title: Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?
abstract: Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.
authors.affiliation: Department of Neurology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mastroeni
authors.forename: Til Ole
authors.initials: TO
authors.lastname: Bergmann
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rizzo
authors.forename: Christoph
authors.initials: C
authors.lastname: Ritter
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Ines
authors.initials: I
authors.lastname: Pohlmann
authors.forename: Norbert
authors.initials: N
authors.lastname: Brueggemann
authors.forename: Angelo
authors.initials: A
authors.lastname: Quartarone
authors.forename: Hartwig Roman
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D019054:Evoked Potentials, Motor; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor