Optimizing behavior depends on the ongoing monitoring and flexible adjustment of responses. Schizophrenia is characterized by responses that are rigid, stereotyped, and perseverative rather than guided by context. We propose to study the neural bases of cognitive functions that are essential to adaptive, flexible responding and how they go awry in schizophrenia. First, we will examine the neural bases of spared and impaired aspects of 'error processing'. An intact error processing system is necessary for detecting and providing feedback regarding the occurrence of errors so that behavioral adjustments can be made. While it is critical to learn from feedback regarding past performance, behavior also has to be responsive to current contingencies. We present evidence that the balance between past and present influences is upset in schizophrenia leading to perseveration - the maladaptive persistence of responses.
Our second aim i s to study the mechanisms underlying perseveration by examining how the requirement to inhibit a prepotent behavior leads to abnormally persistent effects on the response system. We propose to use variations of the antisaccade (AS) paradigm in these experiments because of its well-charted neuroanatomy and neurophysiology. We will combine the spatial precision of event-related functional magnetic resonance imaging (fMRI) with the high temporal resolution of magnetoencephalography (MEG) to identify the regions involved and the timing of their contribution at various stages of AS performance. Since AS performance is the product of coordinated activity across a distributed network, we will also assess the integrity of white matter tracts using Diffusion Tensor Imaging (DTI). Together, these methods will allow us to precisely delineate the neural bases of intact and compromised cognitive function in schizophrenia. In order to adapt to the environment, it is necessary to both learn from the past and to respond to present task demands. Brain networks that are critical to evaluating performance, remediating behavior, and responding flexibly to current task demands are impaired in schizophrenia, and this likely contributes to rigid and maladaptive patterns of behavior. This research will identify the neural basis of both spared and impaired cognitive processes, guide investigations of neuropathology, and provide targets for intervention aimed at improving cognition in schizophrenia. ? ? ?
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