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09 23, 2020;10 (1): 15501.

Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array.

Ahmad A Jiman, David C Ratze, Elissa J Welle, Paras R Patel, Julianna M Richie, Elizabeth C Bottorff, John P Seymour, Cynthia A Chestek, Tim M Bruns
Author Information
  1. Ahmad A Jiman: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  2. David C Ratze: Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
  3. Elissa J Welle: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  4. Paras R Patel: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  5. Julianna M Richie: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  6. Elizabeth C Bottorff: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  7. John P Seymour: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  8. Cynthia A Chestek: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
  9. Tim M Bruns: Department of Biomedical Engineering, University of Michigan, NCRC - B10 - A-169, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA. bruns@umich.edu.
PMID: 32968177 DOI: 10.1038/s41598-020-72512-7

Abstract

Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8-9 µm in diameter, 150-250 µm in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1-91.7 µV and signal-to-noise ratios of 2.0-8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7-4.4 m/s) and efferent (0.7-8.8 m/s) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.

References

McCorry, L. K. Physiology of the autonomic nervous system. Am. J. Pharm. Educ. 71, 78 (2007). [PMID: 17786266]
Agostoni, E., Chinnock, J. E., De BurghDaly, M. & Murray, J. G. Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J. Physiol. 135, 182–205 (1957). [PMID: 13398974]
Andrews, P. L. R. Vagal afferent innervation of the gastrointestinal tract. Prog. Brain Res. 67, 65–86 (1986). [PMID: 3823483]
Berthoud, H. R. & Neuhuber, W. L. Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. Basic Clin. 85, 1–17 (2000). [DOI: 10.1016/S1566-0702(00)00215-0]
Borovikova, L. V. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462 (2000). [PMID: 10839541]
Browning, K. N., Verheijden, S. & Boeckxstaens, G. E. The vagus nerve in appetite regulation, mood, and intestinal inflammation. Gastroenterology 152, 730–744 (2017). [PMID: 27988382]
Berthoud, H. R. The vagus nerve, food intake and obesity. Regul. Pept. 149, 15–25 (2008). [PMID: 18482776]
Waise, T. M. Z., Dranse, H. J. & Lam, T. K. T. The metabolic role of vagal afferent innervation. Nat. Rev. Gastroenterol. Hepatol. 15, 625–636 (2018). [PMID: 30185916]
Qing, K. Y. et al. B fibers are the best predictors of cardiac activity during Vagus nerve stimulation. Bioelectron. Med. 4, 5 (2018). [PMID: 32232081]
Kajekar, R., Proud, D., Myers, A. C., Meeker, S. N. & Undem, B. J. Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea. J. Pharmacol. Exp. Ther. 289, 682–687 (1999). [PMID: 10215640]
Hoffman, H. H. & Schnitzlein, H. N. The numbers of nerve fibers in the vagus nerve of man. Anat. Rec. 139, 429–435 (1961). [PMID: 13963923]
Evans, D. H. L. & Murray, J. G. Histological and functional studies on the fibre composition of the vagus nerve of the rabbit. J. Anat. 88, 320–337 (1954). [PMID: 13192020]
Foley, J. O. & DuBois, F. S. Quantitative studies of the vagus nerve in the Cat. I. The ratio of sensory to motor fibers. J. Comp. Neurol. 67, 49–67 (1937). [DOI: 10.1002/cne.900670104]
Tracey, K. J. The revolutionary future of bioelectronic medicine. Bioelectron. Med. 1, 1 (2014). [DOI: 10.15424/bioelectronmed.2014.00001]
Birmingham, K. et al. Bioelectronic medicines: a research roadmap. Nat. Rev. Drug Discov. 13, 399–400 (2014). [PMID: 24875080]
Pavlov, V. A. & Tracey, K. J. Bioelectronic medicine: updates, challenges and paths forward. Bioelectron. Med. 5, 1 (2019). [PMID: 32232092]
Ben-Menachem, E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol. 1, 477–482 (2002). [PMID: 12849332]
Dawson, J. et al. Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke 47, 143–150 (2016). [PMID: 26645257]
Spindler, P., Bohlmann, K., Straub, H. B., Vajkoczy, P. & Schneider, U. C. Effects of vagus nerve stimulation on symptoms of depression in patients with difficult-to-treat epilepsy. Seizure 69, 77–79 (2019). [DOI: 10.1016/j.seizure.2019.04.001]
Koopman, F. A. et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 113, 8284–8289 (2016). [PMID: 27382171]
Apovian, C. M. et al. Two-year outcomes of vagal nerve blocking (vBloc) for the treatment of obesity in the recharge trial. Obes. Surg. 27, 169–176 (2017). [PMID: 27506803]
Shikora, S. A. et al. Intermittent vagal nerve block for improvements in obesity, cardiovascular risk factors, and glycemic control in patients with type 2 diabetes mellitus: 2-year results of the VBLOC DM2 study. Obes. Surg. 26, 1021–1028 (2015). [DOI: 10.1007/s11695-015-1914-1]
McCallum, G. A. et al. Chronic interfacing with the autonomic nervous system using carbon nanotube (CNT) yarn electrodes. Sci. Rep. 7, 11723 (2017). [PMID: 28916761]
Micera, S. & Navarro, X. Bidirectional Interfaces with the peripheral nervous system. Int. Rev. Neurobiol. 86, 23–38 (2009). [PMID: 19607988]
Larson, C. E. & Meng, E. A review for the peripheral nerve interface designer. J. Neurosci. Methods 332, 108523 (2019). [PMID: 31743684]
Guo, T. et al. Extracellular single-unit recordings from peripheral nerve axons in vitro by a novel multichannel microelectrode array. Sens. Actuators B Chem. 315, 128111 (2020). [DOI: 10.1016/j.snb.2020.128111]
Gabella, G. & Pease, H. L. Number of axons in the abdominal vagus of the rat. Brain Res. 58, 465–469 (1973). [PMID: 4756138]
Prechtl, J. C. & Powley, T. L. The fiber composition of the abdominal vagus of the rat. Anat. Embryol. (Berlin) 181, 101–115 (1990). [DOI: 10.1007/BF00198950]
Ward, M. P. et al. A flexible platform for biofeedback-driven control and personalization of electrical nerve stimulation therapy. IEEE Trans. Neural Syst. Rehabil. Eng. 23, 475–484 (2015). [PMID: 25167554]
Gillis, W. F. et al. Carbon fiber on polyimide ultra-microelectrodes. J. Neural Eng. 15, 016010 (2018). [PMID: 28905812]
Silverman, H. A. et al. Standardization of methods to record Vagus nerve activity in mice. Bioelectron. Med. 4, 3 (2018). [PMID: 32232079]
Zanos, T. et al. Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity. Proc. Natl. Acad. Sci. 115, E4843–E4852 (2018). [PMID: 29735654]
Shikano, Y., Nishimura, Y., Okonogi, T., Ikegaya, Y. & Sasaki, T. Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat. Eur. J. Neurosci. 49, 1298–1312 (2019). [PMID: 30450796]
González-González, M. A. et al. Thin film multi-electrode softening cuffs for selective neuromodulation. Sci. Rep. 8, 16390 (2018). [PMID: 30401906]
Masi, E. B. et al. Identification of hypoglycemia-specific neural signals by decoding murine vagus nerve activity. Bioelectron. Med. 5, 9 (2019). [PMID: 32232099]
Mathews, K. S. et al. Acute monitoring of genitourinary function using intrafascicular electrodes: selective pudendal nerve activity corresponding to bladder filling, bladder fullness, and genital stimulation. Urology 84, 722–729 (2014). [PMID: 25168559]
Wark, H. A. C. et al. A new high-density (25 electrodes/mm) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures. J. Neural Eng. 10, 045003 (2013). [PMID: 23723133]
DiBona, G. & Sawin, L. Role of renal alpha-2-adrenergic receptors in spontaneously hypertensive rats. Hypertension 9, 41–48 (1987). [PMID: 2878879]
DiBona, G. F., Sawin, L. L. & Jones, S. Y. Differentiated sympathetic neural control of the kidney. Am. J. Physiol. 271, R84–R90 (1996). [PMID: 8760207]
Kozai, T. et al. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nat. Mater. 11, 1065–1073 (2012). [PMID: 23142839]
Patel, P. R. et al. Insertion of linear 8.4 μm diameter 16 channel carbon fiber electrode arrays for single unit recordings. J. Neural Eng. 12, 046009 (2015). [PMID: 26035638]
Patel, P. R. et al. Chronic in vivo stability assessment of carbon fiber microelectrode arrays. J. Neural Eng. 13, 066002 (2016). [PMID: 27705958]
Welle, E. J. et al. Ultra-small carbon fiber electrode recording site optimization and improved in vivo chronic recording yield. J. Neural Eng. 17, 026037 (2020). [PMID: 32209743]
Moffitt, M. A. & McIntyre, C. C. Model-based analysis of cortical recording with silicon microelectrodes. Clin. Neurophysiol. 116, 2240–2250 (2005). [PMID: 16055377]
Henze, D. A. et al. Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J. Neurophysiol. 84, 390–400 (2000). [PMID: 10899213]
Yan, D. et al. Microneedle penetrating array with axon-sized dimensions for cuff-less peripheral nerve interfacing. In: 9th International IEEE EMBS Conference on Neural Engineering 827–830 (IEEE, 2019).
Rey, H. G., Pedreira, C. & Quian Quiroga, R. Past, present and future of spike sorting techniques. Brain Res. Bull. 119, 106–117 (2015). [PMID: 25931392]
Chang, R. B., Strochlic, D. E., Williams, E. K., Umans, B. D. & Liberles, S. D. Vagal sensory neuron subtypes that differentially control breathing. Cell 161, 622–633 (2015). [PMID: 25892222]
McAllen, R. M., Shafton, A. D., Bratton, B. O., Trevaks, D. & Furness, J. B. Calibration of thresholds for functional engagement of vagal A, B and C fiber groups in vivo. Bioelectron. Med. 1, 21–27 (2018). [DOI: 10.2217/bem-2017-0001]
Niijima, A. Glucose-sensitive afferent nerve fibers in the liver and their role in food intake and blood glucose regulation. J. Auton. Nerv. Syst. 9, 207–220 (1983). [PMID: 6663009]
Skovsted, P. & Sapthavichaikul, S. The effects of isoflurane on arterial pressure, pulse rate, autonomic nervous activity, and barostatic reflexes. Can. Anaesth. Soc. J. 24, 304–314 (1977). [PMID: 871935]
Carli, F., Ronzoni, G., Webster, J., Khan, K. & Elia, M. The independent metabolic effects of halo thane and isoflurane anaesthesia. Acta Anaesthesiol. Scand. 37, 672–678 (1993). [PMID: 8249557]
Welle, E. J. et al. Fabrication and characterization of a carbon fiber peripheral nerve electrode appropriate for chronic recording. In: Society for Neuroscience 49th Annual Meeting, Chicago, IL (Society for Neuroscience, 2019).
Chaure, F. J., Rey, H. G. & Quian Quiroga, R. A novel and fully automatic spike-sorting implementation with variable number of features. J. Neurophysiol. 120, 1859–1871 (2018). [PMID: 29995603]

Grants

  1. OT2 OD024907/NIH HHS

MeSH Term

Animals
Carbon Fiber
Electrodes, Implanted
Female
Male
Microelectrodes
Monitoring, Physiologic
Rats
Rats, Sprague-Dawley
Vagus Nerve

Chemicals

Carbon Fiber
Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

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