Neuroscience  

Noninvasive brain scans have led to basic science discoveries about the human brain, but they've had only limited impacts on people's day-to-day lives. A number of recent studies showing that brain imaging can help predict an individual's future learning, criminality, health-related behaviors, and response to drug or behavioral treatments.

Noninvasive brain scans, such as functional magnetic resonance imaging (FMRI), have led to basic science discoveries about the human brain, but they've had only limited impacts on people's day-to-day lives. A review article published in the journal Neuron, however, highlights a number of recent studies showing that brain imaging can help predict an individual's future learning, criminality, health-related behaviors, and response to drug or behavioral treatments. The technology may offer opportunities to personalize educational and clinical practices.

"We often wait for failure, in school or in mental health, to prompt attempts to help, but by then a lot of harm has occurred. If we can use neuroimaging to identify individuals at high risk for future failure, we may be able to help those individuals avoid such failure altogether."

Dr. John Gabrieli of the Massachusetts Institute of Technology and his colleagues describe the predictive power of brain imaging across a variety of different future behaviors, including infants' later performance in reading, students' later performance in math, criminals' likelihood of becoming repeat offenders, adolescents' future drug and alcohol use, and addicts' likelihood of relapse.

"Presently, we often wait for failure, in school or in mental health, to prompt attempts to help, but by then a lot of harm has occurred," says Dr. Gabrieli. "If we can use neuroimaging to identify individuals at high risk for future failure, we may be able to help those individuals avoid such failure altogether."

Prior to treatment, patients with social anxiety disorder who exhibited greater posterior activation (left) for angry relative to neutral facial expressions had a better clinical response to cognitive behavioral therapy than patients who exhibited lesser activation (right)

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In particular, Gabrieli focuses on education as he believes brain imaging might help teachers identify those kids who will struggle when learning to read or do math. “Current behavioral testing is pretty good at identifying which children are at potential risk, but it’s still too hit-and-miss to trigger serious help (about half of children who look to be at potential risk turn out not to be at true risk),” he told Medical Daily. “Also, I can imagine that more knowledge from brain-informed outcomes might lead to new kinds of behavioral testing that could be more readily used in schools.”

The study authors also point to the clear ethical and societal issues that are raised by studies attempting to predict individuals' behavior. "Because of their biological nature, brain measures can be overly valued and potentially divert public and scientific interest in behavioral and social factors," they write.

"We will need to make sure that knowledge of future behavior is used to personalize educational and medical practices, and not be used to limit support for individuals at higher risk of failure," says Dr. Gabrieli. "For example, rather than simply identifying individuals to be more or less likely to succeed in a program of education, such information could be used to promote differentiated education for those less likely to succeed with the standard education program."

SOURCE  Cell Press via EurekAlert

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 Brain Imaging  

A team of scientists has developed an entirely non-invasive technique that provides a view of blood flow in the brain. The tool could provide powerful insights into strokes and possibly Alzheimer's disease.

Some of the most damaging brain diseases can be traced to irregular blood delivery in the brain. Now, Stanford University chemists have employed lasers and carbon nanotubes to capture an unprecedented look at blood flowing through a living brain.

The technique was developed for mice but could one day be applied to humans, potentially providing vital information in the study of stroke and migraines, and perhaps even Alzheimer's and Parkinson's diseases. The work is described in the journal Nature Photonics.

Current procedures for exploring the brain in living animals face significant trade-offs. Surgically removing part of the skull offers a clear view of activity at the cellular level. But the trauma can alter the function or activity of the brain or even stimulate an immune response. Meanwhile, non-invasive techniques such as CT scans or MRI visualize function best at the whole-organ level; they cannot visualize individual vessels or groups of neurons.

The first step of the new technique, called near infrared-IIa imaging, or NIR-IIa, calls for injecting water-soluble carbon nanotubes into a live mouse's bloodstream. The researchers then shine a near-infrared laser over the rodent's skull.

"The NIR-IIa light can pass through intact scalp skin and skull and penetrate millimeters into the brain, allowing us to see vasculature in an almost non-invasive way."

The light causes the specially designed nanotubes to fluoresce at wavelengths of 1,300-1,400 nanometers; this range represents a sweet spot for optimal penetration with very little light scattering. The fluorescing nanotubes can then be detected to visualize the blood vessels' structure.

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Amazingly, the technique allows scientists to view about three millimeters underneath the scalp and is fine enough to visualize blood coursing through single capillaries only a few microns across, said senior author Hongjie Dai, a professor of chemistry at Stanford. Furthermore, it does not appear to have any adverse affect on innate brain functions.

"The NIR-IIa light can pass through intact scalp skin and skull and penetrate millimeters into the brain, allowing us to see vasculature in an almost non-invasive way," said first author Guosong Hong, who conducted the research as a graduate student in Dai's lab and is now a postdoctoral fellow at Harvard. "All we have to remove is some hair."

The technique could eventually be used in human clinical trials, Hong said, but will need to be tweaked. First, the light penetration depth needs to be increased to pass deep into the human brain. Second, injecting carbon nanotubes needs approval for clinical application; the scientists are currently investigating alternative fluorescent agents.

For now, though, the technique provides a new technique for studying human cerebral-vascular diseases, such as stroke and migraines, in animal models. Other research has shown that Alzheimer's and Parkinson's diseases might elicit – or be caused in part by – changes in blood flow to certain parts of the brain, Hong said, and NIR-IIa imaging might offer a means of better understanding the role of healthy vasculature in those diseases.

"We could also label different neuron types in the brain with bio-markers and use this to monitor how each neuron performs," Hong said. "Eventually, we might be able to use NIR-IIa to learn how each neuron functions inside of the brain."




SOURCE  Stanford

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 Neuroscience  

Scientists have improved on their original technique for peering into the intact brain, making it more reliable and safer. The results could help scientists unravel the inner connections of how thoughts, memories or diseases arise.

Last year Karl Deisseroth, a Stanford professor of bioengineering and of psychiatry and behavioral sciences, announced a new way of peering into a brain – removed from the body – that provided spectacular fly-through views of its inner connections. Since then laboratories around the world have begun using the technique, called CLARITY, with some success, to better understand the brain's wiring.

However, Deisseroth said that with two technological fixes CLARITY could be even more broadly adopted. The first problem was that laboratories were not set up to reliably carry out the CLARITY process. Second, the most commonly available microscopy methods were not designed to image the whole transparent brain. "There have been a number of remarkable results described using CLARITY," Deisseroth said, "but we needed to address these two distinct challenges to make the technology easier to use."

In a recent Nature Protocols paper, Deisseroth presented solutions to both of those bottlenecks. "These transform CLARITY, making the overall process much easier and the data collection much faster," he said. He and his co-authors, including postdoctoral fellows Raju Tomer and Li Ye and graduate student Brian Hsueh, anticipate that even more scientists will now be able to take advantage of the technique to better understand the brain at a fundamental level, and also to probe the origins of brain diseases.

"This work shares the spirit of the BRAIN Initiative goal of building new technologies to understand the brain – including the human brain."

This paper may be the first to be published with support of the White House BRAIN Initiative, announced last year with the ambitious goal of mapping the brain's trillions of nerve connections and understanding how signals zip through those interconnected cells to control our thoughts, memories, movement and everything else that makes us us.

"This work shares the spirit of the BRAIN Initiative goal of building new technologies to understand the brain – including the human brain," said Deisseroth, who is also a Stanford Bio-X affiliated faculty member.

Eliminating fat

When you look at the brain, what you see is the fatty outer covering of the nerve cells within, which blocks microscopes from taking images of the intricate connections between deep brain cells. The idea behind CLARITY was to eliminate that fatty covering while keeping the brain intact, complete with all its intricate inner wiring.

The way Deisseroth and his team eliminated the fat was to build a gel within the intact brain that held all the structures and proteins in place. They then used an electric field to pull out the fat layer that had been dissolved in an electrically charged detergent, leaving behind all the brain's structures embedded in the firm water-based gel, or hydrogel. This is called electrophoretic CLARITY.

The electric field aspect was a challenge for some labs. "About half the people who tried it got it working right away," Deisseroth said, "but others had problems with the voltage damaging tissue." Deisseroth said that this kind of challenge is normal when introducing new technologies. When he first introduced optogenetics, which allows scientists to control individual nerves using light, a similar proportion of labs were not initially set up to easily implement the new technology, and ran into challenges.

To help expand the use of CLARITY, the team devised an alternate way of pulling out the fat from the hydrogel-embedded brain – a technique they call passive CLARITY. It takes a little longer, but still removes all the fat, is much easier and does not pose a risk to the tissue. "Electrophoretic CLARITY is important for cases where speed is critical, and for some tissues," said Deisseroth, who is also the D.H. Chen Professor. "But passive CLARITY is a crucial advance for the community, especially for neuroscience." Passive CLARITY requires nothing more than some chemicals, a warm bath and time.

Many groups have begun to apply CLARITY to probe brains donated from people who had diseases like epilepsy or autism, which might have left clues in the brain to help scientists understand and eventually treat the disease. But scientists, including Deisseroth, had been wary of trying electrophoretic CLARTY on these valuable clinical samples with even a very low risk of damage. "It's a rare and precious donated sample, you don't want to have a chance of damage or error," Deisseroth said. "Now the risk issue is addressed, and on top of that you can get the data very rapidly."

Fast CLARITY imaging in color

The second advance had to do this rapidity of data collection. In studying any cells, scientists often make use of probes that will go into the cell or tissue, latch onto a particular molecule, then glow green, blue, yellow or other colors in response to particular wavelengths of light. This is what produces the colorful cellular images that are so common in biology research. Using CLARITY, these colorful structures become visible throughout the entire brain, since no fat remains to block the light.

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But here's the hitch. Those probes stop working, or get bleached, after they've been exposed to too much light. That's fine if a scientist is just taking a picture of a small cellular structure, which takes little time. But to get a high-resolution image of an entire brain, the whole tissue is bathed in light throughout the time it takes to image it point by point. This approach bleaches out the probes before the entire brain can be imaged at high resolution.

The second advance of the new paper addresses this issue, making it easier to image the entire brain without bleaching the probes. "We can now scan an entire plane at one time instead of a point," Deisseroth said. "That buys you a couple orders of magnitude of time, and also efficiently delivers light only to where the imaging is happening." The technique is called light sheet microscopy and has been around for a while, but previously didn't have high enough resolution to see the fine details of cellular structures. "We advanced traditional light sheet microscopy for CLARITY, and can now see fine wiring structures deep within an intact adult brain," Deisseroth said. His lab built their own microscope, but the procedures are described in the paper, and the key components are commercially available. Additionally, Deisseroth's lab provides free training courses in CLARITY, modeled after his optogenetics courses, to help disseminate the techniques.

Brain imaging to help soldiers

The BRAIN Initiative is being funded through several government agencies including the Defense Advanced Research Projects Agency (DARPA), which funded Deisseroth's work through its new Neuro-FAST program. Deisseroth said that like the National Institute of Mental Health (NIMH, another major funder of the new paper), DARPA "is interested in deepening our understanding of brain circuits in intact and injured brains to inform the development of better therapies." The new methods Deisseroth and his team developed will accelerate both human- and animal-model CLARITY; as CLARITY becomes more widely used, it will continue to help reveal how those inner circuits are structured in normal and diseased brains, and perhaps point to possible therapies.

Other arms of the BRAIN Initiative are funded through the National Science Foundation (NSF) and the National Institutes of Health (NIH). A working group for the NIH arm was co-led by William Newsome, professor of neurobiology and director of the Stanford Neurosciences Institute, and also included Deisseroth and Mark Schnitzer, associate professor of biology and of applied physics. That group recently recommended a $4.5 billion investment in the BRAIN Initiative over the next 12 years, which NIH Director Francis Collins approved earlier this month.




SOURCE  Stanford University

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 Brain Imaging  

Bridging the worlds of neuroscience and high-tech virtual realty, the Glass Brain, a project of the new Neuroscape Lab at the University of California San Francisco may open up new insights into the complicated mechanisms of the brain.

Researchers have developed a new way to explore the human brain through virtual reality. The system, called Glass Brain, initiated by Philip Rosedale, creator of the famous game Second Life, and Adam Gazzaley, a neuroscientist at the University of California San Francisco, combines brain scanning, brain recording and virtual reality to allow a user to journey through a person’s brain in real-time.

 For a recent demonstration at the South by Southwest (SXSW) Interactive festival in Austin, Texas, Rosedale made his wife a cap studded with electroencephalogram (EEG) electrodes that measure differences in electric potential in order to record brain activity, while he wore a virtual reality headset to explore her brain in 3D, as flashes of light displayed her brain activity from the EEG.

The Glass Brain didn’t actually show what Rosedale’s wife was thinking, but Gazzaley’s team ultimately hopes to get closer to decoding brain signals and displaying them using the virtual reality system.

"High-tech innovations take a decade to move beyond the entertainment industry and reach science and medicine. That needs to change."

Gazzaley and Rosedale are hoping to paint a fuller picture of what is happening in the minds and bodies of those suffering from brain disease with the new Neuroscape lab, which bridges the worlds of neuroscience and high-tech.

In the Neuroscape lab, wireless and mobile technologies set research participants free to move around and interact inside 3D environments, while scientists make functional recordings with an array of technologies. Gazzaley hopes this will bring his field closer to understanding how complex neurological and psychiatric diseases really work and help doctors like him re-purpose technologies built for fitness or fun into targeted therapies for their patients.

“I want us to have a platform that enables us to be more creative and aggressive in thinking how software and hardware can be a new medicine to improve brain health,” said Gazzaley, an associate professor of neurology, physiology and psychiatry and director of the UCSF Neuroscience Imaging Center. “Often, high-tech innovations take a decade to move beyond the entertainment industry and reach science and medicine. That needs to change.”

Image Source - Neuroscape Lab

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GlassBrain, a creation of the Neuroscape lab, creates vivid, color visualizations of the structures of the brain and the white matter that connects them, as they pulse with electrical activity in real time.

Whereas ordinary EEG recordings look like wavy horizontal lines, but GlassBrain turns the data into bursts of rhythmic activity that speed along golden spaghetti-like connections threading through a glowing, multi-colored glass-like image of a brain. Gazzaley is now looking at how to feed this information back to his subjects, for example by using the data from real-time EEG to make video games that adapt as people play them to selectively challenge weak brain processes.

Gazzaley has already used the technology to image the brain of former Grateful Dead drummer Mickey Hart as he plays a hypnotic, electronic beat on a Roland digital percussion device with NeuroDrummer, a game the Gazzaley Lab is designing to enhance brain function through rhythmic training. Hart, whose brain is healthy, is collaborating with Gazzaley to develop the game and performed on NeuroDrummer while immersed in virtual reality on an Oculus Rift at the Neuroscape lab opening on March 5.

The Neuroscape lab will be available to all UCSF researchers who study the brain. Gazzaley ultimately hopes it will aid in the development of therapies to treat diseases as various as Alzheimer’s, post-traumatic stress disorder, attention deficit and hyperactivity disorder, schizophrenia, autism, depression and multiple sclerosis.


SOURCE  UCSF

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 Neuroscience  

For the first time, neuroscientists have systematically mapped the white matter "scaffold" of the human brain, the critical communications network that supports brain function.

For the first time, neuroscientists have systematically identified the white matter "scaffold" of the human brain, the critical communications network that supports brain function.

Their work, published in the open-source journal Frontiers in Human Neuroscience, has major implications for understanding brain injury and disease. By detailing the connections that have the greatest influence over all other connections, the researchers offer not only a landmark first map of core white matter pathways, but also show which connections may be most vulnerable to damage.

"We coined the term white matter 'scaffold' because this network defines the information architecture which supports brain function," said senior author John Darrell Van Horn of the USC Institute for Neuroimaging and Informatics and the Laboratory of Neuro Imaging at USC.

"While all connections in the brain have their importance, there are particular links which are the major players," Van Horn said.

Graphical representation of human brain connectivity scaffold.
Image Source -  USC Institute for Neuroimaging and Informatics

Using MRI data from a large sample of 110 individuals, lead author Andrei Irimia, also of the USC Institute for Neuroimaging and Informatics, and Van Horn systematically simulated the effects of damaging each white matter pathway.

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They found that the most important areas of white and gray matter don't always overlap. Gray matter is the outermost portion of the brain containing the neurons where information is processed and stored. Past research has identified the areas of gray matter that are disproportionately affected by injury.

But the current study shows that the most vulnerable white matter pathways – the core "scaffolding" – are not necessarily just the connections among the most vulnerable areas of gray matter, helping explain why seemingly small brain injuries may have such devastating effects.

"Sometimes people experience a head injury which seems severe but from which they are able to recover. On the other hand, some people have a seemingly small injury which has very serious clinical effects," says Van Horn, associate professor of neurology at the Keck School of Medicine of USC. "This research helps us to better address clinical challenges such as traumatic brain injury and to determine what makes certain white matter pathways particularly vulnerable and important."

The researchers compare their brain imaging analysis to models used for understanding social networks. To get a sense of how the brain works, Irimia and Van Horn did not focus only on the most prominent gray matter nodes – which are akin to the individuals within a social network. Nor did they merely look at how connected those nodes are.

Image Source -  USC Institute for Neuroimaging and Informatics

Rather, they also examined the strength of these white matter connections, i.e. which connections seemed to be particularly sensitive or to cause the greatest repercussions across the network when removed. Those connections which created the greatest changes form the network "scaffold."

"Just as when you remove the internet connection to your computer you won't get your email anymore, there are white matter pathways which result in large scale communication failures in the brain when damaged," Van Horn said.

When white matter pathways are damaged, brain areas served by those connections may wither or have their functions taken over by other brain regions, the researchers explain. Irimia and Van Horn's research on core white matter connections is part of a worldwide scientific effort to map the 100 billion neurons and 1,000 trillion connections in the living human brain, led by the Human Connectome Project and the Laboratory of Neuro Imaging at USC.

Irimia notes that, "these new findings on the brain's network scaffold help inform clinicians about the neurological impacts of brain diseases such as multiple sclerosis, Alzheimer's disease, as well as major brain injury. Sports organizations, the military and the US government have considerable interest in understanding brain disorders, and our work contributes to that of other scientists in this exciting era for brain research."


SOURCE  University of Southern California

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 Neuroscience  

Patients with the most common form of focal epilepsy have widespread, abnormal connections in their brains that could provide clues toward diagnosis and treatment, according to a new study.

P atients with the most common form of focal epilepsy have widespread, abnormal connections in their brains that could provide clues toward diagnosis and treatment, according to a new study published online in the journal Radiology.

Temporal lobe epilepsy is characterized by seizures emanating from the temporal lobes, which sit on each side of the brain just above the ear. Previously, experts believed that the condition was related to isolated injuries of structures within the temporal lobe, like the hippocampus. But recent research has implicated the default mode network (DMN), the set of brain regions activated during task-free introspection and deactivated during goal-directed behavior. The DMN consists of several hubs that are more active during the resting state.

To learn more, researchers performed diffusion tensor imaging, a type of MRI that tracks the movement, or diffusion, of water in the brain's white matter, the nerve fibers that transmit signals throughout the brain. The study group consisted of 24 patients with left temporal lobe epilepsy who were slated for surgery to remove the site from where their seizures emanated. The researchers compared them with 24 healthy controls using an MRI protocol dedicated to finding white matter tracts with diffusion imaging at high resolution. The data was analyzed with a new technique that identifies and quantifies structural connections in the brain.

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Patients with left temporal lobe epilepsy exhibited a decrease in long-range connectivity of 22 percent to 45 percent among areas of the DMN when compared with the healthy controls.

"Using diffusion MRI, we found alterations in the structural connectivity beyond the medial temporal lobe, especially in the default mode network," said Steven M. Stufflebeam, M.D., from the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston.

In addition to reduced long-range connectivity, the epileptic patients had an 85 percent to 270 percent increase in local connectivity within and beyond the DMN. The researchers believe this may be an adaptation to the loss of the long-range connections.

"The increase in local connections could represent a maladaptive mechanism by which overall neural connectivity is maintained despite the loss of connections through important hub areas," Dr. Stufflebeam said.

The results are supported by prior functional MRI studies that have shown decreased functional connectivity in DMN areas in temporal lobe epilepsy. Researchers are not certain if the structural changes cause the functional changes, or vice versa.

"It's probably a breakdown of myelin, which is the insulation of neurons, causing a slowdown in the propagation of information, but we don't know for sure," Dr. Stufflebeam said.

Dr. Stufflebeam and colleagues plan to continue their research, using structural and functional MRI with electroencephalography and magnetoencephalography to track diffusion changes and look at real-time brain activity.


SOURCE  MedicalXpress

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