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Model‐Based Analysis of Lower Thoracic High‐Frequency Spinal Cord Stimulation (HF‐SCS) to Restore Effective Cough
Author(s) -
Zander Hans J.,
Kowalski Krzysztof E.,
DiMarco Anthony F.,
Lempka Scott F.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02120
Subject(s) - stimulation , spinal cord , anatomy , electrophysiology , spinal cord injury , stimulus (psychology) , dorsum , neuroscience , chemistry , excitatory postsynaptic potential , medicine , biomedical engineering , biology , inhibitory postsynaptic potential , psychology , psychotherapist
Background Spinal cord stimulation (SCS, 50 Hz) is a useful method to restore an effective cough in persons with spinal cord injury (SCI). In animal models, dorsal HF‐SCS (~500 Hz) produces similar level of expiratory muscle activation with much lower stimulus amplitudes. Currently, the mechanism of this behavior is unknown. Objective The aim of the present study was to develop a computational model of lower thoracic SCS to investigate the mechanisms of the expiratory muscle activation via HF‐SCS. Methods We created a computer model of an anatomically‐accurate finite element model (FEM) of the lower thoracic (T9) canine spinal cord and surrounding anatomy with an implanted SCS electrode array. This model consisted of two main components: 1) multicompartment cable models of dorsal afferent fibers and 2) ventral motor axons. Model analysis allowed calculation of the extracellular voltages generated during SCS and the corresponding activation thresholds of each fiber type. Results In our simulations, we calculated the activation thresholds for several electrode combinations and stimulation frequencies (50 Hz, 500 Hz). As expected, the activation thresholds of the ventral motor axons were significantly higher than the activation thresholds of dorsal root axons. Therefore, low‐frequency SCS likely functions through the direct activation of ventral motor axons, while high‐frequency SCS operates via recruitment of myelinated afferent fibers at significantly lower stimulation amplitudes. In our simulations, the stimulation frequency did not significantly alter activation thresholds in dorsal or ventral axons. Conclusions Our results suggest that both high‐ and low‐frequency SCS directly activate dorsal rootlets at low amplitudes (~1 mA); however, the trans‐synaptic spinal circuits responsible for eliciting cough are only effective at higher stimulation frequencies. Consequently, low‐frequency stimulation results in effective cough by bypassing this circuitry entirely to directly activate the ventral motor axons at the cost of requiring higher stimulation amplitudes. In future work, we will perform simulations directly assessing the ability of SCS to engage these spinal circuits. We will compare our model results to experimental measurements in an animal model of SCS to produce cough. Disclosure Dr. DiMarco holds two U.S. patents for technology related to the content of this abstract: Method and Apparatus for Electrical Activation of the Expiratory Muscles to Restore Cough (5,999,855) and Bipolar Spinal Cord Stimulation to Activate the Expiratory Muscles to Restore Cough (8,751,004). Support or Funding Information Merit Review Award I01‐RX‐001488 from the U.S. Department of Veterans Affairs, Rehabilitation Research and Development Service.