Abstracts

Rationale: Whether interictal epileptiform discharges (IEDs) can cause cognitive impairment is controversial. We recently used a rat model to show that IEDs in the hippocampus, a common focus for seizures, produce a disruption to ongoing cognition that is process-specific. We wanted to investigate whether these findings translate to humans, and in particular which hippocampal IED characteristics increase vulnerability to transient memory impairment. Methods: Ten patients had depth electrodes implanted into their hippocampi for preoperative seizure localization. EEG was recorded during 2070 trials of a working memory task that required delayed recall to elicit hippocampal function. Eight of ten patients had left sided seizure onset. Hippocampal IEDs were manually and blindly detected offline and classified into three major subtype groups and according to laterality. The impact of IEDs on short-term memory processes was analyzed and adjusted for individual differences between patients. Results: Hippocampal IEDs during in the memory retrieval period increased the likelihood of task errors when they occurred contralateral to the seizure onset zone (p < 0.05) or bilaterally (p < 0.001). IEDs also increased task errors during memory maintenance when they were bilateral (p < 0.01) and particularly with longer repetitive spike-wave complexes (p < 0.01). These memory impairments occurred independently of reaction time, which was not affected by hippocampal IEDs. Conclusions: Hippocampal IEDs disrupt short-term memory retrieval, but not memory encoding as with cortical IEDs in previous literature. Repetitive spike-wave complexes can also disrupt memory maintenance when they are sufficiently long or bilateral. The preferential effect of IEDs contralateral to the seizure focus may relate to neural compensation which may have redistributed function to the more functional hemisphere over time. This study provides biological validity to the use of a rodent model in the study of IED-induced transient cognitive impairment. Moreover, it strengthens the argument that IEDs contribute to a proportion of cognitive impairment in epilepsy that is dependent upon when and where they occur. Funding was provided by NIH Grants F30NS064624 (J.K.K.), R21MH086833 (P.-P.L.-S.), R01NS044295 and R01NS073083 (G.L.H.)