Investigating the oscillation of sensory thresholds through the migraine cycle

所有感觉阈值在偏头痛周期中都是动态的，可能是由下丘脑-丘脑-脑干网络固有的周期性振荡驱动的。一般来说，感觉阈值在发作间期降低，在头痛发作时达到最低点，之后才逐渐恢复。我们的目标是确定在偏头痛患者中解码这种感觉阈值变化的大脑区域，最终目标是深入了解偏头痛发作的起源/生成。为了将我们的目标存档，我们将在自发性偏头痛发作的阈值水平上对感觉输入进行每日纵向测量。功能成像将使用脑干优化的脊椎成像方法，专注于脑干和间脑区域。为了捕捉到自发性偏头痛发作和至少两个发作前的日子，我们将连续八天每天扫描与月经相关的纯偏头痛患者和健康的女性对照组-总是在早上。因此，第7天被计算为月经的开始，对于偏头痛患者也是偏头痛发作的开始(±1天)。由于单纯月经性偏头痛的偏头痛发作只发生在月经前不久或月经期间，这种方法可以预测偏头痛发作。对患者和健康对照组的月经进行平均扫描，将允许将月经控制为一种混乱。在确定了扫描仪内每一天的个体痛阈值后，患者和健康对照组将在三叉神经区(眼部、额部、额头以上)接受一系列电输入，其刺激强度已被确定为该特定日期的个体阈值。由于50%的标准化输入会被认为是痛苦的，50%的刺激不会，数据分析将允许使用回归模型和连通性分析来确定边缘和脑干区域的循环神经元兴奋性和交替功能连通性，这是产生偏头痛发作的先决条件。目前的文献表明，中枢神经系统的以下区域是候选区域：丘脑、下丘脑、伏隔核、中脑导水管周围灰质(PAG)、三叉神经颈复合体(TCC)和延髓头端腹内侧(RVM)。

All sensory thresholds are dynamic during a migraine cycle, possibly driven by a genetically inherent periodic oscillation of the hypothalamo-thalamo-brainstem network. In general, sensory thresholds decrease during the interictal stage and reach a nadir during the headache pain attack, only to gradually recover afterwards. We aim to identify brain areas that decode such sensory thresholds changes in migraine patients with the ultimate goal to gain insight into the origin/generation of migraine attacks. In order to archive our goal we will conduct daily longitudinal measurements of sensory input at the threshold level towards a spontaneous migraine attack. Functional imaging will be done with a dedicated focus on brainstem and diencephalon areas using a brainstem optimized spinal imaging method. In order to capture spontaneous migraine attacks and at least two pre-attack days, we will scan patients with pure menstrually-related migraine and healthy female controls each day–always in the morning- for eight consecutive days. Thereby, the 7th day is calculated to be the start of menstruation and in migraine patients also the start of the migraine attack (± 1 day). Since migraine attacks in pure menstrual migraine only occur shortly before or during menstruation, this method allows to predict migraine attacks. Scanning patients and healthy controls equally towards the menstruation will allow to control menstruation as a confound. After determination of the individual pain threshold on each individual day inside the scanner, patients and healthy controls will be presented with a series of electrical inputs in the trigeminal area (ophthalmic division, on the forehead above the brow in exactly the stimulus intensity that has been determined to be the individual threshold of that specific day. Since 50% of the standardized input will be perceived as painful and 50% of the stimuli will not, data analysis will allow, using regression models and connectivity analysis, to determine the cycling neuronal excitability and alternating functional connectivity of limbic and brainstem areas that are the prerequisite to generate a migraine attack. Current literature suggests the following areas of the central nervous system to be candidates: Thalamus, Hypothalamus, Nucleus accumbens, periaqueductal gray (PAG), trigeminocervical complex (TCC), and rostral ventromedial medulla (RVM).