Altered Topological Properties of Static/Dynamic Functional Networks and Cognitive Function After Radiotherapy for Nasopharyngeal Carcinoma Using Resting-State fMRI.

Xi Leng,Donglin Wu,Fuhong Duan,Huan Lin,Kui Zhao,Shijun Qiu,Qihui Liu,Chunhong Qin,Mingrui Li,Jie An,Hongzhuo Wang

doi:10.3389/fnins.2021.690743

Abstract

ObjectivesThe purpose of this study was to (1) explore the changes in topological properties of static and dynamic brain functional networks after nasopharyngeal carcinoma (NPC) radiotherapy (RT) using rs-fMRI and graph theoretical analysis, (2) explore the correlation between cognitive function and changes in brain function, and (3) add to the understanding of the pathogenesis of radiation brain injury (RBI).MethodsFifty-four patients were divided into 3 groups according to time after RT: PT1 (0–6 months); PT2 (>6 to ≤12 months); and PT3 (>12 months). 29 normal controls (NCs) were included. The subjects’ topological properties were evaluated by graph-theoretic network analysis, the functional connectivity of static functional networks was calculated using network-based statistics, and the dynamic functional network matrix was subjected to cluster analysis. Finally, correlation analyses were conducted to explore the relationship between the altered network parameters and cognitive function.ResultsAssortativity, hierarchy, and network efficiency were significantly abnormal in the PT1 group compared with the NC or PT3 group. The small-world variance in the PT3 group was smaller than that in NCs. The Nodal ClustCoeff of Postcentral_R in the PT2 group was significantly smaller than that in PT3 and NC groups. Functional connectivities were significantly reduced in the patient groups. Most of the functional connectivities of the middle temporal gyrus (MTG) were shown to be significantly reduced in all three patient groups. Most of the functional connectivities of the insula showed significantly reduced in the PT1 and PT3 groups, and most of the functional connectivities in brain regions such as frontal and parietal lobes showed significantly reduced in the PT2 and PT3 groups. These abnormal functional connectivities were correlated with scores on multiple scales that primarily assessed memory, executive ability, and overall cognitive function. The frequency F of occurrence of various states in each subject differed significantly, and the interaction effect of group and state was significant.ConclusionThe disruption of static and dynamic functional network stability, reduced network efficiency and reduced functional connectivity may be potential biomarkers of RBI. Our findings may provide new insights into the pathogenesis of RBI from the perspective of functional networks.

Highlights

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck common in Asia, especially in southern China (Xia et al, 2017)
These abnormal functional connectivities were correlated with scores on multiple scales, such as the Montreal Cognitive Assessment-basic (MoCA-B), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), Digit Symbol Substitution Test (DSST), and DST which primarily assessed memory, executive ability, and overall cognitive function (Table 3)
We introduced the topological properties of dynamic functional networks into the study of radiation brain injury (RBI) for the first time, which could complement the topological properties of static functional suggested that changes in the overall parameters of static and networks, suggesting that small-world networks deserve close dynamic brain functional networks may be used as potential attention

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck common in Asia, especially in southern China (Xia et al, 2017). Radiotherapy (RT) is the treatment of choice for NPC (Li et al, 2018), but RT may lead to the development of serious complications in the central nervous system, namely, radiation brain injury (RBI), which can be temporary and reversible or progressive and irreversible, with clinical manifestations ranging from mild fatigue to neurocognitive dysfunction and even death (Stone and DeAngelis, 2016). It has been found that RBI begins in the early delayed period and can persist into the late delayed period; functional abnormalities in the early delayed period can develop into late irreversible structural brain changes that cause permanent cognitive impairment (Attia et al, 2014). There is an urgent need to detect early and potentially reversible brain functional impairment before severe irreversible structural damage and cognitive impairment occur in patients with NPC. Obtaining sensitive functional imaging markers of RBI helps to reveal the complex pathogenesis of RTinduced cognitive impairment but can facilitate the early identification of RBI or even reverse its course

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