Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.
Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity.
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Charlotte
C
Nettekoven
Max Planck Institute for Neurological Research, 50931 Cologne, Germany, Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
Lukas J
LJ
Volz
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Martha
M
Kutscha
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Eva-Maria
EM
Pool
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Anne K
AK
Rehme
Institute of Neuroscience and Medicine (INM-1, INM-3), Jülich Research Centre, 52428 Jülich, Germany, and Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, 40225 Düsseldorf, Germany.
Simon B
SB
Eickhoff
Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany, Institute of Neuroscience and Medicine (INM-1, INM-3), Jülich Research Centre, 52428 Jülich, Germany, and.
Gereon R
GR
Fink
Max Planck Institute for Neurological Research, 50931 Cologne, Germany, Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany, Institute of Neuroscience and Medicine (INM-1, INM-3), Jülich Research Centre, 52428 Jülich, Germany, and Christian.Grefkes@uk-koeln.de.
Christian
C
Grefkes
D000328:Adult; D018592:Cross-Over Studies; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D016037:Single-Blind Method; D013826:Theta Rhythm / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
functional connectivity; iTBS; neural plasticity; premotor cortex; resting-state fMRI; supplementary motor area