Hermann Bruce, Conant Lisa L, Cook Cole J, Hwang Gyujoon, Garcia-Ramos Camille, Dabbs Kevin, Nair Veena A, Mathis Jedidiah, Bonet Charlene N Rivera, Allen Linda, Almane Dace N, Arkush Karina, Birn Rasmus, DeYoe Edgar A, Felton Elizabeth, Maganti Rama, Nencka Andrew, Raghavan Manoj, Shah Umang, Sosa Veronica N, Struck Aaron F, Ustine Candida, Reyes Anny, Kaestner Erik, McDonald Carrie, Prabhakaran Vivek, Binder Jeffrey R, Meyerand Mary E
Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Neuroimage Clin. 2020;27:102341. doi: 10.1016/j.nicl.2020.102341. Epub 2020 Jul 10.
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患者认知障碍的分类,并对已确定的认知表型的社会人口学、临床和神经生物学相关性进行了特征描述。来自癫痫连接组项目的111例颞叶癫痫患者和83名对照者(平均年龄分别为33岁和39岁,女性分别占57%和61%)接受了神经心理学评估、临床访谈以及高分辨率3T结构和静息态功能磁共振成像检查。一套综合的神经心理学测试组合被简化为核心认知领域(语言、记忆、执行功能、视觉空间、运动速度),然后对其进行聚类分析。对所得的认知亚组在社会人口学和临床癫痫特征以及脑结构和功能连接的差异方面进行了比较。确定了三个认知亚组(正常、语言/记忆/执行功能障碍、全面性障碍),它们在多个特征上以系统的方式存在显著差异。全面性障碍组的特征为开始用药的年龄较早(P<0.05)、患者受教育年限(P<0.001)和父母受教育年限较少(P<0.05)、种族多样性更大(P<0.05)以及终生全面性发作次数更多(P<0.001)。三组在总颅内体积(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)方面也有序地存在差异,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显示出各组在社区结构的全局和局部测量以及枢纽分布方面存在显著差异。静息态功能磁共振成像显示出与聚类成员身份相关的逐步异常,全面性障碍组的连接模式异常最为明显,而认知正常组与对照组无显著差异。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。患者和家族教育及种族方面的认知表型差异,以及总颅内体积的相关差异,引发了关于早期和持续的社会经济地位相关神经发育影响的问题,临床癫痫因素(如终生全面性发作)也有额外作用。认知表型成员的神经影像学特征最显著的是大规模皮质 - 皮质下网络中断以及与双侧海马和小脑萎缩相关的功能连接模式。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风险因素综合影响的特征的影响。