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BMC Neuroscience
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Poster presentation
Using axon models to interpret electrodiagnostic nerve tests
Karl Jensen
1
, Thu NA Luu
1
and Kelvin E Jones*
1,2
Address:
1
Department Electrical and Computer Engineering, University of Alberta, Edmonton, AB, Canada, T6G 2H9 and
2
Faculty of Physical
Education & Recreation, University of Alberta, Edmonton, AB, Canada, T6G 2H9
Email: Kelvin E Jones* - kejones@ualberta.ca
* Corresponding author
Introduction
Automated nerve excitability testing is a relatively new
electrodiagnostic technique that became commercially
available in 2007 [1]. The purpose of an excitability test is
to infer the underlying membrane properties of the nerve
in order to detect ion channel disorders in vivo. This is
accomplished by using both supra- and sub-maximal con-
ditioning stimuli of different amplitudes and latencies
with respect to a test stimulus. The standard clinical pro-
tocol for motor axons includes four tests: 1) strength-
duration; 2) recovery cycle; 3) threshold electrotonus; and
4) current-threshold. The interpretation of the four tests is
complicated and mathematical models have been essen-
tial for explaining unexpected results [2]. This study's
objectives were to: 1) compare two candidate motor axon
models for interpreting nerve excitability studies; 2) per-
form a sensitivity analysis to establish correlations
between membrane biophysics and clinical outcome
measures; and 3) develop an optimization routine for fit-
ting the models to experimental data.
Methods
A minimal model (node and internode) [2] was com-
pared to a multicompartment model with detailed mor-
phology [3]. All modeling and simulations were done
using NEURON [4]. Both models have been previously
published but a full sensitivity analysis and independent
comparison on the complete set of clinical nerve excitabil-
ity protocols has not been done. The minimal model has
been fine-tuned to match excitability results whereas the
multicompartment model was fit to intracellular record-
restricted to changes of ± 40% from default for active
membrane properties.
Results
The minimal model provided a much better fit to data
acquired from healthy control subjects as seen in Figure 1.
The multicompartment model was especially poor at
matching data from the tests 3 & 4 that evaluate ion chan-
nel function in the internodal region. The sensitivity anal-
ysis indicated that the current ion channel models in the
multicompartment model are not capable of capturing
the variation in the healthy control data. Based on the
minimal model, much of the inter-individual variation in
healthy controls arises from differences in resting mem-
brane potential. We conclude that a hybrid model that
uses the morphology of the multicompartment model
and the ion channel kinetics from the minimal model will
provide the most utility for interpreting nerve excitability
tests.
from Seventeenth Annual Computational Neuroscience Meeting: CNS*2008
Portland, OR, USA. 19–24 July 2008
Published: 11 July 2008
BMC Neuroscience 2008, 9(Suppl 1):P43 doi:10.1186/1471-2202-9-S1-P43
This abstract is available from: http://www.biomedcentral.com/1471-2202/9/S1/P43
© 2008 Jensen et al; licensee BioMed Central Ltd. Page 1 of 2
(page number not for citation purposes)
ings of myelinated rat axons. The sensitivity analysis was

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Acknowledgements
Supported by grants from AHFMR
References
1. Digitimer DS5 Isolated Bipolar Constant Current Stimula-
tor and QtracW software [http://www.digitimer.com/clinical/
pstims.htm]
2. Kiernan MC, Isbister GK, Lin CS, Burke D, Bostock H: Acute tetro-
dotoxin-induced neurotoxicity after ingestion of puffer fish.
Ann Neurol 2005, 57:339-348.
3. McIntyre CC, Richardson AG, Grill WM: Modeling the excitability
of mammalian nerve fibers: influence of afterpotentials on
the recovery cycle. J Neurophysiol 2002, 87:995-1006.
4. Carnevale NT, Hines ML: The NEURON Book Cambridge: Cambridge
University Press; 2006.
Performance of minimal (black) versus multicompartment (grey) model on the four testsFigure 1
Performance of minimal (black) versus multicompartment (grey) model on the four tests. Dot-dash line is the mean from
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