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

Award Number: R00MH126161
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/13/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Causal role of delta-beta coupling for goal-directed behavior in anhedonia - 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 substance use disorder. The implication of this proposal is that the knowledge gained can be directly used for the development of novel interventions using precision medicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $249,000 )
2025	2025	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Mental Health Research Grants	000	5	8/19/2025	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2024 ( Subtotal = $249,375 )
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Mental Health Research Grants	002	4	8/2/2024	NON-COMPETING CONTINUATION	$249,000
2024	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Mental Health Research Grants	000	3	12/8/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Mental Health Research Grants	001	3	3/20/2024	EXTENSION WITH OR WITHOUT FUNDS	$375
														Subtotal = $249,375

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Mental Health Research Grants	000	3	9/11/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $747,375

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

Award Number: R00MH126161

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/13/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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