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Neurology Today:
doi: 10.1097/01.NT.0000452480.21578.51
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NIH Plans 12-Year, $4.5 Billion Effort to Map Brain Connections and Neurochemical Processes

Samson, Kurt

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ARTICLE IN BRIEF

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In support of a federal initiative, the National Institutes of Health announced plans for an investment of $400 million each year for fiscal years 2016–2020, focusing on technology development and validation, and $500 million yearly for fiscal years 2020–2025 to focus on integrated applications of these technologies to make fundamental new discoveries about the brain.

The National Institutes of Health (NIH) has announced it will seek $4.5 billion for a major brain research initiative through fiscal year (FY) 2025 to develop, validate, and integrate new technologies to map neuronal circuits, and measure fluctuating electrical and chemical activity within and between such circuits, toward a better understanding of human cognition, and how related problems contribute to neurological and psychiatric disorders.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) working group presented its final report to the Advisory Committee to the Director of NIH on June 5. The committee enthusiastically endorsed it and NIH Director Francis Collins, MD, PhD, accepted the report in its entirety, calling the plan “bold and game changing.”

The report outlines an investment of $400 million each year for fiscal years 2016–2020, focusing on technology development and validation, and $500 million yearly for fiscal 2020–2025 to focus on integrated applications of these technologies to make fundamental new discoveries about the brain.

The working group emphasized that its cost estimates assume that the budget for the BRAIN initiative will “supplement, not supplant,” NIH's existing investment in basic, translational, and clinical neuroscience research.

“While these estimates are provisional and subject to congressional appropriations, they represent a realistic estimate of what will be required for this moon shot initiative,” Dr. Collins said in a statement.

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The BRAIN Initiative is a joint project of the NIH, the Defense Advanced Research Projects Agency (DARPA) of the U.S. Department of Defense, the National Science Foundation (NSF), and the Food and Drug Administration (FDA).

An interim report released in September 2013 called for an investment of $40 million for fiscal year 2014, and President Obama has requested $100 million for NIH's component of the BRAIN project in his fiscal year 2015 budget. In December 2013, NIH announced six funding opportunities in response to high priority areas identified by the BRAIN Working Group's interim report.

The report set seven primary research goals, and seven core principles to guide research, including pursuing human studies and non-human models at the same time. [See “BRAIN's Primary Goals and Principles.”]

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FUNDING DECISIONS IN SEPTEMBER

Story C. Landis, PhD, director of the National Institute of Neurological Disorders and Stroke (NINDS), told Neurology Today in a telephone interview that the NIH had set aside $40 million to launch the BRAIN initiative in FY14. In December 2013, NIH issued six Requests For Applications (RFAs) based on recommendations in the BRAIN working group's interim report. Over 300 applications were received in response to the RFAs and they will be reviewed this month, she said.

Decisions on the most meritorious proposals will be made so that “the first $40 million will be out the door this September.”

With the final report in hand, the NIH will begin to plan the next set of initiatives, Dr. Landis said. One of the first steps will be to for NIH to look at its current research portfolio.

“It is possible that we are already funding projects in some of the high-priority areas identified in the new set of recommendations,” she explained. “For example, we already have made investments in MRI research so we determine where more research is needed. We will also determine what contributions are being made by the private sector.”

As an example, she cited Howard Hughes Medical Institute investigators working at Janelia Farm who have made “great progress” in developing calcium indicator dyes to track neuronal activity.

NSF's role will be in funding multidisciplinary fundamental basic research, she said, while DARPA is interested in creating new treatments that can be ready to use within five years.

“DARPA is milestone-driven and looking at research on treating mental illness, as well as traumatic brain injuries and post-traumatic stress syndrome, especially in veterans,” Dr. Landis said. “People sometimes say that NIH research takes too long to reach patients, but DARPA starts out aiming at human applications. FDA is the newest partner and will pay attention to research relevant to new treatments.”

She noted that there has been a lot of communication between NSF, DARPA, and NIH, and representatives from each organization attended each workshop during the BRAIN initiative report's development.

In addition to the $40 million NIH contribution to the BRAIN initiative for FY 2014, DARPA will spend $50 million, and the NSF $20 million. Private organizations are also contributing, including $60 million from the Allen Institute for Brain Science, $30 million from the Howard Hughes Medical Institute, $28 million from the Salk Institute for Biological Studies, and $4 million from The Kavli Foundation.

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FUNDING NEW TOOLS

Before the announcement, some investigators had expressed concern about the level of national commitment and funding to support the initiative. But Alzheimer's researchers told Neurology Today that the new announcement was welcome news.

David A. Wolk, MD, an assistant professor of neurology and assistant director of the Penn Memory Center at the University of Pennsylvania Perelman School of Medicine in Philadelphia, said the project will help speed collaborative cross-discipline discoveries about the aging brain and cognitive and neurodegenerative issues.

“I think this is an exciting move, and having this amount of funding available for new research should act as an accelerant for new investigations in in conditions which affect cognition and behavior, particularly Alzheimer's disease and other neurodegenerative disorders, as well as normal aging.”

BRAIN's focus on developing newer technologies is also very welcome, he added. Developing new technologies is fundamental if research is to move forward in these disorders and our understanding of the brain more generally, he said.

“Better tools for studying brain function at the molecular, neurotransmitter, and neuronal level integrated with tools for characterizing higher order networks is an important next step, especially if we are able to develop technologies that can do so in living persons with and without disease. This call for combining different resolutions of inquiry in brain research is to be applauded and new tools are on the cusp of being developed, which the additional funding will help speed along. I really appreciate that the report takes a ground-up perspective on these technologies rather than from the top down,” he told Neurology Today in a telephone interview.

“This is an important time to pursue research opportunities for Alzheimer's disease and other neurodegenerative disorders associated with aging,” commented Gary Small, MD, the Parlow-Solomon professor on aging at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), and director of the UCLA Longevity Center.

“We have been focusing on amyloid-beta treatments without much success. Currently these treatments are now targeting people at risk for the disease so there may be a place for this approach early in the disease course,” he told Neurology Today in a telephone interview.

“We need ways to diversify our research investment portfolio, so why not get started on taking a bigger picture of the human brain? Like the Human Genome Project, these big research undertakings always seem daunting and risky at first, but often pan out with important discoveries.”

He said he is concerned that the human brain is so complicated that a major project looking at all of the connections and processes in the brain may be too ambitious at the outset.

“We may be going after too much — perhaps a more focused approach is more practical,” Dr. Small said.

He added that even small discoveries can lead to huge leaps in understanding disease processes and possible treatments to explore.

“The kind of research I do is not so large in scope,” Dr. Small continued. “I break things down into very specific pursuits, especially in Alzheimer's disease. Combining data from different disciplines, like neuroimaging and genetics, can lead to greater understanding of the disease.”

One important aspect of setting aside this much money to study the brain over the next decade is that it should help unify researchers from different disciplines and provide an incentive for more joint collaborations, according to Dr. Small.

“We need to incentivize scientists and provide enough money for this research. That is the only way to get the best and brightest minds focused on finding answers. We have made tremendous progress against cancer, heart disease and HIV/AIDs, but the brain is the final frontier. What good is living to be 130 or 150 years old if your cognitive ability is impaired in half that time?”

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BRAIN'S PRIMARY GOALS AND PRINCIPLES

The new report set seven primary research goals, including:

  • Identifying and providing experimental access to the different brain cell types to determine their roles in health and disease;
  • Generating circuit diagrams that vary in resolution from synapses to the whole brain;
  • Producing a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity;
  • Linking brain activity to behavior with precise interventional tools that change neural circuit dynamics;
  • Producing conceptual foundations for understanding the biological basis of mental processes through development of new theoretical and data analysis tools;
  • Developing innovative technologies to understand the human brain and treat its disorders; and,
  • Creating and supporting integrated brain research networks; and integrating new technological and conceptual approaches produced in the other goals to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception, and action in health and disease.

The report also establishes seven “core” principles that will be followed, including:

  • Pursuing human studies and non-human models in parallel;
  • Crossing boundaries in interdisciplinary collaborations;
  • Integrating spatial and temporal scales;
  • Establishing platforms for preserving and sharing data;
  • Validating and disseminating technology;
  • Consideration of ethical implications of neuroscience research; and,
  • Creating mechanisms to ensure accountability to the NIH, the taxpayer, and the community of basic, translational, and clinical neuroscientists.
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LINK UP FOR MORE INFORMATION

•. The BRAIN Initiative Report — BRAIN 2025: A Scientific Vision: http://bit.ly/brainreport

•. Neurology Today: “A $100 million brain research initiative gets the presidential nod”: http://bit.ly/NT-brain

Wolters Kluwer Health | Lippincott Williams & Wilkins

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