Boosting mind-body mechanisms for mitigating autonomic dysfunction in migraine

摘要 偏头痛（Migraine，简称MGD）是一种常见的（15-20%）高度致残性疾病，具有复杂的神经生物学特性， 以自主神经失调为特征的基础。正念冥想（Mindfulness Meditation，MM）被认为是 一种可以改善自主功能的行为干预。我们自己和其他人的数据发现， 增强的副交感神经驱动（如通过较高水平的高频心率变异性或HF- HRV），仅经过8周的冥想训练。此外，冥想训练促进改善情绪 调节和相应的减少杏仁核的激活，以响应压力，再次显示 通过我们自己的数据和其他人的数据。自主神经功能正常化和杏仁核减少 对紧张性刺激的反应可能是偏头痛患者的重要治疗目标。多模式方法有 显示出改善的临床结果，并已在最近的医学研究所报告中推荐， 痛苦我们认为，这也是身心疗法的情况。MM已经显示出治疗偏头痛的前景， 可能通过自上而下的机制运作，可能降低杏仁核的反应性， 自主神经功能，包括外周（用HF-HRV评估）和中枢（用fMRI评估）。 中央自治网络（Central Autonomic Network，CAN）。 此外，自下而上的治疗，如侵入性和非侵入性耳经皮迷走神经， 电刺激（tVNS）也可减少偏头痛频率和残疾。在tVNS中，迷走神经传入中继到核 延髓孤束（NTS）可调节三叉神经感觉复合体的兴奋性和过度兴奋性 在更高级的大脑结构中（即，“自下而上”的路径）。此外，背侧延髓迷走神经系统 与呼吸同步：NTS接受来自延髓腹侧呼吸群的抑制性输入 (VRG)吸气时的核，呼气时的易化输入。这是一个至关重要的特征， 这一电路，因为它表明，利用这一NTS途径的干预措施应该与 呼吸为此，本课题组研制了呼吸门控耳迷走传入神经刺激仪 （RAVANS），其通过仅在呼气相期间刺激来优化NTS的tVNS靶向。因此，在本发明中， RAVANS tVNS结合了皮质/皮质下过度兴奋的自下而上调制。总之，我们建议 结合RAVANS tVNS的MM训练将在增强（中枢和 外周）自主神经功能和减轻患者对应激源的反应中的杏仁核过度活跃 例偏头痛

Abstract Migraine (MIG) is a prevalent (15-20%) and highly disabling disorder, with complex neurobiological underpinnings characterized by autonomic dysregulation. Mindfulness meditation (MM) has been proposed as a behavioral intervention that may improve autonomic functioning. Our own data, and those of others, found enhanced parasympathetic drive (as evidenced by higher levels of high-frequency heart rate variability, or HF- HRV), after only 8 weeks of meditation training. In addition, meditation training promotes improved emotion regulation and corresponding decreased activation of the amygdala in response to stressors, again as shown by our own data and those of others. Normalization of autonomic functioning and reduction of amygdala response to stressors may be an important therapeutic target in migraineurs. Multimodal approaches have shown improved clinical outcomes, and have been recommended in the recent Institute of Medicine report on pain. We propose that this is also the case for mind-body therapies. MM has shown promise for migraine, and likely operates by top-down mechanisms, potentially reducing amygdala reactivity as well as enhancing autonomic functioning, both peripherally (as assessed with HF-HRV) and centrally (as assessed with fMRI in the Central Autonomic Network, or CAN). Additionally, bottom-up therapies such as invasive and non-invasive auricular transcutaneous vagus nerve stimulation (tVNS) also reduce migraine frequency and disability. In tVNS, vagal afference relayed to nucleus tractus solitarii (NTS) in the medulla may modulate trigeminal sensory complex excitability and hyperexcitability in higher brain structures (i.e., a “bottom-up” pathway). Furthermore, the dorsal medullary vagal system operates in synchrony with respiration: NTS receiving inhibitory inputs from medullary ventral respiratory group (VRG) nuclei during inhalation, and facilitatory input during expiration. This is a critically-important feature of this circuitry, as it suggests that interventions utilizing this NTS pathway should be synchronized with respiration. Hence, our group developed Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), which optimizes tVNS targeting of NTS by stimulating only during the expiratory phase. Thus, RAVANS tVNS incorporates bottom-up modulation of cortical/subcortical hyperexcitability. In sum, we propose that MM training incorporating RAVANS tVNS will have a synergistic effect in enhancing (both central and peripheral) autonomic functioning and in mitigating amygdalar hyperactivity in response to stressors in patients with migraine.