Optimizing Brain Excitability in Depression (TARGET)

February 6, 2026 updated by: Corey Keller, Stanford University

Optimized Methods for Measuring Brain Excitability in Depression

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

145

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Iowa City, California, United States, 52246
        • Recruiting
        • University of Iowa
        • Contact:
        • Sub-Investigator:
          • Aaron D Boes, MD, PhD
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
        • Principal Investigator:
          • Corey J Keller, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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 Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sham TMS, Active TMS with iEEG
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
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.
Device: Sham 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.
Other: Intracranial EEG (iEEG) Recording
Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.
Experimental: Optimized TMS, Non-optimized TMS with EEG
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
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.
Device: Non-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.
Other: EEG Recording
Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.
Experimental: Non-optimized TMS, Optimized TMS with EEG
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
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.
Device: Non-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.
Other: EEG Recording
Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.
Experimental: Active TMS, Sham TMS with iEEG
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
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.
Device: Sham 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.
Other: Intracranial EEG (iEEG) Recording
Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Posterior EL-TEP Amplitude after spTMS
Time Frame: Baseline, end of spTMS (6 hours)
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 Anterior EL-TEP Amplitude after single-pulse TMS (spTMS)
Time Frame: Baseline, end of spTMS (6 hours)
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 intracranial TMS-Evoked Potential (iTEP) Amplitude after TMS-iEEG
Time Frame: Baseline, end of spTMS (20 minutes)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Corey J Keller, MD, PhD, Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2025

Primary Completion (Estimated)

August 30, 2029

Study Completion (Estimated)

November 30, 2029

Study Registration Dates

First Submitted

November 11, 2025

First Submitted That Met QC Criteria

November 19, 2025

First Posted (Actual)

November 21, 2025

Study Record Updates

Last Update Posted (Actual)

February 10, 2026

Last Update Submitted That Met QC Criteria

February 6, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 72673-1
  • 1R01MH139650 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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