Diffusion tensor imaging reveals altered structural connectivity of the mesial frontal lobe in juvenile myoclonic epilepsy

Rationale: Juvenile myoclof thnic epilepsy is the most common idiopathic generalized epilepsy in adults, characterized by myoclonic jerks, often provoked by cognitive stressors. Recently functional MRI (fMRI) showed increased functional connectivity between the motor system and higher cognitive networks. It is still unclear if this is a purely functional effect, or if there are underlying structural changes, facilitating this mechanism. Methods: We acquired brain diffusion tensor images in 28 patients with JME and 28 healthy controls on a GE Signa HDx 3T MRI scanner (2×2×2.4mm, 60 slices, 52 diffusion weighted directions) We performed connectivity based parcellation of a mesial frontal region of interest into the supplementary motor area (SMA) and pre-SMA. Probabilistic tractography from both subregions, the SMA and pre-SMA was carried out and voxel-wise whole brain analysis was applied to reveal group differences in the resulting connectivity maps. Results: Patients with JME showed increased structural connectivity of the pre-SMA region to the central region (p<0.001, cluster size >100 voxels) and this correlated positively with functional connectivity measures from fMRI (R=0.47). Pre-SMA connectivity was also increased to descending motor pathways, while it was reduced to the frontopolar region. TheSMA region on the other hand showed increased structural connectivity to the occipital lobe and temporal neocortex and reducedconnectivity to the central region. Conclusions: DTI based connectivity maps revealed an increased structural connectivity between the pre-SMA region and the central region in JME. This seems to be the structural basis for the increased functional connectivity between the motor system and cognitive areas and provides an explanation how cognitive effort can trigger motor seizures in JME. These alterations may also be the correlate of previously reported morphometric changes in the mesial frontal lobes in JME.