Motor cortex dysfunction in migraine

描述（由申请人提供）：儿童偏头痛是美国五种最常见的儿童疾病之一，影响超过600万儿童和青少年，分别高达每组的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级联反应中起主要作用。为了测量大脑中的这些功能性皮质异常，脑磁图（MEG）可以用于以高空间和时间分辨率检测和定位功能性大脑激活。重要的是，最近在人脑中发现了高频脑信号（HFBS，~2，632 Hz）。HFBS的MEG检测提供了远远超出常规方法的揭示细微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儿童在偏头痛发作期间和发作之间的皮质功能障碍。这一假说是基于以下观察：（1）皮质功能障碍可以量化和定位与新开发的MEG方法。(2)偏头痛患儿的辅助运动皮层在65 - 150 Hz范围内的神经磁激活增强。（3）低频脑信号（<40 Hz）和脑磁图显示偏头痛患儿皮层兴奋性降低。最近的报告表明，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和MEG临床应用十多年的经验，我们提出了以下具体目标：（1）量化在偏头痛发作期间与MEG运动皮层兴奋性的空间和频谱变化;（2）确定偏头痛发作之间的运动诱发磁场（MEF）的空间，频谱，频率和时间异常。MEG数据将在6，000 Hz下数字化。偏头痛中皮质兴奋性的降低将通过使用基于小波的波束形成器在源水平上分析0 - 3，000Hz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患者在低频范围（<40 Hz）的大脑活动，因此使用0 - 3，000 Hz的神经磁信号研究儿童偏头痛患者的运动皮层兴奋性是新颖的。用神经磁频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层，但同样的方法也可以应用于评估其他大脑区域。如果成功的话，可以用脑磁图无创地评估和定位皮质兴奋性的异常。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方法是新颖的，基于对偏头痛机制的更好理解，改进的治疗和预防解决方案可能会保护偏头痛儿童免于进展为具有显著残疾的慢性疾病。 公共卫生相关性：基于最近的发现，皮质兴奋性在偏头痛进展的级联中起主要作用，大脑产生高频脑信号（~2，632 Hz），我们建议使用新的MEG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理解，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.