Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders (R21 Clinical Trial Optional) | PAR 21 288

Opportunity Information: Apply for PAR 21 288

Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders (R21 Clinical Trial Optional) is an NIH discretionary grant opportunity (Funding Opportunity Number PAR 21 288; CFDA 93.242) that supports short, exploratory research projects using invasive neural recordings in humans to answer questions that are directly relevant to mental health. This FOA is a reissue of RFA-20-351 and is designed around a specific scientific gap: despite major progress in neuroscience, there is still limited, high-resolution knowledge of how human neural circuits and fast-changing network dynamics relate to complex mood states, emotions, cognition, and behavior in the context of mental health disorders. The R21 mechanism signals that the program is oriented toward early-stage, high-impact studies that can generate strong preliminary evidence or proof-of-concept insights rather than long, multi-phase development programs.

The central focus is on research that leverages the unique strengths of invasive recording modalities, namely their ability to capture neural activity with both high spatial resolution (pinpointing activity to specific brain regions and circuits) and high temporal resolution (tracking rapid neural dynamics as they unfold). The FOA emphasizes that these approaches offer an unparalleled window into the functioning human brain, which can be difficult or impossible to match with noninvasive methods when the goal is to characterize precise circuit-level mechanisms. A key added value highlighted by the announcement is that the same implanted electrodes used for recording can also be used for stimulation, enabling causal tests. In practical terms, this means applicants are encouraged to move beyond purely correlational observations (for example, a circuit pattern that tends to occur during a symptom state) and to design studies that can probe whether modulating a circuit changes relevant network dynamics or behavioral and emotional outcomes.

Applications are expected to be built around specific, well-justified scientific questions that are particularly suited to invasive recording and stimulation in humans and that have clear translational potential for mental health. The translational emphasis here is about producing knowledge that could meaningfully inform future clinical understanding or downstream approaches, not about building new devices or directly developing treatments within this award. The FOA is explicit that the development of new technologies and therapies is outside its scope. In other words, the program is meant to fund studies that use existing invasive recording and stimulation opportunities to clarify mechanisms and circuit function related to mental health disorders, rather than engineering new hardware, creating new stimulation systems, or running therapy-development pipelines.

The opportunity is labeled "Clinical Trial Optional," meaning proposed work may or may not meet the definition of a clinical trial depending on the study design, and applicants can propose either type as appropriate. This is relevant for teams planning stimulation components or symptom-focused outcome assessments, since some stimulation studies may cross into clinical trial territory depending on intent and endpoints, while other projects may remain mechanistic and observational even if conducted in clinical settings.

Eligibility is broad and includes many types of U.S. organizations and institutions, such as state, county, and local governments; special districts; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; other tribal organizations; public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The FOA also lists additional eligible applicant categories that emphasize inclusion across diverse institution types and geographies, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, U.S. territories or possessions, and certain non-U.S. entities such as foreign organizations and regional organizations. The sponsoring agency is the National Institutes of Health, and the original closing date shown in the source data is 2023-01-13.

In summary, this NIH FOA supports R21 projects that use invasive neural recording, and where appropriate stimulation, in humans to answer targeted, high-value questions about the neural circuitry and dynamics underlying mental health disorders. The program is positioned to accelerate mechanistic understanding with strong translational relevance, while intentionally excluding technology invention and therapy development as primary aims.

• 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 2021-07-28.
• Applicants must submit their applications by 2023-01-13. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 21 288

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