TRACING SEIZURE PATHWAYS USING QUANTITATIVE EEG

使用定量脑电图追踪癫痫发作路径

• 批准号: 6495317
• 负责人: DAVID Lee SHERMAN
• 金额: $ 4.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6495317
• 关键词: anticonvulsants; autoradiography; bioimaging /biomedical imaging; biological signal transduction; brain electrical activity; brain electronic stimulator; brain mapping; electrical potential; electroencephalography; electrophysiology; experimental brain lesion; frontal lobe /cortex; generalized seizures; hypothalamus; laboratory rat; microinjections; neural information processing; neuroanatomy; neuropharmacology; pentylenetetrazole; pyrrolidinediones; statistics /biometry; thalamic nuclei

The field potentials of subcortical elements as well as the cortical EEG provide powerful tools for the study of epilepsy by enabling localization of neural activity to a specific thalamic nucleus. Preliminary data from novel, quantitative analysis of these recordings provide valuable information about the selective involvement of individual subcortical centers in the intact brain during seizure episodes. An original and exciting result has been that the anterior thalamus (AN) belonging to the mammillothalamic tract (MTT) is a critical gateway in the propagation of electrical activity during pentylenetetrazol (PTZ)- induced seizure episodes. in experiments coupling pharmacological and electrical stimulation studies of the MTT, we hope to advance our understanding in an important neurological area. We propose: 1) To test the hypothesis that the subcortical electrical activity from AN shows a higher level of association with cortex than a thalamic center unaffiliated with the MTT using the method of partial coherence analysis and its statistics. We will expand our studies to include the non linear contributions to the CTX-AN connection using the bispectrum and cross-bispectrum. Using original methods of time delay estimation, we will show that the seizure travels from the midbrain centers to cortex. We will also document the exact delay times of the advancing seizure along the MTT. 2) TO identify the effects of a known chemical anticonvulsant, ethosuximide (ESM), on EEG responses during PTZ seizures between cortex and subcortical centers. We will show how the level of subcortical electrical involvement and propagation delays are altered in specific subcortical areas with the application of ESM. 3) To test the hypothesis that electrical stimulation of AN activate's areas along the MTT. Using autoradiography we will investigate the inhibition of seizure activity produced by high frequency electrical stimulation. We will also show that ESM blocks seizure expression during low frequency electrical stimulation of AN. The overall goal is to obtain a better understanding of the functional anatomy and mechanisms underlying generalized epilepsy in its principal activation zones and to help discover effective anticonvulsant treatments for its remedy.

皮质下元素的场电位以及皮质脑电图通过将神经活动定位到特定的丘脑核，为癫痫研究提供了强大的工具。对这些记录进行新颖定量分析的初步数据提供了有关癫痫发作期间完整大脑中各个皮层下中心选择性参与的有价值的信息。一个原始且令人兴奋的结果是，属于乳头丘脑束（MTT）的前丘脑（AN）是戊四氮（PTZ）诱发癫痫发作期间电活动传播的关键门户。在 MTT 的药理学和电刺激研究相结合的实验中，我们希望增进我们对重要神经学领域的理解。我们建议：1）使用部分相干分析及其统计方法来检验以下假设：AN 的皮层下电活动与皮层的关联程度高于与 MTT 无关的丘脑中心。我们将扩大我们的研究范围，包括使用双谱和交叉双谱对 CTX-AN 连接的非线性贡献。使用原始的时间延迟估计方法，我们将证明癫痫从中脑中心传播到皮质。我们还将记录沿 MTT 推进癫痫发作的确切延迟时间。 2) 确定已知的化学抗惊厥药乙舒酰亚胺 (ESM) 对皮层和皮层下中心之间 PTZ 癫痫发作期间脑电图反应的影响。我们将展示如何通过应用 ESM 来改变特定皮层下区域的皮层下电参与水平和传播延迟。 3) 检验电刺激AN 激活沿MTT 区域的假设。使用放射自显影术，我们将研究高频电刺激产生的癫痫活动的抑制。我们还将证明 ESM 在 AN 低频电刺激期间阻断癫痫发作表达。总体目标是更好地了解全身性癫痫主要激活区的功能解剖学和机制，并帮助发现有效的抗惊厥治疗方法。