Assessment of the Use of Multi-Channel Organic Electrodes to Record ENG on Small Nerves: Application to Phrenic Nerve Burst Detection

Effective closed-loop neuromodulation relies on the acquisition of appropriate physiological control variables and the delivery of an appropriate stimulation signal. In particular, electroneurogram (ENG) data acquired from a set of electrodes applied at the surface of the nerve may be used as a potential control variable in this field. Improved electrode technologies and data processing methods are clearly needed in this context. In this work, we evaluated a new electrode technology based on multichannel organic electrodes (OE) and applied a signal processing chain in order to detect respiratory-related bursts from the phrenic nerve. Phrenic ENG (pENG) were acquired from nine Long Evans rats in situ preparations. For each preparation, a 16-channel OE was applied around the phrenic nerve’s surface and a suction electrode was applied to the cut end of the same nerve. The former electrode provided input multivariate pENG signals while the latter electrode provided the gold standard for data analysis. Correlations between OE signals and that from the gold standard were estimated. Signal to noise ratio (SNR) and ROC curves were built to quantify phrenic bursts detection performance. Correlation score showed the ability of the OE to record high-quality pENG. Our methods allowed good phrenic bursts detection. However, we failed to demonstrate a spatial selectivity from the multiple pENG recorded with our OE matrix. Altogether, our results suggest that highly flexible and biocompatible multi-channel electrode may represent an interesting alternative to metallic cuff electrodes to perform nerve bursts detection and/or closed-loop neuromodulation.

[1]  George G. Malliaras,et al.  PEDOT:PSS electrodes for acute experimental evaluation of vagus nerve stimulation on rodents , 2018, 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[2]  E. Ottestad,et al.  History of Peripheral Nerve Stimulation-Update for the 21st Century. , 2020, Pain medicine.

[3]  P. Leleux,et al.  In vivo recordings of brain activity using organic transistors , 2013, Nature Communications.

[4]  C. Gestreau,et al.  Quipazine Elicits Swallowing in the Arterially Perfused Rat Preparation: A Role for Medullary Raphe Nuclei? , 2020, International journal of molecular sciences.

[5]  Christian Bergaud,et al.  In vitro and in vivo biostability assessment of chronically-implanted Parylene C neural sensors , 2017 .

[6]  George G. Malliaras,et al.  Stability of PEDOT:PSS‐Coated Gold Electrodes in Cell Culture Conditions , 2019, Advanced Materials Technologies.

[7]  G. Buzsáki,et al.  NeuroGrid: recording action potentials from the surface of the brain , 2014, Nature Neuroscience.

[8]  John L. Parker,et al.  Technology for Peripheral Nerve Stimulation. , 2015, Progress in neurological surgery.

[9]  K. Mabuchi,et al.  Parylene flexible neural probes integrated with microfluidic channels. , 2005, Lab on a chip.

[10]  John P. Cunningham,et al.  A High-Performance Neural Prosthesis Enabled by Control Algorithm Design , 2012, Nature Neuroscience.

[11]  Christophe Bernard,et al.  High-performance transistors for bioelectronics through tuning of channel thickness , 2015, Science Advances.

[12]  Karl Deisseroth,et al.  Next-generation probes, particles, and proteins for neural interfacing , 2017, Science Advances.

[13]  Julian F. R. Paton,et al.  A working heart-brainstem preparation of the mouse , 1996, Journal of Neuroscience Methods.

[14]  Stéphane Bonnet,et al.  Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation , 2016, Journal of neural engineering.

[15]  M vandeVen,et al.  Impedimetric immunosensors based on the conjugated polymer PPV. , 2005, Biosensors & bioelectronics.

[16]  G. Wallace,et al.  Conducting polymers for neural interfaces: challenges in developing an effective long-term implant. , 2008, Biomaterials.

[17]  V. Fazan,et al.  Morphometric analysis of the phrenic nerve in male and female Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). , 2011, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[18]  K. Morris,et al.  Medullary respiratory neurones and control of laryngeal motoneurones during fictive eupnoea and cough in the cat , 2001, The Journal of physiology.

[19]  Y. Oku,et al.  Laryngeal afferent modulation of swallowing interneurons in the dorsal medulla in perfused rats , 2020, The Laryngoscope.

[20]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[21]  Christophe Bernard,et al.  Localized Neuron Stimulation with Organic Electrochemical Transistors on Delaminating Depth Probes , 2015, Advanced materials.

[22]  B. Jiao,et al.  Vagus nerve stimulation in brain diseases: Therapeutic applications and biological mechanisms , 2021, Neuroscience & Biobehavioral Reviews.

[23]  E. Romero,et al.  Neural morphological effects of long-term implantation of the self-sizing spiral cuff nerve electrode , 2006, Medical and Biological Engineering and Computing.

[24]  G. Malliaras,et al.  Achieving long-term stability of thin-film electrodes for neurostimulation. , 2021, Acta biomaterialia.

[25]  Robert Rieger,et al.  Noise and selectivity of velocity-selective multi-electrode nerve cuffs , 2008, Medical & Biological Engineering & Computing.

[26]  J M Carmena,et al.  In Vitro and In Vivo Evaluation of PEDOT Microelectrodes for Neural Stimulation and Recording , 2011, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[27]  R. O’Connor,et al.  Influence of PEDOT:PSS Coating Thickness on the Performance of Stimulation Electrodes , 2020, Advanced Materials Interfaces.

[28]  Mesut Sahin,et al.  Selective Stimulation of the Canine Hypoglossal Nerve Using a Multi-contact Cuff Electrode , 2004, Annals of Biomedical Engineering.

[29]  K. Chakravarthy,et al.  Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management , 2015, Current Pain and Headache Reports.

[30]  L. Manchikanti,et al.  Peripheral Neuromodulation for the Management of Headache , 2020, Anesthesiology and pain medicine.

[31]  K. Helke,et al.  Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease , 2017, Brain Stimulation.

[32]  T. G. Bautista,et al.  Ponto‐medullary nuclei involved in the generation of sequential pharyngeal swallowing and concomitant protective laryngeal adduction in situ , 2014, The Journal of physiology.

[33]  J. Gottschall The diaphragm of the rat and its innervation. Muscle fiber composition; perikarya and axons of efferent and afferent neurons , 2004, Anatomy and Embryology.

[34]  R. Coimbra,et al.  Electrical stimulation of the vagus nerve improves intestinal blood flow after trauma and hemorrhagic shock. , 2019, Surgery.

[35]  Christophe Bernard,et al.  Controlling Epileptiform Activity with Organic Electronic Ion Pumps , 2015, Advanced materials.

[36]  Ronald J. Triolo,et al.  “Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves” , 2017, Journal of NeuroEngineering and Rehabilitation.

[37]  Gary C Sieck,et al.  Breathing: Motor Control of Diaphragm Muscle. , 2018, Physiology.

[38]  G. Malliaras,et al.  Multimodal Characterization of Neural Networks Using Highly Transparent Electrode Arrays , 2018, eNeuro.

[39]  P. Leleux,et al.  Highly Conformable Conducting Polymer Electrodes for In Vivo Recordings , 2011, Advanced materials.

[40]  V. Fazan,et al.  Sensory and Motor Conduction Velocity in Spontaneously Hypertensive Rats: Sex and Aging Investigation , 2019, Front. Syst. Neurosci..

[41]  George G. Malliaras,et al.  Understanding volumetric capacitance in conducting polymers , 2016 .

[42]  Shih-Pin Chen,et al.  Vagus nerve stimulation inhibits cortical spreading depression , 2016, Pain.

[43]  A. Milby,et al.  Vagus nerve stimulation for epilepsy and depression , 2011, Neurotherapeutics.

[44]  Alain Bel,et al.  Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects , 2016, PloS one.

[45]  Christopher J. Bettinger,et al.  Recent advances in materials and flexible electronics for peripheral nerve interfaces , 2018, Bioelectronic Medicine.

[46]  Ronald J Triolo,et al.  Fascicular anatomy of human femoral nerve: implications for neural prostheses using nerve cuff electrodes. , 2009, Journal of rehabilitation research and development.

[47]  D. Durand,et al.  Functionally selective peripheral nerve stimulation with a flat interface nerve electrode , 2002, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[48]  M. Dutschmann,et al.  Activation of Orexin B receptors in the pontine Kölliker-Fuse nucleus modulates pre-inspiratory hypoglossal motor activity in rat , 2007, Respiratory Physiology & Neurobiology.

[49]  N. Katayama,et al.  Improvement of Diameter Selectivity in Nerve Recruitment Using Multi-cuff Electrodes , 2012 .

[50]  D. Markovic,et al.  Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy , 2011, Epilepsy & Behavior.

[51]  D M Durand,et al.  Spiral nerve cuff electrode for recordings of respiratory output. , 1997, Journal of applied physiology.

[52]  Tingting Xu,et al.  Organic Bioelectronics , 2022 .

[53]  K. Morris,et al.  Central chemoreceptor modulation of breathing via multipath tuning in medullary ventrolateral respiratory column circuits. , 2012, Journal of neurophysiology.

[54]  Guy Carrault,et al.  Closed-Loop Vagus Nerve Stimulation Based on State Transition Models , 2018, IEEE Transactions on Biomedical Engineering.

[55]  S. Zanella,et al.  TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons , 2013, The Journal of Neuroscience.

[56]  Igor A. Lavrov,et al.  Flexible parylene-based multielectrode array technology for high-density neural stimulation and recording , 2008 .

[57]  E. Scavetta,et al.  Stretchable Low Impedance Electrodes for Bioelectronic Recording from Small Peripheral Nerves , 2019, Scientific Reports.

[58]  M. Kilgard,et al.  Flat electrode contacts for vagus nerve stimulation , 2019, PloS one.

[59]  A. Bianchi,et al.  Activation of XII motoneurons and premotor neurons during various oropharyngeal behaviors , 2005, Respiratory Physiology & Neurobiology.

[60]  Y. Oku,et al.  Activity of swallowing‐related neurons in the medulla in the perfused brainstem preparation in rats , 2018, The Laryngoscope.

[61]  Stéphane Bonnet,et al.  Characteristics of the right cervical vagal activity during baseline and Valsalva-like manoeuvre , 2015, 2015 7th International IEEE/EMBS Conference on Neural Engineering (NER).

[62]  A. Leuchter,et al.  Trigeminal nerve stimulation in major depressive disorder: Acute outcomes in an open pilot study , 2013, Epilepsy & Behavior.

[63]  Niloy Bhadra,et al.  Peripheral Nerve and Muscle Stimulation , 2003 .

[64]  T. Stieglitz,et al.  A transverse intrafascicular multichannel electrode (TIME) to interface with the peripheral nerve. , 2010, Biosensors & bioelectronics.

[65]  S. Mackinnon,et al.  Chronic Nerve Compression—an Experimental Model in the Rat , 1984, Annals of plastic surgery.

[66]  S. Senova,et al.  Stimulation du nerf vague dans le traitement de la dépression , 2019 .

[67]  Samit Chakrabarty,et al.  Peripheral nerve bionic interface: a review of electrodes , 2019, International Journal of Intelligent Robotics and Applications.

[68]  S. Kim,et al.  Comparison of in vivo biocompatibilities between parylene-C and polydimethylsiloxane for implantable microelectronic devices , 2013, Bulletin of Materials Science.

[69]  Christophe Bernard,et al.  Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site , 2016, Proceedings of the National Academy of Sciences.