Neuromodulatory effects and reproducibility of the most widely used repetitive transcranial magnetic stimulation protocols.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2023
Historique:
received: 03 02 2023
accepted: 16 05 2023
medline: 26 6 2023
pubmed: 23 6 2023
entrez: 23 6 2023
Statut: epublish

Résumé

Repetitive transcranial magnetic stimulation (rTMS) is widely used in both research and clinical settings to modulate human brain function and behavior through the engagement of the mechanisms of plasticity. Based upon experiments using single-pulse TMS as a probe, the physiologic mechanism of these effects is often assumed to be via changes in cortical excitability, with 10 Hz rTMS increasing and 1 Hz rTMS decreasing the excitability of the stimulated region. However, the reliability and reproducibility of these rTMS protocols on cortical excitability across and within individual subjects, particularly in comparison to robust sham stimulation, have not been systematically examined. In a cohort of 28 subjects (39 ± 16 years), we report the first comprehensive study to (1) assess the neuromodulatory effects of traditional 1 Hz and 10 Hz rTMS on corticospinal excitability against both a robust sham control, and two other widely used patterned rTMS protocols (intermittent theta burst stimulation, iTBS; and continuous theta burst stimulation, cTBS), and (2) determine the reproducibility of all rTMS protocols across identical repeat sessions. At the group level, neither 1 Hz nor 10 Hz rTMS significantly modulated corticospinal excitability. 1 Hz and 10 Hz rTMS were also not significantly different from sham and both TBS protocols. Reproducibility was poor for all rTMS protocols except for sham. Importantly, none of the real rTMS and TBS protocols demonstrated greater neuromodulatory effects or reproducibility after controlling for potential experimental factors including baseline corticospinal excitability, TMS coil deviation and the number of individual MEP trials. These results call into question the effectiveness and reproducibility of widely used rTMS techniques for modulating corticospinal excitability, and suggest the need for a fundamental rethinking regarding the potential mechanisms by which rTMS affects brain function and behavior in humans.

Sections du résumé

BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) is widely used in both research and clinical settings to modulate human brain function and behavior through the engagement of the mechanisms of plasticity. Based upon experiments using single-pulse TMS as a probe, the physiologic mechanism of these effects is often assumed to be via changes in cortical excitability, with 10 Hz rTMS increasing and 1 Hz rTMS decreasing the excitability of the stimulated region. However, the reliability and reproducibility of these rTMS protocols on cortical excitability across and within individual subjects, particularly in comparison to robust sham stimulation, have not been systematically examined.
OBJECTIVES
In a cohort of 28 subjects (39 ± 16 years), we report the first comprehensive study to (1) assess the neuromodulatory effects of traditional 1 Hz and 10 Hz rTMS on corticospinal excitability against both a robust sham control, and two other widely used patterned rTMS protocols (intermittent theta burst stimulation, iTBS; and continuous theta burst stimulation, cTBS), and (2) determine the reproducibility of all rTMS protocols across identical repeat sessions.
RESULTS
At the group level, neither 1 Hz nor 10 Hz rTMS significantly modulated corticospinal excitability. 1 Hz and 10 Hz rTMS were also not significantly different from sham and both TBS protocols. Reproducibility was poor for all rTMS protocols except for sham. Importantly, none of the real rTMS and TBS protocols demonstrated greater neuromodulatory effects or reproducibility after controlling for potential experimental factors including baseline corticospinal excitability, TMS coil deviation and the number of individual MEP trials.
CONCLUSIONS
These results call into question the effectiveness and reproducibility of widely used rTMS techniques for modulating corticospinal excitability, and suggest the need for a fundamental rethinking regarding the potential mechanisms by which rTMS affects brain function and behavior in humans.

Identifiants

pubmed: 37352290
doi: 10.1371/journal.pone.0286465
pii: PONE-D-23-03156
pmc: PMC10289434
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0286465

Subventions

Organisme : NIA NIH HHS
ID : P01 AG031720
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060987
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115949
Pays : United States

Informations de copyright

Copyright: © 2023 Magnuson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

A. Pascual-Leone is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Magstim Inc., Hearts Radiant, TetraNeuron and MedRhythms; and is listed as an inventor on several issued and pending patents on methods and applications for noninvasive brain stimulation, and the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging (Patent Number: 6571123, Method and apparatus for recording an electroencephalogram during transcranial magnetic stimulation, Inventors: John R. Ives, Alvaro Pascual-Leone, Date of patent: May 27, 2003). None of these companies or interests influenced in any way the work reported and do not alter our adherence to PLOS ONE policies on sharing data and materials.

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Auteurs

Justine Magnuson (J)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Department of Neurology, Harvard Medical School, Boston, MA, United States of America.
Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC, CA.

Mehmet A Ozdemir (MA)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Department of Neurology, Harvard Medical School, Boston, MA, United States of America.
Department of Biomedical Engineering, Izmir Katip Celebi University, Izmir, Turkey.

Elon Mathieson (E)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.

Sofia Kirkman (S)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.

Brice Passera (B)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Department of Neurology, Harvard Medical School, Boston, MA, United States of America.

Sumientra Rampersad (S)

Department of Physics, University of Massachusetts, Boston, MA, United States of America.
Department of Electrical and Computer Engineering, Northeastern University, Boston, MA, United States of America.

Alyssa B Dufour (AB)

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
Hinda and Arthur Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA, United States of America.

Dana Brooks (D)

Department of Electrical and Computer Engineering, Northeastern University, Boston, MA, United States of America.

Alvaro Pascual-Leone (A)

Department of Neurology, Harvard Medical School, Boston, MA, United States of America.
Hinda and Arthur Marcus Institute for Aging Research and Deanne and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, United States of America.
Guttmann Brain Health Institute, Institut Guttmann de Neurorehabilitació, Universitat Autonoma de Barcelona, Badalona, Spain.

Peter J Fried (PJ)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Department of Neurology, Harvard Medical School, Boston, MA, United States of America.

Mouhsin M Shafi (MM)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Department of Neurology, Harvard Medical School, Boston, MA, United States of America.

Recep A Ozdemir (RA)

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America.
Department of Neurology, Harvard Medical School, Boston, MA, United States of America.

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