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The thirteenth meeting of the NIH BRAIN Initiative Multi-Council Working Group (MCWG) included discussion of upcoming strategic planning discussions with the NIH Director’s Advisory Committee, as well as consideration of concept clearances for funding opportunities.

On May 16th, 2019, the Multi-Council Working Group (MCWG) to the National Institutes of Health (NIH) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative® held its thirteenth meeting. The group provides ongoing oversight of the long-term scientific vision of the BRAIN Initiative, in the context of the evolving neuroscience landscape. MCWG members include a liaison to the Advisory Council of each of the 10 Institutes and Centers that contribute to the NIH BRAIN Initiative, with additional at-large members appointed to supplement the working group’s expertise. The group also includes ex officio members from DARPA, FDA, IARPA, and NSF—four of NIH’s federal partners involved in the BRAIN Initiative.

In opening remarks, Dr. Walter Koroshetz, NINDS Director, mentioned the success of the recent BRAIN Initiative Investigators (PI) Meeting, which was held from April 11-13, 2019, with approximately 1600 registrants (a 33% increase over last year). The conference included scientific presentations, poster sessions, a three-part communications workshop, and an inaugural photo and video contest. Read more about the 2019 BRAIN PI meeting here.

Dr. John Maunsell, co-chair of the NIH ACD BRAIN Initiative Working Group (WG) 2.0, provided an update on the group’s Report, which was presented to the Advisory Committee of the NIH Director earlier today, June 14th, 2019. The group lauded the success of the first half of the Initiative, noting that it will be important to continue the momentum of technology development. Examples of areas that will require increased effort include research on artificial technology and theory, distributing the new technologies that have been developed, and public engagement around neuroscience. The WG also identified potential large-scale, transformative projects including pinpointing specific circuits implicated in diseases, mapping the entire mouse brain and determining circuits controlling specific behaviors, and learning how the brain retrieves stored information.

Dr. Jim Eberwine, a member of the BRAIN MCWG and Neuroethics Working Group and co-chair of the BRAIN Neuroethics Subgroup (BNS) of the ACD BRAIN Initiative WG 2.0, provided an overview of the BNS, which has been charged with considering the neuroethical implications that arise from BRAIN Initiative funded research and developing a Neuroethics Roadmap for the BRAIN Initiative, also presented to the ACD on June 14th. The report discusses examples of neuroethics-related issues unique to BRAIN, including unexpected consequences of precise brain circuit manipulation with tools developed via the BRAIN Initiative, and companies needing to be aware of potential neuroethical implications of widespread use of their products.

Three concept clearances were presented to the MCWG. The first concerned the development of alternatives to models of the developing human nervous system. This FOA will focus on creating three-dimensional systems that contain human cells, to improve our understanding of brain development, which is currently restricted due to technical limitations and ethical concerns. Two additional concept clearances on marmoset research were also presented, focusing on the development of genetic tools and technologies to improve our understanding of primate brains, and to develop colonies and coordinate distribution of animals for research.

For more information, please view the MCWG meeting summary and the archived videocast of the meeting.

The Advisory Committee to the NIH Director (ACD) BRAIN Initiative Working Group 2.0 and BRAIN Neuroethics Subgroup (BNS) will present reports of their major findings and analysis during the ACD meeting on June 14, 2019.

After more than a year of hard work and tireless efforts, the Advisory Committee to the NIH Director (ACD) BRAIN Initiative Working Group 2.0 and BRAIN Neuroethics Subgroup will present reports of their major findings and analysis during Day 2 of the ACD Meeting on June 14, 2019, beginning approximately 10:15 AM Eastern Time. The meeting will take place in Wilson Hall of Building 1 on the main NIH campus in Bethesda, Maryland.

Drs. Catherine Dulac (Harvard University) and John Maunsell (University of Chicago), co-chairs of the BRAIN Initiative Working Group 2.0, will present a report of the group’s major findings. The group was charged with providing scientific guidance to the ACD on how best to accomplish the ambitious vision for the BRAIN Initiative first outlined in BRAIN 2025: A Scientific Vision, considering the current state of neuroscience. Through a review of BRAIN progress, workshops and town halls, and opportunities for public input, the Working Group has drafted and will present a report to guide the NIH BRAIN Initiative during the second half of its tenure.

Drs. Jim Eberwine (University of Pennsylvania) and Jeff Kahn (Johns Hopkins University), co-chairs of the BRAIN Neuroethics Subgroup (BNS), will also present a report of their group’s major findings. The BNS was charged with developing a Neuroethics Roadmap for the NIH BRAIN Initiative, characterizing the neuroethical implications that may arise as BRAIN Initiative advancements move forward.

Videocast of the meeting will be broadcast live and archived for later viewing.

Direct speech synthesis using auditory cortex recordings… Three-photon imaging of adult mouse brains through intact skulls… Tensor component analysis for unraveling complex neural circuit dynamics…

Decoding neural activity into kinematic and acoustic features yields accurate human speech waveforms

Many individuals with neurological conditions require alternative devices to communicate with the outside world. While these devices are useful, they are limited in their capacity to transmit information because they require selecting letters one-by-one to spell out words, using residual non-verbal movements or control of a cursor via a brain computer interface. Dr. Edward Chang and colleagues at the University of California San Francisco have now devised a method to decode spoken sentences directly from recorded neural activity in human cortical brain regions at the rate of normal speech. Five participants receiving intracortical monitoring for epilepsy treatment read aloud several hundred sentences while the authors used high-density electrocorticography (ECoG) to record activity in the ventral sensorimotor cortex (vSMC), superior temporal gyrus (STG), and inferior frontal gyrus (IFG) regions of their auditory cortices. Building on their previous findings that brain activity corresponds more closely to movements of the speech articulators than to the sounds, the researchers developed a two-stage decoding schema. The first stage decoded speech articulation – a kinematic feature of speech (e.g., lip, mouth, or tongue movements) – directly from neural activity in the vSMC, STG, and IFG brain regions. In the second stage, the speech encoder-decoder was trained to construct the acoustics of speech (e.g., pitch, voicing, or sound distortions) from the previously estimated kinematic features of recorded sentences. Finally, both decoding stages were integrated to produce an accurate recapitulation of the original spoken sentence. Though the decoder was trained on a specific sentence dataset, it could still decode sentences that were not included in the training data. These results represent one of the first platforms to incorporate all aspects of speech in a language decoding program. Synthesizing speech directly from auditory cortex activity not only allows for audible speech to be decoded in real time but also maintains the natural rate and captures pitch and intonation of human speech, which could be promising for completely paralyzed individuals for whom there are no adequate communication devices. For more information, please view the NIH Press Release on this work.

Synthesizing speech directly from decoded neural activity. (Top) Model for decoding speech from electrodes that recording from vSMC, STG and IFG regions of the auditory cortex. Kinematic and acoustic features were decoded, then synthesized into an acoustic (speech) waveform. (Bottom) Spectrograms represent the similarities in visual representation of frequency output of two spoken sentences, compared to decoded, synthesized speech.

Three-photon imaging of mouse brains through intact skulls shows vast improvements over two-photon imaging

To fully appreciate murine neural networks in normal and diseased states, the natural environment of the brain must be preserved as much as possible. Non-invasive technologies, such as MRI, do not provide single cell resolution, and several routine procedures that make the mouse brain more accessible to live fluorescence imaging, including skull thinning and cranial window implantation, potentially alter the brain microenvironment and communication between cell types. In recent years, two-photon optical imaging (2PM) has been used for deep imaging of in vivo mouse brains, but bone scatters light, limiting resolution and depth. Dr. Chris Xu and colleagues from Cornell and Stanford Universities have now demonstrated that three-photon microscopy (3PM) can overcome these problems and achieve greater imaging depth of mouse brains and decreased background through intact mouse skulls. 3PM achieves greater cortical depths and decreased background over 2PM by using three photons to excite a fluorescent molecule to a higher electronic state versus two. The higher order excitation of 3PM is responsible for an improved signal-to-noise ratio resulting in clear, higher contrast images of uncompromised mouse brains as well as larger fields-of-view. The research team also found that they could reduce skull surface roughness by using a glue that matched the refractive index of the skull, which also insulated the skull from the air and preserved transparency for chronic imaging.  This technology also attains cortical depths greater than 500 μm using conventional dyes and captures calcium activity with high spatiotemporal resolution. Dr. Xu and his team’s work indicates 3PM’s superior functionality at imaging mouse brains through intact mouse skull, paving the way for a better understanding of true and biologically relevant neural states at both the level of structure and function. This work was supported by funding from BRAIN Initiative Alliance members, including the National Science Foundation (NSF’s NeuroNex) and Defense Advanced Research Projects Agency (DARPA).

Imaging of a mouse brain through an intact skull preserves cellular structure and function. A three-dimensional reconstruction of a murine cortical brain column imaged through an intact skull. 3PM was used to excite neurons that are labeled by red fluorescent protein. The scale for depth is set at 0, or right below the skull.

Tensor component analysis generates dimensional reduction of neural circuit dynamics within and across trials

Historically, principal component analysis (PCA) has been used to understand complex and large-scale neural activity data. PCA reduces information on neural dynamics within a trial, rather than across trials. Despite PCA’s utility, neural circuits operate on extremely diverse timescales ranging from milliseconds to weeks, or across trials. A subtype of PCA, known as tensor component analysis (TCA), can reduce information in an unbiased and unsupervised fashion across three separate dimensions: time, trials, and neural activity. This information can provide vast insights into cognitive states. Dr. Surya Ganguli and his team at Stanford University used TCA to forge neural descriptions of artificial learning, rodent navigation, and primate motor learning. The goal of these studies was to generate a simplified understanding of all trials, all neural activity in each trial, and the timescale in which these neural circuits operate in the prefrontal cortex (or artificial modeling thereof). Neural activity of the murine prefrontal cortex was recorded using calcium imaging while mice navigated through a maze. TCA determined that neural circuitries involved in rodent navigation could be characterized as discrete behavioral elements based on starting and ending conditions or whether mice received a reward. To determine if TCA could distinguish discrete from continuous neural data sets, studies using a brain-machine interface were conducted. Learning behavior was quantified while a rhesus macaque operated a continuous computer cursor and electrodes recorded neural activity from the motor cortex. TCA analysis revealed the neural circuitries involved in the macaque’s movement errors as well as those involved in correcting errors. These results suggest that TCA provides an understanding of both neural activity that regulates thoughts and actions (fast), and activity that regulates underlying behavior and learning processes (slow). Dr. Ganguli and colleagues offer an extensive framework for uncovering low-dimensional descriptions of recorded neural information. TCA represents an important and broadly applicable approach to analyze the dynamics of any complex biological system – particularly those that were previously studied in only one dimension.

Two-dimensional learning outputs from a primate brain-machine interface estimated using TCA. (A) Schematic of brain-machine interface. (B) Cyan data points represent the beginning of each trial while magenta points represent the end of each trial. (C) Representation of time taken for macaque to move the cursor to a target. The red line signifies when the visuomotor perturbation was introduced (trial #31). (D) Representation of TCA analysis of the top 50 recorded motor cortex activity spikes, or multiunit spike trains (component #1), time (component #2) and trials (component #3). Component #2 and #3 capture learning after visuomotor perturbations were introduced.

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Videocast will be available for the open session of the upcoming BRAIN Multi-Council Working Group (MCWG) meeting on Thursday, May 16, 2019.

The NIH BRAIN Initiative Multi-Council Working Group (MCWG), consisting of non-Federal representatives from various NIH Institutes and Centers participating in BRAIN, at-large members, and ex officio representatives from DARPA, FDA, IARPA and NSF, provides ongoing oversight of the long-term scientific vision of the NIH BRAIN Initiative, in the context of the evolving neuroscience landscape. The thirteenth meeting of the MCWG will occur on Thursday, May 16, 2019, at the Neuroscience Conference Center, Conference Rooms C/D (6001 Executive Boulevard, Rockville, MD 20852). The videocast may be accessed here.

The open session will include presentations on BRAIN 2.0 efforts. First, there will be an update from Dr. John Maunsell, co-chair of the Advisory Committee to the NIH Director (ACD) BRAIN Initiative Working Group (WG) 2.0, which is sharing with the community its initial thoughts on the current state of the BRAIN Initiative and inviting public comment. Please submit comments through the Request for Information (RFI) or by emailing BRAINfeedback@nih.gov by May 15, 2019. There will also be an update from Dr. Jim Eberwine, co-chair of the ACD Working Group on BRAIN 2.0 Neuroethics Subgroup (BNS). The BNS is welcoming comments from the public on draft findings and analysis detailed in the Neuroethics Roadmap. The BNS has also provided analysis and findings to the ACD Working Group on BRAIN 2.0 for inclusion in their initial thoughts. Please submit comments to BNS@nih.gov by May 20, 2019.

A written summary and a link to the video archive of the open session from the May MCWG meeting will be posted on the BRAIN MCWG webpage after it has concluded.

Initial thoughts on BRAIN’s strategic plan from the Advisory Committee to the NIH Director BRAIN Initiative Working Group 2.0 are open for public comment through May 15, 2019. In parallel, a draft Neuroethics Roadmap from the BRAIN Neuroethics Subgroup is now open for public comment through May 20, 2019.

The Advisory Committee to the NIH Director BRAIN Initiative Working Group 2.0, formed in April 2018, has been working tirelessly to assess BRAIN’s progress and advances within the context of the original BRAIN 2025 report, identify key opportunities to apply new and emerging tools to revolutionize our understanding of brain circuits, and designate valuable areas of continued technology development. Over the course of the last year, the Working Group has undertaken a deliberative and open process consisting of portfolio review, scientific workshops, town halls, and public solicitation.

Continuing in this manner, the Working Group is sharing with the community its initial thoughts on the current state of the BRAIN Initiative, including opportunities for keeping pace with the evolving scientific landscape, including the identification of new opportunities for research and technology development, within a solid ethical framework, to ensure BRAIN Initiative research is of the utmost value to the public it intends to serve. Please submit comments through the Request for Information (RFI) or by emailing BRAINfeedback@nih.gov by May 15, 2019.

In parallel, the ACD Working Group on BRAIN 2.0 Neuroethics Subgroup (BNS) was formed to develop a Neuroethics Roadmap for the NIH BRAIN Initiative; review priority areas identified in the BRAIN 2025 Strategic Plan, incorporating updates from the broader BRAIN 2.0 Working Group; and characterize the neuroethical implications that may arise as BRAIN Initiative investments produce new tool/neurotechnologies, and/or those tools/neurotechnologies are applied to advancing the goals of the NIH BRAIN Initiative.

The BNS has conducted a portfolio review and held a public workshop on neuroethical issues posed by research through the BRAIN Initiative. The BNS is now welcoming comments from the public on draft findings and analysis detailed in the Neuroethics Roadmap. The Neuroethics Subgroup has also provided analysis and findings to the Working Group on BRAIN 2.0 for inclusion in the Working Group’s initial thoughts. Please submit comments to BNS@nih.gov by May 20, 2019.

Both groups will consider all public responses as they iterate their findings and analysis, which they will present to the Advisory Committee to the NIH Director (ACD) for consideration at its meeting on June 13-14, 2019.

Three new receipt dates have been added to this funding opportunity announcement (FOA): November 6, 2019; July 1, 2020; and November 10, 2020.

This announcement provides a notice (NOT-NS-19-034) that three new receipt dates have been added to “BRAIN Initiative: Targeted BRAIN Circuits Planning Projects – TargetedBCPP (R34 Clinical Trial Not Allowed)” (RFA-NS-18-014).

The primary goal of this funding opportunity announcement (FOA) is to solicit exploratory research projects using innovative approaches to understand how circuit activity gives rise to a specific behavior or neural system dynamics. The R34 mechanism provides up to two years of funding in the BRAIN Understanding Circuits portfolio. It is intended to support a limited scope of aims and an approach that will establish feasibility, validity, or other technically qualifying results that, if successful, would support, enable, and/or lay the groundwork for a potential, subsequent Targeted BRAIN Circuits Projects – TargetedBCP R01 (up to five years of funding), as described in the companion FOA (RFA-NS-18-030).

The BRAIN Understanding Circuits program encompasses a family of “Integrated and Quantitative Approaches to Understanding Circuits” FOAs. The activity of neural circuits is the substrate of cognitive processes such as perception, attention, reasoning, intention, decision-making, and emotion. These internal activities are translated into patterns of activation that support simple motor behaviors, as well as more complex behaviors.

The three additional receipt dates for RFA-NS-18-014 are November 6, 2019; July 1, 2020; and November 10, 2020.

The next application deadline for the BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) is June 12, 2019 (resubmission deadline is July 12, 2019).

The NIH BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) program aims to enhance diversity in the neuroscience workforce and maintain a strong cohort of new and talented, NIH-supported, independent investigators from diverse backgrounds in BRAIN Initiative research areas.

This program is designed to facilitate a timely transition of outstanding postdoctoral researchers with a research and/or clinical doctorate degree from mentored, postdoctoral research positions to independent, tenure-track or equivalent faculty positions. The program will provide independent NIH research support during this transition in order to help awardees launch competitive, independent research careers.

More information about applications can be found under PAR-18-813 (Independent Clinical Trial Required) and PAR-18-814 (Independent Clinical Trial Not Allowed). Additional resources, including a technical assistance webinar, are available at: https://www.braininitiative.nih.gov/brain-programs/training.

The next deadline for new applications to the BRAIN Initiative Diversity K99/R00 is June 12, 2019 (resubmissions: July 12, 2019).



The fifth annual BRAIN Initiative Investigators Meeting, held from April 11-13, 2019 in Washington, DC, convened approximately 1600 registrants. In tandem, the Advisory Committee to the NIH Director BRAIN Initiative Working Group 2.0 previewed and has now released their draft report, which is open for public comment through May 15, 2019.

From April 11-13, 2019, the Wardman Park Marriott in Washington, DC, hosted the fifth annual BRAIN Initiative Investigators Meeting. The meeting convened approximately 1600 registrants, including BRAIN Initiative awardees, staff, and leadership from the contributing federal agencies (NIH, NSF, DARPA, IARPA, and FDA), as well as representatives and investigators from participating non-federal organizations, members of the media, public, and Congress.

This year’s meeting featured plenary sessions from: Dr. Paola Arlotta (Harvard University), Dr. Patricia Churchland (University of California), Dr. Marcus Meister (California Institute of Technology), and Dr. Edvard Moser (Kavli Institute for Neuroscience). On the first day of the meeting, the NIH Advisory Council to the Director (ACD) BRAIN Initiative Working Group 2.0 and BRAIN Neuroethics Subgroup held a Town Hall, moderated by NIH Director, Dr. Francis Collins. There, the co-chairs of both groups – Drs. Catherine Dulac, John Maunsell, Jim Eberwine, and Jeff Kahn – previewed the findings of their draft report on how best to accomplish the ambitious vision for the BRAIN Initiative, considering the current state of neuroscience. The Working Group’s draft report is now available for public comment via a Request for Information, with the BRAIN Neuroethics Subgroup’s Roadmap being released later this month for public comment. All of the plenary sessions, as well as the Town Hall, were videocast, archived, and are available for streaming on the NIH Videocast website.

For the first time this year, attendee-organized symposia highlighted emerging areas of focus in BRAIN. Some of these topics included: Bridging Animal and Human Brain Research with fMRI, Emerging Technologies in Studying Spinal Cord Circuitry and Dynamics, Advances in Mapping Neural Connectivity, and Neuropharmacology at the Age of the BRAIN Cell-Census. Along with these symposia, Research Highlight Talks provided platforms for BRAIN Initiative awardees to discuss their latest scientific advances. Additionally, Focused Sessions provided forum opportunities for those interested in specialized topics, such as the BRAIN Initiative Informatics Infrastructure and Frontiers of Non-Invasive Brain Imaging. A session on neuroethics featured active collaborations between neuroscientists and neuroethicists, including one on the neuroethical implications of portable magnetic resonance imaging (MRI). For more information, see this coverage from Science Magazine.

Drs. Michael Garwood and Francis Shen, who collaborate with Ben Parkinson and Mailin Lemke (Victoria University of Wellington), as well as William McGeveran and Susan Wolf (University of Minnesota), discuss the neuroethical implications of portable neuroimaging.

The 2019 Meeting also featured a three-part science communications series. On Thursday, April 11, NPR’s Jon Hamilton presented a workshop on talking to the public about BRAIN science to a packed room. On Friday, April 12, Betsy Stark, an Emmy Award winning journalist and former ABC News Business Correspondent, led a workshop on talking to the media about BRAIN science. Finally, on Saturday, April 13, Rohan Verma, Vice President at Ogilvy Public Relations Worldwide, led a workshop on using social media to promote BRAIN science.

Jon Hamilton, correspondent for NPR’s Science Desk, discusses talking to the public about BRAIN science.

Finalists from the first Show Us Your BRAINS! Cool Picture and Video Contest had their photos and videos on display throughout the meeting, where attendees could vote on their favorites. The inaugural winners were announced on the last day of the meeting: Congratulations to Andrew Janson at the SCI Institute for the winning photo submission, and to the Yang and Chung Research Groups for the winning video submission.

The winning photo submission from the first Show Us Your BRAINS! Cool Picture and Video Contest, entitled “Light Me Up”, from Andrew Janson at the Scientific Computing and Imaging Institute. The winning video submission from the first Show Us Your BRAINS! Cool Picture and Video Contest, from X. William Yang’s research group at UCLA and Kwanghun Chung’s research group at MIT.

We look forward to seeing everyone at the sixth annual BRAIN Initiative Investigators Meeting in 2020!