The "BRAIN Initiative: Brain Behavior Quantification and Synchronization (R61/R33 Clinical Trial Optional)" funding opportunity, issued by the National Institutes of Health (NIH), supports research to develop tools and methods to quantify human behaviors and integrate these measurements with real-time brain activity recordings. Funded by NIH institutes such as NIMH, NEI, NIA, NIDA, and NICHD, among others, the initiative aligns with the BRAIN Initiative's goals to create high-resolution, dynamic insights into brain function. Through a phased R61/R33 award mechanism, this opportunity emphasizes developing novel hardware and software (R61 phase) that can be synchronized with established neural activity recording methods (R33 phase). These projects aim to enhance both the accuracy and precision of behavioral measurements in naturalistic settings, enabling transformative insights into brain-behavior relationships with applications in health, neurobehavioral, and neurodegenerative research.

The primary objectives are to advance understanding of how brain activity generates behavior, improve methods for quantifying behavior across various environments, and enable next-generation neuromodulation interventions. In the R61 phase, applicants are expected to design innovative, multimodal behavioral measurement tools, potentially incorporating elements like movement sensors or physiological monitors. These tools should be compatible with neuroimaging technologies and overcome current limitations, such as restricted temporal resolution or environmental sensing capabilities. The R33 phase involves the integration of these tools with neural recording methods, facilitating synchronized collection of behavioral and neural data. Projects that propose clinical trials in the R33 phase should focus on mechanistic studies, with a goal of advancing closed-loop neuromodulatory devices for complex neurobehavioral conditions.

Applicants must submit a Plan for Enhancing Diverse Perspectives (PEDP) to address inclusivity in their research approach, which will be evaluated as part of the scientific merit review. Eligible applicants include higher education institutions, nonprofits, for-profit entities, and government organizations. Foreign entities are also eligible to apply, and proposals involving collaborative, transdisciplinary teams are highly encouraged. Research teams should have expertise spanning neuroscience, behavioral science, ethics, data science, and engineering. Applicants must outline both their scientific approach and neuroethical considerations, detailing participant consent processes, ethical safeguards, and community engagement, especially when involving vulnerable populations.

Key submission requirements include a letter of intent 30 days before the application due date and adherence to NIH’s application guidelines. Applications must include a detailed plan for the R61 phase milestones, which NIH will review to determine eligibility for progression to the R33 phase. Applications lacking a PEDP or neuroethics attachment will be considered incomplete. NIH provides multiple submission options, including ASSIST and Grants.gov Workspace, and encourages applicants to apply early to address any technical issues.

Review criteria for the grant focus on the significance, innovation, and approach of the research, with particular emphasis on how well the tools and methods developed will enhance the precision of brain-behavior measurements. The project's environment, budget justification, timeline feasibility, and neuroethical considerations will also be evaluated. Proposals that include clinical trials should ensure trial designs are adequately powered and have rigorous quality control measures for data management and participant safety.

For FY 2026, NIH intends to allocate approximately $10 million to fund 8-10 awards under this initiative. Each award will be supported for up to 4 years in the R61 phase and 2 years in the R33 phase, with a combined project duration limit of 5 years. The application due date is January 22, 2025, and successful applicants can expect funding to begin in December 2025.