Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective.

BACKGROUND AND HYPOTHESIS: N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be determined whether the physiological changes observed following NMDA-R antagonist administration are consistent with auditory gamma-band activity in ScZ which is dependent on NMDA-R activity. STUDY DESIGN: This systematic review investigated the effects of NMDA-R antagonists on auditory gamma-band activity in preclinical (n = 15) and human (n = 3) studies and compared these data to electro/magneto-encephalographic measurements in ScZ patients (n = 37) and 9 studies in early-stage psychosis. The following gamma-band parameters were examined: (1) evoked spectral power, (2) intertrial phase coherence (ITPC), (3) induced spectral power, and (4) baseline power. STUDY RESULTS: Animal and human pharmacological data reported a reduction, especially for evoked gamma-band power and ITPC, as well as an increase and biphasic effects of gamma-band activity following NMDA-R antagonist administration. In addition, NMDA-R antagonists increased baseline gamma-band activity in preclinical studies. Reductions in ITPC and evoked gamma-band power were broadly compatible with findings observed in ScZ and early-stage psychosis patients where the majority of studies observed decreased gamma-band spectral power and ITPC. In regard to baseline gamma-band power, there were inconsistent findings. Finally, a publication bias was observed in studies investigating auditory gamma-band activity in ScZ patients. CONCLUSIONS: Our systematic review indicates that NMDA-R antagonists may partially recreate reductions in gamma-band spectral power and ITPC during auditory stimulation in ScZ. These findings are discussed in the context of current theories involving alteration in E/I balance and the role of NMDA hypofunction in the pathophysiology of ScZ.

Investigating temporal and prosodic markers in clinical high-risk for psychosis participants using automated acoustic analysis.

AIM: Language disturbances are a candidate biomarker for the early detection of psychosis. Temporal and prosodic abnormalities have been observed in schizophrenia patients, while there is conflicting evidence whether such deficits are present in participants meeting clinical high-risk for psychosis (CHR-P) criteria. METHODS: Clinical interviews from CHR-P participants (n = 50) were examined for temporal and prosodic metrics and compared against a group of healthy controls (n = 17) and participants with affective disorders and substance abuse (n = 23). RESULTS: There were no deficits in acoustic variables in the CHR-P group, while participants with affective disorders/substance abuse were characterized by slower speech rate, longer pauses and higher unvoiced frames percentage. CONCLUSION: Our finding suggests that temporal and prosodic aspects of speech are not impaired in early-stage psychosis. Further studies are required to clarify whether such abnormalities are present in sub-groups of CHR-P participants with elevated psychosis-risk.

Do NMDA-R antagonists re-create patterns of spontaneous gamma-band activity in schizophrenia? A systematic review and perspective.

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. 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). 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. 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.

Stop stereotyping.

Restraining the expression of stereotypes is a necessary requirement for harmonious living, yet surprisingly little is known about the efficacy of this process. Accordingly, in two experiments, here we used a stop-signal task to establish how effectively stereotype-related responses can be inhibited. In Experiment 1, following the presentation of gender-typed occupational contexts, participants reported the sex of target faces (i.e., Go trials) unless an occasional auditory tone indicated they should withhold their response (i.e., Stop trials). In Experiment 2, following the presentation of male and female faces, participants made either stereotypic or counter-stereotypic judgments, unless a stop signal was presented. Regardless of whether stereotyping was probed indirectly (Experiment 1) or directly (Experiment 2), a consistent pattern of results was observed; inhibition was faster for stereotypic compared with counter-stereotypic responses. These findings demonstrate that stopping stereotyping may be less challenging than has widely been assumed.