TRACING SEIZURE PATHWAYS USING QUANTITATIVE EEG

皮层下元素的场电位以及皮层脑电通过将神经活动定位于特定的丘脑核团，为癫痫的研究提供了强大的工具。来自这些记录的新的定量分析的初步数据提供了关于癫痫发作期间单个皮质下中心在完整大脑中的选择性参与的有价值的信息。一个新颖而令人兴奋的结果是，在戊四氮(PTZ)诱导的癫痫发作中，属于乳房丘脑束(MTT)的丘脑前部(An)是电活动传播的关键门户。在将药理和电刺激研究相结合的实验中，我们希望在一个重要的神经学领域增进我们的理解。我们建议：1)利用偏相干分析及其统计学方法，检验来自AN的皮层下电活动与皮层的联系程度高于与MTT值无关的丘脑中枢的假设。我们将扩大我们的研究范围，以包括对CTX的非线性贡献--使用双谱和交叉双谱的联系。使用原始的时延估计方法，我们将证明癫痫发作是从中脑中心到皮质的。我们还将记录沿着MTT线前进的癫痫发作的确切延迟时间。2)研究已知的化学抗惊厥药乙琥胺(ESM)对PTZ惊厥时皮层和皮质下中枢之间脑电反应的影响。我们将展示如何利用ESM的应用改变特定皮质下区域的皮质下电信号受累程度和传播延迟。3)验证这样一种假设，即电刺激激活了沿MTT线的区域。利用放射自显影技术，我们将研究高频电刺激对癫痫发作活动的抑制作用。我们还将展示，在低频电刺激AN的过程中，ESM阻止癫痫的表达。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和机制，并帮助发现有效的抗惊厥治疗方法。

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.