Ultrasound brain stimulation technologies for targeted therapeutics - Nature

IntroductionParkinson’s disease (PD) is the most rapidly expanding neurodegenerative condition1,2, characterized by the progressive degeneration of dopaminergic neurons within the substantia nigra3. Dopamine replacement therapy with levodopa, together with high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN), remain the most effective interventions for alleviating PD-related motor symptoms4,5. Yet despite their widespread clinical use, the neural circuit mechanisms through which these treatments exert their therapeutic effects are still not fully understood6. One of the proposed target circuits of STN-DBS is the monosynaptic cortico-subthalamic hyperdirect pathway, which has been implicated in rapid movement cancellation, in the emergence of pathological synchronization, and as a key substrate through which STN-DBS may influence network dynamics7,8,9,10. Although computational models and animal experiments have highlighted the importance of this pathway11,12,13, direct causal evidence for how dopaminergic state shapes hyperdirect STN excitation in humans remains scarce9,14.

Simulation of multi-focal ultrasound stimulation based on a human skull modelImage source: DGIST DGIST and GIST achieve multi-site brain stimulation using a single ultrasound transducer and demonstrate improvements in neuropathic pain

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