Optimizing Brain Excitability in Depression

NCT07242105 | Recruiting DMC FDA Device

• 2 other identifiers: 72673-11R01MH139650
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Major Depressive Disorder

Keywords

tms; eeg

Outcome Measures

Primary Outcomes (3)

• Changes in Anterior EL-TEP Amplitude after single-pulse TMS (spTMS)

  Changes in Early Local TMS-Evoked Potentials (EL-TEP) following 6 hours of either active or sham spTMS between optimized and non-optimized stimulation conditions in the anterior dlPFC.

  Baseline, end of spTMS (6 hours)

• Changes in Posterior EL-TEP Amplitude after spTMS

  Changes in Early Local TMS-Evoked Potentials (EL-TEP) following 6 hours of either active or sham spTMS between optimized and non-optimized stimulation conditions in the posterior dlPFC.

  Baseline, end of spTMS (6 hours)

• Changes in intracranial TMS-Evoked Potential (iTEP) Amplitude after TMS-iEEG

  Changes in the interaction between gyral/sulcal targets and coil angles (45 vs 90 degrees) on local dlPFC iTEP amplitude.

  Baseline, end of spTMS (20 minutes)

Study Arms (4)

Active TMS, Sham TMS with iEEG

EXPERIMENTAL

Neurosurgical participants receive both active single-pulse Transcranial Magnetic Stimulation (TMS) and sham single-pulse TMS delivered to predefined dlPFC sites while undergoing intracranial EEG recording. The order of active and sham stimulation is randomized.

Device: Active Single-Pulse TMS; Device: Sham Single-Pulse TMS; Other: Intracranial EEG (iEEG) Recording

Sham TMS, Active TMS with iEEG

EXPERIMENTAL

Neurosurgical participants receive sham single-pulse TMS followed by active single-pulse TMS at predefined dlPFC sites during intracranial EEG recording. The order of stimulation conditions is randomized.

Device: Active Single-Pulse TMS; Device: Sham Single-Pulse TMS; Other: Intracranial EEG (iEEG) Recording

Optimized TMS, Non-optimized TMS with EEG

EXPERIMENTAL

Participants receive both TARGET optimized single-pulse TMS and non-optimized (open-loop) single-pulse TMS to the dlPFC while undergoing concurrent scalp EEG. The sequence of optimized and non-optimized stimulation is randomized.

Device: TARGET-optimized TMS; Device: Non-optimized (Open-Loop) TMS; Other: EEG Recording

Non-optimized TMS, Optimized TMS with EEG

EXPERIMENTAL

Participants receive non-optimized (open-loop) single-pulse TMS followed by TARGET optimized single-pulse TMS to the dlPFC with concurrent scalp EEG. The order of stimulation conditions is randomized.

Device: TARGET-optimized TMS; Device: Non-optimized (Open-Loop) TMS; Other: EEG Recording

Interventions

Active Single-Pulse TMS DEVICE

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.

Active TMS, Sham TMS with iEEG; Sham TMS, Active TMS with iEEG

Sham Single-Pulse TMS DEVICE

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.

Active TMS, Sham TMS with iEEG; Sham TMS, Active TMS with iEEG

TARGET-optimized TMS DEVICE

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.

Non-optimized TMS, Optimized TMS with EEG; Optimized TMS, Non-optimized TMS with EEG

Non-optimized (Open-Loop) TMS DEVICE

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.

Non-optimized TMS, Optimized TMS with EEG; Optimized TMS, Non-optimized TMS with EEG

EEG Recording OTHER

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

Non-optimized TMS, Optimized TMS with EEG; Optimized TMS, Non-optimized TMS with EEG

Intracranial EEG (iEEG) Recording OTHER

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

Active TMS, Sham TMS with iEEG; Sham TMS, Active TMS with iEEG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

University of Iowa

Iowa City, California, 52246, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Corey J Keller, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jade T Truong, BS

CONTACT

408-840-3313; kellerlab@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 11, 2025
• First Posted: November 21, 2025
• Study Start: October 23, 2025
• Primary Completion (Estimated): August 30, 2029
• Study Completion (Estimated): November 30, 2029
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)