Collaborative Research: Cortical Spreading Depression and Ionic Electrodiffusion in the Brain

这个项目的一个主要目标是更好地了解皮层扩散性抑制。这是一种大脑紊乱，是偏头痛先兆和许多其他大脑疾病（包括中风和癫痫）的基础。在这种疾病中，大脑的离子环境被完全破坏，神经细胞变得沉默，干扰以每分钟2到5毫米的速度在大脑中传播。当这种情况发生在视觉皮层（处理视觉信息的大脑区域）时，患者会感觉到一种光环，一种暂时的视觉缺陷，慢慢地在视野中传播。偏头痛患者通常在偏头痛发作之前感知到先兆（偏头痛先兆）。因此，更好地理解皮层扩散性抑制的机制将有助于偏头痛和许多其他病理性脑部疾病的管理。这项研究合作将培养研究生谁将在项目的各个方面工作。暑期学校将在佛罗里达国际大学举行，这是一个少数民族服务机构。因此，这一项目，加上现有的机构努力，有可能进一步实现增加少数群体在科学领域的代表性的目标。此外，这种合作努力汇集了不同兴趣和实力的实验学家和理论家，因此为学生提供了专业成长的理想机会。皮层扩散性抑制是大脑中离子浓度的大规模重新分布，导致局部暂时性神经功能丧失。这种干扰以每分钟2到5毫米的速度在大脑中传播，是偏头痛先兆的生理基础。虽然皮层扩散性抑制在七十多年前首次被描述，但导致这种干扰的生理机制仍然难以捉摸，很可能是因为它涉及许多生物物理过程。在这个项目中，将建立一个全面的数学模型和计算装置来模拟这种现象，并利用高空间分辨率获得的实验数据进行验证。数学模型的一个重要方面是，它考虑了离子电扩散，在以前的研究中没有适当考虑的效果，也可能是相关的illucidating机制在许多其他神经生理设置。特别是，将研究电扩散对细胞外记录、脑电图和脑磁图信号的影响，从而改进对这些测量方式的分析。总的来说，这项研究可能会对与这些潜在生物物理过程相关的许多其他大脑病理产生影响。

A major goal of this project is to gain a better understanding of cortical spreading depression. This is a disorder of the brain that is the basis of migraine aura and many other diseases of the brain including stroke and epilepsy. In this disorder the ionic environment of the brain is completely disrupted and the nerve cells turn silent, with a disturbance that spreads at speeds of two to five millimeters per minute across the brain. When this happens in the visual cortex, the brain area that processes visual information, the patient will perceive an aura, a temporary visual defect that slowly travels over the field of view. Migraine sufferers often perceive an aura (migraine aura) prior to a migraine attack. Better understanding the mechanisms of cortical spreading depression will thus help in management of migraine headache and many other pathological brain conditions. This research collaboration will train graduate students who will work on various aspects of the project. Summer schools will be held at Florida International University, which is a minority serving institution. Thus this project, accompanied with existing institutional efforts, has the potential to further the goal of increasing minority representation in the sciences. Further, this collaborative effort brings together experimentalists and theorists of diverse interests and strength, and therefore provides students with an ideal opportunity for professional growth.Cortical spreading depression is a massive redistribution of ionic concentrations in the brain that results in a localized temporary loss of neuronal function. This disturbance spreads through the brain at speeds of two to five millimeters per minute and is the physiological substrate of migraine aura. Although cortical spreading depression was first described over seventy years ago, the physiological mechanisms leading to the disturbance remains elusive, most likely due to the fact that it involves many biophysical processes. In this project, a comprehensive mathematical model and computational apparatus to simulate the phenomena will be constructed and validated with experimental data obtained at high spatial resolution. An important aspect of the mathematical model is that it takes into account ionic electro-diffusion, an effect that has not been properly considered in previous studies, and may also be relevant for illucidating mechanisms in many other neurophysiological settings. In particular, the effects of electro-diffusion on extracellular recordings, electroencephalography and magneto-encephalography signals will be studied, thereby improving analysis of these measurement modalities. Overall this research may have an impact in many other brain pathologies which are linked to these underlying biophysical processes.