Robin von Rotz1, Michael Kometer2, Dario Dornbierer1, Jürg Gertsch3, M Salomé Gachet3, Franz X Vollenweider2, Erich Seifritz1, Oliver G Bosch4, Boris B Quednow5. 1. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, CH-8032, Zurich, Switzerland. 2. Neuropsychopharmacology and Brain Imaging Research Unit, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland. 3. Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012, Bern, Switzerland. 4. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, CH-8032, Zurich, Switzerland. oliver.bosch@bli.uzh.ch. 5. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, CH-8032, Zurich, Switzerland. quednow@bli.uzh.ch.
Abstract
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.
RCT Entities:
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.
Authors: P Palatini; L Tedeschi; G Frison; R Padrini; R Zordan; R Orlando; L Gallimberti; G L Gessa; S D Ferrara Journal: Eur J Clin Pharmacol Date: 1993 Impact factor: 2.953
Authors: Dario A Dornbierer; Diego M Baur; Benjamin Stucky; Boris B Quednow; Thomas Kraemer; Erich Seifritz; Oliver G Bosch; Hans-Peter Landolt Journal: Neuropsychopharmacology Date: 2019-04-08 Impact factor: 7.853
Authors: Zurina Hassan; Oliver G Bosch; Darshan Singh; Suresh Narayanan; B Vicknasingam Kasinather; Erich Seifritz; Johannes Kornhuber; Boris B Quednow; Christian P Müller Journal: Front Psychiatry Date: 2017-08-18 Impact factor: 4.157
Authors: Filipa Raposo Pereira; Paul Zhutovsky; Minni T B Mcmaster; Nikki Polderman; Yvon D A T de Vries; Wim van den Brink; Guido A van Wingen Journal: Hum Brain Mapp Date: 2019-02-05 Impact factor: 5.038
Authors: Alexander Malafeev; Dmitry Laptev; Stefan Bauer; Ximena Omlin; Aleksandra Wierzbicka; Adam Wichniak; Wojciech Jernajczyk; Robert Riener; Joachim Buhmann; Peter Achermann Journal: Front Neurosci Date: 2018-11-06 Impact factor: 4.677