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

剖析海马和其他颞叶结构在癫痫手术患者中的认知作用

• 批准号: 10613065
• 负责人: DANIEL L DRANE
• 金额: $ 11.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613065
• 关键词: Ablation; Activities of Daily Living; Address; Adoption; Adult; Affect; Amaze; Anatomy; Behavioral; Belief; Benchmarking; Brain region; Clinical; Cognition; Cognitive; Comparative Study; Complex; Data; Diffusion Magnetic Resonance Imaging; Epilepsy; Excision; Exhibits; Face; Freedom; Functional Magnetic Resonance Imaging; Fusiform gyrus; Goals; Heterogeneity; Hippocampus (Brain); Human; Individual; Influentials; Knowledge; Language; Lasers; Lead; Learning; Left; Lesion; Living Wills; Location; Measures; Medial; Memory; Methods; Modeling; Names; Nature; Neuropsychological Tests; Neuropsychology; Operative Surgical Procedures; Outcome; Patients; Postoperative Period; Procedures; Prospective Studies; Recovery; Recovery of Function; Relative Risks; Rest; Retrieval; Role; Sampling; Seizures; Semantic memory; Semantics; Stream; Structure; Symptoms; Techniques; Temporal Lobe; Time; United States National Institutes of Health; Work; cognitive function; cognitive recovery; cohort; connectome; entorhinal cortex; follow-up; functional outcomes; improved; improved functioning; individual patient; longitudinal analysis; minimally invasive; multidisciplinary; multimodality; neural circuit; neuroimaging; novel; object recognition; outcome prediction; prospective; rate of change; visual processing

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.

项目概要： 我们已经进行了最大的前瞻性比较研究的激光杏仁核campotomy（SLAH）， 微创手术消融杏仁-海马复合体（AHC）与选择性和标准消融 开放性切除术（OR）癫痫手术（N=425+）。我们证明了SLAH在1年内上级OR 成年人的认知结果（包括情景言语记忆和知觉（语义）识别或名称 物体/面部的检索），同时实现可比较的癫痫发作控制。我们将扩展分析 以前所未有的方式纵向（5-10年结局）利用这一独特的队列研究， 患者包括神经心理学（NP），结构和功能神经影像学和癫痫发作的结果。 我们还收集了大量涉及非AHC的立体定向激光消融[SLA]的病例 结构.这些SLA病例的异质性和激光消融手术区域的病灶性质造成了 这是一个进行损伤行为分析的绝佳机会。我们将扩大我们的神经成像分析， 严格的体素病变症状映射（VLSM）和扩散连接建模的新方法 张量成像和静息态功能磁共振成像。我们将集中讨论负责陈述性记忆的神经回路 和语言，同时确定最佳手术区域，以产生最佳的长期认知和癫痫发作 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，而连接性分析将揭示这些区域在个体中的相互联系 患者（允许我们确定患者水平的相对下降风险）。 我们的初步研究结果表明：1）SLAH患者在多个方面表现出意想不到的改善， 认知功能，这是无与伦比的，在他们的OR同行，和2）二语习得程序节省AHC 和更广泛的内侧TL区域经常导致言语记忆/命名的严重下降，特别是在 语言优势颞极或梭状回灶性消融例。这表明，口头 陈述性记忆依赖于一个超越AHC的广泛网络，这是一个范式转变， 手术计划（即，被认为在手术过程中可消耗的区域实际上是关键的， 函数）。从机械和临床转化的角度来看，这一知识至关重要， 我们的数据和计划分析提供了一种独特且可行的方法来得出强有力的结论 长期的知识差距。我们的数据提出了关于现有陈述性记忆模型的关键问题， 在许多SLAH/SLA病例中作为上级认知结果基础的恢复机制（例如， 功能保留与重组），我们将在本次更新中通过随访患者来解决这一问题。 时间最后，虽然越来越多的癫痫中心采用SLA，由于其改善的认知结果，最终 临床应用依赖于癫痫控制，因此确定SLAH在较长时间内的疗效至关重要。