Dissecting the Cognitive Roles of Hippocampus and Other Temporal Lobe Structures in Patients Undergoing Epilepsy Surgery

项目总结： 我们进行了最大规模的激光杏仁核海马区切开术(SLAH)的前瞻性对比研究。 微创手术消融杏仁核-海马复合体(AHC)与选择性消融和标准消融的比较 开放切除(OR)癫痫手术(425+)。我们在1年内证明了SLAH优于OR 成年人的认知结果(包括情景言语记忆和知觉(语义)再认或名字 取回物体/面部)，同时实现类似的癫痫控制。我们将扩展我们的分析 在纵向上以前所未有的方式(5-10年成果)利用这一独特的经过充分研究的队列 患者包括神经心理(NP)、结构和功能神经成像和癫痫结果。 我们还收集了大量涉及非AHC的立体定向激光消融的病例样本。 结构。这些SLA病例的异质性和激光消融手术区域的焦点性质造成 这是进行损伤行为分析的绝佳机会。我们将扩展我们的神经成像分析，以包括 严格的体素病变症状图(VLSM)和新的扩散连通性建模方法 张量成像和静息功能磁共振成像。我们将重点介绍负责陈述性记忆的神经回路 和语言，同时确定产生最佳长期认知和癫痫发作的最佳手术区域 结果。VLSM使我们能够确定哪些颞叶区域对特定认知至关重要 功能，而连通性分析将揭示这些区域在个体中的相互联系 患者(使我们能够在患者水平上确定下降的相对风险)。 我们的初步研究结果表明：1)SLAH患者表现出出乎意料的改善 认知功能，这在他们的OR同行中是无与伦比的，以及2)第二语言习得程序省去了AHC 而更宽的内侧目标语区域往往会导致言语记忆/命名能力的严重下降，尤其是在 语言占优势的颞极或梭形回局灶性消融4例。这表明口头上 陈述性记忆依赖于一个超越AHC的广泛网络，这是一种范式转变 手术计划(即，在手术过程中被认为是消耗性的区域实际上对 功能)。从机械学和临床翻译的角度来看，这种知识是非常重要的 我们的数据和有计划的分析提供了一种独特而可行的方式来得出可靠的结论 长期存在的知识鸿沟。我们的数据对现有的声明性内存模型提出了关键问题 在许多SLAH/SLA病例中，高级认知结果背后的恢复机制(例如， 功能备份与重组)，我们将在这次更新中通过跟踪我们的患者 时间到了。最后，虽然更多的癫痫中心正在使用SLA，因为它改善了认知结果，但最终 临床采用取决于癫痫控制，因此确定较长时间跨度的SLAH疗效至关重要。

Project Summary: We have conducted the largest prospective comparative study of laser amygdalohippocampotomy (SLAH), a minimally invasive procedure ablating the amygdalo-hippocampal complex (AHC) versus selective and standard open resection (OR) epilepsy surgery (N=425+). We demonstrated that SLAH is superior to OR in 1-year cognitive outcomes in adults (including episodic verbal memory & perceptual (semantic) recognition or name retrieval of objects/faces), while achieving comparable seizure control. We will extend our analysis longitudinally in an unprecedented manner (5-10 year outcome) leveraging this unique cohort of well-studied patients including neuropsychological (NP), structural and functional neuroimaging and seizure outcomes. We have also amassed a large sample of cases involving stereotactic laser ablation [SLA] of non-AHC structures. The heterogeneity of these SLA cases and the focal nature of the laser ablation surgical zones create an amazing opportunity for lesion-behavioral analyses. We will expand our neuroimaging analyses to include rigorous voxel lesion symptom mapping (VLSM) and novel methods of connectivity modeling with diffusion tensor imaging and resting state fMRI. We will focus on the neural circuitry responsible for declarative memory and language, while determining the optimal surgical zones to produce the best long-term cognitive and seizure outcomes. VLSM allows us to determine which temporal lobe regions are critical for specific cognitive functions, while connectivity analyses will reveal the interconnectedness of these regions in the individual patient (allowing us to determine the relative risk of decline at the patient level). Our preliminary findings indicate that: 1) SLAH patients exhibit unexpected improvement in multiple cognitive functions, which is unparalleled in their OR counterparts, and 2) SLA procedures sparing the AHC and broader medial TL regions frequently lead to severe decline in verbal memory/naming, particularly in cases of focal ablations of the language dominant temporal pole or fusiform gyrus. This suggests that verbal declarative memory depends upon a broad network extending beyond the AHC, which is a paradigm shift for surgical planning (i.e., regions thought to be expendable during surgical approach are actually critical to function). This knowledge is fundamentally important from mechanistic and clinical translational points of view, and our data and planned analyses provide a unique and feasible way to draw robust conclusions on these long-standing knowledge gaps. Our data raise pivotal questions about existing declarative memory models and the mechanism of recovery underlying the superior cognitive outcomes in many SLAH/SLA cases (e.g., functional sparing vs. reorganization), which we will address in this renewal by following our patients over time. Finally, while more epilepsy centers are employing SLA due to its improved cognitive outcomes, ultimate clinical adoption rests on seizure control, making it critical to determine SLAH efficacy over a longer time span.