Soft Neural Interfaces for Circuit-Level Analysis of Magnetogenetic Deep Brain Stimulation in Parkinson's Disease Models

Abstract

Magnetogenetic deep brain stimulation (MG-DBS) represents a wireless neuromodulation that has demonstrated long-lasting behavioral benefits in Parkinson's disease models. However, the circuit-level mechanisms underlying these therapeutic effects have remained uncharacterized due to limitations of conventional neural interfaces. We present a bio-integrable soft neural interface featuring ultrasoft liquid-metal probes with bioresorbable stiffeners and customizable interconnects directly printed onto cranial surfaces to match individual skull anatomy and nanoparticle injection sites. This platform enables stable multi-regional recordings from deep brain structures without chronic tissue damage. We systematically investigate MG-DBS therapeutic mechanisms in a Parkinson's disease mouse model. Circuit-level analysis reveals that MG-DBS modulates pathological beta-band oscillations and inter-regional synchrony across the cortico-basal ganglia-thalamic circuit. Direct comparison with conventional electrical DBS demonstrates that MG-DBS effects persisted approximately fifteen-fold longer after stimulation cessation. Our electrophysiological recordings elucidate the mechanistic basis for this sustained therapeutic effect, providing unprecedented insights into magnetogenetic neuromodulation dynamics.