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）如何响应新皮层中正常和癫痫神经元活动而变化？这项建议的重点是调查这个问题，在人类灵长类动物使用光学成像技术结合电生理和药理学研究。光学成像的内在光学信号（OI），在这些研究中的重点技术，取决于光的氧和脱氧血红蛋白的差分吸收。OI可以选择性地测量由于血容量或血氧合引起的皮质组织的变化。对新皮层血流动力学的进一步研究至少有三个重要原因。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会揭示血流动力学相关现象，如由癫痫活动引起的血容量或新皮质组织脱氧的异常变化可能导致组织萎缩和“癫痫脑”的其他病理学方面。第三，量化神经元活动和新皮层血流动力学之间的时间和空间关系是发展光学成像作为一种实用的临床工具定位功能和癫痫新皮层神经外科患者的必要步骤。到目前为止，OI在癫痫研究中的使用有限，原因至少有两个：i）解释在各种光波长下获得的光学信号的问题尚未完全解决，以及ii）特别或定性方法通常用于光学成像数据的分析，很少有工作致力于开发使OI成为定量技术所需的严格统计方法。该项目的主要目标是解决这些问题。本提案将涉及三个具体目标：目标1：量化神经元活动、CBF、CBV、CBO和光学成像变化之间的关系;目标2：开发用于OI数据建模和分析的实用统计方法;目标3：阐明发作和间歇活动期间新皮质中血流动力学变化和光学信号之间的关系。公共卫生相关性：非技术性解释：当大脑区域变得活跃时，氧合和流向这些活跃区域的血液会增加。血液中这些活动依赖性变化既来自正常活动，也来自病理性癫痫活动。该提案将解决两个主要目标，这可能对癫痫治疗产生临床影响。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流和氧合变化。这些信息可能有助于更好地了解癫痫的基本机制。第二，将进一步开发实验光学成像技术，该技术能够以非常高的空间分辨率绘制活动诱发的血氧和血流变化。这种光学成像技术有可能为神经外科医生提供一种新的和更好的方法，用于在外科治疗药物难治性癫痫的过程中识别癫痫脑区。

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.