We propose to use measures of oscillatory activity in the scalp-recorded electroencephalogram (EEG) to examine the functional integrity of the neural circuitry underlying visual perception in schizophrenia. Schizophrenia has been conceptualized as a failure of the integration of cognitive and neural processes, and abnormalities in neural microcircuitry have been proposed as a basis for this disorder. There is growing evidence that oscillations in the upper frequency bands of the EEG, the beta ( : 13-30 Hz) and gamma ( : 30- 100 Hz) bands, mediate particular functions involved in visual perception. We hypothesize that abnormalities of and oscillations may reflect particular neural microcircuit abnormalities involved in schizophrenia. The proposed studies will build upon the previous project period in which we examined the relationships between response-locked oscillations (RLOs), perceptual feature-binding, and schizophrenia symptomatology. In the next project period we propose to use a unified approach to study oscillation abnormalities in schizophrenia: perceptual decision making. This approach involves tracking the evolution of a simple perceptual decision from stimulus to response stages of processing. Studies in animals and humans support a basic model in which stimulus encoding in sensory areas is read-out by multimodal association areas in which perceptual evidence accumulates and decisions are formed. Decision information is then transmitted to motor cortex and a response is made. Oscillation studies suggest that and oscillations may play distinct roles, with oscillations reflecting local computations of sensory and response processes, and oscillations involved in attentional control and maintaining stimulus-response mappings underlying the perceptual decision. Therefore, the perceptual decision making approach will allow us to identify abnormalities in particular aspects of information processing in SZ and relate these abnormalities to the patients'symptomatology. We hypothesize that: 1) SZ have independent deficits in sensory encoding, evidence accumulation, and response selection processes;2) psychotic symptoms, such as disorganization and thought disorder, are closely related to dysfunctional evidence accumulation processes;and 3) top-down control deficits contribute to evidence accumulation impairments and psychotic symptom relationships.
Our specific aims are to: 1) Dissociate feature binding from perceptual decision processes. Our standard Kanisza shape perception task will be modified to support 2 different judgments: shape presence/absence, and distinguishing between inducer attributes. We predict that perception-independent decisional processes will be abnormal and correlated with positive symptoms in SZ. 2) Examine which phases of perceptual decision making (sensory encoding, evidence accumulation, and response selection) are abnormal in SZ, using a coherent motion detection task. We predict that while all three phases will be impaired in SZ, these impairments will be independent of each other. A measure of evidence accumulation will be positively correlated with psychotic symptoms. 3) Examine the role of top-down processes in SZ abnormalities in perceptual decision making by manipulating subjects'expectancies about the stimuli in the coherent motion detection task using cues. We predict that top-down processes will interact with both sensory and decisional processes, and will influence the relationships between decisional processes and psychotic symptoms in SZ. We hope that the results of these studies will lead to a deeper understanding of the cognitive and neural mechanisms underlying schizophrenia, enabling the identification of biomarkers for treatment development.

Public Health Relevance

Schizophrenia affects approximately 1% of the general population and has profound negative consequences for the personal, psychological, and fiscal well being of patients, their families, and society as a whole. This disorder characterizes a major group of patients in the VHA, where the chronically mentally ill (primarily patients with schizophrenia) account for a large proportion of VA mental healthcare costs. To treat and ultimately prevent schizophrenia, 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)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Mental Health and Behavioral Science B (MHBB)
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VA Boston Health Care System
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Oribe, Naoya; Hirano, Yoji; Kanba, Shigenobu et al. (2015) Progressive reduction of visual P300 amplitude in patients with first-episode schizophrenia: an ERP study. Schizophr Bull 41:460-70
del Re, Elisabetta C; Spencer, Kevin M; Oribe, Naoya et al. (2015) Clinical high risk and first episode schizophrenia: auditory event-related potentials. Psychiatry Res 231:126-33
Ghorashi, Shahab; Spencer, Kevin M (2015) Attentional Load Effects on Beta Oscillations in Healthy and Schizophrenic Individuals. Front Psychiatry 6:149
Hirano, Yoji; Oribe, Naoya; Kanba, Shigenobu et al. (2015) Spontaneous Gamma Activity in Schizophrenia. JAMA Psychiatry 72:813-21
Hall, Mei-Hua; Jensen, J Eric; Du, Fei et al. (2015) Frontal P3 event-related potential is related to brain glutamine/glutamate ratio measured in vivo. Neuroimage 111:186-91
Spencer, Kevin M (2014) Time to be spontaneous: a renaissance of intrinsic brain activity in psychosis research? Biol Psychiatry 76:434-5
Spencer, Kevin M; Ghorashi, Shahab (2014) Oscillatory dynamics of Gestalt perception in schizophrenia revisited. Front Psychol 5:68
Oribe, Naoya; Hirano, Yoji; Kanba, Shigenobu et al. (2013) Early and late stages of visual processing in individuals in prodromal state and first episode schizophrenia: an ERP study. Schizophr Res 146:95-102
Ford, Judith M; Dierks, Thomas; Fisher, Derek J et al. (2012) Neurophysiological studies of auditory verbal hallucinations. Schizophr Bull 38:715-23
Mears, Ryan P; Spencer, Kevin M (2012) Electrophysiological assessment of auditory stimulus-specific plasticity in schizophrenia. Biol Psychiatry 71:503-11

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