Causal Role of Rostromedial Prefrontal Cortex for Positive Savoring in Depression

This is a non-invasive brain stimulation and neuroimaging study that will examine how activity in the medial prefrontal cortex influences reward processing, particularly positive savoring, in individuals with depression. The central question is whether modulating medial prefrontal brain regions using transcranial magnetic stimulation (TMS) alters neural and behavioral responses to rewards. Brain activity will be recorded using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) while participants perform reward tasks. The primary objectives are to (1) identify patterns of brain activity linked to impaired reward processing in depression using EEG and fMRI, and (2) determine the causal role of specific prefrontal areas in these processes through targeted TMS. The methods include four sessions over four weeks: a clinical assessment, EEG recording during reward tasks after participants learn/practice positive savoring, an fMRI session, and a TMS session combined with EEG while participants practice positive savoring and perform reward tasks during EEG.

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Key information

Conditions

Left Rostromedial Prefrontal Cortex - Accelerated Intermittent Theta Burst Anhedonia Depressive Disorder Depressive Disorder, Major Left Dorsolateral Prefrontal Cortex - Accelerated Intermittent Theta Burst Left Primary Somatosensory Cortex - Accelerated Intermittent Theta Burst Mental Disorders Mood Disorders Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Florida State University

Tallahassee, Florida, 32306, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Between the ages of 18 and 65
Able to provide informed consent
Have normal or corrected vision
Right handed
Willing to comply with all study procedures and be available for the duration of the study
Speak and understand English
Not color blind
Acceptable suicide risk as determined by less than 5 on the Depression Symptom Index Suicidality Subscale (DSI-SS)
A diagnosis of major depressive disorder (current episode) on the Structured Clinical Interview for the DSM-5 (SCID-5)
Between the ages of 18 and 65

Exclusion criteria

ADHD (currently under treatment)
Neurological disorders and conditions. Including but not limited to: history of epilepsy, seizures (except childhood febrile seizures), dementia, history of stroke, Parkindon's disease, multiple sclerosis, cerebral aneurysm, brain tumors
Medical or neurological illness or treatment for a medical disorder that could interfere with study participation. For example, unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment
Prior brain surgery
Any brain devices/implants, including cochlear implants and aneurysm clips, cardiac pacemaker, or any other implanted electronic device
History of current traumatic brain injury
Pregnancy (for females)
Claustrophobia
DSM-5 diagnosis of present moderate or severe substance use disorder or alcohol use disorder, and past severe substance use disorder or alcohol use disorder, bipolar disorder, or psychotic disorder
Based on the use of MRI, additional exclusion criteria are considered. These include participants having ferrous metal in their body, having non-removable jewelry that is ferrous, having tattoos on the face or neck, history of being a metal worker or having an eye injury involving metal
Anything that in the opinion of the investigator would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Treatment and study plan

Accelerated Intermittent Theta Burst Transcranial Magnetic Stimulation

Device

For accelerated intermittent theta burst stimulation (aiTBS), stimulation intensity will be set at 80% resting motor threshold (rMT), a level that has been established to be safe and effective. aiTBS will consist of bursts containing 3 pulses at 50 Hz. Bursts will be delivered at 5 Hz for 2 seconds at 80% of rMT, followed by 8 seconds without stimulation. This pattern will continue for 60 cycles (1800 pulses), for a total elapsed time of 10 minutes. Participants will be randomized to receive aiTBS to their mPFC, dlPFC, or primary somatosensory cortex (S1) a total of two times in a single session for 10 minutes each (spaced 50 minutes apart) before/after EEG preparation and practicing a positive affect technique (i.e., savoring), and before performing a positive savoring and reward responsivity task during EEG.

Primary outcomes

Late Positive Potential during Positive Savoring

Time frame: From baseline EEG to post-stimulation EEG approximately 2 weeks apart

The late positive potential (LPP) is an established event-related potential that has been shown to be higher when savoring positive feelings elicited by positive images compared to neutral images. Changes in the LPP will be assessed from baseline EEG to post-stimulation EEG and compared between stimulation sites (left rostromedial PFC, left dorsolateral PFC, left primary somatosensory cortex).

Secondary outcomes

Positive Affect Ratings on the Positive and Negative Affect Schedule (PANAS)

Time frame: From the start to the end of a 3 hour study visit

Positive Affect subscale ratings on the Positive and Negative Affect Schedule (PANAS) self-report measure will be collected at the start and end of the stimulation visit, which will be used to assess the secondary outcome of acute positive affect change. The full PANAS measure includes 20 items with Negative Affect (NA) and Positive Affect (PA) subscales of 10 items each. Scores can range from 10-50, with higher scores representing higher levels of either NA or PA. This will be compared across the three stimulation sites.

Sponsors and collaborators

Lead sponsor

Florida State University

Other

Registry information

Acronym: rmPFC-Savoring

Important dates

Study start: 2026
Primary completion: 2028
Study completion: 2028
First posted: Mar 12, 2026
Registry last updated: May 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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