- August 12, 2016
- Cardiff University
- Humans have evolved a disproportionately large brain as a result of sizing each other up in large cooperative social groups, researchers have proposed.
Humans have evolved a disproportionately large brain as a result of sizing each other up in large cooperative social groups, researchers have proposed.
A team led by computer scientists at Cardiff University suggest that the challenge of judging a person’s relative standing and deciding whether or not to cooperate with them has promoted the rapid expansion of human brain size over the last 2 million years.
In a study published in Scientific Reports, the team, which also includes leading evolutionary psychologist Professor Robin Dunbar from the University of Oxford, specifically found that evolution favors those who prefer to help out others who are at least as successful as themselves.
Lead author of the study Professor Roger Whitaker, from Cardiff University’s School of Computer Science and Informatics, said: “Our results suggest that the evolution of cooperation, which is key to a prosperous society, is intrinsically linked to the idea of social comparison — constantly sizing each up and making decisions as to whether we want to help them or not.
“We’ve shown that over time, evolution favors strategies to help those who are at least as successful as themselves.”
In their study, the team used computer modelling to run hundreds of thousands of simulations, or ‘donation games’, to unravel the complexities of decision-making strategies for simplified humans and to establish why certain types of behaviour among individuals begins to strengthen over time.
In each round of the donation game, two simulated players were randomly selected from the population. The first player then made a decision on whether or not they wanted to donate to the other player, based on how they judged their reputation. If the player chose to donate, they incurred a cost and the receiver was given a benefit. Each player’s reputation was then updated in light of their action, and another game was initiated.
Compared to other species, including our closest relatives, chimpanzees, the brain takes up much more body weight in human beings. Humans also have the largest cerebral cortex of all mammals, relative to the size of their brains. This area houses the cerebral hemispheres, which are responsible for higher functions like memory, communication and thinking.
The research team propose that making relative judgements through helping others has been influential for human survival, and that the complexity of constantly assessing individuals has been a sufficiently difficult task to promote the expansion of the brain over many generations of human reproduction.
Professor Robin Dunbar, who previously proposed the social brain hypothesis, said: “According to the social brain hypothesis, the disproportionately large brain size in humans exists as a consequence of humans evolving in large and complex social groups.
“Our new research reinforces this hypothesis and offers an insight into the way cooperation and reward may have been instrumental in driving brain evolution, suggesting that the challenge of assessing others could have contributed to the large brain size in humans.”
According to the team, the research could also have future implications in engineering, specifically where intelligent and autonomous machines need to decide how generous they should be towards each other during one-off interactions.
“The models we use can be executed as short algorithms called heuristics, allowing devices to make quick decisions about their cooperative behaviour,” Professor Whitaker said.
“New autonomous technologies, such as distributed wireless networks or driverless cars, will need to self-manage their behaviour but at the same time cooperate with others in their environment.”
- Roger M. Whitaker, Gualtiero B. Colombo, Stuart M. Allen, Robin I. M. Dunbar. A Dominant Social Comparison Heuristic Unites Alternative Mechanisms for the Evolution of Indirect Reciprocity. Scientific Reports, 2016; 6: 31459 DOI: 10.1038/srep31459
Juliana Cunha, 18.06.2016
Com 60 anos de carreira, 22.794 citações em periódicos, 60 premiações e 710 artigos publicados, Ivan Izquierdo, 78, é o neurocientista mais citado e um dos mais respeitados da América Latina. Nascido na Argentina, ele mora no Brasil há 40 anos e foi naturalizado brasileiro em 1981. Hoje coordena o Centro de Memória do Instituto do Cérebro da PUC-RS.
Suas pesquisas ajudaram a entender os diferentes tipos de memória e a desmistificar a ideia de que áreas específicas do cérebro se dedicariam de maneira exclusiva a um tipo de atividade.
Ele falou à Folha durante o Congresso Mundial do Cérebro, Comportamento e Emoções, que aconteceu esta semana, em Buenos Aires. Izquierdo foi o homenageado desta edição do congresso.
Na entrevista, o cientista fala sobre a utilidade de memórias traumáticas, sua descrença em métodos que prometem apagar lembranças e diz que a psicanálise foi superada pelos estudos de neurociência e funciona hoje como mero exercício estético.
|O neurocientista Ivan Izquierdo durante congresso em Buenos Aires|
Folha – É possível apagar memórias?
Ivan Izquierdo – É possível evitar que uma memória se expresse, isso sim. É normal, é humano, inclusive, evitar a expressão de certas lembranças. A falta de uso de uma determinada memória implica em desuso daquela sinapse, que aos poucos se atrofia.
Fora disso, não dá. Não existe uma técnica para escolher lembranças e então apagá-las, até porque a mesma informação é salva várias vezes no cérebro, por um mecanismo que chamamos de plasticidade. Quando se fala em apagamento de memórias é pirotecnia, são coisas midiáticas e cinematográficas.
O senhor trabalha bastante com memória do medo. Não apagá-las é uma pena ou algo a ser comemorado?
A memória do medo é o que nos mantém vivos. É a que pode ser acessada mais rapidamente e é a mais útil. Toda vez que você passa por uma situação de ameaça, a informação fundamental que o cérebro precisa guardar é que aquilo é perigoso. As pessoas querem apagar memórias de medo porque muitas vezes são desconfortáveis, mas, se não estivessem ali, nos colocaríamos em situações ruins.
Claro que esse processo causa enorme estresse. Para me locomover numa cidade, meu cérebro aciona inúmeras memórias de medo. Entre tê-las e não tê-las, prefiro tê-las, foram elas que me trouxeram até aqui, mas se pudermos reduzir nossa exposição a riscos, melhor. O problema muitas vezes é o estímulo, não a resposta do medo.
Mas algumas memórias de medo são paralisantes, e podem ser mais arriscadas do que a situação que evitam. Como lidar com elas?
Antes parado do que morto. O cérebro atua para nos preservar, essa é a prioridade. Claro que esse mecanismo é sujeito a falhas. Se entendemos que a resposta a uma memória de medo é exagerada, podemos tentar fazer com que o cérebro ressignifique um estímulo. É possível, por exemplo, expor o paciente repetidas vezes aos estímulos que criaram aquela memória, mas sem o trauma. Isso dissocia a experiência do medo.
Isso não seria parecido com o que Freud tentava fazer com as fobias?
Sim, Freud foi um dos primeiros a usar a extinção no tratamento de fobias, embora ele não acreditasse exatamente em extinção. Com a extinção, a memória continua, não é apagada, mas o trauma não está mais lá.
Mas muitos neurocientistas consideram Freud datado.
Toda teoria envelhece. Freud é uma grande referência, deu contribuições importantes. Mas a psicanálise foi superada pelos estudos em neurociência, é coisa de quando não tínhamos condições de fazer testes, ver o que acontecia no cérebro. Hoje a pessoa vai me falar em inconsciente? Onde fica? Sou cientista, não posso acreditar em algo só porque é interessante.
Para mim, a psicanálise hoje é um exercício estético, não um tratamento de saúde. Se a pessoa gosta, tudo bem, não faz mal, mas é uma pena quando alguém que tem um problema real que poderia ser tratado deixa de buscar um tratamento médico achando que psicanálise seria uma alternativa.
E outros tipos de análise que não a freudiana?
Terapia cognitiva, seguramente. Há formas de fazer o sujeito mudar sua resposta a um estímulo.
O senhor veio para o Brasil com a ditadura na Argentina. Agora, vivemos um processo no Brasil que alguns chamam de golpe, é uma memória em disputa. O que o senhor acha disso enquanto cientista?
Eu vim por conta de uma ameaça. Não considero um golpe, mas é um processo muito esperto. Mudar uma palavra ressignifica toda uma memória. Há de fato uma disputa de como essa memória coletiva vai ser construída. A esquerda usa o termo golpe para evocar memórias de medo de um país que já passou por um golpe. Conforme essa palavra é repetida, isso cria um efeito poderoso. Ainda não sabemos como essa memória será consolidada, mas a estratégia é muito esperta.
A jornalista JULIANA CUNHA viajou a convite do Congresso Mundial do Cérebro, Comportamento e Emoções
|Dr. Stephan Junek, Max Planck Institute for Brain Research|
|Estudo mostra que lagartos atingem padrão de sono que, em humanos, permite o surgimento de sonhos|
REINALDO JOSÉ LOPES
COLABORAÇÃO PARA A FOLHA
Será que os lagartos sonham com ovelhas escamosas? Ninguém ainda foi capaz de enxergar detalhadamente o que acontece no cérebro de tais bichos para que seja possível responder a essa pergunta, mas um novo estudo revela que o padrão de atividade cerebral típico dos sonhos humanos também surge nesses répteis quando dormem.
Trata-se do chamado sono REM (sigla inglesa da expressão “movimento rápido dos olhos”), que antes parecia ser exclusividade de mamíferos como nós e das aves. No entanto, a análise da atividade cerebral de um lagarto australiano, o dragão-barbudo (Pogona vitticeps), indica que, ao longo da noite, o cérebro do animal fica se revezando entre o sono REM e o sono de ondas lentas (grosso modo, o sono profundo, sem sonhos), num padrão parecido, ainda que não idêntico, ao observado em seres humanos.
Liderado por Gilles Laurent, do Instituto Max Planck de Pesquisa sobre o Cérebro, na Alemanha, o estudo está saindo na revista especializada “Science”. “Laurent não brinca em serviço”, diz Sidarta Ribeiro, pesquisador da UFRN (Universidade Federal do Rio Grande do Norte) e um dos principais especialistas do mundo em neurobiologia do sono e dos sonhos. “Foi feita uma demonstração bem clara do fenômeno.”
A metodologia usada para verificar o que acontecia no cérebro reptiliano não era exatamente um dragão de sete cabeças. Cinco exemplares da espécie receberam implantes de eletrodos no cérebro e, na hora de dormir, seu comportamento foi monitorado com câmeras infravermelhas, ideais para “enxergar no escuro”. Os animais costumavam dormir entre seis e dez horas por noite, num ciclo que podia ser mais ou menos controlado pelos cientistas do Max Planck, já que eles é que apagavam e acendiam as luzes e regulavam a temperatura do recinto.
O que os pesquisadores estavam medindo era a variação de atividade elétrica no cérebro dos dragões-barbudos durante a noite. São essas oscilações que produzem o padrão de ondas já conhecido a partir do sono de humanos e demais mamíferos, por exemplo.
Só foi possível chegar aos achados relatados no novo estudo por causa de seu nível de detalhamento, diz Suzana Herculano-Houzel, neurocientista da UFRJ (Universidade Federal do Rio de Janeiro) e colunista da Folha. “Estudos anteriores menos minuciosos não tinham como detectar sono REM porque, nesses animais, a alternância entre os dois tipos de sono é extremamente rápida, a cada 80 segundos”, explica ela, que já tinha visto Laurent apresentar os dados num congresso científico. Em humanos, os ciclos são bem mais lentos, com duração média de 90 minutos.
Além da semelhança no padrão de atividade cerebral, o sono REM dos répteis também tem correlação clara com os movimentos oculares que lhe dão o nome (os quais lembram vagamente a maneira como uma pessoa desperta mexe os olhos), conforme mostraram as imagens em infravermelho.
DORMIR, TALVEZ SONHAR
A primeira implicação das descobertas é evolutiva. Embora dormir seja um comportamento aparentemente universal no reino animal, o sono REM (e talvez os sonhos) pareciam exclusividade de espécies com cérebro supostamente mais complexo. “Para quem estuda os mecanismos do sono, é um estudo fundamental”, afirma Suzana.
Acontece que tanto mamíferos quanto aves descendem de grupos primitivos associados aos répteis, só que em momentos bem diferentes da história do planeta – mamíferos já caminhavam pela Terra havia dezenas de milhões de anos quando um grupo de pequenos dinossauros carnívoros deu origem às aves. Ou seja, em tese, mamíferos e aves precisariam ter “aprendido a sonhar” de forma totalmente independente. O achado “resolve esse paradoxo”, diz Ribeiro: o sono REM já estaria presente no ancestral comum de todos esses vertebrados.
O trabalho do pesquisador brasileiro e o de outros especialistas mundo afora tem mostrado que ambos os tipos de sono são fundamentais para “esculpir” memórias no cérebro, ao mesmo tempo fortalecendo o que é relevante e jogando fora o que não é importante. Sem os ciclos alternados de atividade cerebral, a capacidade de aprendizado de animais e humanos ficaria seriamente prejudicada.
Tanto Ribeiro quanto Suzana, porém, dizem que ainda não dá para cravar que lagartos ou outros animais sonham como nós. “Talvez um dia alguém faça ressonância magnética em lagartos adormecidos e veja se eles mostram a mesma reativação de áreas sensoriais que se vê em humanos em sono REM”, diz ela. “Claro que os donos de cachorro têm certeza que suas mascotes sonham, mas o ideal seria fazer a decodificação do sinal neural”, uma técnica que permite saber o que uma pessoa imagina estar vendo quando sonha e já foi aplicada com sucesso por cientistas japoneses.
- April 27, 2016
- For the first time, scientists have demonstrated that an organism devoid of a nervous system is capable of learning. Biologists have succeeded in showing that a single-celled organism, the protist, is capable of a type of learning called habituation. This discovery throws light on the origins of learning ability during evolution, even before the appearance of a nervous system and brain. It may also raise questions as to the learning capacities of other extremely simple organisms such as viruses and bacteria.
For the first time, scientists have demonstrated that an organism devoid of a nervous system is capable of learning. A team from the Centre de Recherches sur la Cognition Animale (CNRS/Université Toulouse III — Paul Sabatier) has succeeded in showing that a single-celled organism, the protist Physarum polycephalum, is capable of a type of learning called habituation. This discovery throws light on the origins of learning ability during evolution, even before the appearance of a nervous system and brain. It may also raise questions as to the learning capacities of other extremely simple organisms such as viruses and bacteria. These findings are published in the Proceedings of the Royal Society B on 27 April 2016.
An ability to learn, and memory are key elements in the animal world. Learning from experiences and adapting behavior accordingly are vital for an animal living in a fluctuating and potentially dangerous environment. This faculty is generally considered to be the prerogative of organisms endowed with a brain and nervous system. However, single-celled organisms also need to adapt to change. Do they display an ability to learn? Bacteria certainly show adaptability, but it takes several generations to develop and is more a result of evolution. A team of biologists thus sought to find proof that a single-celled organism could learn. They chose to study the protist, or slime mold, Physarum polycephalum, a giant cell that inhabits shady, cool areas and has proved to be endowed with some astonishing abilities, such as solving a maze, avoiding traps or optimizing its nutrition. But until now very little was known about its ability to learn.
During a nine-day experiment, the scientists thus challenged different groups of this mold with bitter but harmless substances that they needed to pass through in order to reach a food source. Two groups were confronted either by a “bridge” impregnated with quinine, or with caffeine, while the control group only needed to cross a non-impregnated bridge. Initially reluctant to travel through the bitter substances, the molds gradually realized that they were harmless, and crossed them increasingly rapidly — behaving after six days in the same way as the control group. The cell thus learned not to fear a harmless substance after being confronted with it on several occasions, a phenomenon that the scientists refer to as habituation. After two days without contact with the bitter substance, the mold returned to its initial behavior of distrust. Furthermore, a protist habituated to caffeine displayed distrustful behavior towards quinine, and vice versa. Habituation was therefore clearly specific to a given substance.
Habituation is a form of rudimentary learning, which has been characterized in Aplysia (an invertebrate also called sea hare). This form of learning exists in all animals, but had never previously been observed in a non-neural organism. This discovery in a slime mold, a distant cousin of plants, fungi and animals that appeared on Earth some 500 million years before humans, improves existing understanding of the origins of learning, which markedly preceded those of nervous systems. It also offers an opportunity to study learning types in other very simple organisms, such as viruses or bacteria.
 This single cell, which contains thousands of nuclei, can cover an area of around a square meter and moves within its environment at speeds that can reach 5 cm per hour.
 See “Even single-celled organisms feed themselves in a ‘smart’ manner.” https://www.sciencedaily.com/releases/2010/02/100210164712.htm
 Mild tactile stimulation of the animal’s siphon normally causes the defensive reflex of withdrawing the branchiae. If the harmless tactile stimulation is repeated, this reflex diminishes and finally disappears, thus indicating habituation.
- Romain P. Boisseau, David Vogel, Audrey Dussutour. Habituation in non-neural organisms: evidence from slime moulds. Proceedings of the Royal Society B: Biological Sciences, 2016; 283 (1829): 20160446 DOI: 10.1098/rspb.2016.0446
SOMETHING WAS WRONG with Kai Markram. At five days old, he seemed like an unusually alert baby, picking his head up and looking around long before his sisters had done. By the time he could walk, he was always in motion and required constant attention just to ensure his safety.
“He was super active, batteries running nonstop,” says his sister, Kali. And it wasn’t just boyish energy: When his parents tried to set limits, there were tantrums—not just the usual kicking and screaming, but biting and spitting, with a disproportionate and uncontrollable ferocity; and not just at age two, but at three, four, five and beyond. Kai was also socially odd: Sometimes he was withdrawn, but at other times he would dash up to strangers and hug them.
Things only got more bizarre over time. No one in the Markram family can forget the 1999 trip to India, when they joined a crowd gathered around a snake charmer. Without warning, Kai, who was five at the time, darted out and tapped the deadly cobra on its head.
Coping with such a child would be difficult for any parent, but it was especially frustrating for his father, one of the world’s leading neuroscientists. Henry Markram is the man behind Europe’s $1.3 billion Human Brain Project, a gargantuan research endeavor to build a supercomputer model of the brain. Markram knows as much about the inner workings of our brains as anyone on the planet, yet he felt powerless to tackle Kai’s problems.
“As a father and a neuroscientist, you realize that you just don’t know what to do,” he says. In fact, Kai’s behavior—which was eventually diagnosed as autism—has transformed his father’s career, and helped him build a radical new theory of autism: one that upends the conventional wisdom. And, ironically, his sideline may pay off long before his brain model is even completed.
Just to survive, you’d need to be excellent at detecting any pattern you could find in the frightful and oppressive noise. To stay sane, you’d have to control as much as possible, developing a rigid focus on detail, routine and repetition. Systems in which specific inputs produce predictable outputs would be far more attractive than human beings, with their mystifying and inconsistent demands and their haphazard behavior.
This, Markram and his wife, Kamila, argue, is what it’s like to be autistic.
They call it the “intense world” syndrome.
The behavior that results is not due to cognitive deficits—the prevailing view in autism research circles today—but the opposite, they say. Rather than being oblivious, autistic people take in too much and learn too fast. While they may appear bereft of emotion, the Markrams insist they are actually overwhelmed not only by their own emotions, but by the emotions of others.
Consequently, the brain architecture of autism is not just defined by its weaknesses, but also by its inherent strengths. The developmental disorder now believed to affect around 1 percent of the population is not characterized by lack of empathy, the Markrams claim. Social difficulties and odd behavior result from trying to cope with a world that’s just too much.
That, he thought, is what Kai experiences. The more he investigated the idea of autism not as a deficit of memory, emotion and sensation, but an excess, the more he realized how much he himself had in common with his seemingly alien son.
HENRY MARKRAM IS TALL, with intense blue eyes, sandy hair and the air of unmistakable authority that goes with the job of running a large, ambitious, well-funded research project. It’s hard to see what he might have in common with a troubled, autistic child. He rises most days at 4 a.m. and works for a few hours in his family’s spacious apartment in Lausanne before heading to the institute, where the Human Brain Project is based. “He sleeps about four or five hours,” says Kamila. “That’s perfect for him.”
As a small child, Markram says, he “wanted to know everything.” But his first few years of high school were mostly spent “at the bottom of the F class.” A Latin teacher inspired him to pay more attention to his studies, and when a beloved uncle became profoundly depressed and died young—he was only in his 30s, but “just went downhill and gave up”—Markram turned a corner. He’d recently been given an assignment about brain chemistry, which got him thinking. “If chemicals and the structure of the brain can change and then I change, who am I? It’s a profound question. So I went to medical school and wanted to become a psychiatrist.”
Markram attended the University of Cape Town, but in his fourth year of medical school, he took a fellowship in Israel. “It was like heaven,” he says, “It was all the toys that I ever could dream of to investigate the brain.” He never returned to med school, and married his first wife, Anat, an Israeli, when he was 26. Soon, they had their first daughter, Linoy, now 24, then a second, Kali, now 23. Kai came four years afterwards.
During graduate research at the Weizmann Institute in Israel, Markram made his first important discovery, elucidating a key relationship between two neurotransmitters involved in learning, acetylcholine and glutamate. The work was important and impressive—especially so early in a scientist’s career—but it was what he did next that really made his name.
During a postdoc with Nobel laureate Bert Sakmann at Germany’s Max Planck Institute, Markram showed how brain cells that “fire together, wire together.” That had been a basic tenet of neuroscience since the 1940s—but no one had been able to figure out how the process actually worked.
Measuring these fine temporal distinctions was also a technical triumph. Sakmann won his 1991 Nobel for developing the required “patch clamp” technique, which measures the tiny changes in electrical activity inside nerve cells. To patch just one neuron, you first harvest a sliver of brain, about 1/3 of a millimeter thick and containing around 6 million neurons, typically from a freshly guillotined rat.
To keep the tissue alive, you bubble it in oxygen, and bathe the slice of brain in a laboratory substitute for cerebrospinal fluid. Under a microscope, using a minuscule glass pipette, you carefully pierce a single cell. The technique is similar to injecting a sperm into an egg for in vitro fertilization—except that neurons are hundreds of times smaller than eggs.
It requires steady hands and exquisite attention to detail. Markram’s ultimate innovation was to build a machine that could study 12 such carefully prepared cells simultaneously, measuring their electrical and chemical interactions. Researchers who have done it say you can sometimes go a whole day without getting one right—but Markram became a master.
Still, there was a problem. He seemed to go from one career peak to another—a Fulbright at the National Institutes of Health, tenure at Weizmann, publication in the most prestigious journals—but at the same time it was becoming clear that something was not right in his youngest child’s head. He studied the brain all day, but couldn’t figure out how to help Kai learn and cope. As he told a New York Times reporter earlier this year, “You know how powerless you feel. You have this child with autism and you, even as a neuroscientist, really don’t know what to do.”
AT FIRST, MARKRAM THOUGHT Kai had attention deficit/ hyperactivity disorder (ADHD): Once Kai could move, he never wanted to be still. “He was running around, very difficult to control,” Markram says. As Kai grew, however, he began melting down frequently, often for no apparent reason. “He became more particular, and he started to become less hyperactive but more behaviorally difficult,” Markram says. “Situations were very unpredictable. He would have tantrums. He would be very resistant to learning and to any kind of instruction.”
Preventing Kai from harming himself by running into the street or following other capricious impulses was a constant challenge. Even just trying to go to the movies became an ordeal: Kai would refuse to enter the cinema or hold his hands tightly over his ears.
However, Kai also loved to hug people, even strangers, which is one reason it took years to get a diagnosis. That warmth made many experts rule out autism. Only after multiple evaluations was Kai finally diagnosed with Asperger syndrome, a type of autism that includes social difficulties and repetitive behaviors, but not lack of speech or profound intellectual disability.
“We went all over the world and had him tested, and everybody had a different interpretation,” Markram says. As a scientist who prizes rigor, this infuriated him. He’d left medical school to pursue neuroscience because he disliked psychiatry’s vagueness. “I was very disappointed in how psychiatry operates,” he says.
Over time, trying to understand Kai became Markram’s obsession.
It drove what he calls his “impatience” to model the brain: He felt neuroscience was too piecemeal and could not progress without bringing more data together. “I wasn’t satisfied with understanding fragments of things in the brain; we have to understand everything,” he says. “Every molecule, every gene, every cell. You can’t leave anything out.”
This impatience also made him decide to study autism, beginning by reading every study and book he could get his hands on. At the time, in the 1990s, the condition was getting increased attention. The diagnosis had only been introduced into the psychiatric bible, then the DSM III, in 1980. The 1988 Dustin Hoffman film Rain Man, about an autistic savant, brought the idea that autism was both a disability and a source of quirky intelligence into the popular imagination.
The dark days of the mid–20th century, when autism was thought to be caused by unloving “refrigerator mothers” who icily rejected their infants, were long past. However, while experts now agree that the condition is neurological, its causes remain unknown.
The most prominent theory suggests that autism results from problems with the brain’s social regions, which results in a deficit of empathy. This “theory of mind” concept was developed by Uta Frith, Alan Leslie, and Simon Baron-Cohen in the 1980s. They found that autistic children are late to develop the ability to distinguish between what they know themselves and what others know—something that other children learn early on.
In a now famous experiment, children watched two puppets, “Sally” and “Anne.” Sally has a marble, which she places in a basket and then leaves. While she’s gone, Anne moves Sally’s marble into a box. By age four or five, normal children can predict that Sally will look for the marble in the basket first because she doesn’t know that Anne moved it. But until they are much older, most autistic children say that Sally will look in the box because they know it’s there. While typical children automatically adopt Sally’s point of view and know she was out of the room when Anne hid the marble, autistic children have much more difficulty thinking this way.
This apparent social indifference was viewed as central to the condition. Unfortunately, the theory also seemed to imply that autistic people are uncaring because they don’t easily recognize that other people exist as intentional agents who can be loved, thwarted or hurt. But while the Sally-Anne experiment shows that autistic people have difficulty knowing that other people have different perspectives—what researchers call cognitive empathy or “theory of mind”—it doesn’t show that they don’t care when someone is hurt or feeling pain, whether emotional or physical. In terms of caring—technically called affective empathy—autistic people aren’t necessarily impaired.
Sadly, however, the two different kinds of empathy are combined in one English word. And so, since the 1980s, this idea that autistic people “lack empathy” has taken hold.
“When we looked at the autism field we couldn’t believe it,” Markram says. “Everybody was looking at it as if they have no empathy, no theory of mind. And actually Kai, as awkward as he was, saw through you. He had a much deeper understanding of what really was your intention.” And he wanted social contact.
Markram began to do autism work himself as visiting professor at the University of California, San Francisco in 1999. Colleague Michael Merzenich, a neuroscientist, proposed that autism is caused by an imbalance between inhibitory and excitatory neurons. A failure of inhibitions that tamp down impulsive actions might explain behavior like Kai’s sudden move to pat the cobra. Markram started his research there.
MARKRAM MET HIS second wife, Kamila Senderek, at a neuroscience conference in Austria in 2000. He was already separated from Anat. “It was love at first sight,” Kamila says.
Her parents left communist Poland for West Germany when she was five. When she met Markram, she was pursuing a master’s in neuroscience at the Max Planck Institute. When Markram moved to Lausanne to start the Human Brain Project, she began studying there as well.
Tall like her husband, with straight blonde hair and green eyes, Kamila wears a navy twinset and jeans when we meet in her open-plan office overlooking Lake Geneva. There, in addition to autism research, she runs the world’s fourth largest open-access scientific publishing firm, Frontiers, with a network of over 35,000 scientists serving as editors and reviewers. She laughs when I observe a lizard tattoo on her ankle, a remnant of an adolescent infatuation with The Doors.
When asked whether she had ever worried about marrying a man whose child had severe behavioral problems, she responds as though the question never occurred to her. “I knew about the challenges with Kai,” she says, “Back then, he was quite impulsive and very difficult to steer.”
The first time they spent a day together, Kai was seven or eight. “I probably had some blue marks and bites on my arms because he was really quite something. He would just go off and do something dangerous, so obviously you would have to get in rescue mode,” she says, noting that he’d sometimes walk directly into traffic. “It was difficult to manage the behavior,” she shrugs, “But if you were nice with him then he was usually nice with you as well.”
“Kamila was amazing with Kai,” says Markram, “She was much more systematic and could lay out clear rules. She helped him a lot. We never had that thing that you see in the movies where they don’t like their stepmom.”
At the Swiss Federal Institute of Technology in Lausanne (EPFL), the couple soon began collaborating on autism research. “Kamila and I spoke about it a lot,” Markram says, adding that they were both “frustrated” by the state of the science and at not being able to help more. Their now-shared parental interest fused with their scientific drives.
They started by studying the brain at the circuitry level. Markram assigned a graduate student, Tania Rinaldi Barkat, to look for the best animal model, since such research cannot be done on humans.
Barkat happened to drop by Kamila’s office while I was there, a decade after she had moved on to other research. She greeted her former colleagues enthusiastically.
She started her graduate work with the Markrams by searching the literature for prospective animal models. They agreed that the one most like human autism involved rats prenatally exposed to an epilepsy drug called valproic acid (VPA; brand name, Depakote). Like other “autistic” rats, VPA rats show aberrant social behavior and increased repetitive behaviors like excessive self-grooming.
But more significant is that when pregnant women take high doses of VPA, which is sometimes necessary for seizure control, studies have found that the risk of autism in their children increases sevenfold. One 2005 study found that close to 9 percent of these children have autism.
Because VPA has a link to human autism, it seemed plausible that its cellular effects in animals would be similar. A neuroscientist who has studied VPA rats once told me, “I see it not as a model, but as a recapitulation of the disease in other species.”
Barkat got to work. Earlier research showed that the timing and dose of exposure was critical: Different timing could produce opposite symptoms, and large doses sometimes caused physical deformities. The “best” time to cause autistic symptoms in rats is embryonic day 12, so that’s when Barkat dosed them.
At first, the work was exasperating. For two years, Barkat studied inhibitory neurons from the VPA rat cortex, using the same laborious patch-clamping technique perfected by Markram years earlier. If these cells were less active, that would confirm the imbalance that Merzenich had theorized.
She went through the repetitious preparation, making delicate patches to study inhibitory networks. But after two years of this technically demanding, sometimes tedious, and time-consuming work, Barkat had nothing to show for it.
“I just found no difference at all,” she told me, “It looked completely normal.” She continued to patch cell after cell, going through the exacting procedure endlessly—but still saw no abnormalities. At least she was becoming proficient at the technique, she told herself.
Markram was ready to give up, but Barkat demurred, saying she would like to shift her focus from inhibitory to excitatory VPA cell networks. It was there that she struck gold.
But what did this mean for autistic people? While Barkat was investigating the cortex, Kamila Markram had been observing the rats’ behavior, noting high levels of anxiety as compared to normal rats. “It was pretty much a gold mine then,” Markram says. The difference was striking. “You could basically see it with the eye. The VPAs were different and they behaved differently,” Markram says. They were quicker to get frightened, and faster at learning what to fear, but slower to discover that a once-threatening situation was now safe.
While ordinary rats get scared of an electrified grid where they are shocked when a particular tone sounds, VPA rats come to fear not just that tone, but the whole grid and everything connected with it—like colors, smells, and other clearly distinguishable beeps.
“The fear conditioning was really hugely amplified,” Markram says. “We then looked at the cell response in the amygdala and again they were hyper-reactive, so it made a beautiful story.”
THE MARKRAMS RECOGNIZED the significance of their results. Hyper-responsive sensory, memory and emotional systems might explain both autistic talents and autistic handicaps, they realized. After all, the problem with VPA rats isn’t that they can’t learn—it’s that they learn too quickly, with too much fear, and irreversibly.
They thought back to Kai’s experiences: how he used to cover his ears and resist going to the movies, hating the loud sounds; his limited diet and apparent terror of trying new foods.
“He remembers exactly where he sat at exactly what restaurant one time when he tried for hours to get himself to eat a salad,” Kamila says, recalling that she’d promised him something he’d really wanted if he did so. Still, he couldn’t make himself try even the smallest piece of lettuce. That was clearly overgeneralization of fear.
The Markrams reconsidered Kai’s meltdowns, too, wondering if they’d been prompted by overwhelming experiences. They saw that identifying Kai’s specific sensitivities preemptively might prevent tantrums by allowing him to leave upsetting situations or by mitigating his distress before it became intolerable. The idea of an intense world had immediate practical implications.
The VPA data also suggested that autism isn’t limited to a single brain network. In VPA rat brains, both the amygdala and the cortex had proved hyper-responsive to external stimuli. So maybe, the Markrams decided, autistic social difficulties aren’t caused by social-processing defects; perhaps they are the result of total information overload.
CONSIDER WHAT IT MIGHT FEEL like to be a baby in a world of relentless and unpredictable sensation. An overwhelmed infant might, not surprisingly, attempt to escape. Kamila compares it to being sleepless, jetlagged, and hung over, all at once. “If you don’t sleep for a night or two, everything hurts. The lights hurt. The noises hurt. You withdraw,” she says.
Unlike adults, however, babies can’t flee. All they can do is cry and rock, and, later, try to avoid touch, eye contact, and other powerful experiences. Autistic children might revel in patterns and predictability just to make sense of the chaos.
At the same time, if infants withdraw to try to cope, they will miss what’s known as a “sensitive period”—a developmental phase when the brain is particularly responsive to, and rapidly assimilates, certain kinds of external stimulation. That can cause lifelong problems.
Language learning is a classic example: If babies aren’t exposed to speech during their first three years, their verbal abilities can be permanently stunted. Historically, this created a spurious link between deafness and intellectual disability: Before deaf babies were taught sign language at a young age, they would often have lasting language deficits. Their problem wasn’t defective “language areas,” though—it was that they had been denied linguistic stimuli at a critical time. (Incidentally, the same phenomenon accounts for why learning a second language is easy for small children and hard for virtually everyone else.)
This has profound implications for autism. If autistic babies tune out when overwhelmed, their social and language difficulties may arise not from damaged brain regions, but because critical data is drowned out by noise or missed due to attempts to escape at a time when the brain actually needs this input.
The intense world could also account for the tragic similarities between autistic children and abused and neglected infants. Severely maltreated children often rock, avoid eye contact, and have social problems—just like autistic children. These parallels led to decades of blaming the parents of autistic children, including the infamous “refrigerator mother.” But if those behaviors are coping mechanisms, autistic people might engage in them not because of maltreatment, but because ordinary experience is overwhelming or even traumatic.
The Markrams teased out further implications: Social problems may not be a defining or even fixed feature of autism. Early intervention to reduce or moderate the intensity of an autistic child’s environment might allow their talents to be protected while their autism-related disabilities are mitigated or, possibly, avoided.
The VPA model also captures other paradoxical autistic traits. For example, while oversensitivities are most common, autistic people are also frequently under-reactive to pain. The same is true of VPA rats. In addition, one of the most consistent findings in autism is abnormal brain growth, particularly in the cortex. There, studies find an excess of circuits called mini-columns, which can be seen as the brain’s microprocessors. VPA rats also exhibit this excess.
Moreover, extra minicolumns have been found in autopsies of scientists who were not known to be autistic, suggesting that this brain organization can appear without social problems and alongside exceptional intelligence.
Like a high-performance engine, the autistic brain may only work properly under specific conditions. But under those conditions, such machines can vastly outperform others—like a Ferrari compared to a Ford.
THE MARKRAMS’ FIRST PUBLICATION of their intense world research appeared in 2007: a paper on the VPA rat in the Proceedings of the National Academy of Sciences. This was followed by an overview in Frontiers in Neuroscience. The next year, at the Society for Neuroscience (SFN), the field’s biggest meeting, a symposium was held on the topic. In 2010, they updated and expanded their ideas in a second Frontiers paper.
Since then, more than three dozen papers have been published by other groups on VPA rodents, replicating and extending the Markrams’ findings. At this year’s SFN, at least five new studies were presented on VPA autism models. The sensory aspects of autism have long been neglected, but the intense world and VPA rats are bringing it to the fore.
Nevertheless, reaction from colleagues in the field has been cautious. One exception is Laurent Mottron, professor of psychiatry and head of autism research at the University of Montreal. He was the first to highlight perceptual differences as critical in autism—even before the Markrams. Only a minority of researchers even studied sensory issues before him. Almost everyone else focused on social problems.
But when Mottron first proposed that autism is linked with what he calls “enhanced perceptual functioning,” he, like most experts, viewed this as the consequence of a deficit. The idea was that the apparently superior perception exhibited by some autistic people is caused by problems with higher level brain functioning—and it had historically been dismissed as mere“splinter skills,” not a sign of genuine intelligence. Autistic savants had earlier been known as “idiot savants,” the implication being that, unlike “real” geniuses, they didn’t have any creative control of their exceptional minds. Mottron described it this way in a review paper: “[A]utistics were not displaying atypical perceptual strengths but a failure to form global or high level representations.”
In fact, it has long been clear that detecting and manipulating complex systems is an autistic strength—so much so that the autistic genius has become a Silicon Valley stereotype. In May, for example, the German software firm SAP announced plans to hire 650 autistic people because of their exceptional abilities. Mathematics, musical virtuosity, and scientific achievement all require understanding and playing with systems, patterns, and structure. Both autistic people and their family members are over-represented in these fields, which suggests genetic influences.
“Our points of view are in different areas [of research,] but we arrive at ideas that are really consistent,” says Mottron of the Markrams and their intense world theory. (He also notes that while they study cell physiology, he images actual human brains.)
Because Henry Markram came from outside the field and has an autistic son, Mottron adds, “He could have an original point of view and not be influenced by all the clichés,” particularly those that saw talents as defects. “I’m very much in sympathy with what they do,” he says, although he is not convinced that they have proven all the details.
Mottron’s support is unsurprising, of course, because the intense world dovetails with his own findings. But even one of the creators of the “theory of mind” concept finds much of it plausible.
Simon Baron-Cohen, who directs the Autism Research Centre at Cambridge University, told me, “I am open to the idea that the social deficits in autism—like problems with the cognitive aspects of empathy, which is also known as ‘theory of mind’—may be upstream from a more basic sensory abnormality.” In other words, the Markrams’ physiological model could be the cause, and the social deficits he studies, the effect. He adds that the VPA rat is an “interesting” model. However, he also notes that most autism is not caused by VPA and that it’s possible that sensory and social defects co-occur, rather than one causing the other.
His collaborator, Uta Frith, professor of cognitive development at University College London, is not convinced. “It just doesn’t do it for me,” she says of the intense world theory. “I don’t want to say it’s rubbish,” she says, “but I think they try to explain too much.”
AMONG AFFECTED FAMILIES, by contrast, the response has often been rapturous. “There are elements of the intense world theory that better match up with autistic experience than most of the previously discussed theories,” says Ari Ne’eman, president of the Autistic Self Advocacy Network, “The fact that there’s more emphasis on sensory issues is very true to life.” Ne’eman and other autistic people fought to get sensory problems added to the diagnosis in DSM-5 — the first time the symptoms have been so recognized, and another sign of the growing receptiveness to theories like intense world.
Steve Silberman, who is writing a history of autism titled NeuroTribes: Thinking Smarter About People Who Think Differently, says, “We had 70 years of autism research [based] on the notion that autistic people have brain deficits. Instead, the intense world postulates that autistic people feel too much and sense too much. That’s valuable, because I think the deficit model did tremendous injury to autistic people and their families, and also misled science.”
Priscilla Gilman, the mother of an autistic child, is also enthusiastic. Her memoir, The Anti-Romantic Child, describes her son’s diagnostic odyssey. Before Benjamin was in preschool, Gilman took him to the Yale Child Study Center for a full evaluation. At the time, he did not display any classic signs of autism, but he did seem to be a candidate for hyperlexia—at age two-and-a-half, he could read aloud from his mother’s doctoral dissertation with perfect intonation and fluency. Like other autistic talents, hyperlexia is often dismissed as a “splinter” strength.
At that time, Yale experts ruled autism out, telling Gilman that Benjamin “is not a candidate because he is too ‘warm’ and too ‘related,’” she recalls. Kai Markram’s hugs had similarly been seen as disqualifying. At twelve years of age, however, Benjamin was officially diagnosed with Autism Spectrum Disorder.
According to the intense world perspective, however, warmth isn’t incompatible with autism. What looks like antisocial behavior results from being too affected by others’ emotions—the opposite of indifference.
Indeed, research on typical children and adults finds that too much distress can dampen ordinary empathy as well. When someone else’s pain becomes too unbearable to witness, even typical people withdraw and try to soothe themselves first rather than helping—exactly like autistic people. It’s just that autistic people become distressed more easily, and so their reactions appear atypical.
“The overwhelmingness of understanding how people feel can lead to either what is perceived as inappropriate emotional response, or to what is perceived as shutting down, which people see as lack of empathy,” says Emily Willingham. Willingham is a biologist and the mother of an autistic child; she also suspects that she herself has Asperger syndrome. But rather than being unemotional, she says, autistic people are “taking it all in like a tsunami of emotion that they feel on behalf of others. Going internal is protective.”
At least one study supports this idea, showing that while autistic people score lower on cognitive tests of perspective-taking—recall Anne, Sally, and the missing marble—they are more affected than typical folks by other people’s feelings. “I have three children, and my autistic child is my most empathetic,” Priscilla Gilman says, adding that when her mother first read about the intense world, she said, “This explains Benjamin.”
Because he has musical training and a high IQ, Benjamin can use his own sense of “absolute pitch”—the ability to name a note without hearing another for comparison—to define the problem he’s having. But many autistic people can’t verbalize their needs like this. Kai, too, is highly sensitive to vocal intonation, preferring his favorite teacher because, he explains, she “speaks soft,” even when she’s displeased. But even at 19, he isn’t able to articulate the specifics any better than that.
ON A RECENT VISIT to Lausanne, Kai wears a sky blue hoodie, his gray Chuck Taylor–style sneakers carefully unlaced at the top. “My rapper sneakers,” he says, smiling. He speaks Hebrew and English and lives with his mother in Israel, attending a school for people with learning disabilities near Rehovot. His manner is unselfconscious, though sometimes he scowls abruptly without explanation. But when he speaks, it is obvious that he wants to connect, even when he can’t answer a question. Asked if he thinks he sees things differently than others do, he says, “I feel them different.”
He waits in the Markrams’ living room as they prepare to take him out for dinner. Henry’s aunt and uncle are here, too. They’ve been living with the family to help care for its newest additions: nine-month-old Charlotte and Olivia, who is one-and-a-half years old.
“It’s our big patchwork family,” says Kamila, noting that when they visit Israel, they typically stay with Henry’s ex-wife’s family, and that she stays with them in Lausanne. They all travel constantly, which has created a few problems now and then. None of them will ever forget a tantrum Kai had when he was younger, which got him barred from a KLM flight. A delay upset him so much that he kicked, screamed, and spat.
Now, however, he rarely melts down. A combination of family and school support, an antipsychotic medication that he’s been taking recently, and increased understanding of his sensitivities has mitigated the disabilities Kai associated with his autism.
As the Markrams see it, if autism results from a hyper-responsive brain, the most sensitive brains are actually the most likely to be disabled by our intense world. But if autistic people can learn to filter the blizzard of data, especially early in life, then those most vulnerable to the most severe autism might prove to be the most gifted of all.
Markram sees this in Kai. “It’s not a mental retardation,” he says, “He’s handicapped, absolutely, but something is going crazy in his brain. It’s a hyper disorder. It’s like he’s got an amplification of many of my quirks.”
One of these involves an insistence on timeliness. “If I say that something has to happen,” he says, “I can become quite difficult. It has to happen at that time.”
He adds, “For me it’s an asset, because it means that I deliver. If I say I’ll do something, I do it.” For Kai, however, anticipation and planning run wild. When he travels, he obsesses about every move, over and over, long in advance. “He will sit there and plan, okay, when he’s going to get up. He will execute. You know he will get on that plane come hell or high water,” Markram says. “But he actually loses the entire day. It’s like an extreme version of my quirks, where for me they are an asset and for him they become a handicap.”
If this is true, autistic people have incredible unrealized potential. Say Kai’s brain was even more finely tuned than his father’s, then it might give him the capacity to be even more brilliant. Consider Markram’s visual skills. Like Temple Grandin, whose first autism memoir was titled Thinking In Pictures, he has stunning visual abilities. “I see what I think,” he says, adding that when he considers a scientific or mathematical problem, “I can see how things are supposed to look. If it’s not there, I can actually simulate it forward in time.”
At the offices of Markram’s Human Brain Project, visitors are given a taste of what it might feel like to inhabit such a mind. In a small screening room furnished with sapphire-colored, tulip-shaped chairs, I’m handed 3-D glasses. The instant the lights dim, I’m zooming through a brightly colored forest of neurons so detailed and thick that they appear to be velvety, inviting to the touch.
Critics of the intense world theory are dismayed and put off by this idea of hidden talent in the most severely disabled. They see it as wishful thinking, offering false hope to parents who want to see their children in the best light and to autistic people who want to fight the stigma of autism. In some types of autism, they say, intellectual disability is just that.
“The maxim is, ‘If you’ve seen one person with autism, you’ve seen one person with autism,’” says Matthew Belmonte, an autism researcher affiliated with the Groden Center in Rhode Island. The assumption should be that autistic people have intelligence that may not be easily testable, he says, but it can still be highly variable.
He adds, “Biologically, autism is not a unitary condition. Asking at the biological level ‘What causes autism?’ makes about as much sense as asking a mechanic ‘Why does my car not start?’ There are many possible reasons.” Belmonte believes that the intense world may account for some forms of autism, but not others.
Kamila, however, insists that the data suggests that the most disabled are also the most gifted. “If you look from the physiological or connectivity point of view, those brains are the most amplified.”
The question, then, is how to unleash that potential.
“I hope we give hope to others,” she says, while acknowledging that intense-world adherents don’t yet know how or even if the right early intervention can reduce disability.
The secret-ability idea also worries autistic leaders like Ne’eman, who fear that it contains the seeds of a different stigma. “We agree that autistic people do have a number of cognitive advantages and it’s valuable to do research on that,” he says. But, he stresses, “People have worth regardless of whether they have special abilities. If society accepts us only because we can do cool things every so often, we’re not exactly accepted.”
The MARKRAMS ARE NOW EXPLORING whether providing a calm, predictable early environment—one aimed at reducing overload and surprise—can help VPA rats, soothing social difficulties while nurturing enhanced learning. New research suggests that autism can be detected in two-month-old babies, so the treatment implications are tantalizing.
So far, Kamila says, the data looks promising. Unexpected novelty seems to make the rats worse—while the patterned, repetitive, and safe introduction of new material seems to cause improvement.
In humans, the idea would be to keep the brain’s circuitry calm when it is most vulnerable, during those critical periods in infancy and toddlerhood. “With this intensity, the circuits are going to lock down and become rigid,” says Markram. “You want to avoid that, because to undo it is very difficult.”
For autistic children, intervening early might mean improvements in learning language and socializing. While it’s already clear that early interventions can reduce autistic disability, they typically don’t integrate intense-world insights. The behavioral approach that is most popular—Applied Behavior Analysis—rewards compliance with “normal” behavior, rather than seeking to understand what drives autistic actions and attacking the disabilities at their inception.
Research shows, in fact, that everyone learns best when receiving just the right dose of challenge—not so little that they’re bored, not so much that they’re overwhelmed; not in the comfort zone, and not in the panic zone, either. That sweet spot may be different in autism. But according to the Markrams, it is different in degree, not kind.
Markram suggests providing a gentle, predictable environment. “It’s almost like the fourth trimester,” he says.
“To prevent the circuits from becoming locked into fearful states or behavioral patterns you need a filtered environment from as early as possible,” Markram explains. “I think that if you can avoid that, then those circuits would get locked into having the flexibility that comes with security.”
IN SCIENCE, CONFIRMATION BIAS is always the unseen enemy. Having a dog in the fight means you may bend the rules to favor it, whether deliberately or simply because we’re wired to ignore inconvenient truths. In fact, the entire scientific method can be seen as a series of attempts to drive out bias: The double-blind controlled trial exists because both patients and doctors tend to see what they want to see—improvement.
At the same time, the best scientists are driven by passions that cannot be anything but deeply personal. The Markrams are open about the fact that their subjective experience with Kai influences their work.
But that doesn’t mean that they disregard the scientific process. The couple could easily deal with many of the intense world critiques by simply arguing that their theory only applies to some cases of autism. That would make it much more difficult to disprove. But that’s not the route they’ve chosen to take. In their 2010 paper, they list a series of possible findings that would invalidate the intense world, including discovering human cases where the relevant brain circuits are not hyper-reactive, or discovering that such excessive responsiveness doesn’t lead to deficiencies in memory, perception, or emotion. So far, however, the known data has been supportive.
But whether or not the intense world accounts for all or even most cases of autism, the theory already presents a major challenge to the idea that the condition is primarily a lack of empathy, or a social disorder. Intense world theory confronts the stigmatizing stereotypes that have framed autistic strengths as defects, or at least as less significant because of associated weaknesses.
And Henry Markram, by trying to take his son Kai’s perspective—and even by identifying so closely with it—has already done autistic people a great service, demonstrating the kind of compassion that people on the spectrum are supposed to lack. If the intense world does prove correct, we’ll all have to think about autism, and even about typical people’s reactions to the data overload endemic in modern life, very differently.
Foi publicado hoje na revista científica PLOS ONE artigo com os resultados de nosso estudo neurocientífico sobre a ayahuasca. Fruto de pouco mais de quatro anos de intenso e dedicado trabalho, a pesquisa foi conduzida na UNIFESP com financiamento da FAPESP, com cooperações na USP, UFABC, Louisiana State University (EUA) e da University of Auckland (Nova Zelândia). Além da colaboração da União do Vegetal que nos forneceu Hoasca para fins de pesquisa, e de 20 bravos(as) psiconautas experientes no uso da bebida amazônica. Nossos(as) voluntários(as) se disponibilizaram a participar de um processo em um ambiente e com uma proposta que difere em muito dos usos tradicionais, e era bastante desafiadora. Beberam ayahuasca num laboratório universitário, sem canto nem palo santo, sem reza, dança ou fogueira, no meio da conturbada metrópole paulista. E tiveram que usar uma touca que gravava a atividade elétrica de seus cérebros continuamente num notebook próximo a elas. Sentadas em uma poltrona confortável, doaram pequenas quantidades de sangue a cada 25 minutos. Apesar de não ter a fundamental condução dos guias, curandeiros, mestres ou maestros, que fazem trabalhos tão importantes quanto a bebida em si, e de tomarem ayahuasca uma pessoa por vez, foram acompanhados com carinho e cuidado pela equipe científica, nunca sendo deixados sozinhos ou desamparados, e sempre com os baldinhos à disposição… Tudo isso em prol da colaboração dos saberes tradicionais com os saberes científicos e tecnológicos.Uma pesquisa desse tipo se justifica por várias razões, desde um entendimento mais profundo sobre nossa resposta fisiológica aos compostos químicos presentes na ayahuasca, que nos fornece dados cruciais sobre potenciais terapêuticos e segurança de uso; até informações mais sofisticadas sobre as relações entre cérebro e consciência, o chamado “hard-problem”. Com os resultados dessa jornada aprofundamos e expandimos o conhecimento sobre os efeitos dos componentes moleculares da bebida sagrada, sobre como nossos corpos recebem estas moléculas e que efeitos elas ajudam a desencadear, especialmente no cérebro. Ao minimizarmos as intervenções biomédicas somente ao estritamente necessário e ao adotarmos uma postura observacional, deixando e encorajando que os voluntários passassem a maior parte do tempo de olhos fechados em estado introspectivo, pudemos revelar uma imagem fascinante sobre os efeitos da ayahuasca no cérebro. Este efeito ocorre em duas fases qualitativamente distintas e este perfil bifásico ajuda a explicar contradições de estudos semelhantes feitos anteriormente por outras equipes. Com isso abrimos mais portas para fascinantes investigações futuras sobre os diversos estados de consciência que podem ser alcançados com a bebida amazônica.
Cerca de uma hora após a ingestão da ayahuasca, ocorreram diminuições das ondas alfa (8 a 12 ciclos por segundo), especialmente no córtex temporo-parietal, com uma certa tendência de lateralização para o hemisfério esquerdo. A segunda fase ocorre cerca de uma hora depois (ou seja, cerca de duas horas após a ingestão) e enquanto as ondas alfa foram retornando a um padrão parecido com o que estava antes da ingestão da ayahuasca, os ritmos gama, de frequências muito altas (30 a 100 ciclos por segundo), se intensificaram por quase todo o córtex cerebral, incluindo o córtex frontal. Estas oscilações elétricas em distintas frequências, que ocorrem perpetuamente e simultaneamente em todo o cérebro, são resultado da complexa interação da atividade de bilhões de células cerebrais. E estão relacionadas com todas as funções do cérebro, inclusive os aspectos psicológicos e os estados de consciência. Por exemplo, durante o sono profundo predomina no córtex cerebral uma frequência lenta, de 1 a 4 ciclos por segundo, chamada delta. Enquanto durante a maioria dos sonhos, predomina a frequência teta (4 a 8 ciclos por segundo). Ao caracterizar as principais mudanças nestas frequências de oscilações neurais avançamos na criação de um mapa neurocientífico sobre o estado de consciência desencadeado pela ingestão de ayahuasca.
Há variadas nuances de interpretação para estes dados (e muitos estudos posteriores que podem ser feitos de acordo com cada interpretação, para testas hipóteses específicas). Mas a minha favorita e que discutimos no artigo é de que o ritmo alfa é resultado de atividades inibitórias no cérebro, e o ritmo gama representa atividade neural crucial para a consciência. Quando fechamos os olhos e temos a sensacao de um campo visual escuro, sem imagens, o ritmo alfa se fortalece nas regiões do cérebro que recebem estímulos vindos dos olhos. Ou seja, quando estamos de olhos fechados não apenas a informação que chega dos olhos está ausente, mas as áreas visuais são inibidas por “centros superiores” do córtex, capazes de modular a atividade de áreas sensoriais. E nós temos a experiência subjetiva de um mundo escuro e de ausência de visão. No caso da ayahuasca, encontramos um enfraquecimento dessa inibição em áreas multisensoriais. Ou seja, regiões que estão envolvidas não só com visão, mas com audição, tato, paladar, olfato e também com sensações corpóreas das mais diversas. Faz sentido portanto que esta diminuição de alfa esteja relacionada com o efeito tão comum de experiência de mais sensações e mais estímulos durante o efeito da ayahuasca quando comparado com o estado ordinário de consciência, incluindo as famosas visões de olhos fechados. Já o acelerado gama está relacionado com o que se chama na neurociência de integração. Enquanto áreas diversas do cérebro estão relacionadas a percepções subjetivas distintas, como os cinco sentidos mencionados acima, nossa experiência consciente é unificada. Essa unificação de atividades neurais em áreas anatomicamente distintas ocorre nas oscilações rápidas na frequência gama, que permitem ao cérebro temporariamente juntar as peças de um complexo quebra cabeças de atividade neural. Esse aumento de gama pode ajudar a explicar porque durante a ayahuasca a percepção de sons e imagens, por exemplo, parece se fundir e criar relações peculiares, não perceptíveis durante a consciência ordinária, quando o cérebro tende a organizar a atividade neural relacionada aos cinco sentidos de maneira parcialmente independente. Essa função do gama em unificar ou integrar informações no cérebro é conhecida de longa data, pelo menos desde a obra pioneira do cientista Chileno Francisco Varela. E foi observada em dois indíviduos após tomarem ayahuasca em trabalho do antropólogo Luis Eduardo Luna e colaboradores há uma década. Ao confirmarmos os dados de Luna e colaboradores com nova e mais rigorosa metodologia, com mais pessoas e ao detectarmos a combinação destes efeitos com as reduções em alfa, abrimos portas importantíssimas no entendimento não só dos estados não-ordinários de consciência, mas da teoria neurocientifica sobre a consciência como um todo. Um exemplo é uma teoria proposta recentemente sobre a ação dos psicodélicos que sugere que uma das características principais do cérebro durante o efeito de psicodélicos sejam intensificações do gama. Para Andrew Gallimore, do Japão, que se baseia na influente teoria da informacao integrada, ou IIT (integrated information theory), a mais promissora teoria neurocientífica sobre a consciência, a expansão da consciência com psicodélicos é mesmo possível dentro de uma perspectiva neurocientífica, e provavelmente depende do ritmo gama. Esta expansão da consciência inclui a percepção subjetiva de mais conteúdo, de maior intensidade, incluindo fusões entre os sentidos e possivelmente a experiência subjetiva de intensidades e qualidades não perceptíveis durante a consciência ordinária, como cores mais vívidas e brilhantes e estados emocionais mais intensos do que jamais experienciados fora do estado psicodélico. O gama também tem papel fundamental na teoria da consciência proposta pelo matemático Sir Roger Penrose e pelo anestesiologista Stuart Hameroff. Segundo a teoria deles, oscilações na faixa de 40 ciclos por segundo seriam importantes ao permitir reverberações menores e muito mais aceleradas nos microtúbulos, uma rede de fibras e filamentos que percorre todas as células do nosso corpo – e do cérebro.
Ademais de caracterizar as oscilações e regiões corticais mais importantes no processo neural relacionado à modificação da consciência durante a ayahuasca, fizemos coletas periódicas de sangue para quantificar os princípios ativos da ayahuasca e seus metabólitos. E encontramos que durante a primeira fase a concentração da DMT e da harmina estavam próximas do máximo, sendo que na segunda fase acontecem os picos de harmalina e tetrahidroharmina. Com uma análise estatística sofisticada e inédita, desenvolvida especialmente para este estudo, demonstramos que este efeito bifásico no cérebro esta relacionado à concentração sanguínea de vários componentes do chá. Isto expande a visão científica predominante que foca apenas na famosa DMT. De acordo com este modelo, o papel do cipó é apenas de inibir a digestão da DMT. Mas “ayahuasca” é um dos muitos nomes não só da bebida, mas do cipó jagube ou mariri, catalogado nos anais científicos como Banisteriopsis caapi. Isto revela que, para os povos tradicionais, é o cipó a planta mais importante. E de fato há preparações de ayahuasca feitas somente com o cipó, sem qualquer outra planta. Mas na farmacologia esse quadro foi invertido, dando-se ênfase na psicoatividade da DMT apenas, que não vem do cipó, mas de outras plantas que frequentemente são adicionadas no preparo da bebida, como a rainha no Brasil e Peru (Psychotria viridis) ou a chagropanga na Colômbia (Dyplopteris cabrerana). Mas nossa análise com 10 moléculas (DMT, NMT e DMT-NO; Harmina e harmol; Harmalina e harmalol; THH e THH-OH e também o metabólito serotonérgico IAA) revelou associações importantes entre níveis plasmáticos de DMT, harmina, harmalina e tetraidroharmina, bem como alguns metabólitos como a DMT-NO, e os efeitos cerebrais em alfa e gama em momentos distintos da experiência. Revelamos portanto que a psicoatividade da ayahuasca não pode ser totalmente explicada apenas pelas concentrações de DMT, dando um passo importante para reaproximar o saber científico dos saberes tradicionais.
Descobrimos ainda que a concentração de harmalina (e apenas de harmalina) está correlacionada com o momento em que os voluntários(as) vomitaram. Ou seja, a harmalina desempenha um papel fundamental tanto no cérebro, estando relacionada a intensificação das ondas gama, mas também nos efeitos periféricos da ayahuasca, como o vômito. Isso reforça a idéia de que o vômito tem relações importantes com a experiência psicológica, sendo talvez mais apropriado chamá-lo de purga, termo que reforça a idéia de que ocorre uma associação entre físico e psicológico neste momento da experiência. Esses resultados sobre a harmalina também dão nova importância para as pesquisas pioneiras de Claudio Naranjo, terapeuta Chileno que foi um dos primeiros a estudar ayahuasca desde um ponto de vista médico-científico, nos anos 60. A proposta de Naranjo, de que a harmalina era o principal componente psicoativo da ayahuasca foi, entretanto, quase que totalmente esquecida em prol do foco na DMT a partir dos anos 80. Outro fator importante contra a proposta de Naranjo é que as concentrações de harmalina na ayahuasca são em geral abaixo das doses de harmalina que, sozinha, desencadeiam efeitos psicoativos nítidos, conforme relato subjetivo das pessoas que ingeriram harmalina nos estudos de Naranjo. Mas nunca foi testado o efeito da harmalina combinada com a harmina e a tetraidroharmina, como ocorre na ayahuasca. E então nossos resultados reforçam a idéia de que a harmalina também pode ter contribuições importantes no efeito psicoativo da ayahuasca quando em combinação com as outras beta-carbolinas vindas do cipó. Interessantemente, em quase todos os casos a purga ocorreu após a primeira fase, quando os níveis de DMT estão próximos do máximo que atingem no sangue. Como a elevação da concentração de harmalina no sangue é mais lenta que da DMT e da harmina, vomitar pouco interfere nos efeitos da primeira fase e nas concentrações destas duas moléculas, e ajuda a explicar porque mesmo quem vomita rápido pode ter experiências fortes e profundas. Mas vomitar potencialmente interfere nas concentrações de tetraidroharmina, que é a molécula cujas concentrações sobem mais lentamente, e pode permanecer em circulação por alguns dias, dependendo da capacidade de metabolização de cada indivíduo.
Importante notar ainda que o perfil bifásico foi observado com ingestão de apenas um copo (mas com uma dose grande). Mas sabemos que nos usos rituais é muito frequente os participantes tomarem mais de uma dose, com intervalo de uma hora ou mais. É possível então que nestes casos ocorram variadas combinações de efeitos, como por exemplo a segunda fase de uma primeira dose (aumento de gama) coincidir com a primeira fase de uma segunda dose (diminuição de alfa). Isso potencialmente geraria estados cerebrais (e por correlação, estados de consciência) não observados na pesquisa com apenas uma dose. Isto ajuda a entender porque muitas pessoas relatam que a segunda dose é sempre uma “caixinha de surpresas”, e não apenas a intensificação ou prolongação dos efeitos da primeira toma. Ao depender do perfil metabólico de cada pessoa, do tamanho de cada dose, da proporção destas moléculas na bebida e do intervalo entre elas, pode-se atingir outros estados mesclados entre as duas fases observadas na pesquisa. Some-se a isto as influências ambientais, psicológicas, motivacionais e espirituais e temos uma prática de exploração da consciência que não cabe numa resposta simples e singular sobre qual “o efeito” da ayahuasca.
Do ponto de vista neurocientífico, estas possíveis combinações são muito intrigantes, porque relações entre as frequências alfa e gama no córtex parietal e no frontal estão envolvidas em processos de reavaliação psicológica e emocional. Ou seja, quando fazemos certas formas de introspecção que resultam em ressignificação de eventos emocionais de nossas vidas, estas áreas do cérebro se comunicam através de oscilações elétricas nestas duas faixas de frequência. E estas mesmas frequências e áreas cerebrais estão envolvidas em processos criativos de resolução de problemas. Ou seja, através de nossa pesquisa, a neurociência começa a convergir com o saber ancestral ao reafirmar o potencial da ayahuasca em nutrir a criatividade e o autoconhecimento, facilitando formas de terapia focadas no potencial de cada indíviduo em crescer e se desenvolver de maneira consciente.
Para saber mais, confira abaixo minha palestra na World Ayahuasca Confrence, em Ibiza ano passado (disponível com legendas em português e inglês). Ou ainda a mais antiga “Ayahuasca e as ondas cerebrais“, realizada no Brasil no início deste projeto. Ou se você quer mesmo mergulhar fundo, acesse gratuitamente o artigo científico na íntegra.
Referência: Schenberg EE, Alexandre JFM, Filev R, Cravo AM, Sato JR, Muthukumaraswamy SD, et al. (2015) Acute Biphasic Effects of Ayahuasca. PLoS ONE 10(9): e0137202. doi:10.1371/journal.pone.0137202
Março de 2015
Pode uma planta ser inteligente? Alguns cientistas insistem que são – uma vez que elas podem sentir, aprender, lembrar e até mesmo reagir de formas que seriam familiares aos seres humanos. A nova pesquisa está num campo chamado neurobiologia de plantas – o que é meio que um equívoco, porque mesmo os cientistas desta área não argumentam que as plantas tenham neurónios ou cérebros.
“Elas têm estruturas análogas“, explica Michael Pollan, autor de livros como The Omnivore’s Dilemma (O Dilema do Onívoro) e The Botany of Desire (A Botânica do Desejo). “Elas têm maneiras de tomar todos os dados sensoriais que se reúnem em suas vidas quotidianas … integrá-los e, em seguida, se comportar de forma adequada em resposta. E elas fazem isso sem cérebro, o que, de certa forma, é o que é incrível sobre isso, porque assumimos automaticamente que você precisa de um cérebro para processar a informação”.
E nós supomos que precisamos de ouvidos para ouvir. Mas os pesquisadores, diz Pollan, tocaram uma gravação de uma lagarta comendo uma folha para plantas – e as plantas reagiram. Elas começam a segregar substâncias químicas defensivas – embora a planta não esteja realmente ameaçada, diz Pollan. “Ela está de alguma forma ouvindo o que é, para ela, um som aterrorizante de uma lagarta comendo suas folhas.”
Plantas podem sentir
Pollan diz que as plantas têm todos os mesmos sentidos como os seres humanos, e alguns a mais. Além da audição e do paladar, por exemplo, elas podem detectar a gravidade, a presença de água, ou até sentir que um obstáculo está a bloquear as suas raízes, antes de entrar em contacto com ele. As raízes das plantas mudam de direcção, diz ele, para evitar obstáculos.
E a dor? As plantas sentem? Pollan diz que elas respondem aos anestésicos. “Pode apagar uma planta com um anestésico humano… E não só isso, as plantas produzem seus próprios compostos que são anestésicos para nós.”
De acordo com os pesquisadores do Instituto de Física Aplicada da Universidade de Bonn, na Alemanha, as plantas libertam gases que são o equivalente a gritos de dor. Usando um microfone movido a laser, os pesquisadores captaram ondas sonoras produzidas por plantas que liberam gases quando cortadas ou feridas. Apesar de não ser audível ao ouvido humano, as vozes secretas das plantas têm revelado que os pepinos gritam quando estão doentes, e as flores se lamentam quando suas folhas são cortadas [fonte: Deutsche Welle].
Sistema nervoso de plantas
Como as plantas sentem e reagem ainda é um pouco desconhecido. Elas não têm células nervosas como os seres humanos, mas elas têm um sistema de envio de sinais eléctricos e até mesmo a produção de neurotransmissores, como dopamina, serotonina e outras substâncias químicas que o cérebro humano usa para enviar sinais.
As plantas realmente sentem dor
As evidências desses complexos sistemas de comunicação são sinais de que as plantas sentem dor. Ainda mais, os cientistas supõem que as plantas podem apresentar um comportamento inteligente sem possuir um cérebro ou consciência.
Elas podem se lembrar
Pollan descreve um experimento feito pela bióloga de animais Monica Gagliano. Ela apresentou uma pesquisa que sugere que a planta Mimosa pudica pode aprender com a experiência. E, Pollan diz, por apenas sugerir que uma planta poderia aprender, era tão controverso que seu artigo foi rejeitado por 10 revistas científicas antes de ser finalmente publicado.
Mimosa é uma planta, que é algo como uma samambaia, que recolhe suas folhas temporariamente quando é perturbada. Então Gagliano configurou uma engenhoca que iria pingar gotas na planta mimosa, sem ferir-la. Quando a planta era tocada, tal como esperado, as folhas se fechavam. Ela ficava pingando as plantas a cada 5-6 segundos.
“Depois de cinco ou seis gotas, as plantas paravam de responder, como se tivessem aprendido a sintonizar o estímulo como irrelevante“, diz Pollan. “Esta é uma parte muito importante da aprendizagem – saber o que você pode ignorar com segurança em seu ambiente.”
Talvez a planta estava apenas se cansando de tantos pingos? Para testar isso, Gagliano pegou as plantas que tinham parado de responder às gotas e sacudiu-as.
“Elas continuavam a se fechar“, diz Pollan. “Elas tinham feito a distinção que o gotejamento era um sinal que elas poderiam ignorar. E o que foi mais incrível é que Gagliano as testou novamente a cada semana durante quatro semanas e, durante um mês, elas continuaram a lembrar a lição.”
Isso foi o mais longe que Gagliano testou. É possível que elas se lembrem ainda mais. Por outro lado, Pollan aponta, as abelhas que foram testadas de maneira semelhante se esquecem o que aprenderam em menos de 48 horas.
Plantas: seres sentientes?
“As plantas podem fazer coisas incríveis. Elas parecem se lembrar de estresse e eventos, como essa experiência. Elas têm a capacidade de responder de 15 a 20 variáveis ambientais”, diz Pollan. “A questão é, é correto de chamar isso de aprendizagem? É essa a palavra certa? É correto chamar isso de inteligência? É certo, ainda, dizer que elas são conscientes? Alguns destes neurobiólogos de plantas acreditam que as plantas estão conscientes – não auto-conscientes, mas conscientes, no sentido que elas sabem onde elas estão no espaço … e reagem adequadamente a sua posição no espaço”.
Pollan diz que não há definição consensual de inteligência. “Vá para a Wikipedia e procure por inteligência. Eles se desesperam para dar-lhe uma resposta. Eles têm basicamente um gráfico onde dão-lhe nove definições diferentes. E cerca da metade delas dependem de um cérebro … se referem ao raciocínio abstracto ou julgamento.”
“E a outra metade apenas se referem a uma capacidade de resolver problemas. E esse é o tipo de inteligência que estamos falando aqui. Então a inteligência pode muito bem ser uma propriedade de vida. E a nossa diferença em relação a essas outras criaturas pode ser uma questão da diferença de grau e não de espécie. Podemos apenas ter mais desta habilidade de resolver problemas e podemos fazê-lo de diferentes maneiras.”
Pollan diz que o que realmente assusta as pessoas é “que a linha entre plantas e animais pode ser um pouco mais fina do que nós tradicionalmente acreditamos.”
E ele sugere que as plantas podem ser capaz de ensinar os seres humanos uma ou duas coisas, tais como a forma de processar a informação sem um posto de comando central, como um cérebro.
Confira este vídeo de Michael Pollan.
Tuesday 1 September 2015 4:27PM
What is it that makes you, you? While you’re made up of 10 trillion human cells, 100 trillion microbial cells also live on you and in you. This vast array of microscopic bugs may be your defining feature, and scientists around the world are racing to find out more. Amanda Smith reports.
Microbes, it seems, are the next big thing. Around the world, scientists are researching the human microbiome—the genes of our microbes—in the hope of unlocking quite a different way to understand sickness and health.
At the Microbiome Initiative at the University of California, San Diego, Rob Knight runs the American Gut Project, a citizen science initiative where you can get your microbiome sequenced.
Breast milk is meant to present the baby with a manageable dose of everything in the environment. It samples the entire environment—everything the mother eats, breathes, touches.MAUREEN MINCHIN, AUTHOR OF MILK MATTERS.
‘What we can do right now is put you on this microbial map, where we can compare your microbes to the microbes of thousands of other people we’ve already looked at,’ he says. ‘But what we need to do is develop more of a microbial GPS that doesn’t just tell you where you are, but tells you where you want to go and what you need to do, step by step, in order to get there.’
The Australian Centre for Ecogenomics is also setting up a service where you can get your gut microbes analysed. The centre’s director, Phillip Hugenholtz, predicts that in years to come such a process will be a diagnostic procedure when you go to the doctor, much like getting a blood test.
‘I definitely think that’s going to become a standard part of your personalised medicine’, he says. ‘Micro-organisms are sometimes a very good early indicator of things occurring in your body and so it will become something that you’d go and get done maybe once or twice a year to see what’s going on.’
While this level of interest in the microbiome is new, the first person to realise we’re all teeming with micro-organisms was Dutchman Anton Leeuwenhoek, way back in 1676. Leeuwenhoek was interested in making lenses, and constructed himself a microscope.
‘He was looking at the scum from his teeth, and was amazed to see in this scraped-off plaque from inside his own mouth what he called hundreds of different “animalcules swimming a-prettily”,’ says Tim Spector, professor of genetic epidemiology at Kings College London.
‘He was the first to describe this, and it took hundreds of years before people actually believed that we were completely full of these microbes and we’d co-evolved with them.’
Microbes have come a long way over the last century. Until recent advances in DNA sequencing, all tummy bugs were considered bad.
‘We used to think that there was no such thing as a good microbe in our guts, that they were all out to do us no good, and we’ve basically spent the last 100 years trying to eliminate them with disinfectants and then the last 50 years with antibiotics,’ says Spector.
This has given rise to the ‘hygiene hypothesis’, which contends that by keeping ourselves too clean, we’re denying ourselves the microbes necessary to keep our immune system balanced, resulting in all sorts of chronic diseases.
‘Over the last half-century, as infectious diseases like polio and measles and hepatitis and so-on have plummeted in their frequency, chronic diseases—everything from obesity to diabetes to inflammatory bowel disease—have been skyrocketing,’ says the Microbiome Initiative’s Rob Knight.
‘So the idea is that potentially without exposure to a diverse range of healthy microbes our immune systems might be going into overdrive and attacking our own cells, or overreacting to harmless things we find in the environment.’
In terms of human DNA, we’re all 99.99 per cent identical. However our microbial profiles can differ enormously. We might share just 10 per cent of our dominant microbial species with others.
According to Knight, some of the differences are explained by method of birth.
‘If you come out the regular way you get coated with microbes as you’re passing through your mother’s birth canal,’ he says.
Babies delivered by Caesarian section, on the other hand, have microbes that are mostly found on adult skin, from being touched by different doctors and nurses.
‘One thing that’s potentially interesting about that is differences between C-section and vaginally delivered babies have been reported: higher rates in C-section babies of asthma, allergies, atopic disease, even obesity. All of those have been linked to the microbiome now.’
Also important to the development of healthy microbiota in babies is breastfeeding, according to Maureen Minchin, the author of Milk Matters.
‘We’ve known for over 100 years that breast milk and formula result in very, very different gut flora in babies, but it’s only very recently that anyone has thought to look and see what breast milk does contain, and at last count there were well over 700 species of bacteria in breast milk,’ she says.
According to Minchin, breastfeeding is the bridge between the womb and the world for babies.
‘Breast milk is meant to present the baby with a manageable dose of everything in the environment. It samples the entire environment—everything the mother eats, breathes, touches. Her microbiome is present in that breast milk and will help create the appropriate microbiome in the baby.’
Minchin is an advocate of the World Health Organisation’s recommendation to breastfeed exclusively to six months and then continue breastfeeding while introducing other foods through the first and second year.
So if what babies are fed is important for their microbiome, what about adults? Tim Spector says research into microbes is yielding new information about healthy eating.
‘It’s going to soon revolutionise how we look at food and diet. This is one of the most exciting things in science at the moment, because it’s obviously much easier to change your microbes than it is to change your genes.’
‘Most processed foods only contain about five ingredients, and in a way our epidemic of the last 30 years of obesity and allergy is that our diets have become less and less diverse.’
According to Spector, studies of people with various chronic diseases, obesity and diabetes show a common feature, which is that their gut microbes have a much-reduced diversity compared to healthy people.
He likes to use the analogy of a garden: ‘A neglected garden has very few species, not much fertilised soil, and this allows weeds to take over in great numbers,’ he says.
‘I think this is a nice concept because we’re very good gardeners, humans, and I think we need to start using those principles—fertilising, adding soil, experimenting and avoiding adding nasty toxins to our own bodies as we would our gardens.’
May your gut flora bloom!
August 1, 2015
Lisa Feldman Barrett has an interesting piece up in yesterday’s New York Times that I think is worth some attention here. Barrett is the director of the The Interdisciplinary Affective Science Laboratory, where she studies the nature of emotional experience. Here is the key part of the article, describing her latest findings:
The Interdisciplinary Affective Science Laboratory (which I direct) collectively analyzed brain-imaging studies published from 1990 to 2011 that examined fear, sadness, anger, disgust and happiness. We divided the human brain virtually into tiny cubes, like 3-D pixels, and computed the probability that studies of each emotion found an increase in activation in each cube.
Overall, we found that no brain region was dedicated to any single emotion. We also found that every alleged “emotion” region of the brain increased its activity during nonemotional thoughts and perceptions as well . . .
Emotion words like “anger,” “happiness” and “fear” each name a population of diverse biological states that vary depending on the context. When you’re angry with your co-worker, sometimes your heart rate will increase, other times it will decrease and still other times it will stay the same. You might scowl, or you might smile as you plot your revenge. You might shout or be silent. Variation is the norm.
This highly distributed, variable, and contextual description of emotions matches up quite well with what scientists have found to be true of conceptualization—namely, that it is a situated process drawn from a plurality of bodily forces. For instance, compare Barrett’s findings above to what I wrote about concepts in my paper on concepts and capacities from June (footnote references are in the paper):
In short, concepts are flexible and distributed modes of bodily organization grounded in modality-specific regions of the brain; they comprise semantic knowledge embodied in perception and action; and they underwrite the organization of sensory experience and guide action within an environment. Concepts are tools for constructing in the mind new pathways of relationship and discrimination, for shaping the body, and for attuning it to contrast. Such pathways are recruited in an ecologically specific way as part of the dynamic bringing-to-apprehension of phenomena.
I think the parallel is clear enough, and we would do well to adopt this more ecological view of emotions and concepts into our thinking. The empirical data is giving us a strong argument for talking about the ecological basis of emotion and conceptuality, a basis that continues to grow stronger by the day.
Eighteen vials were rocking back and forth on a squeaky mechanical device the shape of a butcher scale, and Mark Lyte was beside himself with excitement. ‘‘We actually got some fresh yesterday — freshly frozen,’’ Lyte said to a lab technician. Each vial contained a tiny nugget of monkey feces that were collected at the Harlow primate lab near Madison, Wis., the day before and shipped to Lyte’s lab on the Texas Tech University Health Sciences Center campus in Abilene, Tex.
Lyte’s interest was not in the feces per se but in the hidden form of life they harbor. The digestive tube of a monkey, like that of all vertebrates, contains vast quantities of what biologists call gut microbiota. The genetic material of these trillions of microbes, as well as others living elsewhere in and on the body, is collectively known as the microbiome. Taken together, these bacteria can weigh as much as six pounds, and they make up a sort of organ whose functions have only begun to reveal themselves to science. Lyte has spent his career trying to prove that gut microbes communicate with the nervous system using some of the same neurochemicals that relay messages in the brain.
Inside a closet-size room at his lab that afternoon, Lyte hunched over to inspect the vials, whose samples had been spun down in a centrifuge to a radiant, golden broth. Lyte, 60, spoke fast and emphatically. ‘‘You wouldn’t believe what we’re extracting out of poop,’’ he told me. ‘‘We found that the guys here in the gut make neurochemicals. We didn’t know that. Now, if they make this stuff here, does it have an influence there? Guess what? We make the same stuff. Maybe all this communication has an influence on our behavior.’’
Since 2007, when scientists announced plans for a Human Microbiome Project to catalog the micro-organisms living in our body, the profound appreciation for the influence of such organisms has grown rapidly with each passing year. Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. Biologists now believe that much of what makes us human depends on microbial activity. The two million unique bacterial genes found in each human microbiome can make the 23,000 genes in our cells seem paltry, almost negligible, by comparison. ‘‘It has enormous implications for the sense of self,’’ Tom Insel, the director of the National Institute of Mental Health, told me. ‘‘We are, at least from the standpoint of DNA, more microbial than human. That’s a phenomenal insight and one that we have to take seriously when we think about human development.’’
Given the extent to which bacteria are now understood to influence human physiology, it is hardly surprising that scientists have turned their attention to how bacteria might affect the brain. Micro-organisms in our gut secrete a profound number of chemicals, and researchers like Lyte have found that among those chemicals are the same substances used by our neurons to communicate and regulate mood, like dopamine, serotonin and gamma-aminobutyric acid (GABA). These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety. Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients.
At the time of my visit to Lyte’s lab, he was nearly six months into an experiment that he hoped would better establish how certain gut microbes influenced the brain, functioning, in effect, as psychiatric drugs. He was currently compiling a list of the psychoactive compounds found in the feces of infant monkeys. Once that was established, he planned to transfer the microbes found in one newborn monkey’s feces into another’s intestine, so that the recipient would end up with a completely new set of microbes — and, if all went as predicted, change their neurodevelopment. The experiment reflected an intriguing hypothesis. Anxiety, depression and several pediatric disorders, including autism and hyperactivity, have been linked with gastrointestinal abnormalities. Microbial transplants were not invasive brain surgery, and that was the point: Changing a patient’s bacteria might be difficult but it still seemed more straightforward than altering his genes.
When Lyte began his work on the link between microbes and the brain three decades ago, it was dismissed as a curiosity. By contrast, last September, the National Institute of Mental Health awarded four grants worth up to $1 million each to spur new research on the gut microbiome’s role in mental disorders, affirming the legitimacy of a field that had long struggled to attract serious scientific credibility. Lyte and one of his longtime colleagues, Christopher Coe, at the Harlow primate lab, received one of the four. ‘‘What Mark proposed going back almost 25 years now has come to fruition,’’ Coe told me. ‘‘Now what we’re struggling to do is to figure out the logic of it.’’ It seems plausible, if not yet proved, that we might one day use microbes to diagnose neurodevelopmental disorders, treat mental illnesses and perhaps even fix them in the brain.
In 2011, a team of researchers at University College Cork, in Ireland, and McMaster University, in Ontario, published a study in Proceedings of the National Academy of Science that has become one of the best-known experiments linking bacteria in the gut to the brain. Laboratory mice were dropped into tall, cylindrical columns of water in what is known as a forced-swim test, which measures over six minutes how long the mice swim before they realize that they can neither touch the bottom nor climb out, and instead collapse into a forlorn float. Researchers use the amount of time a mouse floats as a way to measure what they call ‘‘behavioral despair.’’ (Antidepressant drugs, like Zoloft and Prozac, were initially tested using this forced-swim test.)
For several weeks, the team, led by John Cryan, the neuroscientist who designed the study, fed a small group of healthy rodents a broth infused with Lactobacillus rhamnosus, a common bacterium that is found in humans and also used to ferment milk into probiotic yogurt. Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal. Recent studies have shown that mice stressed during pregnancy pass on lowered levels of the bacterium to their pups. This type of bacteria is known to release immense quantities of GABA; as an inhibitory neurotransmitter, GABA calms nervous activity, which explains why the most common anti-anxiety drugs, like Valium and Xanax, work by targeting GABA receptors.
Cryan found that the mice that had been fed the bacteria-laden broth kept swimming longer and spent less time in a state of immobilized woe. ‘‘They behaved as if they were on Prozac,’’ he said. ‘‘They were more chilled out and more relaxed.’’ The results suggested that the bacteria were somehow altering the neural chemistry of mice.
Until he joined his colleagues at Cork 10 years ago, Cryan thought about microbiology in terms of pathology: the neurological damage created by diseases like syphilis or H.I.V. ‘‘There are certain fields that just don’t seem to interact well,’’ he said. ‘‘Microbiology and neuroscience, as whole disciplines, don’t tend to have had much interaction, largely because the brain is somewhat protected.’’ He was referring to the fact that the brain is anatomically isolated, guarded by a blood-brain barrier that allows nutrients in but keeps out pathogens and inflammation, the immune system’s typical response to germs. Cryan’s study added to the growing evidence that signals from beneficial bacteria nonetheless find a way through the barrier. Somehow — though his 2011 paper could not pinpoint exactly how — micro-organisms in the gut tickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety. Soon after that, Cryan and a co-author, Ted Dinan, published a theory paper in Biological Psychiatry calling these potentially mind-altering microbes ‘‘psychobiotics.’’
It has long been known that much of our supply of neurochemicals — an estimated 50 percent of the dopamine, for example, and a vast majority of the serotonin — originate in the intestine, where these chemical signals regulate appetite, feelings of fullness and digestion. But only in recent years has mainstream psychiatric research given serious consideration to the role microbes might play in creating those chemicals. Lyte’s own interest in the question dates back to his time as a postdoctoral fellow at the University of Pittsburgh in 1985, when he found himself immersed in an emerging field with an unwieldy name: psychoneuroimmunology, or PNI, for short. The central theory, quite controversial at the time, suggested that stress worsened disease by suppressing our immune system.
By 1990, at a lab in Mankato, Minn., Lyte distilled the theory into three words, which he wrote on a chalkboard in his office: Stress->Immune->Disease. In the course of several experiments, he homed in on a paradox. When he dropped an intruder mouse in the cage of an animal that lived alone, the intruder ramped up its immune system — a boost, he suspected, intended to fight off germ-ridden bites or scratches. Surprisingly, though, this did not stop infections. It instead had the opposite effect: Stressed animals got sick. Lyte walked up to the board and scratched a line through the word ‘‘Immune.’’ Stress, he suspected, directly affected the bacterial bugs that caused infections.
To test how micro-organisms reacted to stress, he filled petri plates with a bovine-serum-based medium and laced the dishes with a strain of bacterium. In some, he dropped norepinephrine, a neurochemical that mammals produce when stressed. The next day, he snapped a Polaroid. The results were visible and obvious: The control plates were nearly barren, but those with the norepinephrine bloomed with bacteria that filigreed in frostlike patterns. Bacteria clearly responded to stress.
Then, to see if bacteria could induce stress, Lyte fed white mice a liquid solution of Campylobacter jejuni, a bacterium that can cause food poisoning in humans but generally doesn’t prompt an immune response in mice. To the trained eye, his treated mice were as healthy as the controls. But when he ran them through a plexiglass maze raised several feet above the lab floor, the bacteria-fed mice were less likely to venture out on the high, unprotected ledges of the maze. In human terms, they seemed anxious. Without the bacteria, they walked the narrow, elevated planks.
Each of these results was fascinating, but Lyte had a difficult time finding microbiology journals that would publish either. ‘‘It was so anathema to them,’’ he told me. When the mouse study finally appeared in the journal Physiology & Behavior in 1998, it garnered little attention. And yet as Stephen Collins, a gastroenterologist at McMaster University, told me, those first papers contained the seeds of an entire new field of research. ‘‘Mark showed, quite clearly, in elegant studies that are not often cited, that introducing a pathological bacterium into the gut will cause a change in behavior.’’
Lyte went on to show how stressful conditions for newborn cattle worsened deadly E. coli infections. In another experiment, he fed mice lean ground hamburger that appeared to improve memory and learning — a conceptual proof that by changing diet, he could change gut microbes and change behavior. After accumulating nearly a decade’s worth of evidence, in July 2008, he flew to Washington to present his research. He was a finalist for the National Institutes of Health’s Pioneer Award, a $2.5 million grant for so-called blue-sky biomedical research. Finally, it seemed, his time had come. When he got up to speak, Lyte described a dialogue between the bacterial organ and our central nervous system. At the two-minute mark, a prominent scientist in the audience did a spit take.
‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’
Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.
But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.
Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.
Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student at his lab and now a neuroscientist at Caltech, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.
The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’
Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.
The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’
Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added, ‘‘We really need a lot more research done before we actually have people trying therapies out.’’
If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’
photo credit: Courtesy of MIT Researchers
Given the fundamental importance of our DNA, it is logical to assume that damage to it is undesirable and spells bad news; after all, we know that cancer can be caused by mutations that arise from such injury. But a surprising new study is turning that idea on its head, with the discovery that brain cells actually break their own DNA to enable us to learn and form memories.
While that may sound counterintuitive, it turns out that the damage is necessary to allow the expression of a set of genes, called early-response genes, which regulate various processes that are critical in the creation of long-lasting memories. These lesions are rectified pronto by repair systems, but interestingly, it seems that this ability deteriorates during aging, leading to a buildup of damage that could ultimately result in the degeneration of our brain cells.
This idea is supported by earlier work conducted by the same group, headed by Li-Huei Tsai, at the Massachusetts Institute of Technology (MIT) that discovered that the brains of mice engineered to develop a model of Alzheimer’s disease possessed a significant amount of DNA breaks, even before symptoms appeared. These lesions, which affected both strands of DNA, were observed in a region critical to learning and memory: the hippocampus.
To find out more about the possible consequences of such damage, the team grew neurons in a dish and exposed them to an agent that causes these so-called double strand breaks (DSBs), and then they monitored the gene expression levels. As described in Cell, they found that while the vast majority of genes that were affected by these breaks showed decreased expression, a small subset actually displayed increased expression levels. Importantly, these genes were involved in the regulation of neuronal activity, and included the early-response genes.
Since the early-response genes are known to be rapidly expressed following neuronal activity, the team was keen to find out whether normal neuronal stimulation could also be inducing DNA breaks. The scientists therefore applied a substance to the cells that is known to strengthen the tiny gap between neurons across which information flows – the synapse – mimicking what happens when an organism is exposed to a new experience.
“Sure enough, we found that the treatment very rapidly increased the expression of those early response genes, but it also caused DNA double strand breaks,” Tsai said in a statement.
So what is the connection between these breaks and the apparent boost in early-response gene expression? After using computers to scrutinize the DNA sequences neighboring these genes, the researchers found that they were enriched with a pattern targeted by an architectural protein that, upon binding, distorts the DNA strands by introducing kinks. By preventing crucial interactions between distant DNA regions, these bends therefore act as a barrier to gene expression. The breaks, however, resolve these constraints, allowing expression to ensue.
These findings could have important implications because earlier work has demonstrated that aging is associated with a decline in the expression of genes involved in the processes of learning and memory formation. It therefore seems likely that the DNA repair system deteriorates with age, but at this stage it is unclear how these changes occur, so the researchers plan to design further studies to find out more.
photo credit: Topic / Shutterstock. It used to be thought that the lymphatic system stopped at the neck, but it has now been found to reach into the brain
In contradiction to decades of medical education, a direct connection has been reported between the brain and the immune system. Claims this radical always require plenty of testing, even after winning publication, but this could be big news for research into diseases like multiple sclerosis (MS) and Alzheimer’s.
It seems astonishing that, after centuries of dissection, a system of lymphatic vessels could have survived undetected. That, however, is exactly what Professor Jonathan Kipnis of the University of Virginia claims in Nature.
Old and new representations of the lymphatic system that carries immune cells around the body. Credit: University of Virginia Health System
“It changes entirely the way we perceive the neuro-immune interaction,” says Kipnis. “We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.”
MS is known to be an example of the immune system attacking the brain, although the reasons are poorly understood. The opportunity to study lymphatic vessels that link the brain to the immune system could transform our understanding of how these attacks occur, and what could stop them. The causes of Alzheimer’s disease are even more controversial, but may also have immune system origins, and the authors suggest protein accumulation is a result of the vessels failing to do their job.
Indeed, Kipnis claims, “We believe that for every neurological disease that has an immune component to it, these vessels may play a major role.”
The discovery originated when Dr. Antoine Louveau, a researcher in Kipnis’ lab, mounted the membranes that cover mouse brains, known as meninges, on a slide. In the dural sinuses, which drain blood from the brain, he noticed linear patterns in the arrangement of immune T-cells. “I called Jony [Kipnis] to the microscope and I said, ‘I think we have something,'” Louveau recalls.
Kipnis was skeptical, and now says, “I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.” Extensive further research convinced him and a group of co-authors from some of Virginia’s most prestigious neuroscience institutes that the vessels are real, they carry white blood cells and they also exist in humans. The network, they report, “appears to start from both eyes and track above the olfactory bulb before aligning adjacent to the sinuses.”
Kipnis pays particular credit to colleague Dr. Tajie Harris who enabled the team to image the vessels in action on live animals, confirming their function. Louveau also credits the discovery to fixing the meninges to a skullcap before dissecting, rather than the other way around. This, along with the closeness of the network to a blood vessel, is presumably why no one has observed it before.
The authors say the vessels, “Express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes.”
The authors add that the network bears many resemblances to the peripheral lymphatic system, but it “displays certain unique features,” including being “less complex [and] composed of narrower vessels.”
The discovery reinforces findings that immune cells are present even within healthy brains, a notion that was doubted until recently.
Meningial lymphatic vessels in mice. Credit: Louveau et al, Nature.
Is mental illness simply the evolutionary toll humans have to pay in return for our unique and superior cognitive abilities when compared to all other species? But if so, why have often debilitating illnesses like schizophrenia persisted throughout human evolutionary history when the affects can be quite negative on an individual’s chances of survival or reproductive success?
In a new study appearing in Molecular Biology and Evolution, Mount Sinai researcher Joel Dudley has led a new study that suggests that the very changes specific to human evolution may have come at a cost, contributing to the genetic architecture underlying schizophrenia traits in modern humans.
“We were intrigued by the fact that unlike many other mental traits, schizophrenia traits have not been observed in species other than humans, and schizophrenia has interesting and complex relationships with human intelligence,” said Dr. Joel Dudley, who led the study along with Dr. Panos Roussos. “The rapid increase in genomic data sequenced from large schizophrenia patient cohorts enabled us to investigate the molecular evolutionary history of schizophrenia in sophisticated new ways.”
The team examined a link between these regions, and human-specific evolution, in genomic segments called human accelerated regions, or HARs. HARs are short signposts in the genome that are conserved among non-human species but experienced faster mutation rates in humans. Thus, these regions, which are thought to control the level of gene expression, but not mutate the gene itself, may be an underexplored area of mental illness research.
The team’s research is the first study to sift through the human genome and identify a shared pattern between the location of HARs and recently identified schizophrenia gene loci. To perform their work, they utilized a recently completed, largest schizophrenia study of its kind, the Psychiatric Genomics Consortium (PGC), which included 36,989 schizophrenia cases and 113,075 controls. It is the largest genome-wide association study ever performed on any psychiatric disease.
They found that the schizophrenic loci were most strongly associated in genomic regions near the HARs that are conserved in non-human primates, and these HAR-associated schizophrenic loci are found to be under stronger evolutionary selective pressure when compared with other schizophrenic loci. Furthermore, these regions controlled genes that were expressed only in the prefrontal cortex of the brain, indicating that HARs may play an important role in regulating genes found to be linked to schizophrenia. They specifically found the greatest correlation between HAR-associated schizophrenic loci and genes controlling the expression of the neurotransmitter GABA, brain development, synaptic formations, adhesion and signaling molecules.
Their new evolutionary approach provides new insights into schizophrenia, and genomic targets to prioritize future studies and drug development targets. In addition, there are important new avenues to explore the roles of HARs in other mental diseases such as autism or bipolar disorder.
POSTED JANUARY 28, 2015, 8:55 PM
Beverly Merz, Harvard Women’s Health Watch
One long-ago summer, I joined the legion of teens helping harvest our valley’s peach crop in western Colorado. My job was to select the best peaches from a bin, wrap each one in tissue, and pack it into a shipping crate. The peach fuzz that coated every surface of the packing shed made my nose stream and my eyelids swell. When I came home after my first day on the job, my mother was so alarmed she called the family doctor. Soon the druggist was at the door with a vial of Benadryl (diphenhydramine) tablets. The next morning I was back to normal and back on the job. Weeks later, when I collected my pay (including the ½-cent-per-crate bonus for staying until the end of the harvest), I thanked Benadryl.
Today, I’m thankful my need for that drug lasted only a few weeks. A report published online this week in JAMA Internal Medicine offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia.
Anticholinergic drugs block the action of acetylcholine. This substance transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates muscle contractions. Anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and drugs to relieve the symptoms of Parkinson’s disease.
What the study found
A team led by Shelley Gray, a pharmacist at the University of Washington’s School of Pharmacy, tracked nearly 3,500 men and women ages 65 and older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle healthcare system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over-the-counter, that each participant took the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of the volunteers developed dementia. When the researchers examined the use of anticholinergic drugs, they found that people who used these drugs were more likely to have developed dementia as those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.
The ACT results add to mounting evidence that anticholinergics aren’t drugs to take long-term if you want to keep a clear head, and keep your head clear into old age. The body’s production of acetylcholine diminishes with age, so blocking its effects can deliver a double whammy to older people. It’s not surprising that problems with short-term memory, reasoning, and confusion lead the list of anticholinergic side effects, which also include drowsiness, dry mouth, urine retention, and constipation.
The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking a tricyclic antidepressant to alleviate early symptoms of undiagnosed dementia; the risk associated with bladder medications was just as high.
“This study is another reminder to periodically evaluate all of the drugs you’re taking. Look at each one to determine if it’s really helping,” says Dr. Sarah Berry, a geriatrician and assistant professor of medicine at Harvard Medical School. “For instance, I’ve seen people who have been on anticholinergic medications for bladder control for years and they are completely incontinent. These drugs obviously aren’t helping.”
Many drugs have a stronger effect on older people than younger people. With age, the kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass with age, both of which change the way that drugs are distributed to and broken down in body tissues. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effectiveness of the others.
What should you do?
In 2008, Indiana University School of Medicine geriatrician Malaz Boustani developed the anticholinergic cognitive burden scale, which ranks these drugs according to the severity of their effects on the mind. It’s a good idea to steer clear of the drugs with high ACB scores, meaning those with scores of 3. “There are so many alternatives to these drugs,” says Dr. Berry. For example, selective serotonin re-uptake inhibitors (SSRIs) like citalopram (Celexa) or fluoxetine (Prozac) are good alternatives to tricyclic antidepressants. Newer antihistamines such as loratadine (Claritin) can replace diphenhydramine or chlorpheniramine (Chlor-Trimeton). Botox injections and cognitive behavioral training can alleviate urge incontinence.
One of the best ways to make sure you’re taking the most effective drugs is to dump all your medications — prescription and nonprescription — into a bag and bring them to your next appointment with your primary care doctor.
Published January 25, 2015
Research done by the state University of Brasilia, or UnB, and Brazil’s state-owned agriculture and livestock research company Embrapa have discovered a protein in coffee with effects similar to morphine, scientists said on Saturday.
A communique from Embrapa said that its Genetics and Biotechnology Resources Division and the UnB successfully “identified previously unknown fragments of protein – peptides – in coffee that have an effect similar to morphine, in other words they have an analgesic and sedative activity.”
Those peptides, the note said, “have a positive differential: their effects last longer in experiments with laboratory mice.”
The two institutions applied for patents to Brazilian regulators for the seven “opioid peptides” identified in the study.
The discovery of the molecules came about through the doctorate research work of Felipe Vinecky of the Molecular Biology Department at UnB, who with the consultation of Embrapa was looking to combine coffee genes to improve the quality of the grain.
The studies also have the support of France’s Center for International Cooperation on Agricultural Research and Development, or CIRAD.
JANUARY 18, 2015
And it got weirder: I inherited the same sociocognitive tools as everyone else, so I made the same assumptions. Consequently, I defied even my own expectations. So I learned to mistrust my own perceptions, always looking over my shoulder, predicting my own behavior as if I were an outside observer. I literally had to re-engineer myself in order to function in society, and that was impossible to do without getting into some major philosophical questions. I freely admit that this process has taken me my entire life and only recently have I had any success. I am just now learning to function in society–I’m a cracked egg. Cracked once from outside, and once from inside. And just now growing up, a decade late.
So it’s no surprise that I’m so stuck on the question of what people’s brains are actually doing when they theorize.
I stumbled onto R. Scott Bakker’s theories after reading his philosophical thriller, Neuropath. Then I found his blog, and I was blown away that someone besides me was obsessed with the role of ingroup/outgroup dynamics in intellectual circles. As someone with no ingroup (at least not yet), it’s very refreshing. But what really blew my mind was that he had a theory of cognitive science that could explain many of my frustrating experiences: the Blind Brain Theory, or BBT.
The purpose of this post is not to explain BBT, so you’ll have to click the link if you want that. I’ll go more into depth on the specifics of BBT later, but for a ridiculously short summary: it’s a form of eliminativism. Eliminativism is the philosophical view that neuroscience reveals our traditional conceptions of the human being, like free will, mind, and meaning, to be radically mistaken. But BBT is unique among eliminativisms in its emphasis of neglect: the way in which blindness, or lack of information, actually *enables* our brains to solve problems, especially the problem of what we are. And from my perspective, that makes perfect sense.
BBT is a profoundly counterintuitive theory that cautions us against intuition itself. And ironically, it substantiates my skeptical intuitions. In short, it shows I’m not the only one who has no clue what she’s doing. If BBT is correct, non-neurotypical individuals aren’t really “impaired.” They simply fit differently with other people. Fewer intersecting lines, that’s all. Bakker has developed his theory further since he published this paper, building on his notion of post-intentional theory (see here for a more general introduction). BBT has stirred up quite a lot of drama.
While we all argue over BBT, absorbed in defending our positions, I feel like an outsider, even among people who understand ingroups. Why? Because most of the people in the debate seem to be discussing something hypothetical, something academic. For me, as I’ve explained, the question of intentionality is a question of everyday life. So I can’t shirk my habit of wondering about biology: what’s going on in the brains of intentionalists? What’s going on in the brains of post-intentionalists? And what’s going on inside my own brain? Bakker would say this is precisely the sort of question a post-intentionalist would ask.
But what happens if the post-intentionalist has never done intentional philosophy? Allow me to explain, with a fictionalized example from my own experience. I use the term “intentional” in both an everyday and philosophical sense, interchangeably:
Intentional, Post-Intentional, and Unintentional Philosophy
Imagine you’re an ordinary person. You just want to get on with your life, but you have a terminal illness. It’s an extremely rare neuropsychiatric syndrome: in order to recover, you must solve an ancient philosophical question. You can’t just come up with any old answer. You actually have to prove you solved it, and
convince everyone alive you at least have to convince yourself that you could convince anyone whose counterargument could possibly sway you. You’re skeptical to the marrow, and very good at Googling.
Remember, this is a terminal illness, so you have limited time to solve the problem.
In college, philosophy professors said you were a brilliant student. Plus, you have a great imagination from always being forced to do bizarre things. So naturally, you think you can solve it.
But it takes more time than you thought it would. Years more time. Enough time that you turn into a mad hermit. Your life collapses around you and you’re left with no friends, family, or work. But your genes are really damn virulent, and they simply don’t contain the stop codons for self-termination, so you persist.
And finally, after many failed attempts, you cough up something that sticks. An intellectual hairball.
But then the unimaginable happens: you come across a horrifying argument. The argument goes that when it comes to philosophy, intention matters. If your “philosophy” is just a means to survive, it is not philosophy at all; only that which is meant as philosophy can be called philosophical. So therefore, your solution is not valid. It is not even wrong.
So, it’s back to the drawing board for you. You have to find a new solution that makes your intention irrelevant. A solution that satisfies both the intentional philosophers, who do philosophy because they want to, and the unintentional philosophers who do it because they are forced to.
And then you run across something called post-intentional philosophy. It seems like a solution, but…
But post-intentional philosophy, as you see, requires a history: namely, a history of pre-post-intentional philosophy. Or, to oversimplify, intentional philosophy! The kind people do on purpose, not with a gun to their head.
You know that problems cannot be solved from the same level of consciousness that created them, so you try to escape what intentional and post-intentional philosophy share: theory. You think you can tackle your problem by finding a way out of theory altogether. A way that allows for the existence of all sorts of brains generating all sorts of things, intentional, post-intentional, and unintentional. A nonphilosophy, not a Laruellian non-philosophy. That way must exist, otherwise your philosophy will leave your very existence a mystery!
What do you do?
Are Theory and Practice Separate? Separable? Or something completely different?
Philosophy is generally a debate, but as an unintentional thinker I can’t help but remain neutral on everything except responsiveness to reality (more on that coming later). In this section I am attempting neither to support nor to attack it, but to explore it.
Bakker’s heuristic brand of eliminativism appears to bank on the ability to distinguish between the general and the specific, the practical and the theoretical. Correct me if I am wrong.
As the case of the “unintentional philosopher” suggests, philosophers themselves are counterexamples to the robustness of this distinction, just like people with impaired intentional cognition offer counterexamples that question folk psychology. If BBT is empirically testable, the practice-vs-theory distinction must remain empirically testable. We should be able to study everyday cognition (“Square One”) independently of theoretical cognition (“Square Two”) and characterize the neurobiological relationship of the two as either completely modular, somewhat modular, or somewhere in between. We should also be able to predict whether someone is an intentionalist or a post-intentionalist by observing their brains.
From a sociobiological perspective, one possibility is that Bakker is literally trying to hack philosophers’ brains: to separate the neural circuitry that connects philosophical cognition with daily functionality.
If that were the case, their disagreement would come as no surprise.
But my real point here, going back to my struggles with my unusual neurobiology, is that I am personally, neurologically, as close to “non-intentional” as people get. And that presents a problem for my ability to understand any of these philosophical distinctions regarding intentionality, post-intentionality, etc. But just as a person with Aspergers syndrome is forced to intellectually explore the social, my relative deficit of intentionality has simultaneously made it unavoidable–necessary for me to explore intentionality. My point about theory and practice is to ask whether this state of affairs is “just my problem,” or whether it says something about the entire project of theory.
If nothing else, it certainly questions the assumption that the doctor is never the patient, that the post-intentional theorist is always, necessarily some sort of detached intellectual observer with no deviation from the intentional norm in his own neurobiology.
Come back later for a completely different view…
Date: January 12, 2015
Source: Lund University
A new study from Lund University in Sweden indicates that inherited viruses that are millions of years old play an important role in building up the complex networks that characterise the human brain.
Researchers have long been aware that endogenous retroviruses constitute around five per cent of our DNA. For many years, they were considered junk DNA of no real use, a side-effect of our evolutionary journey.
In the current study, Johan Jakobsson and his colleagues show that retroviruses seem to play a central role in the basic functions of the brain, more specifically in the regulation of which genes are to be expressed, and when. The findings indicate that, over the course of evolution, the viruses took an increasingly firm hold on the steering wheel in our cellular machinery. The reason the viruses are activated specifically in the brain is probably due to the fact that tumours cannot form in nerve cells, unlike in other tissues.
“We have been able to observe that these viruses are activated specifically in the brain cells and have an important regulatory role. We believe that the role of retroviruses can contribute to explaining why brain cells in particular are so dynamic and multifaceted in their function. It may also be the case that the viruses’ more or less complex functions in various species can help us to understand why we are so different,” says Johan Jakobsson, head of the research team for molecular neurogenetics at Lund University.
The article, based on studies of neural stem cells, shows that these cells use a particular molecular mechanism to control the activation processes of the retroviruses. The findings provide us with a complex insight into the innermost workings of the most basal functions of the nerve cells. At the same time, the results open up potential for new research paths concerning brain diseases linked to genetic factors.
“I believe that this can lead to new, exciting studies on the diseases of the brain. Currently, when we look for genetic factors linked to various diseases, we usually look for the genes we are familiar with, which make up a mere two per cent of the genome. Now we are opening up the possibility of looking at a much larger part of the genetic material which was previously considered unimportant. The image of the brain becomes more complex, but the area in which to search for errors linked to diseases with a genetic component, such as neurodegenerative diseases, psychiatric illness and brain tumours, also increases.”
- Liana Fasching, Adamandia Kapopoulou, Rohit Sachdeva, Rebecca Petri, Marie E. Jönsson, Christian Männe, Priscilla Turelli, Patric Jern, Florence Cammas, Didier Trono, Johan Jakobsson. TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells. Cell Reports, 2015; 10 (1): 20 DOI: 10.1016/j.celrep.2014.12.004
In recent years, neuroscientists have become increasingly interested in the idea that there may be a powerful link between the human brain and gut bacteria. And while a growing body of research has provided evidence of the brain-gut connection, most of these studies so far have been conducted on animals.
Now, promising new research from neurobiologists at Oxford University offers some preliminary evidence of a connection between gut bacteria and mental health in humans. The researchers found that supplements designed to boost healthy bacteria in the gastrointestinal tract (“prebiotics”) may have an anti-anxiety effect insofar as they alter the way that people process emotional information.
While probiotics consist of strains of good bacteria, prebiotics are carbohydrates that act as nourishment for those bacteria. With increasing evidence that gut bacteria may exert some influence on brain function and mental health, probiotics and prebiotics are being increasingly studied for the potential alleviation of anxiety and depression symptoms.
“Prebiotics are dietary fibers (short chains of sugar molecules) that good bacteria break down, and use to multiply,” the study’s lead author, Oxford psychiatrist and neurobiologist Dr. Philip Burnet, told The Huffington Post. “Prebiotics are ‘food’ for good bacteria already present in the gut. Taking prebiotics therefore increases the numbers of all species of good bacteria in the gut, which will theoretically have greater beneficial effects than [introducing] a single species.”
To test the efficacy of prebiotics in reducing anxiety, the researchers asked 45 healthy adults between the ages of 18 and 45 to take either a prebiotic or a placebo every day for three weeks. After the three weeks had passed, the researchers completed several computer tests assessing how they processed emotional information, such as positive and negatively-charged words.
The results of one of the tests revealed that subjects who had taken the prebiotic paid less attention to negative information and more attention to positive information, compared to the placebo group, suggesting that the prebiotic group had less anxiety when confronted with negative stimuli. This effect is similar to that which has been observed among individuals who have taken antidepressants or anti-anxiety medication.
The researchers also found that the subjects who took the prebiotics had lower levels of cortisol — a stress hormone which has been linked with anxiety and depression — in their saliva when they woke up in the morning.
While previous research has documented that altering gut bacteria has a similarly anxiety-reducing effect in mice, the new study is one of the first to examine this phenomenon in humans. As of now, research on humans is in its early stages. A study conducted last year at UCLA found that women who consumed probiotics through regularly eating yogurt exhibited altered brain function in both a resting state and when performing an emotion-recognition task.
“Time and time again, we hear from patients that they never felt depressed or anxious until they started experiencing problems with their gut,” Dr. Kirsten Tillisch, the study’s lead author, said in a statement. “Our study shows that the gut–brain connection is a two-way street.”
So are we moving towards a future in which mental illness may be able to be treated (or at least managed) using targeted probiotic cocktails? Burnet says it’s possible, although they’re unlikely to replace conventional treatment.
“I think pre/probiotics will only be used as ‘adjuncts’ to conventional treatments, and never as mono-therapies,” Burnet tells HuffPost. “It is likely that these compounds will help to manage mental illness… they may also be used when there are metabolic and/or nutritional complications in mental illness, which may be caused by long-term use of current drugs.”
The findings were published in the journal Psychopharmacology.
Date: November 19, 2014
Summary: Our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood, a new study in mice shows. The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream.
A new study in mice, conducted by researchers at Sweden’s Karolinska Institutet together with colleagues in Singapore and the United States, shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function.
The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes — which therefore play an important role in the protection of the brain.
The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.
“We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus,” says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. “In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma.”
The team also showed that the increased ‘leakiness’ of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this ‘leakiness’ could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.
According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.
“These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology,” says Professor Sven Pettersson, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. “Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier.”
- V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, N. Bakocevic, N. L. Guan, P. Kundu, B. Gulyas, C. Halldin, K. Hultenby, H. Nilsson, H. Hebert, B. T. Volpe, B. Diamond, S. Pettersson. The gut microbiota influences blood-brain barrier permeability in mice. Science Translational Medicine, 2014; 6 (263): 263ra158 DOI: 10.1126/scitranslmed.3009759
November 26, 2014
DZNE – German Center for Neurodegenerative Diseases
An international team of researchers has successfully determined the location, where memories are generated with a level of precision never achieved before. To this end the scientists used a particularly accurate type of magnetic resonance imaging technology.
Magnetic resonance imaging provides insights into the brain. Credit: DZNE/Guido Hennes
The human brain continuously collects information. However, we have only basic knowledge of how new experiences are converted into lasting memories. Now, an international team led by researchers of the University of Magdeburg and the German Center for Neurodegenerative Diseases (DZNE) has successfully determined the location, where memories are generated with a level of precision never achieved before. The team was able to pinpoint this location down to specific circuits of the human brain. To this end the scientists used a particularly accurate type of magnetic resonance imaging (MRI) technology. The researchers hope that the results and method of their study might be able to assist in acquiring a better understanding of the effects Alzheimer’s disease has on the brain.
The findings are reported in Nature Communications.
For the recall of experiences and facts, various parts of the brain have to work together. Much of this interdependence is still undetermined, however, it is known that memories are stored primarily in the cerebral cortex and that the control center that generates memory content and also retrieves it, is located in the brain’s interior. This happens in the hippocampus and in the adjacent entorhinal cortex.
“It is been known for quite some time that these areas of the brain participate in the generation of memories. This is where information is collected and processed. Our study has refined our view of this situation,” explains Professor Emrah Düzel, site speaker of the DZNE in Magdeburg and director of the Institute of Cognitive Neurology and Dementia Research at the University of Magdeburg. “We have been able to locate the generation of human memories to certain neuronal layers within the hippocampus and the entorhinal cortex. We were able to determine which neuronal layer was active. This revealed if information was directed into the hippocampus or whether it traveled from the hippocampus into the cerebral cortex. Previously used MRI techniques were not precise enough to capture this directional information. Hence, this is the first time we have been able to show where in the brain the doorway to memory is located.”
For this study, the scientists examined the brains of persons who had volunteered to participate in a memory test. The researchers used a special type of magnetic resonance imaging technology called “7 Tesla ultra-high field MRI.” This enabled them to determine the activity of individual brain regions with unprecedented accuracy.
A Precision method for research on Alzheimer’s
“This measuring technique allows us to track the flow of information inside the brain and examine the areas that are involved in the processing of memories in great detail,” comments Düzel. “As a result, we hope to gain new insights into how memory impairments arise that are typical for Alzheimer’s. Concerning dementia, is the information still intact at the gateway to memory? Do troubles arise later on, when memories are processed? We hope to answer such questions.”
The above story is based on materials provided by DZNE – German Center for Neurodegenerative Diseases. Note: Materials may be edited for content and length.
- Anne Maass, Hartmut Schütze, Oliver Speck, Andrew Yonelinas, Claus Tempelmann, Hans-Jochen Heinze, David Berron, Arturo Cardenas-Blanco, Kay H. Brodersen, Klaas Enno Stephan, Emrah Düzel. Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding. Nature Communications, 2014; 5: 5547 DOI: 10.1038/ncomms6547
November 6 2014, 10.00pm EST
Gut bacteria can manufacture special proteins that are very similar to hunger-regulating hormones. Lighthunter/Shutterstock
We’ve long known that that the gut is responsible for digesting food and expelling the waste. More recently, we realised the gut has many more important functions and acts a type of mini-brain, affecting our mood and appetite. Now, new research suggests it might also play a role in our cravings for certain types of food.
How does the mini-brain work?
The gut mini-brain produces a wide range of hormones and contains many of the same neurotransmitters as the brain. The gut also contains neurons that are located in the walls of the gut in a distributed network known as the enteric nervous system. In fact, there are more of these neurons in the gut than in the entire spinal cord.
The enteric nervous system communicates to the brain via the brain-gut axis and signals flow in both directions. The brain-gut axis is thought to be involved in many regular functions and systems within the healthy body, including the regulation of eating.
Let’s consider what happens to the brain-gut axis when we eat a meal. When food arrives in the stomach, certain gut hormones are secreted. These activate signalling pathways from the gut to the brainstem and the hypothalamus to stop food consumption. Such hormones include the appetite-suppressing hormones peptide YY and cholecystokinin.
Gut hormones can bind and activate receptor targets in the brain directly but there is strong evidence that the vagus nerve plays a major role in brain-gut signalling. The vagus nerve acts as a major highway in the brain-gut axis, connecting the over 100 million neurons in the enteric nervous system to the medulla (located at the base of the brain).
This brings us to the topic of food cravings. Scientists have largely debunked the myth that food cravings are our bodies’ way of letting us know that we need a specific type of nutrient. Instead, an emerging body of research suggests that our food cravings may actually be significantly shaped by the bacteria that we have inside our gut. In order to explore this further we will cover the role of gut microbes.
As many as 90% of our cells are bacterial. In fact, bacterial genes outnumber human genes by a factor of 100 to one.
The gut is an immensely complex microbial ecosystem with many different species of bacteria, some of which can live in an oxygen-free environment. An average person has approximately 1.5 kilograms of gut bacteria. The term “gut microbiota” is used to describe the bacterial collective.
Gut microbiota send signals to the brain via the brain-gut axis and can have dramatic effects on animal behaviour and health.
In one study, for example, mice that were genetically predisposed to obesity remained lean when they were raised in a sterile environment without gut microbiota. These germ-free mice were, however, transformed into obese mice when fed a faecal pellet that came from an obese mouse raised conventionally.
The role of gut microbiota in food cravings
There is growing evidence to support the role of gut microbiota in influencing why we crave certain foods.
We know that mice that are bred in germ-free environments prefer more sweets and have greater number of sweet taste receptors in their gut compared to normal mice. Research has also found that persons who are “chocolate desiring” have microbial breakdown products in their urine that are different from those of “chocolate indifferent individuals” despite eating identical diets.
Many gut bacteria can manufacture special proteins (called peptides) that are very similar to hormones such as peptide YY and ghrelin that regulate hunger. Humans and other animals have produced antibodies against these peptides. This raises the distinct possibility that microbes might be able to directly influence human eating behaviour through their peptides that mimic hunger-regulating hormones or indirectly through antibodies that can interfere with appetite regulation.
There are substantial challenges to overcome before we can apply this knowledge about gut microbiota in a practical sense.
First, there is the challenge of collecting the gut microbes. Traditionally this is collected from stools but gut microbiota is known to vary between different regions of the gut, such as the small intestine and colon. Obtaining bacterial tissue through endoscopy or another invasive collection technique in addition to stool samples may lead to more accurate representation of the gut microbiome.
Second, the type of sequencing that is currently used for gut microbiota screening is expensive and time-consuming. Advances will need to be made before this technology is in routine use.
Probably the greatest challenge in gut microbiota research is the establishment of a strong correlation between gut microbiota patterns and human disease. The science of gut microbiota is in its infancy and there needs to be much more research mapping out disease relationships.
But there is reason to be hopeful. There is now strong interest in utilising both prebiotics and probiotics to alter our gut micro biome. Prebiotics are non-digestible carbohydrates that trigger the growth of beneficial gut bacteria, while probiotics are beneficial live microorganisms contained in foods and supplements.
Faecal transplantation is also now an accepted treatment for those patients that have a severe form of gut bacterial infection called Clostridium difficile, which has been unresponsive to antibiotics.
The use of such targeted strategies is likely to become increasingly common as we better understand how gut microbiota influence our bodily functions, including food cravings.
Date: November 6, 2014
Source: Ecole Polytechnique Fédérale de Lausanne
Ghosts exist only in the mind, and scientists know just where to find them, an EPFL study suggests. Patients suffering from neurological or psychiatric conditions have often reported feeling a strange “presence.” Now, EPFL researchers in Switzerland have succeeded in recreating this so-called ghost illusion in the laboratory.
On June 29, 1970, mountaineer Reinhold Messner had an unusual experience. Recounting his descent down the virgin summit of Nanga Parbat with his brother, freezing, exhausted, and oxygen-starved in the vast barren landscape, he recalls, “Suddenly there was a third climber with us… a little to my right, a few steps behind me, just outside my field of vision.”
It was invisible, but there. Stories like this have been reported countless times by mountaineers, explorers, and survivors, as well as by people who have been widowed, but also by patients suffering from neurological or psychiatric disorders. They commonly describe a presence that is felt but unseen, akin to a guardian angel or a demon. Inexplicable, illusory, and persistent.
Olaf Blanke’s research team at EPFL has now unveiled this ghost. The team was able to recreate the illusion of a similar presence in the laboratory and provide a simple explanation. They showed that the “feeling of a presence” actually results from an alteration of sensorimotor brain signals, which are involved in generating self-awareness by integrating information from our movements and our body’s position in space.
In their experiment, Blanke’s team interfered with the sensorimotor input of participants in such a way that their brains no longer identified such signals as belonging to their own body, but instead interpreted them as those of someone else. The work is published in Current Biology.
Generating a “Ghost”
The researchers first analyzed the brains of 12 patients with neurological disorders — mostly epilepsy — who have experienced this kind of “apparition.” MRI analysis of the patients’s brains revealed interference with three cortical regions: the insular cortex, parietal-frontal cortex, and the temporo-parietal cortex. These three areas are involved in self-awareness, movement, and the sense of position in space (proprioception). Together, they contribute to multisensory signal processing, which is important for the perception of one’s own body.
The scientists then carried out a “dissonance” experiment in which blindfolded participants performed movements with their hand in front of their body. Behind them, a robotic device reproduced their movements, touching them on the back in real time. The result was a kind of spatial discrepancy, but because of the synchronized movement of the robot, the participant’s brain was able to adapt and correct for it.
Next, the neuroscientists introduced a temporal delay between the participant’s movement and the robot’s touch. Under these asynchronous conditions, distorting temporal and spatial perception, the researchers were able to recreate the ghost illusion.
An “Unbearable” Experience
The participants were unaware of the experiment’s purpose. After about three minutes of the delayed touching, the researchers asked them what they felt. Instinctively, several subjects reported a strong “feeling of a presence,” even counting up to four “ghosts” where none existed. “For some, the feeling was even so strong that they asked to stop the experiment,” said Giulio Rognini, who led the study.
“Our experiment induced the sensation of a foreign presence in the laboratory for the first time. It shows that it can arise under normal conditions, simply through conflicting sensory-motor signals,” explained Blanke. “The robotic system mimics the sensations of some patients with mental disorders or of healthy individuals under extreme circumstances. This confirms that it is caused by an altered perception of their own bodies in the brain.”
A Deeper Understanding of Schizophrenia
In addition to explaining a phenomenon that is common to many cultures, the aim of this research is to better understand some of the symptoms of patients suffering from schizophrenia. Such patients often suffer from hallucinations or delusions associated with the presence of an alien entity whose voice they may hear or whose actions they may feel. Many scientists attribute these perceptions to a malfunction of brain circuits that integrate sensory information in relation to our body’s movements.
“Our brain possesses several representations of our body in space,” added Giulio Rognini. “Under normal conditions, it is able to assemble a unified self-perception of the self from these representations. But when the system malfunctions because of disease — or, in this case, a robot — this can sometimes create a second representation of one’s own body, which is no longer perceived as ‘me’ but as someone else, a ‘presence’.”
It is unlikely that these findings will stop anyone from believing in ghosts. However, for scientists, it’s still more evidence that they only exist in our minds.
Watch the video: http://youtu.be/GnusbO8QjbE
- Olaf Blanke, Polona Pozeg, Masayuki Hara, Lukas Heydrich, Andrea Serino, Akio Yamamoto, Toshiro Higuchi, Roy Salomon, Margitta Seeck, Theodor Landis, Shahar Arzy, Bruno Herbelin, Hannes Bleuler, Giulio Rognini. Neurological and Robot-Controlled Induction of an Apparition. Current Biology, 2014; DOI:10.1016/j.cub.2014.09.049
Date: November 5, 2014
Source: University of Washington
Sometimes, words just complicate things. What if our brains could communicate directly with each other, bypassing the need for language?
University of Washington researchers have successfully replicated a direct brain-to-brain connection between pairs of people as part of a scientific study following the team’s initial demonstration a year ago. In the newly published study, which involved six people, researchers were able to transmit the signals from one person’s brain over the Internet and use these signals to control the hand motions of another person within a split second of sending that signal.
At the time of the first experiment in August 2013, the UW team was the first to demonstrate two human brains communicating in this way. The researchers then tested their brain-to-brain interface in a more comprehensive study, published Nov. 5 in the journal PLOS ONE.
“The new study brings our brain-to-brain interfacing paradigm from an initial demonstration to something that is closer to a deliverable technology,” said co-author Andrea Stocco, a research assistant professor of psychology and a researcher at UW’s Institute for Learning & Brain Sciences. “Now we have replicated our methods and know that they can work reliably with walk-in participants.”
Collaborator Rajesh Rao, a UW associate professor of computer science and engineering, is the lead author on this work.
The research team combined two kinds of noninvasive instruments and fine-tuned software to connect two human brains in real time. The process is fairly straightforward. One participant is hooked to an electroencephalography machine that reads brain activity and sends electrical pulses via the Web to the second participant, who is wearing a swim cap with a transcranial magnetic stimulation coil placed near the part of the brain that controls hand movements.
Using this setup, one person can send a command to move the hand of the other by simply thinking about that hand movement.
The UW study involved three pairs of participants. Each pair included a sender and a receiver with different roles and constraints. They sat in separate buildings on campus about a half mile apart and were unable to interact with each other in any way — except for the link between their brains.
Each sender was in front of a computer game in which he or she had to defend a city by firing a cannon and intercepting rockets launched by a pirate ship. But because the senders could not physically interact with the game, the only way they could defend the city was by thinking about moving their hand to fire the cannon.
Across campus, each receiver sat wearing headphones in a dark room — with no ability to see the computer game — with the right hand positioned over the only touchpad that could actually fire the cannon. If the brain-to-brain interface was successful, the receiver’s hand would twitch, pressing the touchpad and firing the cannon that was displayed on the sender’s computer screen across campus.
Researchers found that accuracy varied among the pairs, ranging from 25 to 83 percent. Misses mostly were due to a sender failing to accurately execute the thought to send the “fire” command. The researchers also were able to quantify the exact amount of information that was transferred between the two brains.
Another research team from the company Starlab in Barcelona, Spain, recently published results in the same journal showing direct communication between two human brains, but that study only tested one sender brain instead of different pairs of study participants and was conducted offline instead of in real time over the Web.
Now, with a new $1 million grant from the W.M. Keck Foundation, the UW research team is taking the work a step further in an attempt to decode and transmit more complex brain processes.
With the new funding, the research team will expand the types of information that can be transferred from brain to brain, including more complex visual and psychological phenomena such as concepts, thoughts and rules.
They’re also exploring how to influence brain waves that correspond with alertness or sleepiness. Eventually, for example, the brain of a sleepy airplane pilot dozing off at the controls could stimulate the copilot’s brain to become more alert.
The project could also eventually lead to “brain tutoring,” in which knowledge is transferred directly from the brain of a teacher to a student.
“Imagine someone who’s a brilliant scientist but not a brilliant teacher. Complex knowledge is hard to explain — we’re limited by language,” said co-author Chantel Prat, a faculty member at the Institute for Learning & Brain Sciences and a UW assistant professor of psychology.
Other UW co-authors are Joseph Wu of computer science and engineering; Devapratim Sarma and Tiffany Youngquist of bioengineering; and Matthew Bryan, formerly of the UW.
The research published in PLOS ONE was initially funded by the U.S. Army Research Office and the UW, with additional support from the Keck Foundation.
- Rajesh P. N. Rao, Andrea Stocco, Matthew Bryan, Devapratim Sarma, Tiffany M. Youngquist, Joseph Wu, Chantel S. Prat. A Direct Brain-to-Brain Interface in Humans. PLoS ONE, 2014; 9 (11): e111332 DOI: 10.1371/journal.pone.0111332