Anxiety & Depression Association of America

Optimizing Brain Excitability in Depression

Purpose

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).

Condition

Major Depressive Disorder

Eligibility

Eligible Ages: Between 18 Years and 65 Years
Eligible Sex: All
Accepts Healthy Volunteers: Yes

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 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 ECT failure - History of suicide attempt in the past year - Currently pregnant or breastfeeding - rTMS treatment in the past six months

Study Design

Phase: N/A
Study Type: Interventional
Allocation: Randomized
Intervention Model: Crossover Assignment
Primary Purpose: Basic Science
Masking: Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Active TMS, Sham TMS with iEEG	Neurosurgical participants receive both active single-pulse 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.
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.

Recruiting Locations

More Details

Status: Recruiting
Sponsor: Stanford University

Study Contact

Jade T Truong, BS
408-840-3313
kellerlab@stanford.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.