Taboada-Crispi Alberto, Bringas-Vega Maria L, Bosch-Bayard Jorge, Galán-García Lidice, Bryce Cyralene, Rabinowitz Arielle G, Prichep Leslie S, Isenhart Robert, Calzada-Reyes Ana, VIrues-Alba Trinidad, Guo Yanbo, Galler Janina R, Valdés-Sosa Pedro A
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.
Informatics Research Center, Universidad Central Marta Abreu de las Villas, Santa Clara, Cuba.
Front Neurosci. 2018 Aug 28;12:595. doi: 10.3389/fnins.2018.00595. eCollection 2018.
The goal of this study is to identify the quantitative electroencephalographic (qEEG) signature of early childhood malnutrition [protein-energy malnutrition (PEM)]. To this end, archival digital EEG recordings of 108 participants in the Barbados Nutrition Study (BNS) were recovered and cleaned of artifacts (46 children who suffered an episode of PEM limited to the first year of life) and 62 healthy controls). The participants of the still ongoing BNS were initially enrolled in 1973, and EEGs for both groups were recorded in 1977-1978 (at 5-11 years). Scalp and source EEG Z-spectra (to correct for age effects) were obtained by comparison with the normative Cuban Human Brain Mapping database. Differences between both groups in the z spectra (for all electrode locations and frequency bins) were assessed by -tests with thresholds corrected for multiple comparisons by permutation tests. Four clusters of differences were found: (a) increased theta activity (3.91-5.86 Hz) in electrodes T4, O2, Pz and in the sources of the supplementary motor area (SMA); b) decreased alpha1 (8.59-8.98 Hz) in Fronto-central electrodes and sources of widespread bilateral prefrontal are; (c) increased alpha2 (11.33-12.50 Hz) in Temporo-parietal electrodes as well as in sources in Central-parietal areas of the right hemisphere; and (d) increased beta (13.67-18.36 Hz), in T4, T5 and P4 electrodes and decreased in the sources of bilateral occipital-temporal areas. Multivariate Item Response Theory of EEGs scored visually by experts revealed a neurophysiological latent variable which indicated excessive paroxysmal and focal abnormality activity in the PEM group. A robust biomarker construction procedure based on elastic-net regressions and 1000-cross-validations was used to: (i) select stable variables and (ii) calculate the area under ROC curves (AUC). Thus, qEEG differentiate between the two nutrition groups (PEM vs Control) performing as well as visual inspection of the EEG scored by experts (AUC = 0.83). Since PEM is a global public health problem with lifelong neurodevelopmental consequences, our finding of consistent differences between PEM and controls, both in qualitative and quantitative EEG analysis, suggest that this technology may be a source of scalable and affordable biomarkers for assessing the long-term brain impact of early PEM.
本研究的目的是确定幼儿营养不良[蛋白质能量营养不良(PEM)]的定量脑电图(qEEG)特征。为此,我们找回了巴巴多斯营养研究(BNS)中108名参与者的存档数字脑电图记录,并去除了伪迹(46名在生命第一年经历过PEM发作的儿童)和62名健康对照者的记录。仍在进行的BNS的参与者最初于1973年入组,两组的脑电图均于1977 - 1978年(5 - 11岁时)记录。通过与古巴人脑图谱标准数据库进行比较,获得头皮和源脑电图Z谱(以校正年龄效应)。通过t检验评估两组在z谱(所有电极位置和频率区间)上的差异,并通过排列检验对多重比较的阈值进行校正。发现了四组差异:(a)电极T4、O2、Pz以及辅助运动区(SMA)源区的θ活动增加(3.91 - 5.86 Hz);(b)额中央电极和广泛双侧前额叶区域源区的α1(8.59 - 8.98 Hz)降低;(c)颞顶电极以及右半球中央顶叶区域源区的α2(11.33 - 12.50 Hz)增加;(d)T4、T5和P4电极的β(13.67 - 18.36 Hz)增加,双侧枕颞区域源区的β降低。由专家进行视觉评分的脑电图多变量项目反应理论揭示了一个神经生理潜在变量,表明PEM组存在过度的阵发性和局灶性异常活动。基于弹性网络回归和1000次交叉验证的稳健生物标志物构建程序用于:(i)选择稳定变量,(ii)计算ROC曲线下面积(AUC)。因此,qEEG能够区分两个营养组(PEM组与对照组),其表现与专家对脑电图的视觉检查相当(AUC = 0.83)。由于PEM是一个具有终身神经发育后果的全球公共卫生问题,我们在定性和定量脑电图分析中发现PEM组与对照组之间存在一致差异,这表明该技术可能是评估早期PEM对大脑长期影响的可扩展且经济实惠的生物标志物来源。