Hamed Azami, Yuri Antonacci, Daniel M Blumberger, Heather Brooks, Luca Faes, Corinne E Fischer, Alastair Flint, Nathan Herrmann, Sanjeev Kumar, Damien Gallagher, Linda Mah, Benoit H Mulsant, Nicole Schoer, Bruce G Pollock, Tarek K Rajji
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引用次数: 0
Abstract
Background: Alpha-band default mode network (DMN) connectivity declines with aging and Alzheimer's disease (AD), yet most electroencephalography (EEG) connectivity studies used pairwise (two-order) measures, such as mutual information rate (MIR). We leveraged O-information rate (OIR) to quantify three-order interactions and to separate redundant from synergistic information processing across frontal, temporal, and parietal DMN regions. We hypothesized that, extending established findings of reduced pairwise connectivity, (i) OIR (and its components) would be reduced in older versus younger adults and in AD versus healthy controls (HC); (ii) combining MIR with OIR would improve classification compared with MIR alone; and (iii) OIR measures would correlate positively with global cognition (as assessed by the Montreal Cognitive Assessment (MoCA)).
Methods: Resting-state EEG from two samples-healthy adult lifespan aging (95 younger; 93 older) and AD spectrum (44 HC; 84 amnestic mild cognitive impairment [aMCI]; 41 AD)-was source-localized using eLORETA to DMN regions. Alpha band (8-13 Hz) MIR and OIR were computed through multivariate spectral analysis. Group differences were tested using t-tests or analysis of covariance (ANCOVA) with multiple comparison correction. Classification (OIR, MIR, demographic, and combined feature sets) used cross-validated logistic-regression, linear-SVM, and random-forest models, with bootstrap 95% confidence intervals and DeLong tests for AUC comparisons.
Results: OIR and its redundancy component were significantly reduced in older versus younger adults and in AD versus HC/aMCI, with no HC-aMCI differences. The synergy component showed no group differences. MIR decreased broadly with aging and fronto-parietally in AD. Regarding classification (AD spectrum dataset, cross-validated AUC), OIR-based metrics outperformed MIR (AD vs. HC: 0.93 vs. 0.73; AD vs. aMCI: 0.93 vs. 0.71; aMCI vs. HC: 0.48 vs. 0.46). Combining demographics with all information-theoretic features improved AD vs. HC (0.98; DeLong p = 0.023) but not AD vs. aMCI (0.93), where OIR alone was already at ceiling; no feature set exceeded chance for aMCI vs. HC. After correction, OIR and its redundancy component correlated positively with MoCA scores; MIR and the synergy component did not.
Conclusions: Alpha-band three-order DMN interactions-particularly redundant information processing-decline with aging and AD and provide additional information beyond two-order connectivity for diagnostic classification. OIR offers complementary measures to traditional metrics, and future studies should examine its value when combined with more established AD biomarkers.
背景：α波段默认模式网络（DMN）连通性随着年龄和阿尔茨海默病（AD）而下降，但大多数脑电图（EEG）连通性研究使用成对（二阶）测量，如互信息率（MIR）。我们利用o -信息率（OIR）来量化三阶相互作用，并在额叶、颞叶和顶叶DMN区域分离冗余和协同信息处理。我们假设，扩展已建立的两两连通性降低的发现，(i) OIR（及其组成部分）在老年人与年轻人、AD与健康对照（HC）中会降低；（ii）与单独MIR相比，MIR与OIR结合将改善分类；（iii） OIR测量将与全球认知呈正相关（由蒙特利尔认知评估（MoCA）评估）。方法：使用eLORETA对两个样本的静息状态脑电图进行源定位，分别是健康成人寿命老化（年轻95例，老年93例）和AD谱（HC 44例，aMCI 84例，AD 41例）。通过多变量光谱分析计算α波段（8-13 Hz） MIR和OIR。采用多重比较校正的t检验或协方差分析（ANCOVA）检验组间差异。分类（OIR、MIR、人口统计学和组合特征集）使用交叉验证的逻辑回归、线性支持向量机和随机森林模型，采用自举95%置信区间和DeLong检验进行AUC比较。结果：OIR及其冗余成分在老年人与年轻人、AD与HC/aMCI中显著降低，HC-aMCI无差异。协同成分无组间差异。AD患者MIR随着年龄和额顶叶的增长而明显下降。在分类方面（AD频谱数据集，交叉验证的AUC），基于oir的指标优于MIR （AD vs. HC: 0.93 vs. 0.73; AD vs. aMCI: 0.93 vs. 0.71; aMCI vs. HC: 0.48 vs. 0.46）。将人口统计学与所有信息理论特征相结合，可以改善AD与HC的对比（0.98;DeLong p = 0.023），但不能改善AD与aMCI的对比（0.93），其中单独的OIR已经达到上限；aMCI和HC的特性集没有超出机会。修正后，OIR及其冗余分量与MoCA得分呈正相关；MIR和协同成分则没有。结论：α波段三阶DMN相互作用-特别是冗余信息处理-随年龄和AD而下降，并为诊断分类提供了超越两阶连接的额外信息。OIR为传统指标提供了补充措施，未来的研究应检查其与更成熟的AD生物标志物结合时的价值。
期刊介绍：
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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