Brain-oscillation Synchronised Stimulation of the Prefrontal Cortex

Not Applicable

Completed

• Conditions: Depression
• Interventions: Device: Negative-peak-triggered-TMS; Device: Intermittent theta-burst stimulation; Device: Open-loop replay TMS

• Registration Number: NCT02920840
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

Combining TMS and EEG, this study investigates a personalized therapeutic non-invasive brain stimulation protocol in patients with major depression, whereby the timing of the TMS pulses is synchronized with the instantaneous phase of ongoing brain oscillations in order to modulate the inter-hemispheric left and right dorso-lateral prefrontal cortical brain network.

Detailed Description

Major depressive disorder is a severe psychiatric illness with a lifetime prevalence of about 8-16%. Many patients fail to achieve complete remission of symptoms under antidepressant medication, with about 10% of patients being chronically resistant to several psychopharmacological treatments. Development of alternative non-pharmacological treatments is therefore essential to improve patient care.

Repetitive transcranial magnetic stimulation (rTMS) offers therapeutic potential in this context. Current protocols apply high-frequency rTMS over left dorsolateral prefrontal cortex (DLPFC) to reverse the increased alpha-band oscillatory activity and cortical hypo-excitability in patients with depression. However, translation of rTMS therapy into routine clinical practice has been limited due to low efficacy and high inter-individual variability.

This study aims to optimize rTMS stimulation protocols for MDD by deterministically coupling the timing of TMS to the ongoing oscillatory neural activity in the underlying cortex as measured in real-time with high-density surface EEG. It is hypothesized that alpha phase-locked rTMS of the left DLPFC reverses increased alpha-band oscillatory activity and cortical hypo-excitability more efficiently than current open-loop rTMS protocols used in the treatment of MDD.

Study Timeline

• Status Verified: 2016-09
• Study Start: 2016-09
• Study First Submitted: 2016-09-26
• Study First Submitted QC: 2016-09-28
• Study First Posted: 2016-09-30
• Primary Completion: 2017-04
• Study Completion: 2017-04
• Last Update Submitted: 2020-09-08
• Last Update Posted: 2020-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Negative-peak-triggered-TMS	Negative-peak-triggered-TMS	Intervention: application of 200 brain-state dependent 100 Hz TMS triplet bursts triggered at the negative peak phase of the ongoing endogenous alpha-band oscillation (as detected by surface EEG over left dlPFC)
Intermittent theta-burst stimulation	Intermittent theta-burst stimulation	Intervention: application of 200 TMS triplet bursts (at 100 Hz, inter-burst interval 200ms) over left dorsolateral prefrontal cortex
Open-loop replay TMS	Open-loop replay TMS	Intervention: application of the same sequence of TMS pulses as in condition "Negative-peak-triggered-TMS", i.e. irrespective of ongoing brain state over left dlPFC

Primary Outcome Measures

Name	Time	Method
Change from baseline in cortical excitability 30 minutes after the intervention	30 minutes	TMS-evoked EEG potentials from left dlPFC

Secondary Outcome Measures

Name	Time	Method
Change from baseline in EEG alpha power 30 minutes after the intervention	30 minutes	Left vs. right dlPFC relative spectral power in 8-12 Hz frequency band
Change from baseline in verbal working memory performance 30 minutes after the intervention	30 minutes	Verbal working memory task

Trial Locations

Locations (1)

University Neurology Hospital; 🇩🇪 Tuebingen, BW, Germany