Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Brain. 2023 Mar 1;146(3):935-953. doi: 10.1093/brain/awac150.
Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.
认知障碍是癫痫的常见共病，会对额叶（FLE）和颞叶（TLE）癫痫患者造成不利影响。虽然 TLE 中的其神经基础已被广泛研究，但 FLE 中的功能影像学研究却很少。在这项研究中，我们对 FLE 中认知障碍的神经过程进行了描绘，并直接将 FLE 和 TLE 进行比较，以确定它们的共性和差异。我们使用神经心理学测试和四项功能磁共振成像任务（语言表达[言语流畅性、动词生成]和工作记忆[言语和视空间]）对 172 名成年参与者（56 名 FLE、64 名 TLE 和 52 名对照者）进行了研究。患者组在疾病持续时间和抗癫痫药物负荷方面具有可比性。我们设计了一种多尺度方法来描绘认知过程中的大脑激活和去激活，并追踪 FLE 和 TLE 中的重组。基于体素的分析方法补充了对功能脑区组织的既定模式（i）经典静息态功能系统；和（ii）主要功能连接梯度的任务效应分析，该梯度编码了区域连接图谱的连续变化，将较低级别的感觉和跨模态脑区锚定在频谱的两端。我们表明，FLE 中的认知障碍与注意力和执行系统的激活减少以及默认模式系统的去激活减少有关，这表明与任务相关的招募出现了大范围的紊乱。FLE 中功能障碍的影像学特征与 TLE 中的大致相似，但有些模式是综合征特异性的：FLE 中默认模式去激活更为明显，而 TLE 中在具有语义要求的任务中，后部语言区的募集受损更为明显。FLE 和 TLE 的功能异常总体上受疾病负荷的调节。总的来说，我们的研究阐明了 FLE 中语言和工作记忆障碍的神经过程，确定了两种最常见的局灶性癫痫的共同和综合征特异性改变，并阐明了可能适用于未来矫正策略的系统行为。
