Hippocampal-cortical structural connectivity disruptions in schizophrenia: An integrated perspective from hippocampal shape, cortical thickness, and integrity of white matter bundles

Disruptions in the hippocampal-cortical functional connectivities have been implicated in schizophrenia but less is known about their anatomical disconnectivities and association with clinical symptoms. We assessed the anatomical relationships between hippocampal shape, cortical thickness, and integrity of white matter bundles interconnecting them in this study. A brain mapping technique, large deformation diffeomorphic metric mapping, was used to analyze structural magnetic resonance imaging and diffusion tensor imaging scans of 126 schizophrenia patients and 77 matched healthy controls. We found that schizophrenia patients had surface inward-deformation in bilateral anterior hippocampi and cortical thinning in the regions of bilateral prefrontal, temporal, and occipital cortices compared with healthy controls. Anterior hippocampal shape deformity was associated with cortical thinning in the brain regions involved in visuo-spatial and verbal memory pathways. Canonical analysis revealed that greater disruptions in the hippocampal-cortical connectivity were associated with more severe negative symptoms in schizophrenia. Furthermore, fractional anisotropy in the fornix and cingulum bundles were reduced indicating abnormal integration of white matter between hippocampus and cortex in schizophrenia. Our findings suggested that aberrant structural hippocampal-cortical connectivities may serve as a marker of the illness and provide further structural evidence to support the notion of schizophrenia as a disorder of brain connectivity.