Effects of acute ketamine infusion on visual working memory encoding: a study using ERPs

• ¹ City University London, Psychology, UK
• ² Institute of Psychiatry, UK
• ³ University of Manchester, School of Psychological Sciences, UK
• ⁴ University of Manchester, Neuroscience and Psychiatry Unit, UK

The impairment of working memory (WM) is regarded as a central deficit in schizophrenia spectrum disorders. We have previously demonstrated a relationship between EEG measures of visual stimulus encoding and WM performance in schizophrenia. Specifically, we examined the early visual P1 and the later occurring P3 ERP component. Both ERPs were attenuated in participants with schizophrenia. However, the P1 was predictive of WM performance in healthy controls. The findings emphasise the importance of visual encoding anomalies in explaining WM deficits in schizophrenia. These information processing abnormalities have been suggested to be the result of a NMDA glutamate receptor abnormality. Ketamine, a non-competitive NMDA antagonist, can be used to explore the neurophysiological characteristics of acutely induced glutamate receptor dysfunction in healthy volunteers. In this study, we aimed to test whether the administration of IV ketamine can replicate the cognitive and electrophysiological patterns that our group previously observed in schizophrenia patients and schizotypal individuals. 44 healthy volunteers were randomised to receive IV infusion of ketamine or placebo. A 64 channel EEG was used to obtain event-related potentials in response to a delayed discrimination working memory (WM) task. The two groups were compared in respect to their performance task as well as the amplitude of the P1 and P300 ERPs. The psychiatric scales scores (BPRS, CADSS) were significantly increased in the ketamine group when compared to saline. While there was no difference in terms of reaction times to the task, accuracy in the ketamine group worsened significantly with increase in working memory load than in controls. Ketamine significantly increased the P1 but lead to a decrease in P300. In this study acute NMDA antagonism induced a WM deficit that was associated with visual processing and memory abnormalities. Specifically, ketamine increased the amplitude of the P1 potential and reduced the P300 amplitude. In addition P1 but not P300 predicted performance on the WM task. These effects could be mediated ketamine-induced acute glutamate release in the visual cortex, enhancing neuronal responses to visual stimuli and increasing the signal-to-noise ratio which in turn disrupted higher order cognitive function.