Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants

A series of animal experiments was conducted to characterize changes in the complex impedance of chronically implanted electrodes in neural tissue. Consistent trends in impedance changes were observed across all animals, characterized as a general increase in the measured impedance magnitude at 1 kHz. Impedance changes reach a peak approximately 7 days post-implant. Reactive responses around individual electrodes were described using immuno- and histo-chemistry and confocal microscopy. These observations were compared to measured impedance changes. Several features of impedance changes were able to differentiate between confined and extensive histological reactions. In general, impedance magnitude at 1 kHz was significantly increased in extensive reactions, starting about 4 days post-implant. Electrodes with extensive reactions also displayed impedance spectra with a characteristic change at high frequencies. This change was manifested in the formation of a semi-circular arc in the Nyquist space, suggestive of increased cellular density in close proximity to the electrode site. These results suggest that changes in impedance spectra are directly influenced by cellular distributions around implanted electrodes over time and that impedance measurements may provide an online assessment of cellular reactions to implanted devices.

[1]  X Liu,et al.  Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes. , 1999, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[2]  D. Edell,et al.  Factors influencing the biocompatibility of insertable silicon microshafts in cerebral cortex , 1992, IEEE Transactions on Biomedical Engineering.

[3]  C. Ayata,et al.  Monitoring cellular edema at single-neuron level by electrical resistance measurements , 1997, Journal of Neuroscience Methods.

[4]  B Wolf,et al.  Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. , 1997, Biosensors & bioelectronics.

[5]  W. Grill,et al.  Electrical properties of implant encapsulation tissue , 2006, Annals of Biomedical Engineering.

[6]  D. Kipke,et al.  Repeated voltage biasing improves unit recordings by reducing resistive tissue impedances , 2005, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[7]  D. Szarowski,et al.  Cerebral Astrocyte Response to Micromachined Silicon Implants , 1999, Experimental Neurology.

[8]  S. Retterer,et al.  Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex , 2005, Experimental Neurology.

[9]  G. Shah,et al.  Age-Related Changes in Glucose Transporter-One mRNA Structure and Function , 1997, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[10]  James D. Weiland,et al.  Chronic neural stimulation with thin-film, iridium oxide electrodes , 2000, IEEE Trans. Biomed. Eng..

[11]  Justin C. Williams,et al.  Flexible polyimide-based intracortical electrode arrays with bioactive capability , 2001, IEEE Transactions on Biomedical Engineering.

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

[13]  D. McCreery,et al.  Chronic microstimulation in the feline ventral cochlear nucleus: physiologic and histologic effects , 2000, Hearing Research.

[14]  Ivar Giaever,et al.  A morphological biosensor for mammalian cells , 1993, Nature.

[15]  M. Grattarola,et al.  Modeling the neuron-microtransducer junction: from extracellular to patch recording , 1993, IEEE Transactions on Biomedical Engineering.

[16]  J Jossinet,et al.  Tissue impedance: a historical overview. , 1995, Physiological measurement.

[17]  M. Nicolelis,et al.  Reconstructing the Engram: Simultaneous, Multisite, Many Single Neuron Recordings , 1997, Neuron.

[18]  Suzanne S. Stensaas,et al.  Histopathological evaluation of materials implanted in the cerebral cortex , 1978, Acta Neuropathologica.

[19]  B D Burns,et al.  Recording for several days from single cortical neurons in completely unrestrained cats. , 1974, Electroencephalography and clinical neurophysiology.

[20]  Justin C. Williams,et al.  Stability of chronic multichannel neural recordings: Implications for a long-term neural interface , 1999, Neurocomputing.

[21]  D. Szarowski,et al.  Brain responses to micro-machined silicon devices , 2003, Brain Research.

[22]  D. McCreery,et al.  Histopathologic evaluation of prolonged intracortical electrical stimulation , 1986, Experimental Neurology.

[23]  Patrick A Tresco,et al.  Chronic response of adult rat brain tissue to implants anchored to the skull. , 2004, Biomaterials.

[24]  D. Kipke,et al.  Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex. , 1999, Brain research. Brain research protocols.

[25]  W. Shain,et al.  Three-dimensional hydrogel cultures for modeling changes in tissue impedance around microfabricated neural probes , 2007, Journal of neural engineering.

[26]  R. Normann,et al.  Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex , 1998, Journal of Neuroscience Methods.

[27]  R. Shepherd,et al.  Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study , 1997, Hearing Research.

[28]  C. T. Chan,et al.  Characterization of three-dimensional tissue cultures using electrical impedance spectroscopy. , 1999, Biophysical journal.

[29]  K. E. Jones,et al.  A glass/silicon composite intracortical electrode array , 2006, Annals of Biomedical Engineering.

[30]  W. L. C. Rutten,et al.  Measurement of sealing resistance of cell-electrode interfaces in neuronal cultures using impedance spectroscopy , 1998, Medical and Biological Engineering and Computing.

[31]  M. Loda,et al.  Membranous expression of glucose transporter‐1 protein (GLUT‐1) in embryonal neoplasms of the central nervous system , 2000, Neuropathology and applied neurobiology.

[32]  J. Korf,et al.  Increases in Striatal and Hippocampal Impedance and Extracellular Levels of Amino Acids by Cardiac Arrest in Freely Moving Rats , 1988, Journal of neurochemistry.

[33]  J.C. Williams,et al.  Bias voltages at microelectrodes change neural interface properties in vivo , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[34]  F J Schuier,et al.  Experimental Brain Infarcts in Cats: II. Ischemic Brain Edema , 1980, Stroke.

[35]  Daryl R. Kipke,et al.  Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes , 2006, IEEE Transactions on Biomedical Engineering.

[36]  R A Normann,et al.  The Utah intracortical Electrode Array: a recording structure for potential brain-computer interfaces. , 1997, Electroencephalography and clinical neurophysiology.

[37]  Hideaki Ishiguro,et al.  Phenotypic diversity and kinetics of proliferating microglia and astrocytes following cortical stab wounds , 1996, Glia.

[38]  Daniel R Merrill,et al.  Impedance characterization of microarray recording electrodes in vitro , 2005, IEEE Trans. Biomed. Eng..

[39]  J. Korf,et al.  Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat , 1993, Neuropathology and applied neurobiology.

[40]  R A Normann,et al.  Chronic intracortical microstimulation (ICMS) of cat sensory cortex using the Utah Intracortical Electrode Array. , 1999, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[41]  E. McAdams,et al.  The linear and non-linear electrical properties of the electrode-electrolyte interface , 1995 .

[42]  Patrick A. Tresco,et al.  Impedance characterization of microarray recording electrodes in vitro , 2005, IEEE Transactions on Biomedical Engineering.

[43]  Christopher M.A. Brett,et al.  Electrochemistry: Principles, Methods, and Applications , 1993 .