Cornelia Bargmann, PhD and William T. Newsome, PhD
Cornelia Bargmann and William T. Newsome

Cornelia (Cori) Bargmann, PhD, is a Howard Hughes Medical Institute Investigator, and professor and co-director of the Shelby White and Leon Levy Center for Mind, Brain and Behavior at The Rockefeller University. She studies the relationships between genes, circuits, and behaviors in C. elegans.

William T. Newsome, PhD, is a professor of neurobiology and director of the Neuroscience Institute at Stanford University, and Howard Hughes Medical Institute Investigator. His research focuses on the neural mechanisms underlying visually based decision-making and related issues in cognitive neuroscience.

Dr. Bargmann  and Dr. Newsome co-chair the NIH BRAIN Working Group.

Q: President Obama announced the BRAIN Initiative last April, describing it as one of the “Grand Challenges” of the 21st century. What basic goals have the NIH Director’s working group identified for the initiative? What feedback have you received and what are the next steps?

Our interim report identifies circuit-level analysis of the nervous system as the primary focus of the NIH BRAIN Initiative. The overarching goal is to map the circuits of the brain, measure the dynamic patterns of electrical and chemical activity within those circuits, and understand how their interplay creates unique cognitive and behavioral capabilities. Intrinsic to this is an emphasis on technology development at all levels — molecular, cellular, systems, and behavioral — because new methods and technical resources are accelerating research in all areas of neuroscience, particularly in our rapidly evolving understanding of neural circuit function.

Since the interim report was published in September, we have received feedback from many sources, mostly positive, from within and outside the neuroscience community. There is wide agreement that neural circuit function is a critical, underdeveloped link between molecular/cellular neuroscience and ‘whole brain’ imaging, our most common source of information about the functioning human brain. There is also strong support for developing the revolutionary technologies needed to crack circuit-level problems. The scientific questions we have received fall within three categories: 1) Why didn’t we propose a single, one-sentence goal (like recording every action potential in the brain)?; 2) Why aren’t various other areas of neuroscience included?; and 3) How will this basic research promote translational and clinical neuroscience?

The first two questions are about focus versus breadth. On the one hand, we need an integrative, multipronged approach to understand how the brain functions across widely different temporal and spatial scales, and under widely varying behavioral conditions. On the other hand, the BRAIN Initiative needs to make a clear, measurable impact with modest resources, and cannot do everything. Our decision to focus on neural circuits is based on the compelling scientific timeliness of this level of analysis, and our decision to focus on technology development is based on its potential benefit to all research fields: everyone benefits from better microscopes, recording methods, molecular tools, and so on. The third question is about connecting basic science to clinical neuroscience. We are consulting with clinical colleagues to learn what fundamental knowledge and tools will most effectively promote progress on specific brain disorders. We do hear from clinicians, too, that circuits are the missing level of understanding, and that they need better technologies for probing brain function.

As for ‘next steps,’ the June deadline for our final report already looms large in our minds! The interim report focused on getting off the ground, but the final report must take a longer view. We must articulate and prioritize short-, medium- and long-term goals for the next decade; establish a healthy interaction between technology development and question-driven science; lay out time-lines; and articulate a long-term vision for the research community and the nation that will inspire and enable us all to accomplish more than we dreamed possible.

Q: In December, NIH announced the first six funding RFAs under the BRAIN Initiative. How will these grant opportunities advance the initiative and what impact might they have more broadly on the field?

First, readers might be interested to know that the working group was as curious as the rest of the neuroscience community to see what form the RFAs would take! To prevent conflicts of interest, there is a firewall between the working group’s scientific advisory function and the NIH’s process for RFAs. NIH staff (and DARPA and NSF staff) were present at all our meetings, and they have translated our recommendations into an excellent set of RFAs. They incorporate the core principles we articulated, including the focus on circuits and technology development, the emphasis on tight interdisciplinary interaction between experimentalists and theorists, and between tool-makers and tool-users, and the importance of integrating animal models with human neuroscience. Several RFAs place special emphasis on assembling collaborative groups with different expertise, which can be both challenging and stimulating. The research funded under these RFAs could empower neuroscientists to do more effective research, but that will only happen if the best people apply and are funded. We encourage all SfN members to read the RFAs, talk to their colleagues, and think creatively about how to advance the field. There is a short turnaround on the RFAs because of the enthusiasm for getting the BRAIN Initiative started.

Q: As we enter a time of unprecedented opportunity in neuroscience, the community also faces real fiscal challenges. How would you address the concerns of some that the BRAIN Initiative will divert resources from other important work in neuroscience, and how can the neuroscience community help ensure a sustained and robust investment across the field?

These are difficult times for NIH-funded researchers, and your question is the single greatest concern about the BRAIN Initiative within the scientific community. The working group believes unanimously that the BRAIN Initiative only makes sense if there is vibrant support for neuroscience as a whole, and we have been vocal in expressing our views to NIH officials. In this first year of the BRAIN Initiative, diversion of resources is not a serious concern — the $40M to be disbursed by NIH in FY2014 is less than one percent NIH’s $5.3B investment in neuroscience. If, however, the U.S. is to make a serious, imaginative effort toward breakthrough neuroscience, additional investment is necessary. It is essential that the bulk of this funding be added to, not subtracted from, the NIH budget. Neuroscientists can help by communicating regularly with legislators and the public about the importance of our field to scientific discovery and human health. We have an easier job than most scientists because almost everyone is curious about how the brain works and almost everyone has a personal connection to someone with a brain disorder. There have been numerous positive articles in the press about the BRAIN Initiative from all political perspectives; this is a chance for us to have a positive impact on public support of science.

Q: The BRAIN Initiative is one of a number of major global initiatives. How do you see the goals of these efforts in relation to one another, and how can the BRAIN Initiative be integrated with these international efforts?

The international enthusiasm for brain science is timely and gratifying. Understanding how the collective activity of neural circuits gives rise to cognition, behavior, and all of mental life is unquestionably a grand challenge for science in the 21st century! The different international initiatives appear complementary, and not duplicative. For example, the US initiative is grounded in experiment: it envisions integrated cellular, anatomical, and physiological data sets of unprecedented scope, rendered intelligible through theoretical and behavioral analyses. In contrast, the European initiative’s primary goal is to supplement empirical knowledge by simulating neural circuit function in silico. These two initiatives will inevitably converge, to the benefit of both. Neurotechnology and brain-machine interface initiatives have emerged in Japan and Israel, and China and Japan are poised to make unique contributions in primate transgenic models. It is important to emphasize that basic science is international, and knowledge will flow freely between these players; no country will have a monopoly on its contributions. Whether these international efforts would benefit from formal coordination, or be more effectively served by spontaneous collaborations across the international scientific community, are important issues to work out in the coming years.