RecruitingNot ApplicableNCT07242105

Optimizing Brain Excitability in Depression

Optimized Methods for Measuring Brain Excitability in Depression

Sponsor

Stanford University

Enrollment

145 participants

Start Date

Oct 23, 2025

Study Type

INTERVENTIONAL

Conditions

Major Depressive Disorder

Summary

The goal of this study is to improve depression treatment by establishing reliable prefrontal excitability markers through Targeting with Automated Real-time Guidance for Enhancing TEPs (TARGET).

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria8

Men and women, ages 18 to 65
Diagnosis of major depressive disorder, assessed through a Structured Clinical Interview for DSM-5 (SCID-5)
In a current depressive episode, assessed through a Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (SCID-5)
Moderate-to-severe depression as indicated by a score between 11-20 on the Quick Inventory of Depressive Symptoms (QIDS)
Must comprehend English well to ensure adequate comprehension of the EEG and TMS instructions, and of clinical scales
No current or history of neurological disorders
No seizure disorder or risk of seizures
Neurosurgical patients: Men and women ages 18-65 with medication-refractory epilepsy who are admitted for phase II intracranial monitoring to detect a seizure focus will be considered appropriate for this study. Participants must have the intellectual capacity to understand the consent process and agree to the study.

Exclusion Criteria11

Those with a contraindication for MRIs (e.g. implanted metal)
History of head trauma with loss of consciousness
History of seizures or on medications that reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium)
Neurological or uncontrolled medical disease
Any unstable medical condition
Active substance abuse
Diagnosis of psychotic or bipolar disorder
A prior history of Electroconvulsive Therapy (ECT) failure
History of suicide attempt in the past year
Currently pregnant or breastfeeding
Repetitive Transcranial Magnetic Stimulation (rTMS) treatment in the past six months

Interventions

DEVICEActive Single-Pulse TMS

Single-pulse transcranial magnetic stimulation is delivered to the left dorsolateral prefrontal cortex using a MagVenture X100 stimulator and B65 A/P coil across predefined locations, coil angles, and stimulation intensities.

DEVICESham Single-Pulse TMS

Sham single-pulse TMS is delivered using a flipped coil and concurrent scalp electrical stimulation to mimic auditory and somatosensory sensations without producing cortical stimulation.

DEVICETARGET-optimized TMS

Single-pulse TMS parameters (location, angle, and intensity) are adjusted in real time using the TARGET closed-loop algorithm based on concurrent EEG measurements to deliver optimized stimulation.

DEVICENon-optimized (Open-Loop) TMS

Single-pulse TMS is delivered using a predefined open-loop set of stimulation parameter combinations across multiple dlPFC locations, coil angles, and intensities without real-time adjustment.

OTHEREEG Recording

Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.

OTHERIntracranial EEG (iEEG) Recording

Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.