A simulation study of nerve fiber activation in the lumbar segment under kilohertz-frequency transcutaneously spinal cord stimulation_Journal of Biomedical Engineering

Authors：

 XU Qi ¹ , LI Xinru ¹ , LU Zhixin ¹ , WU Yongchao ²

1. School of Artificial Intelligence and Automation, Huazhong University of Science and Technology, Wuhan 430074, P. R. China;
2. Department of Rehabilitation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China;

Corresponding author：

XU Qi, Email: xuqi@hust.edu.cn

Keywords：

Kilohertz frequency; Transcutaneous spinal cord stimulation; Neuron model; Spinal fiber

DOI：

10.7507/1001-5515.202407004

Video：

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Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of human percutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T₁₂ to L₂, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.

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3.	Rahman M A, Tharu N S, Gustin S M, et al. Trans-spinal electrical stimulation therapy for functional rehabilitation after spinal cord injury. J Clin Med, 2022, 11(6): 1550.
4.	Tharu N S, Alam M, Ling Y T, et al. Combined transcutaneous electrical spinal cord stimulation and task-specific rehabilitation improves trunk and sitting functions in people with chronic tetraplegia. Biomedicines, 2022, 11(1): 34.
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6.	Kapural L, Yu C, Doust M W, et al. Novel 10-kHz high-frequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA-RCT randomized controlled trial. Anesthesiology, 2015, 123(4): 851-860.
7.	de Freitas R M, Capogrosso M, Nomura T, et al. Preferential activation of proprioceptive and cutaneous sensory fibers compared to motor fibers during cervical transcutaneous spinal cord stimulation: a computational study. J Neural Eng, 2022, 19(3): 036012.
8.	de Freitas R M, Capogrosso M, Nomura T, et al. Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. Artif Organs, 2022, 46(10): 2015-2026.
9.	Lempka S F, McIntyre C C, Kilgore K L, et al. Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management. Anesthesiology, 2015, 122(6): 1362-1376.
10.	McIntyre C C, Richardson A G, Grill W M. Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. J Neurophysiol, 2002, 87(2): 995-1006.
11.	Inanici F, Brighton L N, Samejima S, et al. Transcutaneous spinal cord stimulation restores hand and arm function after spinal cord injury. IEEE Trans Neural Sys Rehabil Eng, 2021, 29: 310-319.
12.	Ward A R, Robertson V J. Sensory, motor, and pain thresholds for stimulation with medium frequency alternating current. Arch Phys Med Rehabil, 1998, 79(3): 273-278.
13.	Miller J P, Eldabe S, Buchser E, et al. Parameters of spinal cord stimulation and their role in electrical charge delivery: a review. Neuromodulation, 2016, 19(4): 373-384.
14.	Holsheimer J, Buitenweg J R, Das J, et al. The effect of pulse width and contact configuration on paresthesia coverage in spinal cord stimulation. Neurosurgery, 2011, 68(5): 1452-1461.
15.	Kreydin E, Zhong H, Latack K, et al. Transcutaneous electrical spinal cord neuromodulator (TESCoN) improves symptoms of overactive bladder. Front Syst Neurosci, 2020, 14: 1.
16.	Hofstoetter U S, Krenn M, Danner S M, et al. Augmentation of voluntary locomotor activity by transcutaneous spinal cord stimulation in motor‐incomplete spinal cord‐injured individuals. Artif Organs, 2015, 39(10): E176-E186.
17.	Violante I R, Alania K, Cassarà A M, et al. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci, 2023, 26(11): 1994-2004.
18.	Spielholz N I, Nolan M F. Conventional TENS and the phenomena of accommodation, adaption, habituation, and electrode polarization. J Clin Electrophysiol, 1995, 7: 16-19.
19.	Huang Y, Parra L C. Can transcranial electric stimulation with multiple electrodes reach deep targets?. Brain Stimul, 2019, 12(1): 30-40.
20.	Bryson N, Lombardi L, Hawthorn R, et al. Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration. J Neural Eng, 2023, 20(4): 046015.

1. Megía García A, Serrano-Muñoz D, Taylor J, et al. Transcutaneous spinal cord stimulation and motor rehabilitation in spinal cord injury: a systematic review. Neurorehabil Neural Repair, 2020, 34(1): 3-12.
2. Ladenbauer J, Minassian K, Hofstoetter U S, et al. Stimulation of the human lumbar spinal cord with implanted and surface electrodes: a computer simulation study. IEEE Trans Neural Syst Rehabil Eng, 2010, 18(6): 637-645.
3. Rahman M A, Tharu N S, Gustin S M, et al. Trans-spinal electrical stimulation therapy for functional rehabilitation after spinal cord injury. J Clin Med, 2022, 11(6): 1550.
4. Tharu N S, Alam M, Ling Y T, et al. Combined transcutaneous electrical spinal cord stimulation and task-specific rehabilitation improves trunk and sitting functions in people with chronic tetraplegia. Biomedicines, 2022, 11(1): 34.
5. Moritz C, Field-Fote E C, Tefertiller C, et al. Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial. Nat Med, 2024, 30(5): 1276-1283.
6. Kapural L, Yu C, Doust M W, et al. Novel 10-kHz high-frequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA-RCT randomized controlled trial. Anesthesiology, 2015, 123(4): 851-860.
7. de Freitas R M, Capogrosso M, Nomura T, et al. Preferential activation of proprioceptive and cutaneous sensory fibers compared to motor fibers during cervical transcutaneous spinal cord stimulation: a computational study. J Neural Eng, 2022, 19(3): 036012.
8. de Freitas R M, Capogrosso M, Nomura T, et al. Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. Artif Organs, 2022, 46(10): 2015-2026.
9. Lempka S F, McIntyre C C, Kilgore K L, et al. Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management. Anesthesiology, 2015, 122(6): 1362-1376.
10. McIntyre C C, Richardson A G, Grill W M. Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. J Neurophysiol, 2002, 87(2): 995-1006.
11. Inanici F, Brighton L N, Samejima S, et al. Transcutaneous spinal cord stimulation restores hand and arm function after spinal cord injury. IEEE Trans Neural Sys Rehabil Eng, 2021, 29: 310-319.
12. Ward A R, Robertson V J. Sensory, motor, and pain thresholds for stimulation with medium frequency alternating current. Arch Phys Med Rehabil, 1998, 79(3): 273-278.
13. Miller J P, Eldabe S, Buchser E, et al. Parameters of spinal cord stimulation and their role in electrical charge delivery: a review. Neuromodulation, 2016, 19(4): 373-384.
14. Holsheimer J, Buitenweg J R, Das J, et al. The effect of pulse width and contact configuration on paresthesia coverage in spinal cord stimulation. Neurosurgery, 2011, 68(5): 1452-1461.
15. Kreydin E, Zhong H, Latack K, et al. Transcutaneous electrical spinal cord neuromodulator (TESCoN) improves symptoms of overactive bladder. Front Syst Neurosci, 2020, 14: 1.
16. Hofstoetter U S, Krenn M, Danner S M, et al. Augmentation of voluntary locomotor activity by transcutaneous spinal cord stimulation in motor‐incomplete spinal cord‐injured individuals. Artif Organs, 2015, 39(10): E176-E186.
17. Violante I R, Alania K, Cassarà A M, et al. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci, 2023, 26(11): 1994-2004.
18. Spielholz N I, Nolan M F. Conventional TENS and the phenomena of accommodation, adaption, habituation, and electrode polarization. J Clin Electrophysiol, 1995, 7: 16-19.
19. Huang Y, Parra L C. Can transcranial electric stimulation with multiple electrodes reach deep targets?. Brain Stimul, 2019, 12(1): 30-40.
20. Bryson N, Lombardi L, Hawthorn R, et al. Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration. J Neural Eng, 2023, 20(4): 046015.

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