Motor cortex dysfunction in migraine

描述(申请人提供)：儿童偏头痛是美国最常见的五种儿童疾病之一，影响着600多万儿童和青少年，分别占每个群体的10%和28%。偏头痛研究的最新进展表明，皮质功能障碍在偏头痛的级联反应中起主要作用。为了测量大脑中这些功能性的皮质异常，脑磁图(MEG)可以用来检测和定位高空间和时间分辨率的功能性大脑激活。重要的是，最近在人脑中发现了高频脑信号(HFBS，~2,632赫兹)。脑磁图对HFBS的检测提供了远远超过传统方法来揭示微小的皮质功能障碍的能力。我们假设脑磁图可以定量和非侵入性地评估偏头痛发作期间和发作间期偏头痛儿童的皮质功能障碍。这一假说基于以下观察：(1)用新发展的脑磁图方法可以对皮质功能障碍进行量化和定位。(2)偏头痛儿童辅助运动皮质在65-150赫兹范围内磁活动增强；(3)用低频脑电信号(40赫兹)和脑磁图发现偏头痛患者皮质兴奋性异常。最近的报道表明，偏头痛发作可以通过经颅磁刺激(TMS)、药物和其他方法使皮质兴奋性正常化来治疗和/或预防。基于我们在儿童偏头痛方面的经验和十多年来脑磁图的临床应用，我们建议解决以下具体目标：(1)量化偏头痛发作期间运动皮质兴奋性的空间和频谱变化；(2)确定偏头痛发作之间运动诱发磁场(MEF)的空间、频谱、频率和时间异常。脑磁图数据将以6,000赫兹进行数字化。偏头痛患者皮层兴奋性的异常将通过使用基于小波的波束形成器在源水平上分析0-3,000赫兹的神经磁谱功率来确定。由于脑磁图主要用于研究成人偏头痛低频段(40赫兹)的脑活动，因此利用0-3000赫兹的脑磁信号研究儿童偏头痛的运动皮质兴奋性是很有新意的。用神经磁谱和频率特征量化皮质兴奋性在技术上是创新的。虽然这项建议侧重于运动皮质，但同样的方法也可以应用于其他大脑区域的评估。如果成功，皮层兴奋性的异常可以用脑磁图进行无创性评估和定位。治疗和预防偏头痛发作的有效方法可能是通过TMS、药物和其他方法使皮质兴奋性正常化。鉴于HFBS是一项新发现，我们的MEG方法也是新的，基于更好地了解偏头痛的机制而改进的治疗和预防解决方案可能会保护偏头痛儿童免受发展为严重残疾的慢性疾病。 公共卫生相关性：基于最近的发现，即皮质兴奋性在偏头痛的级联发展中发挥主要作用，以及大脑产生高频大脑信号(~2,632赫兹)，我们建议使用新的脑磁图技术来定量评估急性偏头痛期间的皮质功能障碍。这将大大加深对偏头痛期间大脑活动的科学了解，如果成功，可能会通过非侵入性正常化或维持皮质兴奋性来有效治疗和预防偏头痛。

DESCRIPTION (provided by applicant): Pediatric migraine is one of the five most prevalent childhood disorders in the USA, affecting more than 6 million children and adolescents, up to 10% and 28% of each group, respectively. Recent advances in migraine research have demonstrated the cortical dysfunction plays a primary role in the cascade of migraine. To measure these functional, cortical abnormalities in the brain, magnetoencephalography (MEG) may be used to detect and localize functional brain activation with high spatial and temporal resolutions. Importantly, high-frequency brain signals (HFBS, ~2,632 Hz) have recently been found in the human brain. MEG detection of HFBS provides capability far beyond the conventional methods for revealing subtle cortical dysfunction. We hypothesize that MEG can quantitatively and noninvasively assess cortical dysfunction for children with migraine during and between migraine attacks. This hypothesis is based on the following observations: (1) Cortical dysfunction can be quantified and localized with newly developed MEG methods. (2) Increased neuromagnetic activation in 65-150 Hz has been volumetrically localized in the supplementary motor cortex in children with migraine, and (3) Abnormalities of cortical excitability in migraine have been found by using low frequency brain signals (<40 Hz) and MEG. Recent reports have shown that migraine attacks can be treated and/or prevented by normalizing cortical excitability with transcranial magnetic stimulation (TMS), medications and other methods. Building on our experience in pediatric migraine and clinical applications of MEG for more than a decade, we propose to address the following specific aims: (1) Quantify the spatial and spectral alteration of motor cortex excitability in pediatric migraine during migraine attacks with MEG; (2) Determine the spatial, spectral, frequency and temporal abnormalities of movement-evoked magnetic fields (MEFs) between migraine attacks. MEG data will be digitized at 6,000 Hz. Abnormalities of cortical excitability in migraine will be determined by analyzing neuromagnetic spectral power in 0-3,000 Hz at source levels using wavelet-based beamformer. Since MEG has mainly been used in the study of brain activities in low-frequency ranges (< 40 Hz) in migraine in adults, the study of the motor cortex excitability in pediatric migraine with neuromagnetic signals in 0-3,000 Hz is novel. Quantification of the cortical excitability with neuromagnetic spectral and frequency signatures is technically innovative. Although this proposal focuses on motor cortex, the same methodologies can be applied to evaluate other brain areas as well. If successful, abnormalities of cortical excitability can be noninvasively assessed and localized with MEG. Effective methods for treating and preventing migraine attacks may be possible by normalizing cortical excitability with TMS, medication and other methods. Given that HFBS are a new discovery and our MEG methodologies are novel, improved treatment and prevention solutions based on better understanding of the mechanisms of migraine may protect children with migraine from progressing into a chronic condition with significant disability. PUBLIC HEALTH RELEVANCE: Building on recent discoveries that cortical excitability plays a primary role in the cascade of migraine progression and that the brain generates high-frequency brain signals (~2,632 Hz), we propose to use new MEG technology to quantitatively assess cortical dysfunction during acute migraine. This will add significant depth to the scientific understanding of brain activity during migraines and, if successful, may lead to the effective treatment and prevention of migraine headaches through noninvasive normalization or maintenance of cortical excitability.