The neural signature of abnormal controlled processing in schizophrenia must be written into the electrical activity of cerebral neurons. A nonhuman primate model of controlled processing can serve as a bridge linking minute physiological events in cortical neurons to patterns of altered cognitive control that are indicative of cognitive deficits in schizophrenia. The first step in the proposed translational endeavor is to develop tasks for cross-species studies. We will implement a spatial working memory task developed in the context of single-cell recordings in nonhuman primates, and a sustained visual attention task used to reveal reliable vigilance deficits in schizophrenia patients and their first-degree relatives, to study visual controlled processes in schizophrenia patients, control subjects, and nonhuman primates. Through behavioral studies we will identify characteristics of spatial working memory and sustained visual attention tasks that allow for study of specific visual controlled processing deficits in schizophrenia. Next, we will identify candidate neural signals associated with visual controlled processing through the use of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). We will require candidate neurophysiological signals characterized by fMRI or MEG to exhibit dependency on the amount of controlled processing performed, selective synchrony between prefrontal cortex and visual stream activity, and associations with augmented sensory activity and controlled processing deficits in schizophrenia. From the results of these studies we will design a task that allows for clear delineation of neural mechanims underlying visual controlled processing in humans and nonhuman primates, and apply the task in future studies of schizophrenia. We hypothesize that high frequency neural activity (gamma) serves as a neurophysiological signal of activity in cortical networks mediating visual controlled processing. ? ?
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