Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression

NCT05224063 | Completed DMC FDA Device

• 2 other identifiers: 60980-2R01MH129018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Depression is a highly prevalent condition characterized by persistent low mood, energy, and activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an effective treatment for depression when targeting the dorsolateral prefrontal cortex (dlPFC) of the central executive network (CEN). However, remission rates are suboptimal and individual methods to target the dlPFC are lacking. In this study, we will enroll 50 patients with major depression and in a single rTMS 'dose,' prospective, randomized, double-blind, cross-over design will assess whether rTMS targeted to an individual's central executive network (CEN) assessed by single pulse TMS can enhance network modulation. If successful, this work will lead to a clinical rTMS trial comparing this personalized targeting approach against standard rTMS.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Transcranial Magnetic Stimulation (TMS) / Electroencephalography (EEG) change

  Change in TMS-EEG measures will be assessed before, during, and after each rTMS session. Specifically, the amplitude of the change 30ms after a single TMS pulse in the frontoparietal region will be quantified. Brain changes will be compared between CEN EEG-targeted, neuronavigated, scalp-targeted, and sham rTMS to identify the location, strength, and dose response of change for each condition.

  Up to 2 hours

Study Arms (4)

Individualized CEN-targeted rTMS

EXPERIMENTAL

Individualized CEN-targeted rTMS will combine neuronavigated rTMS and single pulse TMS-EEG to identify the region of the dlPFC making the strongest connection with the parietal node of the CEN. First, regions of the dlPFC strongly connected to the parietal CEN will be identified by applying single TMS pulses in grid-like fashion to ROIs within the dlPFC. For each anatomical dlPFC subunit probed with TMS, the TMS-EEG response will be quantified in the parietal region of the CEN. The dlPFC subunit that demonstrates the strongest TMS-EEG response in parietal cortex will be chosen for rTMS. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.

Device: Individualized CEN-targeted rTMS; Device: Sham rTMS

Neuronavigated rTMS

ACTIVE COMPARATOR

Neuronavigated rTMS will be delivered using neuro-navigation based on participants' own MRI images to target the dlPFC. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.

Device: Neuronavigated rTMS; Device: Sham rTMS

Scalp-targeted rTMS

ACTIVE COMPARATOR

Scalp-targeted rTMS will be delivered using standard BEAM F3 targeting methodology to target the dlPFC. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.

Device: Scalp-targeted rTMS; Device: Sham rTMS

Sham rTMS

SHAM COMPARATOR

Sham rTMS will be delivered for one session to mimic active rTMS conditions. To maximize sham validity, both 1) a direction- sensor TMS coil will alert the operators to flip the coil if the wrong side is being used, and 2) low-intensity electrical stimulation to match the active rTMS frequency will be applied to scalp electrodes under the coil for sham and placed but not activated in the active arm. The rTMS coil will be positioned using neuro-navigation based on participants' own MRI images, mimicking active rTMS. Sham rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the sham rTMS session for adverse events and/or side effects.

Device: Sham rTMS

Interventions

Individualized CEN-targeted rTMS DEVICE

Delivers patterned magnetic stimulation based on individualized CEN targeting

Individualized CEN-targeted rTMS

Neuronavigated rTMS DEVICE

Delivers patterned magnetic stimulation based on MRI images

Neuronavigated rTMS

Scalp-targeted rTMS DEVICE

Delivers patterned magnetic stimulation based on BEAM F3 targeting

Scalp-targeted rTMS

Sham rTMS DEVICE

Delivers placebo magnetic stimulation

Individualized CEN-targeted rTMS; Neuronavigated rTMS; Scalp-targeted rTMS; Sham rTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, ages 18 to 65
• Depression assessed through in-depth Structured Clinical Interview for DMS-5 (SCID-I)
• PHQ9 \> 10 for disease severity
• Must comprehend English well to ensure adequate comprehension of the EEG and TMS instructions, and of clinical scales
• Right-handed
• No current or history of neurological disorders
• No seizure disorder or risk of seizures
• No use of PRN medication within 24 hours of the scheduled study appointment

You may not qualify if:

• Those with a contraindication for MRIs (e.g. implanted metal)
• Any unstable medical condition
• History of head trauma with loss of consciousness
• History of seizures
• Neurological or uncontrolled medical disease
• Active substance abuse
• Diagnosis of psychotic or bipolar disorder
• A prior history of ECT or rTMS failure
• Currently taking medications that substantially reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium)
• Currently pregnant or breastfeeding

Sponsors & Collaborators

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

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: February 4, 2022
• Study Start: January 1, 2023
• Primary Completion: March 27, 2025
• Study Completion: March 27, 2025
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)