Salience network and coordination of brain circuits in schizophrenia. (360G-Wellcome-096002_Z_11_Z)

Structural and functional brain changes have been documented extensively in schizophrenia. Emergence of psychosis during adolescence is a well-established feature of schizophrenia. Aberrant neurodevelopment leading to disrupted coordination of brain circuits has been proposed as a putative cause. Glutamatergic dysfunction has been proposed to underlie this dysconnectivity. During normal adolescence pruning of focal brain circuits leads to the emergence of longer-range connections even in the absence of direct anatomical connectivity. A paralimbic network called Salience Network (insula and anterior cingulate) has been identified as a key circuit that matures in connectivity during adolescence. This network is thought to mediate switching between default-mode and task-active brain states by modulating the recruitment of the relevant large-scale networks, in healthy adults. Objectives: To study the nature of short-range and long-range structural and functional connectivity in sch izophrenia and to demonstrate impaired Salience Network modulation of task-related recruitment of brain circuits, using fMRI. Functional connectivity will be related to glutamate levels in insula and anterior cingulate (measured using spectroscopy). Independent Component Analysis, Graph Networks and Dynamic Causal Modeling will be employed to study functional connectivity. Tractography will be used to analyse structural connectivity. Surface-based morphometry will be employed to study struc tural covariance complementing functional connectivity.