Injectable Nanoelectrodes Enable Wireless Deep Brain Stimulation of Native Tissue in Freely Moving Mice

Abstract

Devices that electrically modulate the central nervous system have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices typically have centimeter-scale dimensions, requiring surgical implantation and wired-in powering. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Herein, we present injectable magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. Importantly, this mechanism of modulation requires no genetic modification of the brain, and allows animals to freely move during stimulation. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local thalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles

“…The concept of using magnetoelectric nanoparticles (MENs) for brain stimulation was first proposed in 2012 [13] and was later demonstrated with MENs-mediated modulation of brain EEG activity [14] with the most recent attempt by Kozielski et al to demonstrate to enhance thalamic neuronal activity in vitro (preprinted) [15]. They used CoFe 2 O 4 -BaTiO 3 MENs due to their relatively strong magneto-electric (ME) effect owing to the strain-induced coupling between the magnetostrictive cobalt ferrite cores and piezoelectric barium titanate shells.…”

Where do we stand now regarding treatment of psychiatric and neurodegenerative disorders? Considerations in using magnetoelectric nanoparticles as an innovative approach

“…The aforementioned results, originated with MENPs‐based studies on human cell lines as well as in vivo experiments on rodent models, support the MENPs' capability for noninvasive stimulation after delivery across the BBB, given the size of the nanoparticles ranges from 30 to 60 nm (Kozielski et al, 2020; Nguyen et al, 2021; Pardo et al, 2020). The experiments showed that MENPs were capable of stimulating the brain for at least 24 h after the administration in the brain.…”

“…No data has been released yet using MENPs as nanocarriers for brain targeting in vivo. Though it is noteworthy that, as described above, recently MENPs were used for wireless activation of motor activity in mice (Kozielski et al, 2020). In this section, we speculate that the use of MENPs, as an innovative mechanism to externally control the targeted drug release, could be translated into a revolutionary new approach for the treatment of psychiatric and neurodegenerative disorders.…”

“…Recently, Kozielski et al demonstrated behavioral changes in mice by subthalamic modulation via the aforementioned MENPs-based physics (Kozielski et al, 2020(Kozielski et al, , 2021. They conducted both in vitro and in vivo studies to prove that neural activity could be indeed triggered by wirelessly applied magnetic fields.…”

“…The ability of MENPs to cross BBB has been demonstrated in several studies using in vitro and in vivo models (Guduru et al, 2015;Hadjikhani et al, 2017;Kaushik et al, 2016;Kozielski et al, 2020;Nair et al, 2013;Nguyen et al, 2021;Pardo et al, 2020;Stewart et al, 2018). Guduru et al for the first time used an animal model (mouse) to demonstrate the ability of MENPs (30 nm, 10 μg) to reach the brain, after intravenous (IV) administration and the use of magnetic field gradients to make MENPs cross the BBB and then guide them towards the target site(s) deep in the brain (Guduru et al, 2015).…”