In conclusion, Motelow et al. provide strong evidence that focal hippocampal seizures lead to depressed subcortical cholinergic arousal, which underlies the loss of consciousness during seizures. This finding offers a novel potential approach to treatment of complex partial seizures by specifically activating cholinergic neurons in the arousal centers (experimental optogenetic tools already exist). However, some additional issues need to be clarified: The authors used only females for their study, but hormonal changes during female ovarian cycles may confound the picture of sedation or arousal (9, 10, 11). Finally, the mechanism of impaired consciousness during focal hippocampal seizures that secondarily generalize as well as the role of other “arousal” candidates remain to be determined.
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