Posts tagged neuroscience

July 23, 2012

Neural precursor cells (NPC) in the young brain suppress certain brain tumors such as high-grade gliomas, especially glioblastoma (GBM), which are among the most common and most aggressive tumors. Now researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité – Universitätsmedizin Berlin have deciphered the underlying mechanism of action with which neural precursor cells protect the young brain against these tumors. They found that the NPC release substances that activate TRPV1 ion channels in the tumor cells and subsequently induce the tumor cells to undergo stress-induced cell-death. (Nature Medicine http://dx.doi.org/10.1038/nm.2827)*.

Despite surgery, radiation or chemotherapy or even a combination of all three treatment options, there is currently no cure for glioblastoma. In an earlier study the research group led by Professor Helmut Kettenmann (MDC) showed that neural precursor cells migrate to the glioblastoma cells and attack them. The neural precursor cells release a protein belonging to the family of BMP proteins (bone morphogenetic protein) that directly attacks the tumor stem cells. The current consensus of researchers is that tumor stem cells are the actual cause for continuous tumor self-renewal.

Kristin Stock, Jitender Kumar, Professor Kettenmann (all MDC), Dr. Michael Synowitz (MDC and Charité), Professor Rainer Glass (Munich University Hospitals, formerly MDC) and Professor Vincenzo Di Marzo (Istituto di Chimica Biomolecolare Pozzuoli, Naples, Italy) now report a new mechanism of action of NPC in astrocytomas. Like glioblastomas, astrocytomas are brain tumors that belong to the family of gliomas. Gliomas are most common in older people and are almost invariably fatal.

As the MDC researchers showed, the NPC also migrate to the astrocytomas. There they do not secrete proteins, but rather release fatty-acid substances (endovanilloids) which are harmful to the cancer cells. However, in order to exert their lethal effect, the endovanilloids need the aid of a specific ion channel, the TRPV1 channel (transient receptor potential vanilloid type 1), also called the vanilloid receptor 1. TRPV1 is already known to researchers as a transducer of painful stimuli. It has, among other things, a binding site for capsaicin, the irritant of hot chili peppers, and is responsible for the hot sensation after eating them. Clinical trials are currently underway to develop new pain treatments by blocking or desensitizing this ion channel.

MDC researchers describe an additional role of the TRPV1 ion channel

In contrast to its use in pain management, this ion channel, which is located on the surface of glioblastoma cells and is much more abundant there than on normal glial cells, must be activated to trigger cell death in gliomas. The activated ion channel mediates stress-induced cell-death in tumor cells. If however TRPV1 is downregulated or blocked, the glioma cells are not destroyed. The MDC researchers are thus the first to identify neural precursor cells as the source of fatty acids that induce tumor cell death and to describe the role of the TRPV1 ion channel in the fight against gliomas.

However, the activity of neural precursor cells in the brain and thus of the body’s own protective mechanism against gliomas diminishes with increasing age. This could explain why these tumors usually develop in older adults and not in children and young people. How can the natural protection of neural precursor cells be harnessed for older brains? According to the researchers, neural precursor cell therapy is not a solution. The benefit this obviously brings in the treatment of young people can have the opposite effect in older adults and may trigger brain tumors.

One possible treatment would be to use drugs to activate the TRPV1 channels. In mice, the group showed that a synthetic substance (arvanil), which is similar to capsaicin, reduced tumor growth. However, this substance has not yet been approved as a drug because the adverse side effects for humans are too severe. It is only used in basic research on mice, which tolerate the substance well. “In principle, however,” the researchers suggest, “synthetic vanilloid compounds may have clinical potential for brain tumor treatment.”

Source: Science Codex

ScienceDaily (July 23, 2012) — A team of University of Alberta researchers has identified a new class of compounds that inhibit the spread of prions, misfolded proteins in the brain that trigger lethal neurodegenerative diseases in humans and animals.

U of A chemistry researcher Frederick West and his team have developed compounds that clear prions from infected cells derived from the brain.

"When these designer molecules were put into infected cells in our lab experiments, the numbers of misfolded proteins diminished — and in some cases we couldn’t detect any remaining misfolded prions," said West.

West and his collaborators at the U of A’s Centre for Prions and Protein Folding Diseases say this research is not yet a cure, but does open a doorway for developing treatments.

"We’re not ready to inject these compounds in prion-infected cattle," said David Westaway, director of the prion centre. "These initial compounds weren’t created for that end-run scenario but they have passed initial tests in a most promising manner."

West notes that the most promising experimental compounds at this stage are simply too big to be used therapeutically in humans or animals.

Human exposure to prion-triggered brain disorder is limited to rare cases of Creutzfeldt-Jakob or mad cow disease. The researchers say the human form of mad cow disease shows up in one in a million people in industrialized nations, but investigating the disease is nonetheless well worth the time and expense.

"There is a strong likelihood that prion diseases operate in a similar way to neurodegenerative diseases such as Alzheimer’s, which are distressingly common around the world," said West.

Source: Science Daily

 23 July 2012 by Will Heaven

Watch where you look – it can be used to predict what you’ll say. A new study shows that it is possible to guess what sentences people will use to describe a scene by tracking their eye movements.

Moreno Coco and Frank Keller at the University of Edinburgh, UK, presented 24 volunteers with a series of photo-realistic images depicting indoor scenes such as a hotel reception. They then tracked the sequence of objects that each volunteer looked at after being asked to describe what they saw.

Other than being prompted with a keyword, such as “man” or “suitcase”, participants were free to describe the scene however they liked. Some typical sentences included “the man is standing in the reception of a hotel” or “the suitcase is on the floor”.

The order in which a participant’s gaze settled on objects in each scene tended to mirror the order of nouns in the sentence used to describe it. “We were surprised there was such a close correlation,” says Keller. Given that multiple cognitive processes are involved in sentence formation, Coco says “it is remarkable to find evidence of similarity between speech and visual attention”.

Word prediction

The team used the discovery to see if they could predict what sentences would be used to describe a scene based on eye movement alone. They developed an algorithm that was able to use the eye gazes recorded from the previous experiment to predict the correct sentence from a choice of 576 descriptions.

Changsong Liu of Michigan State University’s Language and Interaction Research lab, in East Lansing, who was not involved in the study, suggests these results could motivate novel designs for human-machine interfaces that take advantage of visual cues to improve speech recognition software.

Gaze information is already used to help with disambiguation. For example, if a speech recognition system can tell that you are looking at a tree, it is less likely to guess that you just said “three”. Sentence prediction, perhaps in combination with augmented reality headsets that track eye movement, for example, is one possible application.

Coco and Keller are now looking into the role of coordinated visual and linguistic processes in conversations between two people. “People engaged in a dialogue use similar syntactic forms, expressions and eye-movements,” says Coco. One hypothesis is that such “coordinative mimicry” might be important for joint decision-making.

Source: NewScientist

Scientists find evidence that real perceptual experience and mental replay share similar brain activation patterns

Toronto, Canada – Neuroscientists have found strong evidence that vivid memory and directly experiencing the real moment can trigger similar brain activation patterns.

The study, led by Baycrest’s Rotman Research Institute (RRI), in collaboration with the University of Texas at Dallas, is one of the most ambitious and complex yet for elucidating the brain’s ability to evoke a memory by reactivating the parts of the brain that were engaged during the original perceptual experience. Researchers found that vivid memory and real perceptual experience share “striking” similarities at the neural level, although they are not “pixel-perfect” brain pattern replications.

The study appears online this month in the Journal of Cognitive Neuroscience, ahead of print publication.

"When we mentally replay an episode we’ve experienced, it can feel like we are transported back in time and re-living that moment again," said Dr. Brad Buchsbaum, lead investigator and scientist with Baycrest’s RRI. "Our study has confirmed that complex, multi-featured memory involves a partial reinstatement of the whole pattern of brain activity that is evoked during initial perception of the experience. This helps to explain why vivid memory can feel so real."

But vivid memory rarely fools us into believing we are in the real, external world – and that in itself offers a very powerful clue that the two cognitive operations don’t work exactly the same way in the brain, he explained.

In the study, Dr. Buchsbaum’s team used functional magnetic resonance imaging (fMRI), a powerful brain scanning technology that constructs computerized images of brain areas that are active when a person is performing a specific cognitive task. A group of 20 healthy adults (aged 18 to 36) were scanned while they watched 12 video clips, each nine seconds long, sourced from YouTube.com and Vimeo.com. The clips contained a diversity of content – such as music, faces, human emotion, animals, and outdoor scenery. Participants were instructed to pay close attention to each of the videos (which were repeated 27 times) and informed they would be tested on the content of the videos after the scan.

A subset of nine participants from the original group were then selected to complete intensive and structured memory training over several weeks that required practicing over and over again the mental replaying of videos they had watched from the first session. After the training, this group was scanned again as they mentally replayed each video clip. To trigger their memory for a particular clip, they were trained to associate a particular symbolic cue with each one. Following each mental replay, participants would push a button indicating on a scale of 1 to 4 (1 = poor memory, 4 = excellent memory) how well they thought they had recalled a particular clip.

Dr. Buchsbaum’s team found “clear evidence” that patterns of distributed brain activation during vivid memory mimicked the patterns evoked during sensory perception when the videos were viewed – by a correspondence of 91% after a principal components analysis of all the fMRI imaging data.

The so-called “hot spots”, or largest pattern similarity, occurred in sensory and motor association areas of the cerebral cortex – a region that plays a key role in memory, attention, perceptual awareness, thought, language and consciousness.

Dr. Buchsbaum suggested the imaging analysis used in his study could potentially add to the current battery of memory assessment tools available to clinicians. Brain activation patterns from fMRI data could offer an objective way of quantifying whether a patient’s self-report of their memory as “being good or vivid” is accurate or not.

Source: EurekAlert!

July 23, 2012

Ever wonder how the human brain, which is constantly bombarded with millions of pieces of visual information, can filter out what’s unimportant and focus on what’s most useful?

The process is known as selective attention and scientists have long debated how it works. But now, researchers at Wake Forest Baptist Medical Center have discovered an important clue. Evidence from an animal study, published in the July 22 online edition of the journal Nature Neuroscience, shows that the prefrontal cortex is involved in a previously unknown way.

Two types of attention are utilized in the selective attention process – bottom up and top down. Bottom-up attention is automatically guided to images that stand out from a background by virtue of color, shape or motion, such as a billboard on a highway. Top-down attention occurs when one’s focus is consciously shifted to look for a known target in a visual scene, as when searching for a relative in a crowd.

Traditionally, scientists have believed that separate areas of the brain controlled these two processes, with bottom-up attention occurring in the posterior parietal cortex and top-down attention occurring in the prefrontal cortex.

"Our findings provide insights on the neural mechanisms behind the guidance of attention," said Christos Constantinidis, Ph.D., associate professor of neurobiology and anatomy at Wake Forest Baptist and senior author of the study. "This has implications for conditions such as attention deficit hyperactivity disorder (ADHD), which affects millions of people worldwide. People with ADHD have difficulty filtering information and focusing attention. Our findings suggest that both the ability to focus attention intentionally and shifting attention to eye-catching but sometimes unimportant stimuli depend on the prefrontal cortex."

In the Wake Forest Baptist study, two monkeys were trained to detect images on a computer screen while activity in both areas of the brain was recorded. The visual display was designed to let one image “pop out” due to its color difference from the background, such as a red circle surrounded by green. To trigger bottom-up attention, neither the identity nor the location of the pop-out image could be predicted before it appeared. The monkeys indicated that they detected the pop-out image by pushing a lever.

The neural activity associated with identifying the pop-out images occurred in the prefrontal cortex at the same time as in the posterior parietal cortex. This unexpected finding indicates early involvement of the prefrontal cortex in bottom-up attention, in addition to its known role in top-down attention, and provides new insights into the neural mechanisms of attention.

"We hope that our findings will guide future work targeting attention deficits," Constantinidis said.

Provided by Wake Forest University Baptist Medical Center

Source: medicalxpress.com

23 July 2012 by Caroline Williams

The brainiest creatures share a secret – an odd kind of brain cell involved in emotions and empathy that may have accidentally made us conscious

The consciousness connection (Image: Jonathon Burton)

THE origin of consciousness has to be one of the biggest mysteries of all time, occupying philosophers and scientists for generations. So it is strange to think that a little-known neuroscientist called Constantin von Economo might have unearthed an important clue nearly 90 years ago.

When he peered down the lens of his microscope in 1926, von Economo saw a handful of brain cells that were long, spindly and much larger than those around them. In fact, they looked so out of place that at first he thought they were a sign of some kind of disease. But the more brains he looked at, the more of these peculiar cells he found - and always in the same two small areas that evolved to process smells and flavours.

Von Economo briefly pondered what these “rod and corkscrew cells”, as he called them, might be doing, but without the technology to delve much deeper he soon moved on to more promising lines of enquiry.

Little more was said about these neurons until nearly 80 years later when, Esther Nimchinsky and Patrick Hof at Mount Sinai University in New York also stumbled across clusters of these strange-looking neurons. Now, after more than a decade of functional imaging and post-mortem studies, we are beginning to piece together their story. Certain lines of evidence hint that they may help build the rich inner life we call consciousness, including emotions, our sense of self, empathy and our ability to navigate social relationships.

Many other big-brained, social animals also seem to share these cells, in the same spots as the human brain. A greater understanding of the way these paths converged could therefore tell us much about the evolution of the mind.

Admittedly, to the untrained eye these giant brain cells, now known as von Economo neurons (VENs), don’t look particularly exciting. But to a neuroscientist they stand out like a sore thumb. For one thing, VENs are at least 50 per cent, and sometimes up to 200 per cent, larger than typical human neurons. And while most neurons have a pyramid-shaped body with a finely branched tree of connections called dendrites at each end of the cell, VENs have a longer, spindly cell body with a single projection at each end with very few branches. 

Perhaps they escaped attention for so long because they are so rare, making up just 1 per cent of the neurons in the two small areas of the human brain: the anterior cingulate cortex (ACC) and the fronto-insular (FI) cortex.

Their location in those regions suggests that VENs may be a central part of our mental machinery, since the ACC and FI are heavily involved in many of the more advanced aspects of our inner lives. Both areas kick into action when we see socially relevant cues, be it a frowning face, a grimace of pain or simply the voice of someone we love. When a mother hears a baby crying, both regions respond strongly. They also light up when we experience emotions such as love, lust, anger and grief. For John Allman, a neuroanatomist at the California Institute of Technology in Pasadena, this adds up to a kind of “social monitoring network” that keeps track of social cues and allows us to alter our behaviour accordingly (Annals of the New York Academy of Sciences, vol 1225, p 59).

The two brain areas also seem to play a key role in the “salience” network, which keeps a subconscious tally of what is going on around us and directs our attention to the most pressing events, as well as monitoring sensations from the body to detect any changes (Brain Structure and Function, DOI: 10.1007/s00429-012-0382-9).

What’s more, both regions are active when a person recognises their reflection in the mirror, suggesting that these parts of the brain underlie our sense of self - a key component of consciousness. “It is the sense of self at every possible level - so the sense of identity, this is me, and the sense of identity of others and how you understand others. That goes to the concept of empathy and theory of mind,” says Hof.

To Bud Craig, a neuroanatomist at Barrow Neurological Institute in Phoenix, Arizona, it all amounts to a continually updated sense of “how I feel now”: the ACC and FI take inputs from the body and tie them together with social cues, thoughts and emotions to quickly and efficiently alter our behaviour (Nature Reviews Neuroscience, vol 10, p 59).

This constantly shifting picture of how we feel may contribute to the way we perceive the passage of time. When something emotionally important is happening, Craig proposes, there is more to process, and because of this time seems to speed up. Conversely, when less is going on we update our view of the world less frequently, so time seems to pass more slowly.

VENs are probably important in all this, though we can only infer their role through circumstantial evidence. That’s because locating these cells, and then measuring their activity in a living brain hasn’t yet been possible. But their unusual appearance is a signal that they probably aren’t just sitting there doing nothing. “They stand out anatomically,” says Allman, “And a general proposition is that anything that’s so distinctive looking must have a distinct function.”

Fast thinking

In the brain, big usually means fast, so Allman suggests that VENs could be acting as a fast relay system - a kind of social superhighway - which allows the gist of the situation to move quickly through the brain, enabling us to react intuitively on the hop, a crucial survival skill in a social species like ours. “That’s what all of civilisation is based on: our ability to communicate socially, efficiently,” adds Craig.

A particularly distressing form of dementia that can strike people as early as their 30s supports this idea. People who develop fronto-temporal dementia lose large numbers of VENs in the ACC and FI early in the disease, when the main symptom is a complete loss of social awareness, empathy and self-control. “They don’t have normal empathic responses to situations that would normally make you disgusted or sad,” says Hof. “You can show them horrible pictures of an accident and they just don’t blink. They will say ‘oh, yes, it’s an accident’.”

Post-mortem examinations of the brains of people with autism also bolster the idea that VENs lie at the heart of our emotions and empathy. According to one recent study, people with autism may fall into two groups: some have too few VENs, perhaps meaning that they don’t have the necessary wiring to process social cues, while others have far too many (Acta Neuropathologica, vol 118, p 673). The latter group would seem to fit with one recent theory of autism, which proposes that the symptoms may arise from an over-wiring of the brain. Perhaps having too many VENs makes emotional systems fire too intensely, causing people with autism to feel overwhelmed, as many say they do.

Another recent study found that people with schizophrenia who committed suicide had significantly more VENs in their ACC than schizophrenics who died of other causes. The researchers suggest that the over-abundance of VENs might create an overactive emotional system that leaves them prone to negative self-assessment and feelings of guilt and hopelessness (PLoS One, vol 6, p e20936).

VENs in other animals provide some clues, too. When these neurons were first identified, there was the glimmer of hope that we might have found one of the key evolutionary changes, unique to humankind, that could explain our social intelligence. But the earliest studies put paid to that kind of thinking, when VENs turned up in chimpanzees and gorillas. In recent years, they have also been found in elephants and some whales and dolphins.

Like us, many of these species live in big social groups and show signs of the same kind of advanced behaviour associated with VENs in people. Elephants, for instance, display something that looks a lot like empathy: they work together to help injured, lost or trapped elephants, for example. They even seem to show signs of grief at elephant “graveyards” (Biology Letters, vol 2, p 26). What’s more, many of these species can recognise themselves in the mirror, which is usually taken as a rudimentary measure of consciousness. When researchers daub paint on an elephant’s face, for instance, it will notice the mark in the mirror and try to feel the spot with its trunk. This has led Allman and others to speculate that von Economo neurons might be a vital adaptation in large brains for keeping track of social situations - and that the sense of self may be a consequence of this ability.

Yet VENs also crop up in manatees, hippos and giraffes - not renowned for their busy social lives. The cells have also been spotted in macaques, which don’t reliably pass the mirror test, although they are social animals. Although this seems to put a major spanner in the works for those who claim that the cells are crucial for advanced cognition, it could also be that these creatures are showing the precursors of the finely tuned cells found in highly social species. “I think that there are homologues of VENs in all mammals,” says Allman. “That’s not to say they’re shaped the same way but they are located in an analogous bit of cortex and they are expressing the same genes.”

It would make sense, after all, that whales and primates might both have recycled, and refined, older machinery present in a common ancestor rather than independently evolving the same mechanism. Much more research is needed, however, to work out the anatomical differences and the functions of these cells in the different animals.

That work might even help us understand how these neurons evolved in the first place. Allman already has some ideas about where they came from. Our VENs reside in a region of the brain that evolved to integrate taste and smell, so he suggests that many of the traits now associated with the FI evolved from the simple act of deciding whether food is good to eat or likely to make your ill. When reaching that decision, he says, the quicker the “gut” reaction kicks in the better. And if you can detect this process in others, so much the better.

"One of the important functions that seems to reside in the FI has to do with empathy," he says. "My take on this is that empathy arose in the context of shared food - it’s very important to observe if members of your social group are becoming ill as a result of eating something." The basic feeding circuity, including the rudimentary VENs, may then have been co-opted by some species to work in other situations that involve a decision, like working out if a person is trustworthy or to be avoided. "So when we have a feeling, whether it be about a foodstuff or situation or another person, I think that engages the circuitry in the fronto-insular cortex and the VENS are one of the outputs of that circuitry," says Allman.

Allman’s genetics work suggests he may be on to something. His team found that VENs in one part of the FI are expressing the genes for hormones that regulate appetite. There are also a lot of studies showing links between smell and taste and the feelings of strong emotions. Our physical reaction to something we find morally disgusting, for example, is more or less identical to our reaction to a bitter taste, suggesting they may share common brain wiring (Science, vol 323, p 1222). Other work has shown that judging a morally questionable act, such as theft, while smelling something disgusting leads to harsher moral judgements (Personality and Social Psychology Bulletin, vol 34, p 1096). What’s more, Allman points out that our language is loaded with analogies - we might find an experience “delicious”, say, or a person “nauseating”. This is no accident, he says.

Red herring

However, it is only in highly social animals that VENs live exclusively in the scent and taste regions. In the others, like giraffes and hippos, VENs seem to be sprinkled all over the brain. Allman, however, points out that these findings may be a red herring, since without understanding the genes they express, or their function, we can’t even be sure how closely these cells relate to human VENs. They may even be a different kind of cell that just looks similar.

Based on the evidence so far, however, Hof thinks that the ancestral VENs would have been more widespread, as seen in the hippo brain, and that over the course of evolution they then migrated to the ACC and FI in some animals, but not others - though he admits to having no idea why that might be. He suspects the pressures that shaped the primate brain may have been very different to those that drove the evolution of whales and dolphins.

Craig has hit upon one possibility that would seem to fit all of these big-brained animals. He points out that the bigger the brain, the more energy it takes to run, so it is crucial that it operates as efficiently as possible. A system that continually monitors the environment and the people or animals in it would therefore be an asset, allowing you to adapt quickly to a situation to save as much energy as possible. “Evolution produced an energy calculation system that incorporated not just the sensory inputs from the body but the sensory inputs from the brain,” Craig says. And the fact that we are constantly updating this picture of “how I feel now” has an interesting and very useful by-product: we have a concept that there is an “I” to do the feeling. “Evolution produced a very efficient moment-by-moment calculation of energy utilisation and that had an epiphenomenon, a by-product that provided a subjective representation of my feelings.”

If he’s right - and there is a long way to go before we can be sure - it raises a very humbling possibility: that far from being the pinnacle of brain evolution, consciousness might have been a big, and very successful accident.

Source: NewScientist

19 July 2012 by Nicola Guttridge

Whether a tree branch or a computer mouse is the target, reaching for objects is fundamental primate behaviour. Neurons in the brain prepare for such movements, and this neural activity can now be deciphered, allowing researchers to predict what movements will occur. This discovery could help us develop prosthetic limbs that can be controlled by thought alone.

What happens next? (Image: Gallo Images/Rex Features)

To find out what goes on in the brain when we reach for things, biomedical engineers Daniel Moran and Thomas Pearce at Washington University in St Louis, Missouri, trained two rhesus macaques to participate in a series of exercises. When the monkeys reached for items, electrodes measured the activity of neurons in their dorsal premotor cortex, a region of the brain that is involved in the perception of movement.

The monkeys were trained to reach for a virtual object on a screen to receive a reward. In some tasks the monkeys had to reach directly for an object, in others they had to reach around an obstacle to get to the target.

Impulsive grab

Moran and Pearce managed to identify the neural activity corresponding with several aspects of the planned movement, such as angle of reach, hand position and the final target location.

The findings could one day allow the design of prosthetic limbs that can be controlled with thought alone, which is “one of the reasons we did the study”, says Moran.

"The two subjects actually used different strategies to perform the task, and we were able to see this in their neural activity," Moran says. One monkey waited to receive all the information before reaching, but the other reached immediately, even though there was a good chance that an obstacle might appear and the reaching action would need to be rethought.

"If the decoding strategy is a robust finding, then this has wider consequences concerning mind-reading – particularly if we can get equivalent results for more complex strategic differences at higher cognitive levels," says Richard Cooper, a cognitive researcher at Birkbeck, University of London. "However, this is all very speculative."

Source: NewScientist