Neocortical hemodynamics during epileptic activity in primates and humans

描述（由申请人提供）：工作说明：脑血流量（CBF），容量（CBV）和氧合（CBO）如何随新皮层正常和癫痫性神经元活动的变化而变化？本提案的重点是利用光学成像技术结合电生理和药理学研究在人类灵长类动物中研究这个问题。本征光信号（OI）的光学成像技术是这些研究的重点，它依赖于氧血红蛋白和脱氧血红蛋白对光的不同吸收。成骨不全可以选择性地测量因血容量或血氧引起的皮质组织变化。新皮质血流动力学的进一步研究是重要的，至少有三个原因。首先，更好地阐明脑血流动力学和神经元活动之间的定量关系代表了更完整地理解体内脑生理学所需的基础知识。其次，确定正常和癫痫活动之间脑血流动力学耦合的差异，可能有助于揭示与血流动力学相关的现象，如癫痫活动引起的血容量异常变化或新皮质组织脱氧，如何导致组织萎缩和“癫痫脑”的其他病理方面。第三，量化神经元活动和新皮层血流动力学之间的时空关系是发展光学成像作为定位神经外科患者功能和癫痫性新皮层的实用临床工具的必要步骤。迄今为止，OI在癫痫研究中的应用有限，至少有两个原因：i)解释在各种光波长下获得的光信号的问题尚未完全解决，ii)用于光学成像数据分析的特殊或定性方法通常被使用，很少有工作致力于开发使OI成为定量技术所必需的严格统计方法。这个项目的一个主要目标就是解决这些问题。目标1：量化神经元活动、CBF、CBV、CBO和光学成像变化之间的关系；目的2：为成骨不全数据的建模和分析开发实用的统计方法；目的3：阐明发作和发作期间新皮层血流动力学变化与光学信号之间的关系。

DESCRIPTION (provided by applicant): Statement of work: How do cerebral blood flow (CBF), volume (CBV), and oxygenation (CBO) vary in response to normal and epileptic neuronal activity in the neocortex? The focus of this proposal is to investigate this question in primates in humans using optical imaging techniques combined with electrophysiological and pharmacological studies. Optical imaging of intrinsic optical signals (OI), a technique of focus in these studies, depends on the differential absorption of light by oxy- and deoxy-hemoglobin. OI can selectively measure changes in cortical tissue due to either blood volume or blood oxygenation. Further study of neocortical hemodynamics is important for at least three reasons. First, a better elucidation of the quantitative relationships between cerebral hemodynamics and neuronal activity represents basic knowledge required for a more complete understanding of in vivo brain physiology. Second, identifying the differences in the coupling of cerebral hemodynamics between normal and epileptic activity may shed light on how hemodynamic-related phenomena, such as abnormal changes in blood volume or deoxygenation of neocortical tissue elicited by seizure activity may contribute to tissue atrophy and other pathological aspects of the "epileptic brain". Third, quantifying the temporal and spatial relationships between neuronal activity and neocortical hemodynamics is a necessary step towards developing optical imaging as a practical clinical tool for localizing functional and epileptic neocortex in neurosurgical patients. To date, OI has been of limited use in epilepsy research for at least two reasons: i) The problem of interpreting optical signals acquired at the various optical wavelengths has not been fully resolved, and ii) ad hoc or qualitative methods have typically been used for the analysis of optical imaging data, with very little work devoted towards developing rigorous statistical methods necessary for making OI a quantitative technique. A major goal of this project is to resolve these issues. Three specific aims will be addressed in the proposal: Aim 1: To quantify relationships between changes in neuronal activity, CBF, CBV, CBO, and optical imaging; Aim 2: To develop practical statistical methods for modeling and analysis of OI data, and Aim 3: To elucidate the relationships between hemodymanic changes and optical signals in neocortex during ictal and interical activity .