This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Schizophrenia patients have difficulties with executive functioning including the domains of working memory, flexibility, and inhibiting planned motoric responses. Much of schizophrenia research has focused on the role of prefrontal cortex in executive functioning. This study plans to investigate the inhibition of planned responses using a stop-signal task developed to manipulate the number of motor cues before receiving an inhibition cue. This design allows for evaluation of traditional prefrontal regions as well as the striatum. Extensive research using multi-modal techniques have suggested a role for the striatum in schizophrenia, including animal models and structural and functional imaging. Most importantly, previous research indicated that the striatum plays an important role in both the inhibition of planned motoric responses and the anticipation of inhibition (Vink et al. 2005). A further goal of this study is to investigate whether the behavioral and imaging abnormalities in schizophrenia patients are related to the genes predisposing for schizophrenia or mostly to the disease process or other non-specific effects. To determine which processes are related to the genetic vulnerability to the disorder, this study will include the non-psychotic relatives of schizophrenia patients, as schizophrenia patients and their relatives share genes, but not the disease process. We anticipate that the striatum and regions of the prefrontal cortex will be found to be reduced in activity when inhibiting a response in schizophrenia patients and relatives of patients compared to controls. Lastly, we predicted that striatal functioning in controls will increase as these participants anticipate an inhibition cue, however this linear increase will be absent in schizophrenia patients and their relatives.
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