Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents
Introduction: Dorsal column stimulation (DCS) of the spinal cord is emerging as a promising new technology to treat Parkinson's disease (PD). However, optimal stimulation settings that maximize its therapeutic effect on PD symptoms are yet to be determined. To optimize DCS therapy, it is necess...
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Elsevier
2025-09-01
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| Series: | Brain Stimulation |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X25002931 |
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| author | Jacob C. Slack Benjamin Rees Eleonora Borda Jonah Slack Miguel A.L. Nicolelis S. Elizabeth Zauber Kunal Gupta Amol P. Yadav |
| author_facet | Jacob C. Slack Benjamin Rees Eleonora Borda Jonah Slack Miguel A.L. Nicolelis S. Elizabeth Zauber Kunal Gupta Amol P. Yadav |
| author_sort | Jacob C. Slack |
| collection | DOAJ |
| description | Introduction: Dorsal column stimulation (DCS) of the spinal cord is emerging as a promising new technology to treat Parkinson's disease (PD). However, optimal stimulation settings that maximize its therapeutic effect on PD symptoms are yet to be determined. To optimize DCS therapy, it is necessary to understand its impact on pathological brain oscillations and to deliver stimulation triggered by neurophysiological biomarkers of PD. Materials and methods: We developed beta-triggered DCS (BT-DCS), where DCS was triggered by ongoing corticostriatal beta oscillations, and tested it in the bilateral intra-striatal 6-hydroxydopamine (6-OHDA) rat model of PD. To evaluate the translational potential of DCS in humans, we recorded local field potentials (LFPs) from bilateral subthalamic nucleus (STN) electrodes in a sixty-year-old PD subject with freezing of gait (FOG) symptoms before and three days after implantation of DCS leads. Results: DCS triggered by corticostriatal beta oscillations facilitated a pro-locomotion brain state that improved locomotion, reduced akinesia, and desynchronized ongoing oscillations in the rat model. BT-DCS achieved higher efficacy with less overall charge delivery than continuous stimulation. In the PD subject, DCS increased gait velocity and stride length, reduced freezing episodes, and desynchronized subthalamic nucleus (STN) beta oscillations, while modulating phase-amplitude coupling (PAC). When applied simultaneously with deep brain stimulation (DBS), DCS had a combinatory effect on gait improvement. Conclusion: Based on the effective implementation of BT-DCS in modulating supraspinal pathological brain activity in rats, we envision that incorporating a brain biomarker signal in delivering DCS therapy in humans could improve relief from Parkinsonian gait issues. |
| format | Article |
| id | doaj-art-79fa1c240e5c4d4698d31cc1a57a15a9 |
| institution | DOAJ |
| issn | 1935-861X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj-art-79fa1c240e5c4d4698d31cc1a57a15a92025-08-20T02:58:27ZengElsevierBrain Stimulation1935-861X2025-09-011851407142210.1016/j.brs.2025.07.020Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodentsJacob C. Slack0Benjamin Rees1Eleonora Borda2Jonah Slack3Miguel A.L. Nicolelis4S. Elizabeth Zauber5Kunal Gupta6Amol P. Yadav7Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, 27599, USAPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USACenter for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, Chemin des Mines 9, 1202, Geneva, SwitzerlandDepartment of Computer Science, Indiana University, Bloomington, IN, USADepartment of Neurobiology, Duke University, Durham, NC, 27710, USADepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN, 46202, USADepartment of Neurosurgery, Neuroscience Research Center, Department of Cell Biology, Neurobiology, and Anatomy, Froedtert & the Medical College of Wisconsin, Milwaukee, WI, 53226, USALampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, 27599, USA; Department of Neurosurgery, UNC School of Medicine, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; Corresponding author. Joint Department of Biomedical Engineering, University of North Carolina – Chapel Hill and North Carolina State University Chapel Hill, NC, 27599, USA.Introduction: Dorsal column stimulation (DCS) of the spinal cord is emerging as a promising new technology to treat Parkinson's disease (PD). However, optimal stimulation settings that maximize its therapeutic effect on PD symptoms are yet to be determined. To optimize DCS therapy, it is necessary to understand its impact on pathological brain oscillations and to deliver stimulation triggered by neurophysiological biomarkers of PD. Materials and methods: We developed beta-triggered DCS (BT-DCS), where DCS was triggered by ongoing corticostriatal beta oscillations, and tested it in the bilateral intra-striatal 6-hydroxydopamine (6-OHDA) rat model of PD. To evaluate the translational potential of DCS in humans, we recorded local field potentials (LFPs) from bilateral subthalamic nucleus (STN) electrodes in a sixty-year-old PD subject with freezing of gait (FOG) symptoms before and three days after implantation of DCS leads. Results: DCS triggered by corticostriatal beta oscillations facilitated a pro-locomotion brain state that improved locomotion, reduced akinesia, and desynchronized ongoing oscillations in the rat model. BT-DCS achieved higher efficacy with less overall charge delivery than continuous stimulation. In the PD subject, DCS increased gait velocity and stride length, reduced freezing episodes, and desynchronized subthalamic nucleus (STN) beta oscillations, while modulating phase-amplitude coupling (PAC). When applied simultaneously with deep brain stimulation (DBS), DCS had a combinatory effect on gait improvement. Conclusion: Based on the effective implementation of BT-DCS in modulating supraspinal pathological brain activity in rats, we envision that incorporating a brain biomarker signal in delivering DCS therapy in humans could improve relief from Parkinsonian gait issues.http://www.sciencedirect.com/science/article/pii/S1935861X25002931Spinal cord stimulationParkinson's diseaseMovement disordersFreezing of gaitDorsal column stimulationDeep brain stimulation |
| spellingShingle | Jacob C. Slack Benjamin Rees Eleonora Borda Jonah Slack Miguel A.L. Nicolelis S. Elizabeth Zauber Kunal Gupta Amol P. Yadav Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents Brain Stimulation Spinal cord stimulation Parkinson's disease Movement disorders Freezing of gait Dorsal column stimulation Deep brain stimulation |
| title | Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents |
| title_full | Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents |
| title_fullStr | Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents |
| title_full_unstemmed | Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents |
| title_short | Spinal cord stimulation restores locomotion in a Parkinson's disease patient and rodents |
| title_sort | spinal cord stimulation restores locomotion in a parkinson s disease patient and rodents |
| topic | Spinal cord stimulation Parkinson's disease Movement disorders Freezing of gait Dorsal column stimulation Deep brain stimulation |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X25002931 |
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