Notice of Special Interest (NOSI): Explainable Artificial Intelligence for Decoding and Modulating Neural Circuit Activity Linked to Behavior
Notice Number:

Key Dates

Release Date:

November 8, 2022

First Available Due Date:
February 05, 2023
Expiration Date:
February 06, 2026

Related Announcements

PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-184 – NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-196 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

Issued by

National Institute of Mental Health (NIMH)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)


Background and Rationale

The eXplainable Artificial Intelligence (XAI) framework aims to provide strong predictive value along with a mechanistic understanding of AI solutions by combining machine learning techniques with effective explanatory techniques. This Notice of Special Interest (NOSI) solicits applications in the area of XAI applied to neuroscientific questions of encoding, decoding, and modulation of neural circuits linked to behavior. This NOSI encourages collaborations between computationally and experimentally focused investigators. This NOSI seeks the development of machine learning algorithms that are able to mechanistically explain how experimental manipulations affect cognitive, affective, or social processing in humans or animals. Proof-of-concept applications aimed at improving the current state of the technology that uses XAI to provide unbiased, hierarchical explanations of causal relationships between complex neural and behavioral data are also appropriate.

Despite the rapid growth and adoption of machine learning and artificial intelligence (AI) techniques to scientific questions, the lack of insight into the inner workings of these approaches has impeded full scientific understanding that leads to machine-identified neuro-behavioral mechanisms. However, machine learning techniques have often been applied to categorize and predict neural and behavioral outcomes without providing a mechanistic understanding of what drives those predictions and classifications. Understanding the mechnistic factors critical to a machine-learning-based outcomes may lead to the identification of novel neurobehavioral solutions, theories, and potential targets for further studies or for intervention development.XAI consists of artificial intelligence algorithms in which the processes of arriving at final actions (e.g., predictions, classifications, and recommendations) can be easily understood by its users. XAI aims to overcome limitations of classical machine learning, including a lack of transparency and non-generalizability, by keeping the human-in-the-loop. While optimizing for accuracy or performance, a standard AI may learn useful rules from the specific training set. However, it may also learn inappropriate or non-generalizable rules. XAI provides methods to examine existing machine learning models more closely and new approaches that are explicitly designed to provide greater transparency. In a transparent XAI framework, users will have the ability to audit specific machine-identified rules/hypotheses and to discover how how much of the outcome variance those rules explain and how likely it is that the system will generalize outside a specific training set.

XAI is about enhancing machine-human collaborative intelligence in a new model in which researchers and end-users co-work with AI systems rather than using them as tools. As in most successful collaborations, each brings to the table abilities that the other lacks. NIMH promotes a deep mechanistic understanding of normative and abnormal neurobehavioral brain functions linked to mental health and the pathophysiology of psychiatric disorders. NIMH is interested in transforming classical ‘black box’ machine learning models into XAI ‘glass box’ models, without significantly sacrificing performance. The goal of this NOSI is to encourage investigators to apply XAI techniques to further our understanding of the neural circuitry linked to behavior and to improve our understanding of therapeutic strategies to enhance cognitive, affective, or social function. To develop new treatments for mental illness, a better understanding of how to modulate neural dynamics responsible for complex functional domains and/or maladaptive behaviors is critical. In order to achieve this understanding using XAI techniques, collaborations between computational and experimental investigators are strongly encouraged. In the context of mental health, the amount and type of explanatory information accessed may vary based on the stakeholder (clinicians, patients, or researchers) interacting with the AI system. Projects developing XAI for use in animal and/or human research are appropriate to this announcement. Human studies may involve healthy controls, community samples, and/or patient populations.

Examples of XAI research projects of interest to NIMH include, but are not limited to, the following:

  • Employing new or existing in vivo measurements and/or active manipulations of neural circuits datasets from patients, healthy humans, and/or animals. Manipulations may consist of electrical or magnetic brain stimulation, optogenetics, genome editing, pharmacological compounds, or other modalities. Projects where neurostimulation parameters are automatically adjusted to account for changes in neuro-behavioral activity (e.g., closed-loop methods) are encouraged.
  • Applying existing or novel XAI techniques to provide additional explanatory power to traditional machine learning techniques (e.g., counter-factual probes, generalized additive models, generative adversarial network techniques) able to handle fused multimodal (behavioral and neurophysiological) datasets.
  • Developingsigning, applying, and validating XAI models with the sole purpose of explanation in prospective or restospective (secondary data analyses) Mental Health relevant studies/datasets.
  • Rich labeling of a model’s features with semantic information that is understandable by the users (label propagation techniques are encouraged).
  • Estimating the influence of a given feature on model prediction accuracy or deep neural network decisions by using causal statistical methods.
  • Integrating data-driven and theory-driven models (e.g., machine learning models and biophysically informed models).
  • Implementing biologically inspired machine learning techniques that use the anatomy or physiology of the nervous system to constrain or optimize their implementation.
  • Allowing a machine learning algorithm to unbiasedly discover the governing equations underlying a dynamical system by analyzing co-varying multimodal (or parametric) data.
  • Using XAI algorithms to understand biological mechanisms of action and/or complex changes in brain network dynamics mediated by small molecule drugs, promising biologics, behavioral interventions, environmental manipulations, or developmental changes.
  • Expert-in-the-loop machine learning, combining expert knowledge and machine intelligence to create more effective machine learning algorithms. Humans could be involved in both the training and testing stages of building an algorithm.
  • XAI algorithms applied to rigorous clinical studies such as biological and/or behavioral marker-guided adaptive trial designs, to efficiently and quickly mine complex datasets to reveal optimal treatment approaches based on machine-explained predictive markers as well as patient bio-types linked to treatment response.
  • XAI application in the early phases of treatment development to integrate data across species and levels of analyses (i.e., omics, anatomy, physiology, and functional effects) to 1) identify and mechanistically explain potential treatment targets that are amendable to evaluation in animals and/or 2) suggest optimal neurophysiological and behavioral readouts in animals that are predictive of effects in humans

Areas of Low Program Priority

  • Mathematical or computational research on AI not directly related to neural systems
  • Solely behavioral research not involving measurement or manipulation of neural circuits

Office of Research on Women’s Health (ORWH) Specific Interests

The Office of Research on Women’s Health focuses on research that is relevant to the health of women across the life course and advancing science where the consideration of sex and/or gender influences on health are integrated across the biomedical research enterprise, as highlighted in the 2019-2023 Trans-NIH Strategic Plan for Women's Health Research. Computational Psychiatry uses modeling tools, integrating multiple levels and types of analysis, to enhance understanding and treatment of psychiatric illness and prediction of behavior/symptom change. In the context of this FOA, ORWH is interested in supporting studies where principles of computational modeling are employed to explore sex and/or gender differences and/or health disparities questions relevant to psychopathology. Advancing rigorous and ethical research to understand the fundamental relationship between sex and gender-specific symptoms and underlying neurobiological function leading to clinically useful applications/intervention insights for populations of women that bear a disproportionate burden of risks and poorer outcomes are of particular interest.

  • The design and testing of computational models to imitate sex and gender differences in clinical phenotypes enabling investigation of underlying neurobiological function that correlates with psychiatric symptoms/somatic responses
  • To design and test simulation modeling tools for psychiatric symptoms to enable study of emotional, behavioral and physiological responses differences in psychiatric disorders by unique population level psychosocial risk factors (e.g. social determinants frequently associated with poor health in marginalized communities)

Application and Submission Information

This notice applies to due dates on or after February 5, 2023 and subsequent receipt dates through February 5, 2026. 

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

  • PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-184 – NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
  • PA-20-185  - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
  • PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
  • PA-20-196 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)
  • PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed.

Although ORWH is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Mauricio Rangel-Gomez, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-435-6908

Siavash Vaziri, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1576

Damiya Eve Whitaker
Office of Research on Women's Health (ORWH)
Phone: 240-276-6170

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415