Neocortical hemodynamics during epileptic activity in primates and humans

描述(由申请人提供)：工作说明：大脑血流量(CBF)、血容量(CBV)和氧合(CBO)如何随着新皮质中正常和癫痫神经元的活动而变化？这项建议的重点是利用光学成像技术结合电生理学和药理学研究在人类灵长类动物中研究这一问题。在这些研究中，本征光信号的光学成像(OI)是一种聚焦技术，依赖于氧合和脱氧血红蛋白对光的不同吸收。OI可以选择性地测量由于血容量或血液氧合而引起的皮质组织的变化。新皮质血流动力学的进一步研究具有重要意义，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全面地理解活体脑生理学所需的基本知识。其次，识别正常和癫痫活动之间的脑血流动力学耦合的差异，可能有助于揭示血液动力学相关现象，如由癫痫活动引起的血容量异常变化或新皮质组织的脱氧，可能会导致组织萎缩和其他病理方面的“癫痫脑”。第三，量化神经元活动和新皮质血流动力学之间的时间和空间关系是发展光学成像作为神经外科患者功能性和癫痫新皮质定位的实用临床工具的必要步骤。到目前为止，OI在癫痫研究中的应用有限，至少有两个原因：i)解释在不同光学波长采集的光学信号的问题尚未完全解决；ii)通常使用特别或定性的方法来分析光学成像数据，很少致力于开发使OI成为定量技术所需的严格统计方法。这个项目的一个主要目标就是解决这些问题。该提案将涉及三个具体目标：目标1：量化神经元活动、CBF、CBV、CBO和光学成像的变化之间的关系；目标2：为OI数据的建模和分析开发实用的统计方法；以及目标3：阐明发作和相互活动期间新皮质血流动力学变化和光学信号之间的关系。公共卫生相关性：非技术解释：当大脑的区域变得活跃时，氧合作用和流向这些活跃区域的血液会增加。血液中这些依赖活动的变化既是正常活动的结果，也是病理性癫痫活动的结果。这项建议将涉及两个主要目标，这两个目标可能对癫痫的治疗产生临床影响。首先，它将研究癫痫活动如何改变灵长类动物和患有癫痫的人类大脑中的血液流动和氧合变化。这些信息可能有助于更好地理解癫痫的基本机制。其次，将进一步开发一种实验光学成像技术，能够以非常高的空间分辨率绘制活动引起的血液氧合和血流变化。这种光学成像技术有可能为神经外科医生在外科手术治疗难治性癫痫期间识别癫痫脑区域提供一种新的更好的方法。

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 . PUBLIC HEALTH RELEVANCE: Non-technical explanation: When areas of the brain become active, there are increases in the oxygenation and flow of blood to those active regions. These activity-dependent changes in blood result from both normal activity, as well as from pathological epileptic activity. This proposal will address two major goals which could have clinical implications in the treatment of epilepsy. First, it will study how epileptic activity alters blood flow and oxygenation changes in the brain in primates and in humans suffering from epilepsy. This information may be helpful in better understanding the basic mechanisms of epilepsy. Second, an experiment optical imaging technique will be further developed that is capable of mapping activity-evoked changes in blood oxygenation and blood flow with very high spatial resolution. This optical imaging technique has the potential to provide the neurosurgeon with a new and better method for identifying epileptic brain regions during the surgical treatment for medically intractable epilepsy.