This project will use measures of neural synchrony in the scalp-recorded electroencephalogram (EEG) to examine the functional integrity of neural circuitry in schizophrenia. Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. A growing number of studies have reported that individuals with schizophrenia demonstrate abnormal synchronization in the "gamma" band of the EEG (30-100 Hz). Gamma oscillations may mediate perceptual and cognitive processes, and are known to rely upon inhibitory interneurons. Therefore, we propose that abnormalities in gamma-band EEG oscillations in schizophrenia patients reflect dysfunctional synchronization of neural circuitry. In our studies of chronic schizophrenia patients (SZ) and healthy control subjects (HC) we have identified several abnormalities in gamma oscillations related to sensory and perceptual processing. 1) In studies using auditory steady-state responses (ASSRs) to probe the integrity of neural circuitry in auditory cortex, SZ show reductions in the ASSRs evoked by gamma frequency stimulation, but not by stimulation at lower frequencies. 2) The early visual stimulus-evoked oscillation (SEO) appears to be reduced in SZ irrespective of stimuli or task demands. In contrast, the auditory SEO evoked by complex sounds but not simple tones is reduced in SZ, and thus this deficit may be related to stimulus features. 3) In studies utilizing Gestalt stimuli to examine visual feature-binding mechanisms, a response-locked oscillation (RLO) potentially related to feature-binding was reduced in frequency from the gamma to the beta frequency range in SZ. RLO phase locking was positively correlated with thought disorder, conceptual disorganization, and visual hallucination symptoms in SZ. These data and others demonstrate that schizophrenia is associated with abnormalities in a variety of sensory- and perception-related gamma oscillations. To elucidate the dysfunctional neural dynamics that are manifested by gamma oscillations in schizophrenia, we propose the following studies in chronic SZ and matched HC. Oscillatory brain activity will be measured using wavelet-based time-frequency methods.
Our specific aims are to: 1) determine the factors underlying the ASSR gamma driving deficit;2) determine the effects of stimulus features and attentional demands on the deficits of the auditory and visual SEOs;3) reveal the oscillatory dynamics underlying the ASSR and SEO deficits in SZ.

Public Health Relevance

To treat and ultimately prevent neuropsychiatric disorders, we must understand how the mind and brain are interrelated. This project seeks to further this goal by studying how brainwave synchronization is related to perception and thinking in people who are healthy, and in people who have schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Meinecke, Douglas L
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Harvard University
Schools of Medicine
United States
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Mulert, C; Kirsch, V; Pascual-Marqui, Roberto et al. (2011) Long-range synchrony of ? oscillations and auditory hallucination symptoms in schizophrenia. Int J Psychophysiol 79:55-63
Spencer, Kevin M; Nestor, Paul G; Valdman, Olga et al. (2011) Enhanced facilitation of spatial attention in schizophrenia. Neuropsychology 25:76-85
Spencer, Kevin M; Niznikiewicz, Margaret A; Nestor, Paul G et al. (2009) Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia. BMC Neurosci 10:85