Elsevier

World Neurosurgery

Volume 128, August 2019, Pages e732-e743
World Neurosurgery

Original Article
Potential Intra- or Cross-Network Functional Reorganization of the Triple Unifying Networks in Patients with Frontal Glioma

https://doi.org/10.1016/j.wneu.2019.04.248Get rights and content

Background

Patients with frontal glioma might experience cognition alterations together with potential dysfunction of resting-state networks (RSNs). To understand the altered patterns of the intrinsic activity and underlying network interactions between the cognitive-related RSNs is of great importance.

Objective

This study aimed to investigate the characteristics of the altered RSNs, including default mode network, executive control network, and salience network and further elucidate the possible functional reorganization of RSNs in patients with frontal glioma.

Methods

Thirteen patients with frontal glioma and 10 healthy controls (HCs) were enrolled in this study. Independent component analysis was performed to identify the characteristics of the selected RSNs activity. Further, functional connectivity analysis was applied to investigate the relationship between the altered regions. Subsequently, partial correlation analysis was performed to examine associations between the neural activity of RSNs and neurocognitive characteristics.

Results

Compared with the HCs group, the patient group exhibited significant differences in functional connectivity among default mode network, executive control network, and salience network. In addition, the number of the significant functional connectivities between the paired seeds observed in the patients was greater than that in HCs and significantly increased functional connectivity was detected between left posterior cingulate cortex and right angular gyrus. Furthermore, altered neural activities in the RSNs of patients with frontal glioma were positively associated with certain aspects of cognitive function.

Conclusions

Our results suggested underlying network functional reorganization of the triple unifying RSNs in patients with frontal glioma, providing novel insights for improving understanding of brain function.

Introduction

Gliomas are the most frequent primary intracranial neoplasms, accounting for approximately 81% of malignant brain tumors.1 Besides the common clinical manifestations, including headache, nausea, epilepsy, and/or progressive neurologic deficits, tumors may elicit multiple cognitive deficits.2 Thus, improved understanding of the functional alterations in the brains of patients with glioma may provide novel insights into newer mechanisms that might help to explicate the development of brain diseases and to improve patients' quality of life.

Resting-state functional magnetic resonance imaging (rs-fMRI), by virtue of its noninvasiveness and widespread availability, has recently emerged as a prominent technique to assess the intrinsic activity of different brain regions.3, 4, 5 This method has been extensively applied to identify the complex brain functional networks and their disruptions occurring in the gliomas to decipher important resting state networks (RSNs).6, 7, 8 Notably, 3 major networks—the default mode network (DMN), the executive control network (ECN), and the salience network (SN)—have been proposed as the potential neural basis of consciousness by previous studies on the rs-fMRI.9, 10

Indeed, the DMN is one of the most studied brain networks, which comprises of a set of areas including bilateral, discrete, and symmetrical cortical areas, in the medial prefrontal, medial and lateral parietal, and medial and lateral temporal cortices.4, 9 DMN is intimately involved in the monitoring of internally generated processes, including autobiographical memory recollection, self-monitoring, and internal and external cognition.11 The ECN is a frontoparietal cognitive system that is engaged during cognitively demanding tasks and consists of the critical nodes including the dorsolateral prefrontal cortex and posterior parietal cortex. It appears to be a core hub for the control and management of executive functions, such as the manipulation of information in working memory, reasoning, planning, and problem-solving and decision-making in the context of goal-directed behavior.12, 13

The SN predominantly constitutes the anterior insula and the anterior cingulate cortex as integral nodes and is essential for integrating interoceptive, autonomic, and emotional information and play a role in switching the condition of activation and deactivation between the other 2 major networks.10, 14 In the network-based context, enriched understanding of the RSNs indicates that brain function, particularly advanced cognitive functions, may precisely be organized via between-network interactions among the distributed large-scale neural network.14, 15 Thus, a detailed investigation of brain tumor patients with clinical, cognitive symptoms may provide a new perspective on these three intrinsically connected networks.

Previous studies have demonstrated that patients with focal brain lesions due to stroke or tumor may undergo non-local effects of RSNs.16, 17, 18 An increasing number of studies have suggested that gliomas may cause a varying degree of alterations in endogenous functional connectivity (FC), including local and global level effects on the intra- and cross-hemisphere.17, 18, 19 However, network-based studies on patients with brain tumor remain scarce, and only a limited number of studies have included the 3 cognitive networks together. Chen et al.20 revealed that adult survivors of childhood brain tumors exhibited differences in the FC of the brain areas within the DMN, ECN, or the SN. Noticeably, the number of FCs detected in the survivors is greater than the controls. Consistent with this, Maesawa et al.18 also reported the alteration of neural activity in the 3 well-characterized RSNs. Furthermore, changes in connectivity also were associated with cognitive function and were observed not only on the ipsilateral side but also on the contralateral side. Moreover, through rs-fMRI analysis, cortical plasticity along with different types of connectivity reorganization, and function of complex brain networks could be perceived in patients with brain lesions.7, 8, 21, 22

In addition, Kinno et al.7 reported that left frontal glioma induces differential reorganization of 3 syntax-related networks. Motor network plasticity also has been reported in patients with slow-growing brain gliomas.21 Zhang et al.8 revealed a reorganization of cerebro-cerebellar circuit in patients with left hemispheric gliomas and provided evidence for the vital role of the cerebellum in neural plasticity following lesional damage involving the cerebral language network. However, whether patients with frontal glioma exhibit any specific altered patterns of the 3 RSNs remains unidentified. Thus, the potential functional reorganization or intrinsic interaction among the triple networks, and the association of the alternations of RSNs activity and neurocognition performances in patients with frontal glioma, remains to be elucidated. From a “connectomic” perspective, glioma should not be considered as a focal disease, and surgical neuro-oncology is a brain networks surgery.23 A better understanding of the alterations of FC in patients with frontal glioma might contribute to explicate the development of glioma, optimize the preoperative assessment and postoperative rehabilitation treatment, and further improve patients' quality of life.

Therefore, using independent component analysis (ICA), in the present study we attempt to identify the alteration in the unifying triple networks in patients with frontal gliomas compared with demographically matched controls. ICA is predominantly a data-driven method that has been implicated in revealing modulation in RSNs, including DMN, ECN, and SN.24, 25, 26 Furthermore, the FC analysis between the specific regions as defined by ICA, and the association among the altered regions from the viewpoint of functional network reorganization, also were evaluated. We hypothesized that the modulation induced by the frontal glioma was not confined to local brain regions or isolated network, which would correlate with, or reflect cognitive changes observed in patients with frontal gliomas. We further hypothesized that underlying functional reorganization might exist in the RSNs of patients, and there might be network interactions between the triple unifying networks proposed by Menon.14

Section snippets

Subjects

A total of 13 right-handed Han Chinese patients (mean age: 44.5 years old) were recruited from the Department of Neurosurgery, Nanjing Brain Hospital, Jiangsu province, China, and 10 demographically matched controls (mean age: 48.2 years old) were also included in this study. Demographics and clinical data of the patients are summarized in Supplementary Table 1. The inclusion criteria for the patients were as follows: 1) Tumors were histopathologically confirmed brain gliomas by final routine

Pathologic, Demographic, and Neurocognitive Characteristics

Postoperative histopathologic examination revealed that 5 patients had astrocytoma, 1 had glioblastoma, 4 had anaplastic astrocytoma, 2 had anaplastic oligodendroglioma, and 1 had anaplastic granular astrocytoma (Supplementary Table 1). No significant differences were found for age, sex, or education among the 2 groups. Concerning neurocognitive characteristics, the results revealed that patients with glioma exhibited inferior visual spatial, DSST, mapping, similarity, mathematics, and visual

Discussion and Conclusions

In the present study, we investigated 3 well-recognized RSNs—the DMN, ECN, and SN—in patients with frontal glioma. This study demonstrated that these effects were related not only to the local brain lesions but also involved a multiple network disruption. Also, altered RSN neural activity in patients was significantly correlated with their clinical neurocognitive functions. Moreover, the results of FC analysis suggested that increased, or at least a trend of increased intra- or cross-network

Acknowledgments

We express our gratitude to Zhou Chao for his assistance in editing and proofreading the manuscript.

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    Conflict of interest statement: This study was supported by a grant from the clinical medical scientific and technologic project of National Health and Family Planning Commission of the People's Republic of China (No.w201308), a grant from the project of Jiangsu Provincial Medical Youth Talent (No. QNRC2016047), the Nanjing Commission of Health and Family Planning (No. H201540), a grant from the medical scientific and technologic development project of Nanjing (No. YKK12137 and ZKX15035), and a grant from the project of Jiangsu Provincial Medical Innovation Team (No. CXTDA2017050).

    Dongming Liu and Xinhua Hu contributed equally to this work and are co−first authors.

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