Disruption of gamma-delta relationship related to working memory deficits in first-episode psychosis

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizophrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35-45 Hz) and delta (0.5-4 Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta-gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50-150 ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis.