Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders (R21 Clinical Trial Optional)
Can you apply?
This grant is for researchers and research institutions seeking to advance understanding of neural circuitry in mental health disorders through invasive recording and stimulation methodologies, with optional clinical trial components. Eligible applicants typically include researchers at academic medical centers, research hospitals, and academic institutions with NIH-recognized administrative infrastructure. Applicants must hold a doctoral degree in a relevant field (MD, PhD, DO, DVM, DDS, or equivalent) and have demonstrated research capability. The R21 mechanism supports exploratory/developmental research to test new ideas and develop preliminary data, rather than fully developed research programs. U.S. institutions and eligible foreign organizations with appropriate administrative structures may apply. Research must focus on mental health disorders and their underlying neural mechanisms.
This grant is for researchers and research institutions seeking to advance understanding of neural circuitry in mental health disorders through invasive recording and stimulation methodologies, with optional clinical trial components. Eligible applicants typically include researchers at academic medical centers, research hospitals, and academic institutions with NIH-recognized administrative infrastructure. Applicants must hold a doctoral degree in a relevant field (MD, PhD, DO, DVM, DDS, or equivalent) and have demonstrated research capability. The R21 mechanism supports exploratory/developmental research to test new ideas and develop preliminary data, rather than fully developed research programs. U.S. institutions and eligible foreign organizations with appropriate administrative structures may apply. Research must focus on mental health disorders and their underlying neural mechanisms.
Program description
Reissue of RFA-20-351.The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications to pursue invasive neural recording studies focused on mental health-relevant questions. Invasive neural recordings provide an unparalleled window into the human brain to explore the neural circuitry and neural dynamics underlying complex moods, emotions, cognitive functions, and behaviors with high spatial and temporal resolution. Additionally, the ability to stimulate, via the same electrodes, allows for direct causal tests by modulating network dynamics. This funding opportunity aims to target a gap in the scientific knowledge of neural circuit function related to mental health disorders. Researchers should target specific questions suited to invasive recording modalities that have high translational potential. Development of new technologies and therapies are outside the scope of this NOFO.
Who can apply
Eligible applicants
- 501(c)(3) Public Charity
- City / Municipal Government
- County Government
- Nonprofits
- Private University
- Public Authority
- Public K-12 School
- Public University
- Researcher (independent)
- Small Business (SBA-defined)
- Special District
- State Government
- Tribal Nation
- Tribal Organization
Details
This grant is for researchers and research institutions seeking to advance understanding of neural circuitry in mental health disorders through invasive recording and stimulation methodologies, with optional clinical trial components. Eligible applicants typically include researchers at academic medical centers, research hospitals, and academic institutions with NIH-recognized administrative infrastructure. Applicants must hold a doctoral degree in a relevant field (MD, PhD, DO, DVM, DDS, or equivalent) and have demonstrated research capability. The R21 mechanism supports exploratory/developmental research to test new ideas and develop preliminary data, rather than fully developed research programs. U.S. institutions and eligible foreign organizations with appropriate administrative structures may apply. Research must focus on mental health disorders and their underlying neural mechanisms.
How to apply
Application links
Required documents
- R&R SF424 (R&R) form (NIH application form)
- Project Narrative and Research Strategy (typically 15 pages for R21)
- Specific Aims page
- Significance and Innovation section
- Approach section
- Budget and Budget Justification (Form PHS 398)
- Biographical Sketches for key personnel (NIH format CV)
- Institutional support letter and facilities description
- Institutional Review Board (IRB) approval or evidence of IRB engagement for human studies
- Vertebrate Animal Care and Use protocol (if animal work involved)
- Data Management and Sharing Plan
- Authentication of Key Biological and/or Chemical Resources
- Letters of support from collaborators (if applicable)
Program contact
- 👤 National Institutes of Health
- 📧 grantsinfo@nih.gov
- 📞 301-402-2541
Funding track record
Recent awards under CFDA 93.242 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$75,056,208
-
$74,756,329
-
$72,845,834
-
$64,705,159
-
$63,991,707
-
$54,214,022
-
$38,895,082
-
$38,475,557
-
$34,635,977
-
$34,475,710
Top States by Funding
- CA 15 awards $408.1M
- MA 9 awards $230.3M
- NY 6 awards $184.2M
- WA 4 awards $174.9M
- CT 3 awards $138.9M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.242). How funding has trended year over year.
| 2024 | $1,722,300,004 | |
| 2025 | $1,726,864,191 | |
| 2026 est. | $99,221,272 |
FAQ
Who is eligible to apply for this R21 grant?
Researchers with a doctoral degree in relevant fields (PhD, MD, DO, DVM, DDS or equivalent) at institutions with NIH administrative infrastructure, including academic medical centers, universities, and research hospitals. Both domestic and eligible foreign institutions may apply.
What is the R21 mechanism and how does it differ from other NIH grants?
The R21 is an exploratory/developmental research grant designed for new ideas and preliminary work. It typically supports higher-risk projects with smaller budgets than R01 grants, and does not require extensive preliminary data. However, applications must still be scientifically meritorious.
Can this grant support clinical trials?
Yes, this R21 specifically includes a clinical trial optional component, meaning clinical trial research is permitted but not required. Clinical trials may strengthen applications if they advance understanding of neural mechanisms in mental health.
How competitive is this grant mechanism?
R21 grants are competitive but generally less stringent than R01 mechanisms since they expect less preliminary data. Success rates typically range from 15-25% depending on the specific study section and year.
What budget range should I expect?
R21 grants typically support smaller projects than R01s, commonly ranging from $150,000-$300,000 total costs over 2-3 years. Budget must be justified by the scope of exploratory research proposed.
💡 Tips for applicants
- Emphasize the novel or innovative aspects of using invasive recording and stimulation to study mental health neural mechanisms; R21s reward creative, exploratory approaches that may be higher-risk than R01-type research
- Provide preliminary data demonstrating feasibility and scientific premise, even though R21s don't require extensive prior results; this significantly strengthens competitiveness
- Clearly define the specific mental health disorder(s) being studied and explain how the proposed neural circuit measurements will advance mechanistic understanding beyond existing knowledge
- If including clinical components, describe how invasive procedures will be ethically justified, safely conducted, and how outcomes will inform mental health treatment
- Ensure your institution has appropriate infrastructure (IRB, biosafety, animal care facilities if applicable) and clearly outline regulatory/ethical oversight; this is critical for invasive procedures
⚠️ Common mistakes
Applications often fail because they lack sufficient preliminary data to support feasibility of invasive recordings/stimulation in the proposed population, or they underestimate the complexity of regulatory and ethical approvals required for invasive human studies. Another common issue is failing to clearly articulate how the proposed neural circuit measurements will generate new mechanistic insights into mental health disorders rather than simply describing methodology.
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