Reward Circuit Targeted iTBS

NCT ID: NCT05468853

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-28
• Study Completion Date: 2024-09-18

Brief Summary

The objective of this study is to examine the effect of intermittent theta-burst transcranial magnetic stimulation (iTBS) targeting the reward circuit.

Detailed Description

The study will examine the effect of medial prefrontal cortex (MPFC)-iTBS on the reward circuit, reward sensitivity, and anhedonia. The reward circuit will be assessed using functional MRI (fMRI) connectivity and activation during the Doors Task. Reward sensitivity will be assessed using an event-related potential called the reward positivity or RewP. The RewP will be measured using electroencephalography (EEG) during the Doors Task. Anhedonia will be measured using the Dimensional Anhedonia Ratings Scale (DARS).

The Doors Task was designed to examine reward processing in a simple, well-controlled paradigm. On each trial, participants select one of two doors. Gain (50 cents) or loss (25 cents) feedback is provided. Gains elicit a positive potential referred to as the RewP, while losses elicit a negative potential referred to as the feedback reward negativity (FRN). Gains also show increased activation in reward-related brain areas (e.g. ventral striatum) relative to losses in the fMRI signal.

Each participant will complete a baseline session including structural MRI, fMRI and EEG during the Doors task, and transcranial magnetic stimulation (TMS) motor thresholding. The ventral striatum (VS) will be identified on the structural MRI. The MPFC will be identified as a rostral-medial cortical area in prefrontal cortex with high connectivity to the VS. A control site, inion, will be identified using visual inspection of the skull.

Each participant will complete 2 weeks of iTBS sessions. Each week will target a different site (experimental: MPFC; control: inion). iTBS will be performed once a day for 5 consecutive days at each site, with order counter-balanced across participants in a cross-over design. 1 week of washout will follow each week of iTBS. At the end of each week, participants will perform the Doors task while being measured with EEG, and complete the DARS. At the end of the iTBS weeks, participants will also perform the Doors task while being measured with fMRI.

fMRI activation of the MPFC target and VS, and VS-MPFC fMRI connectivity will be compared at baseline, following the MPFC-iTBS week, and following the control-iTBS week. Changes specific to MPFC-iTBS will provide evidence of the effect of MPFC-iTBS on the reward circuit. The RewP and DARS will be compared at baseline, and after each week, respectively. Changes specific to MPFC-iTBS will provide evidence of the effect of MPFC-iTBS on the reward sensitivity and anhedonia. Changes that persist following washout will provide an indication of a lasting effect of MPFC-iTBS.

Conditions

Transcranial Magnetic Stimulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

rmPFC-iTBS

Transcranial magnetic stimulation delivered to the rostral medial prefrontal cortex. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds followed by 8 seconds of no stimulation repeated 20 times at 80% of resting motor threshold. Repeated daily for 5 consecutive days.

Group Type: EXPERIMENTAL

transcranial magnetic stimulation

Intervention Type: DEVICE

Transcranial magnetic stimulation delivered to the scalp targeting medial prefrontal cortex

Inion-iTBS

Transcranial magnetic stimulation delivered to the inion. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds followed by 8 seconds of no stimulation repeated 20 times at 80% of resting motor threshold. Repeated daily for 5 consecutive days.

Group Type: ACTIVE_COMPARATOR

transcranial magnetic stimulation

Intervention Type: DEVICE

Transcranial magnetic stimulation delivered to the inion

Interventions

transcranial magnetic stimulation

Transcranial magnetic stimulation delivered to the scalp targeting medial prefrontal cortex

Intervention Type: DEVICE

transcranial magnetic stimulation

Transcranial magnetic stimulation delivered to the inion

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Right-handed
• Native English speaker or fluent by the age of 6
• Elevated self-reported anhedonia

Exclusion Criteria

• Left-handed
• Metal in head
• Brain tumor, stroke, aneurysm, multiple sclerosis
• Active substance use disorder in last 3 months
• Dementia or other cognitive disorder making unable to engage in treatment
• History or diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or other psychiatic illness that precludes safe participation in trial
• Suicidal risk that precludes safe participation
• obsessive-compulsive disorder
• Inability to stop taking any mediation that significant lowers the seizure threshold (e.g. tricyclic antidepressants, clozapine, etc.)
• Severe traumatic brain injury
• Non-English speaker

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Florida State University

OTHER

Sponsor Role: lead

Responsible Party

Derek Nee

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

FSU MRI Facility

Tallahassee, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY00002776

Identifier Type: -

Identifier Source: org_study_id

R21MH129653

Identifier Type: NIH

Identifier Source: secondary_id

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