Cortical dynamics during psychedelic and anesthetized states induced by ketamine

Ketamine is a unique drug that has psychedelic and anesthetic properties in a dose-dependent manner. Recent studies have shown that ketamine anesthesia appears to maintain the spatiotemporal complexity of cortical activation evoked by transcranial magnetic stimulation, while a psychedelic dose of ketamine is associated with increased spontaneous magnetoencephalographic signal diversity. However, a systematic investigation of the dose-dependent effects of ketamine on cortical complexity using the same modality is required. Furthermore, it is unknown whether the complexity level stabilizes or fluctuates over time for the duration of ketamine exposure. Here we investigated the spatiotemporal complexity of spontaneous high-density scalp electroencephalography (EEG) signals in healthy volunteers during alterations of consciousness induced by both subanesthetic and anesthetic doses of ketamine. Given the fast transient spectral dynamics, especially during the gamma-burst pattern after loss of consciousness, we employed a method based on Hidden Markov modeling to classify the EEG signals into a discrete set of brain states that correlated with different behavioral states. We characterized the spatiotemporal complexity specific for each brain state as measured through the Lempel-Ziv complexity algorithm. After controlling for signal diversity due to spectral changes, we found that the subanesthetic dose of ketamine is associated with an elevated complexity level relative to baseline, while the brain activity following an anesthetic dose of ketamine is characterized by alternating low and high complexity levels until stabilizing at a high level comparable to that during baseline. Thus, spatiotemporal complexity associated with ketamine-induced state transitions has features of general anesthesia, normal consciousness, and altered states of consciousness. These results improve our understanding of the complex pharmacological, neurophysiological, and phenomenological properties of ketamine.