Abstracts

Rationale: A comorbidity of epilepsy is memory impairment. It is thought that inter-ictal epileptiform activity in certain brain regions may interfere with memory formation. In this study, we asked if spikes and high-frequency oscillations (HFO) that spontaneously occur during word presentation in a free recall list learning task decrease the probability of recalling that word correctly. Methods: The patient cohort included 181 subjects who consented to undergo intracranial monitoring and participate in the task. Intracranial EEG was recorded at 500-1600 Hz and analyzed using a spike and HFO detector utilizing a topographical analysis of the depth iEEG wavelet convolution. We quantified spike and HFO events during 118,892 word encoding trials, and confirmed spike and HFO detections using visual validation and annotation editing. The electrode sites were classified using co-registered pre-implant MRI and post-implantation CT images that were segmented on the basis of several published brain atlases.  Results: In the left hemisphere, but not the right, ripples (p< 0.01), fast ripples (p0.05, n=364) nor in the dentate gyrus (p>0.05, n=417). However, spikes in the left entorhinal cortex (prob= -54.2%, p<0.001, n=81) and perirhinal cortex (prob=-15.6%, p<0.01, n=167) did strongly disrupt memory encoding. Encoding was not disrupted by spikes in right mesial temporal lobe structures. Conclusions: These results suggest that normal physiological function in the left entorhinal and perirhinal cortices are required for verbal memory encoding. Also, verbal memory impairment in patients with mesial temporal lobe epilepsy may be attributed, in part, to inter-ictal epileptiform activity in the left entorhinal and perirhinal cortices. Funding: This work was supported by the DARPA Restoring Active Memory (RAM) program (Cooperative Agreement N66001-14-2-4032) and by NSF EPSCoR Award Number 1632738. We thank Medtronic and Blackrock Microsystems for providing neural recording and stimulation equipment. We are indebted to all patients who have selflessly volunteered their time to participate in this study. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of our supporting organizations or the U.S. Government.