Neuroscience

Articles and news from the latest research reports.

89 notes

Training the Older Brain in 3-D: Video Game Enhances Cognitive Control Scientists at UC San Francisco are reporting that they have found a way to reverse some of the negative effects of aging on the brain, using a video game designed to improve cognitive control. The findings, published on Sept. 5 in Nature, show that a specially designed 3-D video game can improve cognitive performance in healthy older adults, they said. The researchers said the study provides a measure of scientific support to the burgeoning field of brain fitness, which has been criticized for lacking evidence that such training can induce lasting and meaningful changes. In the game, which was developed by the UCSF researchers, participants race a car around a winding track while a variety of road signs pop up. Drivers are instructed to keep an eye out for a specific type of sign, while ignoring all the rest, and to press a button whenever that particular sign appears. The need to switch rapidly from driving to responding to the signs – i.e. multitasking – generates interference in the brain that undermines performance. The researchers found that this interference increases dramatically across the adult lifespan. But after receiving just 12 hours of training on the game, spread over a month, the 60- to 85-year-old study participants improved their performance until it surpassed that of 20-somethings who played the game for the first time. The training also improved the participants’ performance in two other important cognitive areas: working memory and sustained attention. And participants maintained their skills at the video game six months after the training had ended. “The finding is a powerful example of how plastic the older brain is,” said Adam Gazzaley, MD, PhD, UCSF associate professor of neurology, physiology and psychiatry and director of the Neuroscience Imaging Center. Gazzaley co-founded the company, Akili Interactive Labs, which is developing the next generation of the video game. Gazzaley, who has made a career out of studying how distraction affects cognitive performance, said his game, NeuroRacer, does more than any ordinary game – be it bridge, a crossword puzzle, or an off-the-shelf video game – to condition the brain. Like a good teacher, he said, NeuroRacer undermines people’s natural tendency to go on automatic pilot once they’ve mastered a skill, and pushes them further than they think they can go. “Normally, when you get better at something, it gets easier,” he said. But with this game, “when you get better, it gets harder.” Brain Training Reverses Age-Related Decline Evidence that the adult brain is capable of learning has been accumulating for more than a dozen years. A study of London taxi drivers, for example, found that their brains had changed as they learned to navigate the city’s notoriously complicated streets. Nevertheless, Gazzaley said the brain’s function often erodes steadily over time in many areas, with some exceptions, like wisdom. Given this, Gazzaley said it’s encouraging that even a small amount of brain training can reverse some of the age-related decline. Gazzaley’s group found evidence of a possible brain mechanism that may explain the improvements he saw in his older subjects, and why these gains transferred to other cognitive areas. Electroencephalograph (EEG) recordings point to changes in a neural network involved in cognitive control, which is necessary to pursue goals. The scientists measured midline frontal theta – or low frequency oscillations – in the prefrontal cortex, as well as the coherence in these waves between frontal and posterior regions of the brain. As the older “drivers” became more adept at the multitasking challenges of NeuroRacer, their brains modulated this key neural network and its activity began to resemble that of young adults. Both of these measures – midline frontal theta and theta coherence – are well established neural markers of cognitive control that have been associated with many of the processes that enable people to pursue their goals. We see this as evidence that the training may have improved our study participants’ ability to stay in an engaged, active state for a longer period of time,” said Joaquin A. Anguera, the paper’s first author and a post-doctoral fellow in Gazzaley’s lab. Indeed, the researchers found that the training-induced changes in this neural network predicted how well participants would do on a different test, called the Test of Variables of Attention (TOVA), which measures sustained attention. “The amount that midline frontal theta went up was related to something that was untrained, this other measure, the TOVA,” Anguera said.  “It implies there’s something that changed that was common to the training and to the task we tested afterwards.” Gazzaley said these findings point toward a common neural basis of cognitive control that is enhanced by the challenging and high-interference conditions of the video game, and this might explain how racing a car in 3-D could improve something as seemingly unrelated as memory. If the finding holds, it could have wide application. Other brain disorders like ADHD, depression and dementia are also associated with deficits in cognitive control. “Follow up studies using functional Magnetic Resonance Imaging and transcranial electrical stimulation are still needed to better understand exactly how this network is involved in the performance changes,” Gazzaley said.

Training the Older Brain in 3-D: Video Game Enhances Cognitive Control

Scientists at UC San Francisco are reporting that they have found a way to reverse some of the negative effects of aging on the brain, using a video game designed to improve cognitive control.

The findings, published on Sept. 5 in Nature, show that a specially designed 3-D video game can improve cognitive performance in healthy older adults, they said. The researchers said the study provides a measure of scientific support to the burgeoning field of brain fitness, which has been criticized for lacking evidence that such training can induce lasting and meaningful changes.

In the game, which was developed by the UCSF researchers, participants race a car around a winding track while a variety of road signs pop up. Drivers are instructed to keep an eye out for a specific type of sign, while ignoring all the rest, and to press a button whenever that particular sign appears. The need to switch rapidly from driving to responding to the signs – i.e. multitasking – generates interference in the brain that undermines performance. The researchers found that this interference increases dramatically across the adult lifespan.

But after receiving just 12 hours of training on the game, spread over a month, the 60- to 85-year-old study participants improved their performance until it surpassed that of 20-somethings who played the game for the first time.

The training also improved the participants’ performance in two other important cognitive areas: working memory and sustained attention. And participants maintained their skills at the video game six months after the training had ended.

“The finding is a powerful example of how plastic the older brain is,” said Adam Gazzaley, MD, PhD, UCSF associate professor of neurology, physiology and psychiatry and director of the Neuroscience Imaging Center. Gazzaley co-founded the company, Akili Interactive Labs, which is developing the next generation of the video game.

Gazzaley, who has made a career out of studying how distraction affects cognitive performance, said his game, NeuroRacer, does more than any ordinary game – be it bridge, a crossword puzzle, or an off-the-shelf video game – to condition the brain. Like a good teacher, he said, NeuroRacer undermines people’s natural tendency to go on automatic pilot once they’ve mastered a skill, and pushes them further than they think they can go.

“Normally, when you get better at something, it gets easier,” he said. But with this game, “when you get better, it gets harder.”

Brain Training Reverses Age-Related Decline

Evidence that the adult brain is capable of learning has been accumulating for more than a dozen years. A study of London taxi drivers, for example, found that their brains had changed as they learned to navigate the city’s notoriously complicated streets. Nevertheless, Gazzaley said the brain’s function often erodes steadily over time in many areas, with some exceptions, like wisdom.

Given this, Gazzaley said it’s encouraging that even a small amount of brain training can reverse some of the age-related decline.

Gazzaley’s group found evidence of a possible brain mechanism that may explain the improvements he saw in his older subjects, and why these gains transferred to other cognitive areas. Electroencephalograph (EEG) recordings point to changes in a neural network involved in cognitive control, which is necessary to pursue goals.

The scientists measured midline frontal theta – or low frequency oscillations – in the prefrontal cortex, as well as the coherence in these waves between frontal and posterior regions of the brain. As the older “drivers” became more adept at the multitasking challenges of NeuroRacer, their brains modulated this key neural network and its activity began to resemble that of young adults.

Both of these measures – midline frontal theta and theta coherence – are well established neural markers of cognitive control that have been associated with many of the processes that enable people to pursue their goals.

We see this as evidence that the training may have improved our study participants’ ability to stay in an engaged, active state for a longer period of time,” said Joaquin A. Anguera, the paper’s first author and a post-doctoral fellow in Gazzaley’s lab.

Indeed, the researchers found that the training-induced changes in this neural network predicted how well participants would do on a different test, called the Test of Variables of Attention (TOVA), which measures sustained attention.

“The amount that midline frontal theta went up was related to something that was untrained, this other measure, the TOVA,” Anguera said.  “It implies there’s something that changed that was common to the training and to the task we tested afterwards.”

Gazzaley said these findings point toward a common neural basis of cognitive control that is enhanced by the challenging and high-interference conditions of the video game, and this might explain how racing a car in 3-D could improve something as seemingly unrelated as memory.

If the finding holds, it could have wide application. Other brain disorders like ADHD, depression and dementia are also associated with deficits in cognitive control.

“Follow up studies using functional Magnetic Resonance Imaging and transcranial electrical stimulation are still needed to better understand exactly how this network is involved in the performance changes,” Gazzaley said.

Filed under aging cognitive performance cognitive control prefrontal cortex neuroscience science

319 notes

Video: The animation describes the paths of traveling performed by an OCD patient who is about to leave his apartment (left) and by a co-morbid OCD and schizophrenia patient performing the same behavior (right). Black circles indicate the number of acts performed in each location. As shown, the COD patient is mostly stationary, while the schizo-OCD patient travels all over the apartment.

The Difference Between Obsession and Delusion

TAU researchers use a zoological method to classify symptoms of OCD and schizophrenia in humans

Because animals can’t talk, researchers need to study their behavior patterns to make sense of their activities. Now researchers at Tel Aviv University are using these zoological methods to study people with serious mental disorders.

Prof. David Eilam of TAU’s Zoology Department at The George S. Wise Faculty of Life Sciences recorded patients with obsessive-compulsive disorder and “schizo-OCD” — which combines symptoms of schizophrenia and OCD — as they performed basic tasks. By analyzing the patients’ movements, they were able to identify similarities and differences between two frequently confused disorders.

Published in the journal CNS Spectrums, the research represents a step toward resolving a longstanding question about the nature of schizo-OCD: Is it a combination of OCD and schizophrenia, or a variation of just one of the disorders?

The researchers concluded that schizo-OCD is a combination of the two disorders. They noted that the behavioral differences identified in the study could be used to help diagnose patients with OCD and other obsessive-compulsive disorders, including schizo-OCD.

The taxonomy of mental disorders

"I realized my methodology for studying rat models could be directly applied to work with humans with mental disorders," Prof. Eilam said. "Behavior is the ultimate output of the nervous system, and my team and I are experts in the fine-grained analysis of behavior, be it of humans or of other animals."

The main features of OCD are, of course, obsessions and compulsions. Obsessions are recurring and persistent thoughts, impulses, or images that are experienced as intrusive and unwanted and cause marked distress or anxiety. In contrast, compulsions are repetitive motor behaviors, such as counting, that occur in response to obsessions and are performed according to strictly applied rules. Schizophrenia is marked by delusions, hallucinations, disorganized speech, abnormal motor behavior, and diminished emotional expression, among other symptoms.

Eilam and graduate student Anat Gershoni of the Zoology Department and Prof. Haggai Hermesh of TAU’s Sackler Faculty of Medicine set out with Dr. Naomi Fineberg of the Queen Elizabeth II Hospital in England to resolve the controversy. To this end, they recorded and compared videos of diagnosed OCD and schizo-OCD patients performing 10 different mundane tasks, like leaving home, making tea, or cleaning a table. The patients met the criteria of the widely used Diagnostic and Statistical Manual of Mental Disorders.

A matter of space

The researchers found that both OCD and schizo-OCD patients exhibited OCD-like behavior in performing the tasks, excessively repeating and adding actions. But schizo-OCD patients additionally acted like schizophrenics.

For a typical OCD patient in the study, the task of leaving home involved standing in one place and repeatedly checking the contents of his pockets before finally taking his keys and cell phone and going to the door. In contrast, a typical schizo-OCD patient traveled around the apartment — switching the lights in the bathroom on and off, then taking his keys and phone to the door, going to scan the bedroom, then taking his keys and phone to the door, going to empty the ashtray, then taking his keys and phone to the door and so on. A typical healthy person would simply pick up his keys and phone and walk out.

Overall, the researchers found that the level of obsessive-compulsive behavior was the same in OCD and schizo-OCD patients. This suggests that both types of patients had the difficulty shifting attention from one task to another that helps define OCD. The schizo-OCD patients, though, did more divergent activity over a larger area than did OCD patients. This suggests that the schizo-OCD patients were continuously shifting attention, which happens in schizophrenia but not OCD.

"While the obsessive compulsive is obsessed with one idea; the schizophrenic’s mind is drifting," said Eilam. "We found that this is reflected in their paths of locomotion. So instead of tracking the thoughts of the patients, we can simply trace their paths of locomotion."

Eilam plans to conduct research comparing repetitive behavior in OCD and autism patients.

Filed under schizophrenia OCD mental disorders compulsive behavior neuroscience psychology science

86 notes

Discovery helps to unlock brain’s speech-learning mechanism

USC scientists have discovered a population of neurons in the brains of juvenile songbirds that are necessary for allowing the birds to recognize the vocal sounds they are learning to imitate.

image

These neurons encode a memory of learned vocal sounds and form a crucial (and hitherto only theorized) part of the neural system that allows songbirds to hear, imitate and learn its species’ songs — just as human infants acquire speech sounds.

The discovery will allow scientists to uncover the exact neural mechanisms that allow songbirds to hear their own self-produced songs, compare them to the memory of the song that they are trying to imitate and then adjust their vocalizations accordingly.

Because this brain-behavior system is thought to be a model for how human infants learn to speak, understanding it could prove crucial to future understanding and treatment of language disorders in children. In both songbirds and humans, feedback of self-produced vocalizations is compared to memorized vocal sounds and progressively refined to achieve a correct imitation.

“Every neurodevelopmental disorder you can think of — including Tourette syndrome, autism and Rett syndrome — entails in some way a breakdown in auditory processing and vocal communication,” said Sarah Bottjer, senior author of an article on the research that appears in the Journal of Neuroscience on Sept. 4. “Understanding mechanisms of vocal learning at a cellular level is a huge step toward being able to someday address the biological issues behind the behavioral issues.”

Bottjer professor of neurobiology at the USC Dornsife College of Letters, Arts and Sciences, collaborated with lead author Jennifer Achiro, a graduate student at USC, to examine the activity of neurons in songbirds’ brains using electrodes to record the activity of individual neurons.

In the basal ganglia — a complex system of neurons in the brain responsible for, among other things, procedural learning — Bottjer and Achiro were able to isolate two different types of neurons in young songbirds: ones that were activated only when the birds heard themselves singing and others that were activated only when the birds heard the songs of adult birds that they were trying to imitate.

The two sets of neurons allow the songbirds to recognize both their current behavior and a goal behavior that they would like to achieve.

“The process of learning speech requires the brain to compare feedback of current vocal behavior to a memory of target vocal sounds,” Achiro said. “The discovery of these two distinct populations of neurons means that this brain region contains separate neural representation of current and goal behaviors. Now, for the first time, we can test how these two neural representations are compared so that correct matches between the two are somehow rewarded.”

The next step for scientists will be to learn how the brain rewards correct matches between feedback of current vocal behavior and the goal memory that depicts memorized vocal sounds as songbirds make progress in bringing their current behavior closer to their goal behavior, Bottjer said.

(Source: news.usc.edu)

Filed under songbirds neural activity basal ganglia vocal learning speech neuroscience science

70 notes

New laser-based tool could dramatically improve the accuracy of brain tumor surgery

Imaging technique tells tumor tissue from normal tissue, could be used in operating room for real-time guidance of surgery

A new laser-based technology may make brain tumor surgery much more accurate, allowing surgeons to tell cancer tissue from normal brain at the microscopic level while they are operating, and avoid leaving behind cells that could spawn a new tumor.

image

This image of a human glioblastoma brain tumor in the brain of a mouse was made with stimulated Raman scattering, or SRS, microscopy. The technique allows the tumor (blue) to be easily distinguished from normal tissue (green) based on faint signals emitted by tissue with different cellular structures.

In a new paper, featured on the cover of the journal Science Translational Medicine, a team of University of Michigan Medical School and Harvard University researchers describes how the technique allows them to “see” the tiniest areas of tumor cells in brain tissue.

They used this technique to distinguish tumor from healthy tissue in the brains of living mice — and then showed that the same was possible in tissue removed from a patient with glioblastoma multiforme, one of the most deadly brain tumors.

Now, the team is working to develop the approach, called SRS microscopy, for use during an operation to guide them in removing tissue, and test it in a clinical trial at U-M. The work was funded by the National Institutes of Health.

A need for improvement in tumor removal

On average, patients diagnosed with glioblastoma multiforme live only 18 months after diagnosis. Surgery is one of the most effective treatments for such tumors, but less than a quarter of patients’ operations achieve the best possible results, according to a study published last fall in the Journal of Neurosurgery.

“Though brain tumor surgery has advanced in many ways, survival for many patients is still poor, in part because surgeons can’t be sure that they’ve removed all tumor tissue before the operation is over,” says co-lead author Daniel Orringer, M.D., a lecturer in the U-M Department of Neurosurgery who has worked with the Harvard team since a chance meeting with a team member during his U-M residency.

image

On the left, the view of the brain that neurosurgeons currently see during an operation using bright-field microscopy. On the right, an SRS microscopy view of the same area of brain - in this case, a mouse brain that has had human brain tumor tissue transplanted into it. SRS might someday allow surgeons to see this same view of patients’ brains.

“We need better tools for visualizing tumor during surgery, and SRS microscopy is highly promising,” he continues. “With SRS we can see something that’s invisible through conventional surgical microscopy.”

The SRS in the technique’s name stands for stimulated Raman scattering. Named for C.V. Raman, one of the Indian scientists who co-discovered the effect and shared a 1930 Nobel Prize in physics for it, Raman scattering involves allows researchers to measure the unique chemical signature of materials.

In the SRS technique, they can detect a weak light signal that comes out of a material after it’s hit with light from a non-invasive laser. By carefully analyzing the spectrum of colors in the light signal, the researchers can tell a lot about the chemical makeup of the sample.

Over the past 15 years, Sunney Xie, Ph.D., of the Department of Chemistry and Chemical Biology at Harvard University – the senior author of the new paper — has advanced the technique for high-speed chemical imaging. By amplifying the weak Raman signal by more than 10,000 times, it is now possible to make multicolor SRS images of living tissue or other materials. The team can even make 30 new images every second — the rate needed to create videos of the tissue in real time.

Seeing the brain’s microscopic architecture

A multidisciplinary team of chemists, neurosurgeons, pathologists and others worked to develop and test the tool. The new paper is the first time SRS microscopy has been used in a living organism to see the “margin” of a tumor – the boundary area where tumor cells infiltrate among normal cells. That’s the hardest area for a surgeon to operate – especially when a tumor has invaded a region with an important function.

As the images in the paper show, the technique can distinguish brain tumor from normal tissue with remarkable accuracy, by detecting the difference between the signal given off by the dense cellular structure of tumor tissue, and the normal healthy grey and white matter.

The authors suggest that SRS microscopy may be as accurate for detecting tumor as the approach currently used in brain tumor diagnosis – called H&E staining.

image

This image shows the same areas of brain, imaged with SRS microscopy (left) and conventional H&E staining, which is the current technique used to diagnose brain tumors at the tissue level. The research suggests that SRS microscopy could be as accurate as H&E staining in allowing doctors to see tumors - without having to remove tissue or inject dyes into the patient.

The paper contains data from a test that pitted H&E staining directly against SRS microscopy. Three surgical pathologists, trained in studying brain tissue and spotting tumor cells, had nearly the same level of accuracy no matter which images they studied. But unlike H&E staining, SRS microscopy can be done in real time, and without dyeing, removing or processing the tissue.

Next steps: A smaller laser, a clinical trial

The current SRS microscopy system is not yet small or stable enough to use in an operating room. The team is collaborating with a start-up company formed by members of Xie’s group, called Invenio Imaging Inc., which is developing a laser to perform SRS through inexpensive fiber-optic components. The team is also working with AdvancedMEMS Inc. to reduce the size of the probe that makes the images possible.

A validation study, to examine tissue removed from consenting U-M brain tumor patients, may begin as soon as next year.

(Source: uofmhealth.org)

Filed under brain tumor glioblastoma brain tissue neuroimaging SRS microscopy neuroscience science

679 notes

Look at What I’M Saying University of Utah Engineers Show Brain Depends on Vision to Hear University of Utah bioengineers discovered our understanding of language may depend more heavily on vision than previously thought: under the right conditions, what you see can override what you hear. These findings suggest artificial hearing devices and speech-recognition software could benefit from a camera, not just a microphone. “For the first time, we were able to link the auditory signal in the brain to what a person said they heard when what they actually heard was something different. We found vision is influencing the hearing part of the brain to change your perception of reality – and you can’t turn off the illusion,” says the new study’s first author, Elliot Smith, a bioengineering and neuroscience graduate student at the University of Utah. “People think there is this tight coupling between physical phenomena in the world around us and what we experience subjectively, and that is not the case.” The brain considers both sight and sound when processing speech. However, if the two are slightly different, visual cues dominate sound. This phenomenon is named the McGurk effect for Scottish cognitive psychologist Harry McGurk, who pioneered studies on the link between hearing and vision in speech perception in the 1970s. The McGurk effect has been observed for decades. However, its origin has been elusive. In the new study, which appears today in the journal PLOS ONE, the University of Utah team pinpointed the source of the McGurk effect by recording and analyzing brain signals in the temporal cortex, the region of the brain that typically processes sound. Working with University of Utah bioengineer Bradley Greger and neurosurgeon Paul House, Smith recorded electrical signals from the brain surfaces of four severely epileptic adults (two male, two female) from Utah and Idaho. House placed three button-sized electrodes on the left, right or both brain hemispheres of each test subject, depending on where each patient’s seizures were thought to originate. The experiment was done on volunteers with severe epilepsy who were undergoing surgery to treat their epilepsy. These four test subjects were then asked to watch and listen to videos focused on a person’s mouth as they said the syllables “ba,” “va,” “ga” and “tha.” Depending on which of three different videos were being watched, the patients had one of three possible experiences as they watched the syllables being mouthed: — The motion of the mouth matched the sound. For example, the video showed “ba” and the audio sound also was “ba,” so the patients saw and heard “ba.” — The motion of the mouth obviously did not match the corresponding sound, like a badly dubbed movie. For example, the video showed “ga” but the audio was “tha,” so the patients perceived this disconnect and correctly heard “tha.” — The motion of the mouth only was mismatched slightly with the corresponding sound. For example, the video showed “ba” but the audio was “va,” and patients heard “ba” even though the sound really was “va.” This demonstrates the McGurk effect – vision overriding hearing. By measuring the electrical signals in the brain while each video was being watched, Smith and Greger could pinpoint whether auditory or visual brain signals were being used to identify the syllable in each video. When the syllable being mouthed matched the sound or didn’t match at all, brain activity increased in correlation to the sound being watched. However, when the McGurk effect video was viewed, the activity pattern changed to resemble what the person saw, not what they heard. Statistical analyses confirmed the effect in all test subjects. “We’ve shown neural signals in the brain that should be driven by sound are being overridden by visual cues that say, ‘Hear this!’” says Greger. “Your brain is essentially ignoring the physics of sound in the ear and following what’s happening through your vision.” Greger was senior author of the study as an assistant professor of bioengineering at the University of Utah. He recently took a faculty position at Arizona State University. The new findings could help researchers understand what drives language processing in humans, especially in a developing infant brain trying to connect sounds and lip movement to learn language. These findings also may help researchers sort out how language processing goes wrong when visual and auditory inputs are not integrated correctly, such as in dyslexia, Greger says.

Look at What I’M Saying

University of Utah Engineers Show Brain Depends on Vision to Hear

University of Utah bioengineers discovered our understanding of language may depend more heavily on vision than previously thought: under the right conditions, what you see can override what you hear. These findings suggest artificial hearing devices and speech-recognition software could benefit from a camera, not just a microphone.

“For the first time, we were able to link the auditory signal in the brain to what a person said they heard when what they actually heard was something different. We found vision is influencing the hearing part of the brain to change your perception of reality – and you can’t turn off the illusion,” says the new study’s first author, Elliot Smith, a bioengineering and neuroscience graduate student at the University of Utah. “People think there is this tight coupling between physical phenomena in the world around us and what we experience subjectively, and that is not the case.”

The brain considers both sight and sound when processing speech. However, if the two are slightly different, visual cues dominate sound. This phenomenon is named the McGurk effect for Scottish cognitive psychologist Harry McGurk, who pioneered studies on the link between hearing and vision in speech perception in the 1970s. The McGurk effect has been observed for decades. However, its origin has been elusive.

In the new study, which appears today in the journal PLOS ONE, the University of Utah team pinpointed the source of the McGurk effect by recording and analyzing brain signals in the temporal cortex, the region of the brain that typically processes sound.

Working with University of Utah bioengineer Bradley Greger and neurosurgeon Paul House, Smith recorded electrical signals from the brain surfaces of four severely epileptic adults (two male, two female) from Utah and Idaho. House placed three button-sized electrodes on the left, right or both brain hemispheres of each test subject, depending on where each patient’s seizures were thought to originate. The experiment was done on volunteers with severe epilepsy who were undergoing surgery to treat their epilepsy.

These four test subjects were then asked to watch and listen to videos focused on a person’s mouth as they said the syllables “ba,” “va,” “ga” and “tha.” Depending on which of three different videos were being watched, the patients had one of three possible experiences as they watched the syllables being mouthed:

— The motion of the mouth matched the sound. For example, the video showed “ba” and the audio sound also was “ba,” so the patients saw and heard “ba.”

— The motion of the mouth obviously did not match the corresponding sound, like a badly dubbed movie. For example, the video showed “ga” but the audio was “tha,” so the patients perceived this disconnect and correctly heard “tha.”

— The motion of the mouth only was mismatched slightly with the corresponding sound. For example, the video showed “ba” but the audio was “va,” and patients heard “ba” even though the sound really was “va.” This demonstrates the McGurk effect – vision overriding hearing.

By measuring the electrical signals in the brain while each video was being watched, Smith and Greger could pinpoint whether auditory or visual brain signals were being used to identify the syllable in each video. When the syllable being mouthed matched the sound or didn’t match at all, brain activity increased in correlation to the sound being watched. However, when the McGurk effect video was viewed, the activity pattern changed to resemble what the person saw, not what they heard. Statistical analyses confirmed the effect in all test subjects.

“We’ve shown neural signals in the brain that should be driven by sound are being overridden by visual cues that say, ‘Hear this!’” says Greger. “Your brain is essentially ignoring the physics of sound in the ear and following what’s happening through your vision.”

Greger was senior author of the study as an assistant professor of bioengineering at the University of Utah. He recently took a faculty position at Arizona State University.

The new findings could help researchers understand what drives language processing in humans, especially in a developing infant brain trying to connect sounds and lip movement to learn language. These findings also may help researchers sort out how language processing goes wrong when visual and auditory inputs are not integrated correctly, such as in dyslexia, Greger says.

Filed under McGurk effect auditory cortex language language processing neuroscience science

152 notes

Discovery Shows Cerebellum Plays Important Role In Sensing Limb Position And Movement Kennedy Krieger Institute researchers find that damage to the cerebellum impairs ability to predict motion outcomes and discrimination between limb positions. Researchers at the Kennedy Krieger Institute announced today study findings showing, for the first time, the link between the brain’s cerebellum and proprioception, or the body’s ability to sense movement and joint and limb position. Published in The Journal of Neuroscience, the study uncovers a previously unknown perceptual deficit among cerebellar patients, suggesting that damage to this portion of the brain can directly impact a person’s ability to sense the position of their limbs and predict movement. This discovery could prompt future researchers to reexamine physical therapy tactics for cerebellar patients, who often have impaired coordination or appear clumsy. The sense of proprioception arises from the brain’s readout of signals from receptors in muscles, joints and ligaments, but also from the brain’s predictions of how motor commands will move the limb. The latter can only contribute to proprioception when a person actively moves their own body. To date, researchers and neurologists believed that proprioception did not occur in the cerebellum, and thus, damage to the cerebellum did not affect proprioception. “Proprioception was previously not considered a factor in the therapy or recovery of cerebellar patients. In fact, previous research has shown that individuals with cerebellum damage and no other clinical neurological impairments have normal proprioception when their limbs are moved passively in a clinical setting,” says Amy J. Bastian, Ph.D., PT, director of the Motion Analysis Laboratory at Kennedy Krieger Institute. “However, when these patients move their limbs actively, they exhibit significant proprioceptive impairment.” Additionally, researchers found that proprioception in healthy subjects was impaired when unpredictable dynamics, or small disturbances to the cerebellum, were incorporated into active movement. This suggests that muscle activity alone is likely insufficient to improve perception of limb placement, and proprioception should be taken into consideration when determining therapeutic practices for cerebellar patients. Study Results and Methodology The study compared 11 healthy people (control group) to 11 patients with cerebellar damage (caused by spinocerebellar ataxia, sporadic cerebellar ataxia or autosomal-dominant cerebellar ataxia type III) but no evidence of white matter damage, spontaneous nystagmus or atrophy to the brainstem. None of the patients included in the study had sensory loss assessed by conventional clinical measures of proprioception and tactile sensation. Participants were compared in three psychophysical tasks designed to assess passive proprioception, active proprioception with simple dynamics, and active proprioception with complex, unpredictable dynamics designed to disrupt the cerebellum. All tasks relied on proprioceptive sense without vision. Results showed that: Cerebellar patients had no deficits in passive proprioception Unlike control subjects, cerebellar patients did not show an improvement between passive and active proprioception with simple dynamics Control patients performed similarly to patients in an active proprioception task with unpredictable, small disruptions to their movement. This study was supported by the Kennedy Krieger Institute, the Johns Hopkins University and the National Institutes of Health.

Discovery Shows Cerebellum Plays Important Role In Sensing Limb Position And Movement

Kennedy Krieger Institute researchers find that damage to the cerebellum impairs ability to predict motion outcomes and discrimination between limb positions.

Researchers at the Kennedy Krieger Institute announced today study findings showing, for the first time, the link between the brain’s cerebellum and proprioception, or the body’s ability to sense movement and joint and limb position. Published in The Journal of Neuroscience, the study uncovers a previously unknown perceptual deficit among cerebellar patients, suggesting that damage to this portion of the brain can directly impact a person’s ability to sense the position of their limbs and predict movement. This discovery could prompt future researchers to reexamine physical therapy tactics for cerebellar patients, who often have impaired coordination or appear clumsy.

The sense of proprioception arises from the brain’s readout of signals from receptors in muscles, joints and ligaments, but also from the brain’s predictions of how motor commands will move the limb. The latter can only contribute to proprioception when a person actively moves their own body. To date, researchers and neurologists believed that proprioception did not occur in the cerebellum, and thus, damage to the cerebellum did not affect proprioception.

“Proprioception was previously not considered a factor in the therapy or recovery of cerebellar patients. In fact, previous research has shown that individuals with cerebellum damage and no other clinical neurological impairments have normal proprioception when their limbs are moved passively in a clinical setting,” says Amy J. Bastian, Ph.D., PT, director of the Motion Analysis Laboratory at Kennedy Krieger Institute. “However, when these patients move their limbs actively, they exhibit significant proprioceptive impairment.”

Additionally, researchers found that proprioception in healthy subjects was impaired when unpredictable dynamics, or small disturbances to the cerebellum, were incorporated into active movement. This suggests that muscle activity alone is likely insufficient to improve perception of limb placement, and proprioception should be taken into consideration when determining therapeutic practices for cerebellar patients.

Study Results and Methodology

The study compared 11 healthy people (control group) to 11 patients with cerebellar damage (caused by spinocerebellar ataxia, sporadic cerebellar ataxia or autosomal-dominant cerebellar ataxia type III) but no evidence of white matter damage, spontaneous nystagmus or atrophy to the brainstem. None of the patients included in the study had sensory loss assessed by conventional clinical measures of proprioception and tactile sensation.

Participants were compared in three psychophysical tasks designed to assess passive proprioception, active proprioception with simple dynamics, and active proprioception with complex, unpredictable dynamics designed to disrupt the cerebellum. All tasks relied on proprioceptive sense without vision.

Results showed that:

  • Cerebellar patients had no deficits in passive proprioception
  • Unlike control subjects, cerebellar patients did not show an improvement between passive and active proprioception with simple dynamics
  • Control patients performed similarly to patients in an active proprioception task with unpredictable, small disruptions to their movement.

This study was supported by the Kennedy Krieger Institute, the Johns Hopkins University and the National Institutes of Health.

Filed under cerebellum proprioception motor movements neuroscience science

84 notes

Stress-related protein speeds progression of Alzheimer’s disease

A stress-related protein genetically linked to depression, anxiety and other psychiatric disorders contributes to the acceleration of Alzheimer’s disease, a new study led by researchers at the University of South Florida has found.

The study is published online today in the Journal of Clinical Investigation.

When the stress-related protein FKBP51 partners with another protein known as Hsp90, this formidable chaperone protein complex prevents the clearance from the brain of the toxic tau protein associated with Alzheimer’s disease.

Under normal circumstances, tau helps make up the skeleton of our brain cells. The USF study was done using test tube experiments, mice genetically engineered to produce abnormal tau protein like that accumulated in the brains of people with Alzheimer’s disease, and post-mortem human Alzheimer’s brain tissue.

The researchers report that FKBP51 levels increase with age in the brain, and then the stress-related protein partners with Hsp90 to make tau more deadly to the brain cells involved in memory formation.

Hsp90 is a chaperone protein, which supervises the activity of tau inside nerve cells. Chaperone proteins typically help ensure that tau proteins are properly folded to maintain the healthy structure of nerve cells.

However, as FKBP51 levels rise with age, they usurp Hsp90’s beneficial effect to promote tau toxicity.

“We found that FKB51 commandeers Hsp90 to create an environment that prevents the removal of tau and makes it more toxic,” said the study’s principal investigator Chad Dickey, PhD, associate professor of molecular medicine at the USF Health Byrd Alzheimer’s Institute. “Basically, it uses Hsp90 to produce and preserve the bad tau.”

The researchers conclude that developing drugs or other ways to reduce FKB51 or block its interaction with Hsp90 may be highly effective in treating the tau pathology featured in Alzheimer’s disease, Parkinson’s disease dementia and several other disorders associated with memory loss.

A previous study by Dr. Dickey and colleagues found that a lack of FKBP51 in old mice improved resilience to depressive behavior.

Filed under alzheimer's disease tau protein chaperone proteins stress protein neuroscience science

215 notes

Alzheimer’s missing link found: Is a promising target for new drugs Yale School of Medicine researchers have discovered a protein that is the missing link in the complicated chain of events that lead to Alzheimer’s disease, they report in the Sept. 4 issue of the journal Neuron. Researchers also found that blocking the protein with an existing drug can restore memory in mice with brain damage that mimics the disease. “What is very exciting is that of all the links in this molecular chain, this is the protein that may be most easily targeted by drugs,” said Stephen Strittmatter, the Vincent Coates Professor of Neurology and senior author of the study. “This gives us strong hope that we can find a drug that will work to lessen the burden of Alzheimer’s.” Scientists have already provided a partial molecular map of how Alzheimer’s disease destroys brain cells. In earlier work, Strittmatter’s lab showed that the amyloid-beta peptides, which are a hallmark of Alzheimer’s, couple with prion proteins on the surface of neurons. By an unknown process, the coupling activates a molecular messenger within the cell called Fyn. In the Neuron paper, the Yale team reveals the missing link in the chain, a protein within the cell membrane called metabotropic glutamate receptor 5 or mGluR5. When the protein is blocked by a drug similar to one being developed for Fragile X syndrome, the deficits in memory, learning, and synapse density were restored in a mouse model of Alzheimer’s. Strittmatter stressed that new drugs may have to be designed to precisely target the amyloid-prion disruption of mGluR5 in human cases of Alzheimer’s and said his lab is exploring new ways to achieve this.

Alzheimer’s missing link found: Is a promising target for new drugs

Yale School of Medicine researchers have discovered a protein that is the missing link in the complicated chain of events that lead to Alzheimer’s disease, they report in the Sept. 4 issue of the journal Neuron. Researchers also found that blocking the protein with an existing drug can restore memory in mice with brain damage that mimics the disease.

“What is very exciting is that of all the links in this molecular chain, this is the protein that may be most easily targeted by drugs,” said Stephen Strittmatter, the Vincent Coates Professor of Neurology and senior author of the study. “This gives us strong hope that we can find a drug that will work to lessen the burden of Alzheimer’s.”

Scientists have already provided a partial molecular map of how Alzheimer’s disease destroys brain cells. In earlier work, Strittmatter’s lab showed that the amyloid-beta peptides, which are a hallmark of Alzheimer’s, couple with prion proteins on the surface of neurons. By an unknown process, the coupling activates a molecular messenger within the cell called Fyn.

In the Neuron paper, the Yale team reveals the missing link in the chain, a protein within the cell membrane called metabotropic glutamate receptor 5 or mGluR5. When the protein is blocked by a drug similar to one being developed for Fragile X syndrome, the deficits in memory, learning, and synapse density were restored in a mouse model of Alzheimer’s.

Strittmatter stressed that new drugs may have to be designed to precisely target the amyloid-prion disruption of mGluR5 in human cases of Alzheimer’s and said his lab is exploring new ways to achieve this.

Filed under alzheimer's disease mGluR5 memory impairment prion proteins medicine neuroscience science

62 notes

Brain study uncovers vital clue in bid to beat epilepsy

People with epilepsy could be helped by new research into the way a key molecule controls brain activity during a seizure.

Researchers have identified the role played by of a protein – called BDNF – and say the discovery could lead to new drugs that calm the symptoms of epileptic seizures.

Scientists analysed the way cells communicate when the brain is most active – such as in epileptic seizures – when electrical signalling by the brain’s neurons is increased.

They found that the BDNF molecule – which is known to be released in the brain during seizures – blocks a specific process known as activity-dependent bulk endocytosis (ABDE).

By blocking this process during an epileptic seizure, BDNF increases the release of neurotransmitters and causes heightened electrical activity in the brain.

Since ADBE is only triggered during high brain activity, drugs designed to target this process could have fewer side effects for normal day to day brain function, researchers say.

Experts say that not all epilepsy patients respond to current drug treatments and the finding could lead to the development of new medicines.

The team, however, offered a word of caution. Since ABDE is also implicated in a range of brain functions, such as creating new memories, more research is needed to establish what the effects of manipulating this molecule might be on these key processes.

The study, led by the University of Edinburgh, is published in the journal Nature Communications. The research was funded by the Wellcome Trust and the Medical Research Council.

Dr Mike Cousin, of the University of Edinburgh’s Centre for Integrative Physiology, who led the research, said: “Around one third of people with epilepsy do not respond to the treatments we currently have available. By studying the way brain cells behave during seizures, we have been able to uncover an exciting new research avenue for research into anti-epileptic therapies.”

Researchers will now focus on identifying specific genes that control this brain process to determine whether they hold the key to new drug treatments.

(Source: eurekalert.org)

Filed under epilepsy seizures BDNF activity-dependent bulk endocytosis brain activity neuroscience science

51 notes

Scientists fish for new epilepsy model and reel in potential drug

NIH-funded study finds zebrafish model may help identify treatments for a severe form of childhood epilepsy

image

According to new research on epilepsy, zebrafish have certainly earned their stripes. Results of a study in Nature Communications suggest that zebrafish carrying a specific mutation may help researchers discover treatments for Dravet syndrome (DS), a severe form of pediatric epilepsy that results in drug-resistant seizures and developmental delays.

Scott C. Baraban, Ph.D., and his colleagues at the University of California, San Francisco (UCSF), carefully assessed whether the mutated zebrafish could serve as a model for DS, and then developed a new screening method to quickly identify potential treatments for DS using these fish. This study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health and builds on pioneering epilepsy zebrafish models first described by the Baraban laboratory in 2005.

Dravet syndrome is commonly caused by a mutation in the Scn1a gene, which encodes for Nav1.1, a specific sodium ion channel found in the brain. Sodium ion channels are critical for communication between brain cells and proper brain functioning.

The researchers found that the zebrafish that were engineered to have the Scn1a mutation that causes DS in humans exhibited some of the same characteristics, such as spontaneous seizures, commonly seen in children with DS. Unprovoked seizure activity in the mutant fish resulted in hyperactivity and whole-body convulsions associated with very fast swimming. These types of behaviors are not seen in normal healthy zebrafish.

“We were also surprised at how similar the mutant zebrafish drug profile was to that of Dravet patients,” said Dr. Baraban. “Antiepileptic drugs shown to have some benefits in patients (such as benzodiazepines or stiripentol) also exhibited some antiepileptic activity in these mutants. Conversely, many of the antiepileptic drugs that do not reduce seizures in these patients showed no effect in the mutant zebrafish.”

In this study, the researchers developed a fast and automated drug screen to quickly test the effectiveness of various compounds in mutant zebrafish. The researchers tracked behavior and measured brain activity in the mutant zebrafish to determine if the compounds had an impact on seizures.

“Scn1a mutants seize often, so it is relatively easy to monitor their seizure behavior at baseline and then again after a drug application,” said Dr. Baraban. “Using zebrafish placed individually in a 96-part petri dish we can accurately quantify this seizure behavior. In this way, we can test almost 100 fish at one time and quickly determine whether a drug candidate has any effect on these spontaneous seizures.”

In the first such application of this approach, UCSF researchers screened 320 compounds and found that clemizole was most effective in inhibiting seizure activity. Clemizole is approved by the U.S. Food and Drug Administration and has a safe toxicology profile. “This finding was completely unexpected. Based on what is currently known about clemizole, we did not predict that it would have antiepileptic effects,” said Dr. Baraban.

These findings suggest that Scn1a mutant zebrafish may serve as a good model of DS and that the drug screen may be effective in quickly identifying novel therapies for epilepsy. 

Dr. Baraban also noted that someday these experiments can be “personalized,” by looking at mutated zebrafish that use genetic information from individual patients. 

(Source: ninds.nih.gov)

Filed under Dravet syndrome epilepsy zebrafish ion channels Scn1a gene mutations neuroscience science

free counters