Funding Opportunity Announcements

The goal of this effort is to support the development and validation of next generation platforms and analytic approaches to precisely quantify behaviors in humans and link them with simultaneously recorded brain activity. Tools used for analyzing behavior should be multi-modal and should be able to be linked to brain activity and thus have the accuracy, specificity, temporal resolution, and flexibility commensurate with tools used to measure and modulate the brain circuits that give rise to those behaviors. This phased award will support novel tool development (i.e., hardware/software) in the R61 phase and synchronization of novel tools for measuring behavior and human brain activity in the R33 phase.

Reissue of RFA-MH-19-135 The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis and manipulation of complex circuits and provide insights into cellular interactions that underlie brain function. Critical advances in the treatment of brain disorders in human populations are hindered by our lack of ability to monitor and manipulate circuitry in safe, minimally-invasive ways. Clinical intervention with novel cell and circuit specific tools will require extensive focused research designed to remove barriers to delivery of gene therapies. In addition to identification and removal of barriers, the need to specifically target dysfunctional circuitry poses additional challenges. Neuroscience has experienced an impressive influx of exciting new research tools in the past decade, especially since the launch of the BRAIN Initiative. However, the majority of these cutting edge tools have been developed for use in model organisms, primarily rodents, fish and flies. These cutting edge tools, such as viral delivery of genetic constructs, are increasingly adaptable to large brains and more importantly are emerging as potential human therapeutic strategies for brain disorders. A pressing need to develop tools for use in large brains, more directly relevant to the human brain is the focus of this initiative. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application. The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged.

The NIH Research Education Program (R25) supports research education activities in the mission areas of the NIH. The overarching goal of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative R25 program is to support educational activities that complement and/or enhance the training of a workforce to meet the nations biomedical, behavioral and clinical research needs in research areas relevant to the BRAIN Initiative. To accomplish the stated over-arching goal, this FOA will support creative educational activities with a primary focus on Courses for Skills Development and Research Experiences. The purpose of this FOA is to encourage applications for the continuation and/or expansion of ongoing and new research education programs that will significantly advance the educational goals of the BRAIN Initiative as described in BRAIN 2025: A Scientific Vision including neuroethics and opportunities to increase the workforce diversity in BRAIN Initiative research areas. Proposed programs are expected to offer hands-on research experiences, an in-depth conceptual understanding of the techniques and tools employed, and the knowledge to apply appropriate analytic approaches to the resulting data. Participants are limited to undergraduate, graduate/medical students, medical residents, postdoctoral scholars, and/or early-career faculty with an emphasis on diversity as defined by NIH (NOT-OD-20-031). Proposed programs will facilitate the development of a sophisticated cadre of future investigators with the knowledge and skills to apply BRAIN Initiative techniques and approaches and data resources (BRAIN cell census data https://bicon.org/data) to research questions about brain function and behavior. Programs appropriate for this FOA must include participants from a regionally/nationally recruited cohort.

This funding opportunity announcement (FOA) supports efforts to disseminate resources and to integrate them into neuroscience research practice. Projects should be highly relevant to specific goals of the BRAIN Initiative, goals that are described in the planning document "BRAIN 2025: A Scientific Vision." They should engage in one or more of the following activities: distribution of tools and reagents; user training on the usage of new technologies or techniques; providing access to existing technology platforms and specialized facilities; minor improvements to increase the scale/efficiency of resource production and delivery; minor adaptations to meet the needs of a user community. Applications strictly focused on technology or software development, rather than dissemination of an existing resource, are not responsive to this FOA. Refinements to microscopes or tools necessary to customize them to the experimental needs of the end users is allowed. Projects should address compelling needs of neuroscience researchers working toward the goals of the BRAIN 2025 report that are otherwise unavailable or impractical in their current form.

Reissue of RFA-NS-18-020: Understanding the dynamic activity of brain circuits is central to the NIH BRAIN Initiative. This FOA seeks applications for proof-of-concept testing and development of new technologies and novel approaches for recording and modulation (including various modalities for stimulation/activation, inhibition and manipulation) of cells (i.e., neuronal and non-neuronal) and networks to enable transformative understanding of dynamic signaling in the central nervous system (CNS). This FOA seeks exceptionally creative approaches to address major challenges associated with recording and modulating CNS activity, at or near cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. It is expected that the proposed research may be high-risk, but if successful, could profoundly change the course of neuroscience research. Proposed technologies should be compatible with experiments in behaving animals, validated under in vivo experimental conditions, and capable of reducing major barriers to conducting neurobiological experiments and making new discoveries about the CNS. Technologies may engage diverse types of signaling beyond neuronal electrical activity such as optical, magnetic, acoustic and/or genetic recording/manipulation. Applications that seek to integrate multiple approaches are encouraged. If suitable, applications are expected to integrate appropriate domains of expertise, including biological, chemical and physical sciences, engineering, computational modeling and statistical analysis.

The purpose of this Funding Opportunity Announcement (FOA) is to encourage investigators to pursue translational activities and small clinical studies to advance the development of therapeutic, and diagnostic devices for disorders that affect the nervous or neuromuscular systems. Activities supported in this program include implementation of clinical prototype devices, non-clinical safety and efficacy testing, design verification and validation activities, obtaining an Investigational Device Exemption (IDE) for a Significant Risk (SR) study, as well as a subsequent small clinical study. The clinical study is expected to provide information about the device function or final design that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use. This FOA is a milestone-driven cooperative agreement program and will involve participation of NIH program staff in negotiating the final project plan before award and monitoring of research progress.

The purpose of this Funding Opportunity Announcement (FOA) is to encourage investigators to pursue a small clinical trial to obtain critical information necessary to advance recording and/or stimulating devices to treat central nervous system disorders and better understand the human brain (e.g., Early Feasibility Study). Clinical studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board (IRB), or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic implants. The clinical trial should provide data to answer key questions about the function or final design of a device. This final device design may require most, if not all, of the non-clinical testing on the path to more advanced clinical trials and market approval. The clinical trial is expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use. Activities supported by this Funding Opportunity include a small clinical trial to answer key questions about the function or final design of a device. As part of the BRAIN Initiative, NIH has initiated a Public-Private Partnership Program (BRAIN PPP) that includes agreements (Memoranda of Understanding, MOU) with a number of device manufacturers willing to make such devices available, including devices and capabilities not yet market approved but appropriate for clinical research. In general it is expected that the devices' existing safety and utility data will be sufficient to enable new IRB NSR or FDA IDE approval without need for significant additional non-clinical data. For more information on the BRAIN PPP, see http://braininitiative.nih.gov/BRAIN_PPP/index.htm

This is a reissue of RFA-MH-19-136. The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application. The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged. Tools that can be used in a number of species/model organisms rather than those restricted to a single species are highly desired. Applications that provide approaches that break through existing technical barriers to substantially improve current capabilities are highly encouraged.

Reissue of RFA-NS-19-011: The purpose of the NIH Blueprint and BRAIN Initiative Diversity Specialized Predoctoral to Postdoctoral Advancement in Neuroscience (D-SPAN) Award is to support a defined pathway across career stages for outstanding graduate students who are from backgrounds that are nationally underrepresented in neuroscience research. This two-phase award will facilitate completion of the doctoral dissertation and transition of talented graduate students to strong neuroscience research postdoctoral positions, and will provide career development opportunities relevant to their long-term career goal of becoming independent neuroscience researchers.

This is a reissue of RFA-MH-19-147. This FOA supports the development of software to visualize and analyze the data as part of programs of building the informatics infrastructure for the BRAIN Initiative. Other informatics programs include developing data standards that are needed to describe the new experiments that are being created by or used in the BRAIN Initiative ( RFA-MH-19-146 ), and creating the data infrastructures that will house the data from multiple experimental groups ( RFA-MH-19-145 ). Each of the programs is aimed at building an infrastructure that is used by a particular sub-domain of experimentalists rather than building a single all-encompassing informatics infrastructure now. Building the infrastructure one experimental area at a time will ensure that the infrastructure is immediately useful to components of the research community. As our understanding of the brain improves, it may be possible to create linkages between these various sub-domain specific informatics programs. Investigators of the informatics programs should keep that goal in mind and build for the future even though the current efforts are more limited in scope.

A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. While currently available technologies can provide some understanding, they may not be sufficient to accomplish this goal. For example, non-invasive technologies are low resolution and/or provide indirect measures such as blood flow, which are imprecise; invasive technologies can provide information at the level of single neurons producing the fundamental biophysical signals, but they can only be applied to tens or hundreds of neurons, out of a total number in the human brain estimated at 85 billion. Other BRAIN FOAs seek to develop novel technology (RFA-NS-17-003) or to optimize existing technology ready for in-vivo proof-of-concept testing and collection of preliminary data (RFA-NS-17-004) for recording or manipulating neural activity on a scale that is beyond what is currently possible. This FOA seeks applications for unique and innovative technologies that are in an even earlier stage of development than that sought in other FOAs, including new and untested ideas that are in the initial stages of conceptualization. In addition to experimental approaches, the support provided under this FOA might enable calculations, simulations, computational models, or other mathematical techniques for demonstrating that the signal sources and/or measurement technologies are theoretically capable of meeting the demands of large-scale recording or manipulation of circuit activity in humans or in animal models. The support might also be used for building and testing phantoms, prototypes, in-vitro or other bench-top models in order to validate underlying theoretical assumptions in preparation for future FOAs aimed at testing in animal models.

This Funding Opportunity Announcement (FOA) solicits applications to develop web-accessible data archives to capture, store, and curate data related to BRAIN Initiative activities. The data archives teams will work with the research community to incorporate tools that allow users to analyze and visualize the data, but the creation of such tools is not part of this FOA. The data archives will use appropriate standards to describe the data, but the creation of such standards is not part of this FOA. A goal of this program is to advance research by creating a community resource data archive with appropriate standards and summary information that is broadly available and accessible to the research community for furthering research.