This MERIT extension application builds on the Pi's major findings during the prior funding period to extend prior themes. A major conclusion, consistent with emerging literature is that different functional brain networks Identified through independent component analysis (ICA) of BOLD activation associated with a variety of functional MRI paradigms are commonly engaged across many tasks, In controls and schizophrenia patients. These include networks subserving complex focused attention, "brain idling" (in the resting state and default mode), working memory/executive decision-making, set maintenance and language. These circuits are focused around four major neural nodes, and using approaches such as functional network connectivity, (FNC) one can demonstrate disrupted relationships among these circuits in schizophrenia that seem to plausibly constitute the neural basis of "disconnectivity." We capitalize on our continuing focus on heteromodal association cortical regions as well as continuing to study functional MRI tasks based around semantic knowledge and "Theory of Mind "that we hypothesize are central to schizophrenia formal thought disorder, but have not been explored in depth using the analytic tools available to our group. Finally we will combine the use of functional and anatomical connectivity analysis techniques, singly and in combination, (the latter using fusion techniques across imaging modalities, including novel combinations of Diffusion Tensor Imaging with fMRI), to elucidate relationships between cognitive system dysfunction leading to symptoms and neural network abnormalities.
Schizophrenia is a common, disabling brain-based disorder commonly hypothesized to be due to disconnection between different brain regions, although this has not been demonstrated directly. This proposal seeks to elucidate the nature of the disconnection by examining connections among different brain circuits, using structural and functional MRI and diffusion tensor imaging.
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