Using axon models to interpret electrodiagnostic nerve tests
© Jensen et al; licensee BioMed Central Ltd. 2008
Published: 11 July 2008
Automated nerve excitability testing is a relatively new electrodiagnostic technique that became commercially available in 2007 . 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 conditioning stimuli of different amplitudes and latencies with respect to a test stimulus. The standard clinical protocol 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 essential for explaining unexpected results . This study's objectives were to: 1) compare two candidate motor axon models for interpreting nerve excitability studies; 2) perform a sensitivity analysis to establish correlations between membrane biophysics and clinical outcome measures; and 3) develop an optimization routine for fitting the models to experimental data.
A minimal model (node and internode)  was compared to a multicompartment model with detailed morphology . All modeling and simulations were done using NEURON . Both models have been previously published but a full sensitivity analysis and independent comparison on the complete set of clinical nerve excitability protocols has not been done. The minimal model has been fine-tuned to match excitability results whereas the multicompartment model was fit to intracellular recordings of myelinated rat axons. The sensitivity analysis was restricted to changes of ± 40% from default for active membrane properties.
Supported by grants from AHFMR
- Digitimer DS5 Isolated Bipolar Constant Current Stimulator and QtracW software. [http://www.digitimer.com/clinical/pstims.htm]
- Kiernan MC, Isbister GK, Lin CS, Burke D, Bostock H: Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish. Ann Neurol. 2005, 57: 339-348. 10.1002/ana.20395.View ArticlePubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- Carnevale NT, Hines ML: The NEURON Book. 2006, Cambridge: Cambridge University PressView ArticleGoogle Scholar
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