Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Brain. 2024 Nov 4;147(11):3918-3932. doi: 10.1093/brain/awae197.
Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.
陈述性记忆包括情节记忆和语义记忆。情节记忆捕捉具有特定时空关系的单一事件，而语义记忆则存储独立于上下文的知识。行为和功能神经影像学研究揭示了这两个记忆系统的共同和独特的神经基础，涉及中颞叶（MTL）区域，如海马体和分布的新皮质。在这里，我们探索了单侧颞叶癫痫（TLE）患者的陈述性记忆系统重组，作为一种人类疾病模型，以测试 MTL 病变程度对记忆功能的影响。我们的队列包括 31 名 TLE 患者和 60 名年龄和性别匹配的健康对照者，所有参与者在多模态 MRI 检查期间进行了情节记忆和语义记忆检索任务。功能 MRI 任务在刺激和试验设计方面非常匹配。利用非线性连接组梯度映射技术，我们在 MTL 和新皮质网络中得出了情节和语义记忆状态下基于任务的功能拓扑。比较 TLE 患者和健康对照组的新皮质和海马体功能梯度，我们观察到在情节记忆状态下，新皮质和 MTL 系统都发生了明显的拓扑重组。新皮质的改变表现为在双侧颞叶和中线顶叶皮质中，TLE 患者的功能分化减少。相比之下，在 MTL 中，患者表现出对侧海马体节段的功能分化更加明显，与癫痫灶和病理核心相对应，表明海马体内部连接受到干扰。在双侧颞叶和同侧角区也发现了语义记忆的重组，而海马体的功能拓扑不受影响。此外，利用 MTL 病理的 MRI 代理，我们观察到海马体微观结构和形态的改变与 TLE 相关的功能重组有关。此外，相关分析和统计中介模型显示，这些功能改变导致了患者在情节记忆中的行为缺陷，但在语义记忆中则没有。总之，我们的发现表明，语义过程依赖于分布的新皮质网络，而情节过程则由一个涉及海马体和新皮质的网络支持。在与 MTL 损伤相关的情况下，如 TLE，这种网络的改变可以为与状态相关的重组提供紧凑的特征。
