Millimeter-sized battery-free epidural cortical stimulators

Refractory neurological and psychiatric disorders are increasingly treated with brain stimulation therapies using implanted neuromodulation devices. Current commercially available stimulation systems, however, are limited by the need for implantable pulse generators and wired power; the complexity of this architecture creates multiple failure points including lead fractures, migration, and infection. Enabling less invasive approaches could increase access to these therapies. Here we demonstrate the first millimeter-sized leadless brain stimulator in large animal and human subjects. This Digitally programmable Over-brain Therapeutic (or DOT) is approximately 1 cm in width yet can produce sufficient energy to stimulate cortical activity on-demand through the dura. This extreme miniaturization is possible using recently developed magnetoelectric wireless power transfer that allows us to reach power levels required to stimulate the surface of the brain without direct contact to the cortical surface. This externally powered cortical stimulation (XCS) opens the possibility of simple minimally invasive surgical procedures to enable precise, long-lasting, and at-home neuromodulation with tiny implants that never contact the surface of the brain. ### Competing Interest Statement JTR, AS, SuAS, SaAS, and JW receive monetary and/or equity compensation from Motif Neurotech. SaAS has consulting agreements with Zimmer Biomet, Boston Scientific, Koh Young, Neuropace, Varian, Sensoria Therapeutics. SuAS has consulting agreements with Viz.AI, Penumbra, and Imperative Care as well as grant funding from Viz.AI and NIH. The terms of these arrangements have been reviewed and approved by Rice University, UTHealth, and Baylor college of Medicine in accordance with their policies on conflict of interest in research. The other authors declare no competing interests. ### Funding Statement Funding for this work was provided by the McNair Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Baylor College of Medicine and affiliated hospitals gave ethical approval for this work. This is not a health-related intervention and there were no health-related outcomes from this study. As a result, this study was not registered with a regulatory agency. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes