Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice

Abstract

Devices that electrically modulate the deep brain have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices are typically centimeter-scale, requiring surgical implantation and wired-in powering, which increases the risk of hemorrhage, infection, and damage during daily activity. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Here, we present injectable, magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. This mechanism of modulation requires no genetic modification of neural tissue, allows animals to freely move during stimulation, and uses nonresonant carrier frequencies. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local subthalamic 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.

Probing Neuro-Endocrine Interactions Through Wireless Magnetothermal Stimulation of Peripheral Organs

“…However, their utility as tools for neuropsychiatric treatment and investigation is less defined. While intracranial or deep brain MNP stimulation has mostly been validated with motor behaviors (55), these particles may be a valuable tool for creating and/or manipulating models of neuropsychiatric disorders (43,56). For instance, MNP stimulation of the prelimbic cortex reduced immobility in the forced-swim test and increased sucrose consumption in stressed mice (56).…”

Implantable Pulse Generators for Deep Brain Stimulation: Challenges, Complications, and Strategies for Practicality and Longevity

“…(Chen et al, 2018). (Middle) Piezoelectric nanoparticles can activate neurons when they are powered using an external magnetic field (Kozielski et al, 2021) or ultrasound (Marino et al, 2015). No genetic modification is needed for this method.…”

“…This approach involves the use of magnetoelectric nanoparticles (MENPs) produced from magnetostrictive CoFe 2 O 4 nanoparticles coated with piezoelectric BaTiO 3 (Kozielski et al, 2021). In vivo studies have demonstrated that MENPs injected cells can be activated under remote non-resonant frequency magnetic stimulation, which is sufficient to cause neural activation to change animal behavior.…”

Translational considerations for the design of untethered nanomaterials in human neural stimulation

“…In cancer theranostics, for example, nanomaterials are mainly used as environmentally-sensitive carriers of drugs or bioactive molecules, and can be actively or passively targeted to tumor cells, while ignoring healthy tissue. For neurostimulation, however, the nanomaterials themselves are typically the cargo, so that they may act as nanotransducers of external signals to modulate neuronal activity [17]. Similar properties have previously been exploited in clinically-approved thermal ablation procedures with magnetic iron oxide particles for some types of tumors [18].…”