Funding Opportunity Announcements

This is a reissue of RFA-MH-21-175 to comply with DMSP policy. 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-MH-22-115 to comply with DMSP policy. 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.

Reissue of RFA-NS-22-027 to comply with DMSP - No new dates are being added. (Reissue of RFA-NS-18-014 and RFA-NS-21-014) This R34 NOFO solicits applications that offer 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, as described in the companion NOFO (RFA-NS-22-026). Applications should be exploratory research projects that use innovative, methodologically-integrated approaches to understand how circuit activity gives rise to mental experience and behavior.

Reissue of RFA-NS-22-026 to comply with DMSP - No new dates are being added.(Reissue of RFA-NS-18-030) This NOFO solicits applications for research projects that use innovative, methodologically-integrated approaches to understand how circuit activity gives rise to mental experience and behavior. The goal is to support projects that can realize a meaningful outcome within 5 years. Applications should address circuit function in the context of specific neural systems such as sensation, perception, attention, reasoning, intention, decision-making, emotion, navigation, communication or homeostasis. Projects should link theory and data analysis to experimental design and should produce predictive models as deliverables. Projects should aim to improve the understanding of circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating dynamic patterns of neural activity. Projects can use non-human and human species, and applications should explain how the selected species offers ideal conditions for revealing general principles about the circuit basis of a specific behavior.

Reissue of RFA-NS-22-028 to comply with DMSP - No new dates are being added. Reissue of:RFA-NS-18-029 and RFA-NS-20-029. This funding opportunity announcement (FOA) is designed to support teams of investigators that seek to cross boundaries of interdisciplinary collaboration to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications are encouraged to propose adventurous and challenging goals that can only be tackled by a synergistic team-based approach and have the potential to be transformative and/or to enable significant advances. These studies at the exploratory stage are intended for the development of experimental capabilities and/or theoretical frameworks in preparation for a future competition for larger-scale or extended efforts, including the BRAIN TargetedBCP R01 or the multi-component, Team-Research BRAIN Circuit Programs (U19). The overall goal of this FOA is to enable a large-scale analysis of neural systems and circuits within the context and during the simultaneous measurement of an ethologically relevant behavior. Toward this end, teams are expected to assemble and leverage multi-disciplinary expertise, and to integrate experimental with computational and theoretical approaches. Teams are expected to bridge fields by incorporating rich information on cell-types, on circuit functionality and connectivity, in conjunction with sophisticated analyses of an ethologically relevant behavior of an organism or a well-defined neural system. Teams are also expected to aim for a mechanistic understanding of the circuits of the central nervous system (CNS) by applying cutting-edge methods such as those for large-scale recording, manipulation, and analysis of neural circuits across multiple regions of the CNS.

Reissue of RFA-NS-22-011 to comply with DMSP. No additional receipt dates added. 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.

The purpose of the NIH BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) program is to enhance workforce 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 to assist awardees in launching competitive, independent research careers.

The goal of the NIH BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) program is to enhance workforce 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 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 to assist awardees in launching competitive, independent research careers.

Reissue of RFA-MH-22-220 to comply with DMSP. 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.

Invasive surgical procedures offer the opportunity for unique intracranial interventions such as the ability to record and stimulate intracranially within precisely localized brain structures in humans. Human studies using invasive technology are often constrained by a limited number of patients and resources available to implement complex experimental protocols and need to be aggregated in a manner that addresses research questions with appropriate statistical power. Therefore, this RFA seeks applications to assemble diverse, integrated, multi-disciplinary teams that cross boundaries of interdisciplinary collaboration to overcome these fundamental barriers and to investigate high-impact questions in human neuroscience. The research should be offered as exploratory research and planning activities to establish feasibility, proof-of-principle and early-stage development that, if successful, would support, enable, and/or lay the groundwork for a potential, subsequent Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain, as described in the companion FOA (RFA-NS-22-041). Projects should maximize opportunities to conduct innovative in vivo neuroscience research made available by direct access to the brain from invasive surgical procedures. Projects should employ approaches guided by specified theoretical constructs and by quantitative, mechanistic models where appropriate. Awardees will join a consortium working group, coordinated by the NIH, to identify consensus standards of practice, including neuroethical considerations, to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community.

This funding opportunity announcement (FOA) invites applications for creating the Data Coordination and Artificial Intelligence Center (DCAIC) for the Brain Behavior Quantification and Synchronization (BBQS) Consortium of the BRAIN Initiative. The FOA will support a single award to a multi-disciplinary team with a single or multiple PIs working on the five interrelated areas:1) Data Management; 2) Data Standards; 3) ML/AI Resources; 4) Data Ecosystem; and 5) Dissemination, Training and Coordination.

The purpose of the The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative Fellows (F32) program is to enhance the research training of promising postdoctorates, early in their postdoctoral training period, who have the potential to become productive investigators in research areas that will advance the goals of the BRAIN Initiative. Applications are encouraged in any research area that is aligned with the BRAIN Initiative, including neuroethics. Applicants are expected to propose research training in an area that clearly complements their predoctoral research. Formal training in analytical tools appropriate for the proposed research is expected to be an integral component of the research training plan. In order to maximize the training potential of the F32 award, this program encourages applications from individuals who have not yet completed their terminal doctoral degree and who expect to do so within 12 months of the application due date. On the application due date, candidates may not have completed more than 12 months of postdoctoral training.

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.

Reissue of RFA-NS-18-019: Understanding the dynamic activity of neural circuits is central to the NIH BRAIN Initiative. The invention, proof-of-concept investigation, and optimization of new technologies through iterative feedback from end users are key components of the BRAIN Initiative. This FOA seeks applications to optimize existing or emerging technologies through iterative testing with end users. The technologies and approaches should have potential to address major challenges associated with 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). These technologies and approaches should have previously demonstrated their transformative potential through initial proof-of-concept testing and are now ready for accelerated refinement. In conjunction, the manufacturing techniques should be scalable towards sustainable, broad dissemination and user-friendly incorporation into regular 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, electrical, magnetic, acoustic 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.

This Funding Opportunity Announcement (FOA) solicits applications for team-centric development and validation of innovative non-invasive imaging technologies that could have a transformative impact on the study of brain function/connectivity. Applications are expected to turn a novel concept into a functional prototype using this phased grant mechanism. The feasibility should be established by the end of its first phase and serve as a foundation for the transition to its second phase. Fully developing the technology into a functional prototype and validating it by in-vivo animal or human function/connectivity imaging are anticipated in the second phase. The research plan should provide a realistic timeline and tangible milestones to support the proposed development effort. Awards will be integrated into the BRAIN Non-Invasive Imaging Consortium, as a coordinated network on brain function/connectivity imaging.

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.

This Funding Opportunity Announcement (FOA) intends to support a group of Specialized Collaboratories that will adopt scalable technology platforms and streamlined sampling strategies and assay cascade to create comprehensive and highly granular brain cell atlases in human, non-human primates, and mouse, in coordination and collaboration with other BICAN projects. In particular, the Specialized Collaboratories are expected to complement the Comprehensive Centers in BICAN with distinct capabilities, competencies, and research aims. The overarching goal of the BICAN is to build reference brain cell atlases that will be widely used throughout the research community, providing a molecular and anatomical foundational framework for the study of brain function and disorders.

This FOA solicits the development of theories, computational models, and analytical tools to derive understanding of brain function from complex neuroscience data. Proposed projects could develop tools to integrate existing theories or formulate new theories; conceptual frameworks to organize or fuse data to infer general principles of brain function; multiscale/multiphysics models to generate new testable hypotheses to design/drive future experiments; new analytical methods to either support or refute a stated hypothesis about brain function. It is expected that the tools developed under this FOA will be made widely available to the neuroscience research community for their use and modification. Investigative studies should be limited to model parameter estimation and/or validity testing of the tools being developed.

This BRAIN Initiative FOA is to further develop molecular tools of high impact that are targetable to brain cell types for the monitoring and manipulation of neural circuits in experimental animals. This FOA is part of the BRAIN Initiative Armamentarium for Brain Cell Access transformative project. This will support iterative improvement of molecular payloads capable of monitoring and manipulating neural cell activity and that can be delivered to specific brain cell types using targeting technologies.

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.

This Funding Opportunity Announcement (FOA) solicits applications for team-centric development and validation of innovative non-invasive imaging technologies that could have a transformative impact on the study of brain function/connectivity. Applications are expected to turn a novel concept into a functional prototype using this phased grant mechanism. The feasibility should be established by the end of its first phase and serve as a foundation for the transition to its second phase. Fully developing the technology into a functional prototype and validating it by in-vivo animal or human function/connectivity imaging are anticipated in the second phase. The research plan should provide a realistic timeline and tangible milestones to support the proposed development effort. Awards will be integrated into the BRAIN Non-Invasive Imaging Consortium, as a coordinated network on brain function/connectivity imaging.

This FOA will support integrated, interdisciplinary research teams that focus on examining dynamic circuit functions related to behavior, using advanced and innovative technologies. The FOA will support programs with a necessarily-synergistic, team science approach. Awards will be made for 5 years, with a possibility of one competing renewal. Applications should incorporate overarching principles of circuit function in the context of specific neural systems underlying sensation, perception, emotion, motivation, cognition, decision-making, motor control, communication, or homeostasis. Applications should incorporate theory-/model-driven experimental design and should offer predictive models as deliverables. Applications should seek to understand circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Applications are expected to employ approaches guided by specified theoretical constructs, and are encouraged to employ quantitative, mechanistic models where appropriate. Applications will be required to manage their data and analysis methods in a framework that will be developed and used in the proposed U19 project and exchanged with other BRAIN U19 awardees for further refinement and development. Model systems, including the possibility of multiple species ranging from invertebrates to humans, can be employed and should be appropriately justified. Programs should employ multi-component teams of research expertise including neurobiologists, statisticians, physicists, mathematicians, engineers, computer scientists, and data scientists, as appropriate - that seek to cross boundaries of interdisciplinary collaboration. Applicants proposing to include human subjects with invasive neural recording must apply to the companion FOA, RFA-NS-XX-XXX.

This FOA will support integrated, interdisciplinary research teams from prior BRAIN technology and/or integrated approaches teams, and/or new projects from the research community that focus on examining circuit functions related to behavior, using advanced and innovative technologies. The goal will be to support programs with a team science approach that can realize meaningful outcomes within 5-plus years. Awards will be made for 5 years, with a possibility of one competing renewal. Applications should address overarching principles of circuit function in the context of specific neural systems underlying sensation, perception, emotion, motivation, cognition, decision-making, motor control, communication, or homeostasis. Applications should incorporate theory-/model-driven experimental design and should offer predictive models as deliverables. Applications should seek to understand circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Applications are expected to employ approaches guided by specified theoretical constructs, and are encouraged to employ quantitative, mechanistic models where appropriate. Applications will be required to manage their data and analysis methods in a prototype framework that will be developed and used in the proposed U19 project and exchanged with other U19 awardees for further refinement and development. Model systems, including the possibility of multiple species ranging from invertebrates to humans, can be employed and should be appropriately justified. Budgets should be commensurate with multi-component teams of research expertise including neurobiologists, statisticians, physicists, mathematicians, engineers, computer scientists, and data scientists, as appropriate - that seek to cross boundaries of interdisciplinary collaboration.

Invasive surgical procedures offer the opportunity for unique intracranial interventions such as the ability to record and stimulate intracranially within precisely localized brain structures in humans. Human studies using invasive technology are often constrained by a limited number of patients and resources available to implement complex experimental protocols and need to be aggregated in a manner that addresses research questions with appropriate statistical power. Therefore, this RFA seeks applications to assemble diverse, integrated, multi-disciplinary teams that cross boundaries of interdisciplinary collaboration to overcome these fundamental barriers and to investigate high-impact questions in human neuroscience. Projects should maximize opportunities to conduct innovative in vivo neuroscience research made available by direct access to the brain from invasive surgical procedures. Projects should employ approaches guided by specified theoretical constructs and by quantitative, mechanistic models where appropriate. 

Awardees will join a consortium work group, coordinated by the NIH, to identify consensus standards of practice, including neuroethical considerations, to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community. 

This is a reissue of RFA-MH-21-135. 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.

Reissue of:RFA-NS-18-029 and RFA-NS-20-029. This funding opportunity announcement (FOA) is designed to support teams of investigators that seek to cross boundaries of interdisciplinary collaboration to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications are encouraged to propose adventurous and challenging goals that can only be tackled by a synergistic team-based approach and have the potential to be transformative and/or to enable significant advances. These studies at the exploratory stage are intended for the development of experimental capabilities and/or theoretical frameworks in preparation for a future competition for larger-scale or extended efforts, including the BRAIN TargetedBCP R01 or the multi-component, Team-Research BRAIN Circuit Programs (U19).The overall goal of this FOA is to enable a large-scale analysis of neural systems and circuits within the context and during the simultaneous measurement of an ethologically relevant behavior. Toward this end, teams are expected to assemble and leverage multi-disciplinary expertise, and to integrate experimental with computational and theoretical approaches. Teams are expected to bridge fields by incorporating rich information on cell-types, on circuit functionality and connectivity, in conjunction with sophisticated analyses of an ethologically relevant behavior of an organism or a well-defined neural system. Teams are also expected to aim for a mechanistic understanding of the circuits of the central nervous system (CNS) by applying cutting-edge methods such as those for large-scale recording, manipulation, and analysis of neural circuits across multiple regions of the CNS.

This Funding Opportunity Announcement (FOA) supports Comprehensive Centers to develop and test technologies that can be scaled to brain-wide atlases of mouse circuit connectivity. Centers will establish data collection, analysis, and dissemination pipelines to demonstrate the feasibility of mapping cell-to-cell connectivity with a minimum resolution of synaptic connections. They will demonstrate the significance of the approach within the context of a chosen CNS sub-volume, by testing specific hypotheses relating circuit structure to function. They will also incorporate toolsets and infrastructure for integrating separately collected data from smaller volumes, as well as from other data collection modalities, and for enabling the neuroscience community to interact with and mine the data for new research questions. Centers will be integrated into the BRAIN CONNECTS Network, consisting of projects from this FOA and its companion announcements, as a coordinated effort aimed at developing wiring diagrams that can span entire brains across multiple scales.

This Funding Opportunity Announcement (FOA) supports Comprehensive Centers to develop and test technologies that can be scaled to brain-wide atlases of human and non-human primate circuit connectivity. Centers will establish data collection, analysis, and dissemination pipelines to demonstrate the feasibility of mapping region-to-region connectivity with a minimum resolution of individual cells and/or axon fibers. They will demonstrate the significance of the approach within the context of a chosen CNS sub-volume, by testing specific hypotheses relating circuit structure to function. They will also incorporate toolsets and infrastructure for integrating separately collected data from smaller volumes, as well as from other data collection modalities, and for enabling the neuroscience community to interact with and mine the data for new research questions. Centers will be integrated into the BRAIN CONNECTS Network, consisting of projects from this FOA and its companion announcements, as a coordinated effort aimed at developing wiring diagrams that can span entire brains across multiple scales.

This Funding Opportunity Announcement (FOA) supports Specialized Projects to develop current or emerging technologies to generate comprehensive atlases of brain connectivity, with an emphasis on human, non-human primate (NHP), and mouse. Projects validating approaches using other species are also permitted if well justified. Applications may address any aspects of the data collection, analysis, and dissemination pipelines, to enable faster and more cost-effective generation and interpretation of brain-wide wiring diagrams. Projects will offer distinct capabilities and competencies aimed at developing and optimizing current technologies or entirely new and potentially risky approaches. They will be integrated into the BRAIN CONNECTS Network, consisting of other Specialized Projects from this FOA, and Comprehensive Centers from its companion announcements, as a coordinated effort aimed at developing wiring diagrams that can span entire brains across multiple scales.

(Reissue of RFA-NS-18-014 and RFA-NS-21-014) This R34 FOA solicits applications that offer 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, as described in the companion FOA (RFA-NS-22-026). Applications should be exploratory research projects that use innovative, methodologically-integrated approaches to understand how circuit activity gives rise to mental experience and behavior.

(Reissue of RFA-NS-18-030) This FOA solicits applications for research projects that use innovative, methodologically-integrated approaches to understand how circuit activity gives rise to mental experience and behavior. The goal is to support projects that can realize a meaningful outcome within 5 years. Applications should address circuit function in the context of specific neural systems such as sensation, perception, attention, reasoning, intention, decision-making, emotion, navigation, communication or homeostasis. Projects should link theory and data analysis to experimental design and should produce predictive models as deliverables. Projects should aim to improve the understanding of circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating dynamic patterns of neural activity. Projects can use non-human and human species, and applications should explain how the selected species offers ideal conditions for revealing general principles about the circuit basis of a specific behavior.

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.

Reissue of RFA-MH-20-128 This Funding Opportunity Announcement (FOA) solicits applications to develop standards that describe experimental protocols that are being conducted as part of the BRAIN Initiative. It is expected that applications will solicit community input at all stages of the process. It is recommended that the first step of standard development will involve sharing data between different key groups in the experimental community in order to ensure that the developing standard will cover the way that all of those groups are collecting data. The developed standard is expected to be made widely available.

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-MH-19-400. This funding opportunity announcement (FOA), in support of the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, is one of several FOAs aimed at supporting transformative discoveries that will lead to breakthroughs in understanding human brain function. Guided by the long-term scientific plan, BRAIN 2025: A Scientific Vision, this FOA specifically seeks to support efforts addressing core ethical issues associated with research focused on the human brain and resulting from emerging technologies and advancements supported by the BRAIN Initiative. The hope is that efforts supported under this FOA might be both complementary and integrative with the transformative, breakthrough neuroscience discoveries supported through the BRAIN Initiative.

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.

Reissue of RFA-NS-18-019: Understanding the dynamic activity of neural circuits is central to the NIH BRAIN Initiative. The invention, proof-of-concept investigation, and optimization of new technologies through iterative feedback from end users are key components of the BRAIN Initiative. This FOA seeks applications to optimize existing or emerging technologies through iterative testing with end users. The technologies and approaches should have potential to address major challenges associated with 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). These technologies and approaches should have previously demonstrated their transformative potential through initial proof-of-concept testing and are now ready for accelerated refinement. In conjunction, the manufacturing techniques should be scalable towards sustainable, broad dissemination and user-friendly incorporation into regular 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, electrical, magnetic, acoustic 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.