Causal Role of Rostromedial Prefrontal Cortex for Positive Savoring in Depression

N/AEnrolling By InvitationNCT07467473

Florida State University48 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Left Rostromedial Prefrontal Cortex - Accelerated Intermittent Theta Burst Left Dorsolateral Prefrontal Cortex - Accelerated Intermittent Theta Burst

Interventions

Accelerated Intermittent Theta Burst Transcranial Magnetic StimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Late Positive Potential during Positive Savoring

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).

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

Secondary Outcomes

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

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.

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