The Resting-state Functional Connectivity Of The Subregions Of The Frontal Pole In Schizophrenia

Objective:Although extensive resting-state functional connectivity(rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal pole(FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controlsSubjects and Methods:A total of 98 patients with schizophrenia and 102 healthy controls were recruited for this study. Nine subjects were excluded because of large head motion or poor image quality. Finally, 91 schizophrenia patients and 100 healthy controls were included in the further analyses. Resting-state fMRI and high-resolution structural imaging were performed using a 3.0-Tesla MR system(Discovery MR750, General Electric, Milwaukee, WI, USA). Two sets of resting-state fMRI data were acquired, which are the EPI sequence and the SENSE-SPIRAL sequence. The preprocessing of resting-state fMRI data of the two sets were with the same procedures using the SPM8. The high-resolution structural imaging were preprocessed using the SPM8. Then, mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis. To exclude the effect of GMV on rsFC changes, we extracted the GMV of the FP subregions and re-evaluated the rsFC changes of each FP subregion after further controlling for the GMV of the FP subregion. Considering that ROIs extracted from the maximal probability maps may result in information overlap across ROIs due to the preprocessing steps of normalization and smoothing, we also defined these ROIs using an alternative method(spheres with a radius of 6 mm centered at the gravity of each FP subregion) to exclude the effect. We repeated our rsFC analyses to test whether different methods for ROI definition influence our results. Finally, we used the pearson correlation analysis to further test whether the rsFCs of the FP subregions with significant group differences were correlated with the clinical variables(i.e., PANSS, duration of the illness, and antipsychotic dosage).Results:The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients.Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia.The schizophrenia patients showed significant decreased GMV in each of the subregions of the FP bilaterally.To investigate whether the rsFC changes are associated with the underlying structural alterations, the rsFC analysis was repeated when the mean normalized GMV of each FPl of each subject was added as a covariate of no interest. All the clusters derived from rsFC analysis without GMV correction remained significant after GMV correction. These findings suggest that rsFC alterations of the FP subregions are relative independent characteristics in schizophrenia but not a result of volumetric atrophy.In patients with schizophrenia, we did not find any significant correlations(p<0.05) between rsFCs of the FPl with significant group differences and any of the clinical parameters, including the PANSS positive scores, PANSS negative scores, duration of illness, and current antipsychotic dosage in chlorpromazine equivalents.Conclusions: 1. These findings suggest a selective(the lateral subregion) functional disconnectionof the FP subregions in schizophrenia. 2. The schizophrenia patients showed significant decreased GMV in each of thesubregios of the FP bilaterally. 3. These findings suggest that rsFC alterations of the FP subregions are relativeindependent characteristics in schizophrenia but not a result of volumetricatrophy.