Posts tagged neuroscience
Articles and news from the latest research reports.
New Technique Helps Stroke Victims Communicate
Stroke victims affected with loss of speech caused by Broca’s aphasia have been shown to speak fluidly through the use of a process called “speech entrainment” developed by researchers at the University of South Carolina’s Arnold School of Public Health.
Aphasia, a severe communication problem caused by damage to the brain’s left hemisphere and characterized by halting speech, occurs in about one-third of people who have a stroke and affects personal and professional relationships. Using the speech entrainment technique, which involves mimicking other, patients showed significant improvement in their ability to speak.
The results of the study are published in a recent issue of the neurology journal Brain.
"This is the first time that we have seen people with Broca’s aphasia speak in fluent sentences,” said Julius Fridriksson, the study’s lead researcher and a professor with the Department of Communication Sciences and Disorders at the Arnold School. “It is a small study that gives us an understanding of how the brain functions after a stroke, and it offers hope for thousands of people who suffer strokes each year."
In Fridriksson’s study, 13 patients completed three separate behavioral tasks that were used to understand the effects of speech entrainment on speech production. During the “speech entrainment–audio visual" portion of the study, participants attempted to mimic a speaker in real-time whose mouth was made visible on the 3.5-inch screen of an iPod Touch and whose speech was heard via headphones.
The “speech entrainment–audio only” condition involved real-time mimicking speech presented via headphones with the screen of the iPod blank. During a spontaneous speech condition, patients spoke about a given topic without external aid.
Each patient also completed a three-week training phase where they practiced speech every day with the aid of speech entrainment. Overall, the training resulted in improved spontaneous speech production, something that is relatively rare in this population. Ultimately the patients were able to produce a short script about their stroke to tell to other people.
Neuroimaging results from the patient subjects have also given Fridriksson and his research team a greater understanding of the mechanism involved in speech entrainment.
"Preliminary results suggest that training with speech entrainment improves speech production in Broca’s aphasia, providing a potential therapeutic method for a disorder that has been shown to be particularly resistant to treatment," Fridriksson said.
Study sheds light on how our brains move limbs
A Queen’s University study is giving new insight into how the neurons in our brains control our limbs. The research might one day help with the design of more functional artificial limbs.
“We’ve taken a step closer to understanding how our arms and legs work and how we move our bodies,” says neuroscience researcher Tim Lillicrap, who worked with neuroscience professor Stephen Scott on the study.
The researchers used a novel network model, coupled with a computer biophysics model of a limb, to explain some of the prominent patterns of neural activity seen in the brain during movements.
The findings refine previous notions of how neurons in the primary motor cortex fire and drive muscles. The primary motor cortex is the region of the brain that sends the largest number of connections to the spinal cord.
When moving an arm or a leg, nerve impulses are sent along nerve fibres to control the movement of limbs. Different movements require different patterns of nerve impulses — the relationship between these neural patterns and the resulting movements is poorly understood.
The study demonstrates that the patterns of activity are related to specific details of limb physics — for example, the patterns of neural activity are tuned (or optimized) for muscle architecture and limb geometry.
Dr. Lillicrap, who did the study as part of his PhD thesis at Queen’s and is now a post-doctoral fellow at Oxford University in England, says better understanding of how the brain controls limbs will help develop artificial limbs in the future.
(Source: queensu.ca)
Research Reveals Exactly How the Human Brain Adapts to Injury
For the first time, scientists at Carnegie Mellon University’s Center for Cognitive Brain Imaging (CCBI) have used a new combination of neural imaging methods to discover exactly how the human brain adapts to injury. The research, published in Cerebral Cortex, shows that when one brain area loses functionality, a “back-up” team of secondary brain areas immediately activates, replacing not only the unavailable area but also its confederates.
“The human brain has a remarkable ability to adapt to various types of trauma, such as traumatic brain injury and stroke, making it possible for people to continue functioning after key brain areas have been damaged,” said Marcel Just, the D. O. Hebb Professor of Psychology at CMU and CCBI director. “It is now clear how the brain can naturally rebound from injuries and gives us indications of how individuals can train their brains to be prepared for easier recovery. The secret is to develop alternative thinking styles, the way a switch-hitter develops alternative batting styles. Then, if a muscle in one arm is injured, they can use the batting style that relies more on the uninjured arm.”
For the study, Just, Robert Mason, senior research psychologist at CMU, and Chantel Prat, assistant professor of psychology at the University of Washington, used functional magnetic resonance imaging (fMRI) to study precisely how the brains of 16 healthy adults adapted to the temporary incapacitation of the Wernicke area, the brain’s key region involved in language comprehension. They applied Transcranial Magnetic Stimulation (TMS) in the middle of the fMRI scan to temporarily disable the Wernicke area in the participants’ brains. The participants, while in the MRI scanner, were performing a sentence comprehension task before, during and after the TMS was applied. Normally, the Wernicke area is a major player in sentence comprehension.
The research team used the fMRI scans to measure how the brain activity changed immediately following stimulation to the Wernicke area. The results showed that as the brain function in the Wernicke area decreased following the application of TMS, a “back-up” team of secondary brain areas immediately became activated and coordinated, allowing the individual’s thought process to continue with no decrease in comprehension performance.
The brain’s back-up team consisted of three types of brain regions: (1) contralateral areas —areas that are in the mirror-image location of the brain; (2) areas that are right next to the impaired area; and (3) a frontal executive area.
“The first two types of back-up areas have similar brain capabilities as the impaired Wernicke area, although they are less efficient at the capability,” Just said. “The third area plays a strategic role as in responding to the initial impairment and recruiting back-up areas with similar capabilities.”
Additionally, the research showed that impairing the Wernicke area also negatively affected the cortical partners with which the Wernicke area had been working. “Thinking is a network function,” Just explained. “When a key node of a network is impaired, the network that is closely collaborating with the impaired node is also impaired. People do their thinking with groups of brain areas, not with single brain areas.”
Mason, the study’s lead author, noted that following the TMS, the impaired area and its partners gradually returned to their previous levels of coordinated activity, while the back-up team of brain areas was still in place. “This means, that for some period of time, there were two cortical teams operating simultaneously, explaining why performance is sometimes improved by TMS,” he said.
This research builds on Just’s previous research on brain resilience after stroke and brain training to remediate dyslexia. The studies are motivated by a computational theory, called 4CAPS, that provides an account of how autonomous brain systems dynamically self-organize themselves in response to changing circumstances, which the researchers believe to be the basis of fluid intelligence.
Childhood trauma leaves its mark on the brain
EPFL scientists have found that childhood trauma leaves a lasting imprint on the brain – a structural change that is related to a predisposition to violence.
It is well known that violent individuals are often themselves the victims of psychological trauma experienced in childhood. Some of these individuals also exhibit alterations in their orbitofrontal cortex. But is there a connection between these physical changes in the brain and a psychologically traumatic childhood? Can one’s experiences modify the physical structure of the brain?
An EPFL team led by Professor Carmen Sandi, member of the National Centers for Competence in Research SYNAPSY, has demonstrated for the first time a correlation between psychological trauma and specific changes in the brain that are related to aggressive behavior. In rats, the experience of pre-adolescent trauma led to aggressive behavior accompanied by structural and functional changes in the brain – the same changes that have been observed in violent human beings. In other words, psychological wounds inflicted in childhood leave a lasting biological trace that persists in the adult brain. The team’s findings have been published in the January 15 edition of the journal Translational Psychiatry.
“This research shows that people exposed to trauma in childhood don’t only suffer psychologically, but their brain also gets altered,” explains Sandi, who is head of EPFL’s Laboratory of Behavioral Genetics and director of the Brain Mind Institute. “This adds an additional dimension to the consequences of abuse, and obviously has scientific, therapeutic and social implications.”
Remarkable results
The researchers were able to unravel the biological foundations of violence using a cohort of male rats that were exposed to psychologically stressful situations when young. After observing that these experiences led to aggressive behavior when the rats reached adulthood, they examined what was happening in the animals’ brains to see if the traumatic period had left a lasting mark.
“In a challenging social situation, the orbitofrontal cortex of a healthy individual is activated in order to inhibit aggressive impulses and to maintain normal interactions,” explains Sandi. “But in the rats we studied, we noticed that there was very little activation of the orbitofrontal cortex. This, in turn, reduces their ability to moderate their negative impulses. This reduced activation is accompanied by the overactivation of the amygdala, a region of the brain that’s involved in emotional reactions.” Other researchers who have studied the brains of violent human individuals have observed the same deficit in orbitofrontal activation and the same concomitant reduced inhibition of aggressive impulses. “It’s remarkable; we didn’t expect to find this level of similarity,” says Sandi.
Antidepressants and cerebral plasticity
The scientists also measured changes in the expression of certain genes in the brain. The neurobiologists focused on genes known to be involved in aggressive behavior for which there are polymorphisms (genetic variants) that predispose carriers to an aggressive attitude. They looked at whether the psychological stress experienced by the rats caused a modification in these genes’ expression. “We found that the level of MAOA gene expression increased in the prefrontal cortex,” says Sandi. This alteration was linked to an epigenetic change; in other words, the traumatic experience ended up causing a long-term modification of this gene’s expression.
Finally, the researchers tried to see if an MAOA gene inhibitor, in this case an antidepressant, could reverse the increase in aggressive behavior induced by the juvenile stress. The treatment was effective. The team will now concentrate its efforts on trying to better understand these mechanisms, and explore whether a treatment could possibly reverse these changes in the brain, and above all, to shed light on whether some people are more vulnerable than others depending on their genetic makeup. “This research could also reveal the possible ability of antidepressants – an ability that’s increasingly being suspected – to renew cerebral plasticity,” says the professor.
Exploring the Brain’s Relationship to Habits
The basal ganglia, structures deep in the forebrain already known to control voluntary movements, also may play a critical role in how people form habits, both bad and good, and in influencing mood and feelings.
"This system is not just a motor system," says Ann Graybiel. "We think it also strongly affects the emotional part of the brain."
Graybiel, an investigator at the McGovern Institute of the Massachusetts Institute of Technology and professor in MIT’s department of brain and cognitive sciences, believes that a core function of the basal ganglia is to help humans develop habits that eventually become automatic, including habits of thought and emotion.
"Many everyday movements become habitual through repetition, but we also develop habits of thought and emotion," she says."If cognitive and emotional habits are also controlled by the basal ganglia, this may explain why damage to these structures can lead not only to movement disorders, but also to repetitive and intrusive thoughts, emotions and desires."
Graybiel’s research focuses on the brain’s relationship to habits—how we make or break them—and the neurobiology of the habit system. She and her team have identified and traced neural loops that run from the outer layer of the brain—“the thinking cap,” as she calls it—to a region called the striatum, which is part of the basal ganglia, and back again. These loops, in fact, connect sensory signals to habitual behaviors.
Her work ultimately could have an impact not just on such classic movement disorders as Parkinson’s and Huntington’s diseases, but in other conditions where repetitive movements commonly occur, such as Tourette Syndrome, autism, or obsessive-compulsive disorder, the latter when sufferers experience unwanted and repeated thoughts, feelings, ideas, sensations or behaviors that make them feel driven to do something, for example, repeatedly washing their hands.
Moreover, the research could have an immediate value for trying to understand “what happens in the brain as addiction occurs, as bad habits form, not just good habits,” she says. “There are many psychiatric and neurologic conditions in which these same brain regions are disordered.
"These conditions may in part be influenced by the very system we are working on," Graybiel adds. "We are working with models of anxiety and depression, stress and some of these movement disorders."
It turns out that the emotional circuits of the brain have strong ties to the striatum, she says. Graybiel’s research suggests that activity in the striatum strongly affects the emotional decisions that people make: whether to accept a good outcome or a potentially bad one, for example, and that there are circuits favoring good outcomes, and, surprisingly, other circuits that favor bad ones.
"This work ties into new research suggesting that there are brain systems for ‘good’ and brain systems for ‘bad,’" she says. "What is intriguing is that we may have identified the circuits that decide between the two."
Transmission of Tangles in Alzheimer’s Mice Provides More Authentic Model of Tau Pathology
Brain diseases associated with the misformed protein tau, including Alzheimer’s disease and frontotemporal lobar degeneration with tau pathologies, are characterized by neurofibrillary tangles (NFTs) comprised of pathological tau filaments. Tau tangles are also found in progressive supranuclear palsy, cortical basal degeneration and other related tauopathies, including chronic traumatic encephalopathy due to repetitive traumatic brain injuries sustained in sports or on the battle field.
By using synthetic fibrils made from pure recombinant protein, Penn researchers provide the first direct and compelling evidence that tau fibrils alone are entirely sufficient to recruit and convert soluble tau within cells into pathological clumps in neurons, followed by transmission of tau pathology to other inter-connected brain regions from a single injection site in an animal model of tau brain disease.
The laboratory of senior author Virginia M.-Y. Lee, Ph.D., MBA, director of the Center for Neurodegenerative Disease Research and professor of Pathology and Laboratory Medicine at the Perelman School of Medicine, University of Pennsylvania, published their findings in the Journal of Neuroscience this week.
“Our new model of tau pathology spread provides an explanation to account for the stereotypical progression of Alzheimer’s and other related tauopathies by implicating the cell-to-cell transmission of pathological tau in this process,” says Lee.
Studies Provide New Insights into Brain-Behavior Relationships
Approximately half a million individuals suffer strokes in the US each year, and about one in five develops some form of post-stroke aphasia, the partial or total loss of the ability to communicate. By comparing different types of aphasia, investigators have been able to gain new insights into the normal cognitive processes underlying language, as well as the potential response to interventions. Their findings are published alongside papers on hemispatial neglect and related disorders in the January, 2013 issue of Behavioural Neurology.
The January issue of Behavioural Neurology, edited by the journal’s co-Editor in Chief, Argye E. Hillis, MD, of the Departments of Neurology, Physical Medicine and Rehabilitation, and Department of Cognitive Science, Johns Hopkins University, Baltimore, Maryland, features papers on two topics that have traditionally captured the interest of behavioral neurologists – aphasia and hemispatial neglect.
The first section on aphasia includes a number of papers that compare post-stroke aphasia with primary progressive aphasia (PPA), in which the predominant deficit is language (with or without apraxia).
Andreia V. Faria, MD, Department of Radiology, Johns Hopkins University School of Medicine, and colleagues from Johns Hopkins and University College, London, report patterns of dysgraphia (spelling impairment) in participants with primary progressive aphasia, and compare these patterns to those in participants with dysgraphia following stroke. They also report the areas of focal atrophy associated with the most common pattern of dysgraphia in PPA and suggest this can not only provide a better understanding of the neural substrates of spelling, but may also provide clues to more effective treatment approaches.
Matthew A. Lambon Ralph, FRSLT (hons), FBPsS, and colleagues from the School of Psychological Sciences, University of Manchester, UK; the Department of Psychology, University of York, UK; and the Stroke and Dementia Research Centre, St George’s University of London, UK, use a novel approach to explore nonverbal semantic processing to demonstrate the qualitative differences between semantic aphasia and semantic dementia. Their conclusions provide further support for the proposal that semantic cognition is underpinned by two principle components: semantic representations and regulatory control processes which regulate and shape activation within the semantic system.
Cynthia K. Thompson, PhD, and colleagues from the Department of Communication Sciences and Disorders, Department of Neurology, Cognitive Neurology and Alzheimer’s Disease Center, and Department of Psychiatry and Behavioral Sciences at Northwestern University, Evanston, Illinois, evaluate the distinct patterns of morphological and syntactic errors in the variants of PPA, and compare them with patterns of errors in post-stroke aphasia.
Other papers compare treatment results of spelling in one individual with logopenic variant PPA (lvPPA) with an individual with post-stroke dysgraphia, and results of a new method of assessment of verbal and nonverbal memory in PPA. The issue is completed by three Clinical Notes including a fascinating case of an unusual form of lvPPA that degenerated into jargon aphasia, a case of nonfluent agrammatic variant PPA due to Pick disease with (what is argued to be) concomitant incidental Alzheimer’s disease pathology, and a case of successful treatment of PPA.
“Together, these papers illustrate how investigating PPA and post-stroke aphasia can yield complementary insights about brain-behavior relationships as well as about potential response to interventions and the normal cognitive processes underlying language,” says Dr Hillis.
Hemispatial neglect is characterized by reduced awareness of stimuli on one side of space. It occurs only after relatively focal (or at least asymmetric) brain damage, most commonly stroke, but is occasionally observed in other syndromes. In this second group of seven papers, Jonathan T. Kleinman, MD, of Johns Hopkins University School of Medicine, and Stanford University School of Medicine, Stanford, California, and colleagues from Johns Hopkins University School of Medicine, report an investigation of perseveration versus hemispatial neglect, and the lesion sites associated with each in acute stroke. The issue also includes an important paper by Junichi Ishizaki, PhD, and co-workers at the Department of Geriatric Behavioral Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan, of impaired visual-spatial attention in Alzheimer’s disease, which shows how a symmetric neurodegenerative disease results in impaired shifting of visual spatial attention, but not hemispatial neglect.
“Hemispatial neglect remains one of the most remarkable syndromes investigated by behavioral neurologists,” comments Dr Hillis. “These novel studies of neglect and related disorders provide new insights into brain-behavior relationships on the basis of detailed analysis of patient performance – and in many cases, their lesion sites.“
(Source: iospress.nl)
Whether in society or nature, decisions are often the result of complex interactions between many factors. Because of this it is usually difficult to determine how much weight the different factors have in making a final decision. Neuroscientists face a similar problem since decisions made by the brain always involve many neurons. Working in collaboration, the University of Tübingen and the Max Planck Institute for Biological Cybernetics, supported within the framework of the Bernstein Network, researchers lead by CIN professor Matthias Bethge have now shown how the weight of individual neurons in the decision-making process can be reconstructed despite interdependencies between the neurons.
When we see a person on the other side of the street who looks like an old friend, the informational input enters the brain via many sensory neurons. But which of these neurons are crucial in passing on the relevant information to higher brain areas, which will decide who the person is and whether to wave and say ‘hello’? A research group lead by Matthias Bethge has now developed an equation that allows them to calculate to what degree a given individual sensory neuron is involved in the decision process.
To approach this question, researchers have so far considered the information about the final decision that an individual sensory neuron carries. Just as an individual is considered suspicious if he or she is found to have insider information about a crime, those sensory neurons whose activity contains information about the eventual decision are presumed to have played a role in reaching the final decision. The problem with this approach is that neurons – much like people – are constantly communicating with each other. A neuron which itself is not involved in the decision may simply have received this information from a neighboring neuron and “joined in” the conversation. Actually, the neighboring cell sends out the crucial signal transmitted to the higher decision areas in the brain.
The new formula that has been developed by scientists addresses this by accounting not just for the information in the activity of any one neuron but also for the communication that takes place between them. This formula will now be used to determine whether only a few neurons that carry a lot of information are involved in the brain’s decision process, or whether the information contained in very many neurons gets combined. In particular, it will be possible to address the more fundamental question: In which decisions does the brain use information in an optimal way, and for which decisions is its processing suboptimal?
Reshaping the brain: scientists reprogram neurons after birth
The cerebral cortex—the gray matter that forms the outer layers of the mammalian cerebrum and cerebellum—is divided into six different layers based on the presence of specialized neurons, and we’ve known that since the early 1900s. Denis Jabaudon is interested in using the tools of modern biology to understand the genetic mechanisms that establish and maintain those layers. Over the past few years, his lab has published papers implicating various genes in the generation of specific neuronal subtypes.
Now they have gone a step further. They have developed a new electrochemical method to transfer genes into specific types of neurons—they call it iontoporation. Using it, they have transformed one type of neuron in a mature brain into a different type entirely.
Although Jabaudon and others have made some headway in working out how the different neurons arise, they still don’t know how plastic they are—if they can change fates after they started differentiating down one particular path. In the context of brain injury, it would be useful to know if certain neural circuits could be reprogrammed and repaired by having the neurons that are already present change fates to adapt to the damage. But this has been challenging to determine, because changing the fate of specific neurons in the latter stages of differentiation has been technically difficult.
Layer 4 mouse spiny neurons have round bodies, with many short dendrites (connections with other cells) that stay within their layer of the brain. They receive sensory signals from the thalamus. Layer 5B output neurons are pyramidal in shape, with a prominent dendrite that extends all the way to layer 1.
Fezf2 is a transcription factor that regulates the activity of other genes. It is expressed throughout the L5B neuron’s entire life, and it is necessary and sufficient for turning early cortical cells into L5B neurons.
When Jabaudon’s colleagues iontoporated Fezf2 into L4 neurons the day after mice were born, a week after the neurons had established their identity, it completely transformed them. You guessed it: the L4 neurons walked, talked, looked, and quacked just like L5B neurons. They looked like L5B’s and began transmitting signals to other nerves just as these cells did. Most significantly, however, they rearranged their intracortical inputs, meaning that they now received signals from layer 2/3 neurons instead of from the thalamus.
The researchers tried their iontoporation as late as ten days after the mice were born, and found that the neurons become less amenable to reprogramming with time, but some features were still malleable for a week after the mice were born—two weeks after the neurons originated.
The authors hope to further explore the molecular mechanisms responsible for the emergence and patterning of different cortical areas during brain development and their plasticity after injury. They hope that one day, reprogramming existing neurons could be a means of nervous system repair.
Lack of Protein Sp2 Disrupts Neuron Creation in Brain
A protein known as Sp2 is key to the proper creation of neurons from stem cells, according to researchers at North Carolina State University. Understanding how this protein works could enable scientists to “program” stem cells for regeneration, which has implications for neural therapies.
Troy Ghashghaei and Jon Horowitz, both faculty in NC State’s Department of Molecular Biomedical Sciences and researchers in the Center for Comparative Medicine and Translational Research, wanted to know more about the function of Sp2, a cell cycle regulator that helps control how cells divide. Previous research from Horowitz had shown that too much Sp2 in skin-producing stem cells resulted in tumors in experimental mice. Excessive amounts of Sp2 prevented the stem cells from creating normal cell “offspring,” or skin cells. Instead, the stem cells just kept producing more stem cells, which led to tumor formation.
“We believe that Sp2 must play a fundamental role in the lives of normal stem cells,” Horowitz says. “Trouble ensues when the mechanisms that regulate its activity are overwhelmed due to its excess abundance.”
Ghashghaei and his team – led by doctoral candidate Huixuan Liang – took the opposite approach. Using genetic tools, they got rid of Sp2 in certain neural stem cells in mice, specifically those that produce the major neurons of the brain’s cerebral cortex. They found that a lack of Sp2 disrupted normal cell formation in these stem cells, and one important result was similar to Horowitz’s: the abnormal stem cells were unable to produce normal cell “offspring,” or neurons. Instead, the abnormal stem cells just created copies of themselves, which were also abnormal.
“It’s interesting that both an overabundance of this protein and a total lack of it result in similar disruptions in how stem cells divide,” Ghashghaei says. “So while this work confirms that Sp2 is absolutely necessary for stem cell function, a lot of questions still remain about what exactly it is regulating, and whether it is present in all stem cells or just a few. We also need to find out if Sp2 deletion or overabundance can produce brain tumors in our mice as in the skin.
“Finally, we are very interested in understanding how Sp2 regulates a very important decision a stem cell has to make: whether to produce more of itself or to produce offspring that can become neurons or skin cells,” Ghashghaei adds. “We hope to address those questions in our future research, because these cellular mechanisms have implications for cancer research, neurodevelopmental diseases and regenerative medicine.”
The results appear online in Development. NC State graduate students Guanxi Xiao, and Haifeng Yin, as well as Dr. Simon Hippenmeyer, a collaborator with the Ghashghaei lab from Austria’s Institute of Science and Technology, contributed to the work. The work was funded by the National Institutes of Health and the American Federation for Aging Research.