Key Dates

Related Announcements

• May 5, 2020 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See PA-20-184

Issued by

National Institute of Mental Health (NIMH)

Purpose

Overview

NIMH is issuing this Notice of Special Interest (NOSI) to encourage research on task-based behavioral measures that engage brain systems relevant to anhedonia. These behavioral measures are expected to be used as a proxy for brain target engagement, therefore neuroimaging or other brain measures with similar spatial resolution should be used to demonstrate that the proposed behavioral tasks engage brain systems relevant to anhedonia. The goal is to identify a battery of behavioral tasks that can be used as quantitative tools for future use in the evaluation of dysfunction within domains of mental health relevant to anhedonia and for future treatment development.

Background

Anhedonia is typically defined as an inability to experience pleasure and/or a lack of interest in pursuing activities that were previously pleasurable. It is both a central feature of major depressive disorder (MDD) and a potential trait marker for vulnerability to other psychiatric conditions and suicidality. Despite its prevalence, there are currently no reliable, validated behavioral measures that can be used for the development and assessment of treatments for anhedonia. Clinical and imaging studies suggest that anhedonia is more multifaceted than a simple loss of pleasure, and more aptly characterized as a state arising from disruptions in the constituent brain systems underlying reward, motivation, and/or hedonic processing. These findings suggest a potential for using behavioral tasks that target these brain systems as transdiagnostic readouts in the development of interventions for anhedonia associated with mental illnesses.

Research Objectives

This NOSI recognizes the need to identify behavioral tasks that can be used as readouts for the engagement of specific brain systems postulated to be dysfunctional in anhedonia. Candidate behavioral tasks are expected to tap into functional domains implicated in anhedonia that can be reliably identified at neurobiological levels (e.g. neuroimaging). The outcomes sought are quantitative behavioral tasks that can be used in the future as a more precise way of defining clinical features of anhedonia for use in both diagnosis and treatment development. It is expected that the knowledge derived from these basic experimental research studies will help to establish links among dysfunctional brain circuits, domains of function, and symptoms of anhedonia while paving the way for back and forward translation, diagnosis and treatment development.

To be considered under this NOSI, applications should:

1. Propose behavioral tasks that target specific brain system(s) relevant to anhedonia.
2. Include neuroimaging and/or other brain activity recording techniques to demonstrate that the chosen task(s) engage the targeted brain subsystem.

Please note that this NOSI encourages basic neuroscience research studies in human subjects that will serve as the initial proof of concept, therefore applications should be submitted to the NIH Parent R01 Basic Experimental Studies with Humans Required (PA-20-184). These basic experimental studies in both healthy and clinical populations are designed to understand a biological or behavioral process and not to test the safety or demonstrate the efficacy/effectiveness of an intervention. Investigators seeking to develop treatments and/or test the effectiveness of treatment and interventions should submit applications under NIMH clinical trial NOFOs

Specific Areas of Research Interest

Examples of specific research areas of interest to NIMH include, but are not limited to, the following:

• The development of behavioral tasks that target novel and/or existing constructs relevant to anhedonia.
• Consideration and assessment of the extent of correlation with existing clinical measures (e.g., Snaith–Hamilton Pleasure Scale, Temporal Experience of Pleasure Scale (TEPS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Development and validation of the Dimensional Anhedonia Rating Scale (DARS) for the domain of anhedonia being targeted, unless there are no established clinical measures for the investigated construct.
• Development of tasks that are applicable across diagnostic categories in which anhedonia is a symptom, recognizing that some tasks may not be appropriate for all patient populations.
• Behavioral tasks and targeted brain system measures that are robust and have sensitivity to detect change in response to active modification with the intent to gain a fundamental understanding of the basic phenomenon of the relation between brain measures and behavior.
• Studies proposing behavioral tasks that include consideration of internal reliability, test-retest reliability, practice effects, ceiling/floor (i.e., range) effects, and optimal task length and difficulty.
• Studies developing novel behavioral tasks that examine cognitive bases of anhedonia and dysfunctions in domains beyond the Research Domain Criteria (RDoC) positive valence domain. These could include, but are not limited to, cognitive systems, negative valence systems (e.g., frustrative non-reward, and anxiety), social processes and other RDoC domains.
• Projects that propose to test novel behavioral tasks that examine co-occurring deficits in cognitive and emotional subconstructs that can be used as early or current predictors of anhedonia.
• Studies employing neuromodulatory methods (e.g. Transcranial Magnetic Stimulation (TMS), Biofeedback) in combination with behavioral and physiological readouts to establish causal relationships between the behavior, domains of function and specific neural mechanisms that are altered in anhedonia.
• Experimental designs that apply computational methods and/or modeling approaches to examine the dynamic relationships among behavior, brain, and functional outcome.
• Studies proposing to develop novel behavioral tasks to be used for early diagnosis of dysfunctions in the domains and brain systems for anhedonia during childhood and adolescence with a goal to enhance early detection strategies and to inform optimal timing of interventions.

This NOSI encourages the inclusion of methods for demonstrating that the candidate task(s) engage the targeted brain system, are quantitative, and show specificity and reliability. Researchers proposing to further develop and validate tasks may want to consult the NIMH Advisory Council workgroup report on behavioral assessment methods for RDoC constructs for a review of existing tasks and discussion of task characteristics

Research Areas of Low Program Priority Under This NOSI

• Studies that propose to use animal models either alone or in combination with human subjects.
• Studies that propose to develop behavioral tasks, but do not include concurrent brain measures that test engagement of brain systems relevant to anhedonia.
• Studies seeking to recapitulate Diagnostic and Statistical Manual (DSM) diagnoses.
• Studies focused on sensorimotor systems and motor planning dysfunctions in anhedonia.

Application and Submission Information

This notice applies to due dates on or after February 5, 2024, and subsequent receipt dates through January 8, 2027. 

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

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

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-MH-24-130” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

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

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

Scientific/Research Contact(s)

Andrew Rossi, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1576
Email: rossia@mail.nih.gov

Aleksandra Vicentic, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1576
Email: vicentica@mail.nih.gov