The Selective Impairment of Resting-State Functional Connectivity of the Lateral Subregion 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 controls. METHOD: One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis. 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. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions. CONCLUSION: These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia.