Aberrant Neuromagnetic Signatures with Chronic Migraine

摘要：慢性偏头痛是偏头痛的一种致残性并发症，头痛发生15次或以上 每月天数。慢性偏头痛患者经常经历药物过度使用头痛， 进一步使这种病症复杂化，并给临床治疗头痛带来更多问题。因为一个人的痛苦 患有慢性偏头痛的患者通常需要进行体力活动，并且通常对标准的 在治疗方面，慢性偏头痛患者的生活质量非常低，这对社会产生了很大的影响。 偏头痛研究中最重要的进展之一是证实了大脑皮层的高和低水平， 使用非侵入性神经成像技术（如脑磁图（MEG））激活。脑磁图检查 偏头痛的研究表明，皮质激活的正常化可以降低偏头痛的发病率， 攻击抗癫痫药物（AED），这可能会改变皮层激活，往往是有效的， 预防偏头痛然而，慢性头痛中的皮质功能障碍可以是过度激活或低激活， 这取决于病理和大脑区域。对潜在的大脑机制知之甚少 并且很少在儿童慢性偏头痛中进行研究。我们假设儿童慢性偏头痛是 与一系列大脑区域的皮质过度和过低激活有关。这个假设是基于 急性偏头痛皮质兴奋性的位置和程度的观察已被定量和 使用先进的MEG方法（如波束成形和小波）进行无创测定。充分发挥两国 在偏头痛和脑磁图的研究经验，我们建议解决以下具体目标：（1）量化 慢性偏头痛儿童异常脑激活的时空和频谱特征 脑磁图头痛发作;（2）确定脑激活的时空和频谱变化， 儿童慢性偏头痛的临床治疗前，期间和之后。本研究的创新之处在于 在慢性偏头痛中测量非常高频的神经磁信号（高达2884 Hz）， 偏头痛的MEG研究通常限于低频范围（< 70 Hz）。由于高频 神经磁信号很好地定位于大脑的局部区域，如果成功的话，我们可以精确地确定 高频MEG数据在拟议的研究中，皮层激活在哪里以及在多大程度上改变， 慢性偏头痛对异常皮层激活的位置和类型有了更清楚的了解 发生时，所有针对皮质兴奋性的治疗（例如AED，经颅磁刺激， 经颅直流电刺激、针灸）--目前显示出巨大的希望--可以指定， 改进，成果显著。鉴于高频神经磁信号是一种新的 作为一种生物标志物，用先进的MEG方法对慢性偏头痛进行更深入的研究是我们研究的关键下一步。 了解偏头痛的病理生理学和我们开发更好的治疗和预防的能力 战略布局

ABSTRACT: Chronic migraine is a disabling complication of migraine with headaches that occurs 15 or more days per month. Patients with chronic migraine frequently experience medication overuse headaches that may further complicate this disorder and cause more problems for clinically treating headaches. Since the pain of a patient with chronic migraine typically worsens with physical activity and is often refractory to standard treatment, patients with chronic migraine have very low qualities of life which in term greatly impacts society. One of the most important advances in migraine research is the confirmation of cortical hyper- and hypo- activation with non-invasive neuroimaging technologies such as magnetoencephalography (MEG). MEG study of migraine has shown that the normalization of cortical activation can reduce the incidence of migraine attacks. Antiepileptic drugs (AED), which may change cortical activation, are frequently effective in the prevention of migraine. However, cortical dysfunction in chronic headaches can be hyper- or hypo-activation which depends on the pathology and brain regions. The underlying cerebral mechanism is poorly understood and has rarely been studied in pediatric chronic migraine. We hypothesize that pediatric chronic migraine is associated with cortical hyper- and hypo-activation in a set of brain areas. This hypothesis is based on the observations that the location and degree of cortical excitability in acute migraine have been quantitatively and noninvasively determined with advanced MEG methods such as beamforming and wavelet. Building on our research experience in migraine and MEG, we propose to address the following specific aims: (1) quantify the spatiotemporal and spectral signatures of aberrant brain activation in children with chronic migraine during headache attacks with MEG; (2) determine the spatiotemporal and spectral changes of brain activation in children with chronic migraine before, during and after clinical treatment. The innovation of the present study is the measurements of very high-frequency neuromagnetic signals (up to 2884 Hz) in chronic migraine because MEG study of migraine is conventionally limited to a low-frequency range (< 70 Hz). Since high-frequency neuromagnetic signals are well localized to focal brain areas, if successful, we can precisely determine with high-frequency MEG data in the proposed study where and to what degree cortical activation changed in chronic migraine. With a clearer understanding of the location and types of aberrant cortical activation occurring, all of the treatments targeted at cortical excitability (e.g. AED, transcranial magnetic stimulation, transcranial direct current stimulation, acupuncture) - which currently show great promise -could be specified, refined and their outcomes significantly improved. Given that high-frequency neuromagnetic signals are a new biomarker, a more in-depth study of chronic migraine with advanced MEG methods is a critical next step in our understanding of migraine pathophysiology and our ability to develop better treatment and prevention strategies.