Basic research suggests that the functional significance of synchronized neural oscillations depends on their frequency. Gamma frequencies, above 30 Hz, appear to facilitate feedforward processes that transmit basic information from sensory cortex to higher cortical regions. Frequency oscillations below 30 Hz appear to reflect the transmission of feedback information from higher cortical regions that modifies functions within sensory cortices and prioritizes elements related to behavioral goals. Although schizophrenia has been proposed to be a disorder of disturbed neural synchronization within and between brain regions, researchers have only begun to examine feedforward and feedback abnormalities reflected in the phase dynamics of electroencephalography (EEG) oscillations. The unanswered research question the proposed work addresses is whether perceptual and cognitive deficits pervasive in schizophrenia are due to deviant neural synchronization that disrupts feedforward and feedback processes within networks of the brain. The proposed work will examine aberrant neural synchronization in schizophrenia within low frequency and gamma bands during a resting state and visual perception. Through the use of visual perceptual tasks that vary in demands of feedforward and feedback processes we will test whether specific synchronization abnormalities are associated with sensory and cognitive elements of atypical visual perception in schizophrenia. Subjects will include people with schizophrenia (PSZ), biological siblings of PSZ (SibPSZ), people with bipolar disorder (PBP), biological siblings of PBP (SibPBP), and a healthy control sample (HC) to determine whether deviant oscillations are specific to schizophrenia and associated with its genetic liability. We will engage in a series of three experiments with the intention of relating deviant synchronization to a specific diagnosis of schizophrenia or to genetic liability for the disease. First, we will determine whether aberrant synchronization of resting state oscillations is present in our sample and how it segregates across diagnostic groups. Second, we will use psychophysical tasks to target low-level visual processes to investigate whether abnormal synchronization of neural oscillations provides evidence for impaired feedforward or feedback processes within visual cortex. Third, we will use form perception tasks to determine whether deviant synchronization between high cortical regions and visual cortex reflect impaired inter-areal feedforward or feedback processes. Laboratory tests that can effectively guide treatment and be used to personalize interventions have long been sought after to transform the treatment of severe mental disorders. Understanding the neural origins of cognitive and perceptual disturbances in schizophrenia will facilitate new interventions (e.g., neural modulation) to more precisely and effectively target each individual's abnormal brain function and to optimize the recovery of veterans with psychotic disorders.

Public Health Relevance

This project examines synchronization of brain activity in schizophrenia. Through studying electrical activity of the brain in people with schizophrenia, the study explores whether abnormal neural synchronization is most evident at rest or during tasks that probe brain function. The work also includes analysis of the dynamics of neural oscillations to determine whether abnormalities are most evident in the feedforward passing of information from sensory brain areas to brain regions with higher cognitive functions (i.e., finding a sought-after object) or the feedback of information from regions of higher functions to sensory areas. To determine if abnormalities also reflect genetic liability for schizophrenia and are specific to the disorder, the work includes biological siblings of the people with schizophrenia, people with bipolar affective disorder and their biological siblings. We hypothesize that schizophrenia is specifically associated with errant feedforward and feedback processes, while genetic liability for schizophrenia is only associated with errant feedback functions.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Special Emphasis Panel (ZRD1)
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Minneapolis VA Medical Center
United States
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