Remote Magnetomechanical Neuromodulation Uncovers Therapeutic Mechanisms for Alleviating Parkinsonian Symptoms in...

To overcome the limitations of invasive neuromodulation systems, we introduce a wireless magnetomechanical approach for remote, minimally-invasive deep brain stimulation (DBS) without chronically implanted hardware. This method leverages biocompatible magnetite nanodiscs (MNDs) with ground vortex magnetization, which undergo in-plane transitions under low-frequency alternating magnetic fields, generating localized piconewton-scale torques. These torques engage endogenous mechanosensory pathways to modulate neural activity, enabling reversible stimulation without genetic modifications. Calcium-imaging validated rapid neuromodulatory effects of MNDs in vitro and ex vivo, motivating the application of magnetomechanical DBS to the subthalamic nucleus in mice. We demonstrated remote control of motor behavior in wild-type mice and significant restoration of motor function in a severe hemiparkinsonian model. Demonstrating efficacy at multiple experimental scales, this work establishes a clinically compatible, electrode-free neuromodulation technology combining nanoscale engineering with mechanosensory signaling, paving the way toward a minimally-invasive DBS approach suitable for outpatient use and for patients ineligible for conventional DBS.