Mechanisms of Memory Enhancement by Deep Brain Stimulation in Humans

深部脑刺激增强人类记忆的机制

• 批准号: 8664952
• 负责人: ITZHAK FRIED
• 金额: $ 33.35万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8664952
• 关键词: Affect; Aging-Related Process; Alzheimer' s Disease; Clinical; Cognition Disorders; Companions; Complex; Coupling; Deep Brain Stimulation; Development; Diffusion Magnetic Resonance Imaging; Disease; Elderly; Electrodes; Encephalitis; Epilepsy; Episodic memory; Event; Exhibits; Heart; Heart Arrest; Hippocampus (Brain); Human; Impaired cognition; Implanted Electrodes; Individual; Injury; Intractable Epilepsy; Investigation; Journals; Laboratories; Learning; Location; Magnetic Resonance Imaging; Measures; Medial; Medicine; Memory; Memory Disorders; Memory Loss; Neurons; New England; North America; Operative Surgical Procedures; Patients; Perforant Pathway; Pharmacologic Substance; Phase; Physiology; Publishing; Research; Resolution; Role; Seizures; Societies; Staging; Stroke; Structure; Symptoms; System; Techniques; Temporal Lobe; Temporal Lobe Epilepsy; Therapeutic; Therapeutic Effect; Theta Rhythm; Traumatic Brain Injury; Variant; base; cost; entorhinal cortex; experience; implantation; information processing; insight; nervous system disorder; novel; novel therapeutic intervention; public health relevance; relating to nervous system; response

DESCRIPTION (provided by applicant): Loss of the ability to transform present experience to what can be later remembered is one of the most dreaded afflictions of the human condition. It is present in various neurological disorders including temporal lobe epilepsy, traumatic brain injury and other hippocampal injuries such as those occurring during stroke, cardiac arrest, or encephalitis. It is also one of the first features of Alzheimer's Disease (AD) which affects millios of people in the US and worldwide, and is an unwelcome companion of the aging process becoming an increased burden on individual and society. Decades of research have established that declarative memory, the ability to remember recently experienced facts and events, depends on the hippocampus and associated structures in the medial temporal lobe (MTL), including the entorhinal cortex. In particular, understanding the role of the hippocampus and its relationship to afferent input from the entorhinal cortex is of considerable significance, as insul to this connective circuitry is very early and disproportionally affected in temporal lobe epilepsy AD and other neurological disorders, resulting in profound effects on memory. The applicant's laboratory has been the leader in single neuron physiology of the human MTL and recently published findings in the New England Journal of Medicine showing dramatic spatial memory enhancement when deep brain stimulation (DBS) of the human entorhinal area was given during the learning phase [13]. The present project will characterize the mechanisms of DBS through simultaneous recording of single neuron and local field potentials (LFPs). The project utilizes a rare opportunity to record the activity of single neurons and LFPs from depth electrodes implanted in patients with intractable epilepsy in order to identify the seizure focus fr potential surgical cure. A primary objective is to characterize the effect of DBS on learning vs. recall phases of memory, including both spatial and non-spatial memory, in addition to understanding its longitudinal effects. The project will elucidate the complex relationship between single neuronal responses, LFP oscillations, and DBS that underlies memory enhancement. Lastly the project will investigate variations in memory enhancement associated with changes in electrode placement through the use of high-resolution magnetic resonance imaging and high-resolution diffusion tensor imaging. By these three lines of investigation the project will develop insight into the mechanisms of memory enhancement associated with DBS in humans, contribute to the understanding of the MTL and its role in memory, and ultimately provide novel therapeutic approaches to human memory disorders.

描述（由申请人提供）：丧失将当前经验转化为以后可以记住的能力是人类最可怕的痛苦之一。它存在于各种神经系统疾病中，包括颞叶癫痫、创伤性脑损伤和其他海马损伤，如中风、心脏骤停或脑炎期间发生的海马损伤。它也是阿尔茨海默病（AD）的第一个特征之一，其影响美国和世界各地的数百万人，并且是衰老过程的不受欢迎的伴侣，成为个人和社会的负担增加。几十年的研究已经证实，陈述性记忆，即记住最近经历的事实和事件的能力，取决于海马体和内侧颞叶（MTL）的相关结构，包括内嗅皮层。特别是，了解海马体的作用及其与来自内嗅皮层的传入输入的关系具有相当大的意义，因为对于这种连接回路的胰岛素在颞叶癫痫AD和其他神经系统疾病中非常早期和早期地受到影响，从而对记忆产生深远的影响。申请人的实验室一直是人类MTL的单神经元生理学的领导者，并且最近在新英格兰医学杂志上发表的研究结果显示，当在学习阶段期间给予人类内嗅区的脑深部刺激（DBS）时，空间记忆显著增强[13]。本项目将通过同时记录单个神经元和局部场电位（LFPs）来表征DBS的机制。该项目利用难得的机会记录植入难治性癫痫患者体内的深部电极的单个神经元和LFP的活动，以确定潜在手术治疗的癫痫发作病灶。一个主要目标是表征DBS对记忆的学习与回忆阶段的影响，包括空间和非空间记忆，以及了解其纵向效应。该项目将阐明单个神经元反应，LFP振荡和DBS之间的复杂关系，这是记忆增强的基础。最后，该项目将通过使用高分辨率磁共振成像和高分辨率扩散张量成像来研究与电极放置变化相关的记忆增强变化。通过这三条调查路线，该项目将深入了解与DBS相关的人类记忆增强机制，有助于理解MTL及其在记忆中的作用，并最终为人类记忆障碍提供新的治疗方法。