The purpose of this Supplemental Application is to study how the brain changes in response to intensive cognitive training in schizophrenia. We will extend upon our original cognitive remediation project and perform a set of neurobiological assessments on a subsample of schizophrenic subjects before, during, and after training. We hypothesize that we will obtain direct evidence for plasticity: improvements in the brain's information processing capabilities at the neural level in response to neuroadaptive cognitive remediation exercises in schizophrenia. ? ? The Original Study: We are employing a set of novel, intensive, computer-based cognitive training exercises that specifically target processing efficiency and attention/working memory using an adaptive training procedure. We are examining the effects of this neuroscience-guided targeted cognitive training (TCT) on cognitive performance, symptom profile, quality of life, and social cue recognition in subjects with schizophrenia, as compared to subjects who undergo a control intervention (graphics-based computer games). ? ? The Supplement: We propose to perform magnetoencephalography (MEG) to examine changes in early cortical event-related responses and in working memory responses, as a function of TCT. We also propose to perform functional magnetic resonance imaging (fMRI) studies of changes in cortical activation patterns during a working memory task and an episodic memory task in response to TCT. ? ? What the Supplement Adds: The overall general design and methods of our study will remain intact. The supplemental funding will be used to acquire, process, manage, and analyze the neurobiological data. We thus will be able to accomplish several innovative goals that make use of the unique subject sample in our study and that greatly enhance the behavioral assessments. We will demonstrate that, in response to TCT, schizophrenic subjects show: ? ? 1. Improvements in the brain's fidelity (amplitude of neuronal response) and efficiency (deployment of neuronal resources) in the processing of early auditory information, via MEG. ? ? 2. Improvements in the brain's efficiency during working memory tasks (via MEG and fMRI). ? ? 3. """"""""Normalization"""""""" of fMRI brain activation patterns during verbal memory processing. ? ? 4. Correlation of """"""""normalized"""""""" brain activation patterns with behavioral improvements in neurocognitive performance. ? ? To the public: We are conducting a research study to find out whether computerized training might help people with schizophrenia or schizoaffective disorder lessen their symptoms and learn new thinking and problem-solving skills. We will also study how the brain changes in people with schizophrenia as they undertake this training. ? ? ?
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