BACKGROUND: We investigated the relationship of piriform cortex (PC) structural network centrality with drug resistance and epilepsy duration as markers of sustained epileptic activity. METHODS: PCs were manually delineated on retrospectively collected 3D-T1-MRI images of patients with temporal lobe epilepsy (TLE). Connectomes were computed from diffusion MRI scans, including the PC as network nodes. Betweenness centrality (BC) and node degree were computed and compared across drug-resistant versus drug-sensitive patients. Correlations of centrality metrics with the duration of epilepsy were calculated. RESULTS: Sixty-two patients (36 females, 43/62 drug-resistant) were included in the main analysis. Greater centrality of the left PC was associated with drug resistance (degree: p = 0.00696, d = 0.85
BC: p = 0.00859, d = 0.59
alpha = 0.0125). Furthermore, left PC centrality was correlated with epilepsy duration (degree: rho = 0.39, p = 0.00181
BC: rho = 0.35, p = 0.0047
alpha = 0.0125). Results were robust to analysis of different parcellation schemes. Exploratory whole-network analysis yielded the largest effects in the left PC. Finer parcellations showed stronger effects for both analyses in the left olfactory cortex rostral to PC. In 28 subjects who had received epilepsy surgery, a trend of smaller centrality in patients with ILAE I outcome was observed in this area. CONCLUSIONS: We demonstrated an increased centrality of the left PC in patients with drug-resistant TLE, which was also associated with the epilepsy duration. Recurring seizures over long periods may lead to changes of network properties of the PC. Large effects immediately rostral to our delineated PC region suggest a role of olfactory cortex anterior to the limen insulae in epileptogenic networks.