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ObjectivesOne third of patients with drug resistant focal mesial temporal lobe epilepsy (MTLE) fail to achieve long-term seizure freedom following temporal lobe resections. Reasons for failure may include ictal onset outside the temporal lobe (TL), termed ‘pseudotemporal lobe epilepsy’ (pTLE), with propagation from strongly connected neighboring areas or temporal plus (TL+) epilepsy, when the epileptogenic zone primarily involves the temporal lobe and also extends to neighboring regions. In such cases the perisylvian and orbito-frontal (OF) cortices, cingulum and temporo-parieto-occipital junction may be implicated. Stereoelectroencephalography (SEEG) is a procedure in which electrodes are stereotactically placed within predefined brain regions to delineate the SOZ and allows evaluation of deep anatomical structures adjacent to the TL. SEEG electrode contacts sample from a core radius of 3–5 mm. It is unclear which sub-regions of target structures should be preferentially implanted to optimally detect the network involved in seizure onset and rapid propagation. Using normalized average group templates of structural connectivity from patients with hippocampal sclerosis (HS), we determine the greatest connectivity to critical sub-regions and based upon this propose optimal locations for SEEG targeting.DesignObservational cross-sectional study.SubjectsTwelve patients with HS (6 right) that had undergone SEEG and pre-operative diffusion imaging were identified from a prospectively maintained database.MethodsWhole brain connectomes with 10 million tracts were generated using cortical seed regions derived from whole brain GIF parcellations. Normalized group templates were generated separately for right and left HS patients. Orbitofrontal cortex (OF), insula (INS), cingulum (Cing) and temporo-parietal-occipital junction (supramarginal gyrus, angular gyrus, precuneus, fusiform gyrus and lingual gyrus) were segmented into surgically targetable subregions. All subregions had similar volumes. Connectivity of the amygdalohippocampal complex (AHC) was defined based on the number of streamlines terminating in the subregions of interest.ResultsLeft HS showed preferential connections to the ipsilateral: posterior part of lateral OF cortex, posterior short gyrus of anterior INS, posterior part of the posterior Cing, middle part of lingual gyrus, posterior part of precuneus and middle part of fusiform gyrus. Right HS showed preferential connections to the ipsilateral: posterior part of the lateral OF cortex, anterior long gyrus of posterior INS, posterior part of posterior Cing, anterior part of lingual gyrus and posterior part of precuneus.ConclusionsUsing whole brain connectomes we determine surgically feasible targets in sub-regions based on greatest connectivity to the AHC. We propose that SEEG targeting utilizing computer-assisted planning may improve the understanding of the overall network connectivity in order to enhance the diagnostic utility of the SEEG implantation. SEEG electrode placement within structures associated with pTLE and TL +may aid in delineating the SOZ if the correct sub-regions are targeted. This should be evaluated prospectively.