Fadaie Fatemeh, Lee Hyo M, Caldairou Benoit, Gill Ravnoor S, Sziklas Viviane, Crane Joelle, Bernhardt Boris C, Hong Seok-Jun, Bernasconi Andrea, Bernasconi Neda
Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Epilepsia. 2021 Nov;62(11):2589-2603. doi: 10.1111/epi.17032. Epub 2021 Sep 7.
Drug-resistant temporal lobe epilepsy (TLE) is typically associated with hippocampal pathology. However, widespread network alterations are increasingly recognized and suggested to perturb cognitive function in multiple domains. Here we tested (1) whether TLE shows atypical cortical hierarchical organization, differentiating sensory and higher order systems; and (2) whether atypical hierarchy predicts cognitive impairment.
We studied 72 well-characterized drug-resistant TLE patients and 41 healthy controls, statistically matched for age and sex, using multimodal magnetic resonance imaging analysis and cognitive testing. To model cortical hierarchical organization in vivo, we used a bidirectional stepwise functional connectivity analysis tapping into the differentiation between sensory/unimodal and paralimbic/transmodal cortices. Linear models compared patients to controls. Finally, we assessed associations of functional anomalies to cortical atrophy and microstructural anomalies, as well as clinical and cognitive parameters.
Compared to controls, TLE presented with bidirectional disruptions of sensory-paralimbic functional organization. Stepwise connectivity remained segregated within paralimbic and salience networks at the top of the hierarchy, and sensorimotor and dorsal attention at the bottom. Whereas paralimbic segregation was associated with atypical cortical myeloarchitecture and hippocampal atrophy, dysconnectivity of sensorimotor cortices reflected diffuse cortical thinning. The degree of abnormal hierarchical organization in sensory-petal streams covaried, with broad cognitive impairments spanning sensorimotor, attention, fluency, and visuoconstructional ability and memory, and was more marked in patients with longer disease duration and Engel I outcome.
Our findings show atypical functional integration between paralimbic/transmodal and sensory/unimodal systems in TLE. Differential associations with paralimbic microstructure and sensorimotor atrophy suggest that system-level imbalance likely reflects complementary structural processes, but ultimately accounts for a broad spectrum of cognitive impairments. Hierarchical contextualization of cognitive deficits promises to open new avenues for personalized counseling in TLE.
耐药性颞叶癫痫（TLE）通常与海马病变相关。然而，广泛的网络改变越来越受到认可，并被认为会干扰多个领域的认知功能。在此，我们测试了：（1）TLE是否表现出非典型的皮质层次组织，区分感觉系统和高阶系统；以及（2）非典型层次结构是否预测认知障碍。
我们研究了72例特征明确的耐药性TLE患者和41名年龄和性别在统计学上匹配的健康对照者，采用多模态磁共振成像分析和认知测试。为了在体内模拟皮质层次组织，我们使用了双向逐步功能连接分析，以探究感觉/单模态与边缘旁/跨模态皮质之间的差异。线性模型将患者与对照者进行比较。最后，我们评估了功能异常与皮质萎缩和微观结构异常以及临床和认知参数之间的关联。
与对照者相比，TLE表现出感觉-边缘旁功能组织的双向破坏。逐步连接在层次结构顶部的边缘旁和显著网络内保持分离，在底部的感觉运动和背侧注意网络内也保持分离。虽然边缘旁分离与非典型的皮质髓鞘结构和海马萎缩相关，但感觉运动皮质的连接障碍反映了弥漫性皮质变薄。感觉-花瓣状流中异常层次组织的程度与广泛的认知障碍相关，这些障碍涵盖感觉运动、注意力、流畅性、视觉构建能力和记忆，并且在病程较长和Engel I级结果的患者中更为明显。
我们的研究结果表明TLE中边缘旁/跨模态与感觉/单模态系统之间存在非典型的功能整合。与边缘旁微观结构和感觉运动萎缩的不同关联表明，系统水平的失衡可能反映了互补的结构过程，但最终导致了广泛的认知障碍。认知缺陷的层次背景化有望为TLE的个性化咨询开辟新途径。
