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• We determined the correspondence between the thalamus and the cortex. • The anisotropy of thalamocortical fiber bundles in patients generally declined. • The abnormalities may be related to damage to the myelin sheath of nerve fibers. • The longer the disease duration, the more serious the damage. Epilepsy is one of the most common diseases of the nervous system. Approximately one-third of epilepsy cases are drug-resistant, among which generalized-onset seizures are very common. The present study aimed to analyze abnormalities of the thalamocortical fiber pathways in each hemisphere of the brains of patients with drug-resistant generalized epilepsy. The thalamocortical structural pathways were identified by diffusion tensor imaging (DTI) in 15 patients with drug-resistant generalized epilepsy and 16 gender/age-matched controls. The thalami of both groups were parcellated into subregions according to the local thalamocortical connectivity pattern. DTI measures of thalamocortical connections were compared between the two groups. Probabilistic tractography analyses showed that fractional anisotropy of thalamocortical pathways in patients with epilepsy decreased significantly, and the radial diffusivity of the left thalamus pathways with homolateral motor and parietal-occipital cortical regions in the drug-resistant epilepsy group increased significantly. In addition to the right thalamus pathway and prefrontal cortical region, fractional anisotropy of all other pathways was inversely correlated with disease duration. The results provide evidence indicating widespread bilateral abnormalities in the thalamocortical pathways in epilepsy patients and imply that the degree of abnormality in the pathway increases with the disease duration. [ABSTRACT FROM AUTHOR]