title: GABAergic modulation of visual gamma and alpha oscillations and its consequences for working memory performance.
abstract: BACKGROUND
  Impressive in vitro research in rodents and computational modeling has uncovered the core mechanisms responsible for generating neuronal oscillations. In particular, GABAergic interneurons play a crucial role for synchronizing neural populations. Do these mechanistic principles apply to human oscillations associated with function? To address this, we recorded ongoing brain activity using magnetoencephalography (MEG) in healthy human subjects participating in a double-blind pharmacological study receiving placebo, 0.5 mg and 1.5 mg of lorazepam (LZP; a benzodiazepine upregulating GABAergic conductance). Participants performed a demanding visuospatial working memory (WM) task.
  
  
  RESULTS
  We found that occipital gamma power associated with WM recognition increased with LZP dosage. Importantly, the frequency of the gamma activity decreased with dosage, as predicted by models derived from the rat hippocampus. A regionally specific gamma increase correlated with the drug-related performance decrease. Despite the system-wide pharmacological intervention, gamma power drug modulations were specific to visual cortex: sensorimotor gamma power and frequency during button presses remained unaffected. In contrast, occipital alpha power modulations during the delay interval decreased parametrically with drug dosage, predicting performance impairment. Consistent with alpha oscillations reflecting functional inhibition, LZP affected alpha power strongly in early visual regions not required for the task demonstrating a regional specific occipital impairment.
  
  
  CONCLUSIONS
  GABAergic interneurons are strongly implicated in the generation of gamma and alpha oscillations in human occipital cortex where drug-induced power modulations predicted WM performance. Our findings bring us an important step closer to linking neuronal dynamics to behavior by embracing established animal models.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, the Netherlands.
authors.forename: Diego
authors.initials: D
authors.lastname: Lozano-Soldevilla
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: ter Huurne
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
authors.forename: Roshan
authors.initials: R
authors.lastname: Cools
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, the Netherlands. Electronic address: ole.jensen@donders.ru.nl.
authors.forename: Ole
authors.initials: O
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000513:Alpha Rhythm / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D065818:Gamma Rhythm / Q000187:drug effects*; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D015225:Magnetoencephalography; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D055815:Young Adult
chemical_list: D018757:GABA Modulators; D008140:Lorazepam