Do NMDA-R Antagonists Re-Create Patterns of Spontaneous Gamma-Band Activity in Schizophrenia? A Systematic Review and Perspective
Bianciardi, B., Uhlhaas, P. J
This systematic review (2021) compared gamma-band oscillations elicited by NMDA-receptor agonists such as ketamine to neural oscillations observed in patients with schizophrenia. Whereas NMDAR agonists consistently upregulate gamma-band power, connectivity parameters of schizophrenia were inconsistent by comparison and thus incongruent with the hypothesis that their pathophysiological signatures are caused by NMDA-R hypofunction.
Abstract
Introduction: NMDA-R hypofunctioninig is a core pathophysiological mechanism in schizophrenia. However, it is unclear whether the physiological changes observed following NMDA-R antagonist administration are consistent with gamma-band alterations in schizophrenia.Methods: This systematic review examined the effects of NMDA-R antagonists on the amplitude of spontaneous gamma-band activity and functional connectivity obtained from preclinical (n = 24) and human (n = 9) studies and compared these data to resting-state EEG/MEG-measurements in schizophrenia patients (n = 27).Results: Overall, the majority of preclinical and human studies observed increased gamma-band power following acute administration of NMDA-R antagonists. However, the direction of gamma-band power alterations in schizophrenia were inconsistent, which involved upregulation (n = 10), decreases (n = 7), and no changes (n = 8) in spectral power. Five out of 6 preclinical studies observed increased connectivity, while in healthy controls receiving Ketamine and in schizophrenia patients the direction of connectivity results was also inconsistent.Discussion: Accordingly, the effects of NMDA-R hypofunctioning on gamma-band oscillations are different than pathophysiological signatures observed in schizophrenia. The implications of these findings for current E/I balance models of schizophrenia are discussed.