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### FARM ROBOT LEARNS WHAT WEEDS LOOK LIKE, SMASHES THEM

#### WEEDING WITH MACHINE LEARNING, NOT HERBICIDES

Bosch | Bonirob is more than 90 percent effective in destroying weeds in carrot cultivation trials.

While the world’s first fully-robotic farm will operate indoors, traditional outdoor farms aren’t immune to the coming robotic revolution.

Bonirob, developed by Bosch's Deepfield Robotics, is billed to eliminate some of the most tedious tasks in modern farming, plant breeding, and weeding. The autonomous robot is built to be a mobile plant lab, able to decide which strains of plant are most apt to survive insects and viruses and how much fertilizer they would need, and then smash any weeds with a ramming rod.

How does it know? Bonirob employs a type of machine learning (a stab at artificial intelligence) called decision tree learning. Researchers show Bonirob lots of pictures of healthy leaves that are tagged to be good, and pictures of weeds that are tagged to be bad, and the machine makes a series of choices based on observed in new data to judge whether a plant in the field is good or bad. Those algorithms are tweaked as the machine collects its own new images.

“Over time, based on parameters such as leaf color, shape, and size, Bonirob learns how to differentiate more and more accurately between the plants we want and the plants we don’t want,” says Amos Albert, general manager of Deepfield.

The robot’s weeding mechanism (a.k.a. ramming death rod) is meant to structurally destroy weeds so that desired plants have a growth advantage. In carrot cultivation trials, the death stick was more than 90 percent effective, according to Deepfield communications lead Birgit Schulz. It's also completely mechanical, which means no herbicides.

Crops like carrots usually require hand-weeding to ensure an optimal harvest, traditionally done by farm workers. Schulz says that a fleet of Bonirobs could share data about which areas need more weeding, and make the process even more effective.

Bonirob is now available as a researcher platform, but farmers will have to wait a little longer. (Although German Chancellor Angela Merkel

.) Deepfield claims that within 20-30 years, Bonirob could change farming as we know it completely.

#### TAGS:

 Palabra(s) clave: BONIROBBOSCHFARMINGWEEDINGRAMMING RODDEATH STICKCARROTSMACHINE LEARNINGAUTONOMYENVIRONMENT

### Feeling anxious? Check your orbitofrontal cortex and cultivate your optimism, study suggests

by Editor

Glass half full or half empty? What you see may depend in part on the size of your orbitofrontal cortex. Optimistic people also tend to be less anxious, research finds.  Image credit: Julie McMahon

A new study links anxiety, the orbitofrontal cortex (OFC), and optimism, finding that healthy adults who have larger OFCs tend to be more optimistic and less anxious.

The new analysis, reported in the journal Social, Cognitive and Affective Neuroscience, offers the first evidence that optimism plays a mediating role in the relationship between the size of the OFC and anxiety.

Anxiety disorders afflict roughly 44 million people in the U.S. These disorders disrupt lives and cost an estimated $42 billion to$47 billion annually, scientists report.

The orbitofrontal cortex, a brain region located just behind the eyes, is known to play a role in anxiety. The OFC integrates intellectual and emotional information and is essential to behavioral regulation. Previous studies have found links between the size of a person's OFC and his or her susceptibility to anxiety. For example, in a well-known study of young adults whose brains were imaged before and after the colossal 2011 earthquake and tsunami in Japan, researchers discovered that the OFC actually shrank in some study subjects within four months of the disaster. Those with more OFC shrinkage were likely to also be diagnosed with post-traumatic stress disorder, the researchers found.

Other studies have shown that more optimistic people tend to be less anxious, and that optimistic thoughts increase OFC activity.

The team on the new study hypothesized that a larger OFC might act as a buffer against anxiety in part by boosting optimism.

Most studies of anxiety focus on those who have been diagnosed with anxiety disorders, said University of Illinois researcher Sanda Dolcos, who led the research with graduate student Yifan Hu and psychology professor Florin Dolcos. "We wanted to go in the opposite direction," she said. "If there can be shrinkage of the orbitofrontal cortex and that shrinkage is associated with anxiety disorders, what does it mean in healthy populations that have larger OFCs? Could that have a protective role?"

The researchers also wanted to know whether optimism was part of the mechanism linking larger OFC brain volumes to lesser anxiety.

The team collected MRIs of 61 healthy young adults and analyzed the structure of a number of regions in their brains, including the OFC. The researchers calculated the volume of gray matter in each brain region relative to the overall volume of the brain. The study subjects also completed tests that assessed their optimism and anxiety, depression symptoms, and positive (enthusiastic, interested) and negative (irritable, upset) affect.

A statistical analysis and modeling revealed that a thicker orbitofrontal cortex on the left side of the brain corresponded to higher optimism and less anxiety. The model also suggested that optimism played a mediating role in reducing anxiety in those with larger OFCs. Further analyses ruled out the role of other positive traits in reducing anxiety, and no other brain structures appeared to be involved in reducing anxiety by boosting optimism.

"You can say, 'OK, there is a relationship between the orbitofrontal cortex and anxiety. What do I do to reduce anxiety?'" Sanda Dolcos said. "And our model is saying, this is working partially through optimism. So optimism is one of the factors that can be targeted."

"Optimism has been investigated in social psychology for years. But somehow only recently did we start to look at functional and structural associations of this trait in the brain," Hu said. "We wanted to know: If we are consistently optimistic about life, would that leave a mark in the brain?"

Florin Dolcos said future studies should test whether optimism can be increased and anxiety reduced by training people in tasks that engage the orbitofrontal cortex, or by finding ways to boost optimism directly.

"If you can train people's responses, the theory is that over longer periods, their ability to control their responses on a moment-by-moment basis will eventually be embedded in their brain structure," he said.

### Fetal cells influence mom's health during pregnancy — and long after

by Editor

Parents go to great lengths to ensure the health and well-being of their developing offspring. The favor, however, may not always be returned.

Dramatic research has shown that during pregnancy, cells of the fetus often migrate through the placenta, taking up residence in many areas of the mother's body, where their influence may benefit or undermine maternal health.

The presence of fetal cells in maternal tissue is known as fetal microchimerism. The term alludes to the chimeras of ancient Greek myth--composite creatures built from different animal parts, like the goat-lion-serpent depicted in an Etruscan bronze sculpture.

According to Amy Boddy, a researcher in the Department of Psychology at Arizona State University (ASU) and lead author of a new study, chimeras exist. Indeed, many humans bear chimerical traits in the form of foreign cells from parents, siblings or offspring, acquired during pregnancy.

"Fetal cells can act as stem cells and develop into epithelial cells, specialized heart cells, liver cells and so forth. This shows that they are very dynamic and play a huge role in the maternal body. They can even migrate to the brain and differentiate into neurons," Boddy says "We are all chimeras."

Fellow ASU researchers Angelo Fortunato, Melissa Wilson Sayres and Athena Aktipis joined Boddy for the new study. Fortunato is with the Biodesign's Institute's Human and Comparative Genomics Lab. Wilson Sayres and Aktipis--both with Biodesign's Center for Evolution and Medicine-- are also researchers with ASU's School of Life Sciences and Department of Psychology, respectively.

#### Mother's little helpers?

While fetal microchimerism is a common occurrence across placental mammals, (including humans), the effects of such cells on maternal health remain a topic of fierce debate in the biological community.

In research appearing in the advanced online edition of the journal Bioessays, Boddy and her colleagues review the available literature on fetal microchimerism and human health, applying an evolutionary framework to predict when fetal cells are inclined to act cooperatively to enhance maternal health and when their behavior is likely to be competitive, occasionally leading to adverse effects on the mother.

Fetal cells may do more than simply migrate to maternal tissues. The authors suggest they can act as a sort of placenta outside the womb, redirecting essential assets from the maternal body to the developing fetus. Cells derived from the fetus--which can persist in maternal tissues for decades after a child is born--have been associated with both protection and increased susceptibility to a range of afflictions, including cancer and autoimmune diseases like rheumatoid arthritis.

But, as co-author Wilson Sayres, cautions, "it's not only a tug of war between maternal and fetal interests. There is also a mutual desire for the maternal system to survive and provide nutrients and for the fetal system to survive and pass on DNA."

If some degree of fetal microchimerism exerts a beneficial effect on maternal and offspring survival, it will likely be selected for by evolution as an adaptive strategy.

A review of existing data on fetal microchimerism and health suggests that fetal cells enter a cooperative relationship in some maternal tissues, compete for resources in other tissues and may exist as neutral entities--hitchhikers simply along for the ride. It is likely that fetal cells play each of these roles at various times.

For example, fetal cells may contribute to inflammatory responses and autoimmunity in the mother, when they are recognized as foreign entities by the maternal immune system. This may account in part for higher rates of autoimmunity in women. (For example, women have three times higher rates of rheumatoid arthritis, compared with men).

Fetal cells can also provide benefits to mothers, migrating to damaged tissue and repairing it. Their presence in wounds--including caesarian incisions--points to their active participation in healing. In other cases, fetal cells from the placenta are swept through the bloodstream into areas including the lung, where they may persist merely as bystanders.

Applying a cooperation and conflict approach, the authors make testable predictions about the circumstances favoring fetal cell cooperation or competition and attendant positive or negative effects on maternal health.

"Cooperation theory and evolutionary analyses are powerful tools for helping us to unravel the complex effects of fetal cells on the maternal body. They can help us to predict when fetal cells are likely to contribute to maternal health and when they may be manipulating maternal tissues for the benefit of the offspring and potentially contributing to maternal disease in the process," says Aktipis.

Evolutionary theory suggests that fetal cells will act cooperatively to enhance maternal health where the economic cost of doing so is low, for example, in tissue maintenance. Where the cost to fetal cells is high, including the division of limited resources between fetus and mother, competition is the more likely outcome, with escalating conflict leading to harmful effects for mother, developing fetus or both.

Fetal cells appear to play a complex role in the female breast and have been detected in over half of all women sampled. Given the co-evolution of maternal and fetal cells over the 160 million year course of placental mammalian evolution, it appears likely that fetal cells are active participants in breast development and lactation.

Milk production is a vital but energy-intensive activity for the mother, requiring subtle regulation. Poor lactation--a common affliction--may be linked with low fetal cell count in breast tissue. (The hypothesis suggests that a simple, non-invasive test for fetal cell abundance in breast milk could provide the first conclusive evidence of fetal cell influence on maternal health).

With respect to breast cancer, existing data paints a complex picture. Fetal cells are generally found in lower abundance in women with breast cancer, compared with healthy women, suggesting they may play a protective role. On the other hand, some data indicates that fetal cells may be linked with a transient increase in the risk of breast cancer in the years immediately following pregnancy.

The thyroid gland performs a broad range of regulatory functions and during pregnancy, is involved in the efficient transfer of heat from the mother to the offspring. Again, fetal cells found in the thyroid are implicated and may be manipulating thyroid activity to enhance heat transfer to the fetus, potentially at the energetic expense of the mother.

Fetal cells occur more frequently in both the blood and thyroid tissue of women with thyroid diseases including Hashimoto's thyroiditis, Graves' disease and thyroid cancer, compared with healthy women. (Intriguingly, cancer of the thyroid is the only non-sex-specific form of cancer found more frequently in women than men.) The authors suggest that the maternal system, in attempting to wrest control from fetal cell influence, may induce hazardous levels of autoimmunity and inflammation.

#### Fetal attraction

The current overview represents a tentative step toward untangling the myriad influences of fetal microchimerism on human health. One of the more tantalizing possibilities raised in the new study is that fetal cells may be commandeering neural pathways overseeing emotion and behavior. They may, for example, hijack mechanisms triggering the release of oxytocin, a hormone long associated with the emotional bonding of mother and infant.

Indeed, fetal cells could be suspects in a broad range of physical and emotional manifestations in the mother, including pregnancy-related afflictions like morning sickness or postpartum depression. Even early onset menopause could be the result of fetal cell efforts to remove the mother from further child-bearing, in order to secure maximum resources for the fetus and eventually, the growing child.

Finally, the authors note, fetal microchimerism may be one piece of a subtle and dizzyingly complex puzzle. Cell traffic is actually bi-directional, with the fetus receiving cells from the mother. Fetal cells from maternal tissue may cross the placental barrier during subsequent pregnancies, potentially influencing the health of later offspring. To further complicate matters, cells from later fetuses can also cross the placenta to enter the microchimeric arena, perhaps introducing sibling rivalries for the mother's limited resources.

Fetal cells may eventually provide a novel and powerful means of diagnosing existing conditions and predicting long-term maternal health. As the authors note, they could also be applied therapeutically in the future, potentially for the treatment of poor lactation, for wound healing, tumor reduction and perhaps even pregnancy-linked psychological disorders.

Identification of fetal cells in maternal gut, liver or brain tissues is only a first step.

To tease out the true function of these cells, researchers need to examine their gene expression and interaction with maternal tissues. Inspection of maternal cells in surrounding tissue will help determine if they are immune cells targeting fetal cell interlopers or normal epithelial cells, existing in harmony.

"If future research bears out the predictions of this framework, it could transform the way we approach, treat and prevent a variety of diseases that affect women, especially new mothers," says Aktipis.

Improved methods of screening will help scientists listen in on the intricate dialog between fetal and maternal cells, deepening our understanding of maternal health and disease.

Note: Material may have been edited for length and content. For further information, please contact the cited source.

#### Publication

Aktipis, A et al. Fetal microchimerism and maternal health: A review and evolutionary analysis of cooperation and conflict beyond the womb. BioEssays, Published Online August 28 2015. doi: 10.1002/bies.201500059

 Palabra(s) clave: Fetal cellsmom's healthpregnancy

#### “La mayor parte de los filósofos actuales se ocupa de menudencias”

Entrevista al filósofo Mario Bunge

por Juan Claudio de Ramón

Es uno de los grandes filósofos vivos, Premio Príncipe de Asturias de Humanidades en 1982, doctor Honoris Causa por 19 universidades y único autor de habla española que se encuentra, con 43 milidarwins, entre los científicos “más famosos de los últimos 200 años” (The Science Hall of Fame). No está mal para ser un heterodoxo. Porque Bunge, profesor emérito de la Universidad de McGill, es un realista: cree, humildemente, que la realidad existe; desde los anillos de Saturno hasta el último quark, las cosas son de verdad. Y la realidad estuvo muy mal considerada por la filosofía del siglo XX, que solo era capaz de ver, de manera oscura y confusa, estructuras, signos y discursos.

Bunge operó de cataratas en su impresionante Tratado de Filosofía Básica en ocho volúmenes, y en más de 50 libros y 500 artículos en los que saca el polvo a la filosofía de la ciencia, física teórica, química, neurociencia, ciencia cognitiva, matemáticas, psicología y sociología. Escribe en inglés y en castellano, en grande y en pequeño, pero siempre con letra clara y sin miramientos, porque es de los que piensa que ningún adversario de valía se molesta por una crítica contundente. Me citó en Montreal, una tarde de mayo del año en que va a cumplir 94. Llama la atención la apostura, la mirada azul que arde lentamente. Sobre la mesa y el sofá hay docenas de libros y revistas desparramadas. Puedo distinguir una biografía de Marx y otra de Popper, las Analectas de Confucio junto a un tratado de Helvetius, los semanarios Science y Nature encima de números atrasados del New York Review of Books. Es otra manera de entender la lujuria.

Continuar leyendo en el sitio http://kwfoundation.org
 Palabra(s) clave: Filosofía

#### 8 EL FINAL DE LA VIDA - EL CUERPO HUMANO - DOCUMENTAL BBC

 Palabra(s) clave: MUERTEBBC

### First computers recognized our faces, now they know what we’re doing

We haven't designed fully sentient artificial intelligence just yet, but we're steadily teaching computers how to see, read, and understand our world. Last month, Google engineers showed off their "Deep Dream," software capable of taking an image and ascertaining what was in it by turning it into a nightmare fusion of flesh and tentacles. The release follows research by scientists from Stanford University, who developed a similar program called NeuralTalk, capable of analyzing images and describing them with eerily accurate sentences.

First published last year, the program and the accompanying study is the work of Fei-Fei Li, director of the Stanford Artificial Intelligence Laboratory, and Andrej Karpathy, a graduate student. Their software is capable of looking at pictures of complex scenes and identifying exactly what's happening. A picture of a man in a black shirt playing guitar, for example, is picked out as "man in black shirt is playing guitar," while pictures of a black-and-white dog jumping over a bar, a man in a blue wetsuit surfing a wave, and little girl eating cake are also correctly described with a single sentence. In several cases, it's unnervingly accurate.

Like Google's Deep Dream, the software uses a neural network to work out what's going on in each picture, comparing parts of the image to those it's already seen and describing them as humans would. Neural networks are designed to be like human brains, and they work a little like children. Once they've been taught the basics of our world — that's what a window usually looks like, that's what a table usually looks like, that's what a cat who's trying to eat a cheeseburger looks like — then they can apply that understanding to other pictures and video.

It's still not perfect. A fully-grown woman gingerly holding a huge donut is tagged as "a little girl holding a blow dryer next to her head," while an inquisitive giraffe is mislabeled as a dog looking out of a window. A cheerful couple in a garden with a birthday cake appears under the heading "a man in a green shirt is standing next to an elephant," with a bush starring as the elephant and, weirdly, the cake standing in for the man. But in most cases, these descriptions are secondary guesses — alongside the elephant suggestion, the program also correctly identifies the cake couple as "a woman standing outside holding a coconut cake with a man looking on."

"The software easily identifies a dog jumping over a bar."

The incredible amount of visual information on the internet has, until recently, had to be manually labeled in order for it to be searchable. When Google first built Google Maps, it relied on a team of employees to dig through and check every single entry, humans given the task of looking at every number captured in the world to make sure it denoted a real address. When they were done, and sick of the tiresome job, they built Google Brain. Where it had previously taken a team weeks of work to complete the task, Google Brain could transcribe all of the Street View data from France in under an hour.

"I consider the pixel data in images and video to be the dark matter of the Internet," Li told The New York Times last year. "We are now starting to illuminate it." Leading the charge for that illumination are web giants such as Facebook and Google, who are keen to categorize the millions of pictures and search results they need to sift through. Previous research focused on single object recognition — in a 2012 Google study, a computer taught itself to recognize a cat — but computer scientists have said this misses the bigger picture. "We've focused on objects, and we've ignored verbs," Ali Farhadi, computer scientist at the University of Washington, told The New York Times.

But more recent programs have focused on more complex strings of data in an attempt trying to teach computers what's happening in a picture rather than simply what's in shot. The Stanford scientists' study uses the kind of natural language we could eventually use to search through image repositories, leading to an easy hypothetical situation where rather than scanning through tens of thousands of family photos, services such as Google Photos can quickly pull up "the one where the dog is jumping on the couch," or "the selfie I took in Times Square." Search results, too, would benefit from the technology, potentially allowing you to search YouTube or Google for the exact scenes you want, rather than simply finding the pictures or videos their uploaders were mindful enough to correctly label.

Neural networks have potential applications out in the real world, too. At CES this year, Nvidia's Jen-Hsun Huang announced his company's Drive PX, a "supercomputer" for your car that incorporated "deep neural network computer vision." Using the same learning techniques as other neural networks, Huang said the technology will be able to automatically spot hazards as you drive, warning you of pedestrians, signs, ambulances, and other objects that it's learned about. The neural network means the Drive PX won't need to have reference images for every kind of car — if it's got four wheels like a car, a grille like a car, and a windscreen like a car, it's probably a car. Larger cars could be SUVs, while cars with lights on top could be police vehicles. Huang's company has been chasing this technology for a while, too, having provided the graphics processing units actually used by the Stanford team.

As the technology to automatically work out what's happening in images is progressing rapidly, its leaders are making their efforts available to all on code repositories such as GitHub. Google's Deep Dream, in particular, has captured the imagination of many with its trippy visual side effects, contorting images into the shapes of dogs and slugs as it attempts to find reference points it understands. But the proliferation of this machine learning has a creepy side too — if your computer can work out exactly what's happening in your pictures, what happens when it works out exactly what you are?

#### First Contracting Human Muscle Grown in Laboratory [1061]

A microscopic view of lab-grown human muscle bundles stained to show patterns made by basic muscle units and their associated proteins (red), which are a hallmark of human muscle. DUKE UNIVERSITY

### First Contracting Human Muscle Grown in Laboratory

Researchers at Duke University report the first lab-grown, contracting human muscle, which could revolutionize drug discovery and personalized medicine.

In a laboratory first, Duke researchers have grown human skeletal muscle that contracts and responds just like native tissue to external stimuli such as electrical pulses, biochemical signals and pharmaceuticals.

The lab-grown tissue should soon allow researchers to test new drugs and study diseases in functioning human muscle outside of the human body.

The study was led by Nenad Bursac, associate professor of biomedical engineering at Duke University, and Lauran Madden, a postdoctoral researcher in Bursac’s laboratory. It appears January 13 in the open-access journal eLife

“The beauty of this work is that it can serve as a test bed for clinical trials in a dish,” said Bursac. “We are working to test drugs’ efficacy and safety without jeopardizing a patient’s health and also to reproduce the functional and biochemical signals of diseases—especially rare ones and those that make taking muscle biopsies difficult.”

Bursac and Madden started with a small sample of human cells that had already progressed beyond stem cells but hadn’t yet become muscle tissue. They expanded these “myogenic precursors” by more than a 1000-fold, and then put them into a supportive, 3D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning muscle fibers.

“We have a lot of experience making bioartifical muscles from animal cells in the laboratory, and it still took us a year of adjusting variables like cell and gel density and optimizing the culture matrix and media to make this work with human muscle cells,” said Madden.

Two lab-grown human muscle bundles stretched in a rectangular frame submerged in a medium. DUKE UNIVERSITY

Madden subjected the new muscle to a barrage of tests to determine how closely it resembled native tissue inside a human body. She found that the muscles robustly contracted in response to electrical stimuli—a first for human muscle grown in a laboratory. She also showed that the signaling pathways allowing nerves to activate the muscle were intact and functional.

To see if the muscle could be used as a proxy for medical tests, Bursac and Madden studied its response to a variety of drugs, including statins used to lower cholesterol and clenbuterol, a drug known to be used off-label as a performance enhancer for athletes.

The effects of the drugs matched those seen in human patients. The statins had a dose-dependent response, causing abnormal fat accumulation at high concentrations. Clenbuterol showed a narrow beneficial window for increased contraction. Both of these effects have been documented in humans. Clenbuterol does not harm muscle tissue in rodents at those doses, showing the lab-grown muscle was giving a truly human response.

“One of our goals is to use this method to provide personalized medicine to patients,” said Bursac. “We can take a biopsy from each patient, grow many new muscles to use as test samples and experiment to see which drugs would work best for each person.”

This goal may not be far away; Bursac is already working on a study with clinicians at Duke Medicine—including Dwight Koeberl, associate professor of pediatrics—to try to correlate efficacy of drugs in patients with the effects on lab-grown muscles. Bursac's group is also trying to grow contracting human muscles using induced pluripotent stem cells instead of biopsied cells.

“There are a some diseases, like Duchenne Muscular Dystrophy for example, that make taking muscle biopsies difficult,” said Bursac. “If we could grow working, testable muscles from induced pluripotent stem cells, we could take one skin or blood sample and never have to bother the patient again.”

Other investigators involved in this study include George Truskey, the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering and senior associate dean for research for the Pratt School of Engineering, and William Krauss, professor of biomedical engineering, medicine and nursing at Duke University.

The research was supported by NIH Grants R01AR055226 and R01AR065873 from the National Institute of Arthritis and Musculoskeletal and Skin Disease and UH2TR000505 from the NIH Common Fund for the Microphysiological Systems Initiative.

Categories: News

 Palabra(s) clave: FirstContracting Human MuscleGrown in Laboratory

### First Human Tests of Memory Boosting Brain Implant a Big Leap Forward

“You have to begin to lose your memory, if only bits and pieces, to realize that memory is what makes our lives. Life without memory is no life at all.” — Luis Buñuel Portolés, Filmmaker

Every year, hundreds of millions of people experience the pain of a failing memory.

The reasons are many: traumatic brain injury, which haunts a disturbingly high number of veterans and football players; stroke or Alzheimer’s disease, which often plagues the elderly; or even normal brain aging, which inevitably touches us all.

Memory loss seems to be inescapable. But one maverick neuroscientist is working hard on an electronic cure. Funded by DARPA, Dr. Theodore Berger, a biomedical engineer at the University of Southern California, is testing a memory-boosting implant that mimics the kind of signal processing that occurs when neurons are laying down new long-term memories.

The revolutionary implant, already shown to help memory encoding in rats and monkeys, is now being tested in human patients with epilepsy — an exciting first that may blow the field of memory prosthetics wide open.

To get here, however, the team first had to crack the memory code.

#### Deciphering Memory

From the very onset, Berger knew he was facing a behemoth of a problem.

We weren’t looking to match everything the brain does when it processes memory, but to at least come up with a decent mimic, said Berger.

“Of course people asked: can you model it and put it into a device? Can you get that device to work in any brain? It’s those things that lead people to think I’m crazy. They think it’s too hard,” he said.

But the team had a solid place to start.

The hippocampus, a region buried deep within the folds and grooves of the brain, is the critical gatekeeper that transforms memories from short-lived to long-term. In dogged pursuit, Berger spent most of the last 35 years trying to understand how neurons in the hippocampus accomplish this complicated feat.

At its heart, a memory is a series of electrical pulses that occur over time that are generated by a given number of neurons, said Berger. This is important — it suggests that we can reduce it to mathematical equations and put it into a computational framework, he said.

Berger hasn’t been alone in his quest.

By listening to the chatter of neurons as an animal learns, teams of neuroscientists have begun to decipher the flow of information within the hippocampus that supports memory encoding. Key to this process is a strong electrical signal that travels from CA3, the “input” part of the hippocampus, to CA1, the “output” node.

This signal is impaired in people with memory disabilities, said Berger, so of course we thought if we could recreate it using silicon, we might be able to restore — or even boost — memory.

#### Bridging the Gap

Yet this brain’s memory code proved to be extremely tough to crack.

The problem lies in the non-linear nature of neural networks: signals are often noisy and constantly overlap in time, which leads to some inputs being suppressed or accentuated. In a network of hundreds and thousands of neurons, any small change could be greatly amplified and lead to vastly different outputs.

It’s a chaotic black box, laughed Berger.

With the help of modern computing techniques, however, Berger believes he may have a crude solution in hand. His proof?

Use his mathematical theorems to program a chip, and then see if the brain accepts the chip as a replacement — or additional — memory module.

Berger and his team began with a simple task using rats. They trained the animals to push one of two levers to get a tasty treat, and recorded the series of CA3 to CA1 electronic pulses in the hippocampus as the animals learned to pick the correct lever. The team carefully captured the way the signals were transformed as the session was laid down into long-term memory, and used that information — the electrical “essence” of the memory — to program an external memory chip.

They then injected the animals with a drug that temporarily disrupted their ability to form and access long-term memories, causing the animals to forget the reward-associated lever. Next, implanting microelectrodes into the hippocampus, the team pulsed CA1, the output region, with their memory code.

The results were striking — powered by an external memory module, the animals regained their ability to pick the right lever.

Encouraged by the results, Berger next tried his memory implant in monkeys, this time focusing on a brain region called the prefrontal cortex, which receives and modulates memories encoded by the hippocampus.

Placing electrodes into the monkey’s brains, the team showed the animals a series of semi-repeated images, and captured the prefrontal cortex’s activity when the animals recognized an image they had seen earlier. Then with a hefty dose of cocaine, the team inhibited that particular brain region, which disrupted the animal’s recall.

Next, using electrodes programmed with the “memory code,” the researchers guided the brain’s signal processing back on track — and the animal’s performance improved significantly.

A year later, the team further validated their memory implant by showing it could also rescue memory deficits due to hippocampal malfunction in the monkey brain.

#### A Human Memory Implant

Last year, the team cautiously began testing their memory implant prototype in human volunteers.

Because of the risks associated with brain surgery, the team recruited 12 patients with epilepsy, who already have electrodes implanted into their brain to track down the source of their seizures.

Repeated seizures steadily destroy critical parts of the hippocampus needed for long-term memory formation, explained Berger. So if the implant works, it could benefit these patients as well.

The team asked the volunteers to look through a series of pictures, and then recall which ones they had seen 90 seconds later. As the participants learned, the team recorded the firing patterns in both CA1 and CA3 — that is, the input and output nodes.

Using these data, the team extracted an algorithm — a specific human “memory code” — that could predict the pattern of activity in CA1 cells based on CA3 input. Compared to the brain’s actual firing patterns, the algorithm generated correct predictions roughly 80% of the time.

It’s not perfect, said Berger, but it’s a good start.

Using this algorithm, the researchers have begun to stimulate the output cells with an approximation of the transformed input signal.

We have already used the pattern to zap the brain of one woman with epilepsy, said Dr. Dong Song, an associate professor working with Berger. But he remained coy about the result, only saying that although promising, it’s still too early to tell.

Song’s caution is warranted. Unlike the motor cortex, with its clear structured representation of different body parts, the hippocampus is not organized in any obvious way.

It’s hard to understand why stimulating input locations can lead to predictable results, said Dr. Thoman McHugh, a neuroscientist at the RIKEN Brain Science Institute. It’s also difficult to tell whether such an implant could save the memory of those who suffer from damage to the output node of the hippocampus.

“That said, the data is convincing,” McHugh acknowledged.

Berger, on the other hand, is ecstatic. “I never thought I’d see this go into humans,” he said.

But the work is far from done. Within the next few years, Berger wants to see whether the chip can help build long-term memories in a variety of different situations. After all, the algorithm was based on the team’s recordings of one specific task — what if the so-called memory code is not generalizable, instead varying based on the type of input that it receives?

Berger acknowledges that it’s a possibility, but he remains hopeful.

I do think that we will find a model that’s a pretty good fit for most conditions, he said. After all, the brain is restricted by its own biophysics — there’s only so many ways that electrical signals in the hippocampus can be processed, he said.

“The goal is to improve the quality of life for somebody who has a severe memory deficit,” said Berger. “If I can give them the ability to form new long-term memories for half the conditions that most people live in, I’ll be happy as hell, and so will be most patients.”

Image Credit: Shutterstock.com

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#### Fixing Fearful Memories [1135]

Horizontal section through the mouse hippocampus | WIKIMEDIA, BRAINMAPS.ORG

### Fixing Fearful Memories

Remote memories can be modified in the presence of a drug that induces epigenetic changes to DNA.

By Abby Olena

Traumatic memories are some of the most tenacious and long-lived. The more recent the memory, the more amenable it is to reconsolidation, where it is recalled and can then be modified to become less fearful. Researchers from MIT have now shown that a DNA modification that is controlled in part by the enzyme histone deacetylase 2 (HDAC2) helps make recent memories more prone to reconsolidation. The work was published last week (January 16) in Cell.

The researchers initially trained mice to fear a cage or a tone by administering a foot shock in the cage or while the tone was played. They then returned the mice to the cage or played the tone, so the animals would recall the fearful memory, tried to extinguish the memory by exposing the mice to the cue consecutively over three days, and compared the reactions of mice that had experienced the foot shock one or thirty days before. Fear could be extinguished in mice that had recently been exposed to the foot shock, but not in the mice where the memory had been in place longer.

“We showed that new fear memories can be modified or extinguished through exposure therapy, but for old memories, the exposure-based therapy is not very effective,” coauthor Li-Huei Tsai told The Los Angeles Times.

The team then showed that after recall in mice with the recent fearful memory, histone 3—one of the proteins around which DNA is packaged—was more acetylated in the hippocampus compared to both naïve mice and to mice in which the memory was more remote. They found that HDAC2, which is responsible for removing acetyl groups from histones, is modified by nitrosylation and dissociated from chromatin during recall of early memories, allowing memories to be modified. When the researchers tried drugs that blocked HDAC2 activity in mice with more remote memories, the mice were better able to reconsolidate fearful memories. They also demonstrated that epigenetic changes that were the result of restricted HDAC2 activity lead to transcription-dependent neuronal plasticity.

“Specific nitrosylation of HDAC2 obviously affects several genes important for reconsolidation updates—apparently as memories age, this mechanism fails,” Jelena Radulovic of Northwestern University’s Feinberg School of Medicine in Chicago, Illinois, who was not involved in the research, told ScienceNOW.

Some HDAC2 inhibitors are already approved by the U.S. Food and Drug Administration for the treatment of cancer, so these drugs could represent possible treatment avenues for conditions like post-traumatic stress disorder. “I hope this will convince people to seriously think about taking this into clinical trials and seeing how well it works,” Tsai said in a statement.

 Palabra(s) clave: EpigeneticsFixing Fearful Memories

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