Laser-Driven Wireless Deep Brain Stimulation Using Temporal Interference and Organic Electrolytic Photocapacitors

Deep brain stimulation (DBS) is a technique commonly used both in clinical and fundamental neurosciences. Classically, brain stimulation requires an implanted and wired electrode system to deliver stimulation directly to the target area. Although techniques such as temporal interference (TI) can provide stimulation at depth without involving any implanted electrodes, these methods still rely on a wired apparatus. Herein we report organic photocapacitors as untethered light-driven electrodes which convert deep-red light into electric current. Pairs of these ultrathin devices can be driven using lasers at two different frequencies to deliver stimulation at depth via temporally interfering fields. We validate this concept of laser TI stimulation using numerical modeling, <i>ex vivo</i> tests with phantom samples, and finally <i>in vivo</i> tests. Wireless organic photocapacitors are placed on the cortex and elicit stimulation in the hippocampus, while not delivering off-target stimulation in the cortex. This laser-driven wireless TI evoked a neuronal response at depth that is comparable to control experiments induced with deep brain stimulation protocols using implanted electrodes. Our work shows that a combination of these two techniques – temporal interference and organic electrolytic photocapacitors – provides a reliable way to target brain structures requiring neither deeply implanted electrodes nor tethered stimulator devices. The laser TI protocol demonstrated here address two of the most important drawbacks in the field of deep brain stimulation and thus holds potential to solve many issues in freely-moving animal experiments or for clinical chronic therapy application.