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Q&A: BRAIN Initiative Director Dr. John Ngai

October 20, 2021

FABBS spoke to Dr. John Ngai about the NIH BRAIN Initiative and how cognitive and behavioral scientists fit into his vision for the program and which contributions he sees as having the most potential.

“Because cognitive and behavioral scientists work at so many intersections—brain, human cognition, language, social behavior, and culture—the perspectives and questions they bring to the work of neuroscientists, physicists, statisticians, computer scientists, mathematicians, and engineers are vital to improving our understanding of brain activity and human behavior.”

John J Ngai
(Photo: courtesy of the National Institutes of Health)

John J. Ngai, Ph.D., is the Director of the NIH’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN®) Initiative, where he oversees the long-term strategy and day-to-day operations of this ground-breaking enterprise. Dr. Ngai earned his bachelor’s degree in chemistry and biology from Pomona College, Claremont, California, and Ph.D. in biology from the California Institute of Technology (Caltech) in Pasadena. He was a postdoctoral researcher at Caltech and at the Columbia University College of Physicians and Surgeons before starting his faculty position at the University of California at Berkeley. Prior to joining NIH, as a UC Berkeley faculty member for over 25 years Dr. Ngai trained 20 undergraduate students, 24 graduate students and 15 postdoctoral fellows in addition to teaching well over 1,000 students in the classroom. His work has led to the publication of more than 75 scientific articles in some of the field’s most prestigious journals and 10 U.S. and international patents. Dr. Ngai has received many awards including from the Sloan Foundation, Pew Charitable Trusts, and McKnight Endowment Fund for Neuroscience. As a faculty member, Dr. Ngai served as the director of Berkeley’s Neuroscience Graduate Program and Helen Wills Neuroscience Institute. He also provided extensive service on NIH study sections, councils and steering groups, including as previous co-chair of the NIH BRAIN® Initiative Cell Census Consortium Steering Group.

Can you tell us a little bit about the BRAIN Initiative, its mission, and progress to date?

The Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is aimed at revolutionizing our understanding of the human brain.

A cornerstone of this mission is the advancement and acceleration of innovative technologies that will enable researchers to build dynamic pictures of the brain capable of showing its depth and complexity—down to how the cells and multitude of neural circuits interact in both space and time.

In developing, utilizing, and sharing the technology that will enable researchers to better understand how brain activity affects biological functions, this research will impact how we treat, cure, and even prevent brain disorders. And on a more fundamental level, understand and explore exactly how the brain enables the human body to record, process, utilize, store, and retrieve vast quantities of information, all at the speed of thought.

The direction—and progress—of BRAIN can be traced back to the visionary strategic plan articulated in the BRAIN 2025 report issued in 2014, and its mandate to “map the circuits of the brain, measure the fluctuating patterns of electrical and chemical activity flowing within those circuits, and understand how their interplay creates our unique cognitive and behavioral capabilities.” A major component of this mandate has been to develop experimental capabilities for recording and manipulating neural activity in diverse model organisms, including humans, during complex behavioral and cognitive processes.

Currently the BRAIN Initiative is funding hundreds of projects ranging from single-investigator to large teams that integrate these experimental capabilities to address fundamental questions of circuit function. One key milestone we’re excited to share is the publication of 17 papers in Nature about work produced by the incredible collaboration behind the BRAIN Initiative Cell Census Network. What this research has unveiled is an atlas of cell types and an anatomical neuronal wiring diagram for the mammalian primary motor cortex, derived from detailed studies of mice, monkeys, and humans. The atlas provides a foundation for more in-depth study of cell types in the rest of the mammalian brain and may help researchers translate findings from animal models to humans, providing an opportunity to learn more about how diseases—such as schizophrenia, addiction, seizure disorders, and Alzheimer’s disease—develop.

To help guide us through the next phase of BRAIN research, the “BRAIN 2.0” Working Group and Neuroethics Working Group reports issued in 2019 provided a critical evaluation of BRAIN’s remarkable progress and highlighted many future opportunities.  Inspired by the BRAIN 2.0 reports, over the next few years BRAIN will launch three large projects that we expect will transform the way we conduct neuroscience research: a comprehensive cell atlas focused on the human brain (the “parts list”); whole mammalian brain connectivity maps (the “wiring diagram”): and tools for accessing brain cell types in multiple species for interrogation and modulation of neural circuits. Together these projects will provide information about the nature of neural circuits and the tools for unraveling the circuit basis of behavior. Our long-term goal is to apply this knowledge toward developing cures for human circuit disorders.

What is the Plan for Enhancing Diverse Perspectives (PEDP)?

Evidence from empirical studies indicates that teams with diverse perspectives out-perform homogeneous teams in terms of creativity and productivity. Thus, with the goal of supporting the best science, the NIH BRAIN Initiative is committed to promoting diversity, equity, and inclusivity in research. The Plan for Enhancing Diverse Perspectives (PEDP) was developed in support of this commitment and is a new requirement in the BRAIN grant application process. The PEDP requires researchers to consider, plan, and articulate how diverse perspectives will be incorporated in their project to advance the proposed specific aims.

Many people ask what it means to include “diverse perspectives” in their grant application. Here, diversity covers many realms embodied in the research team members’ backgrounds, including, for example, gender, race/ethnicity, scientific background, career stage, institutional background, and geographic location, among others.  This diversity of minds takes on a variety of forms which all add to a rich and innovative pursuit of scientific discovery and applies to all aspects of the scientific process—from the people who do the research, to the individuals who participate in the research as part of the study population, to the places where research is done.

We anticipate over time that this new application component will be required in most BRAIN funding opportunity announcements (FOAs).

For further information and for guidance on developing a PEDP, visit the BRAIN Initiative PEDP webpage and view the Frequently Asked Questions (FAQs). You can also email BRAINInitiative_PEDP@nih.gov or the Program official listed in the FOA.

As you look at the neural underpinnings of behavior, what are some of the key questions that would benefit from the engagement of behavioral and cognitive researchers?

We know the toll mental health illness takes on communities and economies. According to the National Institute of Mental Health, in 2019, there were an estimated 51.5 million adults aged 18 or older in the United States with any mental illness. This number represented 20.6% of all U.S. adults.

NIH in general has a history of supporting foundational work that enables not only additional research but facilitates translation to the clinic.  For BRAIN, we hope that the data, technologies, and approaches provide platforms and insights into what could be the next step: the development of novel diagnostics, therapeutics, interventions, and treatments.

The questions we hope behavioral and cognitive researchers will bring to the table can help bridge the gap from how cells and circuits in the brain act to the physical and mental illness an individual may suffer as a result of those behaviors at the cellular level.

You have pointed to the importance of quantifying behavior and developing predictive models. What have been the obstacles to progress in these areas and where are the opportunities?

Indeed, one of the major goals of the BRAIN Initiative and neuroscience more generally is to develop predictive and ultimately testable models of the circuit mechanisms underlying behavior. A challenge—and therefore opportunity—has been in obtaining high precision behavioral data, linking these measurements to activity in specific neural circuits, and then experimentally modulating these circuits to establish cause-effect relationships. One of the opportunities that we’re planning is a new initiative for Brain-Behavior Quantification and Synchronization (BBQS), which was approved in concept at the most recent meeting of our Multi-Council Working Group. The primary goal of this effort is to develop new tools for measuring the full richness of species-appropriate behaviors and linking them to neural circuit activity.

Any advice to behavioral and cognitive scientists who either haven’t thought to submit applications to BRAIN or hadn’t been successful in the past?

One area that we are most excited about is fostering collaborations among researchers and scientists who wouldn’t normally work together, or who wouldn’t normally work on neuroscience research. Because cognitive and behavioral scientists work at so many intersections—brain, human cognition, language, social behavior, and culture—the perspectives and questions they bring to the work of neuroscientists, physicists, statisticians, computer scientists, mathematicians, and engineers are vital to improving our understanding of brain activity and human behavior.

We hope more cognitive and behavioral scientists see themselves in the BRAIN FOAs and encourage them to reach out to the Scientific/Research Contact(s) on the FOA of interest if they have any hesitations about whether it’s a good fit for them. You can also stay up to date with BRAIN Initiative information by subscribing to the Director’s Corner and BRAIN Blog.

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