The National Institute of Mental Health (NIMH) has reissued a Notice of Funding Opportunity (NOFO), PAR-25-290, to advance understanding of neural circuitry related to mental health disorders using invasive recording and stimulation techniques in humans. This R01 Research Project Grant supports studies that employ invasive neural recordings to achieve high spatial and temporal resolution insights into brain activity underlying complex moods, emotions, cognition, and behaviors. It also allows for causal testing via stimulation to modulate neural networks. Projects should address mental health-relevant questions with translational potential but are not required to result in immediate therapies. While this NOFO encourages long-term, detailed research, a companion R21 NOFO (PAR-25-291) supports shorter, exploratory studies.

The program emphasizes collaborative research with multidisciplinary teams including neurosurgery, neuroscience, psychiatry, engineering, ethics, and related fields. Examples of eligible research include acute intra-operative recordings, sub-acute recordings in epilepsy monitoring, chronic recordings using DBS systems, and studies applying novel technological methods such as AI or digital phenotyping. Projects using prospective or retrospective data are encouraged. Applications focused solely on animal studies, traditional therapeutic device trials, or stand-alone technology development without scientific inquiry are ineligible. All submissions must integrate neuroethical considerations and a Plan for Enhancing Diverse Perspectives (PEDP).

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, and various government entities. Applications from underrepresented groups and diverse research environments are strongly encouraged. Foreign institutions and collaborations are permitted. The program does not require cost-sharing, and there are no specified limits for application budgets, which must align with project needs. The maximum project period is five years.

Key dates include an open submission start on January 5, 2025, with the earliest application due date on February 5, 2025, and subsequent standard NIH cycles. Letters of intent are due 30 days before application deadlines. Applications must comply with NIH submission standards, including detailed descriptions of methodologies, ethical considerations, and data management plans. Submissions must use one of several NIH-approved platforms such as ASSIST or Grants.gov Workspace.

Applications will be evaluated for scientific and technical merit through NIH’s peer review process, considering the importance of the research, rigor and feasibility of the approach, and expertise and resources available. Successful applications are expected to demonstrate innovation, translational potential, and inclusivity. Award notifications will follow review and advisory council deliberations, with the first possible start date in December 2025.

This funding opportunity aims to bridge gaps in understanding mental health disorders' neural circuits, potentially informing future brain stimulation therapies and improving mental health care. Detailed application instructions and contact information for scientific, peer review, and financial inquiries are provided within the NOFO.