Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

癫痫越来越被概念化为一种网络障碍。在这项横断面大型分析中，我们整合了神经影像学和连接组分析，以识别 1021 名成年癫痫患者与来自 19 个国际地点的 1564 名健康对照者的萎缩模式的网络关联。在颞叶癫痫中，萎缩区域与高度互连的皮质中枢区域共定位，而特发性全身性癫痫表现出优先受累皮质下中枢。这些形态学异常与不同疾病震中的连接特征相关，指向颞叶癫痫中的颞叶边缘皮质和特发性全身性癫痫中的额中央皮质。年龄对萎缩的负面影响进一步揭示了颞叶连接体结构的强烈影响，但不是特发性全身性癫痫。我们的研究结果在各个地点和单个患者中得到了重现，并且在不同的分析方法中都是稳健的。通过 ENIGMA-Epilepsy 的全球合作，我们对影响常见癫痫病理生理学的宏观特征提供了更深入的见解。