Influence of charges deposited on membranes of human hyperdirect pathway axons on depolarization during subthalamic deep brain stimulation
© 2023 IOP Publishing Ltd..
Objective.The motor hyperdirect pathway (HDP) is a key target in the treatment of Parkinson's disease with deep brain stimulation (DBS). Biophysical models of HDP DBS have been used to explore the mechanisms of stimulation. Built upon finite element method volume conductor solutions, such models are limited by a resolution mismatch, where the volume conductor is modeled at the macro scale, while the neural elements are at the micro scale. New techniques are needed to better integrate volume conductor models with neuron models.Approach.We simulated subthalamic DBS of the human HDP using finely meshed axon models to calculate surface charge deposition on insulting membranes of nonmyelinated axons. We converted the corresponding double layer extracellular problem to a single layer problem and applied the well-conditioned charge-based boundary element fast multipole method (BEM-FMM) with unconstrained numerical spatial resolution. Commonly used simplified estimations of membrane depolarization were compared with more realistic solutions.Main result.Neither centerline potential nor estimates of axon recruitment were impacted by the estimation method used except at axon bifurcations and hemispherical terminations. Local estimates of axon polarization were often much higher at bifurcations and terminations than at any other place along the axon and terminal arbor. Local average estimates of terminal electric field are higher by 10%-20%.Significance. Biophysical models of action potential initiation in the HDP suggest that axon terminations are often the lowest threshold elements for activation. The results of this study reinforce that hypothesis and suggest that this phenomenon is even more pronounced than previously realized.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Journal of neural engineering - 20(2023), 4 vom: 19. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Makaroff, Sergey N [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.07.2023 Date Revised 04.10.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1088/1741-2552/ace5de |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359302882 |
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| 100 | 1 | |a Makaroff, Sergey N |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Influence of charges deposited on membranes of human hyperdirect pathway axons on depolarization during subthalamic deep brain stimulation |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 21.07.2023 | ||
| 500 | |a Date Revised 04.10.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 IOP Publishing Ltd. | ||
| 520 | |a Objective.The motor hyperdirect pathway (HDP) is a key target in the treatment of Parkinson's disease with deep brain stimulation (DBS). Biophysical models of HDP DBS have been used to explore the mechanisms of stimulation. Built upon finite element method volume conductor solutions, such models are limited by a resolution mismatch, where the volume conductor is modeled at the macro scale, while the neural elements are at the micro scale. New techniques are needed to better integrate volume conductor models with neuron models.Approach.We simulated subthalamic DBS of the human HDP using finely meshed axon models to calculate surface charge deposition on insulting membranes of nonmyelinated axons. We converted the corresponding double layer extracellular problem to a single layer problem and applied the well-conditioned charge-based boundary element fast multipole method (BEM-FMM) with unconstrained numerical spatial resolution. Commonly used simplified estimations of membrane depolarization were compared with more realistic solutions.Main result.Neither centerline potential nor estimates of axon recruitment were impacted by the estimation method used except at axon bifurcations and hemispherical terminations. Local estimates of axon polarization were often much higher at bifurcations and terminations than at any other place along the axon and terminal arbor. Local average estimates of terminal electric field are higher by 10%-20%.Significance. Biophysical models of action potential initiation in the HDP suggest that axon terminations are often the lowest threshold elements for activation. The results of this study reinforce that hypothesis and suggest that this phenomenon is even more pronounced than previously realized | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a boundary element fast multipole method (BEM-FMM) | |
| 650 | 4 | |a charge deposition | |
| 650 | 4 | |a deep brain stimulation (DBS) | |
| 650 | 4 | |a effect of axonal terminations and bifurcations | |
| 650 | 4 | |a extracellular solution | |
| 650 | 4 | |a motor hyperdirect pathway (HDP) | |
| 650 | 4 | |a multiscale numerical modeling | |
| 700 | 1 | |a Nummenmaa, Aapo R |e verfasserin |4 aut | |
| 700 | 1 | |a Noetscher, Gregory M |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a McIntyre, Cameron C |e verfasserin |4 aut | |
| 700 | 1 | |a Bingham, Clayton S |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:20 |g year:2023 |g number:4 |g day:19 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1088/1741-2552/ace5de |3 Volltext |
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