Abstracts

Rationale: Cognitive complaints are a common comorbidity of epilepsy. These include deficits in semantic memory, language, psychomotor speed, verbal episodic memory, and executive function (Wang et al., Epilepsy Behav 2011;22:728-734). We hypothesize that inter-ictal spiking disrupts episodic memory. We test the relationship between interictal spiking in and outside of the network generating seizures on memory encoding and recall. Methods: Seventeen patients with drug resistant epilepsy undergoing invasive EEG monitoring were studied. A delayed free recall episodic memory task was used to test memory encoding and recall. We analyzed data recorded on electrodes placed over normal and epileptogenic tissue using a validated automated spike detection algorithm. Subjects memorized a list of 15 common nouns, chosen at random. Subjects then recalled words presented during the encoding period in any order. Behavioral events during the memory task were synchronized with intracranial electrophysiological recordings via TTL pulses. Raw electrophysiologic data was processed in MATLAB prior to statistical analysis.Results: Across 51 sessions for 17 subjects, total spike detections were compared between epileptic and non-epileptic regions of the brain. T-tests confirmed significantly higher inter-ictal spiking in the epileptic regions of the brain for 37 of the 51 total sessions (p<0.001 for each session). Inter-ictal spiking was significantly higher in seizure onset regions of the brain in all 17 subjects (p<0.001 for each subject). In 16 subjects the inter-ictal spiking was significantly higher in non-epileptic regions of the brain during epochs when incorrect memory encoding occurred (p<0.001). Analyses quantified percentage of words correctly recalled, as a function of inter-ictal spiking during the encoding and recall periods. The correlation between percentage recall and inter-ictal spiking was validated parametrically by plotting the average number of spikes detected for every percentage recall value and fitting an ordinary least-squares line to the data (Figure 1). Conclusions: Interictal spiking disrupts episodic memory in patients with epilepsy, both in their ability to encode and recall presented material. Inter-ictal spiking outside of the ictal onset zone appears to have the most detrimental impact on cognition. These findings suggest that altering epileptic networks to reduce spiking in normal brain may positively impact cognition. Potential approaches might include surgical resection of spike and seizure generating regions and interventions (medications or devices) to reduce interictal spikes or their propagation outside of seizure onset regions.