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Sistem micro - electro - mecanic cu aplicatii in reconstructia
microchirurgicala a nervilor periferici – RECONECT


1. Action Potential Initiation in the Hodgkin-Huxley Model; PLoS Computational Biology; January 2009 | Volume 5 | Issue 1 | e1000265
Authors: Lucy J. Colwell, Michael P. Brenner
Keywords: action potential; Hodgkin-Huxley model; numerical simulation
Abstract: A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span) and the rapidity of action potential initiation (the onset rapidity). This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or invitro. Here we apply a method from theoretical physics to derive an analytical characterization of this problem. We analytically compute the probability distribution of onset potentials and analytically derive the inverse relationship between onset span and onset rapidity. We find that the relationship between onset span and onset rapidity depends on the level of synaptic background activity. Hence we are able to elucidate the regions of parameter space for which the Hodgkin-Huxley model is able to accurately describe the behavior of this system.

2. Activity-dependent elimination of neuromuscular Synapses; Journal of Neurocytology 32, 777–794 (2003)
Keywords: action potential; Hodgkin-Huxley model; numerical simulation
Abstract: At developing neuromuscular synapses in vertebrates, different motor axon inputs to muscle fibers compete for maintenance of their synapses. Competition results in progressive changes in synaptic structure and strength that lead to the weakening and loss of some inputs, a process that has been called synapse elimination. At the same time, a single input is strengthened and maintained throughout adult life, consistently recruiting muscle fibers to contract even at rapid firing rates.Work over the last decade has led to an understanding of some of the cell biological mechanisms that underlie competition and how these culminate in synapse elimination.We discuss current ideas about how activity modulates neuromuscular synaptic competition, how competition leads to synapse loss, and how these processes are modulated by cell cell signaling. A common feature of competition at neuromuscular as well as CNS synapses is that temporally correlated activity seems to slow or prevent competition, while uncorrelated activity seems to trigger or enhance competition. Important questions that remain to be addressed include how patterns of motor neuron activity affect synaptic strength, what is the temporal relationship between changes in synaptic strength and structure, and what cellular signals mediate synapse loss. Answers to these questions will expand our understanding of the mechanisms by which activity edits synaptic structure and function, writing permanent changes in neural circuitry.

3. An intrafascicular electrode for recording of action potentials in peripheral nerves
Authors: Mark S. Malagodi, Kenneth W. Horch , Andrew A. Schoenberg
Keywords:Neuroprosthesis - Peripheral nerve electrodes - Sensory recording
Abstract: We are developing a new type of bipolar recording electrode intended for implantation within individual fascicles of mammalian peripheral nerves. In the experiments reported here we used electrodes fabricated from 25 μm diameter Pt wire, 50 μm 90% Pt-10% Ir wire and 7 μm carbon fibers. The electrodes were implanted in the sciatic nerves of rats and in the ulnar nerves of cats. The signal-to-noise ratio of recorded activity induced by nonnoxious mechanical stimulation of the skin and joints was studied as a function of the type of electrode material used, the amount of insulation removed from the recording zone, and the longitudinal separation of the recording zones of bipolar electrode pairs. Both acute and short term (two day) chronic experiments were performed.
The results indicate that a bipolar electrode made from Teflon™-insulated, 25 μm diameter, 90% Pt-10% Ir wire, having a 1–2 mm long recording zone, can be used for recording of peripheral nerve activity when implanted with one wire inside the fascicle and the other lead level with the first lead, but outside the fascicle. No insulating cuff needs to be placed around the nerve trunk.

4. Direct neural sensory feedback and control of a prosthetic arm;Neural Systems and Rehabilitation Engineering, IEEE Transactions on Volume 13, Issue 4, Dec. 2005 Page(s):468 – 472
Authors: Dhillon, G.S.; Horch, K.W.
Keywords: electrodes; peripheral nerves; neural feedback
Abstract: Evidence indicates that user acceptance of modern artificial limbs by amputees would be significantly enhanced by a system that provides appropriate, graded, distally referred sensations of touch and joint movement, and that the functionality of limb prostheses would be improved by a more natural control mechanism. We have recently demonstrated that it is possible to implant electrodes within individual fascicles of peripheral nerve stumps in amputees, that stimulation through these electrodes can produce graded, discrete sensations of touch or movement referred to the amputee's phantom hand, and that recordings of motor neuron activity associated with attempted movements of the phantom limb through these electrodes can be used as graded control signals. We report here that this approach allows amputees to both judge and set grip force and joint position in an artificial arm, in the absence of visual input, thus providing a substrate for better integration of the artificial limb into the amputee's body image. We believe this to be the first demonstration of direct neural feedback from and direct neural control of an artificial arm in amputees.

5. SELECTIVE ELECTRICAL INTERFACES WITH THE NERVOUS SYSTEM;  Annual Review of Biomedical Engineering; Vol. 4: 407-452
Author: Wim L. C. Rutten
Keywords: electrical interface; neurotechnology; neural system
Abstract: To achieve selective electrical interfacing to the neural system it is necessary to approach neuronal elements on a scale of micrometers. This necessitates microtechnology fabrication and introduces the interdisciplinary field of neurotechnology, lying at the juncture of neuroscience with microtechnology. The neuroelectronic interface occurs where the membrane of a cell soma or axon meets a metal microelectrode surface. The seal between these may be narrow or may be leaky. In the latter case the surrounding volume conductor becomes part of the interface. Electrode design for successful interfacing, either for stimulation or recording, requires good understanding of membrane phenomena, natural and evoked action potential generation, volume conduction, and electrode behavior. Penetrating multimicroelectrodes have been produced as one-, two-, and three-dimensional arrays, mainly in silicon, glass, and metal microtechnology. Cuff electrodes circumvent a nerve; their selectivity aims at fascicles more than at nerve fibers. Other types of electrodes are regenerating sieves and cone-ingrowth electrodes. The latter may play a role in brain-computer interfaces. Planar substrate-embedded electrode arrays with cultured neural cells on top are used to study the activity and plasticity of developing neural networks. They also serve as substrates for future so-called cultured probes.

6. Chronically implanted intrafascicular recording electrodes; Annals of Biomedical Engineering, Volume 19, Number 2 / March, 1991; pp. 197-207
Authors: Todd Lefurge, Eleanor Goodall, Kenneth Horch, Larry Stensaas,  Andrew Schoenberg
Keywords: Neuroprosthetics - Peripheral nerve - Implanted electrodes
Abstract: A newly designed intrafascicular electrode for chronic neural recording was studied by implanting 12 electrodes in the radial nerves of 6 cats for 6 months. Action potentials were monitored at specified intervals throughout the experiment. The number and size of the signals recorded suggest that this type of electrode provides information that is appropriate for feedback control in functional electrical stimulation (FES) systems. Histology of the nerve revealed that the implants are biocompatible and that little damage is caused by the presence of the electrode.
7. Blind source separation of peripheral nerve recordings; Journal of  Neural Enineering;  4 (2007); S157-S167  
Authors: W TesfayesusD M Durand
Keywords: prosthetic devices - Peripheral nerve - individual fascicular signals
Abstract:Prosthetic devices can be controlled using signals recorded in parts of the body where sensation and/or voluntary movement have been retained. Although neural prosthetic applications have used single-channel recordings, multiple-channel recordings could provide a significant increase in useable control signals. Multiple control signals can be acquired from recordings of a single implant by using a multi-contact electrode placed over a multi-fasciculated peripheral nerve. These recordings can be separated to recover the individual fascicular signals. Blind source separation (BSS) algorithms have been developed to extract independent source signals from recordings of their mixtures. The hypothesis that BSS algorithms can recover individual fascicular signals from nerve cuff recordings at physiological signal-to-noise ratio (SNR ~ 3–10 dB) was investigated in this study using a finite-element model (FEM) of a beagle hypoglossal nerve with a flattening interface nerve electrode (FINE). Known statistical properties of fascicular signals were used to generate a set of four sources from which the neural signals recorded at the surface of the nerve with a multi-contact FINE were simulated. Independent component analysis (ICA) was then implemented for BSS of the simulated recordings. A novel post-ICA processing algorithm was developed to solve ICA's inherent permutation ambiguities. The similarity between the estimated and original fascicular signals was quantified by calculating their correlation coefficients. The mean values of the correlation coefficients calculated were higher than 0.95 (n = 50). The effects of the geometric layout of the FINE electrode and noise on the separation algorithm were also investigated. The results show that four distinct overlapping fascicular source signals can be simultaneously recovered from neural recordings obtained using a FINE with five or more contacts at SNR levels higher than 8 dB making them available for use as control signals.

8. Neural and connective tissue response to long-term implantation of multiple contact nerve cuff electrodes; Journal of Biomedical Materials Research, Part B – Applied Biomaterials; Volume 50 Issue 2 , Pages 215 - 226
Authors: Warren M. Grill , J. Thomas Mortimer
Keywords: neural prostheses • cat • sciatic nerve • electrical stimulation
Abstract: The objective of this study was to characterize the tissue response to multiple contact spiral nerve cuff electrodes implanted on the sciatic nerve of seven cats for 28-34 weeks. The cuffs were surrounded by fibrous tissue encapsulation consisting of foreign body cells, collagen, and fibroblasts. Focal areas of abnormal neural morphology including perineurial thickening, endoneurial fibrosis, thinly myelinated axons, and focal reduction in the density of myelinated axons were noted in five of seven nerves. In three implants, the percutaneous lead cable was destroyed by the animal pulling on the external leads. Morphological changes were observed in two of three nerves from implants sustaining no known animal induced trauma (group A), and in three of four nerves from implants damaged by the animal pulling at the leads (group B). All nerves appeared normal 2 cm proximal to the cuff. At the cuff level, small regions of one fascicle in each of two nerves (both group B) exhibited abnormalities, while the proximal and distal sections of both nerves were normal. Distal to the cuff, small regions of seven fascicles distributed among three nerves (two group A, one group B) exhibited abnormalities. These nerves were normal at the cuff level but exhibited abnormalities in individual nerve branches distal to the cuff. The incidence and characteristics of the morphological abnormalities at the cuff level are consistent with those observed in previous studies of nerve cuff electrodes, and support the hypothesis that spiral cuff electrodes can be implanted with an internal diameter less than that of the nerve and expand to accommodate the nerve without compression The pattern of morphological abnormalities indicated that mechanical trauma had occurred at some time in the past, and the distribution suggested animal intervention and the lead cable as possible causes.

9. Chronic Response of the Rat Sciatic Nerve to the Flat Interface Nerve Electrode; Annals of Biomedical Engineering, Vol. 31, pp. 633–642, 2003
Keywords: Functional electrical stimulation, Peripheral nerve, Implanted electrodes, Rehabilitation, Nerve compression injury, Nerve physiology, Blood–nerve barrier.
Abstract: The chronic effects of a reshaping nerve electrode, the flat interface nerve electrode ~FINE!, on sciatic nerve physiology, histology, and blood–nerve barrier ~BNB! are presented. The FINE electrode applies a small force to a nerve to reshape the nerve and fascicles into elongated ovals. This increases the interface between the nerve and electrode for selective stimulation and recording of peripheral nerve activity. The hypothesis of this study is that a small force applied noncircumferentially to a nerve can chronically reshape the nerve without effecting nerve physiology, histology, or the blood–nerve barrier permeability. Three FINE electrode designs were implanted on rat sciatic nerves to examine the nerve’s response to small, moderate, and high reshaping forces. The chronic reshaping, physiology, and histology of the nerve were examined at 1, 7, and 28 days postimplant. All FINEs significantly reshape both the nerve and the fascicles compared to controls. FINEs that applied high forces caused a neurapraxia type injury characterized by changes in the animal’s footprint, nerve histology, and the BNB permeability. The physiological changes were greatest at 7 days and fully recover to normal by 14 days postimplant. The moderate force FINE did not result in changes in the footprint or BNB permeability. Only a minor decrease in axon density without accompanying evidence of axon demyelination or regeneration was observe for the moderate force. The small force FINE does not cause any change in nerve physiology histology, or BNB permeability compared to the sham treatment. An electrode that applies a small force that results in an estimated intrafascicular pressure of less than 30 mm Hg can reshape the nerve without significant changes in the nerve physiology or histology. These results support the conclusion that a small force chronically applied to the nerve reshapes the nerve without injury.

10. Coodinated pre and postsynaptic changes involved in developmental activity – dependent synapse elimination; Synaptic Plasticity and Transsynaptic Signaling Book, Pages 441-45
Authors: Phillip G. Nelson, Min J i a ,Min-Xu Li, Rahel G i z a w  ,M aria A. Lanuza,  Josep Tomas
Introduction: A central problem for current neuroscience is to develop an unifying mechanistic hypothesis for the different forms of nervous system plasticity. In addition to the short-term adaptations of synaptic activity like facilitation, the various models that have been studied include long term potentiation (LTP), long term depression (L'TD), various forms of behavioral conditioning such as eye-blink conditioning, sensitization and desensitization and the synaptic and neuronal pruning or removal that is a prominent aspect of development of the nervous system. It seems to be the case that several different mechanisms are involved in these different forms of activity dependent changes in neural function and circuit performance; certainly the relatively simple Hebb model of 1949 (Hebb, 1949) serves as only the broadest guide to understanding such changes. These variations notwithstanding, some general model for understanding neuro-plasticity is emerging and should be a useful conceptual framework for guiding future experiments. A fundamental distinction has been made on practical, experimental grounds between the enormous changes (reductions) in neural circuit structure and function
that occur during development and the changes in circuit connectivity that occur as a result of input in the mature organism and that are considered to underly learning and memory. LTP, LTD and various conditioning paradigms are experimentally approachable models of the latter. The degree of mechanistic overlap between these models and the massive circult changes that occur during development is not fully known, but some convergences have been noted and will be dealt with briefly in this paper. Our major purpose will be to summarize recent data on some of the molecular and cell biologic mechanisms that play important roles in activity-dependent synapse elimination at the mammalian neuromuscular junction in vitro and in vivo.

11. Dynamic use of tactile afferent signals in control of dexterous manipulation; Advances in experimental medicine and biology, 2002;508:397-410.
Author: Roland S. Johansson
Abstract: During object manipulation, humans select and activate neural action programs acquired during ontogenetic development. A basic issue in understanding the control of dexterous manipulation is to learn how people use sensory information to adapt the output of these neural programs such that the fingertip actions matches the requirements imposed by the physical properties of the manipulated object, e.g., weight (mass), slipperiness, shape, and mass distribution. Although visually based identification processes contribute to predictions of required fingertip actions, the digital tactile sensors provide critical information for the control of fingertip forces. The present account deals with the tactile afferent signals from the digits during manipulation and focuses on some specific issues that the neural controller has to deal with to make use of tactile information.

12. N-Terminal Arginylation of Sciatic Nerve and Brain Proteins Following Injury, Neurochemical Research, Vol. 22, No. 12, 1997, pp. 1453-1459
Authors: Y. M. Wang,  N. A. Ingoglia
Keywords: Arginylation; sciatic nerve; injury; brain,
Abstract: N-terminal protein arginylation has been demonstrated in vitro and in situ and has been reported to increase following injury to sciatic nerves of rats. The present study attempts to demonstrate these reactions in vivo by applying [3H]Arg to the cut end of sciatic nerves in anesthetized rats and assaying for N-terminal arginylation using Edman chemistry and acid precipitation of labeled proteins in the proximal nerve segment. No evidence was found for arginylation in an aqueous soluble fraction. However, N-terminal arginylation was detected in a urea soluble fraction at 2 hours after nerve crush. The data show that arginylation of rat sciatic nerve proteins occurs in vivo and suggest that the arginylated proteins formed an aqueous insoluble/urea soluble aggregate after arginylation. In other experiments, rat brains were injured and assayed for arginylation in vitro to test the hypothesis that injury causes an up-regulation of these reactions. Results showed an activation of the reaction at 2 hours post crush and indicate that increases in N-terminal arginylation are likely to be a general response to injury in nervous tissue.

13. Implantation mechanics of tungsten microneedles into peripheral nerve trunks; Med Bio Eng Comput (2007) 45:413–420
Authors: Ken Yoshida , Ina Lewinsky, Mogens Nielsen , Mads Hylleberg
Keywords: tungsten microneedles; peripheral nerve; LIFE
Abstract: 50 lm tungsten microneedles have been used as a means to introduce longitudinal intra-fascicular electrodes (LIFE) into small peripheral nerve fascicles. However, recent attempts to implant LIFEs into larger, human sized nerves with the same needles resulted in buckling failure of the introducer needle. In the present study, the implantation mechanics (penetration forces and penetration dimple depth) of electrosharpened tungsten microneedles ranging in diameters from 50 to 200 lm into freshly excised porcine peripheral nerve trunks between 3 and 5 mm in thickness was characterized to understand the implantation mechanics and to find the minimum needle diameter that would result in successful penetration. The implant success rate was found to be highest with needles having diameters between 80 and 120 lm. The force of successful penetration ranged from 7.2 ± 0.6 to 71.8 ± 19.5 mN, and increased monotonically with needle diameter. It also had a tendency to increase with increasing tip angles. The dimple depth for successful penetrations varied between 1 and 1.5 mm, and also tended to increase with increasing tip angles, although it was generally not affected by increased needle diameter. Only the smallest penetration dimple depth was found to be different from the others and was associated with the smallest diameter needle (50 lm). Analysis based on the critical buckling force and the measured implantation forces indicated a 15 mm long needle of 80 lm diameter would be necessary and sufficient to penetrate medium to large sized nerves.

Authors: Ronald E. Leppanen, Ph.D., D.ABNM, FASNM
Keywords: H-reflex, F-response, electromyography, EMG, intraoperative monitoring, spinal cord, spinal nerve root.
Abstract: Orthodromic ascending somatosensory evoked potentials and antidromic descending neurogenic
somatosensory evoked potentials monitor spinal cord sensory function. Transcranial motor stimulation monitors spinal cord motor function but only activates 4–5% of the motor units innervating a muscle. Therefore, 95–96% of the motor
spinal cord systems activating the motor units are not monitored. To provide more comprehensive monitoring, 11 techniques have been developed to monitor motor nerve root and spinal cord motor function. These techniques include: 1. neuromuscular junction monitoring, 2. recording free-run electromyography (EMG) for monitoring segmental spinal nerve root function, 3. electrical stimulation to help determine the correct placement of pedicle screws, 4. electrical impedance testing to help determine the correct placement of pedicle screws, 5. electrical stimulation of motor spinal nerve roots, 6. electrical stimulation to help determine the correct placement of iliosacral screws, 7. recording H-reflexes, 8. recording F-responses, 9. recording the sacral reflex, 10. recording intralimb and interlimb reflexes and 11. recording monosynaptic and polysynaptic reflexes during dorsal root rhizotomy. These 11 techniques when used in conjunction with somatosensory and transcranial motor evoked potentials provide a multiplesystems approach to spinal cord and nerve root monitoring.

 Keywords: peripheral nerve; LIFE
Abstract:The purpose of this study was to evaluate the value of utilizing longitudinal intrafascicular electrodes (LIFEs) in collecting and analyzing sensory signals from the peripheral nerve. The longitudinal intrafascicular electrodes were made of 25-lm Teflon-insulated Pt/Ir wire and implanted into the fascicle of the superficial peroneal nerves in a feline model. The sensory signals at rest status and induced with various stimulations were recorded. The action potential area, frequency, coefficient of variation (CV) of the peak, and functional spectrum were then analyzed by the MF Lab version 3.01 software package. The results showed that the sensory nerve action potentials (SNAPs) were 0_2 spikes per second at rest state; the count was increased when stimulation was administered. SNAPs were 16_24 spikes per second when scraping stimulation was applied. The pulse intervals and the waveform remained consistent. SNAPs burst and were clustered when stress stimulation was given. The comparison of area, frequency, and CV of the peak showed statistically significant differences between these parameters receiving different stimulations. The functional spectrum analysis showed that the frequency of action potential increased when the stress stimulation was applied. In conclusion, LIFEs can sensitively collect sensory signals and provide a good interface to analyze sensory information from peripheral fasciculi. These data provide useful information for further study of control of electronic prostheses.

16. Morphology after synergistic terminal end-to-side nerve graft repair: Investigation in a nonhuman primate model; European Surgery (2005) 37/4: 220–227
Authors: R. Schmidhammer, T. Hausner, S. Zandieh, L. E. Pelinka, and H. Redl
 Keywords: nerve regeneration, end-to-side, morphology, Schwann cell, collagenic connective tissue.
Abstract: Functional efficacy of synergistic terminal end-to-side nerve graft repair in a median nerve defect model in nonhuman primates was recently published elsewhere. The purpose of this study was to investigate the morphology of the end-to-side repair site and the nerve graft used after synergistic terminal end-to-side nerve graft repair.

17. Peripheral nerve regeneration; European Surgery (2005) 37/4: 187–192
Authors:  V. Sahni, Y. Qi, S. Frostick
 Keywords: peripheral nerve regeneration, growth factors, stem cells.
Abstract: Understanding of the mechanisms underlying peripheral nerve regeneration represents a prerequisite for adequate design for treatment of injured peripheral nerves. Peripheral nerve regeneration is orchestrated by mechanisms involving nerve, muscle, connective tissue and immune cells and mediators released from these cells (growth factors, interleukins, glycoproteins). Success of peripheral nerve repair depends on patient’s age, time from injury, site and extent of nerve lesion (proximal vs. distal). Future studies will evaluate the impact of novel approaches including stem cells, growth factors and extracellular matrix glycoproteins (fibronectin, laminin). Peripheral nerve regeneration involves complex mechanisms, the understanding of which will profoundly aid treatment design.

 Keywords: peripheral nerve regeneration, growth factors, stem cells.
Abstract:The purpose of this experiment was to study the recording and stimulating properties, and biocompatibility of longitudinally implanted intrafascicular electrodes (LIFEs) in a rabbit sciatic nerve model when they were chronically implanted into peripheral fascicles. LIFEs were implanted chronically into sciatic nerve fascicles of rabbits as recording and stimulating electrodes. Motor-evoked potentials (MEPs) and cortical somatosensory- evoked potentials (CSEPs) were recorded by using a transcranial stimulation system (TCS) over 6-month period to observe the change of the signals recorded. At the end of the experiment, the fascicles at the electrodes implanted site were anatomized for histological examination under light microscope and transmission electron microscope. Results showed onset latency (OL) of MEPs and CSEPs had no obvious change during the first month. However, OL significantly increased during the second month, and then became stable 3 months after implantation. The interpeak amplitudes (IPAs) of MEPs had no distinct change during the first month, but significantly decreased over the next period, and then became stable 3 months after implantation. The IPAs of CSEPs, however, decreased slowly over the 6-month period of the study. At the end of the experiment, histological examination indicated that a typical foreign body reaction developed, and electrodes caused mild damage to the fascicles, though inflammatory cells and neuroma were not seen around the electrodes. In conclusion, LIFEs have excellent recording and stimulating characters in addition to biocompatibility with peripheral fascicles. They can be implanted chronically into fascicles and record signals.

Authors:  Jim Hindmarsh, Philip Cornelius
Abstract: We review the development of the Hindmarsh-Rose equations of 1982 and 1984. After a brief description of bifurcations in a model for subthreshold oscillations, that can generate bursting, we show that similar bifurcations will not be found in the Hindmarsh-Rose nor in other similar equations.

20. The Hodgkin-Huxley Model; Book Chapter
Introduction: Our present day understanding and methods of modeling neural excitability have been signi cantly in_uenced by the landmark work of Hodgkin and Huxley. In a series of _ve articles published in 1952 (Hodgkin, Huxley and Katz 1952, Hodgkin and Huxley 1952a.d) these investigators (together with Bernard Katz, who was a coauthor of the lead paper and a collaborator in several of the related studies) unveiled the key properties of the ionic conductances underlying the nerve action potential. For this outstanding achievement, Hodgkin and Huxley were awarded the 1963 Nobel Prize in Physiology and Medicine (shared with John Eccles, for his work on potentials and conductances at motoneuron synapses). The _rst four papers in the series summarize an experimental tour de force in which Hodgkin and Huxley brought to bear new experimental techniques for characterizing membrane properties. The _nal paper in the series places the experimental data into a comprehensive theoretical framework that forms the basis of our modern views of neural excitability. For a discussion and review of these seminal papers, see Rinzel (1990).
Hodgkin and Huxley indeed were aware that their _ndings and ideas had broad implications; they implicitly acknowledged this by the title of their _fth paper (Hodgkin and Huxley 1952d), which was the only one in the series not to explicitly mention the squid by name. Although the squid giant axon ultimately may have served as a means to an end, this is not to deny the squid her proper credit. Her generosity in providing a technically convenient preparation . a gargantuan axon, up to 1 mm in diameter . The Hodgkin-Huxley Model widely appreciated is the fortuitous fact that, relative to most excitable nerve membrane,the squid axon is a simple system with basically only two types of voltage-dependent conductances.Today, we know of many more conductance types that can contribute to theexcitability of nerve cells (Llin´as 1988; also, see Chapter 7 in this volume). The squid axonmembrane was an ideal model system; it presented a suitably generic and tractable problem,the solution of which gave rise to powerful new techniques and fundamental concepts.In this chapter, we explore the Hodgkin-Huxley (HH) model using a GENESIS tutorialsimulation called Squid. Before describing the mathematical model and performing thesimulations, we provide a brief historical overview, so that the reader may better appreciatethe scienti_c impact this work had at the time and how it has come to shape our presentunderstanding of neural excitability. In exploring the HH model in this chapter, we willonly be able to touch on some of the highlights. For a fuller appreciation of the model, werecommend a careful reading of the original paper (Hodgkin and Huxley 1952d). Additionalhistorical and biophysical background on the HH model may also be found in Cole (1968),Hodgkin (1976), and Hille (1984).

21. A Silicon – Based, Three – Dimensional Neural Interface: Manufacturing Processes for an Intracortical Electrode Array; IEEE Transactions on Biomedical Engineering, Vol. 38, No. 8, pag. 758 - 768
Authors: P. K. Campbell, K. E. Jones, R. J. Hubert, K. W. Horch, R. A. Normann
Keywords: peripheral nerve regeneration, growth factors, stem cells.
Abstract: A method has been developed for the manufacture of a "three-dimensional" electrode array geometry for chronic intracortical stimulation. This silicon based array consists of a 4.2 x 4.2 x 0.12 mm thick monocrystalline substrate, from which project 100 conductive, silicon needles sharpened to facilitate cortical penetration. Each needle is electrically isolated from the other needles, and is about 0.09 mm thick at its base and 1.5 mm long. The sharpened end of each needle is coated with platinum to facilitate charge transfer into neural tissue. The following manufacturing processes were used to create this array. 1) Thermomigration of 100 aluminum pads through an n-type silicon block. This creates trails of highly conductive p+ silicon isolated from each other by opposing pn junctions. 2) A combination of mechanical and chemical micromachining which creates individual penetrating needles of the p+ silicon trails. 3) Metal deposition to create active electrode areas and electrical contact pads. 4) Array encapsulation with polyimide. The geometrical, mechanical, and electrical properties of these arrays should make them well suited as interfaces to cortical tissue.
22. Peripheral Nerve Regeneration; Advance of  Biochemical  Engineering/Biotechnology (2005) 94: 67–89
Authors: Mei Zhang · Ioannis V.Yannas
Keywords: Peripheral nerve · Nerve chamber · Nerve regeneration · Microtubes · Myofibroblast capsule
Abstract: The nerve chamber model has dominated the experimental study of peripheral nerve (PN) regeneration with animal models as well as in several clinical applications, such as the treatment of paralysis of limbs following severe trauma. The two stumps resulting from nerve transection are inserted inside a tubular chamber made from one of several materials, occasionally filled with various substances, and the quality of the reconnected nerve is assayed. Recent use of methods for data reduction has led to generation of a large normalized database from independent investigations. Methods for data normalization (reduction) are based on systematic use of the critical axon elongation, Lc, the gap length between the transected stumps at which the frequency of reconnection is just 50% for a given configuration. Four theories are compared for their ability to explain the normalized data. Although the neurotrophic and contact guidance theories explain some of the data, combined use of the more recent microtube theory and pressure cuff theory appears capable of explaining a much larger data set. PN regeneration appears to be upregulated by chamber configurations that facilitate formation of basement membrane microtubes about 10–20 mm in diameter, comprising linear columns of Schwann cells surrounded by basement membrane, into which axons elongate and eventually become myelinated. Regeneration is downregulated by experimental configurations that permit formation of a contractile cell (myofibroblast) capsule around the regenerating nerve that appears to restrict growth of a nerve trunk by application of circumferential mechanical forces.These two processes work competitively to regulate nerve regeneration in the chamber model.

23. Multiple-electrode nerve cuffs for low-velocity and velocity-selective neural recording; Med. Biol. Eng. Comput., 2004, 42, 634-643
Authors: J. Taylor,  N. Donaldson,  J. Winter
Keywords: Nerve cuff, Tripolar recording, Multi-electrode cuff, Velocity selectivity, Small fibre recording
Abstract: In the paper, a method using multiple-electrode nerve cuffs is presented that enables electroneurographic signals (ENG) to be recorded selectively by action potential velocity. The theory uses a one dimensional model of the electrodes in the cuff. Using this model, the transfer function for a single tripole is derived, and it is shown that more than one tripole signal can be recorded from within a cuff. When many tripole signals are available and are temporally aligned by artificial delays and summed, there is a significant increase in the amplitude of the recorded action potential, depending on the cuff length and the action potential velocity, with the greatest gain occurring for low velocities. For example, a cuff was considered that was constrained by surgical considerations to 30mm between the end electrodes. For action potentials with a velocity of 120ms 1, it was shown that, as the number of tripoles increased from one, the peak energy spectral density of the recorded output increased by a factor of about 1.6 with three tripoles, whereas, for 20ms 1, the increase was about 19, with ten tripoles. The time delays and summation act as a velocity-selective filter. With consideration of the energy spectral densities at frequencies where these are maximum (to give the best signal-to-noise ratio), the tuning curves are presented for these velocity-selective filters and show that useful velocity resolution is possible using this method. For a 30 mm cuff with nine tripoles, it is demonstrated that it is possible to resolve at least five distinct velocity bands in the range 20-120ms 1.

24. Modelling the effects of electric fields on nerve fibres: influence of the myelin sheath; Med. Biol. Eng. Comput., 2000, 38, 438-446
Authors: A. G. Richardson, C.C. Mclntyre, W.M. Grill
Keywords: Axon model, Strength-duration relationship, Current-distance relationship, Conduction velocity
Abstract: The excitation and conduction properties of computer-based cable models of mammalian motor nerve fibres, incorporating three different myelin representations, are compared. The three myelin representations are a perfectly insulating single cable (model A), a finite impedance single cable (model B) and a finite impedance double cable (model C). Extracellular stimulation of the three models is used to study their strength-duration and current-distance (I-X) relationships, conduction velocity (CV) and action potential shape. All three models have a chronaxie time that is within the experimental range. Models B and C have increased threshold currents compared with model A, but each model has a slope to the I-X relationship that matches experimental results. Model B has a CV that matches experimental data, whereas the CV of models A and C are above and below the experimental range, respectively. Model C is able to produce a depolarising afterpotential (DAP), whereas models A and B exhibit hyperpolarising afterpotentials. Models A and B are determined to be the preferred models when low-frequency stimulation (< ~25Hz) is used, owing to their efficiency and accurate excitation and conduction properties. For high frequency stimulation (~ 25 Hz and greater), model C, with its ability to produce a DAP, is necessary accurately to simulate excitation behaviour.

Keywords: peripheral nerve activity, intrafascicular electrodes
Abstract: Methods for long-term recording of peripheral nerve activity via intrafascicular electrodes have not been optimized. We compared the longterm functionality of custom-made 95%Pt/5%Ir intrafascicular electrodes containing a proximal spring-like structure to that of conventional straight electrodes. The modified electrode was implanted into the sciatic nerve fascicle of a random hind limb in 14 rabbits for 9 months. A conventional electrode was implanted in the opposite hind limb as a control. Orthodromic and antidromic nerve potentials were sampled and analyzed monthly. Latency, amplitude, and nerve conduction velocity of electrical signals were generally similar within the modified group and straight control group at different time intervals (P > 0.05). However, at the conclusion of the study period, the modified electrode group had a greater number of functioning electrodes (P < 0.05) and a greater total functioning electrode time (P 5 0.006). Intrafascicular electrodes with a spring-like structure demonstrated superior potential for long-term electrophysiological monitoring over straight electrodes.

26. Functional recovery after implantation of artificial nerve grafts in the rat- a systematic review, Journal of Brachial Plexus and Peripheral Nerve Injury
Authors: N. Sinis, A. Kraus, N. Tselis, M. Haerle, F. Werdin, H. E. Schaller
Abstract: The aim of this study was to compare functional data of different nerve-gap bridging materials evaluated in rat experiments by means of a systematic review. A systematic review was conducted, searching MEDLINE, HTS and CENTRAL to identify all trials evaluating functional recovery of artificial nerve conduits in the rat model. Results: There was a trend towards a favourable outcome of conduits coated with Schwann-cells compared to the plain synthetics. Histomorphometry, electrophysiology and muscle-weight correlated poorly with functional outcome. Conclusion: Schwann-cell coated conduits showed promising results concerning functional recovery. Further standardization in outcome reporting is encouraged.

27. Magnetic Stimulation Accelerating Rehabilitation of Peripheral Nerve Injury; Journal of Huazhong University of Science and Technology [Med Sci], 22 (2): 135-139, 2002
Authors: Ahmed Bannaga, GUO Tiecheng, UYANG Xingbiao and al.
Keywords: magnetic stimulation; peripheral nerve injury
Abstract: The effect of magnetic stimulation (MS) on .sciatic nerve injury was observed. After sciatic nerve was crushed in 40 Sprague Dawley (SD) rats, one randomly .selected group (group D) was subjected, from the 4th day post-operatively to 3 min of continuous 70 % of maximum output of MS daily for 8 weeks. The other group (group E) ~rved as a control group. The nerve regeneration and motor function recovery were evaluated by walking track analysis (sciatic function index, SFI; toe spreading reflex, TSR), electrophysiological, histological and acetylcholineestera~ histochemistry. The SFI in the group D was greater than in the group E with the difference being statistically significant (P<0.01). TSR reached its peak on the 4th day in the group D and on the 10th day in the group E respectively. The amplitude and velocity of MCAP and NCAP in the group D was greater than in the group E with the difference being statistically significant (P'~0. 01), while the latency and duration of MCAP and NCAP in the group D were le~s than in the group E with the difference being also statistically significant (P<0.01). Histological examination showed the mean axon count above the lesion for thick myelinated fibers C>6.5 ,am) in the group D was greater than in the control group with the difference being statistically significant (P'~0. 01), while the mean axon count below the lesion for thick myelinated fibers was less than that in the group E with the difference being statistically significant (P.~0. 01). The mean axon count above the lesion for thin myelinated fibers (2--6.5/~m) in the group D was greater than that in the group E with the difference being statistically significant (P<0.05), while the mean axon count below the lesion for thin myelinated in the group D was greater than that in the group E with the difference being statistically significant (P _~9 0. 01). Acetylcholine esterase examination showed that the MS could significantly increa~ the number of the motor neurons. There was no significant difference in the number of the motor neurons between the treatment side and the normal side (P~0.05). It can be concluded that MS can enhance functional recovery and has a considerable effect in the treatment of the peripheral nerve injury.

28. Measurement of the performance of nerve cuff electrodes for recording; Med. Biol. Eng. Comput., 2000, 38, 447-453
Authors: L. N. S. Andreasen, J.J. Struijk, S. Lawrence
Keywords: Cuff electrode, Nerve fibre, Action potential, Model
Abstract:New designs of cuff e/ectrodes for the recording of signa/s from periphera/ nerves are typically tested in acute animal experiments before long-term evaluation takes place. A reproducible, cost-effective and fast method is presented for evaluating cuff electrodes with respect to signal amplitude, noise rejection, and, in some cases, selectivity, as an alternative to acute in vivo experiments. Comparisons with a computer model and with signals obtained from rabbit tibial nerve give good agreement with the new method. It is shown that an imperfect closure of the cuff around the nerve can easily lead to more than 50% loss of the signal amplitude.
Noise from sources external to the cuff is not significantly affected by the closing mechanism, but is strongly reduced by a tripolar cuff configuration as compared with a monopolar one (reduction factor 2.8 to 58, mean = 6.5, n = 6). In dual-channel cuffs, cross-talk is below 1.2% indicating a very high selectivity.

29. Dynamics of firing patterns, synchronization and resonances in neuronal electrical activities: experiments and analysis – review, Acta Mech Sin (2008) 24:593–628
Authors: Qishao Lu,  Huaguang Gu,  Zhuoqin Yang,  Xia Shi,  Lixia Duan,  Yanhong Zheng
 Keywords: Neuron · Firing patterns · Synchronization · Resonance · Noise
Abstract: Recent advances in the experimental and theoretical study of dynamics of neuronal electrical firing activities are reviewed. Firstly, some experimental phenomena of neuronal irregular firing patterns, especially chaotic and stochastic firing patterns, are presented, and practical nonlinear time analysis methods are introduced to distinguish deterministic and stochastic mechanism in time series. Secondly, the dynamics of electrical firing activities in a single neuron is concerned, namely, fast–slow dynamics analysis for classification and mechanism of various bursting patterns, one- or two-parameter bifurcation analysis for transitions of firing patterns, and stochastic dynamics of firing activities (stochastic and coherence resonances, integer multiple and other firing patterns induced by noise, etc.). Thirdly, differenttypes of synchronization of coupled neurons with electricaland chemical synapses are discussed. As noise and timedelay are inevitable in nervous systems, it is found that noiseand time delay may induce or enhance synchronization andchange firing patterns of coupled neurons. Noise-inducedresonance and spatiotemporal patterns in coupled neuronalnetworks are also demonstrated. Finally, some prospects arepresented for future research. In consequence, the idea andmethods of nonlinear dynamics are of great significance inexploration of dynamic processes and physiological functionsof nervous systems.

30. Segmented and "equivalent" representation of the cable equation; Biophysical Journal, Volume 46, Issue 5, Pages 615-623
Keywords: linear cable theory, segmented model for the nodal regions of myelinated fibers
Abstract: The linear cable theory has been applied to a modular structure consisting of n repeating units each composed of two subunits with different values of resistance and capacitance. For n going to infinity, i.e., for infinite cables, we have derived analytically the Laplace transform of the solution by making use of a difference method and we have inverted it by means of a numerical procedure. The results have been compared with those obtained by the direct application of the cable equation to a simplified nonmodular model with "equivalent" electrical parameters.The implication of our work in the analysis of the time and space course of the potential of real fibers has been discussed. In particular, we have shown that the simplified ("equivalent") model is a very good representation of the segmented model for the nodal regions of myelinated fibers in a steady situation and in every condition for muscle fibers. An approximate solution for the steady potential of myelinated fibers has been derived for both nodal and internodal regions. The applications of our work to other cases dealing with repeating structures, such as earthworm giant fibers, have been discussed and our results have been compared with other attempts to solve similar problems.

31. Ultrastructural dimensions of myelinated peripheral nerve fibres in the cat and their relation to conduction velocity, The Journal of Physiology, 308, 125-157.
Author: ER Arbuthnott, IA Boyd, KU Kalu
Abstract: 1. The ultrastructure of all the afferent fibres, or all the efferent fibres, was studied in selected nerves from chronically de-afferentated or de-efferentated cat hind limbs perfusion-fixed with glutaraldehyde.
2. The following parameters were measured: number of lamellae in the myelin sheath (n), axon perimeter (s), external fibre perimeter (S), axon cross-sectional area (A). Fibres were allocated to afferent groups I, II, III or efferent groups α and γ according to the number of lamellae in the myelin sheath.
3. The thickness of the myelin sheath (m) was linearly related to axon perimeter within the range s = 4 μm to s = 20 μm (groups II, III and γ). The relation m = 0·103 s — 0·26 provided a good fit for all afferent and efferent axons in this range in several different anatomical muscle nerves in three cats. The myelin sheaths were thinner in a fourth, presumably younger, cat.
4. The myelin sheaths were relatively thinner for large fibres in groups I and α (s = 20-50 μm). The results are interpreted in one of three ways. Either m tends to a limit of about 2·2 μm, or m is linearly related to s such that for large fibres m = 0·032 s + 1·11.
5. Alternatively, m may be considered to be proportional to log10 s for all sizes of axon so that m = 2·58 log10 S — 1·73. The interpretation that there are two separate linear relations for large and small fibres is favoured.
6. The ratio of axon to external fibre perimeter (g) falls from about 0·70 for group III and small γ fibres in the cat to about 0·62 for group II and large γ fibres and then rises again to 0·70, or even 0·75 for group I and α axons.
7. The above relations between m and s are combined with the observations of Boyd & Kalu (1979) that Θ = 5·7 D for groups I and α and Θ = 4·6 D for groups II, III and γ. It is shown that Θ = 2·5 s approximately for all sizes of axon (s from material fixed for electron microscopy) in rat, cat and man. The accuracy of this equation may be improved by deducting 3 m/sec in the case of small fibres. This conclusion is compatible with experimental observations of the relation between l and D (Hursh, 1939; Lubinska, 1960; Coppin, 1973) and between l and Θ (Coppin & Jack, 1972).
8. From the theoretical analyses of Rushton (1951) and others Θ should be proportional to the external dimensions of the fibre rather than to axon size. It is shown that the thinning of the myelin sheath ought to affect Θ substantially. Thus some other factors must compensate for the thinning of the sheath.
9. Small fibres are significantly more non-circular than large fibres. From the quantitative data of Arbuthnott et al. (1980) it is concluded that non-circularity may contribute to the fact that Θ ∝s rather than Θ ∝S, but cannot wholly account for it. Other possibilities considered are that axoplasmic resistivity or specific nodal conductance may differ for large and small fibres.
10. It is suggested that myelinated peripheral nerve fibres may fall into two distinct classes with different properties, one comprising groups I and α and the other groups II, III and γ. The conclusion predicted from theory may apply to each of these classes separately so that Θ = 2·0 S for the large-fibre class and Θ = 1·6 S for the small-fibre class.

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