Posts tagged neurological disorders
Articles and news from the latest research reports.
Turning human stem cells into brain cells sheds light on neural development
Medical researchers have manipulated human stem cells into producing types of brain cells known to play important roles in neurodevelopmental disorders such as epilepsy, schizophrenia and autism. The new model cell system allows neuroscientists to investigate normal brain development, as well as to identify specific disruptions in biological signals that may contribute to neuropsychiatric diseases.
Scientists from The Children’s Hospital of Philadelphia and the Sloan-Kettering Institute for Cancer Research led a study team that described their research in the journal Cell Stem Cell, published online today.
The research harnesses human embryonic stem cells (hESCs), which differentiate into a broad range of different cell types. In the current study, the scientists directed the stem cells into becoming cortical interneurons—a class of brain cells that, by releasing the neurotransmitter GABA, controls electrical firing in brain circuits.
"Interneurons act like an orchestra conductor, directing other excitatory brain cells to fire in synchrony," said study co-leader Stewart A. Anderson, M.D., a research psychiatrist at The Children’s Hospital of Philadelphia. "However, when interneurons malfunction, the synchrony is disrupted, and seizures or mental disorders can result."
Anderson and study co-leader Lorenz Studer, M.D., of the Center for Stem Cell Biology at Sloan-Kettering, derived interneurons in a laboratory model that simulates how neurons normally develop in the human forebrain.
"Unlike, say, liver diseases, in which researchers can biopsy a section of a patient’s liver, neuroscientists cannot biopsy a living patient’s brain tissue," said Anderson. Hence it is important to produce a cell culture model of brain tissue for studying neurological diseases. Significantly, the human-derived cells in the current study also "wire up" in circuits with other types of brain cells taken from mice, when cultured together. Those interactions, Anderson added, allowed the study team to observe cell-to-cell signaling that occurs during forebrain development.
In ongoing studies, Anderson explained, he and colleagues are using their cell model to better define molecular events that occur during brain development. By selectively manipulating genes in the interneurons, the researchers seek to better understand how gene abnormalities may disrupt brain circuitry and give rise to particular diseases. Ultimately, those studies could help inform drug development by identifying molecules that could offer therapeutic targets for more effective treatments of neuropsychiatric diseases.
In addition, Anderson’s laboratory is studying interneurons derived from stem cells made from skin samples of patients with chromosome 22q.11.2 deletion syndrome, a genetic disease which has long been studied at The Children’s Hospital of Philadelphia. In this multisystem disorder, about one third of patients have autistic spectrum disorders, and a partially overlapping third of patients develop schizophrenia. Investigating the roles of genes and signaling pathways in their model cells may reveal specific genes that are crucial in those patients with this syndrome who have neurodevelopmental problems.
(Source: eurekalert.org)
Decision Making: From Neuroscience to Psychiatry
Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker’s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson’s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders.
Researchers show brain’s battle for attention
We’ve all been there: You’re at work deeply immersed in a project when suddenly you start thinking about your weekend plans. It happens because behind the scenes, parts of your brain are battling for control.
Now, University of Florida researchers and their colleagues are using a new technique that allows them to examine how parts of the brain battle for dominance when a person tries to concentrate on a task. Addressing these fluctuations in attention may help scientists better understand many neurological disorders such as autism, depression and mild cognitive impairment.
Mingzhou Ding, a professor of biomedical engineering, and Xiaotong Wen, an assistant research scientist of biomedical engineering, both of the University of Florida; Yijun Liu of the McKnight Brain Institute of the University of Florida and Peking University, Beijing; and Li Yao of Beijing Normal University, report their findings in the current issue of The Journal of Neuroscience.
Scientists know different networks within the brain have distinct functions. Ding, Wen and their colleagues used a brain imaging technique called functional magnetic resonance imaging and biostatistical methods to examine interactions between a set of areas they call the task control network and another set of areas known as the default mode network.
The task control network regulates attention to surroundings, controlling concentration on a task such as doing homework, or listening for emotional cues during a conversation. The default mode network is thought to regulate self-reflection and emotion, and often becomes active when a person seems to be doing nothing else.
“We knew that the default mode network decreases in activity when a task is being performed, but we didn’t know why or how,” said Ding, a professor of biomedical engineering in the J. Crayton Pruitt department of biomedical engineering. “We also wanted to know what is driving that activity decrease.
“For a long time, the questions we are asking could not be answered.”
In the past, researchers could not distinguish between directions of interactions between regions of the brain, and could come up with only one number to represent an average of the back-and-forth interactions. Ding and his colleagues used a new technique to untangle the interactions in each direction to show how the different brain regions interact with one another.
In their study, the researchers used fMRI to examine the brains of people performing a task that required concentration. The scientists can see the activity in certain areas of the brain at the same time a person is performing a given task. They can see which parts of the brain are active and which are not and correlate this to how successful a person is at a given task. They then applied the Granger causality technique to look at the data they saw in the fMRI. Named for Nobel Prize-winning economist Clive Granger, this technique allows scientists to examine how one variable affects another variable; in this case, how one region of the brain influences another.
“People have hypothesized different functions for signals going in different directions,” Ding said. “We show that when the task control network suppresses the default mode network, the person can do the task better and faster. The better the default mode network is shut down, the better a person performs.”
However, when the default mode network is not sufficiently suppressed, it sends signals to the task control network that effectively distract the person, causing his or her performance to drop. So while the task control network suppresses the default mode network, the default mode network also interferes with the task control network.
“Your brain is a constant seesaw back and forth,” even when trying to concentrate on a task, Ding said.
The Granger causality technique may help researchers learn more about how neurological disorders work. Researchers have found that the default mode network remains unchanged in people with autism whether they are performing a task or interacting with the environment, which could explain symptoms such as difficulty reading social cues or being easily overwhelmed by sensory stimulation. Scientists have made similar findings with depression and mild cognitive impairment. However, until now no one has been able to address what areas of the brain might be regulating the default mode network and which might be interfering with that regulation.
“Now we are able to address these questions,” Ding said.
(Source: news.ufl.edu)
BRAIN Initiative Launched to Unlock Mysteries of Human Mind
Today at the White House, President Barak Obama unveiled the “BRAIN” Initiative — a bold new research effort to revolutionize our understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy, and traumatic brain injury.
The NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is part of a new Presidential focus aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a revolutionary new dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space. Long desired by researchers seeking new ways to treat, cure, and even prevent brain disorders, this picture will fill major gaps in our current knowledge and provide unprecedented opportunities for exploring exactly how the brain enables the human body to record, process, utilize, store, and retrieve vast quantities of information, all at the speed of thought.
Why is the NIH BRAIN Initiative needed?
With nearly 100 billion neurons and 100 trillion connections, the human brain remains one of the greatest mysteries in science and one of the greatest challenges in medicine. Neurological and psychiatric disorders, such as Alzheimer’s disease, Parkinson’s disease, autism, epilepsy, schizophrenia, depression, and traumatic brain injury, exact a tremendous toll on individuals, families, and society. Despite the many advances in neuroscience in recent years, the underlying causes of most of neurological and psychiatric conditions remain largely unknown, due to the vast complexity of the human brain. If we are ever to develop effective ways of helping people suffering from these devastating conditions, researchers will first need a more complete arsenal of tools and information for understanding how the brain functions both in health and disease.
Why is now the right time for the NIH BRAIN Initiative?
In the last decade alone, scientists have made a number of landmark discoveries that now create the opportunity to unlock the mysteries of the brain. We have witnessed the sequencing of the human genome, the development of new tools for mapping neuronal connections, the increasing resolution of imaging technologies, and the explosion of nanoscience. These discoveries have yielded unprecedented opportunities for integration across scientific fields. For instance, by combining advanced genetic and optical techniques, scientists can now use pulses of light in animal models to determine how specific cell activities within the brain affect behavior. What’s more, through the integration of neuroscience and physics, researchers can now use high-resolution imaging technologies to observe how the brain is structurally and functionally connected in living humans.
While these technological innovations have contributed substantially to our expanding knowledge of the brain, significant breakthroughs in how we treat neurological and psychiatric disease will require a new generation of tools to enable researchers to record signals from brain cells in much greater numbers and at even faster speeds. This cannot currently be achieved, but great promise for developing such technologies lies at the intersections of nanoscience, imaging, engineering, informatics, and other rapidly emerging fields of science.
How will the NIH BRAIN Initiative work?
Given the ambitious scope of this pioneering endeavor, it is vital that planning for the NIH BRAIN Initiative be informed by a wide range of expertise and experience. Therefore, NIH is establishing a high level working group of the Advisory Committee to the NIH Director (ACD) to help shape this new initiative. This working group, co-chaired by Dr. Cornelia “Cori” Bargmann (The Rockefeller University) and Dr. William Newsome (Stanford University), is being asked to articulate the scientific goals of the BRAIN initiative and develop a multi-year scientific plan for achieving these goals, including timetables, milestones, and cost estimates.
As part of this planning process, input will be sought broadly from the scientific community, patient advocates, and the general public. The working group will be asked to produce an interim report by fall 2013 that will contain specific recommendations on high priority investments for Fiscal Year (FY) 2014. The final report will be delivered to the NIH Director in June 2014.
How will the NIH BRAIN Initiative be supported?
In total, NIH intends to allocate $40 million in FY14. Given the cross-cutting nature of this project, the NIH Blueprint for Neuroscience Research — an initiative spanning 14 NIH Institutes and Centers — will be the leading NIH contributor to its implementation in FY14. Of course, a goal this audacious will require ideas from the best scientists and engineers across many diverse disciplines and sectors. Therefore, NIH is working in close collaboration with other government agencies, including the Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation (NSF). Strong interest has also been expressed by several private foundations, including the Howard Hughes Medical Institute, the Allen Institute for Brain Science, and The Kavli Foundation, and the Salk Institute for Biological Studies. Private industries have also expressed a high level of interest in participation in this groundbreaking initiative.
Obama proposes $100m to map the human brain
President Barack Obama on Tuesday asked Congress to spend $100 million next year on a new project to map the human brain in hopes of eventually finding cures for disorders like Alzheimer’s, epilepsy and traumatic injuries.
Obama said the so-called BRAIN Initiative could create jobs and eventually lead to answers to ailments including Parkinson’s and autism and help reverse the effect of a stroke. The president told scientists gathered in the White House’s East Room that the research has the potential to improve the lives of billions of people worldwide.
‘‘As humans we can identify galaxies light-years away,’’ Obama said. ‘‘We can study particles smaller than an atom, but we still haven’t unlocked the mystery of the three pounds of matter that sits between our ears.’’
BRAIN stands for Brain Research through Advancing Innovative Neurotechnologies. The idea, which Obama first proposed in his State of the Union address, would require the development of new technology that can record the electrical activity of individual cells and complex neural circuits in the brain ‘‘at the speed of thought,’’ the White House said.
Obama wants the initial $100 million investment to support research at the National Institutes of Health, the Defense Advanced Research Projects Agency and the National Science Foundation. He also wants private companies, universities and philanthropists to partner with the federal agencies in support of the research. And he wants a study of the ethical, legal and societal implications of the research.
The goals of the work are unclear at this point. A working group at NIH, co-chaired by Cornelia ‘‘Cori’’ Bargmann of The Rockefeller University and William Newsome of Stanford University, would work on defining the goals and develop a multi-year plan to achieve them that included cost estimates.
Is Obama’s Plan to Map the Human Brain this Generation’s Equivalent to Landing a Man on the Moon?
President John F. Kennedy’s mission in the 1960s was to land a man on the moon. President Bill Clinton made cracking the human genome one of his top priorities. Now, President Barack Obama says a detailed map of the human brain is necessary to understand how it works and what needs to be done when it’s not working properly. The president is expected to unveil his plans for an estimated $3 billion, decade-long commitment to the Brain Activity Map project next month in his 2014 budget proposal.
Rutgers Today talked with Rutgers University behavioral neuroscientist Timothy Otto, professor and director of the Behavioral and Systems Neuroscience program in the Department of Psychology, about what we know about the brain, how much we still need to discover and if spending billions of dollars in research will enable scientists to develop new treatments for debilitating neurological diseases like Alzheimer’s, Parkinson’s and autism.
Innovative neurology text includes patient videos
Practical Neurology Visual Review, a powerful educational tool for mastering the clinical practice of neurologic diagnosis, is now available in a fully revised and updated Second Editon.
Co-authors are neurologists Jose Biller, MD, of Loyola University Chicago Stritch School of Medicine and Alberto J. Espay, MD, of the University of Cincinnati.
The book previously was known as Practical Neurology DVD Review. It includes online videos of 131 real-world scenarios, and more than 370 multiple-choice questions. QR codes in the book allow easy access to videos via smart phone scanning.
Neurological problems are increasing due to the growing elderly population. But current assessment formats for the education of resident doctors, fellows and medical students underemphasize bedside teaching, Biller and Espay write in the introduction. “Faculty members strained by the pressures of many competing demands may not be in a position to oversee trainees performing physical examinations during their training.”
Practical Neurology Visual Review provides new venues for teaching and learning the essentials of neurology. The videos show patients with both common and unusual neurological problems, ranging from very easy to extremely challenging. The videos are used to teach five fundamental principles of bedside neurology: description and localization of findings, differential diagnosis, evaluation, management and counseling. Each clinical vignette is accompanied by a succinct written discussion.
"This audiovisual electronic teaching format may be somewhat unorthodox," Biller and Espay write. "However, it is actually more effective in its approach because the technology lends itself to displaying the skills necessary for a physician to form a patient’s neurological diagnosis."
The Unstable Repeats—Three Evolving Faces of Neurological Disease
Disorders characterized by expansion of an unstable nucleotide repeat account for a number of inherited neurological diseases. Here, we review examples of unstable repeat disorders that nicely illustrate three of the major pathogenic mechanisms associated with these diseases: loss of function typically by disrupting transcription of the mutated gene, RNA toxic gain of function, and protein toxic gain of function. In addition to providing insight into the mechanisms underlying these devastating neurological disorders, the study of these unstable microsatellite repeat disorders has provided insight into very basic aspects of neuroscience.
When most of us admire a piece of art, it triggers a cascade of complex neural activity; a wash of emotion and meaning that fills our brains and prompts deep thought. But does that happen for people with neurological conditions, too?
Forthcoming Oxford-based exhibition Affecting Perception seeks to explore that very question, through a combination of art, seminars and school workshops. Organised by Martha Crawford, Cosima Gretton and Rachel Stratton, who together form the AXNS collective, the aim is to understand how artists and their work are affected by neurological conditions.
The team is working with the University’s Department of Experimental Psychology and artists who suffer from conditions ranging from dementia to brain damage, in order to help the public understand how art and neuroscience are intertwined. “We’re trying to engage the community with the kind of learning usually kept in the University,” explains Martha Crawford.
Helping them achieve that are Prof. Glyn Humphreys and Prof. Charles Spence, both from the University’s Department of Experimental Psychology. Individually, they’ll be leading seminars during the exhibition which explore the overlap between academia and art. “There’s a coarse level of understanding of neuropsychology outside of academia, which means people are sometimes scared of neurological conditions,” explains Professor Glyn Humphreys. “I think anything we can do to raise awareness has to be a good thing.”
During the course of the four-week exhibition, Prof. Humprheys will talk about visual agnosia: a condition where patients can’t associate visual stimulus with meaning. It’s a rare condition, but it’s of interest to artists and scientists alike. Separating meaning and aesthetic is a trick used by artists to explore the two more thoughtfully; Humphreys’ patients still have little choice but to face the world that way.
Elsewhere, Prof. Spence will talk about subtle forms of synesthesia, called cross-modal correspondences, which affect us all. Synesthesia is that odd condition where stimulating one sense leads to automatic experiences in a second; cross-modal correspondences are more subtle, like the way red stars make many of us think of bitter flavours. Plenty of famous creatives have used the phenomenon to great effect — and during his talk, Spence will explain how it can help amplify our enjoyment of art.
There’s no denying that these are weighty subject indeed. But by understanding them just a little better we can achieve a better grasp on the neurological conditions that many suffer — and break down the stigma attached to them, too.
Affecting Perception runs from 4th-31st March 2013 at venues across Oxford. Admission is free. For more information, visit http://axnscollective.org.
Scientists find genes linked to human neurological disorders in sea lamprey genome
Scientists at the Marine Biological Laboratory (MBL) have identified several genes linked to human neurological disorders, including Alzheimer’s disease, Parkinson’s disease and spinal cord injury, in the sea lamprey, a vertebrate fish whose whole-genome sequence is reported this week in the journal Nature Genetics.
"This means that we can use the sea lamprey as a powerful model to drive forward our molecular understanding of human neurodegenerative disease and neurological disorders," says Jennifer Morgan of the MBL’s Eugene Bell Center for Regenerative Biology and Tissue Engineering. The ultimate goals are to determine what goes wrong with neurons after injury and during disease, and to determine how to correct these deficits in order to restore normal nervous system functions.
Unlike humans, the lamprey has an extraordinary capacity to regenerate its nervous system. If a lamprey’s spinal cord is severed, it can regenerate the damaged nerve cells and be swimming again in 10-12 weeks.
Morgan and her collaborators at MBL, Ona Bloom and Joseph Buxbaum, have been studying the lamprey’s recovery from spinal cord injury since 2009. The lamprey has large, identified neurons in its brain and spinal cord, making it an excellent model to study regeneration at the single cell-level. Now, the lamprey’s genomic information gives them a whole new “toolkit” for understanding its regenerative mechanisms, and for comparing aspects of its physiology, such as inflammation response, to that of humans.
The lamprey genome project was accomplished by a consortium of 59 researchers led by Weiming Li of Michigan State University and Jeramiah Smith of the University of Kentucky. The MBL scientists’ contribution focused on neural aspects of the genome, including one of the project’s most intriguing findings.
Lampreys, in contrast to humans, don’t have myelin, an insulating sheath around neurons that allows faster conduction of nerve impulses. Yet the consortium found genes expressed in the lamprey that are normally expressed in myelin. In humans, myelin-associated molecules inhibit nerves from regenerating if damaged. “A lot of the focus of the spinal cord injury field is on neutralizing those inhibitory molecules,” Morgan says.
"So there is an interesting conundrum," Morgan says. "What are these myelin-associated genes doing in an animal that doesn’t have myelin, and yet is good at regeneration? It opens up a new and interesting set of questions, " she says. Addressing them could bring insight to why humans lost the capacity for neural regeneration long ago, and how this might be restored.
At present, Morgan and her collaborators are focused on analyzing which genes are expressed and when, after spinal cord injury and regeneration. The whole-genome sequence gives them an invaluable reference for their work.