Project Summary / Abstract Neuroimaging studies of schizophrenia in recent years have identified abnormalities in white matter, the brain tissue consisting largely of axons that connect cells in different parts of the brain. These abnormalities, which can be measured non-invasively using a type of imaging called Diffusion Tensor Imaging (DTI), are closely related to cognitive problems that most patients with this illness experience. These cognitive deficits greatly limit the social and occupational functioning of individuals with schizophrenia, and unfortunately do not typically improve with currently available treatments. However, recent scientific advances have found that white matter can continue to develop even in adulthood in response to learning new skills. This raises hope that treatments can be developed to enhance this process of white matter development and thereby improve cognition. In the proposed project, we aim to determine if individuals with schizophrenia also show changes in white matter microstructure when they learn a challenging new skill. To do this we will use DTI to study white matter structure in individuals with schizophrenia before and after they complete a short period of training on playing mock musical instrument as part of a video game. This training requires a high level of eye-hand coordination as well as use of auditory and visual cues to perform well. We will use additional imaging modalities and clinical assessments to test the functional significance of white matter changes with training, and to identify biological mechanisms that contribute to white matter changes. Knowledge gained from the proposed project will inform future efforts to develop novel therapeutics targeting white matter as a new avenue for treating cognitive deficits in schizophrenia.

Project Narrative Schizophrenia spectrum disorders are associated with impairment in the microstructure of white matter, the key brain tissue responsible for fast communication between different brain regions necessary for any complex task. This white matter impairment is linked to problems with cognition in schizophrenia, especially slower processing speed. This project aims to study the potential for correcting white matter deficits in schizophrenia by examining mechanisms underlying white matter structure changes in response to training on playing a mock musical instrument.