Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm

David Baur; Dragana Galevska; Sara Hussain; Leonardo G Cohen; Ulf Ziemann; Christoph Zrenner

doi:10.1016/j.brs.2020.09.005

Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm

Brain Stimul. 2020 Nov-Dec;13(6):1580-1587. doi: 10.1016/j.brs.2020.09.005. Epub 2020 Sep 17.

Authors

David Baur¹, Dragana Galevska¹, Sara Hussain², Leonardo G Cohen², Ulf Ziemann³, Christoph Zrenner¹

Affiliations

¹ Department of Neurology & Stroke, University of Tübingen, Germany; Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany.
² Human Cortical Physiology and Neurorehabilitation Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
³ Department of Neurology & Stroke, University of Tübingen, Germany; Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany. Electronic address: ulf.ziemann@uni-tuebingen.de.

Abstract

Background: Neural oscillations reflect rapidly changing brain excitability states. We have demonstrated previously with EEG-triggered transcranial magnetic stimulation (TMS) of human motor cortex that the positive vs. negative peak of the sensorimotor μ-oscillation reflect corticospinal low-vs. high-excitability states. In vitro experiments showed that induction of long-term depression (LTD) by low-frequency stimulation depends on the postsynaptic excitability state.

Objective/hypothesis: We tested the hypothesis that induction of LTD-like corticospinal plasticity in humans by 1 Hz repetitive TMS (rTMS) is enhanced when rTMS is synchronized with the low-excitability state, but decreased or even shifted towards long-term (LTP)-like plasticity when synchronized with the high-excitability state.

Methods: We applied real-time EEG-triggered 1-Hz-rTMS (900 pulses) to the hand area of motor cortex in healthy subjects. In a randomized double-blind three-condition crossover design, pulses were synchronized to either the positive or negative peak of the sensorimotor μ-oscillation, or were applied at random phase (control). The amplitude of motor evoked potentials was recorded as an index of corticospinal excitability before and after 1-Hz-rTMS.

Results: 1-Hz-rTMS at random phase resulted in a trend towards LTD-like corticospinal plasticity. RTMS in the positive peak condition (i.e., the low-excitability state) induced significant LTD-like plasticity. RTMS in the negative peak condition (i.e., the high-excitability state) showed a trend towards LTP-like plasticity, which was significantly different from the other two conditions.

Conclusion: The level of corticospinal depolarization reflected by phase of the μ-oscillation determines the degree of corticospinal plasticity induced by low-frequency rTMS, a finding that may guide future personalized therapeutic stimulation.

Keywords: Brain oscillation; Brain-state-dependent stimulation; Corticospinal excitability; EEG; LTD-Like plasticity; TMS.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cross-Over Studies
Double-Blind Method
Electroencephalography / methods
Evoked Potentials, Motor / physiology*
Female
Humans
Long-Term Synaptic Depression / physiology*
Male
Middle Aged
Neuronal Plasticity / physiology*
Pyramidal Tracts / physiology*
Sensorimotor Cortex / physiology*
Transcranial Magnetic Stimulation / methods*