Ferreri Florinda, Guerra Andrea, Vollero Luca, Ponzo David, Määtta Sara, Könönen Mervi, Vecchio Fabrizio, Pasqualetti Patrizio, Miraglia Francesca, Simonelli Ilaria, Corbetta Maurizio, Rossini Paolo Maria
Unit of Neurology, Unit of Clinical Neurophysiology and Study Center of Neurodegeneration (CESNE), Department of Neuroscience, University of Padua, Padua, Italy.
Department of Clinical Neurophysiology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
Front Aging Neurosci. 2021 Nov 22;13:737281. doi: 10.3389/fnagi.2021.737281. eCollection 2021.
Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer's disease (AD) is a major scientific challenge. To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.
早期且经济可行地识别出将转化为阿尔茨海默病（AD）的遗忘型轻度认知障碍（aMCI）患者是一项重大科学挑战。为了在某些特征可能代表神经退行性变引起的可塑性重排、从而作为未来转化为AD的预测指标这一假设下，研究aMCI中感觉运动皮层功能的神经生理学特征。我们试图确定：（1）感觉运动网络在aMCI患者中是否表现出特殊改变；（2）感觉运动网络改变在个体水平上是否能预测疾病的长期进展。我们研究了一组aMCI患者感觉运动皮层的多个经颅磁刺激（TMS）-脑电图（EEG）参数，并对他们进行了6年的随访。然后我们确定了临床上转化为AD的aMCI患者[AD前驱期-MCI（pAD-MCI）]和认知保持稳定的患者[非AD前驱期-MCI（npAD-MCI）]。与对照组相比，aMCI患者的运动皮层（M1）兴奋性降低，且在α、β和γ频段的EEG同步性受到破坏[试验间相干性（ITC）降低]。pAD-MCI和npAD-MCI之间M1兴奋性和α-ITC的改变程度相当。重要的是，pAD-MCI中受刺激M1的β和γ-ITC损伤比npAD-MCI更严重。此外，一个与头皮信号波形形状相关的额外参数，反映了TMS诱导的整体活动的时间特异性改变[偶极活动稳定性（sDA）]，能够区分npAD-MCI和将转化为AD的MCI。上述特定的皮层变化反映了aMCI中皮质-基底神经节-丘脑-皮质环路内同步性的缺陷，可能反映了AD的病理过程。这些变化可以在更大的队列中作为AD的神经生理学生物标志物进行测试。
