Internodal mechanism of pathological afterdischarges in myelinated axons.

INTRODUCTION: Recent optical recordings of transmembrane potentials in the axons of pyramidal neurons have shown that the internodal action potentials (APs) predicted in our previous studies do exist. These novel processes are not well understood. In this study we aim to clarify electrical phenomena in peripheral myelinated axons (MAs). METHODS: We used a multi-cable Hodgkin-Huxley-type model to simulate MAs with potassium channels that were either normal or inhibited along a short region of the internodal membrane. A brief stimulus was applied to the first node. RESULTS: We demonstrated peculiarities in the internodal APs induced by a saltatory AP: They existed across internodal membranes, were detectable in periaxonal space but not in intracellular space, propagated continuously, collided near the mid-internodes, and produced internodal sources of afterdischarges. CONCLUSIONS: These results highlight the importance of the MA internodal regions as new therapeutic targets for avoiding afterdischarges provoked by reduced axonal fast potassium channel expression.

A possible link of oxaliplatin-induced neuropathy with potassium channel deficit.

INTRODUCTION: The neurotoxic side effects of oxaliplatin (a reference drug in the treatment of digestive tract tumors) can force suspension of treatment. The mechanisms of neuropathy are unclear. We aimed to simulate oxaliplatin-induced hyperactivity in myelinated axons (MA) based on published experimental data. METHODS: A Hodgkin-Huxley-type multi-cable MA model was used, which took into account active internodal processes and accumulation of ions in MA with 21 nodes. RESULTS: Even a very short (110-220 µm) internodal region devoid of potassium channels was sufficient to produce after-discharges in response to a saltatory action potential. An increase in the density of sodium channels, slowdown of their inactivation, and negative shifts along one node-internode region of the voltage dependence of sodium and potassium activation and of sodium inactivation induced no after-discharge. CONCLUSION: A combination of sodium channel blockers with drugs that obstruct the blockage of potassium channels or contribute to their opening could be effective in preventing oxaliplatin-induced "hyperexcitability."

Influence of motor unit synchronization on amplitude characteristics of surface and intramuscularly recorded EMG signals.

The increase in muscle strength without noticeable hypertrophic adaptations is very important in some sports. Motor unit (MU) synchronisation and higher rate of MU activation are proposed as possible mechanisms for such a strength and electromyogram (EMG) increase in the early phase of a training regimen. Root mean square and/or integrated EMG are amplitude measures commonly used to estimate the adaptive changes in efferent neural drive. EMG amplitude characteristics could change also because of alteration in intracellular action potential (IAP) spatial profile. We simulated MUs synchronization under different length of the IAP profile. Different synchronization was simulated by variation of the percent of discharges in a referent MU, to which a variable percent of remaining MUs was synchronized. Population synchrony index estimated the degree of MU synchronization in EMG signals. We demonstrate that the increase in amplitude characteristics due to MU synchronization is stronger in surface than in intramuscularly detected EMG signals. However, the effect of IAP profile lengthening on surface detected EMG signals could be much stronger than that of MU synchronization. Thus, changes in amplitude characteristics of surface detected EMG signals with progressive strength training could hardly be used as an indicator of changes in neural drive without testing possible changes in IAPs.

Interpretation of EMG integral or RMS and estimates of "neuromuscular efficiency" can be misleading in fatiguing contraction.

In occupational and sports physiology, reduction of neuromuscular efficiency (NME) and elevation of amplitude characteristics, such as root mean square (RMS) or integral of surface electromyographic (EMG) signals detected during fatiguing submaximal contraction are often related to changes in neural drive. However, there is data showing changes in the EMG integral (I(EMG)) and RMS due to peripheral factors. Causes for these changes are not fully understood. On the basis of computer simulation, we demonstrate that lengthening of intracellular action potential (IAP) profile typical for fatiguing contraction could affect EMG amplitude characteristics stronger than alteration in neural drive (central factors) defined by number of active motor units (MUs) and their firing rates. Thus, relation of these EMG amplitude characteristics only to central mechanisms can be misleading. It was also found that to discriminate between changes in RMS or I(EMG) due to alterations in neural drive from changes due to alterations in peripheral factors it is better to normalize RMS of EMG signals to the RMS of M-wave. In massive muscles, such normalization is more appropriate than normalization to either peak-to-peak amplitude or area of M-wave proposed in literature.

Effects of changes in intracellular action potential on potentials recorded by single-fiber, macro, and belly-tendon electrodes.

Some myopathies are accompanied by abnormal calcium homeostasis. Electromyography (EMG) in such patients shows signs of normal or myopathic EMG when detected by a single-fiber electrode and abnormally increased values in macro EMG. As calcium accumulation might be accompanied by changes in intracellular action potential (IAP) and muscle-fiber propagation velocity, we simulated the effects of such changes on motor unit potentials (MUPs) recorded by different kinds of electrodes. We found that: (1) the requirements for what potential can be accepted as a single-fiber action potential (SFAP) are too rigorous; (2) macro MUP amplitude can increase while SFAP amplitude can decrease when there is an increase in the spatial length of IAP spike; and (3) changes in the second phase of a belly-tendon-detected MUP or M wave could be used for noninvasive detection of increased IAP depolarizing (negative) after-potential.

Changes in intracellular action potential profile affect parameters used in turns/amplitude analysis.

The influence of changes in the intracellular action potential (IAP) spatial profile on motor unit potentials (MUPs), number of turns per second (NTs), and mean turn amplitude were simulated and analyzed. We show why measurement of NTs was "the best indicator of neurogenic affection" and why the lower diagnostic yield of turns/amplitude analysis in myopathy could be due to changes in IAP shape caused by elevated free calcium concentration. The results explain the complications observed when interference electromyographic signals obtained during high levels of isometric contractions were analyzed. We show that, in contrast to earlier assumptions, the effect of increased IAP spike duration on NTs was stronger than that of a decrease in muscle fiber propagation velocity (MFPV). The decrease in the NTs could occur without a drop-out of MUs and/or a decrease in their firing rates, and without a change in MFPV and synchronous firing.

Muscle fatigue during dynamic contractions assessed by new spectral indices.

PURPOSE: The aim of the present study was to test the applicability and sensitivity of new electromyography (EMG) spectral indices in assessing peripheral muscle fatigue during dynamic knee-extension exercise. METHODS: Seven subjects completed 10 sets of 15 repetitions of right knee-extension exercise lifting 50% of their one-repetition maximum. Torque (T), knee-joint angle, and the interference EMG of rectus femoris muscle were recorded simultaneously. Maximal voluntary isometric contraction (MVC) was tested before and after exercise. Median spectral frequency (Fmed) and new spectral indices of muscle fatigue (FInsmk) were calculated for each repetition. RESULTS: The rate and range of FInsmk- and Fmed-relative changes against the first repetition of the corresponding set increased gradually across successive repetitions within the set, reflecting accumulation of peripheral muscle fatigue. The maximal change of FInsmk observed in the present experiment was approximately eightfold, whereas that of Fmed was only 32%. Significant between-subject variability in the range of FInsmk changes (P < 0.0001) was found, so a hierarchical cluster analysis of muscle fatigue indices was conducted. Three distinct subgroups of subjects were identified: high (N = 1, FInsmk change > 400%), medium (N = 4, 200% < FInsmk change < 400%), and low (N = 2, FInsmk change < 200%) muscle fatigability. The changes in muscle performance during (last vs first repetition peak T, P = 0.03) and after (post- vs preexercise MVC, P = 0.012) exercise were significantly different between clusters (one-way ANOVA). The rate of fatigue development was also significantly different between clusters (linear regression analysis of Fmed and FInsmk changes). CONCLUSIONS: The new spectral indices are a valid and reliable tool for assessment of muscle fatigability irrespective of EMG signal variability caused by dynamic muscle contractions, and these indices are more sensitive than those traditionally used.

Simulation analysis of the ability of different types of multi-electrodes to increase selectivity of detection and to reduce cross-talk.

Selectivity of different one- and two-dimensional multi-electrodes and their ability to reduce cross-talk were analyzed. Signals from an individual motor unit (MU) were calculated as a single convolution of intracellular action potential (IAP) first temporal derivative and spatially filtered MU impulse response. It was shown that the uptake area (irrespective of the way it was defined) could not characterize electrode properties reliably because its estimate depended on the source parameters. Due to the different decline of individual phases of MU signals with depth, electrode should provide higher spatial and temporal resolution of the main phases for better selectivity and greater suppression of the terminal phases for cross-talk reduction. A two-dimensional normal double differentiating (NDD) electrode provided almost the same or slightly lower selectivity but weaker reduction of cross-talk than a longitudinal double differentiating (LDD) electrode. A transversal double differentiating (TDD) electrode provided a lower selectivity and weaker reduction of cross-talk than a LDD electrode. A new, BiTDD multi-electrode (performing difference between signals detected by two TDD electrodes) provided the best selectivity and reduction of cross-talk. To obtain the smallest cross-talk, a BiTDD electrode should be positioned above the end-plate region, while LDD, TDD, or NDD electrodes-above the ends of muscle that produced it. Signal differentiation improved selectivity but increased cross-talk.