GOALI: Collaborative - Magnetoelectric Nanodevices for Wireless Repair of Neural Circuits Deep in the Brain

GOALI项目位于工程学和医学的交叉点，旨在解决神经退行性疾病这一广泛领域中的以下空白。电场刺激神经网络可以修复导致各种神经退行性疾病的异常神经活动，如阿尔茨海默病(AD)等。此外，最近的研究表明，电场对细胞命运和神经发生有根本性的影响。然而，现有的方法，如(1)通过建立与神经网络的直接电联系来直接脑深部刺激(DBS)和(2)较小侵入性的间接经颅磁刺激(TMS)不能提供在细胞水平上充分控制神经网络所需的空间和时间分辨率，从而有效地使用电来治疗这些疾病，而不会造成任何破坏性的副作用。该项目通过实施纳米技术来填补这一空白，根据该方法，磁电纳米颗粒(MEN)结合了电场和磁场的主要优势，能够无线控制对大脑中选择性区域的高效率、高特异性和高选择性刺激，以治疗特定的神经退行性疾病，而不会产生任何副作用。这些潜在的应用在工程电磁和多铁纳米粒子驱动的系统中具有深远的意义，这些系统可能会影响到个性化精确医学、认知神经科学、神经成像、临床神经学和精神病学等新兴领域。拟议中的系统可以帮助对大脑进行反向工程，从而打开一条从根本上了解大脑的途径。该项目的一个重要组成部分是激励代表性不足的少数群体在工程学和医学的交叉点攻读跨学科学位。GALI计划将特别重视吸引当地的K-12和本科生在FIU和印第安纳大学继续他们的研究。GOALI计划旨在进行全面的研究，以设计基于磁电纳米颗粒(MENS)的系统，以无线刺激大脑深处的局部区域，以修复疾病特有的障碍。人类可以将大脑深处的局部固有电场与磁场连接起来，从而实现对局部电刺激的外部控制，从而修复局部神经回路。与传统的磁性纳米粒子一样，MAN可以作为磁共振成像的图像造影剂，并通过施加磁场梯度来导航跨越血脑屏障。此外，与传统的纳米粒子不同，由于非零磁电效应的存在，人类显示出一种全新的性质。ME效应是由于磁致伸缩和压电元件的耦合而存在的，它允许将大脑深处的内在电场有效地耦合到磁场，而磁场又可以从头骨外部无线控制。因此，男人们允许使用DC。和用于分离这两个功能的交流磁场，(I)直流的应用。用于图像引导的男人跨越血脑屏障并进入疾病特定局部区域的磁场梯度(S)和(Ii)交流电源的应用。磁场通过感应局部交流电来局部刺激这个局部区域(S)。分别是电场。根据亚稳态系统的物理原理，使用电磁系统，纳米颗粒可以有效地保持在准抗磁状态，从而通过交流作用移动到大脑深处的任何位置，以进一步进行局部电刺激。磁场。由于ME效应，人类提供的图像不仅包含结构信息，而且反映了由于神经元活动而产生的局部电场。所有这些效应将在体外和体内使用动物模型进行研究，以了解MAN对神经元和突触激活的潜在机制、皮质神经元活动、神经元兴奋性和突触传递的场控局部效应。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The GOALI project at the intersection of engineering and medicine aims to address the following gap in the broad area of neurodegenerative diseases. Stimulation of the neural network by electric fields can repair the abnormal neural activity responsible for various neurodegenerative diseases such as Alzheimer's Disease (AD) and many others. Further, recently it has been shown that electric fields have fundamental effects on cell fate and neurogenesis. However, the existing approaches such as (1) direct deep-brain stimulation (DBS) by establishing direct electrical contact to the neural network and (2) less-invasive indirect transcranial magnetic stimulation (TMS) don't provide spatial and temporal resolutions required for adequate control of the neural network at the cellular level to effectively cure these diseases using electricity, without causing any devastating side effects. This project fills this gap by implementing a nanotechnology approach, according to which magnetoelectric nanoparticles (MENs) are used to combine the main advantages of electric and magnetic fields to enable wirelessly controlled high-efficacy, high-specificity and high-selectivity stimulation of selective regions in the brain to treat specific neurodegenerative diseases without any side effects. The potential applications are far-reaching into engineering electromagnetic and multiferroic nanoparticle-driven systems which could impact the emerging field of personalized precision medicine, cognitive neuroscience, neuroimaging, clinical neurology, and psychiatry. The proposed system can help reverse engineer the brain and thus open a pathway to fundamental understanding of the brain. An important component of the project is to motivate underrepresented minorities to pursue cross-disciplinary degrees at the intersection of engineering and medicine. A special emphasis will be made to attract local K-12 and undergraduate students to continue their research at FIU and Indiana University.The GOALI proposal aims to conduct comprehensive studies to engineer magnetoelectric nanoparticles (MENs) based system for wireless stimulation of local regions deep in the brain to repair disease specific impediments. MENs can bridge local intrinsic electric fields deep in the brain with magnetic fields and thus enable an external control of local electric stimulation for repairing neural circuits locally. Like traditional magnetic nanoparticles, MENs can be used as image contrast agents in magnetic resonance imaging and navigated across the blood-brain barrier via application of magnetic field gradients. In addition, unlike traditional nanoparticles, MENs display an entirely new property due to the presence of a non-zero magnetoelectric (ME) effect. The ME effect, which exists due to coupled magnetostrictive and piezoelectric components, allows to efficiently couple intrinsic electric fields deep in the brain to magnetic fields which in turn can be wirelessly controlled from outside the skull. Thus, MENs allow to use d.c. and a.c magnetic fields for separating the two functions, (i) application of a d.c. magnetic field gradient for image-guided navigation of MENs across BBB and into a disease-specific local region(s) and (ii) application of an a.c. magnetic field to stimulate this local region(s) locally via inducing local a.c. electric fields, respectively. Based on the physics of metastable systems, using a system of electromagnets, the nanoparticles can be effectively maintained in a quasi-diamagnetic state and thus moved to any point deep in the brain for further local electric stimulation via application of a.c. magnetic fields. Due to the ME effect, the image provided by MENs not only contains structural information but also reflects a local electric field due to the neuronal activity. All these effects will be studied in vitro and in vivo using animal models to understand field-controlled local effects of MENs on the underlying mechanisms of activation of neurons and synapses, the cortical neuronal activity, neuronal excitability, and synaptic transmission.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.