Journal article

Authors list: Curic, Stjepan; Andreou, Christina; Nolte, Guido; Steinmann, Saskia; Thiebes, Stephanie; Polomac, Nenad; Haaf, Moritz; Rauh, Jonas; Leicht, Gregor; Mulert, Christoph

Publication year: 2021

Journal: Frontiers in Psychiatry

Volume number: 12

ISSN: 1664-0640

Open access status: Gold

DOI Link: https://doi.org/10.3389/fpsyt.2021.671007

Publisher: Frontiers Media

Abstract: 
Disturbed functional connectivity is assumed to cause neurocognitive deficits in patients suffering from schizophrenia. A Glutamate N-methyl-D-aspartate receptor (NMDAR) dysfunction has been suggested as a possible mechanism underlying altered connectivity in schizophrenia, especially in the gamma- and theta-frequency range. The present study aimed to investigate the effects of the NMDAR-antagonist ketamine on resting-state power, functional connectivity, and schizophrenia-like psychopathological changes in healthy volunteers. In a placebo-controlled crossover design, 25 healthy subjects were recorded using resting-state 64-channel-electroencephalography (EEG) (eyes closed). The imaginary coherence-based Multivariate Interaction Measure (MIM) was used to measure gamma and theta connectivity across 80 cortical regions. The network-based statistic was applied to identify involved networks under ketamine. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC). Ketamine caused an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01). Significant increases in resting-state gamma and theta power were observed under ketamine compared to placebo (p < 0.05). The source-space analysis revealed two distinct networks with an increased mean functional gamma- or theta-band connectivity during the ketamine session. The gamma-network consisted of midline regions, the cuneus, the precuneus, and the bilateral posterior cingulate cortices, while the theta-band network involved the Heschl gyrus, midline regions, the insula, and the middle cingulate cortex. The current source density (CSD) within the gamma-band correlated negatively with the PANSS negative symptom score, and the activity within the gamma-band network correlated negatively with the subjective changed meaning of percepts subscale of the 5D-ASC. These results are in line with resting-state patterns seen in people who have schizophrenia and argue for a crucial role of the glutamate system in mediating dysfunctional gamma- and theta-band-connectivity in schizophrenia. Resting-state networks could serve as biomarkers for the response to glutamatergic drugs or drug development efforts within the glutamate system.

Harvard Citation style: Curic, S., Andreou, C., Nolte, G., Steinmann, S., Thiebes, S., Polomac, N., et al. (2021) Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System, Frontiers in Psychiatry, 12, Article 671007. https://doi.org/10.3389/fpsyt.2021.671007

APA Citation style: Curic, S., Andreou, C., Nolte, G., Steinmann, S., Thiebes, S., Polomac, N., Haaf, M., Rauh, J., Leicht, G., & Mulert, C. (2021). Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System. Frontiers in Psychiatry. 12, Article 671007. https://doi.org/10.3389/fpsyt.2021.671007