Glioma, which is the most common primary malignant brain tumor in adults, can occur anywhere in the central nervous system (CNS), but mainly in the brain and glial tissue(Ostrom et al., 2014). With the progressive development of glioma in the brain, it often causes alterations in the cerebrum structure of patients, and even causes shifting of the midline in the cerebrum. In addition to the alterations of physiological structure, the infiltration of glioma often causes the alterations of brain function and the functional connectivity (FC) and has corresponding effects on cognitive function. These effects of glioma are not localized frequently and may cause alterations structurally and functionally in distant brain regions in patients with glioma. For instance, it has been found in some studies that patients with unilateral temporal glioma existed homotopic compensatory increase in gray matter (GM) volume and amplitude of low-frequency fluctuation (ALFF) in the contralateral temporal lobe(Hu et al., 2020; D. Liu et al., 2020). Almairac et al. also came to the similar foundings in their studies that there is not only an increase in contralateral GM volume but also an alteration in FC in patients with insular glioma(F. Almairac et al., 2021; Fabien Almairac, Duffau, & Herbet, 2018), which reminded us that the undamaged contralateral brain region played a crucial role in functional compensation in patients with glioma. It may help us better understand the potential compensatory patterns and protect cognitive function in patients with glioma by exploring homotopic alterations in brain.
Voxel-mirrored homotopic connectivity (VMHC) characterizes the internal functional structure of the brain by quantifying the FC between each voxel in one hemisphere and the mirror voxel in the opposite hemisphere(Zhang et al., 2017). Therefore, we could explore the FC between the voxels of the two brain hemispheres in patients with glioma by applying VMHC. VMHC is altered in many psychiatric and neurological disorders(Anderson et al., 2011; Hermesdorf et al., 2016; Kelly et al., 2011), such as the major depressive disorder, early-onset schizophrenia, amyotrophic lateral sclerosis, and stroke(J. Chen et al., 2021; W. Guo et al., 2013; H. J. Li, Xu, Zhang, Hoptman, & Zuo, 2015; Y. Wang et al., 2015; Zhang et al., 2017). These previous studies consistently suggested that the alterations of VMHC were strongly correlated with cognitive function, which suggested that VMHC could be well used to explore the alterations of homotopic function and its physiological significance in many brain diseases. From many previous studies, we are aware of that it clearly show homotopic functional and structural alterations in patients with glioma(F. Almairac et al., 2021; Fabien Almairac et al., 2018; Dongming Liu, 2019; Hu et al., 2020; Y. Liu et al., 2020), suggesting that the healthy contralateral brain regions play a crucial role in compensating for disease progression. Therefore, we can speculate that VMHC can be well used to explore the homotopic functional alterations in patients with glioma.
Functional magnetic resonance (fMRI) has been widely used in the prospective study of glioma and has made great contributions to the investigation of the potential mechanism of glioma. Some brain regions with certain correlation between FCs form some networks with specific functions, such as motor, language, visuo-spatial, and executive functions(Duffau, 2015; Park & Friston, 2013). As stated previously, the large number of data using fMRI to compare glioma patients with HCs indicated that tumor-induced brain FC alterations were not only localized, but also support the effect of tumors across a broad network(Duffau, 2020). For instance, Lang et al. showed that glioma patients have increased FC of the superior parietal cortex (SPC) within the tumor-affected hemisphere. However, some researchers found different alteration of FC in executive control network (ECN)(Y. Liu et al., 2020; Maesawa et al., 2015). Meanwhile, Liu et al. found there existed cross-network functional reorganization of the salience network (SN), default mode network (DMN), and ECN) in patients with frontal glioma. Although many studies have explored the changes of FC within specific, between networks or between distant brain regions, few studies have systematically studied the effect of VMHC in patients with glioma.
Both degree centrality (DC) and regional homogeneity (ReHo) represented the regional functional features within the brain based on voxels. DC represented the number of direct connections between certain given voxels(Di Martino et al., 2013; Zuo et al., 2012), while ReHo represented the consistency in regional spontaneous neural activity(Zang, Jiang, Lu, He, & Tian, 2004). There exists not only abnormal FC, but also abnormal alterations in regional functional parameter (ReHo and DC) in many diseases, such as the parkinson’s diseases, early psychosis, major depressive disorder, and migraineurs(X. Chen et al., 2019; M. Guo et al., 2020; Sun et al., 2018; Tang et al., 2019; Zhang et al., 2016). Actually, there are also regional functional alterations in patients with glioma(Agarwal, Sair, & Pillai, 2017; Y. Liu et al., 2020). However, the alterations of regional indicators in patients with frontal glioma and their clinical significance are still remaining unclear. Meanwhile, the regional functional basis of altered homotopic connectivity also remain unclear.
Therefore, in the present study, we aim to investigate the alterations of VMHC in patients with frontal glioma. Moreover, we attempt to invetigate not only the hemispheric variations of VMHC, but also the variations of regional function, such as DC and ReHo. In addition, we also explored the dynamic variability of VMHC, DC, and Reho to further measure the static and dynamic functional alterations in patients with frontal glioma. Finally, we attempt to explain the physiological significance of the changes in these indicators by analyzing the correlation between these indicators and scale scores. We hypothesized that alterations of static and dynamic VMHC, DC, and ReHo may be compensations of cognitive function in patients with frontal glioma.