Interictal epileptiform activity outside the seizure onset zone impacts cognition

Abstract

See Kleen and Kirsch (doi:10.1093/awx178) for a scientific commentary on this article.Cognitive deficits are common among epilepsy patients. In these patients, interictal epileptiform discharges, also termed spikes, are seen routinely on electroencephalography and believed to be associated with transient cognitive impairments. In this study, we investigated the effect of spikes on memory encoding and retrieval, taking into account the spatial distribution of spikes in relation to the seizure onset zone as well as anatomical regions of the brain. Sixty-seven patients with medication refractory epilepsy undergoing continuous intracranial electroencephalography monitoring engaged in a delayed free recall task to test short-term memory. In this task, subjects were asked to memorize and recall lists of common nouns. We quantified the effect of each spike on the probability of successful recall using a generalized logistic mixed model. We found that in patients with left lateralized seizure onset zones, spikes outside the seizure onset zone impacted memory encoding, whereas those within the seizure onset zone did not. In addition, spikes in the left inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, and fusiform gyrus during memory encoding reduced odds of recall by as much as 15% per spike. Spikes also reduced the odds of word retrieval, an effect that was stronger with spikes outside of the seizure onset zone. These results suggest that seizure onset regions are dysfunctional at baseline, and support the idea that interictal spikes disrupt cognitive processes related to the underlying tissue.

Keywords: cognition; epileptiform discharges; interictal spikes; intracranial EEG; memory.

Figure 1

Delayed Free Recall Task schematic. Blue indicates correctly recalled words and orange indicates incorrectly recalled words. Subjects were presented 15 words during the encoding period, followed by a distractor task that consisted of simple arithmetic problems. After a tone, subjects engaged in free recall, vocalizing presented words in any order. Subjects were presented with 12–60 word lists in each session.

Figure 2

Mean recall (A) and spike lateralization (B) grouped by seizure onset lateralization. Boxplots indicate median, 25th, and 75th percentiles. Significance at ^*P < 0.01, ^***P < 0.001.

Figure 3

Estimated odds of successful recall for each region. Mean odds of successful recall per spike during the encoding period are shown along with 95% CIs. Odds <1 indicate a decrease in the odds of successful recall per spike. Red indicates significant after multiple comparisons correction. L/R = left/right hemisphere.

Figure 4

Per cent change in spike count during failed encoding for each patient. Vertical axis represents the per cent change in spike count. The horizontal axis represents the left temporal lobe as well as the significant left temporal regions from our regional analysis. Boxplots represent the percent change of spikes across all patients with the given SOZ lateralization. Only the recall of words in serial position >5 were included to account for the primacy effect.

Figure 5

Electrode coverage and significant regions. Electrodes (n = 6144; blue dots) across all patients are shown in a 3D view of the left hemisphere (A) and an axial slice (B) on a template brain in Montreal Neurological Institute (MNI) space.