Boosting mind-body mechanisms for mitigating autonomic dysfunction in migraine

增强身心机制以减轻偏头痛的自主神经功能障碍

基本信息

批准号：
10700824
负责人：
RANDY Lyanne GOLLUB
金额：
$ 35.74万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10700824
关键词：
Affective Air Amygdaloid structure Autonomic Dysfunction Autonomic nervous system Behavior Therapy Brain Breathing Cell Nucleus Clinical Combined Modality Therapy Complex Control Groups Data Disease Dorsal Education Emotional Exhibits Frequencies Functional Magnetic Resonance Imaging Headache Hyperactivity Image Individual Inhalation Institute of Medicine (U.S.)Insula of Reil International Intervention Measures Meditation Mental Health Meta-Analysis Migraine Mind-Body Intervention Neurobiology Nucleus solitarius Outcome Pain Pathway interactions Patients Peripheral Phase Randomized Recommendation Reporting Respiration Rest Sensory Structure Sum System Training Transcutaneous Electric Nerve Stimulation Trigeminal System active method afferent nerve chronic pain disability emotion regulation expiration heart rate variability heart rhythm improved mind/body mindfulness meditation multimodality neuroimaging physical conditioning respiratory response stressor therapeutic target treatment response trial design vagus nerve stimulation

项目摘要

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.

抽象的偏头痛 (MIG) 是一种普遍存在 (15-20%) 且高度致残的疾病，具有复杂的神经生物学特征以自主神经失调为特征的基础被提出为正念冥想（MM）。我们自己和其他人的数据发现，可以改善自主功能的行为干预。副交感神经驱动增强（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，冥想训练还能促进情绪改善。杏仁核响应压力源的调节和相应的激活减少，再次如图所示根据我们自己和其他人的数据，自主功能正常化和杏仁核减少。对压力源的反应可能是偏头痛患者的重要治疗目标。显示出改善的临床结果，并在最近的医学研究所报告中推荐我们认为，对于 MM 来说，身心疗法也显示出了治疗偏头痛的希望。可能通过自上而下的机制运作，可能降低杏仁核的反应性并增强自主神经功能，外周（用 HF-HRV 评估）和中枢（用 fMRI 评估）中央自治网络（CAN）。此外，还有自下而上的疗法，例如侵入性和非侵入性耳廓经皮迷走神经治疗刺激（tVNS）还可以减少偏头痛频率和残疾。在 tVNS 中，迷走神经传入传递到神经核。髓质中的孤立束（NTS）可能调节三叉神经感觉复合体的兴奋性和过度兴奋性在更高的大脑结构中（即“自下而上”的通路）。此外，背髓迷走神经系统。与呼吸同步运行：NTS 接收来自延髓腹侧呼吸组的抑制性输入（VRG）吸气期间的细胞核，以及呼气期间的协助输入这是一个至关重要的特征。该电路，因为它表明利用该 NTS 途径的干预措施应与因此，我们小组开发了呼吸门控耳迷走神经传入神经刺激。 (RAVANS)，它通过仅在呼气阶段进行刺激来优化 NTS 的 tVNS 靶向，因此， RAVANS tVNS 结合了皮质/皮质下过度兴奋性的自下而上调制。 MM 训练结合 RAVANS tVNS 将在增强（中枢和外周）自主神经功能和减轻杏仁核过度活跃以应对患者的压力源患有偏头痛。