Noninvasive Mapping of Functional and Effective Connectivity in Children with Drug Resistant Epilepsy - Project Summary For children with drug-resistant epilepsy (DRE), resective surgery is the most effective treatment to achieve seizure-freedom. Its success depends on the resection of the epileptogenic zone (EZ). The gold standard to estimate the EZ is by recording seizures with intracranial EEG (iEEG) and localize their onset, namely the seizure onset zone (SOZ). Yet, the SOZ does not always predict outcome, and its delineation often requires several days of recordings to capture seizures. Moreover, iEEG presents limitations due to its invasiveness and often leads to erroneous results. Noninvasive electrophysiological techniques, which can record interictal spikes from the whole brain, could overcome the iEEG limitations. However, spikes suffer from low specificity to the EZ mostly because they propagate across large brain areas forming epileptic networks. These networks are often larger than the EZ and thus may overlap with eloquent areas that should be preserved. Understanding of the functional architecture of the epileptic networks may allow for selective disruption (or modulation) of key components of these networks to halt seizures without removing the entire network. This approach could potentially improve the post-operative seizure control and help prevent post-operative functional deficits. This application aims to construct normative functional and effective connectivity brain maps from typically developing children, assess whether functional and effective connectivity deviations from normative predict the EZ and surgical outcome in children with DRE, and reveal the relationship between propagating interictal activity and information flow among spikes onset and areas of spread. We hypothesize that: (1) hubs with deviated functional and effective connectivity (i.e., high functional connectivity and outwards information flow) from normative identify the EZ in children with DRE; (2) resection of pathological hubs disrupts the epileptogenic network predicting outcome better than the SOZ; (3) information flows outwards from spike onset to areas of spread; and (4) hubs with deviated (from normative) functional and effective connectivity values overlap with the onset of spike propagation. To test our hypotheses, we will pursue the following specific aims: (1) construct normative maps from noninvasive data and compare with data from children with DRE; (2) assess whether functional and effective connectivity deviations from normative maps predict the EZ and surgical outcome; and (3) reveal the relationship between information flow and epileptiform propagating activity. To pursue these aims, we will record HD-EEG and MEG data from 70 children (4-18 years old) with MRE and 70 age- and gender-matched typically developing children. This application combines the use of cutting-edge pediatric neuroimaging instruments and innovative signal processing tools together with extensive neuroimaging experience with children. Our research will have a direct impact on the life of children with DRE since it will provide a new noninvasive biomarker of the EZ that would limit invasive long-term monitoring, augment presurgical planning, prevent post-operative functional deficits, and improve the surgical outcome, particularly children who were previously ineligible for neurosurgery.
