Noninvasive Targeted Neuromodulation

无创靶向神经调节

• 批准号: 10515789
• 负责人: Jan Kubanek
• 金额: $ 142.81万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515789
• 关键词: Address; Adverse event; Anatomy; Animal Testing; BRAIN initiative; Basic Science; Behavioral; Brain; Brain Diseases; Brain region; Cardiovascular Diseases; Clinic; Darkness; Development; Devices; Diabetes Mellitus; Diagnosis; Discrimination; Effectiveness; Electric Stimulation; Electrophysiology (science); Equation; Evoked Potentials; Eye; Focused Ultrasound; Future; Grain; Health Expenditures; Histologic; Human; Impairment; Implanted Electrodes; Individual; Industrialization; Lateral Geniculate Body; Left; Light; Magnetic Resonance Imaging; Malignant Neoplasms; Mental disorders; Methods; Mission; Monkeys; Neurons; Operating System; Outcome; Patients; Performance; Peripheral Nervous System; Persons; Pharmaceutical Preparations; Physiologic pulse; Production; Protocols documentation; Publications; Research; Research Personnel; Resistance; Resolution; Rice; Safety; Scientist; Site; Skin; Slice; Source; Specific qualifier value; Stimulus; System; Techniques; Thalamic structure; Time; Transducers; Translations; Ultrasonics; United States National Institutes of Health; Visual; Visual Cortex; Visual system structure; Work; base; brain tissue; clinical translation; clinically relevant; contrast enhanced; cranium; effective therapy; electric field; empowered; flexibility; human subject; indexing; magnetic field; meetings; mind control; nervous system disorder; neural circuit; neuroregulation; new technology; nonhuman primate; personalized diagnostics; personalized medicine; pressure; programs; relating to nervous system; scale up; side effect; temporal measurement; tool; ultrasound; visual information; web site

Summary Neurological and psychiatric disorders absorb one-third of the total health care expenditures; more than cancer, cardiovascular diseases, and diabetes combined. On average, approximately one in three patients fails to respond to medication treatments or has intolerable side effects. Neuromodulation, which aims to treat brain disorders at their neural source, provides a new path to effective and personalized treatments. Unfortunately, existing invasive neuromodulation approaches are currently limited to specific patients and brain targets, and noninvasive approaches do not have the necessary spatial resolution. As a consequence, a large proportion of patients do not receive adequate treatment. To address this issue, we have developed a non-invasive approach and hardware that enable noninvasive and targeted neuromodulation. The tool modulates specific brain targets on command and at high spatial and temporal resolution. The approach has the precision of implanted electrodes but is applied remotely and entirely noninvasively. To achieve this, the approach combines two forms of noninvasive energies—focused ultrasonic and magnetic fields. The product of these fields generates localized electrical stimulation (“Lstim”). The ultrasound bestows Lstim with sharp focus and targeting flexibility. The stimulated regions can be as small as a grain of rice deep in the human brain. To realize the potential of the method, we have developed a programmable transducer array that can target specified brain regions rapidly on demand, enabling the stimulation of multiple brain targets in succession or concert. We have validated the neuromodulatory effects of Lstim in the peripheral nervous system of 18 human subjects. We now propose to develop effective and safe Lstim protocols for modulating deep circuits in the brain and thus harness the full power of the approach. We will perform the work in non-human primates to maximize clinical relevance and accelerate translation. Specifically, we will determine which Lstim parameters excite and inhibit neurons most effectively (Aim 1). We will target deep brain visual regions and assess the magnitude and polarity of the neuromodulatory effects using an established electrophysiological readout. We will validate the safety of Lstim using a sensitive behavioral task, contrast-enhanced MRI, and histological examination of brain slices (Aim 2). The completion of these two aims will maximize the effectiveness of a new, non-invasive and targeted neuromodulation technique and validate its safety. The approach has the potential to provide treatment options for a large number of medication-resistant patients. We will disseminate the developed hardware along with the effective protocols for the benefit of clinicians, patients, and researchers.

总结 神经和精神疾病占据了医疗保健总支出的三分之一，超过癌症、心血管疾病和糖尿病的总和。平均而言，大约三分之一的患者对药物治疗无效或出现无法忍受的副作用。神经调节疗法是从神经源治疗脑功能障碍的一种新方法，为有效的个性化治疗提供了新的途径。不幸的是，现有的侵入性神经调节方法目前仅限于特定患者和大脑目标，而非侵入性方法不具有必要的空间分辨率。因此，很大一部分病人得不到适当的治疗。 为了解决这个问题，我们开发了一种非侵入性方法和硬件，可以实现非侵入性和有针对性的神经调节。该工具根据命令并以高空间和时间分辨率调节特定的大脑目标。该方法具有植入电极的精度，但远程应用，完全无创。为了实现这一目标，该方法结合了两种形式的非侵入性能量聚焦超声和磁场。这些场的产物产生局部电刺激（“Lstim”）。超声波赋予Lstim锐利的焦点和靶向灵活性。受刺激的区域可以像人类大脑深处的一粒米一样小。为了实现该方法的潜力，我们开发了一种可编程传感器阵列，可以根据需要快速瞄准特定的艾德大脑区域，从而能够连续或协调地刺激多个大脑目标。 我们已经在18名人类受试者的外周神经系统中验证了Lstim的神经调节效应。我们现在建议开发有效和安全的Lstim协议，用于调制大脑中的深层回路，从而利用该方法的全部功能。我们将在非人类灵长类动物中进行这项工作，以最大限度地提高临床相关性并加速翻译。具体来说，我们将确定哪些Lstim参数最有效地激发和抑制神经元（目标1）。我们将以脑深部视觉区域为目标，使用已建立的电生理读数评估神经调节效应的幅度和极性。我们将使用敏感的行为任务、对比增强MRI和脑切片组织学检查来验证Lstim的安全性（目标2）。 这两个目标的完成将最大限度地提高一种新的、非侵入性的、靶向的神经调节技术的有效性，并验证其安全性。该方法有可能为大量耐药患者提供治疗选择。我们将沿着有效的协议传播开发的硬件，以使临床医生、患者和研究人员贝内。