Abstracts

Rationale: The thalamo-cortical network has long been recognized as a key pathway in both focal and generalized epileptic syndromes (Bertram, 2013). While numerous neuroimaging studies have indeed demonstrated anomalies in this network in both generalized epilepsy (GE) and temporal lobe epilepsy (TLE), both syndromes have rarely been comprehensively assessed to identify common as well as diverging pathological substrates. The current work leveraged an integrative multi-scale neuroimaging and connectomic paradigm to assess shared and dissociable thalamo-cortical signatures of GE and TLE. Methods: We studied 100 patients with GE (mean age = 25.93±8.03 years, 69 males) and 107 with unilateral TLE (mean age = 27.29±7.81 years, 60 males). Based on ILAE criteria (Fisher et al., 2017), all GE patients had been categorized as those with generalized tonic clonic seizures only. As for TLE, all patients demonstrated the unilateral seizure focus and concordant MRI evidence of hippocampal atrophy. The patient groups were respectively compared to 65 age- and sex-matched healthy controls (mean age = 24.98±4.96 years, 49 males). All individuals underwent multimodal MRI on the same 3T scanner, and a series of surface-based (i.e., cortical thickness, thalamic surface-shape, superficial white matter diffusivity) and connectome (i.e., diffusion MRI tractography, functional connectivity) analyses evaluating thalamo-cortical network changes across different scales. Results: Compared to controls, while both patient groups presented with microstructural and macroscopic anomalies in thalamo-cortical networks, their overall pathoconnectomic signature diverged. Specifically, although both patient cohorts presented with a similar pattern of superficial white matter diffusivity and thalamo-cortical structural connectivity (Figure 1, top), they showed markedly distinct morphological and functional findings. Indeed, while TLE showed extensive atrophy of cortical and mediodorsal thalamic divisions, we did not detect any morphological anomalies in GE compared to controls (Figure 1, bottom). Between-cohort divergence was furthermore supported in the functional domain, by showing mainly increased thalamo-cortical connectivity in GE to bilateral default-mode and limbic networks, while TLE showed ipsilateral decreases to somotomotor and prefrontal cortices, together with scattered increases to anterior temporal cortices (Figure 2). Conclusions: Although our data confirms the long-standing notion of thalamo-cortical involvement across the spectrum of focal and generalized epilepsies, we were able to nevertheless identify syndrome-specific pathoconnectomic signatures at the level of both brain structure and function. References:[1] Bertram EH. Neuronal circuits in epilepsy: do they matter? Exp Neurol 2013; 244: 67-74. [2] Fisher RS, Cross JH, D’Souza C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 2017; 58(4): 531-542. Funding: This project is supported by funding from China Scholarship Council (CSC: 201806190190); the SickKids Foundation (NI17-039); the National Sciences and Engineering Research Council of Canada (NSERC; Discovery-1304413); CIHR (FDN-154298); Azrieli Center for Autism Research (ACAR); an MNI-Cambridge collaboration grant; FRQ-S (Chercheur-Boursier); National Science Foundation of China (NSFC: 81422022; 863 project: 2014BAI04B05 and 2015AA020505), China Postdoctoral Science Foundation (2016M603064).