Background  Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing γ-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization.

Methods  Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation.

Results  Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train.

Conclusions  These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.

GAMMA-FREQUENCY band neural activity (30-50 Hz or broader, centered on 40 Hz) has been hypothesized to reflect the synchronization of neural assemblies involved in binding or integration of various features of an object within a single sensory modality, across modalities, and across time.^1-9 For example, gamma synchronization may be involved in the perception of a complex object, such as a cat, which requires integration of many features, such as luminance, color, texture, contours, and position, which are analyzed by discrete neurons or neural systems in the brain.⁶ Although the precise mechanisms of gamma synchronization are unknown, there is evidence of participation of γ-aminobutyric acid (GABA)ergic interneuronal circuits.^5,10 There is also considerable evidence suggestive of abnormalities in GABAergic circuitry in schizophrenia.^11,12 Failure or abnormality in gamma synchronization could result in a variety of perceptual and cognitive abnormalities, including abnormal perceptions, aberrant semantic association, hallucinations, and discontinuities in thinking, that occur in schizophrenia. Clementz et al¹³ recently proposed that transient disturbances of gamma-band response contribute to poor P50 evoked potential auditory response suppression in schizophrenia.

To test whether neural circuits in schizophrenic patients could support normal gamma synchronization at specific frequencies, we evaluated entrainment of the electroencephalogram (EEG) to trains of clicks presented at varying frequencies, including gamma range (40 Hz). When receiving periodic auditory input, neural networks behave like a tuned oscillator with a preferred resonance around 40 Hz,^7,14,15 ie, the EEG synchronizes to the frequency of the periodic stimulus. Anatomically, the primary auditory cortex is probably one of the major sources of the auditory "steady-state" or entrainment response to periodic stimuli, although interconnected temporal lobe and thalamic regions may also be involved. Testing the capacity of this neural circuit to support gamma-range entrainment provides a method to determine the relationship of the power or phase of the output (EEG) to the characteristics of the input (periodic auditory stimuli).