Neuroscience

Articles and news from the latest research reports.

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'Disease in a dish' approach could aid Huntington's disease discovery efforts

Creating induced pluripotent stem cells or iPS cells allows researchers to establish “disease in a dish” models of conditions ranging from Alzheimer’s disease to diabetes. Scientists at Yerkes National Primate Research Center, Emory University have now applied the technology to a model of Huntington’s disease (HD) in transgenic nonhuman primates, allowing them to conveniently assess the efficacy of potential therapies on neuronal cells in the laboratory.

image

(Image caption: Neural progenitor cells derived from transgenic rhesus macaque iPS cells show features of Huntington’s disease pathology, making them a useful tool for therapeutic discovery.)

The results were published this week in Stem Cell Reports.

"A highlight of our model is that our progenitor cells and neurons developed cellular features of HD such as intranuclear inclusions of mutant Huntingtin protein, which most of the currently available cell models do not present," says senior author Anthony Chan, PhD, DVM, associate professor of human genetics at Emory University School of Medicine and Yerkes National Primate Research Center. "We could use these features as a readout for therapy using drugs or a genetic manipulation."

Chan and his colleagues were the first in the world to establish a transgenic nonhuman primate model of HD. HD is an inherited neurodegenerative disorder that leads to the appearance of uncontrolled movements and cognitive impairments, usually in adulthood. It is caused by a mutation that introduces an expanded region where one amino acid (glutamine) is repeated dozens of times in the huntingtin protein.

The non-human primate model has extra copies of the huntingtin gene that contains the expanded glutamine repeats. In the non-human primate model, motor and cognitive deficits appear more quickly than in most cases of Huntington’s disease in humans, becoming noticeable within the first two years of the monkeys’ development.

First author Richard Carter, PhD, a graduate of Emory’s Genetics and Molecular Biology doctoral program, and his colleagues created iPS cells from the transgenic monkeys by reprogramming cells derived from the skin or dental pulp. This technique uses retroviruses to introduce reprogramming factors into somatic cells and induces a fraction of them to become pluripotent stem cells. Pluripotent stem cells are able to differentiate into any type of cell in the body, under the right conditions.

Carter and colleagues induced the iPS cells to become neural progenitor cells and then differentiated neurons. The iPS-derived neural cells developed intracellular and intranuclear aggregates of the mutant huntingtin protein, a classic sign of Huntington’s pathology, as well as an increased sensitivity to oxidative stress.

The sensitivity to oxidative stress was a useful indicator; it could be ameliorated in cell culture, either by a RNA-based gene knockdown approach, or the drug memantine, which is currently being investigated for Huntington’s disease in a human clinical trial.

"We tested two known experimental interventions, but our findings are a proof of principle that this system could be a valuable tool for the discovery and evaluation of other therapies," Chan says.

(Source: news.emory.edu)

Filed under stem cells huntington’s disease iPSCs neurons huntingtin neuroscience science

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2-D or 3-D? That is the Question
The increased visual realism of 3-D films is believed to offer viewers a more vivid and lifelike experience—more thrilling and intense than 2-D because it more closely approximates real life. However, psychology researchers at the University of Utah, among those who use film clips routinely in the lab to study patients’ emotional conditions, have found that there is no significant difference between the two formats. The results were published recently in PLOS ONE.
The study aimed to validate the effectiveness of 3-D film, a newer technology, as compared to 2-D film that is currently widely used as a research tool. Film clips are used in psychological and neuroscience studies as a standardized method for assessing emotional development. Because it is less invasive than other methods, it is especially useful when studying the emotional responses of young people for whom emotional well-being is critical to healthy development.
Author Sheila Crowell, assistant professor of psychology at the U, says that results of the large and tightly controlled study also suggest that as an entertainment medium, 3-D may not provide a different experience from 2-D, insofar as evoking emotional responses go.
“We set out to learn whether technological advances like 3-D enhance the study of emotion, especially for young patients who are routinely exposed to high-tech devices and mediums in their daily lives,” says Crowell. “Both 2-D and 3-D are equally effective at eliciting emotional responses, which also may mean that the expense involved in producing 3-D films is not creating much more than novelty. Further studies are of course warranted, but our findings should be encouraging to researchers who cannot now afford 3-D technologies.”
How the study was conducted
Researchers looked at several measures of emotional state in 408 subjects, including palm sweat, breathing and cardiovascular responses, such as heart rate. These measures are commonly used to gauge emotional responses.
Four film clips were chosen because each prompted one discrete emotion intensely and in context without viewing the entire film. Study participants viewed a 3-D and 2-D clip of approximately five minutes of each film: “My Bloody Valentine” (fear), “Despicable Me” (amusement), “Tangled” (sadness) and “The Polar Express” (thrill or excitement). Participants were randomized to view the films in a design that balanced the pairs of films watched, in which format, and order of presentation. The complex configurations allowed the researchers to compare not only emotional responses, but effects of format and viewing order on the results.
Taken as a whole, the results showed few significant differences between physiological reactions to the films. When accounting for the large number of statistical tests, only one difference was seen between the formats—the number of electrodermal responses (palm sweat) during a thrilling scene from “The Polar Express” 3-D clip. The researchers believe that could be because the 3-D content of the film is of especially high quality, with more and a larger variety of 3-D effects than the others.
Supporting the overall finding is that participants’ individual differences in anxiety, inability to control emotional responses or “thrill seeking” did not alter the psychological or physiological responses to 3-D viewing. In other words, personality differences did not change the results: 2-D is still equally effective for emotion elicitation. According to Crowell, “this could be good news for people who would rather not wear 3-D glasses or pay the extra money to see these types of films.”

2-D or 3-D? That is the Question

The increased visual realism of 3-D films is believed to offer viewers a more vivid and lifelike experience—more thrilling and intense than 2-D because it more closely approximates real life. However, psychology researchers at the University of Utah, among those who use film clips routinely in the lab to study patients’ emotional conditions, have found that there is no significant difference between the two formats. The results were published recently in PLOS ONE.

The study aimed to validate the effectiveness of 3-D film, a newer technology, as compared to 2-D film that is currently widely used as a research tool. Film clips are used in psychological and neuroscience studies as a standardized method for assessing emotional development. Because it is less invasive than other methods, it is especially useful when studying the emotional responses of young people for whom emotional well-being is critical to healthy development.

Author Sheila Crowell, assistant professor of psychology at the U, says that results of the large and tightly controlled study also suggest that as an entertainment medium, 3-D may not provide a different experience from 2-D, insofar as evoking emotional responses go.

“We set out to learn whether technological advances like 3-D enhance the study of emotion, especially for young patients who are routinely exposed to high-tech devices and mediums in their daily lives,” says Crowell. “Both 2-D and 3-D are equally effective at eliciting emotional responses, which also may mean that the expense involved in producing 3-D films is not creating much more than novelty. Further studies are of course warranted, but our findings should be encouraging to researchers who cannot now afford 3-D technologies.”

How the study was conducted

Researchers looked at several measures of emotional state in 408 subjects, including palm sweat, breathing and cardiovascular responses, such as heart rate. These measures are commonly used to gauge emotional responses.

Four film clips were chosen because each prompted one discrete emotion intensely and in context without viewing the entire film. Study participants viewed a 3-D and 2-D clip of approximately five minutes of each film: “My Bloody Valentine” (fear), “Despicable Me” (amusement), “Tangled” (sadness) and “The Polar Express” (thrill or excitement). Participants were randomized to view the films in a design that balanced the pairs of films watched, in which format, and order of presentation. The complex configurations allowed the researchers to compare not only emotional responses, but effects of format and viewing order on the results.

Taken as a whole, the results showed few significant differences between physiological reactions to the films. When accounting for the large number of statistical tests, only one difference was seen between the formats—the number of electrodermal responses (palm sweat) during a thrilling scene from “The Polar Express” 3-D clip. The researchers believe that could be because the 3-D content of the film is of especially high quality, with more and a larger variety of 3-D effects than the others.

Supporting the overall finding is that participants’ individual differences in anxiety, inability to control emotional responses or “thrill seeking” did not alter the psychological or physiological responses to 3-D viewing. In other words, personality differences did not change the results: 2-D is still equally effective for emotion elicitation. According to Crowell, “this could be good news for people who would rather not wear 3-D glasses or pay the extra money to see these types of films.”

Filed under emotions 3-D films anxiety electrodermal activity heart rate psychology neuroscience science

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The Yin and Yang of Overcoming Cocaine Addiction
Yaoying Ma says that biology, by nature, has a yin and a yang—a push and a pull.
Addiction, particularly relapse, she finds, is no exception.
Ma is a research associate in the lab of Yan Dong, assistant professor of neuroscience in the University of Pittsburgh’s Kenneth P. Dietrich School of Arts and Sciences. She is the lead author of a paper published online today in the journal Neuron that posits that it may be possible to ramp up an intrinsic anti-addiction response as a means to fight cocaine relapse and keep the wolves of relapse at bay.
This paper is the first to establish the existence of a brain circuitry that resists a relapse of cocaine use through a naturally occurring neural remodeling with “silent synapses.”
The work is a follow-up on a recent study conducted by Dong and his colleagues, which was published in Nature Neuroscience last November. The team used rat models to examine the effects of cocaine self-administration and withdrawal on nerve cells in the nucleus accumbens, a small region in the brain that is commonly associated with reward, emotion, motivation, and addiction. Specifically, they investigated the roles of synapses—the structures at the ends of nerve cells that relay signals.
The team reported in its Nature Neuroscience study that when a rat uses cocaine, some immature synapses are generated, which are called “silent synapses” because they are semifunctional and send few signals under normal physiological conditions. After that rat stops using cocaine, these “silent synapses” go through a maturation phase and acquire their full function to send signals. Once they can send signals, the synapses will send craving signals for cocaine if the rat is exposed to cues previously associated with the drug.
The current Neuron paper shows that there’s another side of “silent synapse” remodeling. Silent synapses that are generated in a specific cortical projection to the nucleus accumbens by cocaine exposure become “unsilenced” after cocaine withdrawal, resulting in a profound remodeling of this cortical projection. Additional experiments show that silent synapse-based remodeling of this cortical projection decreases cocaine craving. Importantly, this anti-relapse circuitry remodeling is induced by cocaine exposure itself, suggesting that our body has its own way to fight addiction.
Dong, the paper’s senior author, says that the pro-relapse response is predominant after cocaine exposure. But since the anti-relapse response exists inside the brain, it could possibly be clinically tweaked to achieve therapeutic benefits.
Ma notes that this finding “may provide insight into ways to manipulate this yin-yang balance and hopefully provide new neurobiological targets for interventions designed to decrease relapse.”
“The story won’t stop here,” Ma adds. “Our ongoing study is exploring some unusual but simple ways to beef up the endogenous anti-relapse mechanism.”
(Image: PA)

The Yin and Yang of Overcoming Cocaine Addiction

Yaoying Ma says that biology, by nature, has a yin and a yang—a push and a pull.

Addiction, particularly relapse, she finds, is no exception.

Ma is a research associate in the lab of Yan Dong, assistant professor of neuroscience in the University of Pittsburgh’s Kenneth P. Dietrich School of Arts and Sciences. She is the lead author of a paper published online today in the journal Neuron that posits that it may be possible to ramp up an intrinsic anti-addiction response as a means to fight cocaine relapse and keep the wolves of relapse at bay.

This paper is the first to establish the existence of a brain circuitry that resists a relapse of cocaine use through a naturally occurring neural remodeling with “silent synapses.”

The work is a follow-up on a recent study conducted by Dong and his colleagues, which was published in Nature Neuroscience last November. The team used rat models to examine the effects of cocaine self-administration and withdrawal on nerve cells in the nucleus accumbens, a small region in the brain that is commonly associated with reward, emotion, motivation, and addiction. Specifically, they investigated the roles of synapses—the structures at the ends of nerve cells that relay signals.

The team reported in its Nature Neuroscience study that when a rat uses cocaine, some immature synapses are generated, which are called “silent synapses” because they are semifunctional and send few signals under normal physiological conditions. After that rat stops using cocaine, these “silent synapses” go through a maturation phase and acquire their full function to send signals. Once they can send signals, the synapses will send craving signals for cocaine if the rat is exposed to cues previously associated with the drug.

The current Neuron paper shows that there’s another side of “silent synapse” remodeling. Silent synapses that are generated in a specific cortical projection to the nucleus accumbens by cocaine exposure become “unsilenced” after cocaine withdrawal, resulting in a profound remodeling of this cortical projection. Additional experiments show that silent synapse-based remodeling of this cortical projection decreases cocaine craving. Importantly, this anti-relapse circuitry remodeling is induced by cocaine exposure itself, suggesting that our body has its own way to fight addiction.

Dong, the paper’s senior author, says that the pro-relapse response is predominant after cocaine exposure. But since the anti-relapse response exists inside the brain, it could possibly be clinically tweaked to achieve therapeutic benefits.

Ma notes that this finding “may provide insight into ways to manipulate this yin-yang balance and hopefully provide new neurobiological targets for interventions designed to decrease relapse.”

“The story won’t stop here,” Ma adds. “Our ongoing study is exploring some unusual but simple ways to beef up the endogenous anti-relapse mechanism.”

(Image: PA)

Filed under cocaine cocaine addiction nucleus accumbens synapses neurons neuroscience science

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How the Brain Finds What It’s Looking For

Despite the barrage of visual information the brain receives, it retains a remarkable ability to focus on important and relevant items. This fall, for example, NFL quarterbacks will be rewarded handsomely for how well they can focus their attention on color and motion – being able to quickly judge the jersey colors of teammates and opponents and where they’re headed is a valuable skill. How the brain accomplishes this feat, however, has been poorly understood.

image

Now, University of Chicago scientists have identified a brain region that appears central to perceiving the combination of color and motion. They discovered a unique population of neurons that shift in sensitivity toward different colors and directions depending on what is being attended – the red jersey of a receiver headed toward an end zone, for example. The study, published Sept. 4 in the journal Neuron, sheds light on a fundamental neurological process that is a key step in the biology of attention.

“Most of the objects in any given visual scene are not that important, so how does the brain select or attend to important ones?” said study senior author David Freedman, PhD, associate professor of neurobiology at the University of Chicago. “We’ve zeroed in on an area of the brain that appears central to this process. It does this in a very flexible way, changing moment by moment depending on what is being looked for.”

The visual cortex of the brain possesses multiple, interconnected regions that are responsible for processing different aspects of the raw visual signal gathered by the eyes. Basic information on motion and color are known to route through two such regions, but how the brain combines these streams into something usable for decision-making or other higher-order processes remained unclear.

To investigate this process, Freedman and postdoctoral fellow Guilhem Ibos, PhD, studied the response of individual neurons during a simple task. Monkeys were shown a rapid series of visual images. An initial image showed either a group of red dots moving upwards or yellow dots moving downwards, which served as an instruction for which specific colors and directions were relevant during that trial. The subjects were rewarded when they released a lever when this image later reappeared. Subsequent images were composed of different colors of dots moving in different directions, among which was the initial image.

Dynamic neurons

Freedman and Ibos looked at neurons in the lateral intraparietal area (LIP), a region highly interconnected with brain areas involved in vision, motor control and cognitive functions. As subjects performed the task and looked for a specific combination of color and motion, LIP neurons became highly active. They did not respond, however, when the subjects passively viewed the same images without an accompanying task.

When the team further investigated the responses of LIP neurons, they discovered that the neurons possessed a unique characteristic. Individual neurons shifted their sensitivity to color and direction toward the relevant color and motion features for that trial. When the subject looked for red dots moving upwards, for example, a neuron would respond strongly to directions close to upward motion and to colors close to red. If the task was switched to another color and direction seconds later, that same neuron would be more responsive to the new combination.

“Shifts in feature tuning had been postulated a long time ago by theoretical studies,” Ibos said. “This is the first time that neurons in the brain have been shown to shift their selectivity depending on which features are relevant to solve a task.”

Freedman and Ibos developed a model for how the LIP brings together both basic color and motion information. Attention likely affects that process through signals from higher-order areas of the brain that affect LIP neuron selectivity. The team believes that this region plays an important role in making sense of basic sensory information, and they are trying to better understand the brain-wide neuronal circuitry involved in this process.

“Our study suggests that this area of the brain brings together information from multiple areas throughout the brain,” Freedman said. “It integrates inputs – visual, motor, cognitive inputs related to memory and decision making – and represents them in a way that helps solve the task at hand.”

(Source: newswise.com)

Filed under visual system visual cortex parietal cortex neurons neuroscience science

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New research offers help for spinal cord patients
In a study on rats, researchers at the University of Copenhagen have discovered the cause of the involuntary muscle contractions which patients with severe spinal cord injuries frequently suffer. The findings have just been published in the Journal of Neuroscience and, in the long run, can pave the way for new treatment methods.
Three thousand Danish patients suffer from severe spinal cord injuries after being involved in traffic accidents or accidents at work. An injury to the spinal cord is a catastrophe for the individual, and often results in complete or partial paralysis of the person’s arms and legs. Despite the paralysis, several patients experience problems with involuntary muscle contractions or spasms which impair the patient’s quality of life.
The movements are due to the neurotransmitter serotonin, which normally plays a crucial role in relation to our voluntary control of movements by reinforcing the level of activity in the motor neurones when they have to activate the muscles to an extraordinary degree. Research shows that a group of cells in the spinal cord start supplying serotonin in an uncontrolled way following an injury, and this knocks the motor system out of control.
“We now have a qualified idea of why the serotonin level goes out of control, and we have documented that a special serotonin-producing enzyme plays a key role. By targeting the specific enzyme, in the long term we will be able to devise new methods of treatment when we are trying to impact functions in the nervous system,” says associate professor and neurophysiologist Jacob Wienecke.
The prospects of the study are interesting for both spinal cord patients and patients suffering from Parkinson’s disease.
Emergency response kicks in
The enzyme aromatic L-amino acid decarboxylase (AADC) plays an important role in the production of the neurotransmitter serotonin:
“In the first few days after an injury to the spinal cord, we can see there is a very rapid regulation of AADC which results in the uncontrolled production of serotonin. It is our guess that this is the spinal cord’s emergency response trying to boost the enzyme’s capacity,” says Jacob Wienecke.
According to the researchers, it may be the same emergency response which causes the involuntary movements – dyskinesia – that are also experienced by patients with Parkinson’s disease. However, for Parkinson’s patients, it is the dopamine system which is affected, but the enzyme which activates the emergency response is the same.
“It is an interesting perspective, which will hopefully focus efforts on targeting drugs specifically at the AADC cells. Perhaps in the future we can regulate the undesired neural activity in this way so that the unnecessary ‘disturbance on the line’ disappears for the affected patients,” says Jacob Wienecke.
Existing treatment puts a damper on learning
Existing forms of treatment for spinal cord patients currently involve, for example, using the drug baclofen, which suppresses neural activity, and thereby the motor neurones which cause the involuntary movements. The problem with baclofen though is that it impacts motor learning – and thus the patients’ rehabilitation. However, there is still a long way to go. Developing new drugs is a protracted process, and the way is paved with obstacles. Injuries to the spinal column are extremely complex, and primarily result in interruptions to the signalling between the brain and the body.
“Finding a solution to the problem is no easy task. However, a lot suggests that regulating serotonin production more precisely could mitigate undesirable spasms while also supporting the rehabilitation of controlled movements. So far, the study has been carried out on rats, but we have reason to believe that the same mechanisms apply in humans,” says Jacob Wienecke in conclusion.

New research offers help for spinal cord patients

In a study on rats, researchers at the University of Copenhagen have discovered the cause of the involuntary muscle contractions which patients with severe spinal cord injuries frequently suffer. The findings have just been published in the Journal of Neuroscience and, in the long run, can pave the way for new treatment methods.

Three thousand Danish patients suffer from severe spinal cord injuries after being involved in traffic accidents or accidents at work. An injury to the spinal cord is a catastrophe for the individual, and often results in complete or partial paralysis of the person’s arms and legs. Despite the paralysis, several patients experience problems with involuntary muscle contractions or spasms which impair the patient’s quality of life.

The movements are due to the neurotransmitter serotonin, which normally plays a crucial role in relation to our voluntary control of movements by reinforcing the level of activity in the motor neurones when they have to activate the muscles to an extraordinary degree. Research shows that a group of cells in the spinal cord start supplying serotonin in an uncontrolled way following an injury, and this knocks the motor system out of control.

“We now have a qualified idea of why the serotonin level goes out of control, and we have documented that a special serotonin-producing enzyme plays a key role. By targeting the specific enzyme, in the long term we will be able to devise new methods of treatment when we are trying to impact functions in the nervous system,” says associate professor and neurophysiologist Jacob Wienecke.

The prospects of the study are interesting for both spinal cord patients and patients suffering from Parkinson’s disease.

Emergency response kicks in

The enzyme aromatic L-amino acid decarboxylase (AADC) plays an important role in the production of the neurotransmitter serotonin:

“In the first few days after an injury to the spinal cord, we can see there is a very rapid regulation of AADC which results in the uncontrolled production of serotonin. It is our guess that this is the spinal cord’s emergency response trying to boost the enzyme’s capacity,” says Jacob Wienecke.

According to the researchers, it may be the same emergency response which causes the involuntary movements – dyskinesia – that are also experienced by patients with Parkinson’s disease. However, for Parkinson’s patients, it is the dopamine system which is affected, but the enzyme which activates the emergency response is the same.

“It is an interesting perspective, which will hopefully focus efforts on targeting drugs specifically at the AADC cells. Perhaps in the future we can regulate the undesired neural activity in this way so that the unnecessary ‘disturbance on the line’ disappears for the affected patients,” says Jacob Wienecke.

Existing treatment puts a damper on learning

Existing forms of treatment for spinal cord patients currently involve, for example, using the drug baclofen, which suppresses neural activity, and thereby the motor neurones which cause the involuntary movements. The problem with baclofen though is that it impacts motor learning – and thus the patients’ rehabilitation. However, there is still a long way to go. Developing new drugs is a protracted process, and the way is paved with obstacles. Injuries to the spinal column are extremely complex, and primarily result in interruptions to the signalling between the brain and the body.

“Finding a solution to the problem is no easy task. However, a lot suggests that regulating serotonin production more precisely could mitigate undesirable spasms while also supporting the rehabilitation of controlled movements. So far, the study has been carried out on rats, but we have reason to believe that the same mechanisms apply in humans,” says Jacob Wienecke in conclusion.

Filed under spinal cord spinal cord injury serotonin motor neurons spasticity neural activity neuroscience science

201 notes

Reacting to Personal Setbacks: Do You Bounce Back or Give Up? 
Sometimes when people get upsetting news – such as a failing exam grade or a negative job review – they decide instantly to do better the next time. In other situations that are equally disappointing, the same people may feel inclined to just give up.
How can similar setbacks produce such different reactions? It may come down to how much control we feel we have over what happened, according to new research from Rutgers University-Newark. The study, published in the journal Neuron, also finds that when these setbacks occur, the level of control we perceive may even determine which of two distinct parts of the brain will handle the crisis.
“Think of the student who failed an exam,” says Jamil Bhanji, a postdoctoral fellow at Rutgers and one of the study’s co-authors. “They might feel they wouldn’t have failed if they had studied harder, studied differently – something under their control.” That student, Bhanji says, resolves to try new study habits and work hard toward acing the next exam. Functional magnetic resonance imaging (fMRI) used in the study showed activity in a part of the brain called the ventral striatum – which has been shown to guide goals based on prior experiences.
A different student might have failed the same test, but believes it happened because the questions were unfair or the professor was mean, things that he could not control. The negative emotions produced by this uncontrollable setback may cause the student to drop the course.
Overcoming those negative emotions and refocusing on doing well in the class may require a more complicated thought process. In cases like this, fMRI revealed that activity in the ventromedial prefrontal cortex (vmPFC), a part of the brain that regulates emotions in more flexible ways, is necessary to promote persistence.
Mauricio Delgado, an associate professor of psychology at Rutgers’ Newark College of Arts and Sciences and the study’s other co-author, says people whose jobs include delivering bad news should pay attention to these results, because their actions might influence how the news is received.
“You may deliver the news to the student – no sugar coating, here’s your setback,” says Delgado. “But then you make an offer – ‘would you like to review those study habits with me? I’d be happy to do it.’ This puts the student in a situation where they may experience control and be more likely to improve the next time.” This approach, Delgado says, may be far more constructive than curtly delivering a bad grade.
Bhanji says lessons from the study may even guide certain people toward giving up too soon on careers where they could do well. “We wonder why there are fewer women and minorities in the sciences, for example,” he explains. “Maybe in cases like that it’s fair to say there are things we can do to promote reactions to negative feedback that encourage persistence.”
That is not to say everyone should persist. “There are times,” Delgado adds, “when you should not be persistent with your goals. That’s where the striatal system in the brain, which can be a source of more habitual responses, may be a detriment. You keep thinking ‘I can do it, I can do it.’ But maybe you shouldn’t do it. During these times, interpreting the setback more flexibly, via the vmPFC, may be more helpful.”
As research continues, adds Bhanji, important areas to explore will include “figuring out when it’s worth continuing to keep trying and when it’s not.”

Reacting to Personal Setbacks: Do You Bounce Back or Give Up?

Sometimes when people get upsetting news – such as a failing exam grade or a negative job review – they decide instantly to do better the next time. In other situations that are equally disappointing, the same people may feel inclined to just give up.

How can similar setbacks produce such different reactions? It may come down to how much control we feel we have over what happened, according to new research from Rutgers University-Newark. The study, published in the journal Neuron, also finds that when these setbacks occur, the level of control we perceive may even determine which of two distinct parts of the brain will handle the crisis.

“Think of the student who failed an exam,” says Jamil Bhanji, a postdoctoral fellow at Rutgers and one of the study’s co-authors. “They might feel they wouldn’t have failed if they had studied harder, studied differently – something under their control.” That student, Bhanji says, resolves to try new study habits and work hard toward acing the next exam. Functional magnetic resonance imaging (fMRI) used in the study showed activity in a part of the brain called the ventral striatum – which has been shown to guide goals based on prior experiences.

A different student might have failed the same test, but believes it happened because the questions were unfair or the professor was mean, things that he could not control. The negative emotions produced by this uncontrollable setback may cause the student to drop the course.

Overcoming those negative emotions and refocusing on doing well in the class may require a more complicated thought process. In cases like this, fMRI revealed that activity in the ventromedial prefrontal cortex (vmPFC), a part of the brain that regulates emotions in more flexible ways, is necessary to promote persistence.

Mauricio Delgado, an associate professor of psychology at Rutgers’ Newark College of Arts and Sciences and the study’s other co-author, says people whose jobs include delivering bad news should pay attention to these results, because their actions might influence how the news is received.

“You may deliver the news to the student – no sugar coating, here’s your setback,” says Delgado. “But then you make an offer – ‘would you like to review those study habits with me? I’d be happy to do it.’ This puts the student in a situation where they may experience control and be more likely to improve the next time.” This approach, Delgado says, may be far more constructive than curtly delivering a bad grade.

Bhanji says lessons from the study may even guide certain people toward giving up too soon on careers where they could do well. “We wonder why there are fewer women and minorities in the sciences, for example,” he explains. “Maybe in cases like that it’s fair to say there are things we can do to promote reactions to negative feedback that encourage persistence.”

That is not to say everyone should persist. “There are times,” Delgado adds, “when you should not be persistent with your goals. That’s where the striatal system in the brain, which can be a source of more habitual responses, may be a detriment. You keep thinking ‘I can do it, I can do it.’ But maybe you shouldn’t do it. During these times, interpreting the setback more flexibly, via the vmPFC, may be more helpful.”

As research continues, adds Bhanji, important areas to explore will include “figuring out when it’s worth continuing to keep trying and when it’s not.”

Filed under prefrontal cortex striatum setbacks persistence neuroscience science

83 notes

Visualising plastic changes to the brain

Tinnitus, migraine, epilepsy, depression, schizophrenia, Alzheimer’s: all these are examples of diseases with neurological causes, the treatment and study of which is more and more frequently being carried out by means of magnetic stimulation of the brain. However, the method’s precise mechanisms of action have not, as yet, been fully understood. The work group headed by PD Dr Dirk Jancke from the Institut für Neuroinformatik was the first to succeed in illustrating the neuronal effects of this treatment method with high-res images.

Painless therapy
Transcranial magnetic stimulation (TMS) is a painless, non-invasive stimulation method, where an electromagnetic coil held above the head is used to generate a strong magnetic field. This method is deployed to activate or inhibit specific brain regions. Even though the number of its medical applications is constantly on the increase, TMS’ precise neuronal mechanisms of action are not, as yet, very well understood. That is because imaging used for humans, such as fMRI (functional magnetic resonance imaging), do not possess the temporal resolution necessary for recording neural activities in milliseconds. More rapid measurement methods, such as EEG or MEG, on the other hand, are affected by the induced magnetic field, with the results that strong interferences are generated that cover important information regarding immediate TMS-based changes to brain activities.
Observing effect on neurons in real time
High-res images of TMS effects have now for the first time been successfully generated by RUB researchers in animal testing. The work group headed by PD Dr Dirk Jancke, Institut für Neuroinformatik, utilises voltage-sensitive dyes which, anchored in cell membranes, send out fluorescent light signals once neurons get activated or inhibited. By using light, the researchers avoided the problem of measurement of artefacts occurring due to magnetic fields. “We can now demonstrate in real time how one single TMS pulse suppresses brain activity across a considerable region, most likely through mass activation of inhibiting brain cells,” says Dr Jancke. With higher TMS frequencies, each additional TMS pulse generates an incremental increase in brain activity. “This results in a higher cortical activation state, which opens up a time window for plastic changes,” explains Dr Vladislav Kozyrev, the first author of the study.
Chances for patients
The increased neuronal excitability may be utilised to effect specific reorganisation of cell connections by means of targeted learning processes. For example, through visual training after TMS, the ability to identify image contours improves; moreover, a combination of these methods enhances contrast perception in patients with amblyopia - a disorder of sight acquired during child development. For many neurological diseases of the brain, such as epilepsy, depression and stroke, specific models have been developed. “Deployed in animal testing, our technology has delivered high spatiotemporal resolution imaging data of cortical activity changes,” says Dirk Jancke. “We are hoping that these data will enable us to optimise TMS parameters and learning processes in a targeted manner, which are going to be used in future to adapt this technology for medical treatment of humans.”

Visualising plastic changes to the brain

Tinnitus, migraine, epilepsy, depression, schizophrenia, Alzheimer’s: all these are examples of diseases with neurological causes, the treatment and study of which is more and more frequently being carried out by means of magnetic stimulation of the brain. However, the method’s precise mechanisms of action have not, as yet, been fully understood. The work group headed by PD Dr Dirk Jancke from the Institut für Neuroinformatik was the first to succeed in illustrating the neuronal effects of this treatment method with high-res images.

Painless therapy

Transcranial magnetic stimulation (TMS) is a painless, non-invasive stimulation method, where an electromagnetic coil held above the head is used to generate a strong magnetic field. This method is deployed to activate or inhibit specific brain regions. Even though the number of its medical applications is constantly on the increase, TMS’ precise neuronal mechanisms of action are not, as yet, very well understood. That is because imaging used for humans, such as fMRI (functional magnetic resonance imaging), do not possess the temporal resolution necessary for recording neural activities in milliseconds. More rapid measurement methods, such as EEG or MEG, on the other hand, are affected by the induced magnetic field, with the results that strong interferences are generated that cover important information regarding immediate TMS-based changes to brain activities.

Observing effect on neurons in real time

High-res images of TMS effects have now for the first time been successfully generated by RUB researchers in animal testing. The work group headed by PD Dr Dirk Jancke, Institut für Neuroinformatik, utilises voltage-sensitive dyes which, anchored in cell membranes, send out fluorescent light signals once neurons get activated or inhibited. By using light, the researchers avoided the problem of measurement of artefacts occurring due to magnetic fields. “We can now demonstrate in real time how one single TMS pulse suppresses brain activity across a considerable region, most likely through mass activation of inhibiting brain cells,” says Dr Jancke. With higher TMS frequencies, each additional TMS pulse generates an incremental increase in brain activity. “This results in a higher cortical activation state, which opens up a time window for plastic changes,” explains Dr Vladislav Kozyrev, the first author of the study.

Chances for patients

The increased neuronal excitability may be utilised to effect specific reorganisation of cell connections by means of targeted learning processes. For example, through visual training after TMS, the ability to identify image contours improves; moreover, a combination of these methods enhances contrast perception in patients with amblyopia - a disorder of sight acquired during child development. For many neurological diseases of the brain, such as epilepsy, depression and stroke, specific models have been developed. “Deployed in animal testing, our technology has delivered high spatiotemporal resolution imaging data of cortical activity changes,” says Dirk Jancke. “We are hoping that these data will enable us to optimise TMS parameters and learning processes in a targeted manner, which are going to be used in future to adapt this technology for medical treatment of humans.”

Filed under transcranial magnetic stimulation brain activity plasticity brain cells neuroscience science

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Stanford scientists reveal complexity in the brain’s wiring diagram
When Joanna Mattis started her doctoral project she expected to map how two regions of the brain connect. Instead, she got a surprise. It turns out the wiring diagram shifts depending on how you flip the switch.
"There’s a lot of excitement about being able to make a map of the brain with the idea that if we could figure out how it is all connected we could understand how it works," Mattis said. "It turns out it’s so much more dynamic than that."
Mattis is a co-first author on a paper describing the work published August 27 in the Journal of Neuroscience. Julia Brill, then a postdoctoral scholar, was the other co-first author.
Mattis had been a graduate student in the lab of Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, where she helped work on a new technique called optogenetics. That technique allows neuroscientists to selectively turn parts of the brain on and off to see what happens. She wanted to use optogenetics to understand the wiring of a part of the brain involved in spatial memory – it’s what makes a mental map of your surroundings as you explore a new city, for example.
Scientists already knew that when an animal explores habitats, two parts of the brain are involved in the initial exploring phase and then in solidifying a map of the environment – the hippocampus and the septum.
When an animal is exploring an environment, the neurons in the hippocampus fire slow signals to the septum, essentially telling the septum that it’s busy acquiring information. Once the animal is done exploring, those same cells fire off intense signals letting the septum know that it’s now locking that information into memory. The scientists call this phase consolidation. The septum uses that information to then turn around and regulate other signals going into the hippocampus.
"I wanted to study the hippocampus because on the one hand so much was already known – there was already this baseline of knowledge to work off of. But then the question of how the hippocampus and septum communicate hadn’t been accessible before optogenetics," Mattis said.
Neurons in the hippocampus were known to fire in a rhythmic pattern, which is a particular expertise of John Huguenard, a professor of neurology. Mattis obtained an interdisciplinary fellowship through Stanford Bio-X, which allowed her to combine the Deisseroth lab’s expertise in optogenetics with the rhythmic brain network expertise of Julia Brill from the Huguenard lab.
Mattis and Brill used optogenetics to prompt neurons of the hippocampus to mimic either the slow firing characteristic of information acquisition or the rapid firing characteristic of consolidation. When they mimicked the slow firing they saw a quick reaction by cells in the septum. When they mimicked the fast consolidation firing, they saw a much slower response by completely different cells in the septum.
Same set of wires – different outcome. That’s like turning on different lights depending on how hard you flip the switch. “This illustrates how complex the brain is,” Mattis said.
Most scientific papers answer a question: What does this protein do? How does this part of the brain work? By contrast, this paper raised a whole new set of questions, Mattis said. They more or less understand the faster reaction, but what is causing the slower reaction? How widespread is this phenomenon in the brain?
"The other big picture thing that we opened up but didn’t answer is: How can you then tie this back to the circuit overall and learning memory?" Mattis said. "Those would be exciting things to follow up on for future projects."

Stanford scientists reveal complexity in the brain’s wiring diagram

When Joanna Mattis started her doctoral project she expected to map how two regions of the brain connect. Instead, she got a surprise. It turns out the wiring diagram shifts depending on how you flip the switch.

"There’s a lot of excitement about being able to make a map of the brain with the idea that if we could figure out how it is all connected we could understand how it works," Mattis said. "It turns out it’s so much more dynamic than that."

Mattis is a co-first author on a paper describing the work published August 27 in the Journal of Neuroscience. Julia Brill, then a postdoctoral scholar, was the other co-first author.

Mattis had been a graduate student in the lab of Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, where she helped work on a new technique called optogenetics. That technique allows neuroscientists to selectively turn parts of the brain on and off to see what happens. She wanted to use optogenetics to understand the wiring of a part of the brain involved in spatial memory – it’s what makes a mental map of your surroundings as you explore a new city, for example.

Scientists already knew that when an animal explores habitats, two parts of the brain are involved in the initial exploring phase and then in solidifying a map of the environment – the hippocampus and the septum.

When an animal is exploring an environment, the neurons in the hippocampus fire slow signals to the septum, essentially telling the septum that it’s busy acquiring information. Once the animal is done exploring, those same cells fire off intense signals letting the septum know that it’s now locking that information into memory. The scientists call this phase consolidation. The septum uses that information to then turn around and regulate other signals going into the hippocampus.

"I wanted to study the hippocampus because on the one hand so much was already known – there was already this baseline of knowledge to work off of. But then the question of how the hippocampus and septum communicate hadn’t been accessible before optogenetics," Mattis said.

Neurons in the hippocampus were known to fire in a rhythmic pattern, which is a particular expertise of John Huguenard, a professor of neurology. Mattis obtained an interdisciplinary fellowship through Stanford Bio-X, which allowed her to combine the Deisseroth lab’s expertise in optogenetics with the rhythmic brain network expertise of Julia Brill from the Huguenard lab.

Mattis and Brill used optogenetics to prompt neurons of the hippocampus to mimic either the slow firing characteristic of information acquisition or the rapid firing characteristic of consolidation. When they mimicked the slow firing they saw a quick reaction by cells in the septum. When they mimicked the fast consolidation firing, they saw a much slower response by completely different cells in the septum.

Same set of wires – different outcome. That’s like turning on different lights depending on how hard you flip the switch. “This illustrates how complex the brain is,” Mattis said.

Most scientific papers answer a question: What does this protein do? How does this part of the brain work? By contrast, this paper raised a whole new set of questions, Mattis said. They more or less understand the faster reaction, but what is causing the slower reaction? How widespread is this phenomenon in the brain?

"The other big picture thing that we opened up but didn’t answer is: How can you then tie this back to the circuit overall and learning memory?" Mattis said. "Those would be exciting things to follow up on for future projects."

Filed under optogenetics spatial memory neurons hippocampus septum septal cells neuroscience science

184 notes

Yoga Relieves Multiple Sclerosis Symptoms

Paula Meltzer was only 38 when out of nowhere everything she looked at was blurry. For the single mother, who had a lucrative career as a gemologist and spent hours examining valuable pieces of jewelry, it seemed as if – in a split second – her life changed.

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At first doctors thought Meltzer had a brain tumor. What they determined after further tests, however, was that she had multiple sclerosis, an autoimmune disease that affects the brain and central nervous system and was causing optic neuritis, an inflammation of the optic nerve that can cause a partial or complete loss of vision.

“I was living independently, doing my job, taking care of my child – and then I had to look to my parents to take care of me,” Meltzer said.

Almost two decades later, Meltzer, out of a wheelchair and walking without a cane, was one of 14 women with moderate disability due to MS who participated in a pilot trial conducted by the Rutgers School of Health Related Professions. A specially-designed yoga program for these MS patients not only improved their physical and mental well-being but also enhanced their overall quality of life.

“I felt like I became steadier and stronger in my core,” Meltzer said. Prior to yoga, she described herself as a “wall walker,”  someone who felt safer holding onto the wall in order to get around. “To be able to stand on one leg and feel balanced is amazing.”

Susan Gould Fogerite, director of research for the Institute for Complementary and Alternative Medicine in the School of Health Related Professions, said that although there is widespread evidence that yoga is being used as a form of exercise by those with MS, much of the feedback has been anecdotal and there isn’t much empirical data regarding its safety and efficacy.

This is why she and her colleagues, Evan Cohen and David Kietrys, physical therapists and associate professors in the School of Health Related Professions at Stratford, decided to undertake the small pilot study, believing that a specialized yoga program for MS patients – which incorporates mind, body and spirit – would be beneficial to everyday living.

What they discovered at the end of the eight-week trial was that those who participated were better able to walk for short distances and longer periods of time, had better balance while reaching backwards, fine motor coordination, and were better able to go from sitting to standing. Their quality of life also improved in perceived mental health, concentration, bladder control, walking, and vision, with a decrease in pain and fatigue.

 “Yoga is not just exercise, it is a whole system of living,” said Fogerite, an associate professor, who, along with Kietrys, will present the results on September 26 at the Symposium on Yoga Research at the Kripalu Institute in Massachusetts. “The panel of experts who advised us on the trial wanted to make sure that we provided a fully integrated program that included philosophy, breathing practices, postures, relaxation and meditation.”

The yoga pilot trial was held at Still Point Yoga Center in Laurel Springs, a southern New Jersey town close to Philadelphia. Of the 72 individuals who were interested in participating, only 16 were eligible based on medical and other criteria and availability. Of those, 15 were enrolled and 14 completed the program after one person had to withdraw because of an unrelated health problem.

Meltzer and the other women who participated in the trial ranged in age from 34 to 64. Some had been diagnosed with MS within the last two years while others had been living with the illness for up to 26 years. For 90 minutes, twice a week for two months, they practiced techniques and exercises that would improve their posture, help to increase stamina, and teach them how to relax and focus.

“This study, I hope, is one of many that will give us the clinical information we need,” said Fogerite. “Yoga is not currently being widely prescribed for people with MS, although it might turn out to be a very helpful treatment.”

The yoga practices were done by the women in the study sitting, standing, or lying on yoga mats, and using metal folding chairs situated close to the wall to provide them with more support.

“What was so nice about this experience was that although everyone was at a different level of the disease, we felt like we were all together, so I think the camaraderie helped,” said Meltzer. “And it wasn’t just about gaining more mobility and balance in our legs but our arms and necks felt stronger as well.”

Fogerite said a larger randomized controlled trial would be needed to determine whether yoga could be used as a prescribed treatment for individuals with moderate disability due to MS. More than 2.3 million people – two to three times more women than men – throughout the world are diagnosed with this disease which can cause poor coordination, loss of balance, slurred speech, tremors, numbness, extreme fatigue and problems with memory and concentration.

“When I was first diagnosed I no longer felt safe in my own body,” Meltzer said. “I didn’t trust my body at all.  What the program did was really bring that trust back.”

(Source: news.rutgers.edu)

Filed under MS yoga quality of life meditation psychology neuroscience science

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Can Sleep Loss Affect Your Brain Size?

Sleep difficulties may be linked to faster rates of decline in brain volume, according to a study published in the September 3, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.

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Sleep has been proposed to be “the brain’s housekeeper”, serving to repair and restore the brain.

The study included 147 adults 20 and 84 years old. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume.

All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits.

A total of 35 percent of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The assessment looked at how long people slept, how long it took them to fall asleep at night, use of sleeping medications, and other factors.

The study found that sleep difficulties were linked with a more rapid decline in brain volume over the course of the study in widespread brain regions, including within frontal, temporal and parietal areas.

The results were more pronounced in people over 60 years old.

“It is not yet known whether poor sleep quality is a cause or consequence of changes in brain structure,” said study author Claire E. Sexton, DPhil, with the University of Oxford in the United Kingdom. “There are effective treatments for sleep problems, so future research needs to test whether improving people’s quality of sleep could slow the rate of brain volume loss. If that is the case, improving people’s sleep habits could be an important way to improve brain health.”

Filed under sleep sleep difficulties cortical atrophy brain volume neuroscience science

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