Parkinson’s disease leads to a spectrum of cardinal motor symptoms and locomotor deficits that vary in severity with the nature of daily activities and the fluctuating physiology of patients. Many of these deficits remain inadequately addressed by existing therapies that use continuous, activity-agnostic parameters. Instead, adaptive therapies embedding activity-specific parameters have the potential to better address the entire range of symptoms. Here, we expose physiological principles that enable real-time decoding of ongoing locomotor activities across motor fluctuations from the neural dynamics of the subthalamic nucleus. This decoding steered activity-dependent adaptations of deep brain stimulation therapies that improved both cardinal motor symptoms and locomotor deficits across activities of daily living. Our decoding framework provides a blueprint for next-generation neuromodulation therapies that continuously adapt parameters to the behavioral context and fluctuating physiology of each patient.

One Sentence Summary Neural decoders that leverage the physiological principles of activity-dependent encoding in the subthalamic nucleus support the implementation of adaptive deep brain stimulation therapies that alleviate locomotor deficits in people with Parkinson’s disease.

G.C., J.B., and E.M.M. hold patents partially related to this work, on the use of real-time brain decoding to trigger and control neuromodulation therapies for improving gait after neurological disorders (US 10668280). G.C. and J.B. are founders and shareholders of ONWARD Medical, a company with potential interest in the findings reported in this work. J.B. has received honoraria from Medtronic in relation to educational courses. The other authors declare no competing interests.

NCT06791902

This work was funded by the Swiss National Science Foundation (Grant number TMSGI3_218471), the Foundation for the Advancement of Neurology (project NeuroGAIT), the Parkinson Move Foundation, and the Defitech Foundation. The study was supported by Medtronic Inc. through the provision of the investigational Percept Tablet. Medtronic had no role in the design of the study, data collection, analysis or interpretation, or in the writing of the manuscript.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Swiss Ethics Committee (SwissEthics) gave ethical approval for this study (BASEC 2024-D0066, protocol no. 10001378, approved on 21 November 2024). The Swiss regulatory agency (Swissmedic) waived ethical approval for this work (SNCTP 000006185, protocol no. 102731544, approved on 23 December 2024)

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All data associated with this study are present in the paper or the Extended Data Materials. Anonymized data that support the findings of this study and custom code used will be made available upon reasonable request to the corresponding author (Eduardo.Moraudchuv.ch)