Neuroscience

Articles and news from the latest research reports.

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Our brains can (unconsciously) save us from temptation Inhibitory self control – not picking up a cigarette, not having a second drink, not spending when we should be saving – can operate without our awareness or intention. That was the finding by scientists at the University of Pennsylvania’s Annenberg School for Communication and the University of Illinois at Urbana-Champaign. They demonstrated through neuroscience research that inaction-related words in our environment can unconsciously influence our self-control. Although we may mindlessly eat cookies at a party, stopping ourselves from over-indulging may seem impossible without a deliberate, conscious effort. However, it turns out that overhearing someone – even in a completely unrelated conversation – say something as simple as “calm down” might trigger us to stop our cookie eating frenzy without realizing it. The findings were reported in the journal Cognition by Justin Hepler, M.A., University of Illinois; and Dolores Albarracín, Ph.D., the Martin Fishbein Chair of Communication and a Professor of Psychology at Penn. Volunteers completed a study where they were given instructions to press a computer key when they saw the letter “X” on the computer screen, or not press a key when they saw the letter “Y.” Their actions were affected by subliminal messages flashing rapidly on the screen. Action messages (“run,” “go,” “move,” “hit,” and “start”) alternated with inaction messages (“still,” “sit,” “rest,” “calm,” and “stop”) and nonsense words (“rnu,” or “tsi”). The participants were equipped with electroencephalogram recording equipment to measure brain activity. The unique aspect of this test is that the action or inaction messages had nothing to do with the actions or inactions volunteers were doing, yet Hepler and Albarracín found that the action/inaction words had a definite effect on the volunteers’ brain activity. Unconscious exposure to inaction messages increased the activity of the brain’s self-control processes, whereas unconscious exposure to action messages decreased this same activity. “Many important behaviors such as weight loss, giving up smoking, and saving money involve a lot of self-control,” the researchers noted. “While many psychological theories state that actions can be initiated automatically with little or no conscious effort, these same theories view inhibition as an effortful, consciously controlled process. Although reaching for that cookie doesn’t require much thought, putting it back on the plate seems to require a deliberate, conscious intervention. Our research challenges the long-held assumption that inhibition processes require conscious control to operate.” The full article, “Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms,” will be available in the September issue of the journal. (Image: Getty Images)

Our brains can (unconsciously) save us from temptation

Inhibitory self control – not picking up a cigarette, not having a second drink, not spending when we should be saving – can operate without our awareness or intention.

That was the finding by scientists at the University of Pennsylvania’s Annenberg School for Communication and the University of Illinois at Urbana-Champaign. They demonstrated through neuroscience research that inaction-related words in our environment can unconsciously influence our self-control. Although we may mindlessly eat cookies at a party, stopping ourselves from over-indulging may seem impossible without a deliberate, conscious effort. However, it turns out that overhearing someone – even in a completely unrelated conversation – say something as simple as “calm down” might trigger us to stop our cookie eating frenzy without realizing it.

The findings were reported in the journal Cognition by Justin Hepler, M.A., University of Illinois; and Dolores Albarracín, Ph.D., the Martin Fishbein Chair of Communication and a Professor of Psychology at Penn.

Volunteers completed a study where they were given instructions to press a computer key when they saw the letter “X” on the computer screen, or not press a key when they saw the letter “Y.” Their actions were affected by subliminal messages flashing rapidly on the screen. Action messages (“run,” “go,” “move,” “hit,” and “start”) alternated with inaction messages (“still,” “sit,” “rest,” “calm,” and “stop”) and nonsense words (“rnu,” or “tsi”). The participants were equipped with electroencephalogram recording equipment to measure brain activity.

The unique aspect of this test is that the action or inaction messages had nothing to do with the actions or inactions volunteers were doing, yet Hepler and Albarracín found that the action/inaction words had a definite effect on the volunteers’ brain activity. Unconscious exposure to inaction messages increased the activity of the brain’s self-control processes, whereas unconscious exposure to action messages decreased this same activity.

“Many important behaviors such as weight loss, giving up smoking, and saving money involve a lot of self-control,” the researchers noted. “While many psychological theories state that actions can be initiated automatically with little or no conscious effort, these same theories view inhibition as an effortful, consciously controlled process. Although reaching for that cookie doesn’t require much thought, putting it back on the plate seems to require a deliberate, conscious intervention. Our research challenges the long-held assumption that inhibition processes require conscious control to operate.”

The full article, “Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms,” will be available in the September issue of the journal.

(Image: Getty Images)

Filed under brain activity self-control EEG inhibition neuroscience science

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Scientists watch live brain cell circuits spark and fire

NIH-funded scientists show new genetically engineered proteins may be important tool for the President’s BRAIN Initiative

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Scientists used fruit flies to show for the first time that a new class of genetically engineered proteins can be used to watch electrical activity in individual brain cells in live brains. The results, published in Cell, suggest these proteins may be a promising new tool for mapping brain cell activity in multiple animals and for studying how neurological disorders disrupt normal nerve cell signaling. Understanding brain cell activity is a high priority of the President’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

Brain cells use electricity to control thoughts, movements and senses.  Ever since the late nineteenth century, when Dr. Luigi Galvani induced frog legs to move with electric shocks, scientists have been trying to watch nerve cell electricity to understand how it is involved in these actions. Usually they directly monitor electricity with cumbersome electrodes or toxic voltage-sensitive dyes, or indirectly with calcium detectors. This study, led by Michael Nitabach, Ph.D., J.D., and Vincent Pieribone, Ph.D., at the Yale School of Medicine, New Haven, CT, shows that a class of proteins, called genetically encoded fluorescent voltage indicators (GEVIs), may allow researchers to watch nerve cell electricity in a live animal.

Dr. Pieribone and his colleagues helped develop ArcLight, the protein used in this study. ArcLight fluoresces, or glows, as a nerve cell’s voltage changes and enables researchers to watch, in real time, the cell’s electrical activity. In this study, Dr. Nitabach and his colleagues engineered fruit flies to express ArcLight in brain cells that control the fly’s sleeping cycle or sense of smell. Initial experiments in which the researchers simultaneously watched brain cell electricity with a microscope and recorded voltage with electrodes showed that ArcLight can accurately monitor electricity in a living brain. Further experiments showed that ArcLight illuminated electricity in parts of the brain that were previously inaccessible using other techniques. Finally, ArcLight allowed the researchers to watch brain cells spark and fire while the flies were awakening and smelling. These results suggest that in the future neuroscientists may be able to use ArcLight and similar GEVIs in a variety of ways to map brain cell circuit activity during normal and disease states.

(Source: ninds.nih.gov)

Filed under brain cells fruit flies brain mapping GEVIs ArcLight cell activity neuroscience science

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World-first research to explain why actions speak louder than words

An innovative series of experiments could help to unlock the mysteries of how the brain makes sense of the hustle and bustle of human activity we see around us every day.

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Very little is known about the psychological processes which enable us to pick out a potential mugger from a busy street or to spot an old friend approaching us across a crowded room. Such judgements of social intention, which we make countless times each day, enable us to respond in appropriate ways to the dynamic and complex world around us.

George Mather, Professor of Vision Science at the University of Lincoln, UK, and one of the world’s foremost experts on human visual perception, will lead a new research project investigating the mechanisms behind this crucial ability to perceive and interpret the intentions of other people from the way they move.

Numerous experiments have explored the way we use visual signals to extract meaning from our environment, but most have been based on static images, such as photos of different facial expressions.

Other studies into the perception of moving images have relied on very simple animated scenes, like moving patterns of regularly-spaced lines or random dots, devoid of the richness and nuances of scenes from the ‘real world’.

There remains limited scientific understanding of how the human visual system makes sense of the flurry of movement we see around us in modern societies: for example, whether a person approaching us is sprinting or strolling, whether that means they are angry or calm, and how we should react in response.

Professor Mather aims to bridge this gap in the academic literature through a series of world-first experiments. He has been awarded a grant of £287,000 by the UK’s Economic & Social Research Council (ESRC) for a three-year study. The aim is to shed new light on the process by which the human visual system identifies and decodes ‘dynamic cues of social intention’.

Professor Mather said: “It’s true that actions speak louder than words. Perception of movement is fundamental to many of our everyday social interactions. But simply judging speed is in itself a very complex task. When you see somebody walking across your field of view, how do you know how fast they are going? That information can be very useful because it might tell you something about their intentions but it’s surprisingly difficult to make an accurate judgement. A basic problem is that the further away a moving object is, the slower it moves in the image received by the eye. We don’t really understand at the moment how the human visual system is able to compensate for different viewing conditions.”

Motion perception has been a consistent theme of Professor Mather’s research career. In previous studies he has shown that the brain can deduce socially meaningful information from very simple depictions of human movement, such as collections of dots denoting the major joints of the body.

The research in this latest project will answer fundamental questions about how the brain combines ‘low-level’ information about image motion with ‘high level’ knowledge of the social world to make meaningful assessments of the speed and nature of human movements.

(Source: lincoln.ac.uk)

Filed under visual perception social intention motion perception human movements neuroscience psychology science

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Motional layers in the brain Recognising movement and its direction is one of the first and most important processing steps in any visual system. By this way, nearby predators or prey can be detected and even one’s own movements are controlled. More than fifty years ago, a mathematical model predicted how elementary motion detectors must be structured in the brain. However, which nerve cells perform this job and how they are actually connected remained a mystery. Scientists at the Max Planck Institute of Neurobiology in Martinsried have now come one crucial step closer to this “holy grail of motion vision”: They identified the cells that represent these so-called “elementary motion detectors” in the fruit fly brain. The results show that motion of an observed object is processed in two separate pathways. In each pathway, motion information is processed independently of one another and sorted according to its direction. Ramón y Cajal, the famous neuroanatomist, was the first to examine the brains of flies. Almost a century ago, he thus discovered a group of cells he described as “curious elements with two tufts”. About 50 years later, German physicist Werner Reichardt postulated from his behavioural experiments with flies that they possess “elementary motion detectors”, as he referred to them. These detectors compare changes in luminance between two neighbouring photoreceptor units, or facets, in the fruit fly’s eye for every point in the visual space. The direction of a local movement is then calculated from this. At least, that is what the theory predicts. Since that time, the fruit fly research community has been speculating about whether these “two-tufted cells” described by Cajal are the mysterious elementary motion detectors. The answer to this question has been slow in coming, as the tufted cells are extremely small – much too small for sticking an electrode into them and capturing their electrical signals. Now, Alexander Borst and his group at the Max Planck- Institute of Neurobiology have succeeded in making a breakthrough with the aid of a calcium indicator. These fluorescent proteins are formed by the neurons themselves and change their fluorescence when the cells are active. It thus finally became possible for the scientists to observe and measure the activity of the tufted cells under the microscope. The results prove that these cells actually are the elementary motion detectors predicted by Werner Reichardt. As further experiments have shown, the tufted cells can be divided into two groups. One group (T4 cells) only reacts to a transition from dark to light caused by motion, while the other group (T5 cells) reacts oppositely – only for light-to-dark edges. In every group there are four subgroups, each of which only responds to movements in a specific direction – to the right, left, upwards or downwards. The neurons in these directionally selective groups release their information into layers of subsequent nerve tissue that are completely separated from one another. There, large neurons use these signals for visual flight control, generating the appropriate commands for the flight musculature, for example. This could be impressively proven by the scientists: When they blocked the T4 cells, the neurons connected downstream and the fruit flies themselves were shown in behavioural tests to be blind to motions caused by dark-to-light edges. When the T5 cells were blocked, light-to-dark edges could no longer be perceived. In discussions about their research results, which have just been published in the scientific journal Nature, both lead authors, Matt Maisak and Jürgen Haag, were very impressed with the “cleanly differentiated, yet highly ordered” motion information within the brains of the fruit flies. Alexander Borst, head of the study, adds: “That was real teamwork – almost all of the members in my department took part in the experiments. One group carried out the calcium measurements, another worked on the electrophysiology, and a third made the behavioural measurements. They all pulled together. It was a wonderful experience.” And it should continue like this, since the scientists are already turning to the next mammoth challenge: they would now like to identify the neurons that deliver the input signals to the elementary motion detectors. According to Reichardt, the two signals coming from neighbouring photoreceptors in the eye have to be delayed in relation to one another. “That is going to be really exciting!” says Alexander Borst.

Motional layers in the brain

Recognising movement and its direction is one of the first and most important processing steps in any visual system. By this way, nearby predators or prey can be detected and even one’s own movements are controlled. More than fifty years ago, a mathematical model predicted how elementary motion detectors must be structured in the brain. However, which nerve cells perform this job and how they are actually connected remained a mystery. Scientists at the Max Planck Institute of Neurobiology in Martinsried have now come one crucial step closer to this “holy grail of motion vision”: They identified the cells that represent these so-called “elementary motion detectors” in the fruit fly brain. The results show that motion of an observed object is processed in two separate pathways. In each pathway, motion information is processed independently of one another and sorted according to its direction.

Ramón y Cajal, the famous neuroanatomist, was the first to examine the brains of flies. Almost a century ago, he thus discovered a group of cells he described as “curious elements with two tufts”. About 50 years later, German physicist Werner Reichardt postulated from his behavioural experiments with flies that they possess “elementary motion detectors”, as he referred to them. These detectors compare changes in luminance between two neighbouring photoreceptor units, or facets, in the fruit fly’s eye for every point in the visual space. The direction of a local movement is then calculated from this. At least, that is what the theory predicts. Since that time, the fruit fly research community has been speculating about whether these “two-tufted cells” described by Cajal are the mysterious elementary motion detectors.

The answer to this question has been slow in coming, as the tufted cells are extremely small – much too small for sticking an electrode into them and capturing their electrical signals. Now, Alexander Borst and his group at the Max Planck- Institute of Neurobiology have succeeded in making a breakthrough with the aid of a calcium indicator. These fluorescent proteins are formed by the neurons themselves and change their fluorescence when the cells are active. It thus finally became possible for the scientists to observe and measure the activity of the tufted cells under the microscope. The results prove that these cells actually are the elementary motion detectors predicted by Werner Reichardt.

As further experiments have shown, the tufted cells can be divided into two groups. One group (T4 cells) only reacts to a transition from dark to light caused by motion, while the other group (T5 cells) reacts oppositely – only for light-to-dark edges. In every group there are four subgroups, each of which only responds to movements in a specific direction – to the right, left, upwards or downwards. The neurons in these directionally selective groups release their information into layers of subsequent nerve tissue that are completely separated from one another. There, large neurons use these signals for visual flight control, generating the appropriate commands for the flight musculature, for example. This could be impressively proven by the scientists: When they blocked the T4 cells, the neurons connected downstream and the fruit flies themselves were shown in behavioural tests to be blind to motions caused by dark-to-light edges. When the T5 cells were blocked, light-to-dark edges could no longer be perceived.

In discussions about their research results, which have just been published in the scientific journal Nature, both lead authors, Matt Maisak and Jürgen Haag, were very impressed with the “cleanly differentiated, yet highly ordered” motion information within the brains of the fruit flies. Alexander Borst, head of the study, adds: “That was real teamwork – almost all of the members in my department took part in the experiments. One group carried out the calcium measurements, another worked on the electrophysiology, and a third made the behavioural measurements. They all pulled together. It was a wonderful experience.” And it should continue like this, since the scientists are already turning to the next mammoth challenge: they would now like to identify the neurons that deliver the input signals to the elementary motion detectors. According to Reichardt, the two signals coming from neighbouring photoreceptors in the eye have to be delayed in relation to one another. “That is going to be really exciting!” says Alexander Borst.

Filed under elementary motion detectors fruit flies visual system photoreceptors neuroscience science

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Study Reveals That Overthinking Can Be Detrimental to Human Performance

Trying to explain riding a bike is difficult because it is an implicit memory. The body knows what to do, but thinking about the process can often interfere. So why is it that under certain circumstances paying full attention and trying hard can actually impede performance? A new UC Santa Barbara study, published today in the Journal of Neuroscience, reveals part of the answer.

There are two kinds of memory: implicit, a form of long-term memory not requiring conscious thought and expressed by means other than words; and explicit, another kind of long-term memory formed consciously that can be described in words. Scientists consider these distinct areas of function both behaviorally and in the brain.

Long-term memory is supported by various regions in the prefrontal cortex, the newest part of the brain in terms of evolution and the part of the brain responsible for planning, executive function, and working memory. “A lot of people think the reason we’re human is because we have the most advanced prefrontal cortex,” said the study’s lead author, Taraz Lee, a postdoctoral scholar working in UCSB’s Action Lab.

Two previous brain studies have shown that taxing explicit memory resources improved recognition memory without awareness. The results suggest that implicit perceptual memory can aid performance on recognition tests. So Lee and his colleagues decided to test whether the effects of the attentional control processes associated with explicit memory could directly interfere with implicit memory.

Lee’s study used continuous theta-burst transcranial magnetic stimulation (TMS) to temporarily disrupt the function of two different parts of the prefrontal cortex, the dorsolateral and ventrolateral. The dorsal and ventral regions are close to each other but have slightly different functions. Disrupting function in two distinct areas provided a direct causal test of whether explicit memory processing exerts control over sensory resources –– in this case, visual information processing –– and in doing so indirectly harms implicit memory processes.

Participants were shown a series of kaleidoscopic images for about a minute, then had a one-minute break before being given memory tests containing two different kaleidoscopic images. They were then asked to distinguish images they had seen previously from the new ones. “After they gave us that answer, we asked whether they remembered a lot of rich details, whether they had a vague impression, or whether they were blindly guessing,” explains Lee. “And the participants only did better when they said they were guessing.”

The results of disrupting the function of the dorsolateral prefrontal cortex shed light on why paying attention can be a distraction and affect performance outcomes. “If we ramped down activity in the dorsolateral prefrontal cortex, people remembered the images better,” said Lee.

When the researchers disrupted the ventral area of the prefrontal cortex, participants’ memory was just slightly worse. “They would shift from saying that they could remember a lot of rich details about the image to being vaguely familiar with the images,” Lee said. “It didn’t actually make them better at the task.”

Lee’s fascination with the effect of attentional processes on memory stems from his extensive sports background. As he pointed out, there are always examples of professional golfers who have the lead on the 18th hole, but when it comes down to one easy shot, they fall apart. “That should be the time when it all comes out the best, but you just can’t think about that sort of thing,” he said. “It just doesn’t help you.”

His continuing studies at UCSB’s Action Lab will focus on dissecting the process of choking under pressure. Lee’s work will use brain scans to examine why people who are highly incentivized to do well often succumb to pressure and how the prefrontal cortex and these attentional processes interfere with performance.

"I think most researchers who look at prefrontal cortex function are trying to figure out what it does to help you and how that explains how the brain works and how we act," said Lee. "I look at it at the opposite. If we can figure out the ways in which activity in this part of the brain hurts you, then this also informs how your brain works and can give us some clues to what’s actually going on."

Filed under prefrontal cortex implicit memory explicit memory transcranial magnetic stimulation performance neuroscience psychology science

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Cognitive decline with age is normal, routine – but not inevitable

If you forget where you put your car keys and you can’t seem to remember things as well as you used to, the problem may well be with the GluN2B subunits in your NMDA receptors.

And don’t be surprised if by tomorrow you can’t remember the name of those darned subunits.

They help you remember things, but you’ve been losing them almost since the day you were born, and it’s only going to get worse. An old adult may have only half as many of them as a younger person.

Research on these biochemical processes in the Linus Pauling Institute at Oregon State University is making it clear that cognitive decline with age is a natural part of life, and scientists are tracking the problem down to highly specific components of the brain. Separate from some more serious problems like dementia and Alzheimer’s disease, virtually everyone loses memory-making and cognitive abilities as they age. The process is well under way by the age of 40 and picks up speed after that.

But of considerable interest: It may not have to be that way.

“These are biological processes, and once we fully understand what is going on, we may be able to slow or prevent it,” said Kathy Magnusson, a neuroscientist in the OSU Department of Biomedical Sciences, College of Veterinary Medicine, and professor in the Linus Pauling Institute. “There may be ways to influence it with diet, health habits, continued mental activity or even drugs.”

The processes are complex. In a study just published in the Journal of Neuroscience, researchers found that one protein that stabilizes receptors in a young animal – a good thing conducive to learning and memory – can have just the opposite effect if there’s too much of it in an older animal.

But complexity aside, progress is being made. In recent research, supported by the National Institutes of Health, OSU scientists used a genetic therapy in laboratory mice, in which a virus helped carry complementary DNA into appropriate cells and restored some GluN2B subunits. Tests showed that it helped mice improve their memory and cognitive ability.

The NMDA receptor has been known of for decades, Magnusson said. It plays a role in memory and learning but isn’t active all the time – it takes a fairly strong stimulus of some type to turn it on and allow you to remember something. The routine of getting dressed in the morning is ignored and quickly lost to the fog of time, but the day you had an auto accident earns a permanent etching in your memory.

Within the NMDA receptor are various subunits, and Magnusson said that research keeps pointing back to the GluN2B subunit as one of the most important. Infants and children have lots of them, and as a result are like a sponge in soaking up memories and learning new things. But they gradually dwindle in number with age, and it also appears the ones that are left work less efficiently.

“You can still learn new things and make new memories when you are older, but it’s not as easy,” Magnusson said. “Fewer messages get through, fewer connections get made, and your brain has to work harder.”

Until more specific help is available, she said, some of the best advice for maintaining cognitive function is to keep using your brain. Break old habits, do things different ways. Get physical exercise, maintain a good diet and ensure social interaction. Such activities help keep these “subunits” active and functioning.

Gene therapy such as that already used in mice would probably be a last choice for humans, rather than a first option, Magnusson said. Dietary or drug options would be explored first.

“The one thing that does seem fairly clear is that cognitive decline is not inevitable,” she said. “It’s biological, we’re finding out why it happens, and it appears there are ways we might be able to slow or stop it, perhaps repair the NMDA receptors. If we can determine how to do that without harm, we will.”

(Source: oregonstate.edu)

Filed under aging cognitive decline NMDA receptors GluN2B subunit memory neuroscience science

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This is your brain on Vivaldi and Beatles Listening to music activates large networks in the brain, but different kinds of music are processed differently. A team of researchers from Finland, Denmark and the UK has developed a new method for studying music processing in the brain during a realistic listening situation. Using a combination of brain imaging and computer modeling, they found areas in the auditory, motor, and limbic regions to be activated during free listening to music. They were furthermore able to pinpoint differences in the processing between vocal and instrumental music. The new method helps us to understand better the complex brain dynamics of brain networks and the processing of lyrics in music. The study was published in the journal NeuroImage. Using functional magnetic resonance imaging (fMRI), the research team, led by Dr. Vinoo Alluri from the University of Jyväskylä, Finland, recorded the brain responses of individuals while they were listening to music from different genres, including pieces by Antonio Vivaldi, Miles Davis, Booker T. & the M.G.’s, The Shadows, Astor Piazzolla, and The Beatles. Following this, they analyzed the musical content of the pieces using sophisticated computer algorithms to extract musical features related to timbre, rhythm and tonality. Using a novel cross-validation method, they subsequently located activated brain areas that were common across the different musical stimuli. The study revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions were activated by all musical pieces. Notable, areas in the medial orbitofrontal region and the anterior cingulate cortex, which are relevant for self-referential appraisal and aesthetic judgments, were found to be activated during the listening. A further interesting finding was that vocal and instrumental music were processed differently. In particular, the presence of lyrics was found to shift the processing of musical features towards the right auditory cortex, which suggests a left-hemispheric dominance in the processing of the lyrics. This result is in line with previous research, but now for the first time observed during continuous listening to music. "The new method provides a powerful means to predict brain responses to music, speech, and soundscapes across a variety of contexts", says Dr. Vinoo Alluri.

This is your brain on Vivaldi and Beatles

Listening to music activates large networks in the brain, but different kinds of music are processed differently. A team of researchers from Finland, Denmark and the UK has developed a new method for studying music processing in the brain during a realistic listening situation. Using a combination of brain imaging and computer modeling, they found areas in the auditory, motor, and limbic regions to be activated during free listening to music. They were furthermore able to pinpoint differences in the processing between vocal and instrumental music. The new method helps us to understand better the complex brain dynamics of brain networks and the processing of lyrics in music. The study was published in the journal NeuroImage.

Using functional magnetic resonance imaging (fMRI), the research team, led by Dr. Vinoo Alluri from the University of Jyväskylä, Finland, recorded the brain responses of individuals while they were listening to music from different genres, including pieces by Antonio Vivaldi, Miles Davis, Booker T. & the M.G.’s, The Shadows, Astor Piazzolla, and The Beatles. Following this, they analyzed the musical content of the pieces using sophisticated computer algorithms to extract musical features related to timbre, rhythm and tonality. Using a novel cross-validation method, they subsequently located activated brain areas that were common across the different musical stimuli.

The study revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions were activated by all musical pieces. Notable, areas in the medial orbitofrontal region and the anterior cingulate cortex, which are relevant for self-referential appraisal and aesthetic judgments, were found to be activated during the listening. A further interesting finding was that vocal and instrumental music were processed differently. In particular, the presence of lyrics was found to shift the processing of musical features towards the right auditory cortex, which suggests a left-hemispheric dominance in the processing of the lyrics. This result is in line with previous research, but now for the first time observed during continuous listening to music.

"The new method provides a powerful means to predict brain responses to music, speech, and soundscapes across a variety of contexts", says Dr. Vinoo Alluri.

Filed under music brain activity auditory cortex orbitofrontal cortex fMRI neuroscience psychology science

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A ‘Rocking’ Receptor: Crucial Brain-Signaling Molecule Requires Coordinated Motion to Turn On

Study could help yield new drugs for brain disorders

Johns Hopkins biophysicists have discovered that full activation of a protein ensemble essential for communication between nerve cells in the brain and spinal cord requires a lot of organized back-and-forth motion of some of the ensemble’s segments. Their research, they say, may reveal multiple sites within the protein ensemble that could be used as drug targets to normalize its activity in such neurological disorders as epilepsy, schizophrenia, Parkinson’s and Alzheimer’s disease.

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The glutamate-binding segments (blue, yellow) of ionotropic glutamate receptors undergo a “rocking” motion during activation by glutamate (red). (The dotted line provides a point of reference.)

A summary of the results, published online in the journal Neuron on Aug. 7, shows that full activation of so-called ionotropic glutamate receptors is more complex than previously envisioned. In addition to the expected shape changes that occur when the receptor “receives” and clamps down on glutamate messenger molecules, the four segments of the protein ensemble also rock back and forth in relation to each other when fewer than four glutamates are bound.

“We believe that our study is the first to show the molecular architecture and behavior of a prominent neural receptor protein ensemble in a state of partial activation,” says Albert Lau, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine.

Glutamate receptors reside in the outer envelope of every nerve cell in the brain and spinal cord, Lau notes, and are responsible for changing chemical information — the release of glutamate molecules from a neighboring nerve cell — into electrical information, the flow of charged particles into the receiving nerve cell. There would be sharply reduced communication between nerve cells in our brains if these receptors were disabled, he added, and thought and normal brain function in general would be severely compromised. Malfunctioning receptors, says Lau, have been linked with numerous neurological disorders and are therefore potential targets for drug therapies.

Lau explained that each glutamate receptor is a united group of four protein segments that has a pocket for clamping down on glutamate like a Venus fly trap snaring a bug. Below the glutamate-binding segments are four other segments embedded in the cell’s outer envelope to form a channel for charged particles to flow through. When no glutamates are bound to the receptor, the channel is closed; full activation of the receptor and full opening of the channel occur when four glutamates are bound, each to a difference pocket.

Previously, Lau says, investigators thought that the level of receptor activation simply corresponded to the degree to which each glutamate-binding segment changed shape during the glutamate-binding process. Using a combination of computer modeling, biophysical “imaging” of molecular structure, biochemical analysis and electrical monitoring of individual cells, the researchers teased apart some of the steps in between zero activation and full activation. They were able to show that the four glutamate-binding segments, in addition to clamping down on glutamate, also rock back and forth in pairs when fewer than four glutamates are bound.

“It isn’t clear yet how this rocking motion affects receptor function, but we now know that activation depends on more than how much each glutamate-binding segment clamps down,” says Lau. Previous development of drugs targeting the receptor focused on the four glutamate-binding pockets. “Our discovery of this molecular motion could aid the development of drugs by revealing additional drug-binding sites on the receptor,” he adds.

(Source: hopkinsmedicine.org)

Filed under glutamate receptors nerve cells neurological disorders iGluRs neuroscience science

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Scientists Find Key Signal that Guides Brain Development Scientists at The Scripps Research Institute (TSRI) have decoded an important molecular signal that guides the development of a key region of the brain known as the neocortex. The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans and is responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness and other functions. “The mammalian neocortex has a distinctive structure featuring six layers of neurons, and our finding helps explain how this layered structure is generated in early life,” said Ulrich Mueller, chair of TSRI’s Department of Molecular and Cellular Neuroscience and director of the Dorris Neuroscience Center at TSRI. The discovery, which appears in the August 7,2013 issue of Neuron, also is likely to aid research on autism, schizophrenia and other psychiatric conditions. “With studies such as this one, we’re starting to understand the normal functions of molecules whose disruption by gene mutations can cause developmental brain disorders,” Mueller said. Finding Their Proper Place The signal uncovered by Mueller’s team is one that helps guide the migration of baby neurons through the developing neocortex. Such neurons are born from stem-like cells at the bottom of the neocortex, where it wraps around a large, fluid-filled space in the brain called ventricle. The newborn neurons then migrate upward, or radially away from the ventricle, being directed to their proper places in the neocortex’s six-layered, columnar structure by—among others—special guide cells called Cajal-Retzius (CR) cells. Decades ago, scientists discovered a key signaling protein, reelin, which CR cells secrete and baby neocortical neurons must detect to migrate properly. (Mutant mice that lack a functional form of the protein show, among other abnormalities, a reeling gait—thus the name.) There have been hints since then that CR cells and baby neocortical neurons exchange other molecular signals, too. “But in many years of study, no one has been able to find these other signals,” said Mueller. However, in a study published in 2011, Mueller and his laboratory colleagues found a significant clue. Reelin, they discovered, guides neuronal migration at least in part by boosting baby neurons’ expression of a generic cell-adhesion molecule, cadherin2 (Cdh2). Since Cdh2 can be expressed by almost any cell type in the developing neocortex, the team then began to look for other factors that would account for the specificity of the interaction between CR cells and migrating baby neurons. An Interesting Pattern One set of candidates were the nectins—cell-adhesion proteins known to work with cadherins in other contexts. Lead author Cristina Gil-Sanz, a senior research associate in the Mueller laboratory, mapped the expression levels of the four known types of mammalian nectin proteins in the developing mouse cortex and found an interesting pattern. “We observed that nectin1 is expressed specifically by CR cells and nectin3 by migrating neurons,” said Gil-Sanz. “At the same time, we knew from previous research that nectin1 and nectin3 are preferred binding partners.” Gil-Sanz and her colleagues followed up with other experiments and soon confirmed that the hookup of nectin1 on CR cells with nectin3 on baby neurons is essential for proper neuronal migration. “This showed for the first time the importance of direct contacts between CR cells and migrating neurons,” Gil-Sanz said. The experiments also showed that this direct nectin-to-nectin connection is effectively part of the reelin signaling pathway, since reelin’s promotion of Cdh2’s function in migrating neurons turns out to work largely via nectin3. “This helps explain how the interaction occurs specifically between neurons and CR cells, and doesn’t involve other nearby cells that also express Cdh2,” she said. New Possibilities The finding points to the possibility of other cell-specific pairings that work via generic Cdh2-to-Cdh2 adhesions in brain development. “We know that there are four nectin proteins, plus a slew of nectin-like molecules,” said Mueller. “We think that there are others that do this as well, and we’re hoping to find them.” The new study represents a big step toward the full scientific understanding of neuronal migration in the neocortex, and it is likely to be relevant to the study of developmental brain diseases too. Reelin-signaling abnormalities in humans have been linked to autism, depression, schizophrenia and even Alzheimer’s, and, in recent years, cadherin protein mutations also have been linked to disorders including schizophrenia and autism. “Studies like ours provide insight into such findings, by showing that these molecules, in cooperation with nectins, regulate key developmental processes such as the positioning of neurons in the neocortex,” said Mueller.

Scientists Find Key Signal that Guides Brain Development

Scientists at The Scripps Research Institute (TSRI) have decoded an important molecular signal that guides the development of a key region of the brain known as the neocortex. The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans and is responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness and other functions.

“The mammalian neocortex has a distinctive structure featuring six layers of neurons, and our finding helps explain how this layered structure is generated in early life,” said Ulrich Mueller, chair of TSRI’s Department of Molecular and Cellular Neuroscience and director of the Dorris Neuroscience Center at TSRI.

The discovery, which appears in the August 7,2013 issue of Neuron, also is likely to aid research on autism, schizophrenia and other psychiatric conditions. “With studies such as this one, we’re starting to understand the normal functions of molecules whose disruption by gene mutations can cause developmental brain disorders,” Mueller said.

Finding Their Proper Place

The signal uncovered by Mueller’s team is one that helps guide the migration of baby neurons through the developing neocortex. Such neurons are born from stem-like cells at the bottom of the neocortex, where it wraps around a large, fluid-filled space in the brain called ventricle. The newborn neurons then migrate upward, or radially away from the ventricle, being directed to their proper places in the neocortex’s six-layered, columnar structure by—among others—special guide cells called Cajal-Retzius (CR) cells.

Decades ago, scientists discovered a key signaling protein, reelin, which CR cells secrete and baby neocortical neurons must detect to migrate properly. (Mutant mice that lack a functional form of the protein show, among other abnormalities, a reeling gait—thus the name.) There have been hints since then that CR cells and baby neocortical neurons exchange other molecular signals, too. “But in many years of study, no one has been able to find these other signals,” said Mueller.

However, in a study published in 2011, Mueller and his laboratory colleagues found a significant clue. Reelin, they discovered, guides neuronal migration at least in part by boosting baby neurons’ expression of a generic cell-adhesion molecule, cadherin2 (Cdh2). Since Cdh2 can be expressed by almost any cell type in the developing neocortex, the team then began to look for other factors that would account for the specificity of the interaction between CR cells and migrating baby neurons.

An Interesting Pattern

One set of candidates were the nectins—cell-adhesion proteins known to work with cadherins in other contexts. Lead author Cristina Gil-Sanz, a senior research associate in the Mueller laboratory, mapped the expression levels of the four known types of mammalian nectin proteins in the developing mouse cortex and found an interesting pattern. “We observed that nectin1 is expressed specifically by CR cells and nectin3 by migrating neurons,” said Gil-Sanz. “At the same time, we knew from previous research that nectin1 and nectin3 are preferred binding partners.”

Gil-Sanz and her colleagues followed up with other experiments and soon confirmed that the hookup of nectin1 on CR cells with nectin3 on baby neurons is essential for proper neuronal migration. “This showed for the first time the importance of direct contacts between CR cells and migrating neurons,” Gil-Sanz said.

The experiments also showed that this direct nectin-to-nectin connection is effectively part of the reelin signaling pathway, since reelin’s promotion of Cdh2’s function in migrating neurons turns out to work largely via nectin3. “This helps explain how the interaction occurs specifically between neurons and CR cells, and doesn’t involve other nearby cells that also express Cdh2,” she said.

New Possibilities

The finding points to the possibility of other cell-specific pairings that work via generic Cdh2-to-Cdh2 adhesions in brain development. “We know that there are four nectin proteins, plus a slew of nectin-like molecules,” said Mueller. “We think that there are others that do this as well, and we’re hoping to find them.”

The new study represents a big step toward the full scientific understanding of neuronal migration in the neocortex, and it is likely to be relevant to the study of developmental brain diseases too. Reelin-signaling abnormalities in humans have been linked to autism, depression, schizophrenia and even Alzheimer’s, and, in recent years, cadherin protein mutations also have been linked to disorders including schizophrenia and autism. “Studies like ours provide insight into such findings, by showing that these molecules, in cooperation with nectins, regulate key developmental processes such as the positioning of neurons in the neocortex,” said Mueller.

Filed under brain development neocortex Cajal-Retzius cells developmental disorders neuronal migration neuroscience science

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ucsdhealthsciences: Top: Vesicles containing APP (green) and BACE (red) are normally segregated in neurons. Bottom: After neuronal stimulation, known to produce more beta-amyloid, APP and BACE converge in common vesicles, depicted in yellow. Why Don’t We All Get Alzheimer’s Disease? Though one might think the brains of people who develop Alzheimer’s disease (AD) possess building blocks of the disease absent in healthy brains, for most sufferers, this is not true. Every human brain contains the ingredients necessary to spark AD, but while an estimated 5 million Americans have AD – a number projected to triple by 2050 – the vast majority of people do not and will not develop the devastating neurological condition. For researchers like Subhojit Roy, MD, PhD, associate professor in the Departments of Pathology and Neurosciences at the University of California, San Diego School of Medicine, these facts produce a singular question: Why don’t we all get Alzheimer’s disease? In a paper published in the August 7 issue of the journal Neuron, Roy and colleagues offer an explanation – a trick of nature that, in most people, maintains critical separation between a protein and an enzyme that, when combined, trigger the progressive cell degeneration and death characteristic of AD. “It’s like physically separating gunpowder and match so that the inevitable explosion is avoided,” said principal investigator Roy, a cell biologist and neuropathologist in the Shiley-Marcos Alzheimer’s Disease Research Center at UC San Diego. “Knowing how the gunpowder and match are separated may give us new insights into possibly stopping the disease.” The severity of AD is measured in the loss of functioning neurons. In pathological terms, there are two tell-tale signs of AD: clumps of a protein called beta-amyloid “plaques” that accumulate outside neurons and threads or “tangles” of another protein, called tau, found inside neurons. Most neuroscientists believe AD is caused by the accumulating assemblies of beta-amyloid protein triggering a sequence of events that leads to impaired cell function and death. This so-called “amyloid cascade hypothesis” puts beta-amyloid protein at the center of AD pathology. Creating beta-amyloid requires the convergence of a protein called amyloid precursor protein (APP) and an enzyme that cleaves APP into smaller toxic fragments called beta-secretase or BACE. “Both of these proteins are highly expressed in the brain,” said Roy, “and if they were allowed to combine continuously, we would all have AD.” But that doesn’t happen. Using cultured hippocampal neurons and tissue from human and mouse brains, Roy – along with first author Utpal Das, a postdoctoral fellow in Roy’s lab, and colleagues – discovered that healthy brain cells largely segregate APP and BACE-1 into distinct compartments as soon as they are manufactured, ensuring the two proteins do not have much contact with each other. “Nature seems to have come up with an interesting trick to separate co-conspirators,” said Roy.  More here

ucsdhealthsciences:

Top: Vesicles containing APP (green) and BACE (red) are normally segregated in neurons. Bottom: After neuronal stimulation, known to produce more beta-amyloid, APP and BACE converge in common vesicles, depicted in yellow.

Why Don’t We All Get Alzheimer’s Disease?

Though one might think the brains of people who develop Alzheimer’s disease (AD) possess building blocks of the disease absent in healthy brains, for most sufferers, this is not true. Every human brain contains the ingredients necessary to spark AD, but while an estimated 5 million Americans have AD – a number projected to triple by 2050 – the vast majority of people do not and will not develop the devastating neurological condition.

For researchers like Subhojit Roy, MD, PhD, associate professor in the Departments of Pathology and Neurosciences at the University of California, San Diego School of Medicine, these facts produce a singular question: Why don’t we all get Alzheimer’s disease?

In a paper published in the August 7 issue of the journal Neuron, Roy and colleagues offer an explanation – a trick of nature that, in most people, maintains critical separation between a protein and an enzyme that, when combined, trigger the progressive cell degeneration and death characteristic of AD.

“It’s like physically separating gunpowder and match so that the inevitable explosion is avoided,” said principal investigator Roy, a cell biologist and neuropathologist in the Shiley-Marcos Alzheimer’s Disease Research Center at UC San Diego. “Knowing how the gunpowder and match are separated may give us new insights into possibly stopping the disease.”

The severity of AD is measured in the loss of functioning neurons. In pathological terms, there are two tell-tale signs of AD: clumps of a protein called beta-amyloid “plaques” that accumulate outside neurons and threads or “tangles” of another protein, called tau, found inside neurons. Most neuroscientists believe AD is caused by the accumulating assemblies of beta-amyloid protein triggering a sequence of events that leads to impaired cell function and death. This so-called “amyloid cascade hypothesis” puts beta-amyloid protein at the center of AD pathology.

Creating beta-amyloid requires the convergence of a protein called amyloid precursor protein (APP) and an enzyme that cleaves APP into smaller toxic fragments called beta-secretase or BACE.

“Both of these proteins are highly expressed in the brain,” said Roy, “and if they were allowed to combine continuously, we would all have AD.”

But that doesn’t happen. Using cultured hippocampal neurons and tissue from human and mouse brains, Roy – along with first author Utpal Das, a postdoctoral fellow in Roy’s lab, and colleagues – discovered that healthy brain cells largely segregate APP and BACE-1 into distinct compartments as soon as they are manufactured, ensuring the two proteins do not have much contact with each other.

“Nature seems to have come up with an interesting trick to separate co-conspirators,” said Roy. 

More here

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