Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Aalto, Finland.
Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, Neurology, University of Helsinki, Helsinki, Finland.
PLoS Comput Biol. 2023 Nov 9;19(11):e1011613. doi: 10.1371/journal.pcbi.1011613. eCollection 2023 Nov.
New biomarkers are urgently needed for many brain disorders; for example, the diagnosis of mild traumatic brain injury (mTBI) is challenging as the clinical symptoms are diverse and nonspecific. EEG and MEG studies have demonstrated several population-level indicators of mTBI that could serve as objective markers of brain injury. However, deriving clinically useful biomarkers for mTBI and other brain disorders from EEG/MEG signals is hampered by the large inter-individual variability even across healthy people. Here, we used a multivariate machine-learning approach to detect mTBI from resting-state MEG measurements. To address the heterogeneity of the condition, we employed a normative modeling approach and modeled MEG signal features of individual mTBI patients as deviations with respect to the normal variation. To this end, a normative dataset comprising 621 healthy participants was used to determine the variation in power spectra across the cortex. In addition, we constructed normative datasets based on age-matched subsets of the full normative data. To discriminate patients from healthy control subjects, we trained support-vector-machine classifiers on the quantitative deviation maps for 25 mTBI patients and 20 controls not included in the normative dataset. The best performing classifier made use of the full normative data across the entire age and frequency ranges. This classifier was able to distinguish patients from controls with an accuracy of 79%. Inspection of the trained model revealed that low-frequency activity in the theta frequency band (4-8 Hz) is a significant indicator of mTBI, consistent with earlier studies. The results demonstrate the feasibility of using normative modeling of MEG data combined with machine learning to advance diagnosis of mTBI and identify patients that would benefit from treatment and rehabilitation. The current approach could be applied to a wide range of brain disorders, thus providing a basis for deriving MEG/EEG-based biomarkers.
许多脑部疾病都迫切需要新的生物标志物;例如,轻度创伤性脑损伤 (mTBI) 的诊断具有挑战性,因为其临床症状多种多样且不具有特异性。EEG 和 MEG 研究已经证明了几种 mTBI 的人群水平指标,这些指标可以作为脑损伤的客观标志物。然而,即使在健康人群中,EEG/MEG 信号中的 mTBI 和其他脑部疾病的临床有用生物标志物的推导也受到个体间变异性大的阻碍。在这里,我们使用多元机器学习方法从静息状态 MEG 测量中检测 mTBI。为了解决该病症的异质性,我们采用了规范建模方法,将个体 mTBI 患者的 MEG 信号特征建模为相对于正常变化的偏差。为此,我们使用包含 621 名健康参与者的规范数据集来确定皮质功率谱的变化。此外,我们还基于完整规范数据的年龄匹配子集构建了规范数据集。为了将患者与健康对照者区分开来,我们在 25 名 mTBI 患者和 20 名未包含在规范数据集中的对照者的定量偏差图上训练支持向量机分类器。表现最佳的分类器使用了整个年龄和频率范围内的完整规范数据。该分类器能够以 79%的准确率将患者与对照者区分开来。对训练模型的检查表明,θ频带(4-8 Hz)的低频活动是 mTBI 的一个重要指标,这与早期研究一致。结果表明,使用 MEG 数据的规范建模结合机器学习来推进 mTBI 的诊断并识别需要治疗和康复的患者是可行的。当前的方法可以应用于广泛的脑部疾病,从而为基于 MEG/EEG 的生物标志物的推导提供基础。