An Investigation of Large-Scale Brain Networks in Psychosis during the Manic and Depressive States of Bipolar Disorder

The proposed project aims to investigate and characterize the neural correlates of psychosis during the manic and depressive states of bipolar disorder (BD). We will employ a multimodal neuroimaging approach: analysis of functional magnetic resonance imaging metrics (by using both static and dynamic approaches) for characterizing the functional architecture of intrinsic brain activity at a network level; and analysis of diffusion magnetic resonance imaging metrics (by using the fixel-based analysis approach) for characterizing the white matter fiber-specific features and their relationship with the functional organization of brain activity. The present study, by employing such multiple units of advanced neuroimaging analyses, will be the very first to characterize the functional architecture of intrinsic brain activity and its large-scale network organization underlying psychosis during the manic and depressive states of BD, also exploring its relationship with brain’s structure. The results from this study may allow obtaining a better mechanistic understanding of the neurobiology of psychosis in general, as well as building a unified model of the pathophysiology of BD. Moreover, this could even provide further knowledge of the link between brain functioning and phenomenological experience at the physiological level. Our findings will be described in written papers and published in international journals of neuroscience and psychiatry, as well as disseminated at conferences. Finally, these scientific findings could provide us with rich information to serve as a basis to translate into diagnostic and therapeutic applications. Considering that the diagnosis of psychiatric disorders is still based on clinical evaluation and current treatments are relatively unspecific and inadequate, a better understanding of how changes in activity and balances of brain’s networks manifest in psychotic, manic, and depressive states represents a fundamental step to detect specific biomarkers at the individual level and, in turn, implement new and more effective therapies that have a neuroscientific basis, ultimately improving diagnosis and therapies of psychosis and BD.