Normalized Transfer Entropy as a Tool to Identify Multisource Functional Epileptic Networks

Epilepsy is a major health problem worldwide. A significant proportion of patients develop medication-refractory epilepsy (MRE); they are of ten evaluated for possible surgery where the focus of epileptogenic zones (EZ) are removed from the brain. Hence, prior to epilepsy surgery, insertion of depth electrodes into the brain is necessary to identify the EZs. These depth electrodes have multiple contacts that monitor the neuronal activity in multiple locations within the brain along each electrode trajectory. In the present study, we show that normalized transfer entropy measurements demonstrate functional connectivity across multiple sites within the brain of an MRE patient who did not demonstrate a clear EZ using conventional EEG criteria. Interestingly, linear measures of functional connectivity were not predictive of such an epileptic network. Our results suggest that routine evaluation of both linear and non-linear functional connectivity including normalized transfer entropy from depth electrode recordings may be useful to identify multisource epileptogenic networks in MRE patients. Identification of networks that contribute to epilepsy in such patients could potentially allow the clinician to avoid resective surgery and adopt alternate therapies such as vagal nerve stimulation or other emergent alternatives.