Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

Stephanova, D. I.; Daskalova, M.; Alexandrov, Alexandar

doi:10.1007/s10867-006-9008-x

Cited by 12 publications

(5 citation statements)

References 34 publications

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“…To capture these inhomogeneities, one uses a second approach called compartmental modeling, where the system is modeled using a large number of small, locally uniform segments. Simulating numerically the exchange of charges between segments with different dynamic properties has revealed the important roles of myelin morphology and nodal dynamics for the propagation of action potentials [4, 9–12]. This has been the main method to address the effects of demyelination [2, 3, 5], ion-channel noise [13–16], and spike after-potential [4] on axonal propagation.…”

Section: Introductionmentioning

confidence: 99%

Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach

Naud

Longtin

2019

J. Math. Neurosc.

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To establish and exploit novel biomarkers of demyelinating diseases requires a mechanistic understanding of axonal propagation. Here, we present a novel computational framework called the stochastic spike-diffuse-spike (SSDS) model for assessing the effects of demyelination on axonal transmission. It models transmission through nodal and internodal compartments with two types of operations: a stochastic integrate-and-fire operation captures nodal excitability and a linear filtering operation describes internodal propagation. The effects of demyelinated segments on the probability of transmission, transmission delay and spike time jitter are explored. We argue that demyelination-induced impedance mismatch prevents propagation mostly when the action potential leaves a demyelinated region, not when it enters a demyelinated region. In addition, we model sodium channel remodeling as a homeostatic control of nodal excitability. We find that the effects of mild demyelination on transmission probability and delay can be largely counterbalanced by an increase in excitability at the nodes surrounding the demyelination. The spike timing jitter, however, reflects the level of demyelination whether excitability is fixed or is allowed to change in compensation. This jitter can accumulate over long axons and leads to a broadening of the compound action potential, linking microscopic defects to a mesoscopic observable. Our findings articulate why action potential jitter and compound action potential dispersion can serve as potential markers of weak and sporadic demyelination.

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Section: Introductionmentioning

confidence: 99%

Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach

Naud

Longtin

2019

J. Math. Neurosc.

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“…This term is initially introduced by Raminsky et al 28 in 1971 who documented a markedly slowing in nerve conduction in demyelinated fiber to the point of CB by focal application of diphtheria toxin in the ventral root. Stephanova et al 29 also were able to induce “inter-nodal focal demyelination with CB” by myelin wrap reduction in one-three consecutive internodes along the length of human motor nerve fibers.…”

Section: Discussionmentioning

confidence: 99%

Nodal Conduction Block and Internodal Conduction Block in Nodopathy

2024

Journal of Clinical Neuromuscular Disease

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Objectives: In 2015, a new term “nodopathy” was introduced to represent a group of neuropathy because of autoantibodies at the node of Ranvier and paranodal area. This review was conducted to highlight the electrophysiologic characteristics of acute and chronic nodopathies by the newly introduced term: “nodal conduction block (CB); CB without temporal dispersion or slow nerve conduction velocity” and by introducing a new term: “internodal CB; CB with temporal dispersion or/and slow nerve conduction velocity”. Methods: Through PubMed searches, 23 cases of acute (<4 weeks of neuropathy) nodopathy and 12 cases of chronic (>4 weeks of neuropathy) nodopathy are identified. Two other required inclusion criteria are positive nodal antibody test and detailed nerve conduction data with or without figure. All existing data were analyzed to see whether these cases had nodal or internodal CB. Results: Among 23 cases of acute nodopathy, 11 had nodal CB, 9 internodal CB, and 3 mixed CB. Thus, nodal CB was observed in 61% of acute nodopathy cases and internodal CB in 52% of acute nodopathy cases. Among 12 cases of chronic nodopathy, all 12 had internodal CB. Conclusions: Nodal CB is the nerve conduction characteristic of acute nodopathy, but internodal CB does not rule out acute nodopathy. Internodal CB is the nerve conduction characteristic of chronic nodopathy.

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“…Apart from these differences, they do not consider coupling between axons, either via currents or fields, which we consider in this paper. The other papers of the same group, such as [8], follow their 1995 model and hence the differences from our work carry over to these later papers as well.…”

Section: Introductionmentioning

confidence: 91%

On the Geometry of Interacting Axon Tracts in Relation to Their Functional Properties

Chawla

Morgera

2022

Preprint

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It is well known that demyelination associated with multiple sclerosis alters coupling between axons in a diseased nerve tract due to exposure of ion channels. In this work we ask the question whether the presence of electric fields as a coupling mechanism between nerve axons, has any impact on the expected conduction properties of the nerve under focal demyelination. Using an approximate geometry for a bundle of three axons, we allow electric fields generated at a node of Ranvier to influence other nodes of Ranvier on different axons. In order to introduce focal demyelination, we allow a new type of structure, intermediate between a node and an internodal segment. We find that the nerve's conduction profiles are different with and without field-based coupling. This is important because it opens up the possibility for an experimental investigation to study whether field-based coupling predominates over current-based coupling. Fields and currents may also be measured using different methods and so there are implications for bioinstrumentation. From a systems perspective, the study is based on a novel equation which allows electric fields to act as sources of current at axons' nodes of Ranvier, thereby generating new behaviors from the set of coupled partial differential equations that model the electrodynamics of the nerve. In addition to our simulation study of focal demyelination, we present a justification for a certain geometric W-matrix used in our phenomenological 2019 model. We also provide the first simulations of a tract of tortuous axons, showing the impact of tract tortuosity on conduction velocity. The tortuous model is analyzed geometrically to illustrate the mechanism of synchronization. Finally, this same model is shown to be castable as a learning machine - a formulation that has neuroscience implications.

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Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

Cited by 12 publications

References 34 publications

Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach

Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach

Nodal Conduction Block and Internodal Conduction Block in Nodopathy

On the Geometry of Interacting Axon Tracts in Relation to Their Functional Properties

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