This study explored the taxonomy of cognitive impairment within temporal lobe epilepsy and characterized the sociodemographic, clinical and neurobiological correlates of identified cognitive phenotypes. 111 temporal lobe epilepsy patients and 83 controls (mean ages 33 and 39, 57% and 61% female, respectively) from the Epilepsy Connectome Project underwent neuropsychological assessment, clinical interview, and high resolution 3T structural and resting-state functional MRI. A comprehensive neuropsychological test battery was reduced to core cognitive domains (language, memory, executive, visuospatial, motor speed) which were then subjected to cluster analysis. The resulting cognitive subgroups were compared in regard to sociodemographic and clinical epilepsy characteristics as well as variations in brain structure and functional connectivity. Three cognitive subgroups were identified (intact, language/memory/executive function impairment, generalized impairment) which differed significantly, in a systematic fashion, across multiple features. The generalized impairment group was characterized by an earlier age at medication initiation (P < 0.05), fewer patient (P < 0.001) and parental years of education (P < 0.05), greater racial diversity (P < 0.05), and greater number of lifetime generalized seizures (P < 0.001). The three groups also differed in an orderly manner across total intracranial (P < 0.001) and bilateral cerebellar cortex volumes (P < 0.01), and rate of bilateral hippocampal atrophy (P < 0.014), but minimally in regional measures of cortical volume or thickness. In contrast, large-scale patterns of cortical-subcortical covariance networks revealed significant differences across groups in global and local measures of community structure and distribution of hubs. Resting-state fMRI revealed stepwise anomalies as a function of cluster membership, with the most abnormal patterns of connectivity evident in the generalized impairment group and no significant differences from controls in the cognitively intact group. Overall, the distinct underlying cognitive phenotypes of temporal lobe epilepsy harbor systematic relationships with clinical, sociodemographic and neuroimaging correlates. Cognitive phenotype variations in patient and familial education and ethnicity, with linked variations in total intracranial volume, raise the question of an early and persisting socioeconomic-status related neurodevelopmental impact, with additional contributions of clinical epilepsy factors (e.g., lifetime generalized seizures). The neuroimaging features of cognitive phenotype membership are most notable for disrupted large scale cortical-subcortical networks and patterns of functional connectivity with bilateral hippocampal and cerebellar atrophy. The cognitive taxonomy of temporal lobe epilepsy appears influenced by features that reflect the combined influence of socioeconomic, neurodevelopmental and neurobiological risk factors.

本研究探讨了颞叶癫痫认知障碍的分类，并描述了已识别认知表型的社会人口统计学、临床和神经生物学相关性。来自癫痫连接组项目的 111 名颞叶癫痫患者和 83 名对照者（平均年龄 33 岁和 39 岁，分别为 57% 和 61% 女性）接受了神经心理学评估、临床访谈以及高分辨率 3T 结构和静息态功能 MRI。全面的神经心理学测试电池被简化为核心认知领域（语言、记忆、执行、视觉空间、运动速度），然后进行聚类分析。对所得认知亚组的社会人口学和临床癫痫特征以及大脑结构和功能连接的变化进行了比较。确定了三个认知亚组（完整、语言/记忆/执行功能障碍、全身性障碍），这些亚组在多个特征上以系统的方式存在显着差异。全身性损伤组的特点是开始用药年龄较早（ P <0.05）、患者较少（ P <0.001）和父母受教育年限（ P <0.05）、种族多样性较高（ P <0.05）和更多终生全身性癫痫发作（ P <0.001）。三组在颅内总体积 ( P < 0.001) 和双侧小脑皮质体积 ( P < 0.01) 以及双侧海马萎缩率 ( P < 0.014) 方面也存在有序差异，但在皮质体积或厚度的区域测量方面差异最小。 相比之下，皮质-皮质下协方差网络的大规模模式揭示了不同群体在社区结构和中心分布的全球和局部测量方面的显着差异。静息态功能磁共振成像显示，逐步异常是簇成员资格的函数，最异常的连接模式在广泛性损伤组中很明显，而与认知完整组中的对照组没有显着差异。总体而言，颞叶癫痫独特的潜在认知表型与临床、社会人口学和神经影像学相关性存在系统关系。患者、家族教育和种族的认知表型差异，以及颅内容积的相关变化，提出了早期和持续的社会经济地位相关的神经发育影响的问题，以及临床癫痫因素（例如，终生全身性癫痫发作）的额外贡献。认知表型成员的神经影像学特征最显着的是大规模皮质-皮质下网络的破坏以及双侧海马和小脑萎缩的功能连接模式。颞叶癫痫的认知分类似乎受到反映社会经济、神经发育和神经生物学危险因素综合影响的特征的影响。