Acute Effects of Esketamine on the EEG Power Spectrum and Signal Complexity in Prolonged Disorders of Consciousness: A Prospective Exploratory Cohort Study.

Abstract

<h4>Background</h4>Effective treatments for prolonged disorders of consciousness (pDoC) remain limited. Grounded in the entropic brain hypothesis-that psychedelic agents facilitate consciousness recovery by increasing brain complexity-this study investigated esketamine, a nonclassical psychedelic drug, and its effects on electroencephalographic (EEG) neurophysiological metrics in pDoC patients.<h4>Methods</h4>In this prospective exploratory cohort study, 27 patients with pDoC were enrolled, and 22 with sufficient EEG signal quality were included in the final analysis. Patients were diagnosed with vegetative state/unresponsive wakefulness syndrome (VS/UWS) or a minimally conscious state (MCS). Patients received a 1-hour intravenous infusion of esketamine (0.3 mg/kg/h). EEG data were collected at baseline, 1 hour after infusion, and 30 minutes post-discontinuation. The power spectral density and Lempel-Ziv complexity (LZC) were analyzed. The study was registered at ClinicalTrials.gov (NCT06473285) on June 23, 2024.<h4>Results</h4>Esketamine reshaped the EEG power spectrum, suppressing global delta relative power (p_FDR=0.040) while increasing beta (p_FDR=0.040) and gamma (p_FDR=0.009) relative power. The alpha relative power increased selectively in the VS/UWS (p_FDR=0.012). The LZC increased in the parietal (P=0.030) and occipital (P=0.007) regions. In MCS patients, the increase in LZC persisted for 30 minutes post-discontinuation, most prominently in the occipital region, whereas changes in VS/UWS were transient. No behavioral improvements were observed on the Coma Recovery Scale-Revised assessments.<h4>Conclusions</h4>Esketamine-induced neurophysiological alterations in patients with pDoC are characterized by reorganization of the EEG power spectral density and region-specific increases in signal complexity. However, these changes were not accompanied by improvements in behavioral responsiveness.

Topics & conditions

Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.

Keywords