title: Ketamine amplifies induced gamma frequency oscillations in the human cerebral cortex.
abstract: At subanaesthetic doses, ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated remarkable and rapid antidepressant efficacy in patients with treatment-resistant depression. The mechanism of action of ketamine is complex and not fully understood, with altered glutamatergic function and alterations of high-frequency oscillatory power (Wood et al., 2012) noted in animal studies. Here we used magnetoencephalography (MEG) in a single blind, crossover study to assess the neuronal effects of 0.5mg/kg intravenous ketamine on task-related high-frequency oscillatory activity in visual and motor cortices. Consistent with animal findings, ketamine increased beta amplitudes, decreased peak gamma frequency in visual cortex and significantly amplified gamma-band amplitudes in motor and visual cortices. The amplification of gamma-band activity has previously been linked in animal studies to cortical pyramidal cell disinhibition. This study provides direct translatable evidence of this hypothesis in humans, which may underlie the anti-depressant actions of ketamine.
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff CF103AT, UK; Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF103AT, UK.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Shaw
authors.affiliation: Department of Anaesthetics, Intensive Care and Pain Medicine, School of Medicine, Cardiff University, Cardiff CF144XW, UK; Department of Anaesthetics, Intensive Care and Pain Medicine, Cwm Taf University Health Board, Llantrisant CF72 8XR, UK.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Saxena
authors.affiliation: Department of Anaesthetics, Intensive Care and Pain Medicine, School of Medicine, Cardiff University, Cardiff CF144XW, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: E Jackson
authors.affiliation: Department of Anaesthetics, Intensive Care and Pain Medicine, School of Medicine, Cardiff University, Cardiff CF144XW, UK.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Hall
authors.affiliation: Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff CF103AT, UK.
authors.forename: Krish D
authors.initials: KD
authors.lastname: Singh
authors.affiliation: School of Pharmacy, Faculty of Medical and Health Sciences, Auckland University, Auckland 1123, New Zealand; School of Psychology, Faculty of Medical and Health Sciences, Auckland University, Auckland 1123 New Zealand. Electronic address: sd.muthu@auckland.ac.nz.
authors.forename: Suresh D
authors.initials: SD
authors.lastname: Muthukumaraswamy
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D001611:Beta Rhythm / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D065818:Gamma Rhythm / Q000187:drug effects*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D015225:Magnetoencephalography; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D016037:Single-Blind Method; D014793:Visual Cortex / Q000187:drug effects* / Q000502:physiology; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: Gamma oscillations; Ketamine; Magnetoencephalography; Motor cortex; NMDA receptor; Visual cortex