title: Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS.
abstract: The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) - an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability - depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level.
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Juelich Research Centre, 52428 Juelich, Germany; Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nettekoven
authors.affiliation: Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
authors.forename: Lukas J
authors.initials: LJ
authors.lastname: Volz
authors.affiliation: Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
authors.forename: Martha
authors.initials: M
authors.lastname: Leimbach
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Juelich Research Centre, 52428 Juelich, Germany; Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Pool
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Juelich Research Centre, 52428 Juelich, Germany; Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Rehme
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Juelich Research Centre, 52428 Juelich, Germany; Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, 40225 Duesseldorf, Germany.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Eickhoff
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Juelich Research Centre, 52428 Juelich, Germany; Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany.
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Juelich Research Centre, 52428 Juelich, Germany; Department of Neurology, Cologne University Hospital, 50924 Cologne, Germany. Electronic address: Christian.Grefkes@uk-koeln.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Grefkes
mesh_terms: D000328:Adult; D019054:Evoked Potentials, Motor; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
keywords: Cortical plasticity; Dose-dependency; SMA; Variability; dPMC