Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
Clin Neurophysiol. 2024 Nov;167:177-188. doi: 10.1016/j.clinph.2024.09.007. Epub 2024 Sep 17.
The neural activity of the Default Mode Network (DMN) is disrupted in patients with In Alzheimer's disease (AD).
We used a novel multimodal approach to track neural signal propagation within the DMN in AD patients.
Twenty mild to moderate AD patients were recruited. We used transcranial magnetic stimulation (TMS) pulses to probe with a millisecond time resolution the propagation of evoked electroencephalography (EEG) signal following the neural activation of the Precuneus (PC), which is a key hub area of the DMN. Moreover, functional and structural magnetic resonance imaging (MRI) data were collected to reconstruct individual features of the DMN.
In AD patients a probe TMS pulse applied over the PC evokes an increased local activity unmasking underlying hyperexcitability. In contrast, the EEG evoked neural signal did not propagate efficiently within the DMN showing a remarkable breakdown of signal propagation. fMRI and structural tractography showed that impaired signal propagation was related to the same connectivity matrices derived from DMN BOLD signal and transferred by specific white matter bundles forming the cingulum. These features were not detectable stimulating other areas (left dorsolateral prefrontal cortex) or for different networks (fronto-parietal network). Finally, connectivity breakdown was associated with cognitive impairment, as measured with the Clinical Dementia Rating Scale sum of boxes (CDR-SB).
TMS-EEG in AD shows both local hyperexcitability and a lack of signal propagation within the DMN. These neurophysiological features also correlate with structural and cognitive attributes of the patients.
Neuronavigated TMS-EEG may be used as a novel neurophysiological biomarker of DMN connectivity in AD patients.
阿尔茨海默病（AD）患者的默认模式网络（DMN）的神经活动被打乱。
我们使用一种新的多模态方法来跟踪 AD 患者 DMN 中的神经信号传播。
招募了 20 名轻度至中度 AD 患者。我们使用经颅磁刺激（TMS）脉冲以毫秒级的时间分辨率探测在楔前叶（PC）的神经激活后诱发电位脑电图（EEG）信号的传播，PC 是 DMN 的关键枢纽区域。此外，收集功能和结构磁共振成像（MRI）数据以重建 DMN 的个体特征。
在 AD 患者中，施加于 PC 的探针 TMS 脉冲会引发局部活动增加，从而揭示出潜在的过度兴奋性。相比之下，EEG 诱发的神经信号在 DMN 内不能有效地传播，表现出明显的信号传播中断。fMRI 和结构束示踪显示，受损的信号传播与从 DMN BOLD 信号导出并通过形成扣带的特定白质束传递的相同连接矩阵有关。这些特征在刺激其他区域（左侧背外侧前额叶皮质）或不同网络（额顶网络）时无法检测到。最后，连接中断与认知障碍有关，用临床痴呆评定量表总和评分（CDR-SB）测量。
AD 中的 TMS-EEG 显示出局部过度兴奋性和 DMN 内信号传播的缺乏。这些神经生理学特征还与患者的结构和认知属性相关。
神经导航 TMS-EEG 可作为 AD 患者 DMN 连接的新型神经生理学生物标志物。
