BRAIN Initiative: New Concepts and Early-Stage Research for Recording and Modulation in the Nervous System (R21) (Clinical Trial Not Allowed)

RFA-EY-23-001

Companion Funding Opportunity: RFA-NS-24-004 , R01 Research Project
RFA-NS-24-005 , U01 Research Project (Cooperative Agreements)

This NOFO is related to the recommendations in sections II.2, II.3, and II.4 from the BRAIN 2025 Report. These three recommendations call for accelerated development of new large-scale recording technologies and tools for neural circuit manipulation. 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.

Achieving these goals requires the ability to record simultaneously from thousands or tens-of- thousands of neurons contributing to the dynamic activity in a neural circuit. The relevant activity may be in clusters of cells packed closely together or may be in widely distributed circuits. Current microelectrode and imaging technologies are limited in the number of cells from which activity can be isolated and sampled simultaneously, by the size or location of the area to be sampled, by the depth of penetration, and by the invasiveness of the technique that might prohibit their use in human experimentation. Non-invasive technologies suitable for use in humans are currently limited in spatial resolution and temporal dynamics, as well as in their reflection of on-going electrical activity in circuit elements. This NOFO seeks entirely new ideas, concepts and/or approaches from physics and engineering, and biology, for how these limitations might be overcome to enable increased recording capabilities on the scale of one or more orders of magnitude beyond that of current technology.

This NOFO is also related to the goals of the updated BRAIN 2.0 Report, which recommends expanding the functionality and integration of electrophysiological and neurochemical methods. The next generation of recording/modulation technology development should include efforts to improve cell-type and neurochemical specificity. Thus, an equally important goal of this NOFO is to discover novel ideas for technology capable of precisely manipulating activity in circuits. Dissecting the function of neural circuits requires the ability to precisely activate or inactivate brain cells (both neuronal and non-neuronal) in order to investigate underlying mechanisms and demonstrate causality. Current technologies such as microstimulation and optogenetic approaches are limited in specificity, temporal dynamics, and by the invasiveness of the technique.

Applications are expected to propose the development of ideas in the earliest stages for entirely new approaches for neural recording and/or precise manipulation of neural activity. Such ideas could encompass unique and innovative combinations of existing technology that create a synergistic result. An important goal is to stimulate new thinking and concepts for accelerating development of novel technologies that break current barriers to neural recording and/or manipulation. In addition to experimental approaches, this NOFO may support early-stage testing using calculations, simulations, computational models, or other mathematical techniques for demonstrating that the signal sources and/or measurement technologies are theoretically capable of meeting future demands. The support might also be used for building and testing phantoms, prototypes, and in-vitro or other bench-top models, in order to validate underlying theoretical assumptions in preparation for companion NOFOs aimed at proof-of concept testing in animal models.

The technologies that would ultimately evolve from these new approaches should be compatible with experiments in humans and/or behaving animals and should dramatically improve capabilities in order to enable experiments that are currently not possible. Preliminary data are not required; however, they may be included if available.

Applications from individuals not usually associated with neuroscience research or teams that cross boundaries forming interdisciplinary collaborations capable of bringing new and untested ideas are particularly encouraged. Accordingly, applicants might consider, where appropriate, multi-PD/PI applications that integrate appropriate expertise, including but not limited to biological, chemical, and physical sciences, as well as engineering, computational modeling, and statistics.

Application budgets may not exceed $400,000 total direct costs over a maximum three-year funding period. No more than $200,000 in  direct costs may be requested in any single year.

Not required

June 18, 2024

Martha Flanders, PhD
National Eye Institute (NEI)
Telephone: 301-827-5191
Email: BRAIN-FOAs@nih.gov