Visual assessment of structural MRI is, by definition, normal in patients with juvenile myoclonic epilepsy (JME), a major subsyndrome of idiopathic generalized epilepsy (IGE). However, recent quantitative MRI studies have shown structural abnormalities in cortical and thalamic grey matter (GM) in JME. Voxel-based morphometry (VBM) is a fully automated, unbiased, operator-independent MRI analysis technique that detects regionally specific differences in brain tissue composition on a voxel-wise comparison between groups of subjects. Using VBM, we examined structural differences in cortical and subcortical GM volume (GMV) between 25 JME patients (15 women, mean age=22.7+/-5.1 years) and age- and sex-matched 44 control subjects (27 women, mean age=23.1+/-4.3 years). We also performed a correlation analysis to delineate a possible relationship between the GMV increases or reductions and the increasing duration of epilepsy. Group comparison showed GMV increases in the superior mesiofrontal region bilaterally and GMV reductions in the thalamus bilaterally in JME patients (P<0.05, corrected for multiple comparisons using false discovery rate). Correlation analysis revealed that bilateral thalamic GMV had negative correlations with the duration of epilepsy (P<0.05, corrected for multiple comparisons after small volume corrections; P<0.05, Pearson correlation test). Our findings of GMV increases in the superior mesiofrontal regions and progressive thalamic atrophy could further support the pathophysiological concept of the functional abnormalities in thalamocortical circuit in JME.