Deep brain stimulation of terminating axons

Background: Deep brain stimulation (DBS) of the subthalamic region is an established treatment for the motor symptoms of Parkinson's disease. Several types of neural elements reside in the subthalamic region, including subthalamic nucleus (STN) neurons, fibers of passage, and terminating affere...

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Main Authors: Kelsey L. Bower, Cameron C. McIntyre
Format: Article
Language:English
Published: Elsevier 2020-11-01
Series:Brain Stimulation
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X20302357
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author Kelsey L. Bower
Cameron C. McIntyre
author_facet Kelsey L. Bower
Cameron C. McIntyre
author_sort Kelsey L. Bower
collection DOAJ
description Background: Deep brain stimulation (DBS) of the subthalamic region is an established treatment for the motor symptoms of Parkinson's disease. Several types of neural elements reside in the subthalamic region, including subthalamic nucleus (STN) neurons, fibers of passage, and terminating afferents. Recent studies suggest that direct activation of a specific population of subthalamic afferents, known as the hyperdirect pathway, may be responsible for some of the therapeutic effects of subthalamic DBS. Objective: The goal of this study was to quantify how axon termination affects neural excitability from DBS. We evaluated how adjusting different stimulation parameters influenced the relative excitability of terminating axons (TAs) compared to fibers of passage (FOPs). Methods: We used finite element electric field models of DBS, coupled to multi-compartment cable models of axons, to calculate activation thresholds for populations of TAs and FOPs. These generalized models were used to evaluate the response to anodic vs. cathodic stimulation, with short vs. long stimulus pulses.Results: Terminating axons generally exhibited lower thresholds than fibers of passage across all tested parameters. Short pulse widths accentuated the relative excitability of TAs over FOPs.Conclusion(s): Our computational results demonstrate a hyperexcitability of terminating axons to DBS that is robust to variation in the stimulation parameters, as well as the axon model parameters.
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spelling doaj.art-7175483b052742759b582b964643bd6f2022-12-21T22:42:24ZengElsevierBrain Stimulation1935-861X2020-11-0113618631870Deep brain stimulation of terminating axonsKelsey L. Bower0Cameron C. McIntyre1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USACorresponding author. Department of Biomedical Engineering, Case Western Reserve University, 2103 Cornell Road, Rm 6224, Cleveland, OH, 44106, USA.; Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USABackground: Deep brain stimulation (DBS) of the subthalamic region is an established treatment for the motor symptoms of Parkinson's disease. Several types of neural elements reside in the subthalamic region, including subthalamic nucleus (STN) neurons, fibers of passage, and terminating afferents. Recent studies suggest that direct activation of a specific population of subthalamic afferents, known as the hyperdirect pathway, may be responsible for some of the therapeutic effects of subthalamic DBS. Objective: The goal of this study was to quantify how axon termination affects neural excitability from DBS. We evaluated how adjusting different stimulation parameters influenced the relative excitability of terminating axons (TAs) compared to fibers of passage (FOPs). Methods: We used finite element electric field models of DBS, coupled to multi-compartment cable models of axons, to calculate activation thresholds for populations of TAs and FOPs. These generalized models were used to evaluate the response to anodic vs. cathodic stimulation, with short vs. long stimulus pulses.Results: Terminating axons generally exhibited lower thresholds than fibers of passage across all tested parameters. Short pulse widths accentuated the relative excitability of TAs over FOPs.Conclusion(s): Our computational results demonstrate a hyperexcitability of terminating axons to DBS that is robust to variation in the stimulation parameters, as well as the axon model parameters.http://www.sciencedirect.com/science/article/pii/S1935861X20302357Hyperdirect pathwaySubthalamic nucleusAfferent inputsAnodicCathodic
spellingShingle Kelsey L. Bower
Cameron C. McIntyre
Deep brain stimulation of terminating axons
Brain Stimulation
Hyperdirect pathway
Subthalamic nucleus
Afferent inputs
Anodic
Cathodic
title Deep brain stimulation of terminating axons
title_full Deep brain stimulation of terminating axons
title_fullStr Deep brain stimulation of terminating axons
title_full_unstemmed Deep brain stimulation of terminating axons
title_short Deep brain stimulation of terminating axons
title_sort deep brain stimulation of terminating axons
topic Hyperdirect pathway
Subthalamic nucleus
Afferent inputs
Anodic
Cathodic
url http://www.sciencedirect.com/science/article/pii/S1935861X20302357
work_keys_str_mv AT kelseylbower deepbrainstimulationofterminatingaxons
AT cameroncmcintyre deepbrainstimulationofterminatingaxons