title: Circadian modulation of GABA-mediated cortical inhibition.
abstract: Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.
authors.affiliation: Department of Neurology, Christian-Albrechts-University, 24105 Kiel, Germany. n.lang@neurologie.uni-kiel.de
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lang
authors.forename: Holger
authors.initials: H
authors.lastname: Rothkegel
authors.forename: Heidi
authors.initials: H
authors.lastname: Reiber
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
authors.forename: Elke
authors.initials: E
authors.lastname: Sueske
authors.forename: Frithjof
authors.initials: F
authors.lastname: Tergau
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wuttke
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D017286:Polysomnography / Q000379:methods; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid