Spontaneous Brain Activity Changes And Selective Functional Disconnection Of The Orbitofrontal Subregions In Schizophrenia

Part 1: Altered spontaneous brain activity in schizophrenia ObjectiveSchizophrenia is a devastating and disabling neuropsychiatric disorder. The previous studies of spontaneous brain activity in schizophrenia have yielded inconsistent results. We aimed to use a new functional imaging sequence to explore the spontaneous brain activity changes in depth in schizophrenia patients. Materials and MethodsA total of 89 right-handed schizophrenia patients and 89 sex-, age- and handedness-matched healthy controls were included in this study. Sagittal 3D T1-weighted images and sensitivity-encoded spiral imaging sequence were acquired using a 3.0 Tesla MR system. 1. The 3D T1-weighted images and the resting-state functional imaging data were preprocessed using the SPM8. 2. The ALFF/fALFF and ReHo were compared between the two groups. ResultsSchizophrenia patients showed decreased ALFF/fALFF and ReHo mainly in the bilateral occipital cortex,somatosensory cortex and posterior parietal cortex; however, schizophrenia patients showed increased ALFF/fALFF and ReHo were mainly in the bilateral striatum, medial temporal cortex, and medial prefrontal cortex. ConclusionsBased on an improved imaging technique and appropriate validation approaches, we found that schizophrenia patients showed significant changes in spontaneous brain activity. These findings may help us expound the pathophysiological hypothesis of schizophrenia patients.Part 2: Selective Functional Disconnection of the Orbitofrontal Subregions in Schizophrenia ObjectiveThe orbitofrontal cortex is implicated in multiple functions, as a disconnection syndrome, schizophrenia has shown impaired resting-state functional connectivity(rs FC) in the orbitofrontal cortex; however, the orbitofrontal cortex is a rather heterogeneous region and the rs FC changes in the orbitofrontal subregions remain unknown. We aimed to explore the rs FCs changes of each orbitofrontal subregion in schizophrenia patients. Materials and MethodsA total of 98 right-handed schizophrenia patients and 102 sex-, age- and handedness-matched healthy controls were recruited in this study. Sagittal 3DT1-weighted images, echo planar imaging sequence and sensitivity-encoded spiral imaging sequence were acquired using a 3.0 Tesla MR system.1. The relative signal intensity of each orbitofrontal subregion was calculated by dividing the mean signal intensity of the whole brain grey matter and was compared between the two functional imaging sequences to assess which image quality was better. 2. The 3D T1-weighted images and the two sets of resting-state functional imaging data were preprocessed using the SPM8. 3. Human OFC was parcellated into the anterior(OFCa), medial(OFCm), posterior(OFCp), intermediate(OFCi), and lateral(OFCl) subregions bilaterally. We conducted seed-based rs FC analyses using the above orbitofrontal subregions with and without global signal regression. Grey matter volume correction was used to exclude the effect of grey matter volume atrophy, and then we extracted the rs FCs and calculated Spearman’s correlation coefficients between these rs FCs and clinical parameters.Results1. As expected, the SENSE-SPIRAL sequence had a better image quality, and then the f MRI data extracted from this sequence were used for the rs FC analysis. 2. Both healthy controls and schizophrenia patients exhibited similar rs FC patterns for each orbitofrontal subregion, but the spatial extents of some subregions were slightly smaller in patients. 3. Compared with healthy controls, schizophrenia patients consistently showed reduced rs FC between the left OFCi and the left MTG, between the right OFCi and the right MFG, IFG and ITG, between the left OFCl and the left IFG, and between the bilateral OFCm and the right ACC. 4. Compared with the results without GMV correction, all brain regions showing rs FC reduction also remained statistically significant after GMV correction.Conclusions Based on an improved imaging technique, a recently identified subregion model of the OFC and appropriate validation approaches, schizophrenia patients consistently and reliably showed functional disconnection in the left OFCl and the bilateral OFCi and the OFCm, which included the fronto-temporal disconnection and disconnections within the frontal-parietal network, salience network, and right ACC. These findings may expound the pathophysiological hypothesis and guide future researches.