BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed)
Funding Agency:
- National Institutes of Health
This NOFO is related to the recommendations in section III of the BRAIN 2025 Report, with the goal to ‘produce a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity'. Towards this end, the report calls for accelerated development of new and improved technologies for recording and manipulating neural activity at the level of cells and circuits. These new technologies and approaches will provide unprecedented opportunities for exploring how the nervous system encodes, processes, utilizes, stores, and retrieves vast quantities of information. A better understanding of this dynamic neural activity will enable researchers to seek new ways to diagnose, treat, and prevent brain disorders.
This NOFO is part of a suite of RFAs representing different stages of technology development spanning early proof-of-concept and technology validation through optimization and dissemination, as well as studies aimed at understanding the biological and biophysical mechanisms of neural signals and their modulation (for more information, see https://braininitiative.nih.gov/brain-programs/technology-development).
This NOFO seeks applications to optimize instrumentation and device technologies for recording and modulation of neural cells and circuits, to address major challenges and to enable transformative understanding of dynamic signaling in the central nervous system. It is expected that the proposed technologies and approaches have previously demonstrated their transformative potential through initial proof-of-concept testing, and are ready for accelerated refinement through iterative engineering and end-user feedback, appropriate for a path towards sustainable dissemination and user-friendly incorporation into routine neuroscience research.
Applications may propose development of instrumentation hardware and/or devices and associated software. Approaches may utilize any modality such as optical, electrical, magnetic, or acoustic recording/manipulation, to target neuronal electrical signals or other forms of neural activity, including intracellular signaling and engagement of non-neuronal cells in circuit function.
This NOFO is a re-issue of RFA-NS-21-027, which included support for molecular constructs for recording and manipulating neural activity. However, with this re-issue projects primarily focused on molecular technologies are not supported by this NOFO.
Investigators proposing molecular approaches are encouraged to consider the following alternative NOFOs (or their reissue), which is specifically targeted to molecular technologies that are ready for iterative engineering, optimization, and benchmark testing:
RFA-MH-22-245 BRAIN Initiative: Engineering and optimization of molecular technologies for functional dissection of neural circuits (UM1 Clinical Trial Not Allowed)
Projects at an earlier stage of development can consider the following more general NOFOs (or their reissue), which do allow projects primarily focused on development of molecular technologies:
RFA-MH-21-175 BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01 Clinical Trial Not Allowed)
RFA-EY-21-001 BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed)
RFA-NS-25-018 (companion to this FOA) BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed)
For this and the companion NOFO, the aim of the proposed technologies should be to reduce major barriers to conducting neurobiological experiments, including considerations of cost and ease of access, and to enable new discoveries for understanding neural circuit function. Technologies should address major challenges associated with recording and modulating CNS activity, at cellular or circuit resolution, and should contribute to an overall ecosystem of technologies spanning multiple spatial and temporal scales in any region throughout the CNS. Precise cellular or circuit targeting may be attained via experimental design features such as genetic manipulation, in combination with the spatial resolution capabilities of the proposed technology.
Applicants proposing non-invasive neuroimaging technologies (fMRI, PET, etc.) that are not expected to achieve cellular/circuit resolution (see “Applications Not Responsive to this NOFO” below) should consider the following BRAIN Initiative NOFO (or its reissue):
RFA-EB-22-001, BRAIN Initiative: Transformative Brain Non-invasive Imaging Technology Development (UG3/UH3 Clinical Trial Not Allowed).
The approaches should be compatible with experiments in behaving animals, with an expectation that they will be validated with in vivo experiments during the course of the project. Proposed validation experiments must focus on demonstrating the capabilities and potential impact of the technology, rather than advancing the state of biological knowledge as the primary project goal.
Applicants interested in applying new technologies to understand circuit function, rather than developing technologies, should consult the following website for a listing of relevant BRAIN NOFOs: https://braininitiative.nih.gov/brain-programs/understanding-circuits.
Applications are encouraged to integrate multiple approaches, and where appropriate, to leverage diverse domains of expertise from biological, chemical, and physical sciences, engineering, computational modeling, and statistical analysis.
NOFO Goals
Applications are expected to address any or all the following three general goals for the FOA:
1. Develop New Network Recording Capabilities
Recording dynamic neural activity from complete neural networks, over long periods, in any area of the brain is a challenging but essential goal. Advances in the exploration and development of new technologies for neuronal and non-neuronal cell recording, including methods based on electrodes, microelectronics/microchips, imaging, and nanoscience are encouraged.
2. Develop Tools for Circuit Manipulation
The ability to activate and inhibit specific populations of neurons is key to understanding functional circuits. It will advance the scope of knowledge from observation of neural phenomena to a mechanistic understanding of neural causation. A new generation of hardware and software for instrumentation and devices for optogenetics, pharmacogenetics, biochemical, electromagnetic and/or acoustic modulation needs to be developed for use in animals, and potentially translated to humans, to enable the immense potential of circuit manipulation.
3. Link Neural Activity to Behavior
The goal of this FOA is to produce technologies with potential to elucidate central nervous system function in the context of complex behaviors. Proposed technologies should be compatible with experiments in behaving animals, with an expectation of in vivo validation during the course of the project. Novel approaches to link neural activity to specific behaviors, including computational and statistical tools, are encouraged.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
June 02, 2025
Grace M. Hwang, PhD
Edmund (Ned) Talley, PhD
National Institutes of Neurological Disorders and Stroke (NINDS)
Email: BRAIN-FOAs@nih.gov