Consciousness and epilepsy: why are complex-partial seizures complex?

Abstract

Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral changes depend on seizure spread to subcortical structures including the lateral septum. Understanding the contributions of network inhibition to impaired consciousness in TLE is an important goal, as recurrent limbic seizures often result in cortical dysfunction during and between epileptic events that adversely affects patients’ quality of life.

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain

“…Furthermore, symptoms associated with epileptic EEG alterations in animals may be so subtle that they are not easily recognized. Examples are behavioral arrest, increased whisker twitching and chewing, and stereotyped behaviors, such as exploration, grooming, and scratching, which can represent the only symptoms of limbic seizures in rodents 27, 28. Furthermore, paroxysmal events in the hippocampus, as described in the present study, may induce a memory lapse that cannot be easily detected in an animal 22…”

The Default Mode Network and Altered Consciousness in Epilepsy

“…The recent development of an animal model has shed additional light on the mechanisms by which focal temporal lobe seizures cause loss of consciousness via long-range disruption by subcortical activating systems of neocortex [23][24][25]. In particular, fMRI decreases were found in the orbital frontal, anterior cingulate, and posterior cingulate cortex / retrosplenial cortex during seizures similar to changes observed in human patients.…”

“…3) [8,13,57]. For temporal lobe epilepsy, it seems that loss of consciousness occurs by seizure activity arising from the temporal lobe and propagating to subcortical structures; this may inhibit the arousal functions of the thalamus, basal forebrain and upper brainstem, to widely deactivate frontal and parietal association cortex [24,71]. In contrast, temporal lobe seizures that do not cause loss of consciousness may only produce impaired activity at the seizure foci without widespread effects via propagation to midline subcortical structures, and would thus spare cortical regions including the DMN.…”

The Global Workspace (GW) Theory of Consciousness and Epilepsy

“…Recently we proposed a 8 criteria scale in order to capture the different elements for a more objective evaluation of the AOC during seizures (Table 1) [1]. Different hypothesis have been proposed to explain how those seizures could impair consciousness [20]. Intracerebral EEG recordings studies have suggested that alteration of consciousness could be related to the spread of epileptic discharge to cortical structures contralateral to the origin of the seizures and could be more frequent in seizures affecting the dominant hemisphere [31].…”