Causal Role of Rostromedial Prefrontal Cortex for Positive Savoring in Depression

Conditions

• Left Dorsolateral Prefrontal Cortex - Accelerated Intermittent Theta Burst
• Left Primary Somatosensory Cortex - Accelerated Intermittent Theta Burst
• Left Rostromedial Prefrontal Cortex - Accelerated Intermittent Theta Burst

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Not accepted

Interventions

• 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.

Study Details

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.

Key Dates

Start date

Mar 23, 2026

Status verified

May 2026

Primary completion

Jun 30, 2028

Completion

Dec 31, 2028

Study Design

Enrollment

48 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: Left Rostromedial Prefrontal Cortex - Accelerated Intermittent Theta Burst
  Accelerated intermittent theta burst will be delivered to left rostromedial prefrontal cortex, which has been previously shown to manipulate reward sensitivity. We are testing if this also impacts positive savoring as measured by the late positive potential during EEG and positive affect. This is an experimental condition that will be compared to an active comparator and a sham comparator.
• Active Comparator: Left Dorsolateral Prefrontal Cortex - Accelerated Intermittent Theta Burst
  Accelerated intermittent theta burst will be delivered to left dorsolateral prefrontal cortex, which is considered "treatment as usual" for depression.
• Placebo Comparator: Left Primary Somatosensory Cortex - Accelerated Intermittent Theta Burst
  Accelerated intermittent theta burst will be delivered to left primary somatosensory cortex, which is a placebo intervention condition.

Primary Outcome Measure

Late Positive Potential during Positive Savoring [ Time Frame: From baseline EEG to post-stimulation EEG approximately 2 weeks apart ]

Locations (1)

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