Key basic and clinical research questions that need to be answered to understand defective automaticity in schizophrenia will be addressed in five studies. A cross-sectional study of normal participants will test hypotheses that there is a general skill acquisition factor, and that the neostriatum is the common neural substrate in early stages of skill acquisition for a wide variety of tasks. The hypotheses that automation is associated with negative functional connectivity between the mesial temporal lobes and the neostriatum and that increased automatization of skills is associated with focalized fMRI activation in task specific cortical neural networks will also be tested. A second cross-sectional study will compare schizophrenia patients to normal participants on the same tasks used in the first study to test the hypothesis that patients with schizophrenia are slower to automate new skills. The hypothesis that defective automaticity in schizophrenia is associated with abnormal patterns of neural activity reflected in fMRI activation will also be tested. A third cross-sectional study will test hypotheses about conditions that facilitate skill acquisition by comparing the effect of random vs. blocked practice in schizophrenia patients and normal controls. A fourth study uses a longitudinal design to test the hypothesis that prodromal patients who convert to psychosis during the prodromal phase show a decreased rate of automation of new skills compared to prodromal patients who do not convert to psychosis and normal controls. These behavioral differences in prodromal patients who convert to schizophrenia are hypothesized to be reflected in abnormal patterns of fMRI activation. We will determine if rate of skill automation predicts functional outcomes, and changes over the course of the disorder in a fifth study. An important feature of these studies is the use of dual-task probes to provide independent indices of the level of automaticity achieved on different tasks. Elucidating the neural substrate for defective automaticity may contribute to the development of new somatic treatments for schizophrenia by identifying specific brain systems as potential therapeutic targets. Testing hypotheses about the effects of different training conditions on skill acquisition should offer insights into the design of novel behavioral rehabilitation programs for patients with schizophrenia.
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