title: The effects of elevated endogenous GABA levels on movement-related network oscillations.
abstract: The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation-inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15-30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60-90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated.
authors.affiliation: CUBRIC, School of Psychology, Cardiff University, Cardiff, CF103AT, UK. Electronic address: sdmuthu@cardiff.ac.uk.
authors.forename: S D
authors.initials: SD
authors.lastname: Muthukumaraswamy
authors.affiliation: Psychopharmacology Unit, School of Social and Community Medicine, University of Bristol, BS8 2BN, UK.
authors.forename: J F M
authors.initials: JF
authors.lastname: Myers
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, W12 0NN, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wilson
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, W12 0NN, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, W12 0NN, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lingford-Hughes
authors.affiliation: CUBRIC, School of Psychology, Cardiff University, Cardiff, CF103AT, UK.
authors.forename: K D
authors.initials: KD
authors.lastname: Singh
authors.affiliation: The Epilepsy Unit, University Hospital of Wales, Cardiff, CF14 4XW, UK.
authors.forename: K
authors.initials: K
authors.lastname: Hamandi
mesh_terms: D000328:Adult; D001611:Beta Rhythm / Q000187:drug effects / Q000502:physiology*; D003344:Cortical Synchronization / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009068:Movement / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D012815:Signal Processing, Computer-Assisted; D000078308:Tiagabine; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine
keywords: Beta rhythm; Event-related desynchronisation; GABA; Gamma oscillations; Magnetoencephalography; Motor cortex; Tiagabine