Posts tagged neuroscience
Articles and news from the latest research reports.
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.
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.
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.
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.
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)
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
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)
Research confirms Mediterranean diet is good for the mind
The first systematic review of related research confirms a positive impact on cognitive function, but an inconsistent effect on mild cognitive impairment.
Over recent years many pieces of research have identified a link between adherence to a Mediterranean diet and a lower risk of age-related disease such as dementia.
Until now there has been no systematic review of such research, where a number of studies regarding a Mediterranean diet and cognitive function are reviewed for consistencies, common trends and inconsistencies.
A team of researchers from the University of Exeter Medical School, supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care in the South West Peninsula (NIHR PenCLAHRC), has carried out the first such systematic review and their findings are published in Epidemiology.
The team analysed 12 eligible pieces of research, 11 observational studies and one randomised control trial. In nine out of the 12 studies, a higher adherence to a Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline and a reduced risk of Alzheimer’s disease.
However, results for mild cognitive impairment were inconsistent.
A Mediterranean diet typically consists of higher levels of olive oil, vegetables, fruit and fish. A higher adherence to the diet means higher daily intakes of fruit and vegetables and fish, and reduced intakes of meat and dairy products.
The study was led by researcher Iliana Lourida. She said: “Mediterranean food is both delicious and nutritious, and our systematic review shows it may help to protect the ageing brain by reducing the risk of dementia. While the link between adherence to a Mediterranean diet and dementia risk is not new, ours is the first study to systematically analyse all existing evidence.”
She added: “Our review also highlights inconsistencies in the literature and the need for further research. In particular research is needed to clarify the association with mild cognitive impairment and vascular dementia. It is also important to note that while observational studies provide suggestive evidence we now need randomized controlled trials to confirm whether or not adherence to a Mediterranean diet protects against dementia.”
(Source: exeter.ac.uk)
Aging really is ‘in your head’
Scientists answer hotly debated questions about how calorie restriction delays aging process
Among scientists, the role of proteins called sirtuins in enhancing longevity has been hotly debated, driven by contradictory results from many different scientists. But new research at Washington University School of Medicine in St. Louis may settle the dispute.
Reporting Sept. 3 in Cell Metabolism, Shin-ichiro Imai, MD, PhD, and his colleagues have identified the mechanism by which a specific sirtuin protein called Sirt1 operates in the brain to bring about a significant delay in aging and an increase in longevity. Both have been associated with a low-calorie diet.
The Japanese philosopher and scientist Ekiken Kaibara first described the concept of dietary control as a method to achieve good health and longevity in 1713. He died the following year at the ripe old age of 84—a long life for someone in the 18th century.
Since then, science has proven a link between a low-calorie diet (without malnutrition) and longevity in a variety of animal models. In the new study, Imai and his team have shown how Sirt1 prompts neural activity in specific areas of the hypothalamus of the brain, which triggers dramatic physical changes in skeletal muscle and increases in vigor and longevity.
“In our studies of mice that express Sirt1 in the brain, we found that the skeletal muscular structures of old mice resemble young muscle tissue,” said Imai. “Twenty-month-old mice (the equivalent of 70-year-old humans) look as active as five-month-olds.”
Imai and his team began their quest to define the critical junctures responsible for the connection between dietary restriction and longevity with the knowledge from previous studies that the Sirt1 protein played a role in delaying aging when calories are restricted. But the specific mechanisms by which it carried out its function were unknown.
Imai’s team studied mice that had been genetically modified to overproduce Sirt1 protein. Some of the mice had been engineered to overproduce Sirt1 in body tissues, while others were engineered to produce more of the Sirt1 protein only in the brain.
“We found that only the mice that overexpressed Sirt1 in the brain (called BRASTO) had significant lifespan extension and delay in aging, just like normal mice reared under dietary restriction regimens,” said Imai, an expert in aging research and a professor in the departments of Developmental Biology and Medicine.
The BRASTO mice demonstrated significant life span extension without undergoing dietary restriction. “They were free to eat regular chow whenever they wished,” he said.
In addition to positive skeletal muscle changes in the BRASTO mice, the investigators also observed significant increases in nighttime physical activity, body temperature and oxygen consumption compared with age-matched controls.
Mice are characteristically most active at night. The BRASTO mice also experienced better or deeper sleep, and both males and females had significant increases in longevity.
The median life span of BRASTO mice in the study was extended by 16 percent for females and 9 percent for males. Translated to humans, this could mean an extra 13 or 14 years for women, making their average life span almost 100 years, Shin said. For men, this would add another seven years, increasing their average life span to the mid-80s.
Delay in cancer-dependent death also was observed in the BRASTO mice relative to control mice, the researchers noted.
Imai said that the longevity and health profile associated with the BRASTO mice appears to be the result of a shift in the onset of aging rather than the pace of aging. “What we have observed in BRASTO mice is a delay in the time when age-related decline begins, so while the rate of aging does not change, aging and the risk of cancer has been postponed.”
Having narrowed control of aging to the brain, Imai’s team then traced the control center of aging regulation to two areas of the hypothalamus called the dorsomedial and lateral hypothalamic nuclei. They then were able to identify specific genes within those areas that partner with Sirt1 to kick off the neural signals that elicit the physical and behavioral responses observed.
“We found that overexpression of Sirt1 in the brain leads to an increase in the cellular response of a receptor called orexin type 2 receptor in the two areas of the hypothalamus,” said first author Akiko Satoh, PhD, a postdoctoral staff scientist in Imai’s lab.
“We have demonstrated that the increased response by the receptor initiates signaling from the hypothalamus to skeletal muscles,” said Satoh. She noted that the mechanism by which the signal is specifically directed to skeletal muscle remains to be discovered.
According to Imai, the tight association discovered between Sirt1-prompted brain activation and the regulation of aging and longevity raises the tantalizing possibility of a “control center of aging and longevity” in the brain, which could be manipulated to maintain youthful physiology and extend life span in other mammals as well.
(Source: news.wustl.edu)
Sleep Boosts Production of Brain Support Cells
Animal study shows genes involved in brain repair, growth turned on during slumber
Sleep increases the reproduction of the cells that go on to form the insulating material on nerve cell projections in the brain and spinal cord known as myelin, according to an animal study published in the September 4 issue of The Journal of Neuroscience. The findings could one day lead scientists to new insights about sleep’s role in brain repair and growth.
Scientists have known for years that many genes are turned on during sleep and off during periods of wakefulness. However, it was unclear how sleep affects specific cells types, such as oligodendrocytes, which make myelin in the healthy brain and in response to injury. Much like the insulation around an electrical wire, myelin allows electrical impulses to move rapidly from one cell to the next.
In the current study, Chiara Cirelli, MD, PhD, and colleagues at the University of Wisconsin, Madison, measured gene activity in oligodendrocytes from mice that slept or were forced to stay awake. The group found that genes promoting myelin formation were turned on during sleep. In contrast, the genes implicated in cell death and the cellular stress response were turned on when the animals stayed awake.
“These findings hint at how sleep or lack of sleep might repair or damage the brain,” said Mehdi Tafti, PhD, who studies sleep at the University of Lausanne in Switzerland and was not involved with this study.
Additional analysis revealed that the reproduction of oligodendrocyte precursor cells (OPCs) — cells that become oligodendrocytes — doubles during sleep, particularly during rapid eye movement (REM), which is associated with dreaming.
“For a long time, sleep researchers focused on how the activity of nerve cells differs when animals are awake versus when they are asleep,” Cirelli said. “Now it is clear that the way other supporting cells in the nervous system operate also changes significantly depending on whether the animal is asleep or awake.”
Additionally, Cirelli speculated the findings suggest that extreme and/or chronic sleep loss could possibly aggravate some symptoms of multiple sclerosis (MS), a disease that damages myelin. Cirelli noted that future experiments may examine whether or not an association between sleep patterns and severity of MS symptoms exists.
Ground breaking research identifies promising drugs for treating Parkinson’s
New drugs which may have the potential to stop faulty brain cells dying and slow down the progression of Parkinson’s, have been identified by scientists in a pioneering study which is the first of its kind.
Experts from the world leading Sheffield Institute for Translational Neuroscience (SITraN) conducted a large scale drugs trial in the lab using skin cells from people with this progressive neurological condition which affects one in every 500 people in the UK.
The researchers tested over 2,000 compounds to find out which ones could make faulty mitochondria work normally again.
Mitochondria act as the power generators in all cells of our body, including the brain. Malfunctioning mitochondria are one of the main reasons why brain cells die in Parkinson’s.
One of the promising medications identified though the research is a synthetic drug called ursodeoxycholic acid (UDCA).
This licenced drug has been in clinical use for several decades to treat certain forms of liver disease which means that researchers will be able to immediately start a clinical trial to test its safety and tolerability in people with Parkinson’s.
This will discover the optimum dose to ensure that enough of the drug reaches the part of the brain where Parkinson’s develops.
Based on this information, larger randomized controlled trials can be carried out to assess the potential of UDCA to treat Parkinson’s.
The extensive drug screen, which took over five years to complete, was funded by leading research charity Parkinson’s UK, and was carried out in collaboration with the University of Trondheim, Norway.
Dr Oliver Bandmann, Reader in Neurology at SITraN, said: “Parkinson’s is so much more than just a movement disorder.
It can also lead to depression and anxiety, and a host of distressing day to day problems like bladder and bowel dysfunction.
"The best treatments currently available only improve some of the symptoms, rather than tackle the reason why Parkinson’s develops in the first place, so there is a desperate need for new drug treatments which could actually slow down the disease progression”.
"We are hopeful that this group of drugs can one day make a real difference to the lives of people with Parkinson’s”.
The results of the ground breaking study are published in the leading Neuroscience journal BRAIN.
Dr Kieran Breen, Director of Research and Innovation at Parkinson’s UK commented: “This is a really exciting time for Parkinson’s research. For the first time, we are starting to identify drugs that will treat the Parkinson’s – possibly slow down or halt its progression – rather than just the symptoms.
“This will bring us closer to our ultimate goal of a cure for Parkinson’s. We look forward to working closely with Dr Bandmann to develop this treatment”.