Altered functional connectivity and hyperactivity of the caudal hippocampus in schizophrenia Compared with Bipolar Disorder：a resting state fMRI study

Schizophrenia patients frequently present with structural and functional abnormalities of the hippocampus (Hipp). Further, these abnormalities are often associated with specific symptom profiles. we examined basal activation state and functional connectivity (FC) in four subregions of the bilateral Hipp: left caudal (cHipp_L), right caudal (cHipp_R), left rostral (rHipp_L), and right rostral (rHipp_R). Resting-state functional magnetic resonance images were obtained from 62 schizophrenia patients, 57 bipolar disorder (BD) patients, and 45 healthy controls (HCs), and analyzed for fractional amplitude of low-frequency fluctuations (fALFF) as a measure of basal neural activity and for whole-brain FC with the aforementioned hippocampal subregions as seeds. The schizophrenia group exhibited greater fALFF in bilateral cHipp and rHipp subregions compared to BD and HC groups as well as greater FC between the bilateral cHipp and multiple brain regions, including the thalamus, putamen, middle frontal gyrus, parietal cortex, and precuneus. Moreover, fALFF values of the bilateral cHipp were positively correlated with the severity of clinical symptoms as measured by the Positive and Negative Syndrome Scale. These findings confirm a crucial contribution of hippocampal dysfunction, especially of the cHipp, in schizophrenia. Further, hyper-connectivity and hyperactivity of the cHipp could serve as a biomarker for therapeutic development.