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Journal ArticleDOI

A Simulation Study of the Combined Thermoelectric Extracellular Stimulation of the Sciatic Nerve of the Xenopus Laevis: The Localized Transient Heat Block

09 Apr 2012-IEEE Transactions on Biomedical Engineering (IEEE Trans Biomed Eng)-Vol. 59, Iss: 6, pp 1758-1769
TL;DR: The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs.
Abstract: The electrical behavior of the Xenopus laevis nerve fibers was studied when combined electrical (cuff electrodes) and optical (infrared laser, low power sub-5 mW) stimulations are applied. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP). The calculations involve a finite-element model (COMSOL) to represent the electrical properties of the nerve and cuff. Electric-field distribution along the nerve was computed for the given stimulation current profile and imported into a NEURON model, which was built to simulate the electrical behavior of myelinated nerve fiber under extracellular stimulation. The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. Some preliminary experimental data in support of this conclusion are also shown.

Summary (2 min read)

Introduction

  • Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge, also known as Reuse.
  • Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP).
  • This work was supported in part by the UK EPSRC grant EP/H024581.
  • Reversible blocking of nerve conduction in targeted structures can be achieved by using various stimulation schemes based on direct currents (e.g. DC monophasic waveforms [5]) or high frequency alternating currents (HFAC) [6].

II. THERMOELECTRIC STIMULATION MODELING

  • First it was essential to build a model of the generation and propagation of nerve impulses under combined thermoelectric stimulation.
  • The node of Ranvier membrane excitability of Xenopus laevis was first modeled by Frankenhaeuser and Huxley (FH model) [19] and implemented later by Butikoffer [20] and Dean [21].
  • McNeal [22] implemented a myelinated fiber model describing the electrical behavior of all nodes, but it ignored the passive electrical properties of the insulating myelin sheath.
  • The mathematical basis for the extracellular fiber stimulation was given by Rattay [25].
  • The electric field distribution of the surrounding area of the nerve under varying extracellular electrode configurations and stimulus patterns was calculated in COMSOL ® Multiphysics 3.5a.

III. METHODS

  • The authors simulations incorporated three modeling environments.
  • The simulated nerve and electrode geometries, shown in Fig.2, were constructed to closely match those found in their experimental setup (see Section IIID).
  • The starting point for the cuff model was the modeling study of the tripolar cuff electrode nerve stimulation of Goodall et.al [32].
  • The authors used Mathworks Simulink to simulate the equivalent circuit of the electrode-electrolyte interface and fit the parameter values given in Table 2.
  • The main protocol for laser illumination was a continuous illumination, one minute for each laser intensity (time needed to scan through complete electrical stimulation sequence).

IV. RESULTS

  • The time dependent extracellular potentials (created by the stimulus current shown in Fig.3b) just above nodes N20, N21 and N22 are also shown in Fig.4a.
  • The Q10 values used in their model are shown in Table 3.
  • Results in Fig.5b show that for the positions (3) and (4) this relationship is not monotonic and exhibits a minimum value for a certain fiber diameter D, which depends on the distance between the electrodes.
  • Heat block for a fiber in the middle of the nerve – position (2), D=15μm, the stimulus current is 200μA, pulse duration =300μs, all nodes not heated are at the environment temperature (which is T=23 oC for panels a,b and c).
  • The AP which propagated through the nodes N20-N24 (blue lines) blocked due to increased temperature (T= 49oC) of the nodes N25 and N26 (red), also known as (b) AP propagation block.

V. DISCUSSION

  • A model implemented in COMSOL and NEURON was created to simulate the thermoelectric extracellular stimulation of a myelinated nerve fiber.
  • The simulation data are in a good agreement with the experimental data, for example for predicting the minimum stimulation currents, etc.
  • The authors interpret this effect as the local heat block of a fraction of the total number of fibers normally activated with solely electrical stimulation.
  • Similar mechanisms apply to local heating and the generation block, since in that case the AP initiation in the axon is blocked.
  • The amount of energy absorbed in the bath at the maximum laser power is 5mW, therefore overall average increase of temperature in the water solution would be less than 0.01 o C for 30 minutes of continuous laser operation (in each experiment the laser was On for less than 15 minutes in total).

VI. CONCLUSION

  • This work demonstrated that by using localized temperature increase of nodes the transient heat block is possible.
  • The required temperatures for AP generation block seem physiologically safe.
  • Therefore it should be possible to achieve selective activation or inhibition of neural activity by applying focused infra-red light to selectively block specific fibers in a nerve bundle whilst using electrical stimulation to activate some other fibers.
  • Selective stimulation has important therapeutic applications and this strategy might be primarily applicable to peripheral nerve interfacing.
  • The model files are available upon request and on the last author’s web site.

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Citation: Mou, Z., Triantis, I., Woods, V. M., Toumazou, C. and Nikolic, K. (2012). A
simulation study of the combined thermoelectric extracellular stimulation of the sciatic nerve
of the Xenopus laevis: the localized transient heat block. IEEE Transactions on Biomedical
Engineering, 59(6), pp. 1758-1769. doi: 10.1109/TBME.2012.2194146
This is the accepted version of the paper.
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Permanent repository link: https://openaccess.city.ac.uk/id/eprint/14323/
Link to published version: http://dx.doi.org/10.1109/TBME.2012.2194146
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PAPER IDENTIFICATION NUMBER:
1
AbstractThis paper presents the response of the Xenopus
laevis nerve fibers to combinations of electrical (cuff electrodes)
and optical (infrared laser, low power sub-5mW) stimulation.
Assuming that the main effect of the laser irradiation on the
nerve tissue is the localized temperature increase, this paper
analyzes and gives new insights into the function of the
combined thermoelectric stimulation on both excitation and
blocking of the nerve action potentials (AP). The calculations
involve a finite-element model (COMSOL) to represent the
electrical properties of the nerve and cuff. Electric field
distribution along the nerve was computed for the given
stimulation current profile and imported into a NEURON
model, which was built to simulate the electrical behavior of
myelinated nerve fiber under extracellular stimulation. The
main result of this study of combined thermoelectric stimulation
showed that local temperature increase, for the given electric
field, can create a transient block of both the generation and
propagation of the APs. Some preliminary experimental data in
support of this conclusion are also shown.
Index TermsNeural engineering, extracellular stimulation,
finite-element method, NEURON, thermal block
I. INTRODUCTION
Neural disorders or malfunction can cause severe medical
conditions affecting the quality of life for millions of patients
worldwide, with conventional drug treatment often being
ineffective. Electrical stimulation of peripheral nerves has
been developed in various degrees for treatment of conditions
including foot drop, hand grasp, spinal cord injury, pain relief
and epilepsy, to name a few [1]. Whilst in the first two
applications, the stimulation is mostly employed for the
activation of disabled or malfunctioning organs or muscles,
the latter two involve stimulation for the purpose of blocking
unwanted activity. In the case of spinal cord injury (SCI), both
types of stimulation are required; e.g. bladder incontinence
Manuscript received May 30, 2011. This work was supported in part by the
UK EPSRC grant EP/H024581. ZM would like to thank China Scholarship
Council for financial support and Prof. Toumazou for the opportunity to join
the Centre for Bio-Inspired Technology at Imperial College London. ZM also
thanks N.T. Carnevale, from Dep. of Psychology, Yale University for his
generous advice on NEURON modeling
Z.M. is with the Bioengineering College, Chongqing University,
Chongqing 400044China.
I.T. is with the Department of Electrical and Electronic Engineering,
University College London, London WC1E 6EZ, UK.
V.W. and C.T. are with the Department of Electrical and Electronic
Engineering and Institute of Biomedical Engineering, Imperial College
London, London SW7 2AZ, UK (e-mail: c.toumazou@imperial.ac.uk)
K.N. is with the Department of Electrical and Electronic Engineering and
Institute of Biomedical Engineering, Imperial College London, London SW7
2AZ, UK (tel: +44 20-7954-1594, e-mail: k.nikolic@imperial.ac.uk)
due to SCI required stimulation to cause bladder contraction
and sphincter opening, whilst blocking unwanted neural
activity between the bladder and the spine below the area of
injury removes the need for rhizotomy [2]. However such
nerves contain a number of fibre-groups (fascicles) that later
connect to specific organs, including ones that are in no need
for rehabilitative intervention. Additionally, the fibres in these
fascicles can have different diameters and functionality.
A number of methods have been proposed for blocking
nerve conduction typically based on electrical, chemical
and/or thermal methods [3]. As with all types of electrical
neural intervention, invasive techniques using intrafascicluar
electrodes [4], offer better control and accuracy but ultimately
damage the nerve. It is therefore very desirable to develop
non-penetrating interfaces that allow fascicle as well as
directional and fibre-type selectivity. The most established
ones are cuff electrodes [1], with possible multi-electrode
topologies for additional selectivity. Reversible blocking of
nerve conduction in targeted structures can be achieved by
using various stimulation schemes based on direct currents
(e.g. DC monophasic waveforms [5]) or high frequency
alternating currents (HFAC) [6]. Several recent studies have
examined the biophysics of HFAC techniques in both
myelinated and unmyelinated fibres, optimal electrode design
and optimal waveforms [7-8]. In practice, conventional
selectivity methods have exhibited limited success so far, as
they require high stimulus currents and have a limited
resolution evoking unwanted neural activity that can result in
side effects, but they constantly pursue improvements [8].
Overall, neurostimulation for blocking is very desirable;
either directly, to avert undesirable neural activity, or for
refining the selectivity of activating stimulation methods.
Temperature-regulated neural control can be a strong
candidate for blocking nerve propagation with the benefit of
no direct contact between the stimulation source and the
tissue, high spatial resolution, and no electrical interference to
bio-recordings. However, the clinical implementation of
thermal block is very challenging, as irreversible thermal
ablation can occur during long-term stimulation. This has led
to the consideration of multi-modal stimulus inputs for neural
signal manipulation. To date, combined methods have only
been employed in therapeutic applications as a compensation
technique. Ackermann et al [3] investigated nerve cooling to
remove an undesirable response during HFAC blocking.
Thermal neural inhibition (or heat block”) was known
since the experiments of Hodgkin and Katz [9] and Huxley
[10] but only for unmyelinated axons. Raminsky [11] showed
reversible thermal block in demyelinated nerves between 35
and 36 °C and irreversible heating block of myelinated A and
A Simulation Study of the Combined
Thermoelectric Extracellular Stimulation of the
Sciatic Nerve of the Xenopus Laevis: the
Localized Transient Heat Block
Zongxia Mou, Iasonas F. Triantis, Member, IEEE, Virginia M. Woods, Student Member, IEEE,
Christofer Toumazou, Fellow IEEE, and Konstantin Nikolic, Member, IEEE

PAPER IDENTIFICATION NUMBER:
2
C-fibres of the cat was shown in [12]. The influence of
temperature on the response of the myelinated sciatic frog’s
nerve was studied by Rattay and Aberham [13]. They showed
how changing kinetics of the gating mechanisms of the
sodium ion channels was responsible for the faster onset of
APs and reduction of the AP amplitude. However,
temperature was typically considered to be a global, spatially
uniform parameter. In recent research an alternative method
has emerged, with the use of a laser coupled to an optic fiber,
offering the ability to focus light to a very narrow beam and
examine the effects of local heating on the neural behavior.
The assumption is that the main effect of the laser radiation on
the nerve is due to water absorption of the light, heating and
consequent increase of temperature. Recently it has been
discovered that very short, high-energy laser pulses can
activate nerves [14-17]. This technique has been further
developed and a commercial illumination system for this
purpose is available. However the exact mechanism of neural
activation by a burst of intense laser pulses is still not fully
understood [18].
Here we examine the theoretical and experimental
consequences of extracellular thermoelectric stimulation on a
model of the Xenopus sciatic nerve. We use a nerve cuff
electrode for electrical stimulation and a laser diode coupled
to an optic fiber for inducing localized thermal effects. In Sec.
II and III we give a description of our model and experimental
setup. Results are given in Sec. IV including a demonstration
of the thermoelectric block of neural signals. Two cases of the
heat block are identified: generation block where the
creation of the AP and the temperature block take place at the
same node, and propagation block when an already
propagating AP is stopped due to elevated temperature of only
one or several nodes along a myelinated axon. We found that
much higher temperatures are needed to induce the latter.
Finally, the paper concludes by assessing the merits of
combined optical and electrical stimulation for advancing
selectivity in peripheral neural interfacing.
II. THERMOELECTRIC STIMULATION MODELING
First it was essential to build a model of the generation and
propagation of nerve impulses under combined
thermoelectric stimulation. A variety of mathematical and
computer models has been used to study the electrical
behavior of neural myelinated fibers. The node of Ranvier
membrane excitability of Xenopus laevis was first modeled by
Frankenhaeuser and Huxley (FH model) [19] and
implemented later by Butikoffer [20] and Dean [21].
However, this model has only a single node without
considering the mutual interaction among adjacent segments
of the excitable membrane. McNeal [22] implemented a
myelinated fiber model describing the electrical behavior of
all nodes, but it ignored the passive electrical properties of the
insulating myelin sheath. FitzHugh [23] and Bostock [24] first
considered the role of the myelin internode (in addition to the
active nonlinear properties at the nodes). The mathematical
basis for the extracellular fiber stimulation was given by
Rattay [25]. The complete description of an active nerve fiber
under extracellular stimulation is essential for an investigation
of the thermoelectric effects on AP initiation and blocking.
NEURON software (v7.1 [26]) was used to simulate the
electrical behavior of the nerve axons. We assume that the
myelin sheath is a perfect insulator and incorporate the FH
model at each node of Ranvier. The electric field distribution
of the surrounding area of the nerve under varying
extracellular electrode configurations and stimulus patterns
was calculated in COMSOL
®
Multiphysics 3.5a. The main
advantage of this framework over the other proposed models
is that spatial properties of the extracellular stimulus can be
selected arbitrarily, so that one can simulate a variety of
electrode-neuron geometries of practical interest.
Additionally, special attention is paid to the phenomenon of
the influence of ambient temperature, as well as heating
specific nodes, on nerve kinetics. Recently COMSOL was
used for simulating a Hodgkin-Huxley model of APs in neural
fibers and corresponding electric field creation in the
extracellular space [27]. Some other studies on peripheral
nerve electrode simulations employed Maxwell3D in
combination with NEURON [28].
III. METHODS
Our simulations incorporated three modeling
environments. An electrode model in Simulink accounted for
the electrical drop due to the electrode-electrolyte interface.
The voltage representation of the current-mode stimulus was
imported into a finite-element model of the cuff electrode
(COMSOL). The extracellular potential along a fiber within
the nerve bundle was then exported into NEURON software,
where the electrical response of the neural membrane was
calculated. Thermal stimulation was realized in the membrane
model by defining the local temperature at every node in
NEURON. A tripolar cuff was used to stimulate the sciatic
nerve of a Xenopus laevis (Fig.1a,b,c). Fig.1a shows our
experimental setup which was replicated for the simulation
studies: a cuff electrode surrounded the sciatic nerve with a
laser fiber near the position of the central cathode (Fig.1b).
d
The recording cuff system with amplifiers, connected to the
data acquisition system, is shown in Fig. 1d. Fig.1c shows the
a
b
C
A1
A2
d
C
A2
A1
i(t)
N20
N21
N19
N22 N40
N0 N18
c
Fig. 1. (a) The cuff electrodes (provided by M. Schüettler from IMTEK,
Freiburg, Germany) and the frog’s sciatic nerve used in experiments and for
computer simulations. The stimulation cuff is on the left hand side together
with the optical fiber (vertical yellow tube) used for illuminating the nerve
bundle by the laser. The recording tripolar cuff is on approximately 1cm
distance to the right of the cathode electrode of the stimulation cuff and
consists of three ring electrodes on 1cm distance each. (b) A schematic
presentation of the nerve and stimulation tripolar cuff and the optical fiber (or
several fibers), (c) cuff electrodes, the cathode (C) and two anodes (A1 and
A2), stimulation current source and a myelinated axon with 41 nodes of
Ranvier (labeled N0-N40). (d) The recording cuff and the amplification and
recording system.

PAPER IDENTIFICATION NUMBER:
3
concept of the stimulation system used in our simulation
models. The cuff electrode was connected in a tripolar
configuration and a current flowed from cathode to anode. We
assumed that all the fibers are longitudinal. In our simulations
we consider a myelinated fiber with 41 nodes of Ranvier (N0
N40) and 41 myelinated sections. Note that node N20 (the
node where an AP was initiated), can have a variable position
relative to the center of the cathode (C).
A. COMSOL model: Geometry, materials properties
A finite element model of a peripheral nerve and tripolar
cuff electrode were implemented in the COMSOL simulation
environment. The simulated nerve and electrode geometries,
shown in Fig.2, were constructed to closely match those found
in our experimental setup (see Section IIID). The starting
point for the cuff model was the modeling study of the tripolar
cuff electrode nerve stimulation of Goodall et.al [32]. The
conductivity and dielectric permeability of each material type
used in our model were found in the literature (Table 1), but
the saline conductivity was obtained in our experiments to
ensure the accuracy of our electrode model. Fig. 2a shows the
geometry of the cuff-nerve system, vertical and radial cross
sections. The z-axis (vertical axis) represents the longitudinal
center line of the nerve bundle.
Fig.2b illustrates the cuff-nerve configuration within the
COMSOL model. A 2D axially symmetric, homogeneous,
isotropic volume conductor of the nerve was constructed in
COMSOL using the conductive media AC module to solve
Maxwell’s equations. A time-dependent solver was used in all
models. Rotation of the 2D picture around the r-axis produces
the 3D model of the actual cuff electrode (Fig 1a). Fig. 2b also
shows the electric potential contours, a quasi static solution at
the end of a stimulus pulse.
B. Electrode-electrolyte interface
The effect of the electrode-electrolyte interface was taken
into consideration when calculating the potential drop across
the interface during the stimulus current flow. The details of
the experimental investigation of this system were reported
elsewhere [33] and we only present here the equivalent circuit
of the electrode-electrolyte interface (Fig.3a) and a final result
(Fig.3b). We used Mathworks Simulink to simulate the
equivalent circuit of the electrode-electrolyte interface and fit
the parameter values given in Table 2. The stimulus current
flows across the interface and the output voltages obtained in
Matlab simulations were saved as a function of time into a
text file. This file was then imported into the COMSOL model
of a cuff-nerve system, to provide the boundary values for the
electrode potentials i.e. it represents the stimulation signal.
Fig. 3b gives an example of the electrical signal created after
the electrode-electrolyte interface, and demonstrates the
shape change of the square current pulse due to the
charge-discharge effect of the capacitance and resistance in
the interface.
C. NEURON model
Sciatic nerve fibers of Xenopus laevis were implemented in
the NEURON simulation environment [26]. Our model for
the nerve fiber assumed a myelinated axon including 41 nodes
of Ranvier and 41 internodes (myelin sections). The number
of nodes was arbitrarily chosen with the sole purpose of
having enough nodes to avoid any end effects in the
simulations. The starting equation of the axon model is the
classical Hodgkin-Huxley type equation [25]:


= 










󰇛󰇜
TABLE I
ELECTRICAL PARAMETER VALUES FOR THE MATERIAL SYSTEMS IN THE MODEL
Parameter
Contact
[29]
Cuff
[30]
Nerve &
Epineur. [31]
Saline
Conductivity (S/m)
8.9 x10
6
6.7 x 10
-14
0.6
0.8
Relative Permittivity
1
4
10
5
80
TABLE II
FITTED VALUES FOR PLATINUM BLACK-SALINE INTERFACE IN FIG. 3A
Electrode
C
dl
(nF)
R
ct
(Ω)
C
W
(μF)
R
W
(Ω)
R
S
(Ω)
Cathode
1.0 k
135.3
3.98
265.7
190.8
Anode
0.5
245.1
1 x 10
5
18.99 k
Fig. 2. (a) Cross section of the nerve and electrodes. R is the radius of the
nerve bundle (R=0.6 mm, h=0.15 mm). (b) Geometry of the system used in
COMSOL and the electric potential contours obtained in the simulations.
Rectangle N represents the nerve bundle (0.6 x 16 mm). Rectangle Saline is
the longitudinal section of the saline (6 x16 mm). A1, A2 (0.5 mm) are the
anodes and C (0.5 mm) is the cathode. The metallic contacts were embedded
in the polyimide substrate. The distance between cuff and nerve border is
0.15mm. The boundary conditions are described in Appendix B.
Fig. 3. (a) Equivalent circuit of the electrode-electrolyte interface. C
dl
is the
double layer capacitance, R
ct
charge transfer resistance, C
w
the Warburg
diffusion capacitive element, R
w
the Warburg diffusion resistive element and
R
s
solution bulk resistance. The Anode represents the combined impedance
of both anodes. (b) Electrical stimulus signal calculated with the electrode
model for square current pulse (amplitude = 147 A, duration = 300 s) and
measured across points A and B in panel (a).

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  • ...…(Williams and Constandinou, 2013), voltage stimulation with current control (Luan and Constandinou, 2012), hybrid electro-optical stimulation (Duke et al., 2012; Mou et al., 2012), or integrating current controlled stimulation with microfluidics to reduce stimulation thresholds (Song et al., 2011)....

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  • ...Laser induced heating has also been demonstrated for neural inhibition as part of a hybrid electrical stimulation/thermal inhibition device (Mou et al., 2012; Duke et al., 2013)....

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  • ...Conversely during slow heating the changes to ionic channels dominate and in particular changes to Na+ and K+ activation/deactivation dynamics prevent action potential initiation and propagation (Mou et al., 2012; Duke et al., 2013)....

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  • ...For more details about the electrode-electrolyte model and the nerve model which is in this case Xenopus laevis sciatic nerve see Mou et al. (2012)....

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  • ...The peripheral nerve was a carefully extracted sciatic nerve (from a dissected African clawed frog - Xenopus laevis) of approximately 10 cm length, that had been tied at both ends and immersed in amphibian Ringer’s solution [35]....

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Journal ArticleDOI
TL;DR: The results indicate that an increase in baseline temperature is a likely contributor to hybrid force generation, and suggests that extraneural INS of peripheral nerves at physiologically relevant repetition rates is possible using hybrid electro-optical stimulation.
Abstract: Objective. Optical methods of neural activation are becoming important tools for the study and treatment of neurological disorders. Infrared nerve stimulation (INS) is an optical technique exhibiting spatially precise activation in the native neural system. While this technique shows great promise, the risk of thermal damage may limit some applications. Combining INS with traditional electrical stimulation, a method known as hybrid electro-optical stimulation, reduces the laser power requirements and mitigates the risk of thermal damage while maintaining spatial selectivity. Here we investigate the capability of inducing force generation in the rat hind limb through hybrid stimulation of the sciatic nerve. Approach. Hybrid stimulation was achieved by combining an optically transparent nerve cuff for electrical stimulation and a diode laser coupled to an optical fiber for infrared stimulation. Force generation in the rat plantarflexor muscles was measured in response to hybrid stimulation with 1 s bursts of pulses at 15 and 20 Hz and with a burst frequency of 0.5 Hz. Main results. Forces were found to increase with successive stimulus trains, ultimately reaching a plateau by the 20th train. Hybrid evoked forces decayed at a rate similar to the rate of thermal diffusion in tissue. Preconditioning the nerve with an optical stimulus resulted in an increase in the force response to both electrical and hybrid stimulation. Histological evaluation showed no signs of thermally induced morphological changes following hybrid stimulation. Our results indicate that an increase in baseline temperature is a likely contributor to hybrid force generation. Significance. Extraneural INS of peripheral nerves at physiologically relevant repetition rates is possible using hybrid electro-optical stimulation. (Some figures may appear in colour only in the online journal)

46 citations


Cites background from "A Simulation Study of the Combined ..."

  • ...Recent modeling studies demonstrated that this is due to non-uniform rate increases in the temperature-dependent Hodgkin–Huxley gating mechanisms [28]....

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References
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Book
01 Jan 2006
TL;DR: Covering details of NEURON's inner workings, and practical considerations specifying anatomical and biophysical properties to be represented in models, this book uses a problem-solving approach that includes many examples to challenge readers.
Abstract: Assuming no previous knowledge of computer programming or numerical methods, The NEURON Book provides practical advice on how to get the most out of the NEURON software program. Although written primarily for neuroscientists, teachers and students, readers with a background in the physical sciences or mathematics and some knowledge about brain cells and circuits, will also find it helpful. Covering details of NEURON's inner workings, and practical considerations specifying anatomical and biophysical properties to be represented in models, this book uses a problem-solving approach that includes many examples to challenge readers.

1,233 citations

Journal ArticleDOI
TL;DR: It is shown that even when the stimulus is a constant-current pulse, the membrane current at the nodes varies considerably with time, and the strength-duration curve calculated from the model is consistent with previously published experimental data.
Abstract: Excellent models have been presented in the literature which relate membrane potential to transverse membrane current and which describe the propagation of action potentials along the axon, for both myelinated and nonmyelinated fibers. There is not, however, an adequate model for nerve excitation which allows one to compute the threshold of a nerve fiber for pulses of finite duration using electrodes that are not in direct contact with the fiber. This paper considers this problem and presents a model of the electrical properties of myelinated nerve which describes the time course of events following stimulus application up to the initiation of the action potential. The time-varying current and potential at all nodes can be computed from the model, and the strength-duration curve can be determined for arbitrary electrode geometries, although only the case of a monopolar electrode is considered in this paper. It is shown that even when the stimulus is a constant-current pulse, the membrane current at the nodes varies considerably with time. The strength-duration curve calculated from the model is consistent with previously published experimental data, and the model provides a quantitative relationship between threshold and fiber diameter which shows there is less selectivity among fibers of large diameter than those of small diameter.

876 citations


Additional excerpts

  • ...The threshold of neural activation is approximately inversely proportional to the square root of fiber diameter (Ithresh ∼ 1/ √ D), as was previously shown in [22] and [32]....

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  • ...McNeal [22] implemented a myelinated fiber model describing the electrical behavior of all nodes, but it ignored the passive electrical properties of the insulating myelin sheath....

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Journal ArticleDOI
TL;DR: It is important to know whether the characteristic relation between action potential and resting potential holds over a wide range of temperature, and the use of an internal recording electrode facilitates this study.
Abstract: The effect of temperature on the electrical activity of nerve and muscle has been studied intermittently since the time of Bernstein (1902). Among the most important investigations are those of Lucas (1908), Verzar (1912), Adrian (1921), Gasser (1931), Bremer & Titeca (1933, 1946), Auger & Fessard (1936), Schoepfle & Erlanger (1941), Cardot & Arvanitaki (1941), Lorente de No (1947), Tasaki & Fujita (1948) and Lundberg (1948). There appears to be general agreement that the resting potential has a low temperature coefficient, but the evidence concerning the effect of temperature on spike amplitude is conflicting. The experiments of Gasser (1931) suggest that the temperature coefficient of the spike is large and positive, while those of Schoepfle & Erlanger (1941) indicate that it is small and negative. Recent work on the giant axon of the squid suggests that the effect of temperature should be examined with this preparation. In particular, it is important to know whether the characteristic relation between action potential and resting potential holds over a wide range of temperature. The use of an internal recording electrode facilitates this study, since membrane potentials can be measured directly and are independent of the amount of external short circuiting. Another important advantage of this technique is that the temperature of the preparation can be altered rapidly by changing the sea water in which the axon is immersed.

869 citations


"A Simulation Study of the Combined ..." refers methods in this paper

  • ...Thermal neural inhibition (or “heat block”) was known since the experiments of Hodgkin and Katz [9] and Huxley [10] but...

    [...]

  • ...Thermal neural inhibition (or “heat block”) was known since the experiments of Hodgkin and Katz [9] and Huxley [10] but only for unmyelinated axons....

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Journal ArticleDOI
TL;DR: A critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses is provided.
Abstract: Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strate- gies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

802 citations


"A Simulation Study of the Combined ..." refers background in this paper

  • ...2194146 conditions including foot drop, hand grasp, spinal cord injury (SCI), pain relief, and epilepsy, to name a few [1]....

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  • ...The most established ones are cuff electrodes [1], with possible multielectrode topologies for addi-...

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Journal ArticleDOI
TL;DR: In this paper, the near infrared absorption spectrum of liquid water at 20°C was investigated using a PbS cell detector system and the total spectral range investigated was from 0.70 to 2.50μ.
Abstract: The near infrared absorption spectrum of liquid water at 20°C has been reinvestigated using a PbS cell detector system. The total spectral range investigated was from 0.70 to 2.50μ. A curve is included which shows five prominent absorption bands at 0.76, 0.97, 1.19, 1.45, and 1.94μ; and a table gives experimental results of water absorption at 20°C.

699 citations

Frequently Asked Questions (2)
Q1. What are the contributions in this paper?

This paper presents the response of the Xenopus laevis nerve fibers to combinations of electrical ( cuff electrodes ) and optical ( infrared laser, low power sub-5mW ) stimulation. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials ( AP ). The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. 

This work presents a proof-of-concept investigation, but further work on geometric optimization ( both experimentally and theoretically ) is necessary to fully realize a functional interface for selective nerve stimulation.