Schizophrenia is thought to be associated with brain dysconnectivity. We propose to investigate structural connectivity disturbances (brain miswiring) in frontostriatal connections in early psychosis. The primary focus of this proposal is frontostriatal connectivity, which is the initial component of frontostriatal circuits that modulate executive function and reward processing, which are disturbed in schizophrenia and affective psychosis. We plan to define the normal brain wiring pattern between frontal cortex and striatum in healthy control (HC) subjects, using diffusion magnetic resonance (dMRI) tractography and, then, to test for deviations from this normal pattern, in early psychosis patients. As brain wiring reflects brain development, measures of brain miswiring in early psychosis could serve as developmental biological markers identifying those early psychosis patients who might benefit from early intervention. We will analyze data obtained from patients with early psychosis and matched HCs as part of the Human Connectome Project for Early Psychosis (HCP-EP) in a case control design using our structural and dMRI protocols. Using these subjects allows us to: (1) mitigate the confounds of medication and chronicity; (2) use a transdiagnostic approach including affective and non-affective psychoses subtypes to identify brain biomarker abnormalities which underlie specific psychosis subtypes; and, (3) perform brain-behavior correlations using the HCP Toolbox. The overarching goal of this proposal is to investigate the normal frontostriatal brain wiring pattern in HCs and in early psychosis. We will analyze WM connections, using tractography in novel ways to measure wiring patterns in frontostriatal connectivity. We propose 2 novel and complementary strategies to do this by studying 1) the geometric pattern of brain connections; and, 2) the overlap of projection zones of these connections. We have 3 aims. (1) to define the frontostriatal brain wiring pattern in HCs; (2) to define the frontostriatal brain wiring pattern in early psychosis; and (3) to investigate brain-behavior correlations. We hypothesize that (1) a. HCs will show a more integrative/convergent pattern of frontostriatal brain wiring than will early psychosis patients; b. affective psychosis subjects will show an intermediate degree of integrative pattern between non- affective psychosis subjects and HCs; and, (2) early psychosis patients and HCs will show frontostriatal dissociations in cognitive and affective function. Impaired cognitive control will be linked to a less integrative/convergent pattern of frontostriatal associative striatum circuitry and impaired reward processing will be linked to a less integrative pattern of frontostriatal limbic striatum circuitry. We will also explore sex as a biological variable as gender-specific brain development, thus brain wiring, may differ in early psychosis. We expect through this project to demonstrate the importance of frontostriatal connectivity in early psychosis, and the usefulness of our novel measures of miswiring as neuroimaging biomarkers in early psychosis.
Using diffusion magnetic resonance imaging tractography, we will investigate the pattern of structural connectivity (brain wiring) between the frontal cortex and striatum in early psychosis patients and matched healthy controls. Using such patients will allows us to: (1) mitigate the confounds of medication and chronicity; and, (2) use a transdiagnostic approach including affective and non-affective psychoses subtypes to cut across traditional diagnostic categories and to identify brain biomarker abnormalities which underlie all psychoses, as well as those of specific subtypes.
