Neuronal oscillations and synchronicity associated with gamma-hydroxybutyrate during resting-state in healthy male volunteers

Rationale Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, an anesthetic agent, and a treatment for neuropsychiatric disorders. In previous electroencephalography (EEG) studies, GHB was shown to induce an electrophysiological pattern of “paradoxical EEG-behavioral dissociation” characterized by increased delta and theta oscillations usually associated with sleep during awake states. However, no detailed source localization of these alterations and no connectivity analyses have been performed yet. Objectives and methods We tested the effects of GHB (20 and 35 mg/kg, p.o.) on current source density (CSD), lagged phase synchronization (LPS), and global omega complexity (GOC) of neuronal oscillations in a randomized, double-blind, placebo-controlled, balanced cross-over study in 19 healthy, male participants using exact low-resolution electromagnetic tomography (eLORETA) of resting-state high-density EEG recordings. Results Compared to placebo, GHB increased CSD of theta oscillations (5–7 Hz) in the posterior cingulate cortex (PCC) and alpha1 (8–10 Hz) oscillations in the anterior cingulate cortex. Higher blood plasma values were associated with higher LPS values of delta (2–4 Hz) oscillations between the PCC and the right inferior parietal lobulus. Additionally, GHB decreased GOC of alpha1 oscillations. Conclusion These findings indicate that alterations in neuronal oscillations in the PCC mediate the psychotropic effects of GHB. Theta oscillations emerging from the PCC in combination with stability of functional connectivity within the default mode network might explain the GHB-related “paradoxical EEG-behavioral dissociation.” Our findings related to GOC suggest a reduced number of relatively independent neuronal processes, an effect that has also been demonstrated for other anesthetic agents.