Cortical wiring cost abnormalities in mesial temporal lobe epilepsy with hippocampal sclerosis: implications for postoperative seizure recurrence

OBJECTIVE Postoperative seizure recurrence in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) has been linked to alterations in structural network organization. However, existing studies have primarily focused on white matter pathways, while gray matter wiring attributes remain largely unknown. This study aimed to investigate whether alterations in gray matter wiring costs are associated with postoperative seizure recurrence in mTLE with HS. METHODS Forty-seven patients with unilateral mTLE who underwent surgery and 48 matched healthy controls were enrolled in the study. All patients had pathologically confirmed HS and were classified as seizure-free (SF; n = 27) or non–seizure-free (NSF; n = 20) with ≥ 2 years of follow-up. Based on preoperative 3D T1-weighted MRI, surface-based geodesic metrics were computed as proxies of cortical wiring costs. Global and local wiring costs were compared across groups, and a support vector machine (SVM) classifier was used to determine their individual-level classification value for postoperative seizure outcomes. RESULTS Global wiring costs decreased in the ipsilateral temporal cortex in patients with mTLE-HS, with a more significant and widespread reduction in the NSF group. Local wiring costs showed diffuse intra- and interregional abnormalities within the sensorimotor and default mode networks in patient groups, with more pronounced disturbances in the NSF group. These wiring abnormalities were not affected by hippocampal subfield atrophy, epilepsy duration, or antiseizure medications, and could train SVM models to distinguish NSF patients from SF patients (area under the receiver operating characteristic curve = 0.86). CONCLUSIONS Abnormalities of cortical wiring costs were observed in mTLE-HS, particularly in patients with postoperative seizure recurrence. These abnormalities may reflect increased long-range connectivity and short-range reorganization within gray matter, offering novel insights into the underlying pathophysiology of this illness and providing potential for outcome prediction.