Connectome architecture for gray matter atrophy and surgical outcomes in temporal lobe epilepsy.

Objective: Temporal lobe epilepsy (TLE) has been recognized as a network disorder with widespread gray matter atrophy. However, the role of connectome architecture in shaping morphological alterations and identifying atrophy epicenters remains unclear. Furthermore, individualized modeling of atrophy epicenters and their potential clinical applications have not been well established. This study aims to explore how gray matter atrophy correlates with normal connectome architecture, identify potential atrophy epicenters, and employ individualized modeling approach to evaluate the impact of different epicenter patterns on surgical outcomes in patients with TLE.

Methods: This study utilized anatomic MRI data from 126 refractory TLE patients who underwent anterior temporal lobectomy and 60 healthy controls (HCs), along with normative functional and structural connectome data, to investigate the relationship between gray matter volume (GMV) changes and functional or structural connectivity. Two models were employed to identify atrophy epicenters: a data-driven approach evaluating nodal and neighbor atrophy rankings, and a network diffusion model (NDM) simulating the spread of pathology from different seed regions. K-means clustering was applied in patient-tailored modeling to uncover distinct epicenter subtypes.

Results: Our findings indicate that the pattern of gray matter atrophy in TLE is constrained primarily by structural connectivity rather than by functional connectivity. Using the structural connectome, we pinpointed the hippocampus and adjacent temporo-limbic regions as key atrophy epicenters. The patient-tailored modeling revealed significant variability in epicenter distribution, allowing us to categorize them into two distinct subtypes. Notably, patients in subtype 2, with epicenters localized to the ipsilateral temporal pole and medial temporal lobe, exhibited significantly higher seizure-free rates compared to patients in subtype 1, whose epicenters situated in frontocentral regions.

Significance: These findings highlight the central role of structural connectivity in shaping TLE-related morphological changes. Individualized epicenter modeling may enhance surgical decisions and improve prognostic stratification in TLE management.