Ketamine amplifies induced gamma frequency oscillations in the human cerebral cortex

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 0.5 mg/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.