Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Logan University, Chesterfield, MO, USA.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; School of Medicine, Universidad de Santander (UDES), Bucaramanga, Colombia.
Brain Stimul. 2020 Jul-Aug;13(4):970-978. doi: 10.1016/j.brs.2020.03.011. Epub 2020 Mar 27.
BACKGROUND: The therapeutic potential of transcutaneous auricular VNS (taVNS) is currently being explored for numerous clinical applications. However, optimized response for different clinical indications may depend on specific neuromodulation parameters, and systematic assessments of their influence are still needed to optimize this promising approach. HYPOTHESIS: We proposed that stimulation frequency would have a significant effect on nucleus tractus solitarii (NTS) functional MRI (fMRI) response to respiratory-gated taVNS (RAVANS). METHODS: Brainstem fMRI response to auricular RAVANS (cymba conchae) was assessed for four different stimulation frequencies (2, 10, 25, 100 Hz). Sham (no current) stimulation was used to control for respiration effects on fMRI signal. RESULTS: Our findings demonstrated that RAVANS delivered at 100 Hz evoked the strongest brainstem response, localized to a cluster in the left (ipsilateral) medulla and consistent with purported NTS. A co-localized, although weaker, response was found for 2 Hz RAVANS. Furthermore, RAVANS delivered at 100 Hz also evoked stronger fMRI responses for important monoamine neurotransmitter source nuclei (LC, noradrenergic; MR, DR, serotonergic) and pain/homeostatic regulation nuclei (i.e. PAG). CONCLUSION: Our fMRI results support previous localization of taVNS afference to pontomedullary aspect of NTS in the human brainstem, and demonstrate the significant influence of the stimulation frequency on brainstem fMRI response.
背景：经皮耳迷走神经刺激（taVNS）的治疗潜力目前正在探索应用于多种临床应用。然而，不同临床适应证的最佳反应可能取决于特定的神经调节参数，需要系统评估它们的影响，以优化这种很有前途的方法。
假设：我们提出刺激频率将对呼吸门控 taVNS（RAVANS）的孤束核功能磁共振成像（fMRI）反应有显著影响。
方法：评估了四个不同刺激频率（2、10、25、100 Hz）对耳 RAVANS（耳甲腔）的脑干 fMRI 反应。假刺激（无电流）用于控制呼吸对 fMRI 信号的影响。
结果：我们的发现表明，100 Hz 的 RAVANS 诱发了最强的脑干反应，定位于左侧（同侧）延髓的一个簇中，与推测的孤束核一致。对于 2 Hz 的 RAVANS，也发现了一个局部但较弱的反应。此外，100 Hz 的 RAVANS 还诱发了重要单胺能神经递质源核（LC，去甲肾上腺素能；MR、DR、血清素能）和疼痛/稳态调节核（即 PAG）更强的 fMRI 反应。
结论：我们的 fMRI 结果支持 taVNS 传入在人类脑干中定位到桥脑延髓区的孤束核的先前定位，并证明了刺激频率对脑干 fMRI 反应的显著影响。
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