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.

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.

Deep brain stimulation (DBS) is among the most successful paradigms in both translational and reverse translational neuroscience. DBS has developed into a standard treatment for movement disorders such as Parkinson’s disease (PD) in recent decades, however, specific mechanisms behind DBS’s efficacy and side effects remain unrevealed. Several hypotheses have been proposed, including neuronal firing rate and pattern theories that emphasize the impact of DBS on local circuitry but detail distant electrophysiological readouts to a lesser extent. Furthermore, ample preclinical and clinical evidence indicates that DBS influences neurotransmitter dynamics in PD, particularly the effects of subthalamic nucleus (STN) DBS on striatal dopaminergic and glutamatergic systems; pallidum DBS on striatal dopaminergic and GABAergic systems; pedunculopontine nucleus DBS on cholinergic systems; and STN-DBS on locus coeruleus (LC) noradrenergic system. DBS has additionally been associated with mood-related side effects within brainstem serotoninergic systems in response to STN-DBS. Still, addressing the mechanisms of DBS on neurotransmitters’ dynamics is commonly overlooked due to its practical difficulties in monitoring real-time changes in remote areas. Given that electrical stimulation alters neurotransmitter release in local and remote regions, it eventually exhibits changes in specific neuronal functions. Consequently, such changes lead to further modulation, synthesis, and release of neurotransmitters. This narrative review discusses the main neurotransmitter dynamics in PD and their role in mediating DBS effects from preclinical and clinical data.