Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans

Not Applicable

Active, not recruiting

• Conditions: Major Depressive Disorder; Epilepsy
• Interventions: Device: Intracranial electrodes; Device: TMS

• Registration Number: NCT05996900
• Lead Sponsor: Stanford University

Brief Summary

Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. The goal of this proposal is to characterize the key markers of the brain's response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings. These markers will improve the understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of the brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators need to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.

Goals of the study are to 1) establish a detailed mechanistic understanding of the brain changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain and clinical changes.

Study Timeline

• Study First Submitted: 2023-07-18
• Study First Submitted QC: 2023-08-09
• Study First Posted: 2023-08-18
• Study Start: 2023-09-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-05
• Last Update Posted: 2023-12-06
• Primary Completion: 2027-01-01
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

• Men and women, ages 18 to 65
• Medication-refractory epilepsy requiring phase II monitoring
• Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent
• No current or history of major neurological disorders other than epilepsy

Exclusion Criteria

• Those with a contraindication for MRIs (e.g. implanted metal)
• Any unstable medical condition
• Neurological or uncontrolled medical disease
• Active substance abuse
• Currently pregnant or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
TBS via direct electrical stimulation	Intracranial electrodes	-
Sham TBS via transcranial magnetic stimulation	TMS	-
TBS via transcranial magnetic stimulation	TMS	-
Sham TBS via direct electrical stimulation	Intracranial electrodes	-

Primary Outcome Measures

Name	Time	Method
TMS-iEEG change after one TBS session	45 minutes	Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG).

Secondary Outcome Measures

Name	Time	Method
ES-iEEG change between two sequential TBS sessions	45 minutes	Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.
ES-iEEG change after one TBS session	45 minutes	Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG.
TMS-iEEG change between two sequential TBS sessions	45 minutes	Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States