Academic Unit of Neurology, Trinity College Dublin, The University of Dublin, Ireland.
Academic Unit of Neurology, Trinity College Dublin, The University of Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, The University of Dublin, Ireland.
Neuroimage Clin. 2019;22:101707. doi: 10.1016/j.nicl.2019.101707. Epub 2019 Feb 2.
To localise and characterise changes in cognitive networks in Amyotrophic Lateral Sclerosis (ALS) using source analysis of mismatch negativity (MMN) waveforms.
The MMN waveform has an increased average delay in ALS. MMN has been attributed to change detection and involuntary attention switching. This therefore indicates pathological impairment of the neural network components which generate these functions. Source localisation can mitigate the poor spatial resolution of sensor-level EEG analysis by associating the sensor-level signals to the contributing brain sources. The functional activity in each generating source can therefore be individually measured and investigated as a quantitative biomarker of impairment in ALS or its sub-phenotypes.
MMN responses from 128-channel electroencephalography (EEG) recordings in 58 ALS patients and 39 healthy controls were localised to source by three separate localisation methods, including beamforming, dipole fitting and exact low resolution brain electromagnetic tomography.
Compared with controls, ALS patients showed significant increase in power of the left posterior parietal, central and dorsolateral prefrontal cortices (false discovery rate = 0.1). This change correlated with impaired cognitive flexibility (rho = 0.45, 0.45, 0.47, p = .042, .055, .031 respectively). ALS patients also exhibited a decrease in the power of dipoles representing activity in the inferior frontal (left: p = 5.16 × 10, right: p = 1.07 × 10) and left superior temporal gyri (p = 9.30 × 10). These patterns were detected across three source localisation methods. Decrease in right inferior frontal gyrus activity was a good discriminator of ALS patients from controls (AUROC = 0.77) and an excellent discriminator of C9ORF72 expansion-positive patients from controls (AUROC = 0.95).
Source localization of evoked potentials can reliably discriminate patterns of functional network impairment in ALS and ALS subgroups during involuntary attention switching. The discriminative ability of the detected cognitive changes in specific brain regions are comparable to those of functional magnetic resonance imaging (fMRI). Source analysis of high-density EEG patterns has excellent potential to provide non-invasive, data-driven quantitative biomarkers of network disruption that could be harnessed as novel neurophysiology-based outcome measures in clinical trials.
利用失匹配负波（MMN）波形的源分析，定位并描述肌萎缩侧索硬化症（ALS）患者认知网络的变化。
ALS 患者的 MMN 波形平均延迟增加。MMN 归因于变化检测和无意识注意转换。因此，这表明生成这些功能的神经网络组件发生了病理性损伤。源定位可以通过将传感器水平的信号与产生这些功能的大脑源相关联，减轻脑电图（EEG）传感器水平分析的空间分辨率较差的问题。因此，可以单独测量和研究每个产生源的功能活动，作为 ALS 或其亚表型的损伤的定量生物标志物。
对 58 例 ALS 患者和 39 名健康对照者的 128 通道脑电图（EEG）记录进行 MMN 反应源定位，采用三种独立的源定位方法，包括束形成、偶极拟合和精确低分辨率脑电磁层析成像。
与对照组相比，ALS 患者左侧顶后、中央和背外侧前额叶皮质的功率显著增加（错误发现率=0.1）。这种变化与认知灵活性受损相关（rho=0.45，0.45，0.47，p=0.042，0.055，0.031）。ALS 患者还表现出代表额下回（左侧：p=5.16×10，右侧：p=1.07×10）和左颞上回活动的偶极子功率降低（p=9.30×10）。这些模式在三种源定位方法中都被检测到。右侧额下回活动的降低是 ALS 患者与对照组之间的良好鉴别指标（AUROC=0.77），也是 C9ORF72 扩张阳性患者与对照组之间的极好鉴别指标（AUROC=0.95）。
诱发电位的源定位可以可靠地区分 ALS 患者和 ALS 亚组在无意识注意转换过程中功能网络损伤的模式。在特定脑区检测到的认知变化的鉴别能力与功能磁共振成像（fMRI）相当。高密度 EEG 模式的源分析具有提供非侵入性、数据驱动的网络破坏定量生物标志物的巨大潜力，可作为临床试验中基于神经生理学的新型结果测量手段。
