569. Gamma frequency auditory processing abnormalities in schizophrenia

Abstract

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 both within a single sensory modality, across modalities, and across time. Furthermore, basic science evidence suggests gamma range synchronization depends on the glutamatergically mediated interplay between excitator projection neurons (glutamatergic) and GABAergic circuits, for which post-mortem studies suggest abnormalities in schizophrenia. 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, such as seen in schizophrenia. We thus investigated the ability of chronic schizophrenics to support gamma range auditory entrainment as compared with gender, age, and handedness matched control subjects. Synchronization of the electroencephalogram (EEG) to different rates (20 to 40 Hz) of auditory stimulation was recorded, and 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. Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenics showed delayed onset of phase synchronization, and delayed desynchronization, to the click train. The EEG power findings were mimicked by a formal neural circuit model of deficient recurrent inhibition, a model based on our in vitro evidence that PCP and other NMDA channel blocker psychotomimetics have stronger blocking effects at NMDA receptors on GABAergic interneurons than those on projection neurons. Anatomically, the primary auditory cortex is probably one of the major sources of the auditory “steady state” or entrainment EEG response to periodic stimuli, and it is of note that we recently have found, in a first episode schizophrenia population, bilaterally reduced MRI volume of Heschl’s gyrus (primary auditory cortex).