Anterior Thalamic Mediation of Experimental Seizures: Selective EEG Spectral Coherence

Abstract

Summary:Purpose: Physiological evidence has shown that the anterior thalamus (AN) and its associated efferents/ afferents constitute an important propagation pathway for pentylenetetrazol (PTZ)-mediated generalized seizures in rodents. Previous work demonstrated metabolic, physical, chemical, and electrical stimulation data supporting a role for AN in the expression of PTZ seizures. We now extend these observations through examination of neuroelectric signal indicators during seizure epochs. We show that the EEG recorded from AN is highly coherent with surface cortical (CTX) EEG during the immediate preconvulsant period and during the ictal stateough.Methods: Awake rats were continuously infused with PTZ until clonic seizures were recorded by using both subcortical AN, posterior thalamus (PT), or hippocampal (HPC) bipolar electrodes and cortical EEG. Through the signal-analysis techniques of ordinary and partial coherence, it was possible to focus selectively on signal correlations between AN and CTX (AN/CTX) by removing the effects of unaffiliated regions such as PT and HPC.Results: Coherence of PT/CTX was observed to be modest, and partial coherence of PT/CTX with the effects of AN/CTX removed did not improve the signal coherence of PT/CTX (PT/ CTX-AN). In contrast, AN/CTX coherence was observed to be high, with undiminished correlation when PT/CTX influence was removed (AN/CTX-PT). The most robust band of AN/ CTX coherence was centered around the spike-wave clonic frequency of 1-3 Hz. Partial multiple coherence-analysis techniques were used to remove the possible signal contributions from hippocampus in addition to PT. The AN/CTX coherence remained fully preserved in the low-frequency bands.Conclusions: These data provide electrophysiologic evidence supporting the special role of the anterior thalamus in the propagation of seizure activity between subcortex and cortex. Key Words: Anterior thalamus-EEG-Coherence-Seizure-Pentylenetetrazol.The precise neuronal pathways underlying the propagation and generalization of epileptic seizure activity remain largely unknown (1-6). Numerous studies have been performed to analyze the electrophysiology of focal cortical and hippocampal epileptic foci, and the local spread of these electrical paroxysms (7-10). Identification of specific cortical-subcortical pathways mediating seizure propagation between deep and surface neuronal elements has yet remained elusive, despite studies supporting the contribution of deep brain regions in clinical and EEG seizure expression (1-6). Mapping such connectivity would greatly improve our understanding of seizure mechanisms on a systems level, and offer potential sites for target-specific therapy, such as deep brain stimulation.Previously we established that the thalamic anterior nuclear complex (AN), a thalamic element of the limbic system, is an important gating center for the propagation of pentylenetetrazol (PTZ) seizure activity (11-15). Experiments supporting the hypothesis of AN mediation of convulsive activity include selective up...

Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy

“…It is conceivable that stimulation site at the anterior part of ANT complex modulates the critical nodes in the seizure propagation pathways. In fact, experimental evidence suggests that ANT plays a major role in seizure spread and generalization in pentylenetetrazole (PTZ) model in rats [16,23]. Stimulation at anterior aspect of ANT using currently available DBS devices reaches most likely the anteriomedial (AM) and the anterior principal (Apr) subnuclei ( Figure 2B).…”

Effects of Ionotropic Glutamate Receptor Blockers on Pentylenetetrazole-Induced Seizures in Krushinskii–Molodkina Rats

“…Electroencephalographic data and fMRI results have shown that the anterior nuclei of thalamus and their interaction with the cortex play an important role in the genesis of convulsions to pentylenetetrazol [10,27]. In addition, realization of myoclonic convulsions involves most limbic structures, including the hippocampus, which have tight connections with the anterior nuclei of the thalamus.…”

Regenerative Medicine for Epilepsy: From Basic Research to Clinical Application

“…Subsequently the treated rats showed significant behavioral ameliorations with reduced abnormal neurogenesis in the hippocampus. Anterior thalamus may be a good target of electrical stimulation for epilepsy, in that the suppression of anterior thalamic activity seems to limit the propagation pathways for generalized seizures [59]. Alternatively, the substantia nigra pars reticulata, subthalamic nucleus, cerebellum and cerebral cortex may be other targets for electrical stimulation when contemplating with arresting seizure propagation against epilepsy [60–62].…”