思覺失調症的graph theory研究
基礎閱讀World J Psychiatr 2012 February 22; 2(1): 1-12 Graph-based network analysis in schizophrenia
Key words: Schizophrenia; Graph theory; Small world networks; Brain networks; Brain connectivity
陽明大學林慶波教授團隊2015 於PNAS所發表的Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia Chun-Yi Zac Lo, Tsung-Wei Su, Chu-Chung Huang, Chia-Chun Hung, Wei-Ling Chen, Tsuo-Hung Lan, Ching-Po Lin and Edward T. Bullmore
Abstract
Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients’ networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.
KEYWORDS:
brain network; dysconnectivity; graph theory; hubs; psychosis
論文第一作者羅畯義博士指出，近年來，由於MRI技術的蓬勃發展，使我們能藉由非侵入的方式偵測腦區之間的運作與連結關係；而當我們將大腦描繪成由點與線所構成的網路系統，並透過圖型理論分析，發現一般健康人的大腦處於最佳化網路的連結狀態，同時具有高度群聚性（連結關係緊密，表示各腦區分工完善）及高效率連結（傳遞訊息快）的特性；然而，思覺失調症患者的大腦神經網路，則趨向於連結較雜亂的架構，具有「較低的群聚性和過高的連結效率」特性，而由於有異常的神經連結，因此造成思考與感覺的混亂，而出現幻聽、幻覺及妄想等症狀。
羅畯義博士表示，他們的研究團隊運用靜息態功能性磁振影像，在台灣進行收案、取像與分析，發現黃種人思覺失調症患者的大腦網路同樣呈現較為隨機的架構，與過去以白種人為主體的研究結果相吻合，這說明「大腦網路隨機化」為跨人種在思覺失調症皆會出現的重要標記。
他們的研究進一步發現，思覺失調症患者的大腦網路，在主要神經網路節點受到攻擊時（如受其他疾病影響導致腦區無法運作），有較高的整體網路抵抗力；而且，在思覺失調症患者的一些健康近親（包括父母、子女或兄弟姊妹）的大腦網路中，也有相似的隨機化連結情形，也就是比一般健康受試者的神經網路雜亂；同時，患者近親的大腦網路架構受到攻擊時，亦有較高的抵抗性。羅畯義博士解釋說，在病人與健康近親身上都發現這些相同的特徵──大腦網路隨機化以及對於網路架構受攻擊的抵抗力較高，表示它們不是單單由疾病引發，而是由基因所調控，也就是呈現為一個『內在表現型』（即潛在特徵）或者遺傳風險標記。
