Randomized Controlled Trial

. 2023 Sep 15;94(6):454-465.

doi: 10.1016/j.biopsych.2023.04.011. Epub 2023 Apr 20.

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography

Affiliations

¹ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
² Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Krembil Centre for Neuroinformatics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
³ Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁴ Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California.
⁵ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
⁶ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
⁸ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Krembil Centre for Neuroinformatics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁹ Non-Invasive Neurostimulation Therapies Laboratory, Vancouver, British Columbia, Canada; Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁰ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Psychiatry, University of California San Diego, La Jolla, California.
¹² Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹³ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: daphne.voineskos@camh.ca.

PMID: 37084864
DOI: 10.1016/j.biopsych.2023.04.011

Randomized Controlled Trial

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography

Rebecca Strafella et al. Biol Psychiatry. 2023.

. 2023 Sep 15;94(6):454-465.

doi: 10.1016/j.biopsych.2023.04.011. Epub 2023 Apr 20.

Authors

Affiliations

¹ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
² Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Krembil Centre for Neuroinformatics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
³ Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁴ Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California.
⁵ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
⁶ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
⁸ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Krembil Centre for Neuroinformatics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁹ Non-Invasive Neurostimulation Therapies Laboratory, Vancouver, British Columbia, Canada; Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁰ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Psychiatry, University of California San Diego, La Jolla, California.
¹² Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹³ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: daphne.voineskos@camh.ca.

PMID: 37084864
DOI: 10.1016/j.biopsych.2023.04.011

Abstract

Background: Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation-electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders.

Methods: TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for treatment-resistant depression, comparing a separated (54-minute interval) and contiguous (0-minute interval) schedule of 2 × 600-pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the left dorsolateral prefrontal cortex at baseline and posttreatment. One hundred fourteen participants had usable TMS-EEG at baseline, and 98 at posttreatment. TMS-evoked potential components (N45, N100) were examined via global mean field analysis.

Results: The N100 amplitude decreased from baseline to posttreatment, regardless of the treatment group (F_1,106 = 5.20, p = .02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F_1,102 = 11.30, p = .001, p_corrected = .0004). Responders showed higher posttreatment N45 amplitude than nonresponders (F_1,94 = 4.11, p = .045, p_corrected = .016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F_4,106 = 6.28, p = .00014).

Conclusions: These results provide further evidence for an association between the neurophysiological effects of iTBS and treatment efficacy in treatment-resistant depression. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers.

Keywords: Electroencephalography; Major depressive disorder; Markers; TMS-EEG; iTBS; rTMS.

PubMed Disclaimer

Comment in

Neurophysiological Biomarkers as a Springboard for the Refinement of Transcranial Magnetic Stimulation Therapy: Stratification, Mechanisms of Action, and Next Steps.
Murphy N. Murphy N. Biol Psychiatry. 2023 Sep 15;94(6):443-444. doi: 10.1016/j.biopsych.2023.06.016. Biol Psychiatry. 2023. PMID: 37611984 No abstract available.

Cited by

Neurophysiological markers of disease severity and cognitive dysfunction in major depressive disorder: A TMS-EEG study.
Li D, Li X, Li J, Liu J, Luo R, Li Y, Wang D, Zhou D, Zhang XY. Li D, et al. Int J Clin Health Psychol. 2024 Jul-Sep;24(3):100495. doi: 10.1016/j.ijchp.2024.100495. Epub 2024 Aug 30. Int J Clin Health Psychol. 2024. PMID: 39282218 Free PMC article.
Identifying neural circuitry abnormalities in neuropathic pain with transcranial magnetic stimulation and electroencephalogram co-registration.
Huang Z, Wang Y, Yan Y, Liu Y, Chen J, Liu H, Li J, Gao Z, Che X. Huang Z, et al. Neurotherapeutics. 2025 Mar;22(2):e00496. doi: 10.1016/j.neurot.2024.e00496. Epub 2024 Nov 28. Neurotherapeutics. 2025. PMID: 39613525 Free PMC article.
TMS-evoked potential in the dorsolateral prefrontal cortex to assess the severity of depression disease: a TMS-EEG study.
Li X, Chen M, Liu Q, Zheng C, Yu C, Hou G, Chen Z, Chen Y, Chen Y, Zhu G, Zhou D, Xu W. Li X, et al. Front Pharmacol. 2023 Jun 5;14:1207020. doi: 10.3389/fphar.2023.1207020. eCollection 2023. Front Pharmacol. 2023. PMID: 37342593 Free PMC article.
Neuroimaging Insights into the Public Health Burden of Neuropsychiatric Disorders: A Systematic Review of Electroencephalography-Based Cognitive Biomarkers.
Gkintoni E, Vantarakis A, Gourzis P. Gkintoni E, et al. Medicina (Kaunas). 2025 May 28;61(6):1003. doi: 10.3390/medicina61061003. Medicina (Kaunas). 2025. PMID: 40572691 Free PMC article.
Enhancing prefrontal modulation by phase-locking intermittent theta burst stimulation to a concurrent transcranial alternating current stimulation.
Zimmermann N, Koenig T, Riesen AS, Morishima Y. Zimmermann N, et al. Imaging Neurosci (Camb). 2025 Jan 3;3:imag_a_00415. doi: 10.1162/imag_a_00415. eCollection 2025 Jan 3. Imaging Neurosci (Camb). 2025. PMID: 40433300 Free PMC article.

See all "Cited by" articles

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography

Affiliations

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography

Authors

Affiliations

Abstract

Comment in

Similar articles

Cited by

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Abstract

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Related information

LinkOut - more resources

Full Text Sources

Medical