Early auditory gamma-band responses in patients at clinical high risk for schizophrenia.

Background: Gamma-band oscillations and their synchronization have been implicated in the coordination of activity between distributed neuronal assemblies in the service of sensory registration of stimuli and perceptual binding of their features. Prior electroencephalographic (EEG) studies of chronic schizophrenia patients have documented deficits in the magnitude and/or phase synchrony of stimulus-evoked gamma oscillations, findings that have been linked to neurotransmission abnormalities involving GABA and NMDA-glutamate receptors. However, it remains unclear whether these abnormalities are present at the onset of the illness, or indeed, whether they are present during the prodromal period preceding illness onset. Accordingly, we examined the magnitude and phase synchrony of the transient gamma-band response (GBR) elicited by an auditory stimulus in young patients with schizophrenia and in patients at clinical high risk for psychosis based on their manifestation of putatively prodromal symptoms. Methods: EEG was recorded during an auditory oddball target detection task in three groups: young schizophrenia patients early in their illness (YSZ; n = 19), patients at clinical high risk for psychosis (CHR; n = 55), and healthy controls (HC; n = 42). Single-trial EEG epochs and the average event-related potential time-locked to standard tones from the oddball task were subjected to time-frequency decomposition using Morlet wavelet transformations. The GBR between 50 and 100 ms following the tone onset was quantified in terms of evoked power, total power, and the phase-locking factor (PLF) reflecting cross-trial phase synchrony. Results: GBR evoked power was significantly reduced in YSZ (p < 0.01) and CHR (p < 0.05) patients, relative to HC. Similarly, GBR PLF was significantly reduced in YSZ (p < 0.01) and showed a marginal reduction in CHR patients (p = 0.057), relative to HC. GBR total power was not reduced in CHR patients (p = 0.68) and showed only a trend level reduction in YSZ (p = 0.072). Within the CHR group, there were no significant GBR differences between the patients who converted to a psychotic disorder and those who did not convert to psychosis during a 12-month follow-up period. Conclusion: Reductions in the transient auditory GBR, as reflected by evoked power and phase synchrony, are evident in the early stages of schizophrenia and appear to precede psychosis onset. However, the absence of total power GBR abnormalities in CHR patients, with only a trend toward reduction in YSZ patients, suggests that the magnitude of the GBR is intact early in the course of schizophrenia, whereas the phase synchrony of this response is deficient. Given that the GBR failed to distinguish the CHR patients who converted to psychosis from those who did not convert, the role of GBR disruption in the emergence of psychosis warrants further investigation. Asynchronous gamma activity may represent an elemental neurobiological abnormality in schizophrenia that is also evident in patients at high clinical risk for psychosis regardless of their longer-term clinical outcomes.