Objective:Transcutaneous vagus nerve stimulation (tVNS) is a promising potential intervention for Alzheimer's disease (AD) due to its influence on brain functions and mechanisms important in disease progression. Regions of interest include projection to the nucleus of the solitary tract, locus coeruleus, and hippocampus. Deterioration of the hippocampus is one of the most prominent early characteristics of AD, particularly during the mild cognitive impairment (MCI) stage. tVNS could modify function of the hippocampus. We examined resting state functional connectivity from the bilateral hippocampus in response to tVNS in patients with MCI.Participants and Methods:Fifty older adults (28 women, 60-89 years of age) diagnosed with MCI were assessed. MCI was confirmed via diagnostic consensus conference with a neurologist and neuropsychologist (sources of information: Montreal Cognitive Assessment Test [MoCA], Clinical Dementia Rating scale [CDR], Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised [HVLT-R] and medical record review). Resting state functional magnetic resonance imaging (fMRI) was collected on a 3T Siemens Prisma scanner while participants received either unilateral tVNS (left tragus, n = 25) or sham stimulation (left ear lobe, n = 25). fMRI data were processed using CONN toolbox v18b and hippocampal seed to voxel (whole brain) analyses were conducted with voxel and cluster level multiple comparison correction.Results:Contrasting tVNS and sham stimulation, whole-brain seed-to-voxel analysis demonstrated significant changes in connectivity from the left hippocampus to several cortical and subcortical regions bilaterally. Specifically, there was increased connectivity to prefrontal regions and cingulate gyri, and decreased connectivity to anterior and medial temporal lobes. A seed-to-voxel analysis from the right hippocampus indicated significant decrease in connectivity to a single cluster of regions in the left anterior temporal lobe in response to tVNS.Conclusions:In conclusion, tVNS modified connectivity from the hippocampus to multiple brain regions implicated in semantic and salience functions, in which disruption correlates with deterioration in AD. These findings indicate afferent target engagement of tVNS. Future work is needed to investigate the long-term effects of tVNS in patients with MCI and whether it could contribute to meaningful cognitive change and subsequent improvements in quality of life.

中文翻译：

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43 经皮迷走神经刺激对轻度认知障碍海马功能连接的影响

目的：经皮迷走神经刺激（tVNS）由于其对大脑功能和疾病进展中重要机制的影响而成为治疗阿尔茨海默病（AD）的一种有前途的潜在干预措施。感兴趣的区域包括孤束核、蓝斑和海马的投影。海马体退化是 AD 最突出的早期特征之一，特别是在轻度认知障碍 (MCI) 阶段。tVNS 可以改变海马体的功能。我们检查了 MCI 患者对 tVNS 反应时双侧海马的静息状态功能连接。 参与者和方法：对 50 名诊断为 MCI 的老年人（28 名女性，60-89 岁）进行了评估。MCI 通过神经科医生和神经心理学家的诊断共识会议得到确认（信息来源：蒙特利尔认知评估测试 [MoCA]、临床痴呆评定量表 [CDR]、功能活动问卷 (FAQ)、霍普金斯语言学习测试 - 修订版 [HVLT-R] ] 和病历审查）。在 3T 西门子 Prisma 扫描仪上收集静息态功能磁共振成像 (fMRI)，同时参与者接受单侧 tVNS（左耳屏，n = 25）或假刺激（左耳垂，n = 25）。使用 CONN 工具箱 v18b 处理 fMRI 数据，并通过体素和簇水平多重比较校正进行海马种子到体素（全脑）分析。结果：对比 tVNS 和假刺激，全脑种子到体素分析显示出显着变化从左侧海马体到双侧多个皮质和皮质下区域的连接。具体来说，与前额叶区域和扣带回的连接性增加，与前颞叶和内侧颞叶的连接性减少。右侧海马体的种子到体素分析表明，对 tVNS 的反应，与左前颞叶单个区域的连接性显着下降。结论：总而言之，tVNS 改变了从海马体到与 tVNS 相关的多个大脑区域的连接性。语义和显着性功能，其中破坏与 AD 恶化相关。这些发现表明 tVNS 的传入目标参与。未来的工作需要调查 tVNS 对 MCI 患者的长期影响，以及它是否有助于有意义的认知改变和随后生活质量的改善。