Modeling and simulation of multifocal motor neuropathy (MMN)

Master Assignment

Modeling and simulation of multifocal motor neuropathy (MMN)

Background

A curious neurological disorder, multifocal motor neuropathy (MMN), is a peripheral neuropathy characterised by focal nerve lesions where action potential propagation is blocked. This phenomenon is only observed in motor but not in sensory axons, despite the fact that both these axons run in the same nerve and can even run in the same fascicle.

In this assignment, you will explore which particular features of motor and sensory nerves are responsible for this differential sensitivity in action potential propagation block. Candidate characteristics are the subtle differences in ion-channel composition between motor and sensory axons, differences in Ih-currents, or the presence of larger persistent inward sodium currents in sensory nerves.

You will build a a model of a a single myelinated axon. Model characteristics should include ionic concentration gradients, ionic fluxes, detailed characteristics of relevant ion-channels and pumps in the axolemma, electrical conduction properties of the axon core, and geometric features of the axon and myelin sheath. If possible, the model should include effects of temperature on ion-channel activity, too. As a starting point, the model described in [1] seems appropriate. Another model is described in [2-3], which is based on the Nygren and Halter model. Model simulations will be compared with real-world observations from patients with MMN, recorded in the UMC Utrecht.

For this master assignment, we seek a student with a background in Applied Physics, Applied Mathematics or Biomedical Engineering, with a strong interest in neuroscience, biophysics and computational modeling.

This project has been initiated and proposed by Dr Hessel Franssen, neurologist/clinical neurophysiologist and Maria Kovalchuk MD, both from the University Medical Center Utrecht, and will be performed as a collaboration with the Clinical Neurophysiology group at the University of Twente.

Literature

[1] Nygren A. and Halter J.A. A General Approach to Modeling Conduction and Concentration Dynamics in Excitable Cells of Concentric Cylindrical Geometry, J theor Biol 199: 329-358, 1999

[2] Stephanova D.I. and Bostock H. A distributed parameter model of the myelinated human motor nerve: temporal and spatial distributions of action potentials and ionic currents, Biol Cybern 73, 275-280, 1995.

[3] Stephanova D.I. and Bostock H. A distributed parameter model of the myelinated human motor nerve: temporal and spatial distributions of electrotonic potentials and ionic currents. Biol Cybern 74: 543-547, 1996

[4] Cameron C et al. Modeling the Excitability of Mammalian Nerve Fibers:

Influence of Afterpotentials on the Recovery Cycle, J Neurophysiol 87:995-1006,2002

For more information, please contact:

H.Fransen@umcutrecht.nl or m.j.a.m.vanputten@utwente.nl