Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI

BACKGROUND AND PURPOSE: The frequency of seizures is an important factor that can alter functional brain connectivity. Analysis of this factor in patients with epilepsy is complex because of disease- and medication-induced confounders. Because patients with hot-water epilepsy generally are not on long-term drug therapy, we used seed-based connectivity analysis in these patients to assess connectivity changes associated with seizure frequency without confounding from antiepileptic drugs. MATERIALS AND METHODS: Resting-state fMRI data from 36 patients with hot-water epilepsy (18 with frequent seizures [>2 per month] and 18 with infrequent seizures [2 per month]) and 18 healthy age- and sex-matched controls were analyzed for seed-to-voxel connectivity by using 106 seeds. Voxel wise paired t-test analysis (P < .005, corrected for false-discovery rate) was used to identify significant intergroup differences between these groups. RESULTS: Connectivity analysis revealed significant differences between the 2 groups (P < .001). Patients in the frequent-seizure group had increased connectivity within the medial temporal structures and widespread areas of poor connectivity, even involving the default mode network, in comparison with those in the infrequent-seizure group. Patients in the infrequent-seizure group had focal abnormalities with increased default mode network connectivity and decreased left entorhinal cortex connectivity. CONCLUSIONS: The results of this study suggest that seizure frequency can alter functional brain connectivity, which can be visualized by using resting-state fMRI. Imaging features such as diffuse network abnormalities, involvement of the default mode network, and recruitment of medial temporal lobe structures were seen only in patients with frequent seizures. Future studies in more common epilepsy groups, however, will be required to further establish this finding.