Focused ultrasound for memory disorders

聚焦超声治疗记忆障碍

基本信息

批准号：
10638189
负责人：
VINCENT P FERRERA
金额：
$ 79.45万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10638189
关键词：
Address Affect Alzheimer&apos s Disease Alzheimer&apos s disease patient Area Attention deficit hyperactivity disorder Autopsy Behavioral Blood - brain barrier anatomy Brain Brain region Chemicals Clinical Trials Cognitive deficits Computer software Contralateral Corpus striatum structure Data Decision Making Deep Brain Stimulation Dementia Dorsal Dose Drug Delivery Systems Drug Targeting Dyskinetic syndrome Dysmetria Electric Stimulation Focused Ultrasound Focused Ultrasound Therapy Frequencies Functional Magnetic Resonance Imaging Goals Histology Human Impaired cognition Impairment Intravenous Ipsilateral Length Magnetic Resonance Imaging Maps Measures Mediating Medical Memory Memory Disorders Memory impairment Mental disorders Methods Microbubbles Motor Motor Cortex Movement Neurotransmitters Parkinson Disease Patients Performance Perfusion Persons Pharmaceutical Preparations Physiologic pulse Physiological Physiology Predisposition Prefrontal Cortex Research Safety Schizophrenia Short-Term Memory Speed Structure Testing Thermometry Time Tremor Water Work arterial spin labeling autism spectrum disorder awake brain behavior caudate nucleus effectiveness testing executive function experience experimental study gamma-Aminobutyric Acid human data improved intravenous injection member nervous system disorder neural circuit neuroregulation nonhuman primate noninvasive brain stimulation novel novel therapeutics preclinical efficacy preclinical safety pressure programs tissue oxygenation tool touchscreen

Address Affect Alzheimer&apos s Disease Alzheimer&apos s disease patient Area Attention deficit hyperactivity disorder Autopsy Behavioral Blood - brain barrier anatomy Brain Brain region Chemicals Clinical Trials Cognitive deficits Computer software Contralateral Corpus striatum structure Data Decision Making Deep Brain Stimulation Dementia Dorsal Dose Drug Delivery Systems Drug Targeting Dyskinetic syndrome Dysmetria Electric Stimulation Focused Ultrasound Focused Ultrasound Therapy Frequencies Functional Magnetic Resonance Imaging Goals Histology Human Impaired cognition Impairment Intravenous Ipsilateral Length Magnetic Resonance Imaging Maps Measures Mediating Medical Memory Memory Disorders Memory impairment Mental disorders Methods Microbubbles Motor Motor Cortex Movement Neurotransmitters Parkinson Disease Patients Performance Perfusion Persons Pharmaceutical Preparations Physiologic pulse Physiological Physiology Predisposition Prefrontal Cortex Research Safety Schizophrenia Short-Term Memory Speed Structure Testing Thermometry Time Tremor Water Work arterial spin labeling autism spectrum disorder awake brain behavior caudate nucleus effectiveness testing executive function experience experimental study gamma-Aminobutyric Acid human data improved intravenous injection member nervous system disorder neural circuit neuroregulation nonhuman primate noninvasive brain stimulation novel novel therapeutics preclinical efficacy preclinical safety pressure programs tissue oxygenation tool touchscreen

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项目摘要

Summary/Abstract Working memory (WM) is a core component of executive function. WM is impaired in conditions that affect roughly 20M people in the US alone, including Alzheimer’s disease (5.8M), Parkinson’s disease (1.2M), schizophrenia (1.5M), attention deficit hyperactivity disorder (6.1M) and autism spectrum disorders (7.3M). Despite this, there are few non-addictive medical treatments that are effective in ameliorating working memory deficits. Focused ultrasound (FUS) is an emerging noninvasive method of brain stimulation that has the ability to reach deep brain structures. FUS has been used for direct neuromodulation and to open the blood-brain barrier (BBB) for targeted drug delivery. The proposed experiments will test the effects of FUS neuromodulation and drug delivery on working memory performance in awake, behaving nonhuman primates (NHP) as a step toward developing novel therapies for dementia. The experiments will also address the mechanism of action of FUS neuromodulation and BBB opening in cortico-striatal circuits using a suite of MRI methods (BOLD, DTI, UTE, pcASL, and qBOLD). Finally, we will address the safety of FUS neuromodulation and BBB opening in cortical and deep brain structures; this has not been done previously and establishing safety in NHP is a critical step prior to a clinical trial. We have demonstrated that FUS can be used to improve behavioral performance during decision making in NHP and now propose to evaluate FUS for improving WM. Aim 1 will test the effects of FUS neuromodulation alone on working memory capacity and span in intact and impaired NHP, and compare FUS to electrical deep brain stimulation. Aim 2 will test the effects of FUS- mediated blood-brain barrier opening and drug delivery and on working memory. Aim 3 will investigate the mechanism of FUS neuromodulation using noninvasive MRI. Broader Impact: This project will provide preclinical safety and efficacy data for human neuromodulation studies focusing on cognitive deficits associated with neurological and psychiatric disorders.

摘要/摘要工作记忆（WM）是执行功能的核心组成部分。 WM在影响的条件下受到损害仅在美国，大约有2000万人，包括阿尔茨海默氏病（580万），帕金森氏病（1.2m），精神分裂症（1.5m），注意力缺陷多动障碍（6.1m）和自闭症谱系障碍（730万）。尽管如此，很少有非添加性医疗治疗可有效改善工作记忆缺陷。聚焦超声（FUS）是一种具有能力的脑刺激的无创方法达到深脑结构。 FUS已用于直接神经调节并打开血脑靶向药物输送的障碍（BBB）。提出的实验将测试FUS的影响神经调节和药物提供在清醒中的工作记忆表现，表现非人类隐私（NHP）作为开发痴呆症新颖疗法的一步。实验还将解决使用一套MRI套件，在皮质 - 纹状体回路中FUS神经调节和BBB开口的作用机理方法（BOLD，DTI，UTE，PCASL和QBOLD）。最后，我们将解决FUS神经调节的安全性和BBB在皮质和深脑结构中开放；这以前尚未完成并建立 NHP的安全是临床试验之前的关键步骤。我们已经证明了FUS可用于改进 NHP决策过程中的行为绩效，现在建议评估FUS改善WM的FUS。 AIM 1将仅测试仅FUS神经调节对工作记忆能力和完整范围的影响 NHP受损，并将FUS与电脑刺激进行比较。 AIM 2将测试FUS的影响 - 介导的血脑屏障开放和药物输送以及工作记忆。 AIM 3将调查使用非侵入性MRI的FUS神经调节机理。更广泛的影响：该项目将提供临床前的安全性和人类神经调节研究的有效数据，重点是认知缺陷与神经和精神疾病有关。