Key Dates

Related Announcements

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Issued by

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

National Center for Complementary and Integrative Health (NCCIH)

Purpose

This is a Request for Information (RFI) from the NIH BRAIN Initiative that solicits input about advancing human neuroscience research on brain-behavior relationships through coordinated efforts involving neural stimulation and recording.

This RFI seeks input from scientific research communities, healthcare providers, patient advocacy groups, people with lived experience of brain or behavioral health disorders, educators, and other interested parties. The NIH encourages organizations (e.g., patient advocacy groups, professional organizations) to submit a single response reflective of the views of the organization and membership as a whole.

Background

Since 2014, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space. It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders. As one of several federal agencies involved in the BRAIN Initiative, NIH's contributions to the BRAIN initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas. This plan was updated and enhanced in 2019 by: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." 

The wide availability of large neurocognitive datasets such as the Human Connectome Project and the Adolescent Brain Cognitive Development study has facilitated large-scale network approaches across populations, which has enabled novel insights about fundamental brain function and neurocognitive dysfunction. However, complementary data involving controlled perturbations may prove useful to further advance brain-based causal explanations and thereby enhance our ability to translate findings to clinical application. This request for information seeks input on the use of systematic circuit perturbation in combination with neural recordings and appropriate behavioral assessments, collected with methodological rigor, well-vetted experimental standards, and sufficient sample sizes to account for human variability to inform understanding of brain-behavioral relationships.

There has been significant progress recently in using neural stimulation and recording approaches to understand brain networks and behavior, including application of varied computational approaches to study dynamics related to perturbations to a complex system, and methodological advances in measuring complex behavior in humans. This indicates the timeliness of considering if and how coordinated efforts to collect carefully designed experimental data characterizing network-level perturbations and their cognitive and behavioral outcomes may advance human neuroscience.

As noted in the BRAIN 2025 report, there are scientific, experimental, and ethical issues that are specific to human neuroscience, whether fundamental, translational, or clinical. To address current challenges and pave the way for transformative, impactful projects in basic research, NIH is seeking input from the community about understanding brain-behavioral relationships through coordinated efforts involving neural stimulation and recording.

Information Requested

Information is requested on the challenges and opportunities in understanding brain-behavioral relationships through neural stimulation and recording. We are particularly interested in feedback on the following topics, but respondents are encouraged to weigh in on other relevant topics:

• Key insights to be gained through coordinated efforts using perturbations and recordings in humans
  • What important new questions about fundamental brain function would be enabled via coordinated efforts across labs that would not be possible under current research constraints?
  • Does the current state of knowledge on the mechanisms of invasive and noninvasive stimulation approaches pose relevant questions or limitations on their use to probe network and fundamental brain function, and/or develop and test theoretical and computational models?
  • How can theory and modeling be best integrated with perturbations to understand how brain structure, function and dynamics subserve behavior?
• Considerations in ensuring perturbation-recording experiments are motivated and constrained by behavior
  • What levels of behavior (for example, task-based vs. naturalistic behavior in a lab setting vs. real-world behavior) might be most sensitive to perturbation effects from stimulation, acutely and chronically?
  • What considerations need to go into assessing online vs. offline effects (short-term and long-term) on behavior with invasive and non-invasive stimulation approaches?
  • What are the limitations to the breath, depth, and generalizability of behavioral testing that can be achieved as part of a broad effort to understand specific neural systems and circuit features and function?   
• Considerations related to population heterogeneity and effect generalizability
  • What considerations need to go into recruitment of inclusive and diverse samples for stimulation-recording studies? (See Diversity and Inclusion in Clinical Trials for details on NIH’s commitment to inclusivity in clinical trial research; note that basic research studies involving humans can fall within the NIH definition of a clinical trial.)
  • What strategies could be employed to avoid methodological and/or phenotypic biases that might impact interpretation of brain and behavioral data?
  • What considerations might guide minimal sample size estimation towards establishing reproducible brain-behavior associations?
•  Other practical considerations in establishing coordinated efforts involving non-invasive and invasive stimulation approaches 
  • What are the critical practical challenges and obstacles that would need to be addressed to enable coordinated efforts?
  • What incentives might be most effective in motivating key research partners to participate in a large-scale effort?
  • What considerations need to go into collecting, aggregating and curating data to ensure wide and responsible use?  
• Neuroethical considerations critical to study design and data collection and use with neurostimulation approaches for research purposes in humans
• Additional research gaps in human neuroscience that could be addressed using neural recordings and stimulation methods, and/or other recent technologies developed through the BRAIN Initiative

How to Submit a Response

Responses must be submitted to BRAIN-CircuitPerturbation@nih.gov by August 1^st, 2024. Responses should use the subject “RFI - Coordinated Neural Stimulating and Recording Efforts".

This RFI is for planning purposes only and should not be construed as a solicitation for applications or an obligation on the part of the government. The government will not pay for the preparation of any information submitted or for the government’s use of that information.

The NIH will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder's submission. Responses to the RFI may be reflected in future funding opportunity announcements. The information provided will be analyzed, may appear in reports, and may be shared publicly on an NIH website. Respondents are advised that the government is under no obligation to acknowledge receipt of the information or provide feedback to respondents with respect to any information submitted. No proprietary, classified, confidential, or sensitive information should be included in your response. The government reserves the right to use any non-proprietary technical information in any resultant solicitation(s), policies or procedures.

Inquiries

Please direct all inquiries to:

Clayton Bingham, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301.827.5832
Email: clayton.bingham@nih.gov

Vani Pariyadath, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301.443.3209
Email: vani.pariyadath@nih.gov

Andrew Breeden, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301.451.3185
Email: andrew.breeden@nih.gov