Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada; Analytical Neurophysiology Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Prog Neurobiol. 2024 May;236:102604. doi: 10.1016/j.pneurobio.2024.102604. Epub 2024 Apr 10.
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.
颞叶癫痫（TLE）是成人中最常见的药物难治性癫痫。虽然主要与内侧颞叶病理学有关，但最近的证据表明 TLE 中的大脑改变不仅局限于边缘区中心，还会影响宏观功能和认知功能，尤其是记忆。我们使用连接组全脑流形学习和有效连接的生成模型，研究了 TLE 患者静息状态下的大规模神经回路之间的功能拓扑和定向信号流模式。通过对 95 名 TLE 患者和 95 名健康对照者的多站点队列进行研究，我们观察到前者的功能拓扑存在异常，表现为感觉和跨模态联合皮质之间的分化减少，双侧颞叶-边缘和腹内侧前额皮质的效应最为显著。这些发现跨越了所有研究地点，存在于左侧和右侧偏侧化的患者中，在具有内侧颞叶硬化症组织病理学验证和手术后无癫痫发作的患者亚组中得到验证。此外，在 30 名 TLE 患者和 40 名健康对照者的独立队列中也得到了复制。进一步的分析表明，分化减少与颞叶边缘皮质系统和其他脑网络的功能信号流入和流出减少有关。结构和弥散加权 MRI 数据的平行分析表明，拓扑改变与 TLE 相关的皮质变薄无关，但部分由远离边缘回路的白质微观结构变化介导。最后，我们发现功能改变的程度与记忆功能障碍的行为标志物之间存在很强的关联。我们的工作说明了 TLE 中宏观功能失衡的复杂情况，它可以作为连接微观结构变化和认知障碍的中间标志物。
