From the Department of Clinical and Experimental Epilepsy (L.C., L.A.A., K.T., S.B.V., M.C., M.G., M.K.S., P.J.T., G.P.W., J.S.D., M.J.K.) and Neuroradiological Academic Unit (S.B.V.), UCL Queen Square Institute of Neurology, London; MRI Unit (L.C., L.A.A., K.T., S.B.V., M.C., M.G., M.K.S., P.J.T., G.P.W., J.S.D., M.J.K.), Epilepsy Society, Chalfont St Peter, Buckinghamshire, UK; Departments of Bioengineering (L.C., X.H., D.S.B.), Physics and Astronomy (D.S.B.), Electrical and Systems Engineering (D.S.B.), Neurology (D.S.B.), and Psychiatry (D.S.B.), University of Pennsylvania, Philadelphia; Department of Neurology (K.T.), Medical University of Vienna, Austria; Centre for Medical Image Computing (S.B.V.), University College London, UK; Department of Neurology (M.G.), University Hospital Zurich, Switzerland; Santa Fe Institute (D.S.B.), NM; Department of Medicine, Division of Neurology (G.P.W.), Queen's University, Kingston, Canada; and Department of Neurology (M.R.S.), Thomas Jefferson University, Philadelphia, PA.
Neurology. 2020 Oct 27;95(17):e2427-e2441. doi: 10.1212/WNL.0000000000010645. Epub 2020 Aug 26.
To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.
FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality.
Individuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS.
In TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.
以任务态 fMRI 为框架，研究颞叶癫痫（TLE）中复发性继发性全身性发作的功能相关性，以检测癫痫特有的网络重排。由于丘脑调节颞叶起始性发作的传播，并在认知过程中促进皮质同步，我们假设继发性全身性发作（即局灶性双侧强直阵挛发作[FBTCS]）的发生与丘脑功能障碍、连接改变和全脑网络中心性有关。
FBTCS 发生在三分之一的 TLE 患者中，是疾病严重程度的主要决定因素。在这项横断面研究中，我们分析了 113 名药物难治性 TLE 患者（55 例左侧/58 例右侧），他们进行了一项语言流畅性 fMRI 任务，该任务引起了强烈的丘脑激活。33 名患者（29%）在研究前一年至少经历过一次 FBTCS。我们通过多尺度方法比较了 TLE-FBTCS 患者和无 FBTCS 患者，该方法包括分析统计参数映射（SPM）12 衍生的激活测量值、任务调节的丘脑功能连接（心理生理相互作用）和中心性的图论度量。
与无 FBTCS 患者相比，TLE-FBTCS 患者双侧丘脑、左侧丘脑和左侧海马的任务相关激活减少。在 TLE-FBTCS 中，我们还发现任务相关的丘脑-颞叶和丘脑-运动连接增加，以及更高的丘脑度和中间中心性。基于联合丘脑功能标志物的受试者工作特征曲线准确地区分了有和无 FBTCS 的个体。
在 TLE-FBTCS 中，与增强的丘脑-颞叶连接和全脑丘脑网络嵌入共存的是任务相关的丘脑募集受损。改变的丘脑功能特征被提出作为活跃的继发性泛化的影像学生物标志物。
