Widespread changes in network activity allow non-invasive detection of mesial temporal lobe seizures

Decades of experience with intracranial recordings in patients with epilepsy have demonstrated that seizures can occur in deep cortical regions such as the mesial temporal lobes without showing any obvious signs of seizure activity on scalp electroencephalogram. Predicated on the idea that these seizures are purely focal, currently, the only way to detect these 'scalp-negative seizures' is with intracranial recordings. However, intracranial recordings are only rarely performed in patients with epilepsy, and are almost never performed outside of the context of epilepsy. As such, little is known about scalp-negative seizures and their role in the natural history of epilepsy, their effect on cognitive function, and their association with other neurological diseases. Here, we developed a novel approach to non-invasively identify scalp-negative seizures arising from the mesial temporal lobe based on scalp electroencephalogram network connectivity measures. We identified 25 scalp-negative mesial temporal lobe seizures in 10 patients and obtained control records from an additional 13 patients, all of whom underwent recordings with foramen ovale electrodes and scalp electroencephalogram. Scalp data from these records were used to train a scalp-negative seizure detector, which consisted of a pair of logistic regression classifiers that used scalp electroencephalogram coherence properties as input features. On cross-validation performance, this detector correctly identified scalp-negative seizures in 40% of patients, and correctly identified the side of seizure onset for each seizure detected. In comparison, routine clinical interpretation of these scalp electroencephalograms failed to identify any of the scalp-negative seizures. Among the patients in whom the detector raised seizure alarms, 80% had scalp-negative mesial temporal lobe seizures. The detector had a false alarm rate of only 0.31 per day and a positive predictive value of 75%. Of the 13 control patients, false seizure alarms were raised in only one patient. The fact that our detector specifically recognizes focal mesial temporal lobe seizures based on scalp electroencephalogram coherence features, lends weight to the hypothesis that even focal seizures are a network phenomenon that involve widespread neural connectivity. Our scalp-negative seizure detector has clear clinical utility in patients with temporal lobe epilepsy, and its potential easily translates to other neurological disorders, such as Alzheimer's disease, in which occult mesial temporal lobe seizures are suspected to play a significant role. Importantly, our work establishes a novel approach of using computational approaches to non-invasively detect deep seizure activity, without the need for invasive intracranial recordings.