Functional MRI in Schizophrenia

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Project Summary/Abstract The hippocampus (HPC) is one area of the brain that is broadly implicated in the pathophysiology of schizophrenia (SZ). Functional connectivity models of SZ suggest that disturbances also exist in the functional connections between the HPC and multiple other brain regions and networks. Aberrant HPC resting-state functional connectivity (rsFC) has been reported with multiple brain regions and networks, but has not yet been consistent across the literature. Such inconsistency is mainly caused by the inherent limitation of the BOLD- based rsFC techniques in large susceptibility regions like HPC. Due to this limitation, HPC (as well as other susceptible regions) is often essentially excluded from contributing to whole-brain rsFC analyses. The inconsistency of findings for abnormal HPC rsFC not only severely hampers our understanding of the role of HPC in SZ neuropathology, but also markedly constrains the generalization of findings from various preliminary studies with small sample sizes, and may ultimately stunt the validation of potential biomarkers for SZ diagnosis and treatment. In this proof-of-concept study, we propose a single-shot single-label background-suppressed dynamic arterial spin labeling (sbDASL) technique to study rsFC with the HPC, both for the importance of elucidating its role in the pathophysiology of SZ, but also because it provides an ideal case to validate this novel imaging technique more broadly to examine FC with other areas and for whole brain analyses. The proposed sbDASL technique overcomes several current limitations of existing techniques in the study of rsFC in SZ. Most importantly, sbDASL improves the spatial and temporal resolution of existing DASL-based approaches for robust assessment of HPC rsFC. In the proposal, we will seek to develop the sbDASL technique and demonstrate its superiority in detecting HPC rsFC anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) in healthy subjects, and its improved reproducibility at baseline and sensitivity to acute caffeine challenge, compared to the BOLD technique. We will compare the effect sizes of the HPC rsFC with ACC and PCC in antipsychotic-free patients with SZ, relative to matched healthy controls, using sbDASL and BOLD. We will further explore the capability of sbDASL, compared to BOLD, in differentiating between SZ patients and healthy controls using rsFC measures across multiple brain networks.