dialogue between the gut microbiota and the brain https://institutducerveau-icm.org/en/actualite/deciphering-a-direct-dialogue-between-the-gut-microbiota-and-the-brain/ https://institutducerveau-icm.org/en/actualite/deciphering-a-direct-dialogue-between-the-gut-microbiota-and-the-brain/#respond Sat, 16 Apr 2022 14:30:03 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23634 Products derived from the intestinal microbiota enter the bloodstream and modulate the host's physiological processes, such as immunity, metabolism, and brain For more information ]]> Products derived from the intestinal microbiota enter the bloodstream and modulate the host’s physiological processes, such as immunity, metabolism, and brain function. Scientists from the Institut Pasteur (a research partner of Université Paris Cité), the Paris Brain Institute, Inserm and CNRS have discovered in an animal model that neurons in the hypothalamus directly detect variations in bacterial activity and adapt appetite and body temperature accordingly. These results show the existence of a direct dialogue between the gut microbiota and the brain, a discovery that could be exploited for new therapeutic approaches against metabolic disorders such as diabetes or obesity. These results will be published in Science on 15 April 2022.

The gut microbiota is the largest reservoir of bacteria in the body. A growing body of research shows how dependent the host and its gut microbiota are on each other and highlights the importance of the gut-brain axis.

At the Institut Pasteur, neurobiologists from the Perception and Memory unit, immunobiologists from the Microenvironment and Immunity unit, and microbiologists from the Biology and Genetics of the Bacterial Wall unit, in association with the “Structural Dynamics of Networks” of the Paris Brain Institute, have pooled their expertise to understand how gut bacteria can have a direct effect on the activity of certain brain neurons.

The scientists were particularly interested in the NOD2 (Nucleotide Oligomerization Domain) receptor, which is present inside cells, in particular immune cells. This receptor detects the presence of muropeptides, compounds of the bacterial walls, which can be considered as by-products of the intestinal microbiota.

Furthermore, it was already known that variants of the gene coding for the NOD2 receptor are associated with certain diseases of the digestive system, such as Crohn’s disease, but also with certain neurological diseases or mood disorders.

These data did not yet allow to conclude that there is a direct relationship between the functioning of brain neurons and bacterial activity in the gut. This is what the consortium of scientists has brought to light in this new study.

Using brain imaging techniques, the scientists first observed in mice that the NOD2 receptor is expressed by neurons in different regions of the brain, and in particular in a centre called the hypothalamus. They then discovered that these same neurons have their electrical activity repressed when they encounter bacterial muropeptides from the intestine. Muropeptides are released by bacteria as they proliferate. “Muropeptides in the gut, blood and brain are considered to be markers of bacterial proliferation,” explains Ivo G. Boneca, head of the Biology and Genetics of the Bacterial Wall unit at the Pasteur Institute (CNRS/Inserm).

Conversely, in the case where the NOD2 receptor is defective, these neurons are no longer repressed by muropeptides; the brain then loses control over food intake and body temperature.

As a result, the mice gain weight and are more likely to develop type 2 diabetes, especially in older females.

Surprisingly, the scientists have shown that it is the neurons that directly perceive the bacterial muropeptides, whereas this task is usually assigned to the cells of the immune system. “It is amazing to discover that bacterial fragments act directly on a nerve centre as strategic as the hypothalamus, which is known to manage vital functions such as body temperature, reproduction, hunger and thirst,” comments Pierre-Marie Lledo, CNRS researcher and head of the Perception and Memory unit at the Institut Pasteur.

Thus, the neurons seem to detect bacterial activity (proliferation and death) to directly measure the impact of food intake on the intestinal ecosystem. “It is possible that an excessive food intake or a particular food may encourage the exaggerated expansion of certain bacteria or pathogens, thus endangering the intestinal balance,” emphasizes Gérard Eberl, head of the Microenvironment and Immunity Unit at the Institut Pasteur (Inserm).

Given the impact of muropeptides on hypothalamic neurons and metabolism, it is possible to question their role in other brain functions, and thus understand the association between certain brain diseases and NOD2 genetic variants. This discovery opens the way to new interdisciplinary projects for the research teams and, in the long term, to new therapeutic approaches against brain diseases or metabolic diseases such as diabetes and obesity.

Source 

Bacterial sensing via neuronal Nod2 regulates appetite and body temperature. Gabanyi I, Lepousez G, Wheeler R, Vieites-Prado A, Nissant A, Wagner S, Moigneu C, Dulauroy S, Hicham S, Polomack B, Verny F, Rosenstiel P, Renier N, Boneca IG, Eberl G, Lledo PM. Science. 2022 Apr 15

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World Parkinson’s Day 2022: where does research stand? https://institutducerveau-icm.org/en/actualite/world-parkinsons-day-2022-where-does-research-stand/ https://institutducerveau-icm.org/en/actualite/world-parkinsons-day-2022-where-does-research-stand/#respond Mon, 11 Apr 2022 07:01:59 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23507 On the occasion of World Parkinson's Day, which will be held on 11 April 2022, the Paris Brain Institute takes stock of the latest advances in research and the For more information ]]> On the occasion of World Parkinson’s Day, which will be held on 11 April 2022, the Paris Brain Institute takes stock of the latest advances in research and the challenges that remain in the fight against the second most common neurodegenerative disease after Alzheimer’s disease.

While treatments have made great progress in reducing patients’ motor symptoms, scientists are still working to better understand the mechanisms behind neurodegeneration, to improve the diagnosis and prognosis of patients in order to set up more relevant clinical trials, and to optimise existing therapies so that they benefit patients as long as possible. The teams at the Paris Brain Institute are carrying out numerous complementary studies on Parkinson’s disease, from the most fundamental to the most applied research. Here is a closer look at three particularly promising projects.

PROJECT #1: Unravelling the molecular and cellular mechanisms of neurodegeneration to develop new therapeutic approaches: focus on microglial cells.

Parkinson’s disease is characterised by the degeneration of a population of neurons located in a deep region of the brain, called the substantia nigra. In recent years, several major players in the death of these neurons have been identified. The aggregation of the protein a-synuclein inside neuronal cells is the first of these. The exploration of familial forms of the disease has also highlighted the role of mitochondria – the cell’s powerhouses – and brain inflammation in the process of neuronal degeneration.

PROJECT #1: Unravelling the molecular and cellular mechanisms of neurodegeneration to develop new therapeutic approaches: focus on microglial cells.

A growing body of literature links the function of genes involved in familial forms of Parkinson’s disease to the regulation of mechanisms related to immunity and inflammation. This is particularly the case for the LRRK2 and PRKN(Parkin) genes. In the central nervous system, immunosurveillance is provided by microglial cells. Although these cells are active in the brains of people with Parkinson’s disease, their precise contribution to the neurodegenerative process remains to be clarified. The team of Olga Corti (Inserm) and Jean-Christophe Corvol (Sorbonne University, AP-HP) at the Paris Brain Institute is developing an innovative project based on the use of human cerebral organoids (mini-brains) and complex co-cultures of human cells to explore the role of the microglial component in the context of mutations in the LRRK2 and PRKN genes. A better understanding of the role of microglia and immune pathways in Parkinson’s disease could open up new therapeutic avenues to prevent neuronal death and thus slow disease progression. The models developed in the context of this project could also constitute relevant tools for screening therapeutic molecules, as they incorporate cells from patients with Parkinson’s disease.

(Project led by Olga Corti and Philippe Ravassard at the Paris Brain Institute, in collaboration with Michela Deleidi at the DZNE, Tübingen).

PROJECT #2: Refining the diagnosis and prognosis of patients using brain imaging and artificial intelligence

 There is not one but many Parkinson’s diseases. Each patient has different symptoms and a different course of the disease. Today, diagnosis and monitoring of the disease is based on clinical observation. The identification of biomarkers, in particular through brain imaging, is crucial for a more reliable diagnosis of the disease. Thanks to artificial intelligence, the challenge is to be able to develop predictive algorithms of the future evolution of each patient, in order to adapt their treatment and also to integrate them into clinical trials appropriate to the characteristics of their disease.

PROJECT #2: Refining the diagnosis and prognosis of patients using brain imaging and artificial intelligence

The MOV’IT team, led by Marie Vidailhet (Sorbonne University, AP-HP) and Stéphane Lehéricy (Sorbonne University, AP-HP), has used a magnetic resonance imaging biomarker, neuromelanin, which has recently led to major advances in the monitoring of Parkinson’s disease. In particular, the Paris Brain Institute team developed an artificial intelligence algorithm that automatically detects changes in the volume and signal of the region mainly affected in the disease, the substantia nigra, by monitoring neuromelanin. They found differences between patients at a prodromal stage of the disease and those in whom clinical signs have already appeared. This automatic, rapid, and assessor-independent algorithm is therefore a valuable tool for studying changes in neuromelanin in the substantia nigra, allowing direct and non-invasive assessment of neurodegenerative changes in this structure. These measurements could provide relevant biomarkers for assessing the efficacy of treatments modifying the course of Parkinson’s disease.

PROJECT #3: Improving existing therapies with new technologies

 Until the advanced stage of Parkinson’s disease, drug treatment based on L-DOPA, a dopamine precursor, makes it possible to compensate for the lack of dopamine production by the damaged neurons, and greatly reduces motor symptoms. Over time, the effectiveness of this treatment diminishes, and abnormal movements appear. Deep brain stimulation can then take over. This neurosurgical method, which requires millimetre-level precision, involves implanting electrodes in the centre of the patient’s subthalamic nucleus, a deep brain structure. It modulates the electrical activity of this region and thus makes it possible to correct the dysfunctions induced by the dopamine deficit. The ‘Experimental Neurosurgery’ team, led by Brian Lau (CNRS) and Carine Karachi (Sorbonne University, AP-HP) at the Paris Brain Institute is seeking to gain an ever more detailed understanding of normal and pathological brain anatomy and physiology. Recently, the team was able to offer several patients the implantation of a new stimulation device, capable of recording intracerebral activity in an embedded manner. This advance opens up important perspectives, such as recording this activity at different moments of daily life, to better understand the dysfunctions of the deep brain networks in the disease and the effects of deep brain stimulation.

PROJECT #3: Improving existing therapies with new technologies

Another project, developed at the Paris Brain Institute by Nathalie George (CNRS) in this team, concerns neurofeedback methods. These approaches consist of teaching patients to regulate certain brain activities associated with the disease themselves, for example by varying a curve displayed on a screen representing their brain activity. Before these devices can be used in a clinical trial in patients, many issues remain to be clarified, including the mechanisms of learning neurofeedback, the regulation of brain activity and the role of pathological brain activity in the disease. It should be noted that neurofeedback will require very sophisticated signal analysis methods and recordings under very controlled conditions if it is to be used in a clinical context.

Learn more about Parkinson disease

Parkinson’s disease in brief

The tremor, the best-known symptom of Parkinson’s disease, is not the most common. The motor impairment characteristic of the disease takes various forms in patients, such as akinesia, a slowness, delay or even difficulty in initiating movement, or hypertonia, a stiffness or even permanent contraction of certain muscles. The first symptoms are the consequence of a silent phase of the disease developing over several years, during which the nerve cells of a specific region of the brain, the substantia nigra pars compacta, are gradually destroyed. These cells are so-called dopaminergic neurons: they use a neurotransmitter called dopamine to perform their function. The substantia nigra and dopamine play a key role in the control of movement, which explains the visible symptoms of Parkinson’s disease, but also in many other, less easily observable cognitive and behavioural functions, such as difficulties in concentrating, chronic loss of motivation or a depressive syndrome. The most important risk factor for developing Parkinson’s disease is age, with a prevalence of 0.04% in people between 40 and 49 years of age, which increases to 2% in people over 80 years of age. 5% of cases of Parkinson’s disease are familial, i.e. inherited through the mutation of a dominant or recessive gene. Parkinson’s disease, like many neurological diseases, is said to be multifactorial. Many environmental factors and genetic predisposition conferring a higher risk of developing the disease have been identified in recent years.

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Discovery of the mechanisms behind epileptic seizures in autoimmune encephalitis https://institutducerveau-icm.org/en/actualite/discovery-of-the-mechanisms-behind-epileptic-seizures-in-autoimmune-encephalitis/ https://institutducerveau-icm.org/en/actualite/discovery-of-the-mechanisms-behind-epileptic-seizures-in-autoimmune-encephalitis/#respond Thu, 07 Apr 2022 13:33:30 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23495 An unprecedentedly precise exploration of the molecular and electrophysiological basis of a form of autoimmune encephalitis, conducted by the "Cellular Excitability For more information ]]> An unprecedentedly precise exploration of the molecular and electrophysiological basis of a form of autoimmune encephalitis, conducted by the “Cellular Excitability and Neuronal Network Dynamics” team at the Paris Brain Institute, elucidates for the first time a scenario for the onset of epileptic seizures in this pathology. The results, published in Progress in Neurobiology, pave the way for the identification of new therapeutic targets for drug-resistant epilepsy.

Epileptic seizure and autoimmune encephalitis

Autoimmune encephalitis occurs as a result of an attack on the central nervous system by an individual’s own immune cells. It is an important cause to look for in adult and childhood epilepsy, once the classic seizure triggers have been excluded: an autoimmune cause is thought to be involved in up to 30% of cases. The identification of an autoimmune cause also has major implications for medical treatment. In this case, anti-inflammatory drugs may be effective in treating the symptoms, while conventional anti-epileptic drugs are ineffective. Prompt treatment of autoimmune seizures is crucial because the neuronal hyperactivity associated with seizures can lead to significant cognitive and neurological consequences.

In autoimmune encephalitis, several proteins can be targeted by immune cells, such as NMDA receptors, leading to very severe neuropsychiatric disorders, or the synaptic protein LGI1, the most common target in patients with autoimmune epilepsy, which modulates the activity of the potassium channel KV1.1 at the synapse.

A new study model, combined with unprecedented cellular exploration

How can antibodies targeting the LGI1 protein induce such severe epileptic seizures? To explore this question, Paul Baudin, first author of the study, led by Vincent Navarro (Sorbonne University, AP-HP), associated with Séverine Mahon (Inserm) and Stéphane Charpier (Sorbonne University) in the team “Cellular Excitability and Dynamics of Neuronal Networks“, blocked the KV1.1 channel in the motor cortex of rats. This resulted in seizures identical to those observed in patients. By analysing brain activity using electroencephalography (EEG), the researchers were able to identify a specific wave in the motor cortex preceding the onset of the seizure. These initial data reinforce the major homology between the patients and the animal model of encephalitis targeting the LGI1 protein, by blocking the KV1.1 channel.

Using this model, the researchers conducted an in-depth exploration at the cellular level of the consequences of blocking the KV1.1 channel. Combining multi-electrode recordings at the level of the motor cortex, set up with Delphine Roussel from the electrophysiology platform of the Paris Brain Institute, EPhys, and intracellular recordings, the expertise of Stéphane Charpier and Séverine Mahon in the team, they identified major changes in the activity of the synapses and the excitability of the neurons.

A scenario for the onset of seizures

Thanks to this unique approach, the researchers were able to propose a scenario for the onset of seizures and their very frequent repetition. After a first seizure, the neurons are inhibited and then gradually depolarise, i.e. the levels of activation and synchronisation of the neurons are increasingly high, until a new seizure is initiated. The study of the intrinsic characteristics of the neurons shows that they have become hyperexcitable, i.e. much more sensitive to the slightest stimulation. These data also explain the increase in the frequency of seizures in patients over time.

The Paris Brain Institute team suggests a central role for potassium channels in epilepsy associated with antibody-related autoimmune encephalitis. This result, for Prof. Vincent Navarro, opens up major perspectives for therapeutic research, notably on the anti-epileptic potential of potassium channel modulators.

Source

Kv1.1 channels inhibition in the rat motor cortex recapitulates seizures associated with anti-LGI1 encephalitis. Baudin P, Whitmarsh S, Cousyn L, Roussel D, Lecas S, Lehongre K, Charpier S, Mahon S, Navarro V. Prog Neurobiol. 2022 Mar 10

 

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Master iMIND : registrations are open https://institutducerveau-icm.org/en/actualite/__trashed/ https://institutducerveau-icm.org/en/actualite/__trashed/#respond Wed, 06 Apr 2022 09:20:53 +0000 Alban Orsini https://institutducerveau-icm.org/?post_type=actualite&p=23477 The application campaign for the Master 2 iMIND - International Master in Neurodegenerative Diseases, will take place from March 29th to June 1st 2022! 

This For more information ]]> The application campaign for the Master 2 iMIND – International Master in Neurodegenerative Diseases, will take place from March 29th to June 1st 2022! 

This international master’s degree dedicated to neurodegenerative diseases is an international and interdisciplinary training course, allowing students to design an individualized study program through course modules and research projects involving all national and international partners. 

iMIND brings together researchers from the Paris Brain Institute, as well as other neuroscience institutes associated with Sorbonne University, such as the Neuroscience Paris Seine Institute or the Institut de la Vision, in order to offer courses aimed at immersing students in current and innovative research themes on brain function and dysfunction. 

The Paris Brain Institute and Sorbonne University work in close collaboration to promote French excellence in the teaching of neuroscience and nervous system diseases. This is why the Paris Brain Institute will offer again this year up to 4 scholarships of 600€/month (after selection) during the first semester for international students wishing interested in iMIND program. 

You can find more details about this training here and you can register on the application platform here. 

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HYPNOTIC SUGGESTION INFORMED BY NEUROSCIENCE https://institutducerveau-icm.org/en/actualite/hypnotic-suggestion-informed-by-neuroscience/ https://institutducerveau-icm.org/en/actualite/hypnotic-suggestion-informed-by-neuroscience/#respond Mon, 21 Mar 2022 11:06:43 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23386 Within the walls of the Pitié-Salpêtrière AP-HP hospital, where Charcot explored hypnosis at the end of the 19th century, the research team led by Professor For more information ]]> Within the walls of the Pitié-Salpêtrière AP-HP hospital, where Charcot explored hypnosis at the end of the 19th century, the research team led by Professor Lionel Naccache at the Paris Brain Institute (Inserm/CNRS/Sorbonne University), has just reported an original observation that sheds light on the cerebral and psychological mechanisms of hypnotic suggestion. This research work has just been published in the journal Frontiers in Neuroscience.

 

Hypnotic suggestion can voluntarily induce a wide range of conscious mental states in an individual and can be used both in research on the biology of consciousness and in therapy where it can, for example, reduce the painful experience associated with surgery in a conscious subject.

 

In this work, first authored by neuroscience PhD student Esteban Munoz-Musat, the authors induced transient deafness in a healthy woman while dissecting the brain stages of her auditory perception using the high-density electroencephalography (EEG) technique, which allows the dynamics of brain function to be tracked at the fine scale of a thousandth of a second.

 

The researchers recorded the brain activity of the volunteer in normal and hypnotic deafness situations. They formulated the following three predictions, which derive from the known cerebral mechanisms of auditory perception and from the theory of the global conscious neuronal workspace developed since 2001 by Stanislas Dehaene, Jean-Pierre Changeux and Lionel Naccache:

 

  • The early cortical stages of the perception of an auditory stimulus should be preserved during hypnotic deafness;
  • Hypnotic deafness should be associated with a total disappearance of the P300 that signals the entry of auditory information into the global conscious neural space;
  • This block should be associated with an inhibitory mechanism voluntarily triggered by the individual who agrees to follow the hypnotic induction instruction.

 

Remarkably detailed and extensive analyses of this volunteer’s brain activity confirmed all three predictions and highlighted the likely involvement of a frontal lobe region known for its inhibitory role: the anterior cingulate cortex.

 

The research team was then able to propose a precise brain scenario for the phenomenon of hypnotic induction that specifically affects the stages of awareness while preserving the early unconscious stages of perception.

 

This original work provides an important proof of concept and will be extended to a larger group of individuals. In addition to their importance for biological theories of consciousness and subjectivity, these results also open therapeutic perspectives not only in the field of medical hypnosis, but also in the related field of functional neurological disorders which are very frequent (nearly 20% of neurological emergencies), and in which patients suffer from disabling symptoms. These symptoms are often sensitive to hypnotic induction and seem to share several key factors with hypnosis.

 

Summary of the physiology of auditory perception

 

The significance and scope of these results require the following reminder: the auditory perception of an external stimulus begins in the inner ear where the variations in air pressure induced by this sound are converted into electrical impulses, then continues in the various neural relays of the auditory pathways before reaching the auditory cortex at around 15 milliseconds. From this entry into the cortex, auditory perception follows three main serial stages that can be identified using functional neuroimaging tools such as the EEG.

 

First, the so-called primary auditory regions actively construct a mental map of the acoustic characteristics of the perceived sound. This first stage can be identified by a brain wave (the P1 wave which occurs less than 100 thousandths of a second after the sound). Then primary and secondary auditory regions that calculate in real time the statistical regularities of the auditory scene on the scale of the elapsed second – and which therefore anticipate what the following sounds should be – detect to what extent this stimulus transgresses their predictions.

 

This second stage is identifiable by a brain wave discovered in the late 1970s: the MMN (MisMatch Negativity) (around 120 and 200 milliseconds). Finally, around 250-300 milliseconds after the sound, the neuronal representation of the auditory stimulus reaches a vast cerebral network that extends between the anterior (prefrontal) and posterior (parietal) regions of the brain.

 

Crucially, whereas the first two cortical stages of auditory perception operate unconsciously, the P300 is the signature of the subjective awareness of that sound, which then becomes relatable to oneself: “I hear sound X”.

 

Source

Hypnotic Induction of Deafness to Elementary Sounds: An Electroencephalography Case-Study and a Proposed Cognitive and Neural Scenario

Esteban Munoz Musat, Benjamin Rohaut, Aude Sangare, Jean-Marc Benhaiem and Lionel Naccache

Frontiers in Neuroscience, 17th March 2022.

DOI : 10.3389/fnins.2022.756651

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Restoring consciousness through deep brain stimulation https://institutducerveau-icm.org/en/actualite/restoring-consciousness-through-deep-brain-stimulation/ https://institutducerveau-icm.org/en/actualite/restoring-consciousness-through-deep-brain-stimulation/#respond Mon, 21 Mar 2022 10:57:45 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23384 A research team involving neuroscience researchers and clinicians from the CEA, the Foch Hospital, the University of Versailles Saint-Quentin-en-Yvelines, Inserm, For more information ]]> A research team involving neuroscience researchers and clinicians from the CEA, the Foch Hospital, the University of Versailles Saint-Quentin-en-Yvelines, Inserm, the Collège de France and the Paris Brain Institute, has provided proof that deep brain stimulation can restore consciousness when it is impaired. This result, the fruit of more than 5 years of work in animals, would pave the way for clinical trials in patients who do not recover consciousness. It is published in Science Advances.

 

Consciousness is a dynamic and complex process that coordinates the activity of different brain regions, particularly the brainstem, the thalamus and the cortex.

 

There are two hierarchical levels of consciousness. The first is that of awakening, or vigilance, characterised by openness to the world. It corresponds to the activation of very deep structures of the brain nested in the brain stem. The second is “conscious access”, characterised by the conscious perception of an information. Each time we become aware of a piece of information, for example a musical note, this content of consciousness is encoded by the simultaneous activation of groups of neurons distributed in different areas of the cortex. Loss of consciousness has been linked to a strong disruption of communication between different areas of the cerebral cortex, and between the cortex and the thalamus, a region of the brain halfway between the brainstem and the cortex.

Brain imaging studies suggest that restoring these communications between the cortex and thalamus may be the key to recovery from chronic disorders of consciousness. Several teams around the world have come up with the idea of re-establishing them through electrical stimulation.

 

Although initial results had already shown that such stimulation could restore the first level of consciousness (the awake state), none had been able to demonstrate whether such stimulation could also restore the second level of consciousness, ‘conscious access’.

 

What if the thalamus centre was the right target to stimulate to restore the two hierarchical levels of altered consciousness? This is the hypothesis tested by the French research team behind this work published in Science Advances and involving the CEA, the Foch Hospital, the University of Versailles Saint-Quentin-en-Yvelines, Inserm, the Collège de France and the Paris Brain Institute.

 

Electrical stimulation of the thalamus restores lost consciousness

 

To test their hypothesis, the researchers applied general anaesthesia to a non-human primate in order to suppress the two components of consciousness, namely arousal and conscious access. A deep brain stimulation electrode, a device equivalent to that used in patients with Parkinson’s disease, was implanted beforehand. The result: during general anaesthesia, electrical stimulation of the central part of the thalamus woke up the anaesthetised animals.

 

The electrical stimulation immediately induced the clinical observation of eye opening, resumption of spontaneous breathing, and limb movements. Stopping the stimulation by cutting off the electrical current immediately put the animal back into a state of deep sedation, that of general anaesthesia. This experiment thus demonstrated that deep brain stimulation can restore the first level of consciousness.

 

Thanks to the technology of brain imaging by functional MRI, and also an examination by electroencephalography, the researchers succeeded for the first time in finely measuring, during stimulation of the thalamus, the two levels of consciousness (awakening and conscious access). They closely observed the brain activations of the animal during anaesthesia and during the periods of ‘awakening’ induced by the stimulation. In addition, headphones were used to make the primate listen to a series of different sounds in a complex composition. While the brain had lost its ability to integrate the complexity of the sound composition under the effect of deep anaesthesia, it regained this ability as soon as the brain stimulation was started. An algorithmic analysis applied to the functional MRI signal at rest (outside the periods of application of the sound compositions) was able to demonstrate that cerebral stimulation brought back to the brain a wealth of activity lost under general anaesthesia. Thus, brain stimulation of the thalamus was able to restore the two fundamental and hierarchical dimensions of consciousness.

 

This scientific work provides a key piece of evidence for future clinical trials in patients with chronic disorders of consciousness.

 

After a severe head injury or stroke, patients may never regain a normal state of consciousness. From the initial coma treated in intensive care, the patient moves on to a chronic state of altered consciousness for which there is no validated treatment. Hope could come from the neurosciences which, over the last twenty years, have made considerable progress in understanding the neurobiological phenomenon of consciousness.

 

Source

 

Deep brain stimulation of the thalamus restores signatures of consciousness in a nonhuman primate model in Science Advances : https://www.science.org/doi/10.1126/sciadv.abl5547

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First demonstration of the neuroprotective effect of remyelination in multiple sclerosis patients https://institutducerveau-icm.org/en/actualite/first-demonstration-of-the-neuroprotective-effect-of-remyelination/ https://institutducerveau-icm.org/en/actualite/first-demonstration-of-the-neuroprotective-effect-of-remyelination/#respond Thu, 24 Feb 2022 15:42:41 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23154 In an article recently published in the European Journal of Neurology, Vito Ricigliano (AP-HP), Benedetta Bodini (AP-HP/Sorbonne University) and their collaborators For more information ]]> In an article recently published in the European Journal of Neurology, Vito Ricigliano (AP-HP), Benedetta Bodini (AP-HP/Sorbonne University) and their collaborators at the Paris Brain Institute, demonstrate the protective effect of myelin repair on the tissues surrounding lesions in patients with multiple sclerosis. This discovery underlines the potential of new therapeutic strategies and provides new elements to evaluate the efficacy of remyelinating drugs currently being tested.

 

How to prevent or reduce neuronal degeneration, which is the cause of clinical disability in multiple sclerosis (MS)? At present, doctors have treatments available to control the inflammatory component of the disease but are powerless to deal with the degenerative component.

 

The study of experimental models has shown that myelin repair can protect the integrity of neurons and prevent neurodegeneration, which spreads from the demyelinating lesion all along the nerves that are not yet demyelinated but will degenerate directly,” explains Benedetta Bodini, neurologist and last author of the article.

 

In fact, in multiple sclerosis, the damage to the neurons is not only at the level of the myelin lesions visible on MRI, but extends to the regions surrounding them, the peri-lesional tissue. Researchers and clinicians at the Paris Brain Institute wanted to study whether spontaneous recovery of myelin – or remyelination – in the lesions could protect patients from microstructural damage to the surrounding tissue.

 

Lesions, perilesions and indices of myelin content change. a. Examples of lesional (white), proximal perilesional (yellow) and distal perilesional (brown) regions in the MRI of a patient with MS. b. White matter lesion (white) and its corresponding perilesions are represented with color maps, based on the delta of the mean diffusivity in each proximal and distal perilesional voxel from the first to the second time-point. c-e. Detail of the same white matter lesion of Fig. 1b, showing demyelinated voxels at baseline (red, c), dynamically demyelinating voxels over the follow-up (blue, d) and remyelinating voxels over the follow-up (green, e).

 

To do this, they monitored the amount of myelin in the lesions over time using PET-MRI and combined this with an assessment of the microstructural damage to the peri-lesional tissues using diffusion MRI, in 20 patients with multiple sclerosis. Their analyses were conducted at the single lesion level, i.e. over 500 lesions studied.

 

We show for the first time in vivo in MS patients that remyelination protects not only the lesion but also the surrounding tissue. This result highlights the importance of coupling existing anti-inflammatory therapies with a remyelination strategy to protect all tissues, even those that appear normal” explains Vito Ricigliano, neurologist and first author of the study.

 

There is great heterogeneity among patients in their ability to remyelinate. In this study, the scientists also show that in the same patient, some lesions can repair themselves very well and others much less so, and that this difference is reflected in the damage to the peri-lesional tissue.

 

Clinical trials of remyelinating therapies are underway, notably in the team of Bruno Stankoff and Catherine Lubetzki at the Paris Brain Institute. Thanks to the use of PET-MRI, researchers will be able to study the effectiveness of the treatments, not only on the clinical signs, but also at the cellular level with the repair of myelin and the reduction of the microstructural damage to the surrounding tissues.

 

Source

Spontaneous remyelination in lesions protects the integrity of surrounding tissues over time in multiple sclerosis. Ricigliano VAG, Tonietto M, Hamzaoui M, Poirion É, Lazzarotto A, Bottlaender M, Gervais P, Maillart E, Stankoff B, Bodini B. Eur J Neurol. 2022 Feb 12.

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Identification of new risk factors or early signs of Alzheimer’s disease https://institutducerveau-icm.org/en/actualite/identification-of-new-risk-factors-or-early-signs-of-alzheimers-disease/ https://institutducerveau-icm.org/en/actualite/identification-of-new-risk-factors-or-early-signs-of-alzheimers-disease/#respond Wed, 23 Feb 2022 16:48:58 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23129 What risk factors are associated with Alzheimer's up to 15 years before the onset of the first symptoms? This is a vital question for specialists of this For more information ]]> What risk factors are associated with Alzheimer’s up to 15 years before the onset of the first symptoms? This is a vital question for specialists of this neurodegenerative disease – which develops over many years before becoming clinically visible – who aim to improve early prevention for at-risk patients. A multidisciplinary team of researchers from the Paris Brain Institute’s (INSERM/CNRS/Sorbonne University) Aramis project led by Stanley Durrleman (Inria), from INSERM/University of Bordeaux, and from Cegedim Health Data, analysed the anonymised health records of nearly 80,000 patients consulting general practitioners in France and the United Kingdom, taken from the THIN® database. The scientists identified ten pathologies developed more frequently by patients reporting Alzheimer’s dementia within 15 years than by other patients of the same age. Their results are published in the prestigious journal The Lancet Digital Health.

 

 

Despite the growing number of findings, our knowledge of the risk factors and early symptoms of Alzheimer’s disease remains patchy and based on specific risk factor approaches. Until now, there has been no exhaustive, agnostic study conducted on a very large sample of patients that analyses possible risk factors well ahead of the Alzheimer’s diagnosis.

 

For the first time, a team of researchers has accessed the anonymised medical data of nearly 40,000 patients with Alzheimer’s disease and of the same number of control subjects who did not develop neurodegenerative diseases over the period studied. The data was extracted from the THIN® (The Health Improvement Network) database owned by Cegedim Group, an innovative technology and services company specializing in healthcare data.

 

The Aramis team’s expertise in mathematical modelling made it possible to perform an analysis without predefined hypotheses, and test the possible link between the onset of Alzheimer’s disease and 123 health factors. Statistical explorations of historical medical records yielded a list of the 10 most common conditions experienced by patients who go on to develop Alzheimer’s disease within 15 years. Depression topped the list, followed by anxiety, exposure to high stress, hearing loss, constipation, cervical spondyloarthritis, memory loss, fatigue (and discomfort), and finally falls and sudden weight loss. “The connections made allowed us to confirm known associations, such as hearing problems or depression, and other less known factors or early symptoms, such as cervical spondylosis or constipation. However, we are only reporting statistical associations. These will have to be the subject of further studies to understand the underlying mechanisms,’ says researcher Thomas Nedelec, from the Aramis team, “The question remains as to whether the health problems encountered are risk factors, symptoms, or warning signs of the disease”.

 

Epidemiologist and Inserm research director Carole Dufouil, and neurologist Stéphane Epelbaum, helped validate the methodology and interpret the relevance of these statistical associations. Although these results still need to be refined, they are already valuable for health professionals and all those involved in prevention, who could try to address these risk factors as soon as they are detected and hope to prevent the disease.

 

This work opens up several prospects, the first of which will be to expand and diversify the corpus of data studied. A grant from the European programme for the study of neurodegenerative diseases (Joint Programme – Neurodegenerative Disease Research) will enable the Aramis researchers to add data from Sweden and Australia to the existing pool and thus to extend their analyses to more than 26 million data from anonymised health records. This will also enable research to be extended to other degenerative diseases (Parkinson’s, Charcot’s disease, multiple sclerosis, etc.). “We hope, through this approach, to identify the common basis of these diseases and the specificities associated with each one,” concludes Stanley Durrleman.

 

 

Source

Identifying health conditions associated with Alzheimer’s disease up to 15 years before

diagnosis: an agnostic study of French and British health records, The Lancet Digital Health, February 23 2022. https://www.thelancet.com/journals/landig/article/PIIS2589-7500(21)00275-2/fulltext

 

Thomas Nedelec, PhD (1) ; Baptiste Couvy-Duchesne, PhD (1,3) ; Fleur Monnet, MSc (4), Timothy

Daly, MPhil (5) ; Manon Ansart, PhD (1) ; Laurène Gantzer, MSc (4) ; Béranger Lekens, MSc (4) ;

Stéphane Epelbaum, PhD (1,2) ; Carole Dufouil, PhD (6,7)* ; Stanley Durrleman, PhD (1)*

 

(1) Paris Brain Institute, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Inria, Aramis project team, F-75013, Paris, France

(2) AP-HP, Hôpital de la Pitié Salpêtrière, Institute of Memory and Alzheimer’s Disease (IM2A), Centre of Excellence for Neurodegenerative Disease (CoEN), Department of Neurology, F-75013, Paris, France.

(3) Institute for Molecular Bioscience, the University of Queensland, St Lucia, Queensland, Australia

(4) Cegedim R&D, Boulogne-Billancourt, France

(5) Sciences, Normes, Démocratie (UMR 8011), Philosophy Department, Sorbonne Université, Paris, France

(6) Univ. Bordeaux, Inserm, UMR 1219, Inserm, CIC1401-EC, F-33000 Bordeaux, France.

(7) Pole de Santé Publique Centre Hospitalier Universitaire (CHU) de Bordeaux, F-33000 Bordeaux, France

 

*equal contributions

 

Find out more

About Paris Brain Institute

Created in 2010, the Paris Brain Institute is an international scientific and medical research centre of excellence, located in Paris at the heart of the Pitié-Salpêtrière Hospital. Its innovative model brings together patients, doctors, researchers and entrepreneurs with a common goal: to understand the brain and accelerate the discovery of new treatments for nervous system diseases. The Institute thus includes a network of more than 700 researchers and clinicians (AP-HP, Sorbonne University, Inserm and CNRS), 10 cutting-edge technological platforms, 1 clinical investigation centre, 1 training organisation and more than 2,000m² dedicated to incubating startups. Since 2017, it has also been the health partner of Station F; this location gives it a competitive advantage in the field of connected health. In 2020, the Paris Brain Institute celebrated its tenth anniversary.

About the University of Bordeaux

With more 54,000 students, 3,200 researchers and teachers, and 2,800 staff members, the University of Bordeaux is one of the leading French public research and higher education institutions, located in a dynamic and culturally rich, fast-developing region.

Ranked among the top universities in France, the University of Bordeaux is renowned for the quality of its academic courses and research. It is a multi-disciplinary, research-focused institution with a strong ambition to develop as a leading, international campus. The University of Bordeaux is leading an ambitious, competitive development program in partnership with local higher education institutes and national research organizations, in order to promote Bordeaux as a “Campus of Excellence”.

About Inria

Inria is the French national institute for research in digital science and technology. World-class research, technological innovation and entrepreneurial risk are its DNA. Within 200 project-teams, most of which are shared with major research universities, more than 3,500 researchers and engineers explore new avenues, often in an interdisciplinary manner and in collaboration with industrial partners, to meet ambitious challenges. As a technological institute, Inria supports the diversity of innovation paths: from open source software publishing to the creation of technological startups (Deeptech).

About THIN®

THIN® (The Health Improvement Network) is a large European database of anonymized Electronic Health Records collected at the physicians’ level, owned by Cegedim group. THIN® anonymized longitudinal patient data currently covers large populations of over 69 million patients across several European countries (France, the UK, Spain, Italy Belgium and Romania). It aims at enabling advancements in patient care and outcomes by assisting leading healthcare authorities, academics and research centers with healthcare research and analysis.

About Cegedim Health Data

Cegedim Health Data is part of the Cegedim Group, an innovative technology, services and real world data group that has specialized in healthcare for more than 50 years. Cegedim Health Data provides anonymized Real-World Data and Evidence (RWD-E) platforms and advanced studies to drive cutting-edge improvements in patient outcomes in the interests of public health. Through THIN®️ (The Health Improvement Network), a data history of over 25 years and millions of anonymized patient records are immediately accessible. Our life science users can use THIN® data across the pharma value chain, from R&D, market access, and medical, to marketing.

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Bone marrow transplant: What is the impact of chemotherapy on the brain? https://institutducerveau-icm.org/en/actualite/bone-marrow-transplant/ https://institutducerveau-icm.org/en/actualite/bone-marrow-transplant/#respond Mon, 21 Feb 2022 16:30:22 +0000 Heena Djivan https://institutducerveau-icm.org/?post_type=actualite&p=23091 More than 50,000 bone marrow-derived stem cell transplants are performed worldwide each year to treat a wide range of conditions, including brain diseases. Before For more information ]]> More than 50,000 bone marrow-derived stem cell transplants are performed worldwide each year to treat a wide range of conditions, including brain diseases. Before the cells are transplanted, the patients are given chemotherapy to destroy the immune cells and thus prevent the transplanted cells from being rejected by the body. Until now, little was known about the effects of such treatment on the brain. In a new study, researchers from the Paris Brain Institute (Inserm/CNRS/Sorbonne University) and the Institut Pasteur, have looked into this problem. Using an animal model, they discovered how pre-transplant chemotherapy facilitated the replacement of the brain’s innate immune cells, the microglia, by other immune cells derived from the transplanted stem cells (macrophages). These results are published in Nature Medicine.

  

Many brain diseases lead to progressive demyelination of the central nervous system with devastating neurological symptoms and risk of premature death (e.g. leukodystrophy). Gene therapy aimed at correcting disease-causing genetic mutations directly in bone marrow stem cells, and their subsequent autologous transplantation into patients, has developed in recent years and is now a treatment of choice for many of these conditions.

 

Clinical studies have shown that the use of chemotherapy prior to bone marrow stem cell transplantation, using a chemotherapeutic agent called busulfan, allows for efficient engraftment and tolerance of the genetically modified cells by the body. However, many questions remain, particularly concerning the mechanisms involved and the impact of this pre-transplant treatment on the patients’ brains.

 

Therefore, the scientists studied the consequences of this treatment on various brain cell populations in an animal model. They looked at microglial cells, brain immune cells that are essential for maintaining healthy brain physiology in normal and pathological states. These cells have a strong capacity for self-renewal throughout life.

 

In their work, the scientists show that after busulfan chemotherapy, microglial cells completely lose this regenerative capacity, and that many of these cells die by senescence.

 

However, this process would not be harmful to the brain, since after transplantation, the disappeared cells are quickly replaced by bone marrow-derived cells (macrophages). The microglial cells eliminated by busulfan chemotherapy leave empty niches in the brain that are soon filled by bone marrow-derived macrophages. These macrophages then adopt the morphology and behaviour of normal microglia. Future studies will aim to determine whether these macrophages adopt all the properties of endogenous microglial cells in the brain.

 

Microglial cells play an essential role in the functioning of the brain and in the pathophysiology of many severe neurological diseases, both genetic and complex, such as multiple sclerosis and Alzheimer’s disease. Understanding the fate of these cells after the transplant process is essential both to clarify the consequences of chemotherapy and to develop new therapeutic strategies for serious neurodegenerative diseases,” explains Nathalie Cartier, Inserm research director in the NeuroGenCell team at the Paris Brain Institute (ICM), and the study’s last co-author.

This study sheds light for the first time on a mechanism explaining how stem cell-derived macrophages enter the brain after bone marrow cell transplantation. This better understanding is essential for developing new strategies for gene and cell therapy applied to diseases of the central nervous system“, emphasises Pierre-Marie Lledo, CNRS research director and head of the Perception and Memory unit within the “Genes, Synapses and Cognition” laboratory (CNRS/Institut Pasteur) and the study’s last co-author.

Source

 

Hematopoietic stem cell transplantation chemotherapy causes microglia senescence and peripheral macrophage engraftment in the brain. Nature Medicine, February 2022

https://www.nature.com/articles/s41591-022-01691-9

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Artificial Intelligence-based MRI biomarker of Isolated REM Sleep Behavior Disorder and Parkinson’s disease https://institutducerveau-icm.org/en/actualite/artificial-intelligence-based-mri-biomarker-of-isolated-rem-sleep-behavior-disorder-and-parkinsons-disease/ https://institutducerveau-icm.org/en/actualite/artificial-intelligence-based-mri-biomarker-of-isolated-rem-sleep-behavior-disorder-and-parkinsons-disease/#respond Fri, 18 Feb 2022 06:00:08 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23059 Rahul Gaurav, a research Engineer in the MOV’IT team led by Pr. Stéphane Lehéricy and Pr. Marie Vidailhet, at the Paris Brain Institute, developed an artificial For more information ]]> Rahul Gaurav, a research Engineer in the MOV’IT team led by Pr. Stéphane Lehéricy and Pr. Marie Vidailhet, at the Paris Brain Institute, developed an artificial intelligence framework to investigate fully automatic neurodegeneration in the substantia nigra (SN) using neuromelanin-sensitive MRI in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), a prodromal form of Parkinsonism. The findings, published in Movement Disorders, indicated that this model was fast, user-independent and showed comparable performance with the manual method for detecting neuromelanin-based SN volume and signal changes in the patients with iRBD and Parkinson’s disease (PD). Considering the accuracy and speed of this approach, as it takes less than a fraction of a second to segment SN in a single subject, this method could be a crucial step towards the implementation of a non-rater dependent fully automatic method for studying neuromelanin changes in clinical settings and large-scale neuroimaging studies by eliminating the human factor as much as possible.

 

iRBD is characterized by abnormal behaviors and loss of normal muscle atonia during REM sleep. Most iRBD subjects develop Parkinson’s disease (PD) or dementia with Lewy bodies, diseases in which there is a loss of the dopaminergic neurons of the SN. At PD onset, 30 to 60% of dopaminergic neurons are already lost in the SN. As most iRBD subjects are in a prodromal parkinsonism stage, many present a mild SN impairment. Neurodegenerative changes in the SN in parkinsonism can be detected using neuromelanin-sensitive MRI technique. Neuromelanin is a pigment contained in dopaminergic neurons. Characterizing the neuromelanin signal variations by investigating the SN using manual segmentation is a time-consuming task leading to substantial inter-individual variability across raters. Hence, there is a critical need of a robust automatic framework to facilitate quantification of the neuromelanin changes in the SN.

 

To answer this question, Dr Gaurav developed an artificial intelligence framework that can fully automatically investigate the SN neuromelanin changes in iRBD and PD patients as compared to the controls. Subjects were prospectively recruited as part of the ICEBERG study (ClinicalTrials.gov: NCT02305147) at Paris Brain Institute. The RBD status was confirmed using video polysomnography at the Sleep department of the Pitié-Salpêtrière hospital led by Pr. Isabelle Arnulf. MRI data were acquired using 3 Tesla (PRISMA, Siemens, Germany) at the CENIR-MRI core facility of the Paris Brain Institute.

 

All SN measurements differed significantly between the subjects with iRBD and PD, and healthy controls. The iRBD patients demonstrated neurodegenerative SN changes at a lower level than in PD patients. Hence, this fast rater-independent automatic framework can help study the SN neuromelanin changes allowing direct non-invasive assessment of neurodegenerative changes. Furthermore, these measurements could represent target biomarkers for disease-modifying treatments.

 

Pr. Lehéricy’s team is further studying whether neuromelanin imaging technique could serve as a predictor of conversion in these patients or to estimate the time before the appearance of clinical motor signs and the evolution of neuromelanin changes in relation to the striatal dopaminergic function.

 

Source:

Gaurav, R., Pyatigorskaya N., Biondetti, E., Valabrègue, R., Yahia-Cherif, L., Mangone G., Leu-Semenescu S., Corvol J.C., Vidailhet, M., Arnulf I., and Lehéricy, S., 2022. Deep Learning-Based Neuromelanin MRI changes of Isolated REM Sleep Behavior Disorder. Movement Disorders. Mar 10. doi: 10.1002/mds.28933.

https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28933

 

To contact the corresponding author:

Homepage : www.rahulgaurav.com

Twitter : @SayRahulGaurav

Email : rahul.gaurav@icm-institute.org

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Our eye movements reveal our emotions during sleep https://institutducerveau-icm.org/en/actualite/emotions-during-sleep/ https://institutducerveau-icm.org/en/actualite/emotions-during-sleep/#respond Wed, 16 Feb 2022 10:54:27 +0000 Théophile Lacrampe https://institutducerveau-icm.org/?post_type=actualite&p=23054 Dream or nightmare, our sleep is often rich in emotions. A study conducted by Jean-Baptiste Maranci (Sorbonne University), Isabelle Arnulf (AP-HP/Sorbonne For more information ]]> Dream or nightmare, our sleep is often rich in emotions. A study conducted by Jean-Baptiste Maranci (Sorbonne University), Isabelle Arnulf (AP-HP/Sorbonne University) and their collaborators at the Paris Brain Institute and the Pitié-Salpêtrière Hospital (AP-HP), shows an association between dream emotions and the different types of eye movements observed during sleep. These results, published in Scientific reports, open a direct window on the regulation of emotions during dreams and the benefits of sleep on mental health.

 

Sleep and dreams are mysterious states, and their functions are still being explored by neuroscience researchers. Among them, the regulation of emotions has often been proposed. One phase that is particularly conducive to dreams is REM sleep, which stands for Rapid Eye Movement, because in this phase of sleep the eyes start to move, while the rest of the body is paralysed. But what is the purpose of these eye movements?

 

Previous studies have shown that they are more frequent during REM sleep in patients suffering from depression, but also in people at risk for a depressive disorder, suggesting a link between this phase of sleep and the regulation of mood and emotions. Several hypotheses have been proposed on the role of these rapid eye movements, which would follow the dream scenario in the same way as we look at a scene when awake. Another hypothesis, however, links rapid eye movements to the reactivation of emotional memory during dreaming.

 

To better understand this link between REM sleep and emotions during dreams, Jean-Baptiste Maranci (Sorbonne University), Isabelle Arnulf (AP-HP/Sorbonne University) and their collaborators combined different video, audio, and eye activity recordings (video-polysomnography) in 20 patients with REM sleep behaviour disorder, a state in which people “enact” their dreams.

 

The faces of people during REM sleep behaviour disorder are a real open book on emotions in dreams. Thanks to them, we have direct access to the emotional content of the dream,” explains Isabelle Arnulf, head of the sleep pathology department at the Pitié-Salpêtrière Hospital (AP-HP) and researcher at the Paris Brain Institute.

 

This original approach enabled the researchers to show a strong association between the negative emotions expressed by the patients and the eye movements when they occurred ‘in bursts’, i.e. grouped together (as opposed to more isolated movements). This association is reminiscent of a technique used in awake trauma patients who recall negative events while moving their eyes to heal.

 

These results suggest that rapid eye movements in bursts may be important for digesting negative emotions during REM sleep,” explains Jean-Baptiste Maranci, first author of the study.

 

The team of researchers also found that positive emotions are instead associated with slow eye movements, while negative emotions are never linked to them.

 

These results are a further advance supporting the role of REM sleep in the regulation of emotions in dreams and the benefit of sleep on mental health. They also suggest that eye movements and their different types can provide information on the emotional content of dreams.

 

Source

Eye movement patterns correlate with overt emotional behaviours in rapid eye movement sleep.

Maranci JB, Nigam M, Masset L, Msika EF, Vionnet MC, Chaumereil C, Vidailhet M, Leu-Semenescu S, Arnulf I. Sci Rep. 2022 Feb 2

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