Abstracts

Rationale: The optimal treatment of patients with uncontrollable seizures often involves identifying the epileptogenic tissue and aiming for its complete resection. However, cognitive deficits ensuing such surgical resections, especially of non-lesional brain sites, remain of critical concern. Moreover, it remains unclear to what extent the epileptic tissue is capable of generating physiological responses to cognitive stimuli, and if so, how these responses are affected by ongoing spontaneous epileptic activity. Methods: We recruited six patients with intracranial electrode coverage in either visual association cortex (N=3) or in the medial temporal lobes (MTL, N=3) who participated in site-relevant cognitive experiments. We identified the epileptic focus in each patient and measured their spontaneous high-frequency oscillations (HFOs, 80 - 500 Hz) as well as stimulus-locked physiological responses in high-frequency broadband (HFB, 70 - 180 Hz) range and explored their interaction and behavioral correlates. We compared the temporal and spectral profiles of HFOs and HFB signals and calculated the probability of temporal discordance during the same behavioral tasks. In addition, we introduce a computerized method on the basis of which pathological and physiological high-frequency activities can be automatically differentiated and performed the prediction with a supervised SVM classifier. Results: Consistently in all subjects, we found abundant normal physiological responses to relevant cognitive stimuli in the epileptic sites, but they were likely to be missed or delayed when spontaneous HFOs occurred approximately 850-1050ms before, till about 150-250ms after, the onset of relevant cognitive stimuli. Ongoing spontaneous HFOs in the MTL also significantly impacted the subjects' reaction time, hit rate, and confidence scoring during the memory task (p < 0.5). The SVM classifier successfully separated HFOs from HFBs using our proposed features, achieving an AUC value of 0.98.  Conclusions: Our findings clearly suggest that non-lesional brain structures involved with epileptogenicity elicit normal physiological responses to cognitive stimuli, but these responses are transiently impaired by preceding spontaneous high-frequency oscillations with subsequent behavioral effects. We highlight a compelling mechanism for cognitive deficits in patients with focal epilepsy. We also offer clinicians a quantitative tool for differentiating pathological and physiological activities in epileptic sites and indirectly assessing their possible cognitive reserve function and approximating the risk of resective surgery. Funding: No funding