Aberrant Neuromagnetic Signatures with Chronic Migraine

描述(由申请人提供)：慢性偏头痛是偏头痛的一种致残并发症，每个月发生15天或更长时间。慢性偏头痛患者经常经历药物滥用头痛，这可能会使这种疾病进一步复杂化，并给临床治疗头痛带来更多问题。由于慢性偏头痛患者的疼痛通常会随着体力活动的增加而恶化，而且往往对标准治疗难以奏效，因此慢性偏头痛患者的生活质量非常低，从长远来看，这将极大地影响社会。偏头痛研究中最重要的进展之一是用脑磁图(MEG)等非侵入性神经成像技术证实了皮质的过度激活和过度激活。对偏头痛的脑磁图研究表明，皮质激活的正常化可以减少偏头痛发作的发生率。抗癫痫药物(AED)可以改变皮质的激活，在预防偏头痛方面经常有效。然而，慢性头痛的皮质功能障碍可能是过度激活，也可能是过度激活，这取决于病理和大脑区域。对其潜在的脑机制了解甚少，在儿童慢性偏头痛中也鲜有研究。我们假设儿童慢性偏头痛与一组大脑皮质的过度和过度激活有关。 区域。这一假说是基于观察到的，即通过波束成形和小波等先进的脑磁图方法，已经定量和非侵入性地确定了急性偏头痛患者大脑皮质兴奋性的位置和程度。基于我们在偏头痛和脑磁图方面的研究经验，我们建议解决以下具体目标：(1)量化慢性偏头痛儿童在使用脑磁图头痛发作期间异常脑激活的时空和光谱特征；(2)确定慢性偏头痛儿童在临床治疗前、中和之后脑激活的时空和光谱变化。本研究的创新之处在于对慢性偏头痛患者的超高频神经磁信号(最高可达2884赫兹)的测量，因为脑磁图对偏头痛的研究通常局限于低频范围(70赫兹)。由于高频神经磁信号可以很好地定位于大脑局部区域，如果成功，我们可以在拟议的研究中使用高频脑磁图数据精确地确定慢性偏头痛患者皮质激活的位置和程度。随着对皮质异常激活发生的位置和类型有了更清楚的了解，所有针对皮质兴奋性的治疗(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--可以被具体化、精细化，其结果显著改善。鉴于高频神经磁信号是一种新的生物标志物，使用先进的脑磁图方法对慢性偏头痛进行更深入的研究是我们理解偏头痛病理生理学以及开发更好的治疗和预防策略的能力的关键下一步。

DESCRIPTION (provided by applicant): 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.