Ketamine amplifies induced gamma frequency oscillations in the human cerebral cortex

Eur Neuropsychopharmacol. 2015 Aug;25(8):1136-46. doi: 10.1016/j.euroneuro.2015.04.012. Epub 2015 May 27.


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.

Keywords: Gamma oscillations; Ketamine; Magnetoencephalography; Motor cortex; NMDA receptor; Visual cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology*
  • Beta Rhythm / drug effects
  • Beta Rhythm / physiology
  • Cross-Over Studies
  • Gamma Rhythm / drug effects*
  • Humans
  • Ketamine / pharmacology*
  • Magnetoencephalography
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Motor Cortex / drug effects*
  • Motor Cortex / physiology
  • Single-Blind Method
  • Visual Cortex / drug effects*
  • Visual Cortex / physiology
  • Visual Perception / drug effects
  • Visual Perception / physiology
  • Young Adult


  • Antidepressive Agents
  • Ketamine