title: Quadri-Pulse Theta Burst Stimulation using Ultra-High Frequency Bursts - A New Protocol to Induce Changes in Cortico-Spinal Excitability in Human Motor Cortex.
abstract: Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce changes in cortico-spinal excitability, commonly referred to as long-term potentiation (LTP)-like and long-term depression (LTD)-like effects in human motor cortex (M1). Here, we aimed to test the plasticity-inducing capabilities of a novel protocol that merged TBS and QPS. 360 bursts of quadri-pulse TBS (qTBS) were continuously given to M1 at 90% of active motor threshold (1440 full-sine pulses). In a first experiment, stimulation frequency of each burst was set to 666 Hz to mimic the rhythmicity of the descending cortico-spinal volleys that are elicited by TMS (i.e., I-wave periodicity). In a second experiment, burst frequency was set to 200 Hz to maximize postsynaptic Ca2+ influx using a temporal pattern unrelated to I-wave periodicity. The second phase of sinusoidal TMS pulses elicited either a posterior-anterior (PA) or anterior-posterior (AP) directed current in M1. Motor evoked potentials (MEPs) were recorded before and after qTBS to probe changes in cortico-spinal excitability. PA-qTBS at 666 Hz caused a decrease in PA-MEP amplitudes, whereas AP-qTBS at 666 Hz induced an increase in mean AP-MEP amplitudes. At a burst frequency of 200 Hz, PA-qTBS and AP-qTBS produced an increase in cortico-spinal excitability outlasting for at least 60 minutes in PA- and AP-MEP amplitudes, respectively. Continuous qTBS at 666 Hz or 200 Hz can induce lasting changes in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1.
authors.affiliation: Department of Pediatrics, Technical University of Munich, Heiglhofstr. 63, Munich, Germany.
authors.forename: Nikolai H
authors.initials: NH
authors.lastname: Jung
authors.affiliation: Zentralinstitut für Medizintechnik at Technical University of Munich (IMETUM), Boltzmannstr. 11, Garching, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gleich
authors.affiliation: Zentralinstitut für Medizintechnik at Technical University of Munich (IMETUM), Boltzmannstr. 11, Garching, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gattinger
authors.affiliation: Department of Pediatrics, Technical University of Munich, Heiglhofstr. 63, Munich, Germany.
authors.forename: Catrina
authors.initials: C
authors.lastname: Hoess
authors.affiliation: Department of Pediatrics, Technical University of Munich, Heiglhofstr. 63, Munich, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Haug
authors.affiliation: Danish Research Center for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, Hvidovre, Denmark.|Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: Department of Pediatrics, Technical University of Munich, Heiglhofstr. 63, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mall
mesh_terms: D000293:Adolescent; D000328:Adult; D004576:Electromyography; D005071:Evoked Potentials / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult