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Current theories of schizophrenia suggest that the pathophysiology of the disorder may be the result of a deficit in the coordination of neural activity within and between areas of the brain, which may lead to impairments in basic cognitive functions such as contextual disambiguation and dynamic grouping (Phillips and Silverstein, 2003). This notion has been supported by recent studies showing that patients with schizophrenia are characterized by reduced synchronous, oscillatory activity in the gamma-frequency band during sensory processing (Spencer et al. 2003, Green et al. 2003, Wynn et al. 2005). However, it is currently unclear to what extent high-frequency gamma-band oscillations (> 60 Hz) contribute to impaired neural synchronization as research has so far focussed on gamma-band oscillations between 30 and 60 Hz. In addition, it is not known whether deficits in high-frequency oscillations are already present at the onset of the disorder and to what extent reductions may be related to the confounding influence of antipsychotic medication. Finally, the neural generators underlying impairments in synchronous oscillatory activity in schizophrenia have not been investigated yet. To address these questions, we recorded MEG activity during a visual closure task (Mooney faces task) in medicated chronic schizophrenia patients, drug-naive first-episode schizophrenia patients and healthy controls. MEG data were analysed for spectral power between 25 and 150 Hz, and beamforming techniques were used to localize the sources of oscillatory gamma-band activity. In healthy controls, we observed that the processing of Mooney faces was associated with sustained high-frequency gamma-band activity (> 60 Hz). A time-resolved analysis of the neural generators underlying perceptual closure revealed a network of distributed sources in occipito-temporal, parietal and frontal regions, which were differentially activated during specific time intervals. In chronic schizophrenia patients, we found a pronounced reduction of high-frequency gamma-band oscillatory activity that was accompanied by an impairment in perceptual organization and involved reduced source power in various brain regions associated with perceptual closure. First-episode patients were also characterized by a deficit in high-frequency gamma-band activity and reductions of source power in multiple areas; these impairments, however, were less pronounced than in chronic patients. Regarding behavioral performance, first-episode patients were not impaired in their ability to detect Mooney faces, but exhibited a loss in specificity of face detection. In conclusion, our results suggest that schizophrenia is associated with a widespread reduction in high-frequency oscillations that indicate local network abnormalities. These dysfunctions are independent of medication status and already present at illness onset, suggesting a possible progressive deficit during the course of the disorder.
Oscillatory activity in human electro- or magnetoencephalogram has been related to cortical stimulus representations and their modulation by cognitive processes. Whereas previous work has focused on gamma-band activity (GBA) during attention or maintenance of representations, there is little evidence for GBA reflecting individual stimulus representations. The present study aimed at identifying stimulus-specific GBA components during auditory spatial short-term memory. A total of 28 adults were assigned to 1 of 2 groups who were presented with only right- or left-lateralized sounds, respectively. In each group, 2 sample stimuli were used which differed in their lateralization angles (15° or 45°) with respect to the midsagittal plane. Statistical probability mapping served to identify spectral amplitude differences between 15° versus 45° stimuli. Distinct GBA components were found for each sample stimulus in different sensors over parieto-occipital cortex contralateral to the side of stimulation peaking during the middle 200–300 ms of the delay phase. The differentiation between "preferred" and "nonpreferred" stimuli during the final 100 ms of the delay phase correlated with task performance. These findings suggest that the observed GBA components reflect the activity of distinct networks tuned to spatial sound features which contribute to the maintenance of task-relevant information in short-term memory.