Author Insights: After a Year of Planning, Initiative to Probe the Brain Moving Forward

For its part in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the National Institutes of Health is initially focused on accelerating technology development to improve brain research. (Image: NIH)

For its part in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the National Institutes of Health is initially focused on accelerating technology development to improve brain research. (Image: NIH)

A major federally funded project designed to unlock the mysteries of the brain is under way and, after a year of planning, the initiative’s focus has begun to sharpen. A Viewpoint appearing today online in JAMA Neurology explains the intent of the project, the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which one day may give scientists and physicians insights to treat or prevent disease or illness stemming from brain malfunction.

The BRAIN Initiative, launched April 2, 2013, is a partnership with the National Institutes of Health (NIH), the National Science Foundation, the Defense Advanced Research Projects Agency, private foundations, and researchers. For fiscal year 2014, President Obama called for a total of $110 million to support the BRAIN Initiative. The NIH will receive $40 million and focus on several areas of research, such as generating a census of brain cell types, creating structural maps of the brain, and linking neuronal activity to behavior.

Coauthor of the Viewpoint, Cornelia I. Bargmann, PhD, an investigator with the Howard Hughes Medical Institute, The Rockefeller University, New York City, talked with news@JAMA about the BRIAN Initiative.

news@JAMA: Why study the brain?

Dr Bargmann: The goal of the initiative is to understand how the brain functions as an organized unit, to develop a foundation of knowledge that will ultimately allow us to understand which circuits go wrong for different disorders, or how different kinds of defects spread from one initial insult to the brain. We want to really understand the brain as a whole and not just individual pieces.

news@JAMA: Why is this important?

Dr Bargmann: Some kinds of dysfunction of the brain, such as autism, schizophrenia, depression, Alzheimer disease, traumatic brain injury, or post-traumatic stress disorder, will affect 1 in 3 American at some point of their lives. Although they have different causes, they are fundamentally associated with defects in brain function.

news@JAMA: When can we expect results that directly improve an individual’s health?

Dr Bargmann: It’s important to not raise false hopes and make empty promises. The BRAIN Initiative is intended to stimulate technology development and put tools in the hands of scientists and physician scientists to make discoveries that can lead to the treatment or prevention of diseases such as Alzheimer disease.

It’s the first step in building the foundational knowledge. Look at cancer treatment in the past few decades. We can see where science in the 1980s led to new therapies only approved in the late 1990s, such as Gleevec, and only now is it leading to a large armamentarium of anticancer treatments.

news@JAMA: What do you say to those who, when the BRAIN Initiative was announced, were saying the project lacked focus with no defined goals.

Dr Bargmann: When the Brain Initiative was first announced, it was pretty vague. But the NIH developed a year-long planning process to make the Brain Initiative more concrete. It’s trying to look at all the areas that contribute to our understanding of the working of the brain. The planning process hopefully identified what’s achievable, what’s ambitious, and what’s fantastical.

news@JAMA: Reading your Viewpoint, it seems you fully support the BRAIN Initiative.

Dr Bargmann: Everyone should be excited about the BRAIN Initiative. I’m a neuroscientist, and I think knowing how the brain works is the coolest thing we can know.

Author Insights: Neuroimaging for Headache is Overused and Provides Little Additional Benefit

Brian C. Callaghan, MD, MS, an assistant professor of neurology at the University of Michigan Health System in Ann Arbor, and colleagues suggest headache neuroimaging is common, costly, and overused. (Image: University of Michigan)

Brian C. Callaghan, MD, MS, an assistant professor of neurology at the University of Michigan Health System in Ann Arbor, and colleagues suggest headache neuroimaging is common, costly, and overused. (Image: University of Michigan)

Although most headaches are caused by benign conditions, sometimes they signal the presence of a more dangerous condition, such as a brain tumor or aneurysm. To determine if such a condition is present, a physician, often at the request of the patient, will order neuroimaging with computed tomography (CT) or magnetic resonance imaging (MRI).

But a research letter appearing Monday in JAMA Internal Medicine suggests neuroimaging for headache generally goes against current recommendations from multiple guidelines; is overused, costing the health system hundreds of millions of dollars; increases patient radiation exposure; and can detect incidental findings that lead to other tests and procedures for often benign conditions.

Using the National Ambulatory Medical Care Survey, the study authors found that from 2007 through 2010, there were 51.1 million adult headache visits, mostly to primary care physicians (54.8%); 88% were by patients younger than 65 years and 78% were by female patients. Neuroimaging occurred for 12.4% of all headache visits during that period, costing a total of $3.9 billion, and the use of neuroimaging for headaches has increased substantially in recent years, from 5.1% in 1995 to 14.7% in 2010.

Lead author Brian C. Callaghan, MD, MS, an assistant professor of neurology at the University of Michigan Health System in Ann Arbor, discusses his team’s findings.

news@JAMA: Why has the use of neuroimaging for routine headaches increased in recent years?

Dr Callaghan: My speculation is that imaging use in general has been increasing across the board as MRI and CT become more accessible. But the number one reason physicians give scans for headache is patient reassurance, not to detect a bad intracranial condition. The next reason is legal—physicians not willing to miss the very rare condition.

news@JAMA: Do reassurance and concerns about potential legal consequences have societal costs?

Dr Callaghan: The major problem is that we’re ordering lots of tests, and it’s a huge amount of money. Headache neuroimaging is one of the big-ticket items where we spend a lot of money, and we don’t get much bang for our buck.

news@JAMA: Why do patients seek reassurance, and is there a cost to seeking such reassurance?

Dr Callaghan: If you ask most patients who have had bad headaches why they want a scan, they would say that they worry about a brain tumor. But they don’t think about the other things that can harm them. They don’t appreciate some of the downstream consequences, like radiation exposure from CT or undergoing an MRI scan and getting a false-positive for something else that leads to more tests and procedures.

news@JAMA: How should physicians reassure patients who request imaging because they worry their headaches signal a serious condition?

Dr Callaghan: There are some circumstances where neuroimaging is warranted, but if the physician feels this is not one of those circumstances, he or she has to have a conversation with the patient to explain why the headaches are occurring and why an imaging test, with its potential side effects, is not warranted.

Poliolike Cases in California Under Investigations, But Appear Unlikely to Pose Public Health Threat

Unusual cases of poliolike illnesses in California have created a buzz, but experts and public health officials say they do not pose a public health threat. Image: Tagxedo

Unusual cases of poliolike illnesses in California have created a buzz, but experts and public health officials say they do not pose a public health threat. Image: Tagxedo

News about a poliolike illness detected in California has created quite a stir in the news media, but there is some disagreement about how concerning these rare cases are.

In the autumn of 2012, Keith Van Haren, MD, a pediatric neurologist at the Lucile Packard Children’s Hospital at Stanford University in California, and other neurologists across the state noticed an unusual trend: the emergence of several cases of sudden-onset paralysis in children who also had motor neuron injury. He and his colleagues normally can expect to see 1 such case a year, he said. But as he and his colleagues describe in an abstract released in February that will be presented at the American Academy of Neurology’s annual meeting in late April, 5 such cases were reported within a period of 18 months, including 2 that tested positive for human enterovirus 68. This virus has been linked to clusters of respiratory illness, and at least 1 case involving neurological symptoms had previously been reported. According to Van Haren, a total of 20 such cases have been detected in California in the past 18 months.

“The physician community is taking this very seriously, and is invested in figuring out the cause,” Van Haren cautioned. “But it remains rare.”

Benjamin Haynes, a Centers for Disease Control and Prevention (CDC) spokesperson, said the agency is closely monitoring the situation and has consulted with officials from the California Department of Public Health. But so far, it does not appear that the number of cases rise above the background rates of sudden-onset paralysis that would be expected in California in a given year, Haynes said. Acute flaccid paralysis can have a number of causes, including tick paralysis, Guillain-Barré syndrome, and botulism. However, it is not a condition physicians are required to report to the CDC, so the data are limited.

“At this time, CDC does not think the situation in California poses a public health threat, but we encourage parents to speak with their doctors or pediatricians if they have concerns,” Haynes said.

But Van Haren, who is accustomed to seeing patients with more typical presentations of acute paralysis, said he and his colleagues believe these cases are occuring more frequently than the baseline rate, and noted that there are no data on this particular subset of patients. Additionally, he said these patients are presenting with more severe disability and experiencing less recovery than would be expected with most cases of acute flaccid paralysis.

The California Department of Health has not found any common cause among the cases, but will continue to investigate, according to a statement from Gil Chavez, MD, MPH, Deputy Director of the Center for Infectious Disease and State Epidemiologist.

“BigBrain” Model Offers Microscopic Views of Human Brain

In the “BigBrain” research, investigators used a special tool called a microtome to cut sections from a preserved brain into 7404 slivers 20 m thick. (Image: Amunts, Zilles, Evans et al.)

In the “BigBrain” research, investigators used a special tool called a microtome to cut sections from a preserved brain into 7404 slivers 20 micrometers thick. (Image: Amunts, Zilles, Evans et al.)

Researchers have for the first time created a 3-dimensional (3-D) model of the human brain so precise that it could allow scientists to see microscopic details, such as single layers or sublayers of the cerebral cortex.

Currently used magnetic resonance imaging (MRI) has a spatial resolution of about 1 mm. But the new 3-D model exceeds that by about 50-fold, with a spatial resolution of 20 micrometers. “This allows us a completely new level of insight into the brain’s organization,” coauthor Alan Evans, PhD, of the Montreal Neurological Institute of McGill University in Canada, said during a teleconference describing the research. The project’s details are published online today in the journal Science.

The research team, led by Katrin Amunts, DrMed, director of the Institute of Neuroscience and Medicine at the Jülich Research Center in Germany, created the model using a deceased 65-year-old woman’s healthy brain. They sliced the brain into 7404 sections, each about as thick as a human hair. Digitized images of the histological sections generated a 1-TB dataset, which is more than 100 000 times larger than a typical MRI. The team has had to develop new software that enables them to probe such a vast amount of data.

“This… is big science comes to the brain,” Evans said. Hence, the model is dubbed “BigBrain.” The research is part of the European Brain Project, which intends to reconstruct the human brain in supercomputer models and simulations. In April, President Obama announced a $100 million US initiative to map the human brain.

BigBrain’s clinical applications include locating more precise targets for deep brain stimulation to treat Parkinson disease or Alzheimer disease, an approach currently in clinical trials. “This could serve as a new atlas for neurosurgery,” Amunts said. The model also could help researchers locate abnormalities in neurotransmitter receptors that may be linked with specific brain diseases.

Public access to the BigBrain dataset is being provided at no cost, with free registration at the CBRAIN portal.

Clot Removal Appears No Better Than Standard Therapy for Ischemic Stroke

A new study shows that invasive blood clot removal is no more effective than standard treatment for severe ischemic stroke, even in patients with more functional brain tissue. (Image: Donald Erickson/iStockphoto.com)

A new study shows that invasive blood clot removal is no more effective than standard treatment for severe ischemic stroke, even in patients with more functional brain tissue. (Image: Donald Erickson/iStockphoto.com

It seems logical that patients with more functional brain tissue after a severe ischemic stroke would reap greater benefits from removing the triggering clot than survivors with less viable tissue. But research presented today at the International Stroke Conference in Honolulu showed that clot removal was no more effective than standard antiplatelet therapy such as aspirin, even when researchers used brain scans to determine which patients with sufficient viable tissue might benefit from clot removal. Continue reading

Physicians May Make a Difference in Concussion Surveillance

Physicians and other independent observers may help improve concussion surveillance during ice hockey and other athletic events, according to a new study. (Image: Christopher O Driscoll/iStockphoto.com)

Physicians and other independent observers may help improve concussion surveillance during ice hockey and other athletic events, according to a new study. (Image: Christopher O Driscoll/iStockphoto.com)

A small study of college ice hockey players in Canada in which physicians and other independent observers watched games from the stands and evaluated injured players indicates that college hockey players’ concussion rates there may have improved over the past 2 years but remain vastly underreported.

Appearing today in Neurosurgical Focus, a peer-reviewed online journal, the study followed up 20 men and 25 women who played ice hockey for college teams in Canada during the 2011-2012 season. All players underwent comprehensive preseason neuropsychological testing and magnetic resonance imaging (MRI) scans. At each game, a sports medicine physician and an independent observer watched the action from seats positioned higher than rink level to get a clear view of injuries. Continue reading

Venous Problems Not Linked With Multiple Sclerosis, Study Finds

New research provides evidence that reinforces skepticism about the idea that venous problems contribute to multiple sclerosis, a disease characterized by the demyelination of the nerves. (Image: JAMA, ©AMA)

A new imaging study has found no link between venous abnormalities in the central nervous system and multiple sclerosis (MS). The findings, which were published in the journal Radiology, add to a growing body of evidence suggesting that a risky surgical treatment targeting veins in the neck is unlikely to help patients with the disorder.

The experimental surgical procedure has become sought by some MS patients wanting relief from the effects of the neurodegenerative disorder. The rationale for the surgery derives from a hypothesis (advanced by scientist Paolo Zamboni, MD, of the University of Ferrara in Italy) that patients with MS have chronic cerebrospinal venous insufficiency (CCSVI), a narrowing of certain veins in the neck and chest that are purported to cause or contribute to the progression of MS by compromising blood drainage from the brain and upper spinal cord, leading to a build-up of iron and inflammation in the central nervous system. But there has been growing concern about the risks associated with the procedure, as well as the lack of strong evidence supporting its benefits. Earlier this year, the US Food and Drug Administration warned patients that this unproven treatment has resulted in serious injuries and death. Continue reading