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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.

The purpose of this Funding Opportunity Announcement (FOA) is to encourage grant applications for investigator-initiated prospective observational comparative effectiveness research (CER) to the National Institute of Neurological Disorders and Stroke (NINDS). The study must address questions within the mission and research interests of the NINDS and may evaluate preventive strategies, diagnostic approaches, or interventions including drugs, biologics, and devices, or surgical, behavioral, and rehabilitation therapies. Information about the mission and research interests of the NINDS can be found at the NINDS website (https://www.ninds.nih.gov/). Studies proposed should provide a cost-effective means of collecting data with a meaningful bearing on current clinical practice. Awards made under this FOA will initially support a milestone-driven planning phase (UG3) for up to 2 years, with possible transition to a observational study phase of up to five years (UH3). Only UG3 projects that have met the scientific milestones and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA. The UG3 phase for observational studies will permit both scientific and operational planning activities. Scientific planning activities include small-scale data collection to assess the feasibility and/or acceptability of data collection, storage, and planned analyses. Operational planning activities include, at a minimum, development of recruitment and retention strategies, case report forms, data management system and other tools for data and quality management. The UH3 phase of the award will support the conduct of investigator-initiated observational study.

This funding opportunity announcement (FOA) is a reissue due to an omission of TRAINING RECORD review questions in Section V. This FOA encourages applications for the Chronic, Non-Communicable Diseases and Disorders Across the Lifespan: Fogarty International Research Training Award (NCD-LIFESPAN) D43 program for institutional research training programs in low-and middle-income countries (LMICs, as defined by the World Bank classification system). Applications may be for collaborations between institutions in the U.S and an eligible LMIC or may involve just LMIC institutions if there is a previous track record of externally funded research and/or research training programs by the lead LMIC institution. The proposed institutional research training program is expected to sustainably strengthen the NCD research capacity of the LMIC institutions, and to train in-country experts to develop and conduct research on NCDs across the lifespan, with the long-range goal of developing and implementing evidence-based interventions relevant to their countries. The main focus of research training covered in the application must be relevant to the interests of at least one of the participating NIH ICs as stated by each in this FOA. Other NCD topics may be included as secondary and complementary focus areas. This Funding Opportunity Announcement (FOA) allows support of trainees as the lead investigator of an independent clinical trial; or a separate ancillary study to an existing trial; or to gain research experience in a clinical trial led by another investigator, as part of their research and career development.

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.

The overarching purpose of this Funding Opportunity Announcement (FOA) is to promote the discovery and/or early evaluation of strong candidate biomarkers and biomarker signatures that can be used as tools to facilitate the clinical development of neurotherapeutics and their use in clinical practice. Specifically, the focus of this FOA is on the identification and initial biological, analytical and clinical evaluation of biomarkers and biomarker signatures for neurological and neuromuscular disorders. Although research supported by this FOA can include animal studies, it must also include preliminary human evaluation using carefully standardized human samples or datasets. The goal of this initiative is to deliver candidate biomarkers or biomarker signatures that are ready for definitive analytical and clinical validation studies.

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 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 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-18-030) 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-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.