Ke Xie , Jessica Royer , Sara Larivière , Raul Rodriguez-Cruces , Stefan Frässle , Donna Gift Cabalo , Alexander Ngo , Jordan DeKraker , Hans Auer , Shahin Tavakol , Yifei Weng , Chifaou Abdallah , Thaera Arafat , Linda Horwood , Birgit Frauscher , Lorenzo Caciagli , Andrea Bernasconi , Neda Bernasconi , Zhiqiang Zhang , Luis Concha , Boris C. Bernhardt
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Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. 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引用次数: 0
摘要
颞叶癫痫(TLE)是成人中最常见的药物抵抗性癫痫。虽然颞叶癫痫主要与颞中叶病理学有关,但最近的证据表明,颞叶癫痫的大脑改变超出了颞叶旁中心,影响了宏观功能和认知功能,尤其是记忆。利用全连接体流形学习和有效连接生成模型,我们研究了静息状态下 TLE 大尺度神经回路之间的功能拓扑和定向信号流模式。在对95名TLE患者和95名健康对照者的多点队列研究中,我们观察到前者的非典型功能拓扑图,其特征是感觉皮层和跨模态联想皮层之间的分化减少,在双侧颞叶边缘和腹内侧前额叶皮层的影响最为明显。这些发现在所有研究部位都是一致的,存在于左侧化和右侧化的患者中,并在组织病理学验证为中颞叶硬化和手术后无癫痫发作的患者亚组中得到了验证。此外,这些结果还在由30名TLE患者和40名健康对照者组成的独立队列中得到了验证。进一步的分析表明,分化减少与进出颞叶皮层系统和其他大脑网络的功能信号流减少有关。对结构和弥散加权核磁共振成像数据的平行分析表明,地形改变独立于与 TLE 相关的皮质变薄,但部分是由白质微结构变化介导的,而白质微结构变化又从边缘环路辐射开来。最后,我们发现功能改变的程度与记忆功能障碍的行为标记之间存在密切联系。我们的研究说明了系统性红斑狼疮的宏观功能失衡的复杂情况,它可以作为连接微结构变化和认知障碍的中间标志物。
Atypical connectome topography and signal flow in temporal lobe epilepsy
Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.
期刊介绍:
Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.