The purpose of the Notice is to notify the applicants that, following the original release date, the following corrections were made to PAR-20-235, "Behavioral Tasks Targeting Brain Systems Relevant to Anhedonia (R01 Basic Experimental Studies with Humans Required)" on July 28, 2020.
Previous Language:
Section IV. Application and Submission Information
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: Every application should include the elements and research approaches described in Section I, "Funding Opportunity Description." All applications under this FOA are expected to:
- Include approaches to demonstrate active modification of the targeted brain system through behavioral training or other means (e.g., noninvasive neuromodulation)
All applications under this FOA are expected to:
- Propose behavioral tasks that target specific brain system(s) relevant to anhedonia.
- Include neuroimaging and/or other brain activity recording techniques to demonstrate that the chosen task(s) engage the targeted brain subsystem.
- Include approaches to demonstrate active modification of the targeted brain system through behavioral training or other means (e.g., noninvasive neuromodulation).
This FOA strongly encourages:
Please note that this FOA supports basic neuroscience research studies in human subjects that will serve as the initial proof of concept. These basic experimental studies in both healthy and clinical populations are designed to understand a biological or behavioral process. They are not designed to test the safety or demonstrate the efficacy/effectiveness of an intervention. Investigators aiming to develop treatments and/or test the effectiveness of treatment and interventions should not apply under this FOA but instead submit applications under NIMH clinical trial FOAs
Specific Areas of Research Interest
Examples of specific research areas of interest to NIMH include, but are not limited to, the following:
Applications are required to include methods for demonstrating that the candidate task(s) engage the targeted brain system, are quantitative, and show specificity and reliability (see Data Rigor section). Rationale should be provided for the selection and levels of types of modifiers of anhedonia measures including variation in behavioral training, noninvasive neuromodulation, or pharmacologic agents, for example. Researchers proposing to further develop and validate tasks under the RDoC are advised to consider the NIMH Advisory Council workgroup report on behavioral assessment methods for RDoC constructs.
Studies that propose computational approaches solely for the analysis of high dimensional data for the purpose of defining RDoC functional dimensional constructs and domains will not be supported through this FOA, and should instead consider applying through: https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-19-242.html
Data Rigor
Translating discoveries into evidence-based treatments is predicated on the existence of strong, well-powered, adequately-controlled, and replicated data. In addition, the value of such research is greatly enhanced when detailed information is made available about study design, execution, analysis and interpretation. Examples of critical elements are detailed in NOT-OD-15-103.
Research areas not supported by this FOA:
All applications submitted to this FOA must propose basic experimental studies involving humans, referred to in NOT-OD-18-212 as “prospective basic science studies involving human participants.” These studies fall within the NIH definition of a clinical trial and also meet the definition of basic research. Types of studies that should submit under this FOA include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind (see PA-19-091).
- The development of behavioral tasks that target novel constructs relevant to anhedonia beyond those defined within the RDoC positive valence domain (e.g., reward valuation, reward sensitivity and reward learning, see https://www.nimh.nih.gov/research/research-funded-by-nimh/rdoc/index.shtml).
- Consideration and assessment of the extent of correlation with existing clinical measures (e.g., Snaith–Hamilton Pleasure 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 and that inclusion of clinical populations is not a requirement of this FOA.
- 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. (see #3 above).
- Behavioral task parameters should be empirically tested to optimize measurement characteristics (i.e., psychometric properties), including such considerations as 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 biases in anhedonia and dysfunctions in domains beyond the 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.
- Projects that explore whether candidate tasks for targeting brain systems relevant to anhedonia are applicable across diagnostic categories.
- Studies that propose behavioral tasks that are amenable to tracking dynamic changes in anhedonia over time.
- Studies employing neuromodulatory methods (e.g. 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.
- Projects that explore whether candidate behavioral tasks are sensitive to treatment for anhedonia (e.g. psychosocial and/or pharmacological approaches).
- Experimental designs that apply computational methods and/or modeling approaches as part of the main project to analyze high dimensional data to identify the relationship among performance on a given behavioral task, changes in a corresponding functional domains, and changes in neurobiological systems which contribute to anhedonia.
- 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.
- 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.
Published announcement modified on July 28, 2020 to read:
Section IV. Application and Submission Information
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: Every application should include the elements and research approaches described in Section I, "Funding Opportunity Description." All applications under this FOA are expected to:
-
- Propose behavioral tasks that target specific brain system(s) relevant to anhedonia.
- Include neuroimaging and/or other brain activity recording techniques to demonstrate that the chosen task(s) engage the targeted brain subsystem.
- Include approaches to demonstrate active modification of the targeted brain system through behavioral training or other means (e.g., noninvasive neuromodulation).
All applications submitted to this FOA must propose basic experimental studies involving humans, referred to in NOT-OD-18-212 as “prospective basic science studies involving human participants.” These studies fall within the NIH definition of a clinical trial and also meet the definition of basic research. Types of studies that should submit under this FOA include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind (see PA-19-091).
Please note that this FOA supports basic neuroscience research studies in human subjects that will serve as the initial proof of concept. These basic experimental studies in both healthy and clinical populations are designed to understand a biological or behavioral process. They are not designed to test the safety or demonstrate the efficacy/effectiveness of an intervention. Investigators aiming to develop treatments and/or test the effectiveness of treatment and interventions should not apply under this FOA but instead submit applications under NIMH clinical trial FOAs
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 constructs relevant to anhedonia beyond those defined within the RDoC positive valence domain (e.g., reward valuation, reward sensitivity and reward learning, see https://www.nimh.nih.gov/research/research-funded-by-nimh/rdoc/index.shtml).
- Consideration and assessment of the extent of correlation with existing clinical measures (e.g., Snaith–Hamilton Pleasure 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 and that inclusion of clinical populations is not a requirement of this FOA.
- 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. (see #3 above).
- Behavioral task parameters should be empirically tested to optimize measurement characteristics (i.e., psychometric properties), including such considerations as 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 biases in anhedonia and dysfunctions in domains beyond the 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.
- Projects that explore whether candidate tasks for targeting brain systems relevant to anhedonia are applicable across diagnostic categories.
- Studies that propose behavioral tasks that are amenable to tracking dynamic changes in anhedonia over time.
- Studies employing neuromodulatory methods (e.g. 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 as part of the main project to analyze high dimensional data to identify the relationship among performance on a given behavioral task, changes in a corresponding functional domains, and changes in neurobiological systems which contribute to anhedonia.
- 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.
Applications are required to include methods for demonstrating that the candidate task(s) engage the targeted brain system, are quantitative, and show specificity and reliability (see Data Rigor section). Rationale should be provided for the selection and levels of types of modifiers of anhedonia measures including variation in behavioral training, noninvasive neuromodulation, or pharmacologic agents, for example. Researchers proposing to further develop and validate tasks under the RDoC are advised to consider the NIMH Advisory Council workgroup report on behavioral assessment methods for RDoC constructs.
Studies that propose computational approaches solely for the analysis of high dimensional data for the purpose of defining RDoC functional dimensional constructs and domains will not be supported through this FOA, and should instead consider applying through: https://grants.nih.gov/grants/guide/rfa-files/rfa-mh-19-242.html
Research areas not supported by this FOA:
- 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.
Data Rigor
Translating discoveries into evidence-based treatments is predicated on the existence of strong, well-powered, adequately controlled, and replicated data. In addition, the value of such research is greatly enhanced when detailed information is made available about study design, execution, analysis and interpretation. Examples of critical elements are detailed in NOT-OD-15-103.
