Temporal Interference Stimulation Enhances Neural Regeneration

Neural regeneration therapies aim to treat neurodegeneration by promoting the maturation of exogenous or endogenous neural progenitor cells (NPCs). However, their efficacy has been limited. Deep brain stimulation (DBS) via implanted electrodes has been shown to promote neurogenesis. However, its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) has emerged as a strategy for non-invasive, high-precision DBS using multiple kHz-range electric fields with a frequency difference within the range of neural activity. Here, we report the validation of neural regeneration augmentation by TI stimulation. We demonstrate that TI stimulation with a theta-band frequency difference enhances the maturation of embryonic neural progenitor cells in vitro. We then demonstrate that theta-band TI stimulation of the hippocampus enhances endogenous hippocampal neurogenesis in an in vivo mouse model of Alzheimer's disease. By uncovering frequency-specific control of stem cell fate, we propose a clinically relevant regeneration strategy which avoids pharmacological or genetic manipulation. Our results demonstrate focal, non-invasive augmentation of deep-brain neural regeneration.