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.
