Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders (R21 Clinical Trial Optional) | PAR 25 291

Opportunity Information: Apply for PAR 25 291

The National Institutes of Health (NIH) is offering an R21 grant opportunity titled "Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders (Clinical Trial Optional)" under funding opportunity number PAR 25 291. This NOFO is a reissue of RFA-20-351 and is designed to push forward human neuroscience research that can directly clarify how brain circuits function in ways that are relevant to mental health conditions. The core idea is to support projects that take advantage of rare but powerful opportunities to record neural activity invasively in humans, typically in clinical contexts where electrodes are already implanted for medical reasons, and to use those recordings to answer targeted questions about mood, emotion, cognition, and behavior.

The opportunity is centered on invasive neural recording because it offers a level of detail that noninvasive tools often cannot match. By collecting signals with high spatial and temporal resolution, researchers can examine neural circuitry and fast-changing neural dynamics as they unfold during specific tasks, symptoms, or behavioral states. A key feature emphasized in the announcement is that the same implanted electrodes can sometimes be used not only to record but also to stimulate. That stimulation capability makes it possible to move beyond observation and run more causal tests, for example by perturbing a network and evaluating how changes in neural dynamics relate to shifts in symptoms, affective state, or cognitive performance. In practical terms, NIH is encouraging studies that leverage this combined record-and-stimulate setup to close specific gaps in understanding about circuit-level mechanisms involved in mental health disorders.

NIH is looking for proposals that focus on clearly defined, mental health-relevant scientific questions that are particularly well suited to invasive methods and that have strong translational potential. The translational emphasis here is about generating insights that could meaningfully inform how the field conceptualizes disorders, symptoms, or circuit dysfunction in humans, rather than remaining purely descriptive. At the same time, the NOFO draws a boundary around what it will support: the development of new technologies and the development of new therapies are explicitly outside the scope. In other words, applicants should not frame the project as an engineering program to invent new devices or as a clinical development effort to create or validate a new treatment. The fit is strongest for hypothesis-driven or question-driven studies that use existing invasive recording and stimulation opportunities to reveal mechanisms in humans.

This is a discretionary, NIH-administered grant program in the health category (CFDA 93.242) using the R21 activity code, and it is labeled "clinical trial optional," meaning applicants may propose studies that include a clinical trial component when appropriate, but they are not required to do so. The listed award ceiling is $200,000. The opportunity is open to a broad range of applicants across government, academia, nonprofit, and industry settings, including state and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized tribes and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and additional eligible entities. The NOFO also highlights inclusion of organizations such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and even non-U.S. (foreign) entities and regional organizations, signaling broad eligibility as long as the proposed work aligns with NIH requirements.

Key logistics included in the source data are that the opportunity was created on 2024-11-22, and the original closing date listed is 2028-01-07. Overall, the program is best understood as a mechanism to capitalize on clinically available invasive neural access in humans to answer focused, high-impact questions about the neural circuitry underlying mental health-related functions and dysfunctions, using recording and, when feasible, stimulation to connect brain dynamics to behavior and symptoms in a way that can sharpen the field's mechanistic understanding.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders (R21 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2024-11-22.
• Applicants must submit their applications by 2028-01-07.
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 291

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: