Inactivation of the hippocampus by electrical stimulation to preview post-surgical verbal recognition memory deficits

通过电刺激使海马失活以预览术后言语识别记忆缺陷

• 批准号: 10556967
• 负责人: Spencer Kellis
• 金额: $ 59.53万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556967
• 关键词: Ablation; Affect; Anesthesia procedures; Anesthetics; Animals; Anterior; Binding; Cerebral cortex; Clinical; Complication; Contralateral; Decision Making; Electric Stimulation; Electrodes; Epilepsy; Excision; Frequencies; Goals; Head; Hippocampus; Human; Impairment; Individual; Language; Lasers; Lesion; Literature; Lobectomy; Location; Maps; Measures; Medical; Memory; Memory impairment; Modernization; Monitor; Motor; Operative Surgical Procedures; Outcome; Patients; Performance; Phase; Postoperative Period; Predisposition; Procedures; Process; Proxy; Reporting; Research; Resected; Retrieval; Role; Seizures; Sensory; Speech; Surgical complication; Techniques; Temporal Lobe Epilepsy; Testing; Tissues; Translating; awake; design; experience; experimental study; interstitial; memory process; memory recognition; memory retrieval; neural; neurophysiology; response; risk minimization; standard of care; tool; verbal

PROJECT SUMMARY Patients who have undergone hippocampal resection to treat mesial temporal lobe epilepsy (MTLE) frequently experience memory deficits. Clinicians have few tools to preview these deficits when planning surgeries; the Wada test, which anesthetizes each hemisphere to test memory function available in the contralateral hemisphere, is the current medical standard. It was developed when temporal lobectomy was the primary surgical treatment for MTLE. In contrast, modern surgical techniques such as open selective amygdalohippocampectomy (AH) and laser interstitial thermal therapy (LITT) enable precise, selective lesions while minimizing damage to surrounding tissue. The difference in scale between the preview and the resection is one variable contributing to inconsistency in the utility of the Wada test to accurately preview memory deficits. Clinicians need a test which more precisely targets the tissue to be removed, and thus more accurately predicts functional consequences of losing the tissue. We propose using electrical stimulation (ES) through stereoelectroencephalography (SEEG) depth electrodes, placed in the hippocampus for clinical seizure monitoring, to generate temporary memory deficits at the spatial scale of intended surgical resection. Although ES of the hippocampus has been frequently employed to study the hippocampus' role in memory processes, its clinical utility to preview the memory deficits after hippocampectomy is less studied. Because the Wada test remains the clinical standard, we have designed our study to match its testing paradigm. Within this framework, our proposal will study where (Aim 1), when (Aim 2), and how (Aim 3) to stimulate the hippocampus to produce memory impairment. While the involvement of the hippocampus in memory function is undisputed, it is not clear which subregion(s) of the hippocampus should be stimulated to impair memory function. We believe stimulating both the head and body of the hippocampus will lead to impairment, but in Aim 1 we will also test stimulation of the head and body individually to see whether more localized stimulation can produce the desired effect. Similarly, the hippocampus has been implicated in both encoding and retrieval memory processes, but it is not known which of these processes should be disrupted by ES to impair memory function. In Aim 2 we will test stimulation in these phases individually and in both phases to determine which leads to the best impairment. Finally, in Aim 3 we will examine how the frequency of stimulation affects impairment of memory function. The literature reports studies using a wide range of frequencies, from 5 to 200 Hz. Because higher frequencies are more likely to generate epileptic activity, we limit our testing to a lower range of frequencies. We will evaluate ES at 5 Hz, which matches endogenous neurophysiological modulation within the hippocampus, and 50 Hz, which has long been a clinical standard used to disrupt function throughout neural tissue. This proposal, a new research direction, will establish the baseline results needed to translate ES of the hippocampus into a clinically viable tool to preview memory deficits resulting from resection of the hippocampus in the treatment of MTLE.

项目概要 经常接受海马切除术治疗内侧颞叶癫痫 (MTLE) 的患者 经历记忆缺陷。临床医生在计划手术时几乎没有工具可以预览这些缺陷；这 Wada 测试，麻醉每个半球以测试对侧可用的记忆功能 半球，是目前的医学标准。它是在颞叶切除术为主要技术时开发的 MTLE 的手术治疗。相比之下，现代外科技术，例如开放选择性 杏仁核海马切除术 (AH) 和激光间质热疗 (LITT) 可实现精确、选择性的病变 同时最大限度地减少对周围组织的损害。预览和切除之间的比例差异 是导致 WADA 测试准确预测记忆缺陷的效用不一致的一个变量。 临床医生需要一种更精确地针对要切除的组织的测试，从而更准确地预测 失去组织的功能后果。我们建议通过电刺激（ES） 立体脑电图 (SEEG) 深度电极，放置在海马体中用于临床癫痫发作 监测，以在预期手术切除的空间尺度上产生暂时的记忆缺陷。虽然 海马体的 ES 经常被用来研究海马体在记忆过程中的作用， 预测海马切除术后记忆缺陷的临床实用性研究较少。因为和田测试 仍然是临床标准，我们设计了我们的研究以匹配其测试范式。在这个框架内， 我们的提案将研究在何处（目标 1）、何时（目标 2）以及如何（目标 3）刺激海马体产生 记忆障碍。虽然海马体参与记忆功能是无可争议的，但尚不清楚 应刺激海马体的哪个子区域以损害记忆功能。我们相信刺激 海马体的头部和身体都会导致损伤，但在目标1中我们还将测试刺激 分别对头部和身体进行测试，看看更多的局部刺激是否可以产生预期的效果。 同样，海马体也与编码和检索记忆过程有关，但它并不是 已知 ES 应该扰乱这些过程中的哪一个来损害记忆功能。在目标 2 中我们将测试 单独或在两个阶段中对这些阶段进行刺激，以确定哪个阶段会导致最好的损伤。 最后，在目标 3 中，我们将研究刺激频率如何影响记忆功能损伤。这 文献报道了使用各种频率（5 到 200 Hz）的研究。因为频率较高 更有可能产生癫痫活动，因此我们将测试限制在较低的频率范围内。我们将评估ES 5 Hz 与海马内的内源性神经生理调节相匹配，50 Hz 则与海马内的内源性神经生理调节相匹配 长期以来一直是用于破坏整个神经组织功能的临床标准。这项提议是一项新的研究 方向，将建立将海马体 ES 转化为临床可行的所需的基线结果 用于预览 MTLE 治疗中海马切除术导致的记忆缺陷的工具。