# Causal role of delta-beta coupling for goal-directed behavior in anhedonia

> **NIH NIH R00** · FLORIDA STATE UNIVERSITY · 2024 · $249,000

## Abstract

Anhedonia - the inability to seek-out and experience pleasure - is a common symptom in depression that
predicts treatment resistance and is sometimes exacerbated by first-line antidepressants. Anhedonia falls
within the "Positive Valence System" of the Research Domain Criteria framework that comprises two
primary components: "liking" and "wanting." The "liking," or consummatory, component reflects the
evaluation of rewards reliant on the medial prefrontal cortex and ventral striatum. The "wanting," or
anticipatory, component modulates the degree to which effort is expended in goal-directed behavior reliant
on the lateral prefrontal cortex and dorsal striatum. Previous research found decreased neural activity in
both of these neural circuits in depressed patients with anhedonia but has not causally investigated the
role of these neural circuits, or their temporal dynamics, in different components of reward-based
decision-making. The preliminary data found decreased goal-directed behavior in depressed patients with
anhedonia and reduced cross-frequency coupling between the phase of delta oscillations (2-4 Hz) in
lateral prefrontal cortex and task-modulated beta oscillations (15-30 Hz) ( delta-beta coupling). The
objective of this research plan is to dissect the causal role of frontal-striatal circuity in different components
of reward-based decision-making and their impairment in anhedonia. The central hypothesis is that
anhedonia arises from decreased goal-directed behavior and disruption of delta-beta coupling in lateral
prefrontal cortex and dorsal striatum. The rationale is that spatially and temporally-targeted non-invasive
brain stimulation during performance of a reward-based decision-making task will provide causal evidence
for which network dynamics are impaired in anhedonia. In the K99 phase, this research (1) Causally
dissociated the neural circuits that implement goal-directed behavior and reward-evaluation in
decision-making and (2) Increased goal-directed behavior in depressed patients with anhedonia using
network-targeted non-invasive brain stimulation. Now, the R00 phase will (3) Investigate target
engagement of delta-beta coupling in a potential treatment paradigm with network-targeted stimulation in a
randomized clinical trial for depressed patients with symptoms of anhedonia. This proposal is significant
because it causally evaluates mechanistic models of the networks and cognitive processes that are
disrupted in anhedonia. The work is innovative because it uses concurrent neurophysiology and neurostimulation, integrates high-resolution spatial and temporal investigation tools, and utilizes individualized stimulation parameters such as subcortical-targeting with functional-connectivity and task-specific frequency targeting. The positive impact of this proposal is a refined definition of anhedonia based in biological mechanism that may have transdiagnostic relevance for other psychiatric illnesses such as schizophrenia and substan...

## Key facts

- **NIH application ID:** 10927445
- **Project number:** 5R00MH126161-04
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Justin M Riddle
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2021-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927445

## Citation

> US National Institutes of Health, RePORTER application 10927445, Causal role of delta-beta coupling for goal-directed behavior in anhedonia (5R00MH126161-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10927445. Licensed CC0.

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