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.
