The N400, a negative event-related potential (ERP) peaking approximately 400 ms after stimulus onset, is known to reflect the processing of semantic information. While scalp recordings have contributed to understanding the psychological processes underlying the N400, they have been limited in identifying its neural basis. However, recent intracranial ERP recordings and fMRI studies have shed light on the crucial role of the anterior medial temporal lobe (AMTL) in semantic information processing. These findings suggest that the N400 partially represents activity in the AMTL structures. To investigate the neural underpinnings of the N400 effect, we simultaneously recorded ERPs and event-related fMRI during a semantic priming paradigm in a sample of 12 young, healthy subjects. Additionally, we collected ERPs and structural brain data from older healthy adults and patients with amnestic mild cognitive impairment (aMCI), a population characterized by neurodegenerative changes in the AMTL. In our fMRI results, we identified bilateral loci in the AMTL as the global maxima. Employing an EEG-informed fMRI analysis, we explored trial-to-trial fluctuations in semantic processing by linking single-trial N400 amplitudes to the Blood Oxygen Level Dependent (BOLD) signal. This approach provided the first direct evidence linking the N400 recorded at the scalp level to the corresponding BOLD signal in the AMTL. Consistent with these findings, patients with aMCI exhibited a diminished N400 effect compared to healthy older adults. Furthermore, voxel-based morphometry analysis revealed a correlation between the magnitude of the N400 effect and the integrity of the AMTL. By integrating data from simultaneous EEG-fMRI, and patient studies, our research advances our understanding of the neural substrate of the N400 and highlights the critical involvement of the AMTL in semantic processing.

N400 是一种负事件相关电位 (ERP)，在刺激开始后约 400 毫秒达到峰值，已知可以反映语义信息的处理。虽然头皮录音有助于理解 N400 背后的心理过程，但它们在识别其神经基础方面受到限制。然而，最近的颅内 ERP 记录和功能磁共振成像研究揭示了前内侧颞叶 (AMTL) 在语义信息处理中的关键作用。这些发现表明 N400 部分代表 AMTL 结构中的活性。为了研究 N400 效应的神经基础，我们以 12 名年轻健康受试者为样本，在语义启动范式中同时记录了 ERP 和事件相关的 fMRI。此外，我们还收集了健康老年人和遗忘性轻度认知障碍 (aMCI) 患者的 ERP 和结构性大脑数据，该人群的特点是 AMTL 发生神经退行性变化。在我们的功能磁共振成像结果中，我们将 AMTL 中的双侧位点确定为全局最大值。采用脑电图信息的功能磁共振成像分析，我们通过将单次试验 N400 振幅与血氧水平相关 (BOLD) 信号联系起来，探索了语义处理中的试验间波动。这种方法提供了第一个直接证据，将头皮水平记录的 N400 与 AMTL 中相应的 BOLD 信号联系起来。与这些发现一致的是，与健康老年人相比，aMCI 患者的 N400 效应减弱。此外，基于体素的形态测量分析揭示了 N400 效应的大小与 AMTL 完整性之间的相关性。通过整合同步 EEG-fMRI 和患者研究的数据，我们的研究增进了我们对 N400 神经基质的理解，并强调了 AMTL 在语义处理中的关键参与。