Leveraging electrophysiologic correlates of word encoding to map seizure onset zone in focal epilepsy: Task-dependent changes in epileptiform activity, spectral features, and functional connectivity

Objective: Verbal memory dysfunction is common in focal, drug-resistant epilepsy (DRE). Unfortunately, surgical removal of seizure-generating brain tissue can be associated with further memory decline. Therefore, localization of both the circuits generating seizures and those underlying cognitive functions is critical in presurgical evaluations for patients who may be candidates for resective surgery. We used intracranial electroencephalographic (iEEG) recordings during a verbal memory task to investigate word encoding in focal epilepsy. We hypothesized that engagement in a memory task would exaggerate local iEEG feature differences between the seizure onset zone (SOZ) and neighboring tissue as compared to wakeful rest (“nontask”). Methods: Ten participants undergoing presurgical iEEG evaluation for DRE performed a free recall verbal memory task. We evaluated three iEEG features in SOZ and non-SOZ electrodes during successful word encoding and compared them with nontask recordings: interictal epileptiform spike (IES) rates, power in band (PIB), and relative entropy (REN; a functional connectivity measure). Results: We found a complex pattern of PIB and REN changes in SOZ and non-SOZ electrodes during successful word encoding compared to nontask. Successful word encoding was associated with a reduction in local electrographic functional connectivity (increased REN), which was most exaggerated in temporal lobe SOZ. The IES rates were reduced during task, but only in the non-SOZ electrodes. Compared with nontask, REN features during task yielded marginal improvements in SOZ classification. Significance: Previous studies have supported REN as a biomarker for epileptic brain. We show that REN differences between SOZ and non-SOZ are enhanced during a verbal memory task. We also show that IESs are reduced during task in non-SOZ, but not in SOZ. These findings support the hypothesis that SOZ and non-SOZ respond differently to task and warrant further exploration into the use of cognitive tasks to identify functioning memory circuits and localize SOZ.