Posts tagged neuroscience
Articles and news from the latest research reports.
Nasal inhalation of oxytocin improves face blindness
Prosopagnosia (face blindness) may be temporarily improved following inhalation of the hormone oxytocin.
This is the finding of research led by Dr Sarah Bate and Dr Rachel Bennetts of the Centre for Face Processing Disorders at Bournemouth University that will be presented today, Friday 6 September, at the British Psychological Society’s Joint Cognitive and Developmental annual conference at the University of Reading.
Dr Bate explained: “Prosopagnosia is characterised by a severe impairment in face recognition, whereby a person cannot identify the faces of their family or friends, or even their own face”
The researchers tested twenty adults (10 with prosopagnosia and 10 control participants). Each participant visited the laboratory on two occasions, approximately two weeks apart. On one visit they inhaled the oxytocin nasal spray, and on the other visit they inhaled the placebo spray. The two sprays were prepared by an external pharmaceutical company in identical bottles, and neither the participants nor the researchers knew the identity of the sprays until the data had been analysed.
Regardless of which spray the person inhaled, the testing sessions had an identical format. Participants inhaled the spray, then sat quietly for 45 minutes to allow the spray to take effect. They then participated in two face processing tests: one testing their ability to remember faces and the other testing their ability to match faces of the same identity.
The researchers found that the participants with prosopagnosia achieved higher scores on both face processing tests in the oxytocin condition. Interestingly, no improvement was observed in the control participants, suggesting the hormone may be more effective in those with impaired face recognition systems.
The initial ten participants with prosopagnosia had a developmental form of the condition. Individuals with developmental prosopagnosia have never experienced brain damage, and this form of face blindness is thought to be very common, affecting one in 50 people. Much more rarely, people can acquire prosopagnosia following a brain injury. At a later date, the researchers had the opportunity to test one person with acquired prosopagnosia, and also observed a large improvement following oxytocin inhalation in this individual.
Dr Bate said: “This study provides the first evidence that oxytocin may be used to temporarily improve face recognition in people with either developmental or acquired prosopagnosia. The effects of the hormone are thought to last 2-3 hours, and it may be that the nasal spray can be used to improve face recognition on a special occasion. However, much more research needs to be carried out, as we don’t currently know whether there are benefits or risks associated with longer-term inhalation of the hormone.”
(Source: alphagalileo.org)
What Is the Brain Telling Us About the Diagnoses of Schizophrenia and Bipolar Disorder?
We live in the most exciting and unsettling period in the history of psychiatry since Freud started talking about sex in public.
On the one hand, the American Psychiatric Association has introduced the fifth iteration of the psychiatric diagnostic manual, DSM-V, representing the current best effort of the brightest clinical minds in psychiatry to categorize the enormously complex pattern of human emotional, cognitive, and behavioral problems. On the other hand, in new and profound ways, neuroscience and genetics research in psychiatry are yielding insights that challenge the traditional diagnostic schema that have long been at the core of the field.
“Our current diagnostic system, DSM-V represents a very reasonable attempt to classify patients by their symptoms. Symptoms are an extremely important part of all medical diagnoses, but imagine how limited we would be if we categorized all forms of pneumonia as ‘coughing disease,” commented Dr. John Krystal, Editor of Biological Psychiatry.
A paper by Sabin Khadka and colleagues that appears in the September 15th issue of Biological Psychiatry advances the discussion of one of these roiling psychiatric diagnostic dilemmas.
One of the core hypotheses is that schizophrenia and bipolar disorder are distinct scientific entities. Emil Kraepelin, credited by many as the father of modern scientific psychiatry, was the first to draw a distinction between dementia praecox (schizophrenia) and manic depression (bipolar disorder) in the late 19th century based on the behavioral profiles of these syndromes. Yet, patients within each diagnosis can have a wide variation of symptoms, some symptoms appear to be in common across these diagnoses, and antipsychotic medications used to treat schizophrenia are very commonly prescribed to patients with bipolar disorder.
But at the level of brain circuit function, do schizophrenia and bipolar differ primarily by degree or are there clear categorical differences? To answer this question, researchers from a large collaborative project called BSNIP looked at a large sample of patients diagnosed with schizophrenia or bipolar disorder, their healthy relatives, and healthy people without a family history of psychiatric disorder.
They used a specialized analysis technique to evaluate the data from their multi-site study, which revealed abnormalities within seven different brain networks. Generally speaking, they found that schizophrenia and bipolar disorder showed similar disturbances in cortical circuit function. When differences emerged between these two disorders, it was usually because schizophrenia appeared to be a more severe disease. In other words, individuals with schizophrenia had abnormalities that were larger or affected more brain regions. Their healthy relatives showed subtle alterations that fell between the healthy comparison group and the patient groups.
The authors highlight the possibility that there is a continuous spectrum of circuit dysfunction, spanning from individuals without any familial association with schizophrenia or bipolar to patients carrying these diagnoses. “These findings might serve as useful biological markers of psychotic illnesses in general,” said Khadka.
Krystal agreed, adding, “It is evident that neither our genomes nor our brains have read DSM-V in that there are links across disorders that we had not previously imagined. These links suggest that new ways of organizing patients will emerge once we understand both the genetics and neural circuitry of psychiatric disorders sufficiently.”
(Image: ALAMY)
Image: A. Amyloid-beta plaques in Alzheimers B. Neurofibrillary tangles (tau) in Alzheimer’s C. Lewy bodies (alpha-synuclein) in Parkinson’s D. TDP-43 inclusions in motor neurons in ALS
Prion-like proteins drive several diseases of aging
Two leading neurology researchers have proposed a theory that could unify scientists’ thinking about several neurodegenerative diseases and suggest therapeutic strategies to combat them.
The theory and backing for it are described in the September 5, 2013 issue of Nature.
Mathias Jucker and Lary Walker outline the emerging concept that many of the brain diseases associated with aging, such as Alzheimer’s and Parkinson’s, are caused by specific proteins that misfold and aggregate into harmful seeds. These seeds behave very much like the pathogenic agents known as prions, which cause mad cow disease, chronic wasting disease in deer, scrapie in sheep, and Creutzfeldt-Jakob disease in humans.
Walker is research professor at Yerkes National Primate Research Center, Emory University. Jucker is head of the Department of Cellular Neurology at the Hertie Institute for Clinical Brain Research at the University of Tübingen and the German Center for Neurodegenerative Diseases.
Unlike prion diseases, which can be infectious, Alzheimer’s, Parkinson’s, and other neurodegenerative diseases can not be passed from person to person under normal circumstances. Once all of these diseases take hold in the brain, however, it is increasingly apparent that the clumps of misfolded proteins spread throughout the nervous system and disrupt its function.
The authors were the first to show that a protein that is involved in Alzheimer’s disease – known as amyloid-beta – forms prion-like seeds that stimulate the aggregation of other amyloid-beta molecules in senile plaques and in brain blood vessels. Since then, a growing number of laboratories worldwide have discovered that proteins linked to other neurodegenerative disorders also share key features with prions.
Age-related neurodegenerative disorders remain stubbornly resistant to the discovery of effective treatments. Jucker and Walker propose that the concept of pathogenic protein seeding not only could focus research strategies for these seemingly unrelated diseases, but it also suggests that therapeutic approaches designed to thwart prion-like seeds early in the disease process could eventually delay or even prevent the diseases.
Biologists Uncover Details of How We Squelch Defective Neurons
Biologists at the University of California, San Diego have identified a new component of the cellular mechanism by which humans and animals automatically check the quality of their nerve cells to assure they’re working properly during development.
In a paper published in this week’s issue of the journal Neuron, the scientists report the discovery in the laboratory roundworm C. elegans of a “quality check” system for neurons that uses two proteins to squelch the signals from defective neurons and marks them for either repair or destruction.
“To be able to see, talk and walk, nerve cells in our body need to communicate with their right partner cells,” explains Zhiping Wang, the lead author in the team of researchers headed by Yishi Jin, a professor of neurobiology in UC San Diego’s Division of Biological Sciences and a professor of cellular and molecular medicine in its School of Medicine. “The communication is mediated by long fibers emitting from neurons called axons, which transmit electric and chemical signals from one cell to the other, just like cables connecting computers in a local wired network. In developing neurons, the journey of axons to their target cells is guided by a set of signals. These signals are detected by ‘mini-receivers’—proteins called guidance receptors—on axons and translated into ‘proceed,’ ‘stop,’ ‘turn left’ or ‘turn right.’ Thus, the quality of these receivers is very important for the axons to interpret the guiding signals.”
Jin, who is also an Investigator of the Howard Hughes Medical Institute, says defective protein products and environmental stress, such as hyperthermia, can sometimes jeopardize the health and development of cells. “This may be one reason why pregnant women are advised by doctors to avoid saunas and hot tubs,” she adds.
The scientists discovered the quality check system in roundworms, and presumably other animals including humans, consists of two parts: a protein-cleaning machine containing a protein called EBAX-1, and a well-known protein assembly helper called heat-shock protein 90 known as “hsp90.”
“Hsp90 facilitates the assembly of guidance receivers during the production and also fixes flawed products whenever they are detected,” says Andrew Chisholm, a professor of neurobiology and cell and developmental biology, who also helped lead the study. “The EBAX-containing protein-cleaning machine is in charge of destroying any irreparable products so that they don’t hang around and affect the performance of functional receivers. The EBAX-1 protein plays as a defectiveness detector in this machine and a connector to Hsp90. It captures defective products and presents them for either repair or destruction.”
A human neurodevelopmental disorder called “horizontal gaze palsy with progressive scoliosis” is associated with the defective production of one of the protein guidance receivers. This team of researchers showed that the defective human protein can interact with EBAX proteins. The authors hope that by investigating the action of EBAX-1 protein, their findings will provide clues to develop remedies or drugs to retreat human disorders in the future.
Robots Could One Day Help Surgeons Remove Hard to Reach Brain Tumors
NIBIB-funded scientists and engineers are teaming up with neurosurgeons to develop technologies that enable less invasive, image-guided removal of hard-to-reach brain tumors. Their technologies combine novel imaging techniques that allow surgeons to see deep within the brain during surgery with robotic systems that enhance the precision of tissue removal.
A robot that worms its way in
The median survival rate for patients with glioblastomas, or high grade primary brain cancer, is less than two years. One factor contributing to this low rate is the fact that many deep-seated and pervasive tumors are not entirely accessible or even visible when using current neurosurgical tools and imaging techniques.
But several years ago, J. Marc Simard, M.D., a professor of neurosurgery at the University of Maryland School of Medicine in Baltimore (UMB), had an insight that he hoped might address this problem. At the time, he had been watching a TV show in which plastic surgeons were using sterile maggots to remove damaged or dead tissue from a patient.
“Here you had a natural system that recognized bad from good and good from bad,” said Simard. “In other words, the maggots removed all the bad stuff and left all the good stuff alone and they’re really small. I thought, if you had something equivalent to that to remove a brain tumor that would be an absolute home run.”
Image: Initial prototype for the minimally invasive neurosurgical intracranial robot. Image courtesy of University of Maryland.
And so Simard teamed up with Rao Gullapalli, Ph.D., professor of diagnostic radiology and nuclear medicine also at UMB, as well as Jaydev Desai, Ph.D., professor of mechanical engineering at the University of Maryland, College Park, to develop a small neurosurgical robot that could be used to remove deep-seated brain tumors.
Within four years, the team had designed, constructed, and tested their first prototype, a finger-like device with multiple joints, allowing it to move in many directions. At the tip of the robot is an electrocautery tool, which uses electricity to heat and ultimately destroy tumors, as well as a suction tube for removing debris.
“The idea was to have a device that’s small but that can do all the work a surgeon normally does,” said Simard. “You could place this small robotic device inside a tumor and have it work its way around from within, removing pieces of diseased tissue.”
A key component of the team’s device is its ability to be used while a patient is undergoing MRI. By replacing normal vision with continuously updated MRI, the surgeon is able to visualize deep-seated tumors and monitor the robot’s movement without having to create a large incision in the brain.
In addition to reducing incision size, Simard says the ability to view the brain under continuous MRI also helps surgeons keep track of tumor boundaries throughout an operation. “When we’re operating in a conventional way, we get an MRI on a patient before we do the surgery, and we use landmarks that can either be affixed to the scalp or are part of the skull to know where we are within the patient’s brain. But when the surgeon gets in there and starts to remove the tumor, the tissues shift around so that now the boundaries that were well-established when everything was in place don’t exist anymore, and you’re confronted once again with having to distinguish normal brain from tumor. This is very difficult for a surgeon using direct vision, but with MRI, the ability to discriminate tumor from non-tumor is much more powerful.”
Steve Krosnick, M.D., a program director at NIBIB, says real-time MRI guidance during brain tumor surgery would be a tremendous advantage. “Unlike pre-operative MRI or intermittent MRI, which requires interruption of the surgical procedure, real-time intra-operative MRI offers rapid delineation of normal tissue from tumor while accounting for brain shifts that occur during surgery.”
But designing a neurosurgical device that can be used inside an MRI magnet is no easy task. One of the first issues you have to consider, said Gullapalli, is a surgeon’s access to the brain. “When you scan a person’s brain during an MRI, he’s deep inside the machine’s tunnel. The problem is, how do you get your hands on the brain while the patient’s in the scanner?”
The team’s solution was to give the surgeon robotic control of the device in order to circumvent the need to access the brain directly. In other words, a surgeon can insert the robot into the brain while the patient is outside of the scanner. Then, when the patient moves into the scanner, the surgeon can sit in a different room and –while watching MRI images of the brain on a monitor—move the robot deep inside the brain and direct it to electrocauterize and aspirate the tissue.
Jaydev Desai, the team’s mechanical engineer, says the most challenging aspect of the project has been designing a robot that can be controlled inside the magnetic field of an MRI. While robots are often controlled via electromagnetic motors, this was not an option because, besides being magnetic, these motors create significant image distortion, making it impossible for the surgeon to perform the task. Other potential mechanisms such as hydraulic systems were off the table due to concerns about fluid leakage.
Instead, Desai decided to use shape memory alloy (SMA)—a material that alters its shape in response to changes in temperature—to control the robot’s movement. In the most recent prototype—developed by Desai and his team at the Robotics, Automation, and Medical Systems (RAMS) laboratory at the University of Maryland, College Park—a system of cables, pulleys and SMA springs are used. This cable and pulley system is an improvement from their previous prototype which caused some image distortion.
Image: The newest prototype for the minimally invasive neurosurgical intracranial robot uses a system of pulleys and springs to move the robot. Source: Jaydev Desai, University of Maryland
With continued support from NIBIB, Desai and colleagues are now working to further reduce image distortion and to test the safety and efficacy of their device in swine as well as in human cadavers. Though it will be several years before their device finds its way into the operating room, Simard is excited by the prospect. “Advancing brain surgery to this level where tiny machines or robots could navigate inside people’s heads while being directed by neurosurgeons with the help of MRI imaging…It’s beyond anything that most people dream of.”
Scoping the brain
On the opposite side of the country, a different group of engineers and neurosurgeons is also working to develop an image-guided, robotically-controlled neurosurgical tool. Lead by Eric Seibel, Ph.D., a professor of mechanical engineering at the University of Washington, the team is attempting to adapt a scanning fiber endoscope—a tool initially developed by Seibel to image inside the narrow bile ducts of the liver—so that it can be used to visualize the brain during surgery.
An endoscope is a thin, tube-like instrument with a video camera attached to its end that can be inserted through a small incision or natural opening in the body to produce real-time video during surgery. Endoscopes are an essential component of minimally invasive surgeries because they allow surgeons to view the inside of the body on a monitor without having to make a large incision.
However, there are many parts of the body such as small vessels and ducts as well as areas deep in the brain that are inaccessible to conventional endoscopes. Although ultrathin endoscopes have recently been developed, Seibel says these smaller scopes come with the price of greatly reduced image resolution.
“Right now, with the current state of the art ultrathin endoscopes, I calculate based on the field of view and their resolution that the person looking at that display would see so little as to be classified in the US as legally blind,” said Seibel.
Image: Microfabricated optical fiber scanner emitting red laser light, with scan amplitude of 1 mm peak-to-peak. Image courtesy of Eric Seibel, University of Washington
But with support from NIBIB over ten years ago, Seibel began working on a new type of endoscope that could fit into tiny crevices in the body while retaining high image quality. His end product was a new type of endoscope that, despite having the diameter of a toothpick, can provide doctors with microscopic views of the inside of the body.
Seibel retained image quality while significantly reducing the size of his scope by eschewing traditional endoscope models. Instead of a light source and a video camera, Seibel’s scope consists of a single optical fiber—approximately the size of a human hair—located in the middle of the scope. The fiber releases white laser light (a combination of green, red, and blue lasers) when vibrated at a particular frequency. By directing the laser light through a series of lenses in the scope, it can be reflected widely within the body, providing a 100 degree field of view. As the white laser light interacts with tissue, it picks up coloration and scatters it back to a ring of additional optical fibers which transmit this information to a monitor.
“It’s almost like putting your eyes inside the body so you can see with the wide field view of your human vision,” said Seibel.
In collaboration with three neurosurgeons and an electrical engineer, Seibel is now working to secure his novel endoscope to the tip of a robotically controlled micro-dissection neurosurgical tool.
As opposed to larger traditional endoscopes, Seibel say his scanning fiber endoscope is barely noticeable.
“It’ s like a piece of wet spaghetti,” said Seibel. “It’s even smaller then a piece of wet spaghetti in diameter, but it feels like that. So when it is actually at the tip of the surgeon’s tool, the surgeon wouldn’t feel it dragging behind her.”
One advantage of having the endoscope under robotic control is that the brain can be imaged at a higher magnification.
“A surgeon couldn’t hold a microscope steady in her hand while performing surgery, but the robot can,” said Seibel.
Microscopic detail is essential when trying to determine the border between healthy tissue—which if removed could lead to neurological deficits—and cancerous tissue—which if left in the brain could allow a tumor to return.
Krosnick says he’s excited by the combination of high-quality imaging and robotic enabled micro-neurosurgery. “It addresses a critical need, which is to discern tumor margins at high resolution while minimizing disruption to normal structures.”
Seibel believes this discrimination between cancerous and healthy tissue could be enhanced even further by taking advantage of the fact that his scanning endoscope is also able to detect fluorescence. One of the main focuses of his current research is a collaboration with Jim Olson, M.D., Ph.D. at the Fred Hutchinson Cancer Research Center, who is the inventor of a substance called “tumor paint”.
Tumor paint is a fluorescent probe that attaches to cancerous but not healthy cells when injected into the body. Seibel says the ultimate goal would be to give a patient an injection of tumor paint and then use his endoscope to create an image of the fluorescing cancer cells as well as a colored anatomic image of the brain. The two images could then be merged on a screen for the surgeon to view during an operation.“You would be able to see all the structure that a surgeon would see, but you’d also see those molecular pinpoints of light that are cancer cells…and from there the robot can be used to resect, or remove, these small cells of cancer, and it can do it very precisely because you don’t have the shaking of a human holding it.”
Image: Tumor paint is made of a compound extracted from scorpion venom that can travel through the blood brain barrier and bind specifically to tumor cells. Source: iStockphoto
Seibel concluded by saying, “There’s a real niche for video-quality, high-resolution, multi-modal imaging that’s in a tiny package so that it can be put on microscopic tools for minimally invasive medicine. I really feel it’s an enabling technology that could move the whole field forward.”
Krosnick is enthusiastic about the progress the two teams have made so far. “These are innovative technologies that, if effective, could significantly add to the brain surgery armamentarium. They’re still early in development, but I think both show considerable promise.” He concluded by emphasizing that, like all new devices, these technologies would need to undergo a series of clinical trials to ensure that they are safe and effective before making their way into an operating room.
(Source: nibib.nih.gov)
TB and Parkinson’s Disease Linked By Unique Protein
UCSF Researchers Seek Way to Boost Parkin to Fight Both Diseases
A protein at the center of Parkinson’s disease research now also has been found to play a key role in causing the destruction of bacteria that cause tuberculosis, according to scientists led by UC San Francisco microbiologist and tuberculosis expert Jeffery Cox, PhD.
The protein, named Parkin, already is the focus of intense investigation in Parkinson’s disease, in which its malfunction is associated with a loss of nerve cells. Cox and colleagues now report that Parkin also acts on tuberculosis, triggering destruction of the bacteria by immune cells known as macrophages. Results appear online today (September 4, 2013) in the journal Nature.
The finding suggests that disease-fighting strategies already under investigation in pre-clinical studies for Parkinson’s disease might also prove useful in fighting tuberculosis, according to Cox. Cox is investigating ways to ramp up Parkin activity in mice infected with tuberculosis using a strategy similar to one being explored by his UCSF colleague Kevan Shokat, PhD, as a way to ward off neurodegeneration in Parkinson’s disease.
Globally, tuberculosis kills 1.4 million people each year, spreading from person to person through the air. Parkinson’s disease, the most common neurodegenerative movement disorder, also affects millions of mostly elderly people worldwide.
Cox homed in on the enzyme Parkin as a common element in Parkinson’s and tuberculosis through his investigations of how macrophages engulf and destroy bacteria. In a sense the macrophage — which translates from Greek as “big eater” — gobbles down foreign bacteria, through a process scientists call xenophagy.
Mycobacterium tuberculosis, along with a few other types of bacteria, including Salmonella and leprosy-causing Mycobacterium leprae, are different from other kinds of bacteria in that, like viruses, they need to get inside cells to mount a successful infection.
The battle between macrophage and mycobacterium can be especially intense. M. tuberculosis invades the macrophage, but then becomes engulfed in a sac within the macrophage that is pinched off from the cell’s outer membrane. The bacteria often escape this intracellular jail by secreting a protein that degrades the sac, only to be targeted yet again by molecular chains made from a protein called ubiquitin. Previously, Cox discovered molecules that escort these chained mycobacteria to more secure confinement within compartments inside cells called lysosomes, where the bacteria are destroyed.
The cells of non-bacterial organisms ranging in complexity from baker’s yeast to humans also use a similar mechanism — called autophagy — to dispose of their own unneeded molecules or worn out cellular components. Among the most abundant and crucial of these components are the cell’s mitochondria, metabolic powerhouses that convert food molecules into a source of energy that the cell can readily use to carry out its everyday housekeeping chores, as well as its more specialized functions.
Like other cellular components, mitochondria can wear out and malfunction, and often require replacement. The process through which mitochondria are disposed of, called mitophagy, depends on Parkin.
Cox became curious about the enzyme when he learned that specific, naturally occurring variations in the Parkin gene, called polymorphisms, are associated with increased susceptibility to tuberculosis infection.
“Because of the commonalities between mitophagy and the xenophagy of intracellular mycobacteria, as well as the links between Parkin gene polymorphisms and increased susceptibility to bacterial infection in humans, we speculated that Parkin may also be recruited to M. tuberculosis and target it for xenophagy,” Cox said.
In both mouse and human macrophages infected with M. tuberculosis in the lab, Parkin played a key role in fighting the bacteria, Cox and colleagues found. In addition, genetically engineered mice lacking Parkin died when infected with M. tuberculosis, while mice with normal Parkin survived infection.
The involvement of Parkin in targeting both damaged mitochondria and infectious mycobacteria arose long ago in evolution, Cox argues. As part of the Nature study, the research team found that Parkin-deficient mice and flies – creatures quite distant from humans in evolutionary time – also are more sensitive than normal mice and flies to intracellular bacterial infections.
Looking back more than 1 billion years, Cox noted that mitochondria evolved from bacteria that were taken up by cells in a symbiotic relationship.
In the same way that the immune system recognizes infectious bacteria as foreign, Cox said, “The evolutionary origin of mitochondria from bacteria suggests that perhaps mitochondrial dysfunction triggers the recognition of a mitochondrian as non-self.”
Having now demonstrated the importance of Parkin in fighting mycobacterial infection, Cox has begun working with Shokat to find a way to boost Parkin activity against cell-invading bacteria. “We are exploring the possibility that small-molecule drugs could be developed to activate Parkin to better fight tuberculosis infection,” Cox said.
(Source: newswise.com)
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.
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.
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.
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)
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.
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.
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.
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)