Association of Magnetoencephalographically Measured High-Frequency Oscillations in Visual Cortex With Circuit Dysfunctions in Local and Large-scale Networks During Emerging Psychosis

Key PointsQuestionAre high-frequency oscillations in visual cortex impaired during early stages of psychosis? FindingsIn this cross-sectional study, there were significant impairments in the variability, power, and connectivity of neural oscillations during visual processing in clinical high-risk participants and patients with first-episode psychosis that were associated with impaired functioning and cognitive deficits. Moreover, the increased variability of gamma -band oscillations in visual cortex was also associated with the persistence of subthreshold psychotic symptoms in clinical high-risk participants. MeaningImpaired high-frequency oscillations in visual cortex are an important aspect of circuit dysfunction, which could constitute a biomarker for clinical staging of emerging psychosis. ImportancePsychotic disorders are characterized by impairments in neural oscillations, but the nature of the deficit, the trajectory across illness stages, and functional relevance remain unclear. ObjectivesTo examine whether changes in spectral power, phase locking, and functional connectivity in visual cortex are present during emerging psychosis and whether these abnormalities are associated with clinical outcomes. Design, Setting, and ParticipantsIn this cross-sectional study, participants meeting clinical high-risk criteria for psychosis, participants with first-episode psychosis, participants with affective disorders and substance abuse, and a group of control participants were recruited. Participants underwent measurements with magnetoencephalography and magnetic resonance imaging. Data analysis was carried out between 2018 and 2019. Main Outcomes and MeasuresMagnetoencephalographical activity was examined in the 1- to 90-Hz frequency range in combination with source reconstruction during a visual grating task. Event-related fields, power modulation, intertrial phase consistency, and connectivity measures in visual and frontal cortices were associated with neuropsychological scores, psychosocial functioning, and clinical symptoms as well as persistence of subthreshold psychotic symptoms at 12 months. ResultsThe study participants included those meeting clinical high-risk criteria for psychosis (n=119; mean [SD] age, 22 [4.4] years; 32 men), 26 patients with first-episode psychosis (mean [SD] age, 24 [4.2] years; 16 men), 38 participants with affective disorders and substance abuse (mean [SD] age, 23 [4.7] years; 11 men), and 49 control participants (mean age [SD], 23 [3.6] years; 16 men). Clinical high-risk participants and patients with first-episode psychosis were characterized by reduced phase consistency of beta/gamma -band oscillations in visual cortex (d=0.63/d=0.93). Moreover, the first-episode psychosis group was also characterized by reduced occipital gamma -band power (d=1.14) and altered visual cortex connectivity (d=0.74-0.84). Impaired fronto-occipital connectivity was present in both clinical high-risk participants (d=0.54) and patients with first-episode psychosis (d=0.84). Importantly, reductions in intertrial phase coherence predicted persistence of subthreshold psychosis in clinical high-risk participants (receiver operating characteristic area under curve=0.728; 95% CI, 0.612-0.841; P=.001). Conclusions and RelevanceHigh-frequency oscillations are impaired in the visual cortex during emerging psychosis and may be linked to behavioral and clinical impairments. Impaired phase consistency of gamma -band oscillations was also associated with the persistence of subthreshold psychosis, suggesting that magnetoencephalographical measured neural oscillations could constitute a biomarker for clinical staging of emerging psychosis. This study examines whether changes in spectral power, phase locking, and functional connectivity in visual cortex are present during emerging psychosis and whether these abnormalities are associated with clinical outcomes.