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In ENIGMA-Epilepsy DTI, we will investigate voxelwise white matter (WM) variation in a phenotypically heterogeneous group of people with epilepsy compared to a group of neurologically healthy controls. Previous DTI studies have illustrated microstructural disruptions in the majority of WM tracts for people with temporal lobe epilepsy¹⁷, with the most profound changes occurring ipsilateral to the side of seizure onset, close to the seizure onset zone. Previous DTI investigations have also revealed significant impairments of the thalamocortical circuitry in juvenile myoclonic epilepsy¹⁸, childhood absence epilepsy¹⁹ and idiopathic generalized epilepsy²⁰. Cellular studies have similarly implicated the thalamocortical circuitry in the generation of spike-wave seizures, which are a common feature of generalized epilepsy²¹.

Similar to ENIGMA-Epilepsy GRAY MATTER, ENIGMA-Epilepsy DTI will initially consider WM changes in people with epilepsy as a whole – testing the hypothesis that people with epilepsy have widespread disruptions of the white matter skeleton when compared to neurologically healthy controls. Follow-up analyses may explore more specific patterns of WM alteration in sub-groups of epilepsy patients; e.g. focal epilepsies, generalized epilepsies and mesial temporal lobe epilepsy, all in large* numbers of patients.