From the BRAIN Director: Reflecting on Another Year of Exciting BRAIN Research

BRAIN Director, Dr. John Ngai

The National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative continues to grow as reflected by more than 200 new research projects funded in fiscal year 2021, totaling over $540 million. In keeping with the extraordinary breadth of BRAIN, this year’s research portfolio spans a broad array of scientific endeavors – from single-cell biology to synapses to circuits – in model organisms like fruit flies and zebrafish and also with support from human research participants. This year’s BRAIN awards demonstrate our commitment to studying human neurological, neurodegenerative, and neuropsychiatric diseases that burden individuals and families. We continue to be intentional about striking a balance between basic research into uncharted territories of the brain and leveraging discoveries from these efforts to improve therapies for human health in the near-term.

While it will take years to unravel all of the complexity of the cells and circuits that govern how we breathe, think, create and live, the promise of many newly developed technologies is already shedding light on specific neurological conditions. Newly funded disease-related projects are testing and optimizing new interventions for relieving epilepsy, treatment-resistant depression, stroke injury, Tourette syndrome, spinal cord injury, and Alzheimer’s. As we continue to gain precise tools to probe damaged neural circuits that underlie many of these conditions and others, we expect to do even more human-focused investigation toward learning how to rewire errant circuits into healthy function.

Funding excellent research means supporting a community of science informed by diverse perspectives, as reflected by more than 40 new diversity supplements and career development awards explicitly focused on enhancing diversity. As I’ve noted, diversity broadly defined – of talent, topics, research environments, and other domains – drives research excellence. Through these and other mechanisms including the new Plan for Enhancing Diverse Perspectives application requirement, we recognize the ongoing efforts of many in our community to support inclusive practices in research and hope to make these efforts more commonplace.

We have also been keeping close tabs on ensuring that BRAIN funds a mix of science that builds on prior knowledge with the potential to break new ground. Some innovative new neurotechnology projects we’ll be watching include visual prosthetics, 3D human brain imaging, transcranial stimulation, brain-machine interfaces, and more. The increasingly complex intersection of neuroscience, technology, and society will undoubtedly invoke novel ethical questions, and the NIH BRAIN Initiative continues to embed ethical considerations throughout its vision. Also essential is a deliberate, proactive focus on making tools and resources available to all who can use them for research – and ultimately, for healthcare.

The close of fiscal year 2021 also marks a new beginning as we set in place an exciting framework for the next chapter in neuroscience. Stemming from recommendations from the 2019 interim review of BRAIN, this year we are launching new large-scale efforts that reimagine and accelerate the way we conduct neuroscience research and translate this knowledge toward cures. BRAIN is moving forward with three Transformative Projects: the Human Brain Cell Atlas, Next Generation Technologies for Brain Microconnectivity Analysis, and the Armamentarium for Brain Cell Access. While the Next Generation Technologies for Brain Microconnectivity Analysis is still in early phases of development, additional Congressional support enabled us to accelerate the launch of the Human Brain Cell Atlas and the Armamentarium for Brain Cell Access earlier this year. These funds supported efforts to develop scalable tools and technologies aimed at mapping larger brains, and for pilot projects developing platforms and reagents that provide cell-type specific access across vertebrate species including non-human primates and humans.

I am excited for these new Transformative Projects for at least two reasons. First, they consolidate and advance the wealth of knowledge and tools that have emerged to date from BRAIN investments – such as what we have learned from the Brain Initiative Cell Census Network (BICCN). The BICCN’s recent comprehensive analysis of the primary motor cortex at unprecedented scale and depth opens the window for neuroscientists to understand the inner workings of the cerebral cortex, arguably the most complex part of the most complex organ of the body. The analysis, which involved more than 250 researchers across more than 45 institutions, illustrates the power of diverse scientific perspectives for addressing questions of this complexity. With the Brain Cell Atlas and Microconnectivity programs, we build on these and other prior efforts to uncover the “ground truth” for mammalian brains, including the human brain. Defining the “parts list” (Brain Cell Atlas program) and the “wiring diagram” (Microconnectivity program) are essential steps toward understanding how the human brain functions and honing-in on the aspects that fail with disease. 

Second, these ambitious Transformative Projects will supply the necessary push for a new generation of discovery simply not possible now because this research is too costly and complicated for individual researchers to tackle on their own. The Armamentarium for Brain Cell Access will create and implement methods to access and manipulate specific cell-types across multiple species, including humans, without relying on germline modification. The long-term goal here is to standardize and democratize these efforts to ultimately build a toolkit enabling precision interventions for human brain circuit therapies, ensuring the broadest access to these exciting research opportunities. As one example, we plan to enlist scientists at minority serving institutions and those in Institutional Development Award eligible states to develop research resources for the Armamentarium Transformative Project.

The three, interlocking Transformative Projects, together with all of the science we support, are designed to go far beyond BRAIN toward developing tools that empower researchers to answer fundamental unanswered questions about the circuit basis of complex behaviors in both health and disease. These questions and their answers are central to the missions of many NIH Institutes and Centers and the broader research community. In the 8 years since BRAIN launched, we have made remarkable progress toward meeting our primary goal of accelerating neuroscience research through new knowledge and new technologies. More exciting discoveries are just around the corner – I am excited to tell you about them, so watch this space!

With respect and gratitude,

John Ngai, Ph.D.

Director, NIH BRAIN Initiative