Charting the Course for the Next Phase of the NIH BRAIN Initiative

NINDS Director Walter J. Koroshetz, NIMH Director Joshua A. Gordon, NICHD Director Diana W. Bianchi, NIA Director Richard Hodes, NIAAA Director George Koob, NCCIH Director Helene Langevin, NIBIB Director Bruce J. Tromberg, NIDCD Director Debara L. Tucci, NEI Acting Director Santa Tumminia, NIDA Director Nora D. Volkow, ORWH Director Janine A. Clayton, and OBSSR Director William T. Riley

There’s a lot to be excited about when it comes to the BRAIN Initiative, especially now that the NIH ACD BRAIN Initiative Working Group 2.0, and the BRAIN Neuroethics Subgroup (BNS) have delivered their final reports. The BRAIN Initiative is a collaborative effort between multiple federal research agencies and ten NIH Institutes, funded by the U.S. Congress through the 21st Century Cures Act. In the six years since the inception of the BRAIN Initiative, a tremendous number of scientific advances have generated exciting new tools for exploring neural circuits that underlie brain function. For instance, BRAIN-funded scientific advances include: new probes for recording and perturbing the activity of neurons and neuronal ensembles (e.g., improved DREADDs, genetically-encoded sensors for dopamine and calcium); advances in single-cell genomic profiling (e.g., Drop-seq); microscopy (e.g., Swept Confocally-Aligned Planar Excitation Microscopy (SCAPE) and 3-photon microscopy); and human neuroimaging (e.g., calcium sensors for direct readout of neural activity by MRI). These new tools are already contributing to an advanced understanding of how brain circuit activity enables behavior.

In fact, BRAIN-sponsored advances stood out as some of the highlights at the 2019 Annual Meeting of the Society for Neuroscience, the largest gathering of brain scientists in the world.  Events there included a mini-symposium and a busy social highlighting BRAIN neurotechnologies, neuroethics sessions, a meeting of the BRAIN Initiative Alliance, a planning session for the International Brain Initiative, and myriad talks and poster presentations. Through these events, scientists highlighted the support of the BRAIN Initiative in developing game-changing tools and resources, many of which are already beginning to be distributed to the wider basic neuroscience community. Even now, these BRAIN Initiative technologies are impacting clinical research. BRAIN-funded studies include a clinical trial of an experimental brain device, developed in the lab of Dr. Nader Pouratian, that enables blind patients to better distinguish light and motion, and a new method developed by Dr. Edward Chang and his team to use brain activity to reconstruct human speech. With these scientific advances and many others, the BRAIN Initiative has truly made spectacular progress.

Building on this considerable progress, the NIH BRAIN Initiative in the coming years is poised to lead to tremendous advancements. Accordingly, the NIH has recently completed a year-long effort to revise the strategic plan guiding the BRAIN Initiative. In 2013, a working group of the Advisory Committee to the NIH Director (ACD) outlined strategic priorities to guide the BRAIN Initiative in BRAIN 2025, a scientific vision that coalesced support for BRAIN across the neuroscience community and has been embraced by BRAIN partners both nationally and internationally. The BRAIN 2025 report emphasized that the Initiative would need to adapt in response to a changing scientific landscape. As such, the ACD convened a new group of external experts in April 2018 to review the progress of the BRAIN Initiative and identify new gaps and opportunities, given the rapid advancements that have occurred.

Drs. Catherine Dulac and John Maunsell co-chaired this group of external scientific experts, the NIH ACD BRAIN Initiative Working Group 2.0, and presented their findings at the June 2019 meeting of the ACD, following up in a teleconference on October 21, 2019. The report, From Cells to Circuits, Toward Cures, encompasses over a year of the group’s tireless efforts. The group reported that NIH should continue to advance the BRAIN Initiative through projects centered in single or small teams of laboratories. They emphasized that the BRAIN Initiative needs to continue to attract and leverage the expertise of diverse scientists, including engineers, geneticists, chemists, mathematicians, physicists, computational scientists, and basic and clinical neuroscientists to develop more powerful tools to map, monitor, and modulate neural circuits. In addition, the group saw the unique opportunity of the BRAIN Initiative to take on ambitious team science projects for achieving research goals that will transform the future of neuroscience and lead to new treatments for neuro/mental/substance use disorders. A balanced approach of individual lab research and team science will propel BRAIN Initiative research into the future. Finally, to collectively accelerate the pace of scientific discovery, the 2.0 Working Group suggested increased resources devoted to data harmonization and sharing, technology dissemination, clinical translation, training, public engagement, and neuroethics.

As the BRAIN Initiative moves forward, it must do so responsibly and ethically. Thus, in parallel with the BRAIN Initiative Working Group 2.0 activities, the BRAIN Neuroethics Subgroup (BNS) examined the challenges that face investigators, the medical community, and society as a whole as we develop new abilities to precisely monitor and modulate brain activity and predict behavior.  Drs. James Eberwine and Jeffrey Kahn co-chaired this group of external experts, which detailed their findings in the complementary report, The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society, at the June and October ACD meetings. The report focuses on enhancing the integration of neuroscience and neuroethics, providing additional resources for addressing neuroethics issues and opportunities, assessing the development and use of innovative animal and neural-circuit model systems, establishing guidelines for the neuroscience data ecosystem, and initiating conversations and collaborations to address neuroscience applications beyond biomedical and clinical contexts.

Dr. Francis Collins, NIH Director, accepted the ACD endorsed reports, and NIH will carefully consider how to integrate both sets of findings in future BRAIN Initiative priorities and investments. We are thrilled that such thoughtful and hard work went into tackling these complicated and challenging issues, and we thank the co-chairs and members of both working groups for their diligent efforts over the last year and a half. The groups’ presentations to the ACD can be viewed here. Fiscal year 2019 saw over 180 new NIH BRAIN awards, with NIH support for more than 270 investigators and a total budget of almost $425 million; as such, these reports could not be more timely. At NIH, we are immediately and enthusiastically developing an implementation strategy guided by the work of the 2.0 Working Group and BNS. The discussions surrounding the next phase of the BRAIN Initiative – its opportunities and potential – leave us nothing short of excited to see what the second half of the Initiative brings.