Brain Mapping Initiative Moving Forward

Megan Brooks

May 08, 2013

Work has begun in earnest on the ambitious task of mapping the brain's roughly 100 billion neurons and the trillions of connections in between, then figuring out how it all drives thinking and behavior — hopefully, illuminating common neurologic diseases in the process.

On April 2, as reported by Medscape Medical News, President Barack Obama unveiled details of the BRAIN Initiative, a large-scale effort to map brain activity, and announced an initial government investment of $100 million in FY 2014.

"Our most immediate goal is to organize ourselves," said William Newsome, PhD, the Stanford University neurobiologist who is co-chairing the working group of 15 scientists with Cornelia "Cori" Bargmann, PhD, neurobiologist from The Rockefeller University in New York, New York.

The duo of Dr. Newsome and Dr. Bargmann are perfect co-chairs, Story C. Landis, PhD, director of the National Institute of Neurological Disorders and Stroke, told Medscape Medical News.

"They both work on neural circuits. Cori works on neural circuits in the nematode — 302 neurons that keep the little worm functioning — and Bill Newsome has worked on neural circuits in primates, so they span the range of neural circuits," she said.

Dr. William Newsome

Dr. Newsome told Medscape Medical News the working group officially received their charge from National Institutes of Health (NIH) Director Francis Collins, MD, PhD, in an April 16 teleconference.

"The important background for the charge is the scientific understanding that mental states such as perceptions, thoughts, and actions arise from dynamic patterns of brain activity that are distributed across many brain circuits and structures," he said. "By exploring these patterns of activity, and by using simpler nervous systems as models for incisive experimental investigation, we can develop a deeper understanding of how the brain produces complex behaviors."

Dr. Story C. Landis


Ethical Concerns?

Dr. Landis said to address possible ethical issues that have been raised with the BRAIN Initiative and more generally with neuroscience research, "the President's Commission for the Study of Biomedical Issues will be engaged, but it's not exactly clear how yet. Everybody wonders about mind control, especially if you talk about nanotechnology, but that is obviously not happening."

Everybody wonders about mind control, especially if you talk about nanotechnology, but that is obviously not happening. Dr. Story C. Landis

Dr. Newsome said the long-term goal of the BRAIN Initiative is to lay a foundation of scientific knowledge that will lead to "real breakthroughs in understanding and treating neurological and psychiatric disease. These breakthroughs, for which we all yearn deeply, cannot be guaranteed on any specific timeline."

Nonetheless, the working group is in the process of considering timelines for achieving specific scientific goals, "although these will of necessity be tentative," Dr. Newsome said. "As Niels Bohr famously said, 'Prediction is always difficult, especially when it involves the future'."

A preliminary report from the working group is due to the NIH by September 2013 and a final report by June 2014. "The goal is that in September there will be preliminary recommendations to the NIH for initiatives that would be funded with 2014 dollars. This is being fast-tracked," Dr. Landis said.

The group will hold a series of workshops over the late spring and summer to review the latest relevant technology developments for the project. Dr. Newsome said the time is right for this undertaking because of the ongoing revolution in technologies available for studying the brain.  

"New innovations in optical recording of neural activity make it possible for researchers to simultaneously monitor the activity of hundreds of neurons — soon to be thousands, and perhaps tens of thousands," he told Medscape Medical News.

For example, he said a technique called optogenetics lets scientists control how neurons fire in live animals and reveals how the neurons affect behavior. The technique was pioneered by his colleague at Stanford, Karl Deisseroth, MD, PhD, professor of bioengineering and of psychiatry and behavioral sciences, who was 1 of the 13 scientists to propose the brain activity map initiative in an article in Science in March.

In 2010, optogenetics was highlighted in the article "Insights of the Decade" in the journal Science.

Dr. Deisseroth and colleagues at Stanford also developed an imaging technique called CLARITY, which makes the brain transparent, allowing scientists to see inside. They described the technique in Nature April 10.

CLARITY stands for Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue-hYdrogel and works by replacing the lipid that normally holds the brain's components in place with a clear gel. The result is tissue that is transparent and permeable, making it possible to image intact brain with high resolution down to the level of cells and molecules without the need for slicing. The technique has been used to date mostly with intact postmortem mouse brains but has also been used with a human brain.

Dr. Newsome said the CLARITY method is nothing less than "astounding." But these techniques are just the beginning; "more technological innovations are on the horizon," he said. "All of these advances create research possibilities that were barely imaginable 10 years ago. In many cases, experimentalists will have to completely rethink what questions we ask, and what experimental designs will enable us to get at those questions."

He noted that new theoretical and computational approaches will be necessary to make sense of these extraordinarily large data sets.

Asked for his personal feelings on the task at hand, Dr. Newsome said 2 words come to mind: excitement and trepidation. "Excitement because I believe in the importance of the project and the excellence of the team that has been assembled to articulate a national plan. Trepidation because my spring and summer were already fully planned, and I am not sure where the time is going to come from to another job as well! But we will work it out," he told Medscape Medical News.

Differing Opinions

Dr. Landis noted that not everyone is on board with the project, which, she says, isn't surprising.

"There are people in the neuroscience community who think this [initiative] is wonderful and there are people in the neuroscience community who, because of the sequester and how difficult funding is, are asking whether or not this is the most important thing that we could be doing with our funds," she said.

"There are some people who say it's too much money given how little money we have and there are others who say it's not nearly enough. I think it's also very complicated because we don't really know yet what it is, at this stage," Dr. Landis added.

Still, in her view, "I think it's incredibly exciting and we will end up with some wonderful recommendations and we will be able to implement them in and they will make a huge difference in our understanding of the brain," she said.