Abstract
Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-d-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers. In a single-blind, pseudo-randomized, placebo-controlled crossover design, nineteen male, right-handed volunteers were measured using 64 channel electroencephalography (EEG). Psychopathology was assessed with the PANSS interview and the 5D-ASC questionnaire, including a subscale to detect auditory alterations with regard to AVD/AVH (AUA-AVD/AVH). Interhemispheric connectivity analysis was performed using eLORETA source estimation and lagged phase synchronization (LPS) in the gamma-band range (30–100 Hz). Ketamine induced positive symptoms such as hallucinations in a subgroup of healthy subjects. In addition, interhemispheric gamma-band connectivity was found to be altered under ketamine compared to placebo, and subjects with AUA-AVD/AVH under ketamine showed significantly higher interhemispheric gamma-band connectivity than subjects without AUA-AVD/AVH. These findings demonstrate a relationship between NMDAR functioning, interhemispheric connectivity in the gamma-band frequency range between bilateral auditory cortices and the emergence of AVD/AVH in healthy subjects. The result is in accordance with the interhemispheric miscommunication hypothesis of AVH and argues for a possible role of glutamate in AVH in schizophrenia.
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Acknowledgements
We wish to thank the individuals who participated in this study. We would like to thank Sigrid Bozcor for support concerning the statistical analysis. This work was prepared as part of Stephanie Thiebes’ dissertation at the University of Hamburg.
Funding
This research was performed within the collaborative research center SFB 936 C6 to Christoph Mulert and supported by the German Research Foundation (DFG). Jürgen Gallinat was supported by DFG SFB 936 C7.
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Thiebes, S., Steinmann, S., Curic, S. et al. Alterations in interhemispheric gamma-band connectivity are related to the emergence of auditory verbal hallucinations in healthy subjects during NMDA-receptor blockade. Neuropsychopharmacol 43, 1608–1615 (2018). https://doi.org/10.1038/s41386-018-0014-z
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DOI: https://doi.org/10.1038/s41386-018-0014-z
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