Periodic Reporting for period 1 - META-BRAIN (MagnetoElectric and Ultrasonic Technology for Advanced BRAIN modulation)
Okres sprawozdawczy: 2024-01-01 do 2024-12-31
Alterations in neurological function due to various causes (e.g. stroke, trauma, neurodegeneration, epilepsy, neuropsychiatric diseases, chronic pain, and sensory deficits, among others) commonly exhibit alterations in brain rhythms and activity patterns. As a common strategy for the restoration of physiological activity in these various pathologies, there is an urgent clinical need for the precise control of neural activity, which can benefit from state-of-the-art technological developments in a variety of fields: nanotechnology, nano- and microelectronics, new materials, brain science, clinical experience, and computation. META-BRAIN (MagnetoElectric and Ultrasonic Technology for Advanced BRAIN modulation) brings together seven expert partners (six institutions) in these fields with the aim of achieving precise spatiotemporal control of brain activity.
Our overall objectives are to achieve a precise spatiotemporal control of brain activity using remote magnets and/or ultrasound. We aim at minimal invasiveness, high spatial resolution, remote and wireless control of brain activity, while obtaining detailed mechanistic and scientific understanding of the principles, both experimental and theoretical. Our final objective is to provide novel useful principles and tools with valuable clinical applications.
In this project we will use two innovative strategies. Our main strategy uses magnetoelectric (ME) nanoarchitectures, that can be activated by low amplitude, non-invasive, remote magnetic fields, which generate electric fields capable of stimulating brain tissue. This novel principle of brain activity control would minimize the amplitude of the required magnetic fields, be wireless, and have enhanced spatial resolution, from single neurons to cortical areas. As an alternative stimulation/recording strategy we will also develop minimally invasive technology based on ultrasound (US) stimulation. To this end, we will implement a novel neural interface composed of Capacitive Micromachined Ultrasonic Transducer (CMUT) for spatially precise neuromodulation. We will perform our developmental work and experiments hand-in-hand with theoretical models that will simulate, quantify, and predict the optimal arrangements for stimulation and closed-loop systems. We also evaluate in detail the potential for clinical translation to humans with our clinical partners and we will make a detailed plan for it.
Our overall objectives are to achieve a precise spatiotemporal control of brain activity using remote magnets and/or ultrasound. We aim at minimal invasiveness, high spatial resolution, remote and wireless control of brain activity, while obtaining detailed mechanistic and scientific understanding of the principles, both experimental and theoretical. Our final objective is to provide novel useful principles and tools with valuable clinical applications.
In this project we will use two innovative strategies. Our main strategy uses magnetoelectric (ME) nanoarchitectures, that can be activated by low amplitude, non-invasive, remote magnetic fields, which generate electric fields capable of stimulating brain tissue. This novel principle of brain activity control would minimize the amplitude of the required magnetic fields, be wireless, and have enhanced spatial resolution, from single neurons to cortical areas. As an alternative stimulation/recording strategy we will also develop minimally invasive technology based on ultrasound (US) stimulation. To this end, we will implement a novel neural interface composed of Capacitive Micromachined Ultrasonic Transducer (CMUT) for spatially precise neuromodulation. We will perform our developmental work and experiments hand-in-hand with theoretical models that will simulate, quantify, and predict the optimal arrangements for stimulation and closed-loop systems. We also evaluate in detail the potential for clinical translation to humans with our clinical partners and we will make a detailed plan for it.
During the first 12 months of the project, there has been an effort on the fabrication of the different components of the systems, such as the nanoparticles, sensors, or coils to generate magnetic fields. In addition to the hardware, software has been developed to control the coils, incorporating all the specifications outlined in a deliverable.
We have synthesized magnetoelectric nanoparticles of different shapes and sizes (15-50 nm). These particles are composed of core and shell, which provide magnetic and piezoelectric electric properties, evaluated their magnetic properties, and their effect verified on cell differentiation studies. They have also been tested on the cerebral cortex tissue and their modulation of neuronal activity has been proven. We have also fabricated graphene microtransistor arrays and characterized them for in vitro and in vivo DC-coupled recordings. This arrays were tested under magnetic fields and it was found to be non affected. Coils of different characteristics and software for their control were developed and tested in experiments. These developments are theoretically guided by computer models that do simulations of the electric and magnetic fields at different scales: from the nanoparticle to the brain tissue level. The coils have been tested in experiments in cerebral cortex in vitro, testing different arrangements, intensities and frequencies for optimizing nanoparticle control. There has been also studies on the biocompatibility of nanoparticles, taking into accout dosage, composition, and their effects on cells in culture, demonstrating that we can work using secure limits for neurons and brain tissues. In parallel, we are beginning to fabricate arrays for ultrasonic stimulation.
We have synthesized magnetoelectric nanoparticles of different shapes and sizes (15-50 nm). These particles are composed of core and shell, which provide magnetic and piezoelectric electric properties, evaluated their magnetic properties, and their effect verified on cell differentiation studies. They have also been tested on the cerebral cortex tissue and their modulation of neuronal activity has been proven. We have also fabricated graphene microtransistor arrays and characterized them for in vitro and in vivo DC-coupled recordings. This arrays were tested under magnetic fields and it was found to be non affected. Coils of different characteristics and software for their control were developed and tested in experiments. These developments are theoretically guided by computer models that do simulations of the electric and magnetic fields at different scales: from the nanoparticle to the brain tissue level. The coils have been tested in experiments in cerebral cortex in vitro, testing different arrangements, intensities and frequencies for optimizing nanoparticle control. There has been also studies on the biocompatibility of nanoparticles, taking into accout dosage, composition, and their effects on cells in culture, demonstrating that we can work using secure limits for neurons and brain tissues. In parallel, we are beginning to fabricate arrays for ultrasonic stimulation.
Our results after these 12 months demonstrate that we can get modulation of the cerebral cortex local activity in vitro when we deposit in the tissue magnetoelectric nanoparticles. Through our theoretical explorations, along with the experiments, we investigate how these particles act in the neural tissue, the electric fields that they generate and their impact on neurons. These are the first steps to optimize the spatiotemporal control over brain activity. We will soon start exploring the use of ultrasounds with novel devices that are been fabricated for this project and that contain a great deal of innovation. Both technologies should allow a remote modulation of the brain activity. All these advances are only possible through the collaboration of partners with highly diverse and complementary expertise. An international workshop has been organized by META BRAIN in Switzerland in April 2025 on “Advanced nanotechnologies for brain interfacing” with international experts, which will be a significant step not only for the discussion of the techonological frontiers in the field, discussing new ideas and solutions to problems, but also for the internalisation of the project. The first steps on the exploitation have been taken in the creation of the list of Key Exploitable Results, and they will continue in the next two years of the project. Our final objective is to put these technologies to the service of society, where the neuropsychiatric diseases (e.g. >1M cases of new brain strokes/year in Europe) are highly prevalent, impactful and have a high cost at all levels.