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Theta burst stimulation in humans: a need for better understanding effects of brain stimulation in health and disease

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Abstract

Repetitive transcranial stimulation (rTMS) paradigms have been used to induce lasting changes in brain activity and excitability. Previous methods of stimulation were long, often ineffective and produced short-lived and variable results. A new non-invasive brain stimulation technique was developed in John Rothwell’s laboratory in the early 2000s, which was named ‘theta burst stimulation’ (TBS). This used rTMS applied in burst patterns of newly acquired 50 Hz rTMS machines, which emulated long-term potentiation/depression-like effects in brain slices. This stimulation paradigm created long-lasting changes in brain excitability, using efficient, very rapid stimulation, which would affect behaviour, with the aim to influence neurological diseases in humans. We describe the development of this technique, including findings and limitations identified since then. We discuss how pitfalls facing TBS reflect those involving both older and newer, non-invasive stimulation techniques, with suggestions of how to overcome these, using personalised, ‘closed loop’ stimulation methods. The challenge in most non-invasive stimulation techniques remains in identifying their exact mechanisms of action in the context of neurological disease models. The development of TBS provides the backdrop for describing John’s contribution to the field, inspiring our own scientific endeavour thanks to his unconditional support, and unfailing kindness.

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Acknowledgements

We are grateful to Professor John Rothwell for supervising our respective PhDs and for providing his support in our development as clinician scientists after this was completed. He has guided the development of TBS, and supported its implementation across disciplines, remaining open to criticism and investigating mechanisms of action at neuropharmacological and electrophysiological levels. He has provided new ways of identifying reasons for variability in the results obtained (Rothwell 2011, Hamada et al. 2013). He has been a role model for implementing our scientific endeavours with kindness, humility, and perseverance. He is one of the rare basic scientists to have provided a comprehensive body of clinical work, having collaborated very effectively with clinicians throughout his career.

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Authors and Affiliations

  1. Chelsea and Westminster NHS Foundation Trust, West Middlesex University Hospital, Twickenham Road, Isleworth, TW7 6AF, UK

    Elisabeth Rounis

  2. Medical School and Healthy Aging Center, Chang Gung University, Taoyuan, Taiwan

    Ying-Zu Huang

  3. Department of Neurology and Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Ying-Zu Huang

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  1. Elisabeth Rounis
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  2. Ying-Zu Huang
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Correspondence to Ying-Zu Huang.

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Communicated by Sven Bestmann.

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Rounis, E., Huang, YZ. Theta burst stimulation in humans: a need for better understanding effects of brain stimulation in health and disease. Exp Brain Res 238, 1707–1714 (2020). https://doi.org/10.1007/s00221-020-05880-1

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