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You are lying in the USI after a stroke. You have survived and now you rest, you recover and you are closely watched for four to seven days. At this point, you will be transferred to a rehab center to begin the arduous process of relearning movements and speeches. Stroke has seriously damaged your cerebral cortex, the largest and most recently developed region of the mammalian brain, necessary for all thoughts and actions associated with the human being. But if all this is wrong? And if neither rest nor your cortex do what we think they do? After an intuition, neuroscientists discovered unexpected resilience in rodent brains. When convalescence periods were reduced to only 48 hours after cortex injury and even part of the cortex was removed, the mice were able to perform tasks supposedly dependent on the part of the brain that was missing. And they performed better than mice who had three days or more of recovery time to allow the brain to revitalize and compensate for the lack of brain tissue. It is as if another part of the brain could simply perform complex tasks in case of resumption of normal activities within 48 hours. The results can change recovery protocols for brain trauma in humans, and change the way we think the cortex and what it does. Because something is happening in the brain of mice, which does not have much conventional meaning.
"We were looking for something else," says Randy Bruno, a neuroscientist at Columbia University's Zuckerman Brain Behavior Institute and lead author of the journal today. Nature. "In fact, it was just a control experience that we started doing. It was just a little mental health test before we started. One of the postdoctoral assistants working in Bruno's lab, Kate Hong noticed one day after surgery that the mice were on alert and grooming themselves. She thought, let's not wait, let's test them now. The timing of the experiment has made it different from the standard control experiments routinely performed by neuroscientists around the world. "It was very surprising," says Hong, the first author of the paper. She also notes that experience was a "control" that many other groups have already done. We did it a little differently, but the result was the opposite of what other groups had seen. And in "very surprising," Hong refers to the fact that "The animals we were studying were doing perfectly well without much of the cortex."
"The brain can repair itself or change its wiring so it can repair the damage," says Hong. The team decided to close the window in which mouse brains could reorganize after brain damage. "I've never seen people test this quickly. I think part of that is because they want animals to recover and instinctively it seems like you should let the animal rest and then they will do better. But in this case, it seems that the opposite is true. "
Place orders for mutant mice
To carry out this study, molecular biologists borrow a gene from bacteria that make a photosensitive protein and use it to genetically modify mice. This process produces a mutant strain of mice for scientific research called "transgenic mice". This occurs offsite. "There are nonprofit companies that have a library of different types of transgenic mice," says Hong. "They keep them and you can just order them."
The mice then have a piece of their skull replaced with a pane "literally a window in the brain," explains Bruno, describing a process called "optogenetics" where light is directed through the window to mutant mouse brains to activate or remove brain cells. .
The mice were placed in a black box and trained to search for objects with their whiskers. "Humans are probably the only mammals that do not have big facial whiskers," says Bruno.
Think of the domestic cat, a dog, a monkey. If you look at the whale hanging at the Natural History Museum, you will see that it has huge mustaches … Many mammals use their whiskers for a tactile sensation. We use our fingers … They move their whiskers as we move our fingertips. They actually palpate surfaces with them. They rub them. Their ability to distinguish textures, whether something is rough or smooth, or their ability to distinguish form, is really similar to our ability. If you measure this in a psychophysical way, what they can detect is about the same as ours. Even if we use the skin of the fingertips and they use these funny structures resembling hair, it turns out that the neural machinery is very similar … It's just a stiff hair. At the base of the mustache are all the different receptors that you find in your skin. So, all the things you use in your skin to distinguish texture and shape, and whether it's an object or [not]they all have the same nerve endings, except that the nerve endings wrap the bottom of the mustache.
During the experiment, if the mice in the dark box hit an object with their mustaches, they used their mouse paws to pull a lever and take a sip of water to quench their thirst.
The researchers then used the laser to temporarily cut the excitatory cells from the barrel cortex (the sensory cortex of the mouse). The laser light displaces the electrical ions in such a way as to block the excitatory cortical cells. "They are the [cells] that process a lot of information and send a lot of information around your brain or rodent brain to do any behavior. So we disable them directly, "says Bruno, adding:
This light will cross the tissues. The cortex is not very thick. Your cortex, the rodent's cortex, is about the thickness of a room. The light will pass through the cells. He will hit the cells at the top of the brain and he will hit the cells a little deeper into the cortex …. We hold a small light guide – just an optical fiber above the mouse's head, and the light passes through the glass, hits the cells and goes out.
The result: the mice could not whip anymore. They were also unable to perform the task the day after permanent removal of their sensory cortex. But 48 hours after removing the cortex, the mice fully recovered their ability to complete the task, as if nothing had happened. "It was a huge surprise, because he suggested that tactile sensations, such as whiskers-based touch, may not be completely dependent on the cortex," Hong said via the Zuckerman Institute press release. "These findings challenge the commonly cortex-centric view of how the brain directs the perception of touch."
The results not only raise questions about how best to rehabilitate patients after stroke or brain trauma, but also whether the subcortical primitive brain regions are more involved in cognitive and behavioral processes. This could recalibrate the GPS of the brain. field in a whole new direction of research.
"Rather than being limited to a particular brain region, sensory information is spread across many areas," Hong said in the press release. "This redundancy allows the brain to solve problems in many ways and can be used to protect the brain from injury."
The team had to determine whether there was a day of rest or re-exposure to the task at the origin of the spontaneous recovery. They therefore performed another phase of the experiment where they waited an extra day before re-exposing the mice to the test. Mice with three days of rest had incomplete and slower rehabilitation. The results indicate that exposure to activities on the second day, rather than day one or day three or later, is the ideal point for spontaneous recovery.
The intelligent part of the brain
The cerebral cortex is the "smart" part of the brain, the area where thought, perception, self-awareness, memories, language, mathematics, voluntary movement, social behavior, and other abundant cognitive functions are treated. . The cerebral cortex envelops the subcortical structures of the brain. Subcortical structures treat involuntary functions such as temperature regulation, heart rate, breathing, sleep, and emotional reactions such as fear and pleasure.
If some of your basic behaviors are not managed by the intelligent part of your brain, they are managed by the subcortical structures, it means that we have to think about how to rehabilitate the subcortical structure, rather than thinking to what we do for the cortex, "explains Bruno, who adds in a press release:" We tend to immobilize people who have suffered a stroke; Recovering seemingly simple tasks – walking, grasping – can be a long way. Our results suggest that, in some cases, patients may be reintroduced earlier in these activities to accelerate their recovery. "
What's really going on?
The brain has a miraculous ability to compensate for a deficit. This new research shows that relearning or rewiring may not be ideal, at least in rodents. If you expose the rodent to a task within 48 hours of the injury, there is no need to rewire it or re-learn it and recovery is better than when the brain rests, reconnects and re-learns. So what's going on?
We may not have damaged something necessary for the behavior, "says Bruno. "What we did was we disrupted the brain. There is something special to know about the cortex, which makes it difficult when you try to study how it works, namely that the cortex is the most connected, most connected thing in the brain. He talks to all the parts of your nervous system involved in the behavior … If you make a mistake and you see the behavioral changes, you have to ask yourself, "Have I just shown that the cortex is necessary for the behavior ? What about information about the task …? Is this the memory engram? [a memory engram, or memory trace, is a theoretical idea about how memories are stored in the brain.] I've basically removed connections from other parts of the brain. Have I just played with something that really does the work? "
The researchers note that damage to the dorsolateral striatum prevents behavioral recovery. The striatum is important for actions and habituation. This does not exclude the possibility that the animal is still in full cognitive recovery and simply unable to demonstrate it.
Bruno suspects that damaging or eliminating the cortex disrupts the rest of the brain, disrupting cognitive-behavioral "game" animals (including humans) every day. It may take about a day to recover and return to the game. Wait too long, the game is over or at least the rules change. "It's like a patient sitting at the USI for a week after a stroke. They do not play the game, "says Bruno. Throughout our history, this is not how things worked. "Our ancestors … they wandered everywhere, they had a brain injury, they had a stroke. I mean, I'm sure they did not do anything right away. They probably had to recover a little, but they had to continue to survive, is not it? He hesitates, warning that there is a study on mice and not humans. Yet speculation is a necessary part of science.
He keeps on:
There is an excellent quote from a researcher, 100 years ago, "The cortex is the whispering thing in the ear of all the subcortical structures." I do not quote it textually, but the idea is to do more sophisticated things. You need this new intelligent part of your brain, not to tell the subcortical structures what to do, but to bias them in certain ways, as our behaviors become more complex. So, depending on the context of what you were doing, [the cortex] could have pushed them in a slightly different direction.
Removing part of the cerebral cortex causes a "disturbance". What is a "disturbance"?
"Can I offer an analogy?" Asks Bruno.
When you write a letter or write a story, you sit in your chair and you write or tap, you create a story in your head. You write words, you know things about sentence structure, grammar and words. You put it all together. If I had to come and kick under the chair while you were writing, I would see you stop writing a little bit. I have not proven that the president is involved in the drafting process. I did not show that the chair had information about phrases, words or a story. All I have done is to disrupt the systems – you – who write. Of course, you will get up. You could shout at me first, but if you want to continue writing, you will do what you are going to do and you will continue to write. And I think that's what we saw here … The plasticity that I think goes hand in hand with relearning. I think the plasticity that is happening is [that] other areas adapt quickly. The subcortical structures, they adapt quickly to not hear all that background gossip that they usually hear from the cortex. It's a strange silence that they are suddenly confronted with.
This strange silence is the disturbance, the chair being expelled from below. It takes a day for the subcortical structures to find their bearings and return to the game.
Speculation and analogies are as important to neuroscience as they are to theoretical physics. Neuroscientists must use all their cognitive resources to try to find this alert and conscious body incredibly complex and still largely mysterious, perched above our shoulders.
I consider myself an inverted engineer, "says Bruno. "We're really trying to understand the system, the brain, as biologists, but also almost like a computer scientist or an electrical engineer – not that the brain is a computer – but we're really trying to separate it.
Oh, and another strange thing: bigger brain damage = better performance
Even more bizarre, the researchers noted that the larger the lesions on the cortex, the better the mice.
"It was a strange result," says Hong, who hesitates before adding: "I would not say we are convinced that if we [tested] many more animals than we would see. It was a kind of trend that we noticed. I guess the answer is we do not know. Basically, this implied that the less the cortex is active, the better the behavior of the animal and the cortex interferes in some way with the animal 's learning ability.
Bruno says that neuroscientists seriously joke that the intelligent part of the brain, which is the cortex in mice (and humans), may be overturning and that all this cerebral chatting is detrimental to learning and performance. . "What you might call" the thought of the mouse "… a lot of things in the cortex and cortex can interfere.
And after
You have to do a lot more research to completely unpack what's going on in the brains of these mice. And it remains to be seen if humans can experience similar spontaneous recovery. It may be that mice are more remarkable than we have ever thought. But the results change the scientific perspective a bit.
I think that part of what really struck me in this study was that we generally think of the brain as [pauses] we try to understand how this area is X, this area is Y. A lot of the field is focused on determining what that area is doing, "says Hong. "What this study really shows is that many parts of the brain can cooperate to do the same thing. So, if you really want to understand how the brain processes something as simple as touching, we really have to look at the whole brain and see all the pathways, all the components of the brain, how they interact to act on a behavior . "
Dr. Randy Bruno in his lab (left) and Dr. Kate Hong (right) discover spontaneous recovery from rodent trauma in rodents(left) John Abbott for Zuckerman Institute, Columbia University (right) Shane Verdi
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You are lying in the USI after a stroke. You have survived and now you rest, you recover and you are closely watched for four to seven days. At this point, you will be transferred to a rehab center to begin the arduous process of relearning movements and speeches. Stroke has seriously damaged your cerebral cortex, the largest and most recently developed region of the mammalian brain, necessary for all thoughts and actions associated with the human being. But if all this is wrong? And if neither rest nor your cortex do what we think they do? After an intuition, neuroscientists discovered unexpected resilience in rodent brains. When convalescence periods were reduced to only 48 hours after cortex injury and even part of the cortex was removed, the mice were able to perform tasks supposedly dependent on the part of the brain that was missing. And they performed better than mice who had three days or more of recovery time to allow the brain to revitalize and compensate for the lack of brain tissue. It is as if another part of the brain could simply perform complex tasks in case of resumption of normal activities within 48 hours. The results can change recovery protocols for brain trauma in humans, and change the way we think the cortex and what it does. Because something is happening in the brain of mice, which does not have much conventional meaning.
"We were looking for something else," says Randy Bruno, a neuroscientist at Columbia University's Zuckerman Brain Behavior Institute and lead author of the journal today. Nature. "In fact, it was just a control experience that we started doing. It was just a little mental health test before we started. One of the postdoctoral assistants working in Bruno's lab, Kate Hong noticed one day after surgery that the mice were on alert and grooming themselves. She thought, let's not wait, let's test them now. The timing of the experiment has made it different from the standard control experiments routinely performed by neuroscientists around the world. "It was very surprising," says Hong, the first author of the paper. She also notes that experience was a "control" that many other groups have already done. We did it a little differently, but the result was the opposite of what other groups had seen. And in "very surprising," Hong refers to the fact that "The animals we were studying were doing perfectly well without much of the cortex."
"The brain can repair itself or change its wiring so it can repair the damage," says Hong. The team decided to close the window in which mouse brains could reorganize after brain damage. "I've never seen people test this quickly. I think part of that is because they want animals to recover and instinctively it seems like you should let the animal rest and then they will do better. But in this case, it seems that the opposite is true. "
Place orders for mutant mice
To carry out this study, molecular biologists borrow a gene from bacteria that make a photosensitive protein and use it to genetically modify mice. This process produces a mutant strain of mice for scientific research called "transgenic mice". This occurs offsite. "There are nonprofit companies that have a library of different types of transgenic mice," says Hong. "They keep them and you can just order them."
The mice then have a piece of their skull replaced with a pane "literally a window in the brain," explains Bruno, describing a process called "optogenetics" where light is directed through the window to mutant mouse brains to activate or remove brain cells. .
The mice were placed in a black box and trained to search for objects with their whiskers. "Humans are probably the only mammals that do not have big facial whiskers," says Bruno.
Think of the domestic cat, a dog, a monkey. If you look at the whale hanging at the Natural History Museum, you will see that it has huge mustaches … Many mammals use their whiskers for a tactile sensation. We use our fingers … They move their whiskers as we move our fingertips. They actually palpate surfaces with them. They rub them. Their ability to distinguish textures, whether something is rough or smooth, or their ability to distinguish form, is really similar to our ability. If you measure this in a psychophysical way, what they can detect is about the same as ours. Even if we use the skin of the fingertips and they use these funny structures resembling hair, it turns out that the neural machinery is very similar … It's just a stiff hair. At the base of the mustache are all the different receptors that you find in your skin. So, all the things you use in your skin to distinguish texture and shape, and whether it's an object or [not]they all have the same nerve endings, except that the nerve endings wrap the bottom of the mustache.
During the experiment, if the mice in the dark box hit an object with their mustaches, they used their mouse paws to pull a lever and take a sip of water to quench their thirst.
The researchers then used the laser to temporarily cut the excitatory cells from the barrel cortex (the sensory cortex of the mouse). The laser light displaces the electrical ions in such a way as to block the excitatory cortical cells. "They are the [cells] that process a lot of information and send a lot of information around your brain or rodent brain to do any behavior. So we disable them directly, "says Bruno, adding:
This light will cross the tissues. The cortex is not very thick. Your cortex, the rodent's cortex, is about the thickness of a room. The light will pass through the cells. He will hit the cells at the top of the brain and he will hit the cells a little deeper into the cortex …. We hold a small light guide – just an optical fiber above the mouse's head, and the light passes through the glass, hits the cells and goes out.
The result: the mice could not whip anymore. They were also unable to perform the task the day after permanent removal of their sensory cortex. But 48 hours after removing the cortex, the mice fully recovered their ability to complete the task, as if nothing had happened. "It was a huge surprise, because he suggested that tactile sensations, such as whiskers-based touch, may not be completely dependent on the cortex," Hong said via the Zuckerman Institute press release. "These findings challenge the commonly cortex-centric view of how the brain directs the perception of touch."
The results not only raise questions about how best to rehabilitate patients after stroke or brain trauma, but also whether the subcortical primitive brain regions are more involved in cognitive and behavioral processes. This could recalibrate the GPS of the brain. field in a whole new direction of research.
"Rather than being limited to a particular brain region, sensory information is spread across many areas," Hong said in the press release. "This redundancy allows the brain to solve problems in many ways and can be used to protect the brain from injury."
The team had to determine whether there was a day of rest or re-exposure to the task at the origin of the spontaneous recovery. They therefore performed another phase of the experiment where they waited an extra day before re-exposing the mice to the test. Mice with three days of rest had incomplete and slower rehabilitation. The results indicate that exposure to activities on the second day, rather than day one or day three or later, is the ideal point for spontaneous recovery.
The intelligent part of the brain
The cerebral cortex is the "smart" part of the brain, the area where thought, perception, self-awareness, memories, language, mathematics, voluntary movement, social behavior, and other abundant cognitive functions are treated. . The cerebral cortex envelops the subcortical structures of the brain. Subcortical structures treat involuntary functions such as temperature regulation, heart rate, breathing, sleep, and emotional reactions such as fear and pleasure.
If some of your basic behaviors are not managed by the intelligent part of your brain, they are managed by the subcortical structures, it means that we have to think about how to rehabilitate the subcortical structure, rather than thinking to what we do for the cortex, "explains Bruno, who adds in a press release:" We tend to immobilize people who have suffered a stroke; Recovering seemingly simple tasks – walking, grasping – can be a long way. Our results suggest that, in some cases, patients may be reintroduced earlier in these activities to accelerate their recovery. "
What's really going on?
The brain has a miraculous ability to compensate for a deficit. This new research shows that relearning or rewiring may not be ideal, at least in rodents. If you expose the rodent to a task within 48 hours of the injury, there is no need to rewire it or re-learn it and recovery is better than when the brain rests, reconnects and re-learns. So what's going on?
We may not have damaged something necessary for the behavior, "says Bruno. "What we did was we disrupted the brain. There is something special to know about the cortex, which makes it difficult when you try to study how it works, namely that the cortex is the most connected, most connected thing in the brain. Il parle à toutes les parties de votre système nerveux impliquées dans le comportement… Si vous vous trompez et que vous voyez les changements de comportement, vous devez vous demander: «Est-ce que je viens de montrer que le cortex est nécessaire pour le comportement? Qu'il a des informations sur la tâche …? Est-ce que c'est l'engramme de la mémoire? [a memory engram, or memory trace, is a theoretical idea about how memories are stored in the brain.] J'ai fondamentalement enlevé des connexions d'autres parties du cerveau. Est-ce que je viens de jouer avec quelque chose qui fait vraiment le travail? "
Les chercheurs notent que les dommages au striatum dorsolatéral empêchent la récupération comportementale. Le striatum est important pour les actions et l'habituation. Cela n’exclut pas la possibilité que l’animal soit encore en pleine récupération cognitive et simplement incapable de le démontrer.
Bruno soupçonne que l’endommagement ou l’élimination du cortex perturbe le reste du cerveau, perturbant ainsi chaque jour les animaux de «jeu» cognitivo-comportementaux (y compris les humains). Cela peut prendre environ une journée pour récupérer du coup et revenir dans le jeu. Attendez trop longtemps, la partie est terminée ou au moins les règles changent. «C'est comme un patient assis à l'USI pendant une semaine après un accident vasculaire cérébral. Ils ne jouent pas le jeu », dit Bruno. Tout au long de notre histoire, ce n’est pas ainsi que les choses fonctionnaient. «Nos ancêtres… ils erraient partout, ils avaient une lésion cérébrale, ils avaient un accident vasculaire cérébral. Je veux dire, je suis sûr qu'ils n'ont rien fait tout de suite. Ils ont probablement dû récupérer un peu, mais ils ont dû continuer à survivre, n'est-ce pas? »Il hésite, avertissant qu'il s'agit d'une étude sur des souris et non des humains. Pourtant, la spéculation est une partie nécessaire de la science.
Il continue:
Il y a une excellente citation d'un chercheur, il y a 100 ans, «le cortex est la chose qui murmure à l'oreille de toutes les structures sous-corticales.» Je ne le cite pas textuellement, mais l'idée est de faire des choses plus sophistiquées. Vous avez besoin de cette nouvelle partie intelligente de votre cerveau, non pas pour dire aux structures sous-corticales quoi faire, mais pour les biaiser de certaines manières, car nos comportements deviennent plus complexes. Donc, en fonction du contexte de ce que vous faisiez, [the cortex] aurait pu les pousser dans une direction légèrement différente.
Enlever une partie du cortex cérébral provoque une «perturbation». Qu'est-ce qu'une «perturbation»?
«Puis-je offrir une analogie?» Demande Bruno.
Lorsque vous écrivez une lettre ou que vous écrivez une histoire, vous êtes assis sur votre chaise et vous écrivez ou vous tapez, vous créez un récit dans votre tête. Vous écrivez des mots, vous connaissez des choses sur la structure des phrases, la grammaire et les mots. Vous mettez tout cela ensemble. Si je devais venir et donner un coup de pied sous la chaise pendant que tu écrivais, je verrais que tu arrêterais d'écrire un peu. Je n'ai pas prouvé que le président est impliqué dans le processus de rédaction. Je n'ai pas montré que la chaise avait des informations sur des phrases, des mots ou une histoire. Tout ce que j'ai fait, c'est de perturber les systèmes – vous – qui écrivent. Bien sûr, vous allez vous lever. Vous pourriez crier sur moi en premier, mais si vous voulez continuer à écrire, vous ferez ce que vous allez faire et vous continuerez à écrire. Et je pense que c'est ce que nous avons vu ici… La plasticité que je pense va de pair avec le réapprentissage. Je pense que la plasticité qui se passe est [that] les autres zones s’adaptent rapidement. Les structures sous-corticales, elles s'adaptent rapidement pour ne pas entendre tout ce bavardage d'arrière-plan qu'elles ont l'habitude d'entendre du cortex. C'est un silence étrange auquel ils sont soudainement confrontés.
Ce silence étrange est la perturbation, la chaise étant expulsée de dessous. Il faut un jour aux structures sous-corticales pour se repérer et revenir dans le jeu.
La spéculation et les analogies sont aussi importantes pour les neurosciences que pour la physique théorique. Les neuroscientifiques doivent utiliser toutes leurs ressources cognitives pour essayer de trouver cet organe d'alerte et conscient incroyablement complexe et encore largement mystérieux, perché au-dessus de nos épaules.
Je me considère comme un ingénieur inversé », explique Bruno. «Nous essayons vraiment de comprendre le système, le cerveau, en tant que biologistes, mais aussi presque comme un informaticien ou un ingénieur en électricité – non pas que le cerveau soit un ordinateur – mais nous essayons vraiment de séparer la chose.
Oh et une autre chose étrange: de plus gros dégâts cérébraux = meilleures performances
Une chose encore plus bizarre, les chercheurs ont remarqué que plus les lésions sur le cortex étaient grandes, meilleures étaient les souris.
"C'était un résultat étrange", déclare Hong, qui hésite avant d'ajouter: "Je ne dirais pas que nous sommes convaincus que si nous [tested] beaucoup plus d'animaux que nous verrions. C'était une sorte de tendance que nous avons remarquée. Je suppose que la réponse est que nous ne savons pas. Fondamentalement, cela impliquait que moins le cortex est actif, meilleur est le comportement de l'animal et le cortex interfère d'une certaine manière avec la capacité d'apprentissage de l'animal.
Bruno dit que les neuroscientifiques plaisantent sérieusement que la partie intelligente du cerveau, qui est le cortex chez la souris (et l’homme), est peut-être en train de renverser et que tout ce bavardage cérébral nuit à l’apprentissage et aux performances. «Ce que vous pourriez appeler« la pensée de la souris »… beaucoup de choses dans le cortex et le cortex peuvent interférer.
What’s next
A lot more research is needed to fully unpack what’s happening in the brains of these mice. And it remains to be seen if humans can experience similar spontaneous recovery. It might simply turn out that mice are more remarkable than we ever thought. But the findings shift the scientific perspective a little.
I think part of what really struck me about this study was, we typically think of the brain as [pauses] we try to figure out how this area does X, this area does Y. A large part of the field is concentrated on figuring out, what does this one area do,” says Hong. “What this study really shows is that many different parts of the brain can cooperate to do the same thing. So if you really want to understand how the brain processes something even as simple as touch, we really need to look at the whole brain and see all of the pathways, all the brain components, how they interact with each other to mediate a behavior."
Dr. Randy Bruno in his Lab (left) and Dr. Kate Hong (right) discover spontaneous recovery after brain trauma in rodents(left) John Abbott for Columbia University’s Zuckerman Institute, (right) Shane Verdi
