What Happens in the Brain to Make Music Rewarding?

What Happens in the Brain to Make Music Rewarding?

  7:57:00 AM    Science Lover

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A new study reveals what happens in our brain when we decide to purchase a piece of music when we hear it for the first time. The study, conducted at the Montreal Neurological Institute and Hospital -- The Neuro, McGill University and published in the journal Science on April 12, pinpoints the specific brain activity that makes new music rewarding and predicts the decision to purchase music.

A new study reveals what happens in our brain when we decide to purchase a piece of music when we hear it for the first time. (Credit: © Warren Goldswain / Fotolia)

Participants in the study listened to 60 previously unheard music excerpts while undergoing functional resonance imaging (fMRI) scanning, providing bids of how much they were willing to spend for each item in an auction paradigm. "When people listen to a piece of music they have never heard before, activity in one brain region can reliably and consistently predict whether they will like or buy it, this is the nucleus accumbens which is involved in forming expectations that may be rewarding," says lead investigator Dr. Valorie Salimpoor, who conducted the research in Dr. Robert Zatorre's lab at The Neuro and is now at Baycrest Health Sciences' Rotman Research Institute. "What makes music so emotionally powerful is the creation of expectations. Activity in the nucleus accumbens is an indicator that expectations were met or surpassed, and in our study we found that the more activity we see in this brain area while people are listening to music, the more money they are willing to spend."

The second important finding is that the nucleus accumbens doesn't work alone, but interacts with the auditory cortex, an area of the brain that stores information about the sounds and music we have been exposed to. The more a given piece was rewarding, the greater the cross-talk between these regions. Similar interactions were also seen between the nucleus accumbens and other brain areas, involved in high-level sequencing, complex pattern recognition and areas involved in assigning emotional and reward value to stimuli.

In other words, the brain assigns value to music through the interaction of ancient dopaminergic reward circuitry, involved in reinforcing behaviours that are absolutely necessary for our survival such as eating and sex, with some of the most evolved regions of the brain, involved in advanced cognitive processes that are unique to humans.

"This is interesting because music consists of a series of sounds that when considered alone have no inherent value, but when arranged together through patterns over time can act as a reward, says Dr. Robert Zatorre, researcher at The Neuro and co-director of the International Laboratory for Brain, Music and Sound Research. "The integrated activity of brain circuits involved in pattern recognition, prediction, and emotion allow us to experience music as an aesthetic or intellectual reward."

"The brain activity in each participant was the same when they were listening to music that they ended up purchasing, although the pieces they chose to buy were all different," adds Dr. Salimpoor. "These results help us to see why people like different music -- each person has their own uniquely shaped auditory cortex, which is formed based on all the sounds and music heard throughout our lives. Also, the sound templates we store are likely to have previous emotional associations."

An innovative aspect of this study is how closely it mimics real-life music-listening experiences. Researchers used a similar interface and prices as iTunes. To replicate a real life scenario as much as possible and to assess reward value objectively, individuals could purchase music with their own money, as an indication that they wanted to hear it again. Since musical preferences are influenced by past associations, only novel music excerpts were selected (to minimize explicit predictions) using music recommendation software (such as Pandora, Last.fm) to reflect individual preferences.

The interactions between nucleus accumbens and the auditory cortex suggest that we create expectations of how musical sounds should unfold based on what is learned and stored in our auditory cortex, and our emotions result from the violation or fulfillment of these expectations. We are constantly making reward-related predictions to survive, and this study provides neurobiological evidence that we also make predictions when listening to an abstract stimulus, music, even if we have never heard the music before. Pattern recognition and prediction of an otherwise simple set of stimuli, when arranged together become so powerful as to make us happy or bring us to tears, as well as communicate and experience some of the most intense, complex emotions and thoughts.

Listen to the music excerpts used in the study: http://www.zlab.mcgill.ca/science2013/

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3-D Printer Can Build Synthetic Tissues

3-D Printer Can Build Synthetic Tissues

  4:26:00 PM    Science Lover

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A custom-built programmable 3D printer can create materials with several of the properties of living tissues, Oxford University scientists have demonstrated.

A custom-built programmable 3D printer can create materials with several of the properties of living tissues, Oxford University scientists have demonstrated: Droplet network c.500 microns across with electrically conductive pathway between electrodes mimicking nerve. (Credit: Oxford University/G Villar)

The new type of material consists of thousands of connected water droplets, encapsulated within lipid films, which can perform some of the functions of the cells inside our bodies.

These printed 'droplet networks' could be the building blocks of a new kind of technology for delivering drugs to places where they are needed and potentially one day replacing or interfacing with damaged human tissues. Because droplet networks are entirely synthetic, have no genome and do not replicate, they avoid some of the problems associated with other approaches to creating artificial tissues -- such as those that use stem cells.

The team report their findings in this week's Science.

'We aren't trying to make materials that faithfully resemble tissues but rather structures that can carry out the functions of tissues,' said Professor Hagan Bayley of Oxford University's Department of Chemistry, who led the research. 'We've shown that it is possible to create networks of tens of thousands connected droplets. The droplets can be printed with protein pores to form pathways through the network that mimic nerves and are able to transmit electrical signals from one side of a network to the other.'

Each droplet is an aqueous compartment about 50 microns in diameter. Although this is around five times larger than living cells the researchers believe there is no reason why they could not be made smaller. The networks remain stable for weeks.

'Conventional 3D printers aren't up to the job of creating these droplet networks, so we custom built one in our Oxford lab to do it,' said Professor Bayley. 'At the moment we've created networks of up to 35,000 droplets but the size of network we can make is really only limited by time and money. For our experiments we used two different types of droplet, but there's no reason why you couldn't use 50 or more different kinds.'

The unique 3D printer was built by Gabriel Villar, a DPhil student in Professor Bayley's group and the lead author of the paper.

The droplet networks can be designed to fold themselves into different shapes after printing -- so, for example, a flat shape that resembles the petals of a flower is 'programmed' to fold itself into a hollow ball, which cannot be obtained by direct printing. The folding, which resembles muscle movement, is powered by osmolarity differences that generate water transfer between droplets.

Gabriel Villar of Oxford University's Department of Chemistry said: 'We have created a scalable way of producing a new type of soft material. The printed structures could in principle employ much of the biological machinery that enables the sophisticated behaviour of living cells and tissues.'

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Diabetes Drug Makes Brain Cells Grow

Diabetes Drug Makes Brain Cells Grow

  2:00:00 PM    Science Lover

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The widely used diabetes drug metformin comes with a rather unexpected and alluring side effect: it encourages the growth of new neurons in the brain. The study reported in the July 6th issue of Cell Stem Cell, a Cell Press publication, also finds that those neural effects of the drug also make mice smarter.

New research finds that the widely used diabetes drug 
metformin comes with a rather unexpected and alluring 
side effect: it encourages the growth of new neurons in 
the brain. (Credit: iStockphoto/Guido Vrola)

The discovery is an important step toward therapies that aim to repair the brain not by introducing new stem cells but rather by spurring those that are already present into action, says the study's lead author Freda Miller of the University of Toronto-affiliated Hospital for Sick Children. The fact that it's a drug that is so widely used and so safe makes the news all that much better.

Earlier work by Miller's team highlighted a pathway known as aPKC-CBP for its essential role in telling neural stem cells where and when to differentiate into mature neurons. As it happened, others had found before them that the same pathway is important for the metabolic effects of the drug metformin, but in liver cells.

"We put two and two together," Miller says. If metformin activates the CBP pathway in the liver, they thought, maybe it could also do that in neural stem cells of the brain to encourage brain repair.

The new evidence lends support to that promising idea in both mouse brains and human cells. Mice taking metformin not only showed an increase in the birth of new neurons, but they were also better able to learn the location of a hidden platform in a standard maze test of spatial learning.

While it remains to be seen whether the very popular diabetes drug might already be serving as a brain booster for those who are now taking it, there are already some early hints that it may have cognitive benefits for people with Alzheimer's disease. It had been thought those improvements were the result of better diabetes control, Miller says, but it now appears that metformin may improve Alzheimer's symptoms by enhancing brain repair.

Miller says they now hope to test whether metformin might help repair the brains of those who have suffered brain injury due to trauma or radiation therapies for cancer.

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New Energy Source for Future Medical Implants: Sugar

New Energy Source for Future Medical Implants: Sugar

  7:50:00 PM    Science Lover

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MIT engineers have developed a fuel cell that runs on the same sugar that powers human cells: glucose. This glucose fuel cell could be used to drive highly efficient brain implants of the future, which could help paralyzed patients move their arms and legs again.

This silicon wafer consists of glucose fuel cells of varying sizes; 
the largest is 64 by 64 mm. Image: (Credit: Sarpeshkar Lab)

The fuel cell, described in the June 12 edition of the journal PLoS ONE, strips electrons from glucose molecules to create a small electric current. The researchers, led by Rahul Sarpeshkar, an associate professor of electrical engineering and computer science at MIT, fabricated the fuel cell on a silicon chip, allowing it to be integrated with other circuits that would be needed for a brain implant.

The idea of a glucose fuel cell is not new: In the 1970s, scientists showed they could power a pacemaker with a glucose fuel cell, but the idea was abandoned in favor of lithium-ion batteries, which could provide significantly more power per unit area than glucose fuel cells. These glucose fuel cells also utilized enzymes that proved to be impractical for long-term implantation in the body, since they eventually ceased to function efficiently.

The new twist to the MIT fuel cell described in PLoS ONE is that it is fabricated from silicon, using the same technology used to make semiconductor electronic chips. The fuel cell has no biological components: It consists of a platinum catalyst that strips electrons from glucose, mimicking the activity of cellular enzymes that break down glucose to generate ATP, the cell's energy currency. (Platinum has a proven record of long-term biocompatibility within the body.) So far, the fuel cell can generate up to hundreds of microwatts -- enough to power an ultra-low-power and clinically useful neural implant.

"It will be a few more years into the future before you see people with spinal-cord injuries receive such implantable systems in the context of standard medical care, but those are the sorts of devices you could envision powering from a glucose-based fuel cell," says Benjamin Rapoport, a former graduate student in the Sarpeshkar lab and the first author on the new MIT study.

Rapoport calculated that in theory, the glucose fuel cell could get all the sugar it needs from the cerebrospinal fluid (CSF) that bathes the brain and protects it from banging into the skull. There are very few cells in the CSF, so it's highly unlikely that an implant located there would provoke an immune response. There is also significant glucose in the CSF, which does not generally get used by the body. Since only a small fraction of the available power is utilized by the glucose fuel cell, the impact on the brain's function would likely be small.

Karim Oweiss, an associate professor of electrical engineering, computer science and neuroscience at Michigan State University, says the work is a good step toward developing implantable medical devices that don't require external power sources.

"It's a proof of concept that they can generate enough power to meet the requirements," says Oweiss, adding that the next step will be to demonstrate that it can work in a living animal.

A team of researchers at Brown University, Massachusetts General Hospital and other institutions recently demonstrated that paralyzed patients could use a brain-machine interface to move a robotic arm; those implants have to be plugged into a wall outlet.

Mimicking biology with microelectronics

Sarpeshkar's group is a leader in the field of ultra-low-power electronics, having pioneered such designs for cochlear implants and brain implants. "The glucose fuel cell, when combined with such ultra-low-power electronics, can enable brain implants or other implants to be completely self-powered," says Sarpeshkar, author of the book "Ultra Low Power Bioelectronics." This book discusses how the combination of ultra-low-power and energy-harvesting design can enable self-powered devices for medical, bio-inspired and portable applications.

Sarpeshkar's group has worked on all aspects of implantable brain-machine interfaces and neural prosthetics, including recording from nerves, stimulating nerves, decoding nerve signals and communicating wirelessly with implants. One such neural prosthetic is designed to record electrical activity from hundreds of neurons in the brain's motor cortex, which is responsible for controlling movement. That data is amplified and converted into a digital signal so that computers -- or in the Sarpeshkar team's work, brain-implanted microchips -- can analyze it and determine which patterns of brain activity produce movement.

The fabrication of the glucose fuel cell was done in collaboration with Jakub Kedzierski at MIT's Lincoln Laboratory. "This collaboration with Lincoln Lab helped make a long-term goal of mine -- to create glucose-powered bioelectronics -- a reality," Sarpeshkar says. Although he has just begun working on bringing ultra-low-power and medical technology to market, he cautions that glucose-powered implantable medical devices are still many years away.

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Brain Imaging Study Finds Evidence of Basis for Caregiving Impulse

Brain Imaging Study Finds Evidence of Basis for Caregiving Impulse

  7:17:00 PM    Science Lover

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Distinct patterns of activity -- which may indicate a predisposition to care for infants-- appear in the brains of adults who view an image of an infant face -- even when the child is not theirs, according to a study by researchers at the National Institutes of Health and in Germany, Italy, and Japan.

Researchers have found that distinct patterns of activity --
which may indicate a predisposition to care for infants --
appear in the brains of adults who view an image of an
infant face -- even when the child is not theirs.
(Credit: © Jamey Ekins / Fotolia)

Seeing images of infant faces appeared to activate in the adult's brains circuits that reflect preparation for movement and speech as well as feelings of reward.

The findings raise the possibility that studying this activity will yield insights into care giving behavior, but also in cases of child neglect or abuse.

"These adults have no children of their own. Yet images of a baby's face triggered what we think might be a deeply embedded response to reach out and care for that child," said senior author Marc H. Bornstein, Ph.D., head of the Child and Family Research Section of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the NIH institute that collaborated on the study.

While the researchers recorded participants' brain activity, the participants did not speak or move. Yet their brain activity was typical of patterns preceding such actions as picking up or talking to an infant, the researchers explained. The activity pattern could represent a biological impulse that governs adults' interactions with small children.

From their study results, the researchers concluded that this pattern is specific to seeing human infants. The pattern did not appear when the participants looked at photos of adults or of animals -- even baby animals.

Along with Dr. Bornstein, the research was carried out by first author Andrea Caria, Ph.D., of the University of Tuebingen, in Germany; Paola Venuti of the Department of Cognitive Science of University of Trento in Italy; Gianluca Esposito of the RIKEN Brain Science Institute in Saitama, Japan; researchers from the Max Planck Institute for Biological Cybernetics and Eberhard Karls University, in Tuebingen, Germany.

Their findings appear in the journal NeuroImage.

To collect the data, the researchers showed seven men and nine women a series of images while recording their brain activity with a functional magnetic resonance imaging scanner. In the scanner, participants viewed images of puppy and kitten faces, full-grown dogs and cats, human infants and adults.

When the researchers compared the areas and strength of brain activity in response to each kind of image, they found that infant images evoked more activity than any of the other images in brain areas associated with three main functions:

• Premotor and preverbal activity -- The researchers documented increased activity in the premotor cortex and the supplemental motor area, which are regions of the brain directly under the crown of the head. These regions orchestrate brain impulses preceding speech and movement but before movement takes place.
• Facial recognition -- Activity in the fusiform gyrus -- on each side of the brain, about where the ears are -- is associated with processing of information about faces. Activity the researchers detected in the fusiform gyrus may indicate heightened attention to the movement and expressions on an infant's face, the researchers said.
• Emotion and reward -- Activity deep in the brain areas known as the insula and the cingulate cortex indicated emotional arousal, empathy, attachment and feelings linked to motivation and reward, the researchers said. Other studies have documented a similar pattern of activity in the brains of parents responding to their own infants.

Participants also rated how they felt when viewing adult and infant faces. They reported feeling more willing to approach, smile at, and communicate with an infant than an adult. They also recorded feeling happier when viewing images of infants.

Taken together, the researchers contend, the findings suggest a readiness to interact with infants that previously has been only inferred, and only from parents. Such brain activity in nonparents could indicate that the biological makeup of humans includes a mechanism to ensure that infants survive and receive the care they need to grow and develop.

However, signs of readiness to care for a child that appear in the brains of some or even most adults do not necessarily mean the same patterns will appear in the brains of all adults, Dr. Bornstein said. "It's equally important to investigate what's happening in the brains of those who have neglected or abused children," he said. "Additional studies could help us confirm and understand what appears to be a parenting instinct in adults, both when the instinct functions and when it fails to function."

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Brain Co-Opts the Body to Promote Moral Behavior, Study Finds

Brain Co-Opts the Body to Promote Moral Behavior, Study Finds

  8:19:00 PM    Science Lover

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The human brain may simulate physical sensations to prompt introspection, capitalizing on moments of high emotion to promote moral behavior, according to a USC researcher.

Girl being reflective. Researchers found that individuals who were told stories designed to evoke compassion and admiration for virtue sometimes reported that they felt a physical sensation in response. (Credit: © Paul Hill / Fotolia)

Mary Helen Immordino-Yang of the USC Brain and Creativity Institute and the USC Rossier School of Education found that individuals who were told stories designed to evoke compassion and admiration for virtue sometimes reported that they felt a physical sensation in response. These psycho-physical "pangs" of emotion are very real -- they're detectable with brain scans -- and may be evidence that pro-social behavior is part of human survival.

Immordino-Yang's hypothesis, borne out thus far by her research, is that the feeling or emotional reactions in the body may sometimes prompt introspection, and can ultimately promote moral choices and motivation to help or emulate others.

"These emotions are foundational for morality and social learning. They have the power to change the course of your very life," Immordino-Yang said.

Her article appears in the July issue of Emotion Review.

In one instance cited in the article, a participant responded to a story of a little boy's selflessness toward his mother by reporting that he felt like there was a "balloon or something under my sternum, inflating and moving up and out." While pondering this physical sensation, the participant paused for a moment and considered his own relationship with his parents. Ultimately, he voiced a promise to express more gratitude toward them.



Researchers noted similar reactions to varying degrees in the test's other participants. Immordino-Yang's team has performed about 50 of these qualitative analyses in Beijing and at USC. The researchers provide the emotional story, then record the participant's reaction, and also use brain scans to record the physiological response.

"It's a systematic but naturalistic way to induce these emotions." Immordino-Yang said. After being told an emotional true story during a private, taped interview, the participant is simply asked to describe how he or she feels.

Immordino-Yang said she isn't surprised at the findings, though she is excited by them.

"We are an intensely social species," she said. "Our very biology is a social one. For centuries poets have described so-called gut feelings during social emotions. Now we are uncovering the biological evidence."

Future analysis of the data her team has gathered will focus on discovering to what degree culture and individual styles and experiences influence these reactions, as well as how they develop in children and how they can be promoted by education.

This research was supported by the Brain and Creativity Institute, the USC Provost's grant for Advancing Scholarship in the Humanities and Social Sciences, and the Rossier School of Education.

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Brain Performs Near Optimal Visual Search

Brain Performs Near Optimal Visual Search

  12:46:00 AM    Science Lover

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In the wild, mammals survive because they can see and evade predators lurking in the shadowy bushes.

Transportation Security Administration screeners can 
pick out dangerous objects in an image of our messy 
and stuffed suitcases. This ability to recognize target 
objects surrounded by distracters is one of the 
remarkable functions of our nervous system. 
(Credit: © Daniel Schmid / Fotolia)

That ability translates to the human world. Transportation Security Administration screeners can pick out dangerous objects in an image of our messy and stuffed suitcases. We get out of the house every morning because we find our car keys on that cluttered shelf next to the door.

This ability to recognize target objects surrounded by distracters is one of the remarkable functions of our nervous system.

"Visual search is an important task for the brain. Surprisingly, even in a complex task like detecting an object in a scene with distracters, we find that people's performance is near optimal. That means that the brain manages to do the best possible job given the available information," said Dr. Wei Ji Ma, assistant professor of neuroscience at Baylor College of Medicine. A report on research by him and colleagues from other institutions appears online in the journal Nature Neuroscience.

Recognizing the target is more than figuring out each individual object.

"Target detection involves integrating information from multiple locations," said Ma. "Many objects might look like the target for which you are searching. It is a cognitive judgment as well as a visual one."

One factor that must be taken into account is reliability of the information.

"We study that in particular," said Ma. "If you are a detective, you weight different pieces of information based on the reliability of the source. Similarly, the brain has to weight different pieces of visual information."

In his study, he and his colleagues used computer screens to show subjects sets of lines that might or might not contain a line oriented in a particular way. To manipulate reliability, they randomly varied the contrast of each line, making the target easier or more difficult to detect. Each screen was shown for only a fraction of a second, making the search task very difficult.

"We found that even in this complex task, people came close to being optimal in detecting the target," he said. "That means that humans can in a split second integrate information across space while taking into account the reliability of that information. That is important in our daily lives."

The task was deliberately made very hard so that people made mistakes, he said, but their answers were as good as they could be given the noise that is inherent to visual observations.

In the second part of their study, they determined that this ability might rely on groups (populations) of neurons that respond differently to different line orientations. Using such populations, they were able to construct a neural network that could weight information by the appropriate reliability.

They simulated this task on the computer and reproduced the behavior of human subjects, giving credence to their argument that the task requires populations of neurons.

"The visual system is automatically and subconsciously doing complex tasks," said Ma. "People see objects and how they relate to one another. We don't just see with our eyes. We see with our brains. Our eyes are the camera, but the process of interpreting the image in our brains is seeing."

The next question is when does a visual task become so complex that the human brain fails to be optimal?

Others who took part in this research include Ronald van den Berg, a postdoc in Ma's lab, Vidhya Navalpakkam of the California Institute of Technology in Pasadena, Jeffrey M. Beck of University College London, and Alexandre Pouget of the University of Rochester in Rochester, New York.

Funding for this work came from the National Eye Institute, the National Science Foundation, the Gatsby Charitable Foundation, the Netherlands Organisation for Scientific Research, the U.S. Department of Defense's Multidisciplinary University Research Initiative (MURI), the National Institute on Drug Abuse and the James S. McDonnell Foundation.

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Brains Wired So We Can Better Hear Ourselves

Brains Wired So We Can Better Hear Ourselves

  8:02:00 PM    Science Lover

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Like the mute button on the TV remote control, our brains filter out unwanted noise so we can focus on what we're listening to. But when it comes to following our own speech, a new brain study from the University of California, Berkeley, shows that instead of one homogenous mute button, we have a network of volume settings that can selectively silence and amplify the sounds we make and hear.

Activity in the auditory cortex when we speak and listen 
is amplified in some regions of the brain and muted in 
others. In this image, the black line represents muting 
activity when we speak. (Credit: Courtesy 
of Adeen Flinker)

Neuroscientists from UC Berkeley, UCSF and Johns Hopkins University tracked the electrical signals emitted from the brains of hospitalized epilepsy patients. They discovered that neurons in one part of the patients' hearing mechanism were dimmed when they talked, while neurons in other parts lit up.

Their findings, published Dec. 8, 2010 in the Journal of Neuroscience, offer new clues about how we hear ourselves above the noise of our surroundings and monitor what we say. Previous studies have shown a selective auditory system in monkeys that can amplify their self-produced mating, food and danger alert calls, but until this latest study, it was not clear how the human auditory system is wired.

"We used to think that the human auditory system is mostly suppressed during speech, but we found closely knit patches of cortex with very different sensitivities to our own speech that paint a more complicated picture," said Adeen Flinker, a doctoral student in neuroscience at UC Berkeley and lead author of the study.

"We found evidence of millions of neurons firing together every time you hear a sound right next to millions of neurons ignoring external sounds but firing together every time you speak," Flinker added. "Such a mosaic of responses could play an important role in how we are able to distinguish our own speech from that of others."

While the study doesn't specifically address why humans need to track their own speech so closely, Flinker theorizes that, among other things, tracking our own speech is important for language development, monitoring what we say and adjusting to various noise environments.

"Whether it's learning a new language or talking to friends in a noisy bar, we need to hear what we say and change our speech dynamically according to our needs and environment," Flinker said.

He noted that people with schizophrenia have trouble distinguishing their own internal voices from the voices of others, suggesting that they may lack this selective auditory mechanism. The findings may be helpful in better understanding some aspects of auditory hallucinations, he said.

Moreover, with the finding of sub-regions of brain cells each tasked with a different volume control job -- and located just a few millimeters apart -- the results pave the way for a more detailed mapping of the auditory cortex to guide brain surgery.

In addition to Flinker, the study's authors are Robert Knight, director of the Helen Wills Neuroscience Institute at UC Berkeley; neurosurgeons Edward Chang, Nicholas Barbaro and neurologist Heidi Kirsch of the University of California, San Francisco; and Nathan Crone, a neurologist at Johns Hopkins University in Maryland.

The auditory cortex is a region of the brain's temporal lobe that deals with sound. In hearing, the human ear converts vibrations into electrical signals that are sent to relay stations in the brain's auditory cortex where they are refined and processed. Language is mostly processed in the left hemisphere of the brain.

In the study, researchers examined the electrical activity in the healthy brain tissue of patients who were being treated for seizures. The patients had volunteered to help out in the experiment during lulls in their treatment, as electrodes had already been implanted over their auditory cortices to track the focal points of their seizures.

Researchers instructed the patients to perform such tasks as repeating words and vowels they heard, and recorded the activity. In comparing the activity of electrical signals discharged during speaking and hearing, they found that some regions of the auditory cortex showed less activity during speech, while others showed the same or higher levels.

"This shows that our brain has a complex sensitivity to our own speech that helps us distinguish between our vocalizations and those of others, and makes sure that what we say is actually what we meant to say," Flinker said.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Science Updates or its staff.

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Genetic "Light Switches" Control Muscle Movement The technique will improve research on neuromuscular disorders and could one day help paralyzed patients.

Genetic "Light Switches" Control Muscle Movement The technique will improve research on neuromuscular disorders and could one day help paralyzed patients.

  9:57:00 AM    Science Lover

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Using light-sensitive proteins from a single-celled alga and a tiny LED "cuff" placed on a nerve, researchers have triggered the leg muscles of mice to contract in response to millisecond pulses of light.

Light movement: This image shows a cross-section of a mouse sciatic nerve genetically engineered to produce a light-sensitive protein (shown in green). Stanford researchers used this protein to trigger muscle movements in the animal’s leg.
Credit: Nature

The study, published in the journal Nature Medicine, marks the first use of the nascent technology known as optogenetics to control muscle movements. Developed by study coauthor Karl Deisseroth, an associate professor of bioengineering and of psychiatry and behavioral science at Stanford University, optogenetics makes it possible to stimulate neurons with light by inserting the gene for a protein called channelrhodopsin-2, from a green alga. When a modified neuron is exposed to blue light, the protein initiates electrical activity inside the cell that then spreads from neuron to neuron. By controlling which neurons make the protein, as well as which cells are exposed to light, scientists can control neural activity in living animals with unprecedented precision. The paper's other senior author, Scott Delp, a professor of bioengineering, mechanical engineering, and orthopedic surgery at Stanford, says that the optical control method provides "fantastic advantages over electrical stimulation" for his study of muscles and the biomechanics of human movement.

Members of Deisseroth's lab had engineered mice to produce channelrhodopsin-2 in both the central and the peripheral nervous systems. Michael Llewellyn, a former graduate student in Delp's lab, developed a tiny, implantable LED cuff to apply light to the nerve evenly. He placed the cuff on the sciatic nerves of anesthetized mice and triggered millisecond pulses of light. This caused the leg muscles of the mice to contract. When Llewellyn compared the muscle contractions stimulated by light to those generated using a similar electrical cuff, he found that the light-triggered contractions were much more similar to normal muscle activity.

Muscles are made up of two different fibers: small, slow, fatigue-resistant fibers that are typically used for tasks that require fine motor control over longer periods, and larger, faster fibers that can produce higher forces but are more fatigue-prone. In the body, the small, slow fibers are activated first, with the large, fast fibers reserved for quick bursts of power or speed. When muscles are stimulated with electrical pulses, the fast fibers activate first. With the optogenetic switch, however, the fibers were recruited in the normal, physiological order: slow fibers first, fast fibers second. By altering the intensity of the light, Llewellyn found that he could even trigger only the slow fibers--a feat not possible with electrical stimulation.

In the near term, Delp says, the technology will improve the studies that his lab and others do on muscle activity in animal models of stroke, palsies, ALS, and other neuromuscular disorders. He also hopes that in time--a long time, he concedes--such optical switches could be used to help patients with physical disabilities caused by nerve damage such as stroke, spinal cord injury, or cerebral palsy. One possibility, he says, would be to use optical stimulation in place of functional electrical stimulation (FES), in which electrical current is applied to specific nerves or muscles to trigger muscle contractions. The U.S. Food and Drug Administration has already approved FES devices that can restore hand function and bladder control to some paralyzed people. However, FES can quickly lead to muscle fatigue. Delp hopes that, particularly with grasping functions, using optical stimulation might result in better fatigue resistance and perhaps finer muscle control.

"This is a brilliant study, really beautiful science," says Robert Kirsch, a bioengineer at Case Western Reserve University and associate director of the Cleveland Functional Electrical Stimulation Center; he was not involved in the research. "I think there are many [clinical implications]," he says, although, like Delp and Llewellyn, he notes that many high hurdles must be cleared--not least of which is developing a safe, effective way to deliver the channelrhodopsin-2 gene to nerve cells in humans. Otherwise, Kirsch says, "my one objection would be their implication that they've solved the fatigue problem with FES. I'm pretty sure that hasn't happened." Instead, Kirsch believes that most of the fatigue seen in FES patients is due to muscle atrophy and weakness that develop in the chronically paralyzed.

C.J. Heckman, a professor of physiology at Northwestern University's Feinberg School of Medicine, agrees: "It is true that a lot of the fatigue seen in FES patients is due to chronic muscle atrophy." But, he says, "if you could stimulate the muscles in the correct recruitment order repeatedly over time, you could potentially recover a lot of muscle function." This could help paralysis patients preserve their slow muscle fibers, "which would be a huge deal," Heckman says. This is because those fibers do a huge percentage of the work muscles do--everything from maintaining posture to typing on a keyboard.

Delp also thinks that stimulation-based exercise could be an important application for optical muscle control, as could helping wheelchair-bound people stand to reach for books or plates in a cabinet. "I'm not super-high on controlling locomotion"--that is, walking--"with either electrical or optical stimulation, though," Delp says. "It's an incredibly complicated command-and-control scheme that's really hard to coordinate."

In the meantime, Delp and Llewellyn have begun an effort to use a different light-sensitive protein, halorhodopsin, to inhibit motor nerves in mice, with the idea of treating or even curing muscle spasticity, often a serious side effect to brain or spinal injury. Current treatments are far from ideal; doctors may inject botulinum toxin into the affected muscles every few months to paralyze them, use oral medications such as Valium that affect the whole body instead of just the affected muscle, or, in the most severe cases, cut the nerves or tendons of the spastic muscle--a permanent treatment that leaves the patient with no control over that muscle. Delp hopes that genetically engineering the nerves with halorhodopsin might enable people to use light to reversibly relax muscles affected with spasticity.

"I think that's a great idea for treating spasticity," says Jerry Silver, a neuroscientist at Case Western. There may be some difficulties along the way, though, he says. Working with Case colleagues, Silver has started a company called LucCell to develop clinical applications of optogenetics. In one company project, scientists are trying to use halorhodopsin and other inhibitory opsins in animal models to turn off the muscle that controls the bladder sphincter; their ultimate goal is to restore bladder function to paralyzed people. Though they have seen some physiological changes in how the sphincter muscle behaves, they haven't been able to get it to relax enough. "We're learning it's easier to turn things on than turn things off," he says. Still, the team is persisting, looking for better ways to deliver the gene to nerve cells and for ways to increase production of the protein on the cell's surfaces.

"It all depends on the ability to get the transgene in the right place in the person's genome without causing problems," agrees Llewellyn. "It's the main obstacle."

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Brains Wiring: More Like the Internet Than a Pyramid?

Brains Wiring: More Like the Internet Than a Pyramid?

  10:51:00 AM    Science Lover

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The brain has been mapped to the smallest fold for at least a century, but still no one knows how all the parts talk to each other.

New research suggests that the distributed network 
of the Internet may be a better model for the human 
brain than a top-down hierarchy. 
(Credit: iStockphoto/Henrik Jonsson)

A study in Proceedings of the National Academy of Sciences answers that question for a small area of the rat brain and in so doing takes a big step toward revealing the brain's wiring.

The network of brain connections was thought too complex to describe, but molecular biology and computing methods have improved to the point that the National Institutes of Health have announced a $30 million plan to map the human "connectome."

The study shows the power of a new method for tracing brain circuits.

USC College neuroscientists Richard H. Thompson and Larry W. Swanson used the method to trace circuits running through a "hedonic hot spot" related to food enjoyment.

The circuits showed up as patterns of circular loops, suggesting that at least in this part of the rat brain, the wiring diagram looks like a distributed network.

Neuroscientists are split between a traditional view that the brain is organized as a hierarchy, with most regions feeding into the "higher" centers of conscious thought, and a more recent model of the brain as a flat network similar to the Internet.

"We started in one place and looked at the connections. It led into a very complicated series of loops and circuits. It's not an organizational chart. There's no top and bottom to it," said Swanson, a member of the National Academy of Sciences and the Milo Don and Lucille Appleman Professor of Biological Sciences at USC College.

The circuit tracing method allows the study of incoming and outgoing signals from any two brain centers. It was invented and refined by Thompson over eight years. Thompson is a research assistant professor of biological sciences at the College.

Most other tracing studies at present focus only on one signal, in one direction, at one location.

"[We] can look at up to four links in a circuit, in the same animal at the same time. That was our technical innovation," Swanson said.

The Internet model would explain the brain's ability to overcome much local damage, Swanson said.

"You can knock out almost any single part of the Internet and the rest of it works."

Likewise, Swanson said, "There are usually alternate pathways through the nervous system. It's very hard to say that any one part is absolutely essential."

Swanson first argued for the distributed model of the brain in his acclaimed book Brain Architecture: Understanding the Basic Plan (Oxford University Press, 2003).

The PNAS study appears to support his view.

"There is an alternate model. It's not proven, but let's rethink the traditional way of regarding how the brain works," he said.

"The part of the brain you think with, the cortex, is very important, but it's certainly not the only part of the nervous system that determines our behavior."

The research described in the PNAS study was supported by the National Institute of Neurological Disorders and Stroke in the National Institutes of Health.

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Nerve-Cell Transplants Help Brain-Damaged Rats Fully Recover Lost Ability to Learn

Nerve-Cell Transplants Help Brain-Damaged Rats Fully Recover Lost Ability to Learn

  10:34:00 AM    Science Lover

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Nerve cells transplanted into brain-damaged rats helped them to fully recover their ability to learn and remember, probably by promoting nurturing, protective growth factors, according to a new study.

Location of hippocampus in the human brain. Researchers transplanted nerve cells into brain-damaged rats in a study focusing on the hippocampus, which is considered to be the seat of learning and memory. (Credit: Gray's Anatomy / Courtesy of Wikimedia Commons)

Building on previous investigation of transplants in the nervous system, this critical study confirms that cell transplants can help the brain to heal itself. Ultimately, it may lead to new therapies to help dementia patients. More generally, scientists can now develop and test new ways to help repair an injured nervous system -- whether through new drugs, genetically modified cells, transplanted neural (nerve) and non-neural brain cells, or other means.

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