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Large-scale analysis of interindividual variability in single and paired-pulse TMS data: results from the ‘Big TMS Data Collaboration’

Daniel T. Corp, Hannah G. K. Bereznicki, Gillian M. Clark, George J. Youssef, Peter J. Fried, Ali Jannati, Charlotte B. Davies, Joyce Gomes-Osman, View ORCID ProfileMelissa Kirkovski, Natalia Albein-Urios, Paul B. Fitzgerald, Giacomo Koch, Vincenzo Di Lazzaro, Alvaro Pascual-Leone, Peter G. Enticott, the Big TMS Data Collaboration
doi: https://doi.org/10.1101/2021.01.24.428014
Daniel T. Corp
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
2Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: daniel.corp@deakin.edu.au
Hannah G. K. Bereznicki
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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Gillian M. Clark
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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George J. Youssef
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
3Centre for Adolescent Health, Murdoch Children’s Research Institute, Parkville, Australia
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Peter J. Fried
2Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Ali Jannati
2Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
4Neuromodulation Program and Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
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Charlotte B. Davies
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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Joyce Gomes-Osman
2Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
5Department of Physical Therapy, University of Miami Miller School of Medicine, Miami, FL
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Melissa Kirkovski
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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  • ORCID record for Melissa Kirkovski
Natalia Albein-Urios
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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Paul B. Fitzgerald
6Monash Alfred Psychiatry Research Centre, Central Clinical School, The Alfred and Monash University, Melbourne, Australia
7Epworth Centre for Innovation in Mental Health, Epworth HealthCare and Central Clinical School, Melbourne, Australia
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Giacomo Koch
8Non-invasive Brain Stimulation Unit, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
9Department of Biomedical and Specialty Surgical Sciences, Section of Human Physiology, University of Ferrara, Italy
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Vincenzo Di Lazzaro
10Unit of Neurology, Neurophysiology and Neurobiology, Università Campus Bio-Medico, Rome, Italy
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Alvaro Pascual-Leone
11Hinda and Arthur Marcus Institute for Aging Research. Hebrew SeniorLife, Boston, MA, USA
12Department of Neurology, Harvard Medical School, Boston, MA, USA
13Guttmann Brain Health Institute, Institut Guttmann de Neurorehabilitació, Universitat Autonoma de Barcelona, Barcelona, Spain
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Peter G. Enticott
1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
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Abstract

Objective Interindividual variability of single and paired-pulse TMS data has limited the clinical and experimental applicability of these methods. This study brought together over 60 TMS researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability.

Methods 118 corresponding authors provided deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and pp TMS data.

Results 687 healthy participant’s TMS data was pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual’s single pulse TMS amplitude. Baseline MEP amplitude, M1 hemisphere, and biphasic AMT significantly predicted SICI response. Baseline MEP amplitude, test stimulus intensity, interstimulus interval, monophasic RMT, monophasic AMT, and biphasic RMT significantly predicted ICF response. Age, M1 hemisphere, and TMS machine significantly predicted motor threshold.

Conclusions This large-scale analysis has identified a number of factors influencing participants’ responses to single and paired pulse TMS. We provide specific recommendations to increase the standardisation of TMS methods within and across laboratories, thereby minimising interindividual variability in single and pp TMS data.

Highlights

  • 687 healthy participant’s TMS data was pooled across 35 studies

  • Significant relationships between age and resting motor threshold

  • Significant relationships between baseline MEP amplitude and SICI/ICF

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations and nomenclature

    TMS
    Transcranial magnetic stimulation
    MEP
    motor evoked potential
    pp
    paired-pulse
    SICI
    short-interval intracortical inhibition
    ICF
    intracortical facilitation
    IV
    independent variable
    DV
    dependent variable
    Normalised MEP
    DV for SICI and ICF analyses (conditioned MEP amplitude expressed as a percentage of the baseline MEP amplitude)
    CS
    conditioning stimulus (initial pulse for paired-pulse TMS protocols)
    TS
    test stimulus (second pulse for pp TMS protocols, or unconditioned / baseline MEPs for pp protoocol)
    ISI
    interstimulus interval
    RMT
    resting motor threshold
    AMT
    active motor threshold
    Pulse waveform
    monophasic or biphasic pulse waveforms
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Posted January 26, 2021.
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    Large-scale analysis of interindividual variability in single and paired-pulse TMS data: results from the ‘Big TMS Data Collaboration’
    Daniel T. Corp, Hannah G. K. Bereznicki, Gillian M. Clark, George J. Youssef, Peter J. Fried, Ali Jannati, Charlotte B. Davies, Joyce Gomes-Osman, Melissa Kirkovski, Natalia Albein-Urios, Paul B. Fitzgerald, Giacomo Koch, Vincenzo Di Lazzaro, Alvaro Pascual-Leone, Peter G. Enticott, the Big TMS Data Collaboration
    bioRxiv 2021.01.24.428014; doi: https://doi.org/10.1101/2021.01.24.428014
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    Large-scale analysis of interindividual variability in single and paired-pulse TMS data: results from the ‘Big TMS Data Collaboration’
    Daniel T. Corp, Hannah G. K. Bereznicki, Gillian M. Clark, George J. Youssef, Peter J. Fried, Ali Jannati, Charlotte B. Davies, Joyce Gomes-Osman, Melissa Kirkovski, Natalia Albein-Urios, Paul B. Fitzgerald, Giacomo Koch, Vincenzo Di Lazzaro, Alvaro Pascual-Leone, Peter G. Enticott, the Big TMS Data Collaboration
    bioRxiv 2021.01.24.428014; doi: https://doi.org/10.1101/2021.01.24.428014

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