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Effects of gamma-hydroxybutyrate on neurophysiological correlates of performance and conflict monitoring


Dornbierer, Dario A; Kometer, Michael; Von Rotz, Robin; Studerus, Erich; Gertsch, Jürg; Gachet, M Salomé; Vollenweider, Franz X; Seifritz, Erich; Bosch, Oliver G; Quednow, Boris B (2019). Effects of gamma-hydroxybutyrate on neurophysiological correlates of performance and conflict monitoring. European Neuropsychopharmacology, 29(4):539-548.

Abstract

Performance and conflict monitoring (PM and CM) represent two essential cognitive abilities, required to respond appropriately to demanding tasks. PM and CM can be investigated using event-related brain potentials (ERP) and associated neural oscillations. Namely, the error-related negativity (ERN) represents a correlate of PM, whereas the N2 component reflects the process of CM. Both ERPs originate in the anterior cingulate cortex (ACC) and PM specifically has been shown to be susceptible to gamma-aminobutyric acid (GABA) A receptor activation. Contrarily, the specific effects of GABAB receptor (GABABR) stimulation on PM and CM are unknown. Thus, the effects of gamma-hydroxybutyrate (GHB; 20 and 35 mg/kg), a predominant GABABR agonist, on behavioral and electrophysiological correlates of PM and CM were here assessed in 15 healthy male volunteers, using the Eriksen–Flanker paradigm in a randomized, double-blind, placebo-controlled, cross-over study. Electroencephalographic (EEG) data were analyzed in the time and time-frequency domains. GHB prolonged reaction times, without affecting error rates or post-error slowing. Moreover, GHB decreased ERN amplitudes and associated neural oscillations in the theta/alpha1 range. Similarly, neural oscillations associated with the N2 were reduced in the theta/alpha1 range, while N2 amplitude was conversely increased. Hence, GHB shows a dissociating effect on electrophysiological correlates of PM and CM. Reduced ERN likely derives from a GABABR-mediated increase in dopaminergic signaling, disrupting the generation of prediction errors, whereas an enhanced N2 suggests an increased susceptibility towards external stimuli. Conclusively, GHB is the first drug reported, thus far, to have opposite effects on PM and CM, underlined by its unique electrophysiological signature.

Abstract

Performance and conflict monitoring (PM and CM) represent two essential cognitive abilities, required to respond appropriately to demanding tasks. PM and CM can be investigated using event-related brain potentials (ERP) and associated neural oscillations. Namely, the error-related negativity (ERN) represents a correlate of PM, whereas the N2 component reflects the process of CM. Both ERPs originate in the anterior cingulate cortex (ACC) and PM specifically has been shown to be susceptible to gamma-aminobutyric acid (GABA) A receptor activation. Contrarily, the specific effects of GABAB receptor (GABABR) stimulation on PM and CM are unknown. Thus, the effects of gamma-hydroxybutyrate (GHB; 20 and 35 mg/kg), a predominant GABABR agonist, on behavioral and electrophysiological correlates of PM and CM were here assessed in 15 healthy male volunteers, using the Eriksen–Flanker paradigm in a randomized, double-blind, placebo-controlled, cross-over study. Electroencephalographic (EEG) data were analyzed in the time and time-frequency domains. GHB prolonged reaction times, without affecting error rates or post-error slowing. Moreover, GHB decreased ERN amplitudes and associated neural oscillations in the theta/alpha1 range. Similarly, neural oscillations associated with the N2 were reduced in the theta/alpha1 range, while N2 amplitude was conversely increased. Hence, GHB shows a dissociating effect on electrophysiological correlates of PM and CM. Reduced ERN likely derives from a GABABR-mediated increase in dopaminergic signaling, disrupting the generation of prediction errors, whereas an enhanced N2 suggests an increased susceptibility towards external stimuli. Conclusively, GHB is the first drug reported, thus far, to have opposite effects on PM and CM, underlined by its unique electrophysiological signature.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Pharmacology (medical), Biological Psychiatry, Pharmacology, Neurology, Psychiatry and Mental health, Clinical Neurology
Language:English
Date:1 April 2019
Deposited On:13 Mar 2019 10:06
Last Modified:20 Apr 2019 01:05
Publisher:Elsevier
ISSN:0924-977X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.euroneuro.2019.02.004
PubMed ID:30824339

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Language: English
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Embargo till: 2020-02-26