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Behavioral Tasks Targeting Brain Subsystems Relevant to Anhedonia

NAMHC Concept Clearance

Presenter:

Andrew F. Rossi, Ph.D.
Division of Neuroscience and Basic Behavioral Science

Goal:

This initiative seeks to develop task-based behavioral measures, which will be validated with neuroimaging and then used as behavioral readouts serving as a proxy for engagement of brain subsystems relevant to anhedonia. The goal is to use these newly developed behavioral tasks as quantitative tools to advance treatment development. Studies may include healthy volunteers and clinical populations. Projects that focus on early development and adolescence are strongly encouraged.  Research projects should aim to: 1) propose behavioral tasks that target brain subsystem(s) relevant to anhedonia assessed with neuroimaging and/or other brain activity recording techniques; 2) demonstrate that chosen task(s) engage the targeted brain subsystem through neuroimaging or other brain measure; and 3) show active modification of the targeted brain system through behavioral training or other means (e.g., noninvasive neuromodulation). This initiative strongly encourages development of novel behavioral tasks that go beyond the Research Domain Criteria (RDoC) positive valence domain (e.g., reward valuation, reward sensitivity and reward learning) and those that target novel candidate subconstructs. Candidate behavioral tasks should be quantifiable and reliable (test-retest). The extent of correlation with existing clinical measures (e.g., Snaith–Hamilton Pleasure Scale, DARS) for the domain of anhedonia being targeted should be addressed unless there are no established clinical measures for the investigated construct. Importantly, behavioral tasks and targeted brain system measures should be robust and have sensitivity to detect change due to treatment interventions (although treatment trials are beyond the scope of this concept). Candidate behavioral tasks are expected to tap into altered functional domains relevant to anhedonia that can be reliably identified at neurobiological levels and serve as a more precise way of defining clinical features of anhedonia for use in both diagnosis and treatment development.

Rationale:

Anhedonia is associated with a wide range of disorders and its clinical presentation varies greatly. Research over the last two decades suggests that anhedonia is not a unitary symptom, but rather the result of a failure of one or several brain subsystems underlying reward, motivation, and hedonic processing. This is a timely opportunity for NIMH to support research to develop behavioral tasks targeting functional subconstructs of anhedonia that can be validated with imaging and/or other neural measures, thus serving as quantitative tools to assess treatment efficacy. This initiative will complement prior NIMH initiatives that have focused on:

  • Dimensional and computational approaches to understanding mental illness (RDoC);
  • Targeting impaired cognition as a potential therapeutic target for schizophrenia (CNTRICS);
  • Computationally defined behaviors;
  • The NIMH FAST-MAS trial that used behavior- and brain-based measures for demonstrating engagement of neural circuitry related to the hedonic response in anhedonia patients.

Thus, the proposed concept will build on the aforementioned investments while addressing a gap in NIMH portfolio by encouraging studies that aim to develop a battery of neural imaging-validated behavioral tasks for use as quantitative measures (or tools) to advance treatment development.