Ketamine on working memory - what are the underlying EEG correlates

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Neurodegenerative disorders are associated with a decline in working memory and thought to be accompanied by dysfunctional connectivity and altered theta/gamma amplitude within the hippocampal-prefrontal circuit (HC-PFC). The hippocampus and prefrontal cortex both have dense populations of N-methyl-D-aspartate (NMDA) receptors. Ketamine, a NMDA receptor antagonist, is of interest as a mechanistic model of glutamatergic dysfunction mimicking cognitive impairments in animal and human studies. In this study, we sought to identify an EEG fingerprint of working memory under normal and impaired conditions of functional connectivity and amplitude in the theta and gamma frequency bands. Long-Evans rats received a baseline saline injection followed by an acute and repeated sub-anaesthetic doses of ketamine (10 mg/kg, s.c.) 30 min prior to performing a Delayed-non-match to position task, and amplitude as well as functional phase based connectivity changes were studied in the retrosplenial, frontal association, lateral parietal association and cingulate cortex, with the cingulate serving as the seed. The task showed to be measuring working memory, yet ketamine didn’t influence performance neither acutely nor after repeated exposure. The EEG revealed no specific effect of ketamine on working memory either, but we did identify an EEG fingerprint of WM, which showed a dissociation between amplitude and network connectivity for the different brain regions and frequency bands. The main effects of WM were found in the higher theta band in the network, whereas no changes were occurring in the gamma bands. Ketamine didn’t show an effect in the low theta band possibly owing to compensatory mental effort. Working memory in this study didn’t show to be impaired by acute or repeated ketamine, which also was reflected in the behavioural data, not necessarily ruling out ketamine as a good model for degenerative diseases, as ketamine effects were visible, but might bear evidence for the task having been learned too well and/or the exposure to ketamine not being sufficient to functionally disrupt the system.
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