The Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R21 Clinical Trial Not Allowed) funding opportunity, released by the National Institute of Mental Health (NIMH), part of the National Institutes of Health (NIH), supports the development of next-generation brain stimulation devices for treating mental health disorders. This Notice of Funding Opportunity (NOFO), issued under Funding Opportunity Number PAR-25-286, is a reissue of PAR-22-038 and aligns with evolving agency priorities. The initiative encourages the design and engineering of novel devices or significant enhancements to current FDA-approved or cleared devices to improve spatiotemporal precision, closed-loop capabilities, and other advanced functionalities.

The purpose of this grant is to address the limitations of existing brain stimulation treatments such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), which are effective but have notable drawbacks, such as cognitive side effects and variability in treatment response. This funding opportunity seeks innovations that go beyond these current modalities to develop devices specifically tailored to mental health applications. Devices should be informed by current neuroscience findings and aim to modulate distributed brain networks, integrating multi-focal or closed-loop techniques. These projects should ideally be engineering-based, involving bench testing and potentially animal or limited human proof-of-concept studies, but not full clinical trials.

Funding will support research teams proposing design-directed, developmental, or discovery-driven technology development using integrative, multidisciplinary approaches. Applications must be submitted by diverse teams including experts in engineering, device development, neuroscience, computational science, and clinical research. Proposed projects may involve invasive or non-invasive devices and are encouraged to utilize new forms of energy (e.g., ultrasound) or technologies that significantly advance the field, including improvements in spatial resolution and real-time behavioral and neural data integration.

Eligible applicants include a broad range of U.S. and international entities such as higher education institutions, nonprofit organizations, for-profit companies, and various levels of government. All applicants must comply with NIH registration and submission procedures through platforms such as ASSIST or Grants.gov. The application package must include an Intellectual Property (IP) Strategy, Research Plan, and plans for data sharing with the National Institute of Mental Health Data Archive (NDA). Specific application sections must outline the translational potential, regulatory pathway, industry collaborations, and device validation strategies.

The application process follows the NIH standard R21 due dates with upcoming deadlines on February 16, June 16, and October 16 each year through October 2027. Applications are evaluated on scientific merit using criteria focused on the importance, innovation, rigor, feasibility, and investigator expertise. Funding is contingent on scientific review, available appropriations, and program priorities. The project period may not exceed two years, and budgets are capped at $275,000 total, with no more than $200,000 in any single year.

This grant does not support clinical trials or incremental improvements to existing devices, nor does it support studies focused solely on testing existing tools in scientific or clinical hypotheses. Instead, it supports early-stage, high-risk projects that offer innovative solutions for brain stimulation-based treatment of mental health disorders. Interested applicants are encouraged to consult with NIH contacts before submission to ensure alignment with program goals.