Modulation of Hippocampal Circuitry and Memory Function with Focused Ultrasound in Amnestic MCI

遗忘型 MCI 中聚焦超声对海马回路和记忆功能的调节

• 批准号: 10460625
• 负责人: SUSAN Y BOOKHEIMER
• 金额: $ 62.37万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10460625
• 关键词: Acoustics; Affect; Alzheimer associated neurodegeneration; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Anterior; Area; Behavioral; Biological Markers; Blood; Blood flow; Brain; Brain region; Cerebrovascular Circulation; Clinical; Clinical Trials; Data; Deep Brain Stimulation; Devices; Diagnosis; Dose; Double-Blind Method; Episodic memory; Focused Ultrasound; Frequencies; Functional Magnetic Resonance Imaging; Hearing; Hippocampus (Brain); Human; Learning; Magnetic Resonance Imaging; Measures; Memory; Morphology; Neuropsychology; Operative Surgical Procedures; Participant; Patients; Performance; Perfusion; Phase; Physiologic pulse; Population; Prosthesis; Randomized; Rest; Sampling; Site; Structure; Surface; Techniques; Testing; Thick; Time; Treatment outcome; Up-Regulation; amnestic mild cognitive impairment; base; behavior measurement; blood-based biomarker; brain magnetic resonance imaging; cranium; effective therapy; entorhinal cortex; follow-up; healthy aging; improved; mild cognitive impairment; multimodal neuroimaging; neuroimaging; neuroregulation; neurosurgery; relating to nervous system; temporal measurement; ultrasound; white matter

ABSTRACT For patients with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) there are few effective treatments for memory enhancement. Strategies that directly manipulate neural activity are promising but currently have serious limitations. Deep brain stimulation (DBS) of the entorhinal cortex (ERc), a part of the brain important for memory, in a small sample of patients has been shown to improve memory, but DBS is highly invasive and requires neurosurgery. Other neuromodulation techniques that do not require surgery are limited in that they target only surface brain structures. In MCI and AD, it is the deep brain structures, including the ERc and the hippocampus (HC) that are most affected. Low intensity focused ultrasound pulsation (LIFUP) uses acoustic energy waves with frequencies higher than humans can hear to penetrate the skull to effect specifically targeted deep brain regions. Therefore, LIFUP could be targeted at the deep brain structures critical for episodic memory formation, the same regions that are affected in MCI and AD. We are the first to do just this and our preliminary data shows that LIFUP: increases perfusion of the ERc; increased functional connectivity of the ERc/HC memory network and may improve behavioral memory performance. Our LIFUP set-up is safe to use inside a magnetic resonance imaging (MRI) machine which allows for simultaneous brain modulation and real- time measurement of the modulation using MRI. We will use each participant’s structural brain MRI to aim LIFUP at the ERc. This will allow us to directly test the effects of LIFUP on activity in the ERc, in other brain regions connected to the ERc (e.g. HC), as well as on blood flow in the HC and other brain areas important for memory. Applying this to patients with MCI, we will try to determine the dose, booster effect and duration of LIFUP effects on brain and blood flow, structure and function, determine whether these LIFUP-related changes improve memory in this population and evaluate the effect of LIFUP on blood-based biomarkers of AD-related neurodegeneration. Understanding how the parameters of LIFUP dose and booster session effect the impact and duration of LIFUP on brain, biomarker and memory performance will be a significant step towards constructing a comprehensive clinical trial. The ability to change the activity and blood flow of brain regions by targeting them with LIFUP would be an important step towards developing a non-invasive memory prosthetic that would make a very significant contribution to AD treatment.

抽象的 对于轻度认知障碍（MCI）和阿尔茨海默氏病（AD）的患者 记忆增强的治疗方法。承诺直接操纵神经活动的策略，但 目前有严重的局限性。内嗅皮层（ERC）的深脑刺激（DB），大脑的一部分 对于记忆很重要的是，在一小部分患者样本中已显示可改善记忆力，但DBS高度很高 侵入性并需要神经外科手术。其他不需要手术的神经调节技术受到限制 因为它们仅针对表面大脑结构。在MCI和AD中，它是深脑结构，包括ERC 以及受影响最大的海马（HC）。低强度的超声搏动（LIFUP）使用 频率高于人类的声波波的声波可以渗透到头骨上以特殊作用 有针对性的深脑区域。因此，LIFUP可以针对对情节至关重要的深脑结构 内存形成，与MCI和AD中影响的相同区域。我们是第一个这样做的人和我们的 初步数据表明，LIFUP：增加ERC的灌注；提高功能连接的连通性 ERC/HC内存网络，可能会改善行为内存性能。我们的LIFUP设置安全使用 在磁共振成像（MRI）机器内部，可进行简单的大脑调制和实现 使用MRI对调制的时间测量。我们将使用每个参与者的结构大脑MRI来瞄准LIFUP 在ERC。这将使我们能够直接测试LIFUP对ERC活动的影响，在其他大脑区域 连接到ERC（例如HC），以及HC和其他大脑区域的血流，对记忆很重要。 将此应用于MCI患者，我们将尝试确定剂量，增强作用和LIFUP效应持续时间 在大脑和血流，结构和功能上，确定这些与LIFUP相关的变化是否有所改善 该人群中的记忆并评估LIFUP对广告相关的血液基标记物的影响 神经变性。了解LIFUP剂量和助推器会话的参数如何影响影响 大脑，生物标志物和记忆性能的生命持续时间将是迈向的重要一步 构建全面的临床试验。通过通过 用LIFUP瞄准它们将是开发非侵入性记忆假肢的重要一步 这将为AD治疗做出非常重要的贡献。