Increased Homotopic Connectivity in the Prefrontal Cortex Modulated by Olanzapine Predicts Therapeutic Efficacy in Patients with Schizophrenia

Abstract

Background. Previous studies have revealed the abnormalities in homotopic connectivity in schizophrenia. However, the relationship of these deficits to antipsychotic treatment in schizophrenia remains unclear. This study explored the effects of antipsychotic therapy on brain homotopic connectivity and whether the homotopic connectivity of these regions might predict individual treatment response in schizophrenic patients. Methods. A total of 21 schizophrenic patients and 20 healthy controls were scanned by the resting-state functional magnetic resonance imaging. The patients received olanzapine treatment and were scanned at two time points. Voxel-mirrored homotopic connectivity (VMHC) and pattern classification techniques were applied to analyze the imaging data. Results. Schizophrenic patients presented significantly decreased VMHC in the temporal and inferior frontal gyri, medial prefrontal cortex (MPFC), and motor and low-level sensory processing regions (including the fusiform gyrus and cerebellum lobule VI) relative to healthy controls. The VMHC in the superior/middle MPFC was significantly increased in the patients after eight weeks of treatment. Support vector regression (SVR) analyses revealed that VMHC in the superior/middle MPFC at baseline can predict the symptomatic improvement of the positive and negative syndrome scale after eight weeks of treatment. Conclusions. This study demonstrated that olanzapine treatment may normalize decreased homotopic connectivity in the superior/middle MPFC in schizophrenic patients. The VMHC in the superior/middle MPFC may predict individual response for antipsychotic therapy. The findings of this study conduce to the comprehension of the therapy effects of antipsychotic medications on homotopic connectivity in schizophrenia.

Neuroimaging biomarkers for detecting schizophrenia: A resting-state functional MRI-based radiomics analysis

“…Therefore, DC and VMHC may be more appropriate than conventional FC in studying neuropsychiatric disorders whose pathological mechanisms were unclear ( Jiang et al., 2019 ). We found that DC and VMHC are physiologically meaningful and beneficial in understanding the underlying mechanism of SZ, DC- and VMHC-based features can distinguish SZ patients from HCs, in agreement with other studies ( de Filippis et al., 2019 ; Liu et al., 2018 ; Shan et al., 2021 ; Shi et al., 2021a ; Tang et al., 2019 ; Zang et al., 2021 ).…”

“…DC, a data-derived measurement method, measures the FC strengths across the entire brain at a voxel level and may proxy the global brain activity synchronizations or FC density ( Buckner et al., 2009 ; Li et al., 2019b ). VMHC reflects the homotopic FC between the two hemispheres by determining the correlation coefficient between voxel and the contralateral hemisphere's mirror voxel ( Lu et al., 2021 ; Shan et al., 2021 ). The two measures do not rely on prior information about the target brain regions.…”

“…In this study, many brain regions showing abnormalities in VMHC belong to the default mode network (DMN), such as MTG and MFG. Recently, a growing body of literature has assessed the crucial roles of disrupted DMN connectivity and abnormal brain activity in the neural mechanisms underlying SZ and DMN disturbances are closely associated with SZ psychopathology and cognitive impairment ( Gong et al., 2020 ; Hu et al., 2017 ; Mingoia et al., 2012 ; Schneider et al., 2011 ; Shan et al., 2021 ; Wen et al., 2021 ; Yan et al., 2020 ; Zhao et al., 2018b , 2019 ). The amygdala, hippocampus, FuG, and PhG are important parts of the limbic system, which regulates instinctive, cognitive, and emotional behavior.…”

“…First, although there is a larger sample size than other studies evaluating SZ using machine learning ( de Filippis et al., 2019 ; Shan et al., 2021 ; Wang et al., 2020a ), the sample size is still small and increasing the sample and centers will make the findings more generalizable. Second, prior studies have identified the presence of abnormal cerebellum activation in SZ patients ( de Filippis et al., 2019 ; Shan et al., 2021 ; Xie et al., 2021 ). Thus, cerebellar DC and VMHC abnormalities may be potential biomarkers of SZ.…”

“…Degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) are new rs-fMRI indicators used to evaluate FCs across the whole brain at a voxel level ( Jiang et al., 2019 ; Li et al., 2019b ; Zhang et al., 2019 ). More work is needed in order to determine the utility of DC and VMHC for SZ ( de Filippis et al., 2019 ; Shan et al., 2021 ; Shi et al., 2021a ).…”