Spatially selective stimulation of the pig vagus nerve to modulate target effect versus side effect

被引:34
作者
Blanz, Stephan L. [1 ,2 ,3 ]
Musselman, Eric D. [4 ]
Settell, Megan L. [1 ,2 ]
Knudsen, Bruce E. [1 ,2 ]
Nicolai, Evan N. [1 ,2 ,5 ,6 ]
Trevathan, James K. [1 ,2 ]
Verner, Ryan S. [7 ]
Begnaud, Jason [7 ]
Skubal, Aaron C. [1 ,2 ]
Suminski, Aaron J. [2 ,8 ]
Williams, Justin C. [1 ,2 ,8 ]
Shoffstall, Andrew J. [9 ,10 ]
Grill, Warren M. [3 ,11 ,12 ,13 ]
Pelot, Nicole A. [4 ]
Ludwig, Kip A. [1 ,2 ,8 ]
机构
[1] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53706 USA
[2] Wisconsin Inst Translat Neuroengn WITNe, Madison, WI 53705 USA
[3] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA
[4] Duke Univ, Dept Biomed Engn, Durham, NC USA
[5] Mayo Clin, Grad Sch Biomed Sci, Rochester, MN USA
[6] Mayo Clin, Rochester, MN USA
[7] LivaNova USA Inc, Houston, TX USA
[8] Univ Wisconsin, Dept Neurol Surg, Madison, WI 53706 USA
[9] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH USA
[10] Louis Stokes Cleveland VA Med Ctr, APT Ctr, Cleveland, OH USA
[11] Duke Univ, Dept Elect & Comp Engn, Durham, NC USA
[12] Duke Univ, Dept Neurobiol, Durham, NC USA
[13] Duke Univ, Dept Neurosurg, Durham, NC USA
关键词
vagus nerve; VNS; neuromodulation; effect vs side effect; HEART-RATE-VARIABILITY; CONDUCTION-VELOCITY; VAGAL-STIMULATION; SPECTRAL-ANALYSIS; FIBERS; ACTIVATION; ELECTRODE; DIAMETER; MECHANISMS; SEIZURES;
D O I
10.1088/1741-2552/acb3fd
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Electrical stimulation of the cervical vagus nerve using implanted electrodes (VNS) is FDA-approved for the treatment of drug-resistant epilepsy, treatment-resistant depression, and most recently, chronic ischemic stroke rehabilitation. However, VNS is critically limited by the unwanted stimulation of nearby neck muscles-a result of non-specific stimulation activating motor nerve fibers within the vagus. Prior studies suggested that precise placement of small epineural electrodes can modify VNS therapeutic effects, such as cardiac responses. However, it remains unclear if placement can alter the balance between intended effect and limiting side effect. We used an FDA investigational device exemption approved six-contact epineural cuff to deliver VNS in pigs and quantified how epineural electrode location impacts on- and off-target VNS activation. Detailed post-mortem histology was conducted to understand how the underlying neuroanatomy impacts observed functional responses. Here we report the discovery and characterization of clear neuroanatomy-dependent differences in threshold and saturation for responses related to both effect (change in heart rate) and side effect (neck muscle contractions). The histological and electrophysiological data were used to develop and validate subject-specific computation models of VNS, creating a well-grounded quantitative framework to optimize electrode location-specific activation of nerve fibers governing intended effect versus unwanted side effect.
引用
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页数:21
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