Why Are Sensory Axons More Vulnerable for Ischemia than Motor Axons?

Objective:In common peripheral neuropathies, sensory symptoms usually prevail over motor symptoms. This predominance of sensory symptoms may result from higher sensitivity of sensory axons to ischemia.Methods:We measured median nerve compound sensory action potentials (CSAPs), compound muscle action potentials (CMAPs), and excitability indices in five healthy subjects during forearm ischemia lasting up to disappearance of both CSAPs and CMAPs.Results:Ischemia induced: (1) earlier disappearance of CSAPs than CMAPs (mean ± standard deviation 30±5 vs. 46±6 minutes), (2) initial changes compatible with axonal depolarization on excitability testing (decrease in threshold, increase in strength duration time constant (SDTC) and refractory period, and decrease in absolute superexcitability) which were all more prominent in sensory than in motor axons, and (3) a subsequent decrease of SDTC reflecting a decrease in persistent Na+ conductance during continuing depolarisation.Interpretation:Our study shows that peripheral sensory axons are more vulnerable for ischemia than motor axons, with faster inexcitability during ischemia. Excitability studies during ischemia showed that this was associated with faster depolarization and faster persistent Na+ channel inactivation in sensory than in motor axons. These findings might be attributed to differences in ion channel composition between sensory and motor axons and may contribute to the predominance of sensory over motor symptoms in common peripheral neuropathies. © 2013 Hofmeijer et al

Modeling pathological brain rhythms: constructing a neural mass model from single cell dynamics

Neural mass models (NMM) describe neural activity on a macroscopic scale, which can be compared to the electroencephalogram (EEG). This allows a better understanding of the processes responsible for various EEG patterns, including pathological rhythms as diffuse slowing or burst-suppression [1]. Using available models which contain explicit expressions for the synaptic response and number of synapses [2], pathological conditions that modulate synaptic function, such as anesthetics [3] and hypoxia, can be included easily. However, it is less obvious how to incorporate conditions which alter the excitability of neurons, such as hyperkalemia or channel blockers. Here, we present a method for constructing a neural mass model by using the relation between synaptic input of a single cell model and its firing rate. This allows an easy implementation for pathological conditions. We describe the average firing rate of a single population of neurons receiving one type of synaptic input, but this can readily be extended to multiple populations. A set of differential equations describes, traditionally, the average synaptic conductance [2]. Assuming Poisson statistics for the input, we can derive another equation, which describes the time evolution of the standard deviation of the synaptic conductance across the population. The average and standard deviation of the conductance then determine the distribution and the corresponding average of the firing rates in the population. As initial verification, the constructed mean field model is numerically compared to a network of single cells. From the single cell model we determine the dependence of the firing rate on (constant) synaptic conductance numerically. Furthermore, we show that, for fluctuating inputs, the firing rate is well approximated by the instantaneous synaptic conductance. 120 Hodgkin-Huxley type cells were connected all-to-all with inhibitory synapses: a simple configuration which results in intrinsic oscillations. Each cell receives inhibitory external input as well, consisting of Poisson trains. We find a close agreement between the constructed neural mass model and the network simulation (Figure 1). Figure 1. Comparison of step response of the derived NMM and a detailed network model The proposed method can easily be extended to model heterogeneous populations, multiple types of synapses, spatial structures, propagation delays, and bursting dynamics [4]. Any pathophysiology can readily be incorporated by adapting the single cell model. This allows for testing hypotheses on processes underlying abnormal EEGs

Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy

Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2 lowered from 150 to 20 mmHg) during 6 h in 55 cultures. Three hours after restoration of normoxia, half of the cultures were treated with ghrelin for 24 h, while the other, non-supplemented, were used as a control. All cultures were processed immunocytochemically for detection of the synaptic marker synaptophysin. We observed that hypoxia led to drastic decline of the number of synapses, followed by some recovery after return to normoxia, but still below the prehypoxic level. Additionally, synaptic vulnerability was selective: large- and small-sized neurons were more susceptible to synaptic damage than the medium-sized ones. Ghrelin treatment significantly increased the synapse density, as compared with the non-treated controls or with the prehypoxic period. The effect was detected in all neuronal subtypes. In conclusion, exogenous ghrelin has a robust impact on the recovery of cortical synapses after hypoxia. It raises the possibility that ghrelin or its analogs may have a therapeutic potential for treatment of postanoxic encephalopathy

Reproducability of corticomuscular coherence:A comparison between static and perturbed tasks

Corticomuscular coherence (CMC) is used to quantify functional corticomuscular coupling during a static motor task. Although the reproducibility of CMC characteristics such as peak strength and frequency within one session is good, reproducibility of CMC between sessions is limited (Pohja et al. 2005, NeuroImage). Reproducible CMC characteristics are required in order to assess changes in corticomuscular coupling in a longitudinal study design, for example during rehabilitation. We recently demonstrated that the presence of CMC in the population in substantially increased when position perturbations are applied during an isotonic force task. Here, we assessed the reproducibility of perturbed CMC compared to unperturbed CMC. Subjects (n=10) performed isotonic wrist flexion contractions against the handle of a wrist manipulator (WM) while EEG (64 channels) and EMG of the m.flexor carpi radialis were recorded in two experimental sessions separated by at least one week. The handle of the WM either kept a neutral angle (baseline task) or imposed a small angle perturbation (perturbed task). In the baseline task, 3 subjects had significant CMC in both the first and the second sessions. In the other 7 subjects no significant CMC was found in both sessions. Between sessions, significant CMC was always found in overlapping frequency bands and generally on overlapping electrodes. In the subjects with CMC a significant cross correlation coefficient between the spectra in the two sessions was present (mean 0.57; 0.3 - 0.79). In the perturbed task CMC was present in 8 subjects in both sessions and absent in 1 subject in the two sessions. One subject had CMC only in the second session. For the subjects with CMC, the correlation coefficient between the spectra of the two sessions was significantly larger than zero with a mean of 0.68 (range 0.38 - 0.88). The presence and absence of CMC within subjects could be reproduced very well between the sessions. This was also demonstrated by the significant correlation between the spectra in the two sessions ; the degree of correlation was variable over subjects both in the baseline and the perturbed task. The reproducibility characteristics of CMC in a perturbed task are comparable or slightly better with respect to an unperturbed task. However, comparison is limited by the small number of subjects with CMC in the baseline task. Perturbed CMC is present in more subjects, which is crucial when developing methods to track corticomuscular coupling over multiple sessions, for example during rehalibitation.handles MIMO systems, and can deal with short measurement time

Reliability and agreement of intramuscular coherence in tibialis anterior muscle

Background: Neuroplasticity drives recovery of walking after a lesion of the descending tract. Intramuscular coherence analysis provides a way to quantify corticomotor drive during a functional task, like walking and changes in coherence serve as a marker for neuroplasticity. Although intramuscular coherence analysis is already applied and rapidly growing in interest, the reproducibility of variables derived from coherence is largely unknown. The purpose of this study was to determine the test-retest reliability and agreement of intramuscular coherence variables obtained during walking in healthy subjects. Methodology/Principal Findings: Ten healthy participants walked on a treadmill at a slow and normal speed in three sessions. Area of coherence and peak coherence were derived from the intramuscular coherence spectra calculated using rectified and non-rectified M. tibialis anterior Electromyography (EMG). Reliability, defined as the ability of a measurement to differentiate between subjects and established by the intra-class correlation coefficient, was on the limit of good for area of coherence and peak coherence when derived from rectified EMG during slow walking. Yet, the agreement, defined as the degree to which repeated measures are identical, was low as the measurement error was relatively large. The smallest change to exceed the measurement error between two repeated measures was 66% of the average value. For normal walking and/or other EMG-processing settings, not rectifying the EMG and/or high-pass filtering with a high cutoff frequency (100 Hz) the reliability was only moderate to poor and the agreement was considerably lower. Conclusions/significance: Only for specific conditions and EMG-processing settings, the derived coherence variables can be considered to be reliable measures. However, large changes (>66%) are needed to indicate a real difference. So, although intramuscular coherence is an easy to use and a sufficiently reliable tool to quantify intervention-induced neuroplasticity, the large effects needed to reveal a real change limit its practical use

De terminologie van het EEG: het is tijd om scherper te worden

De terminologie van het EEG is gegroeid, niet ontworpen. Enkele bronnen van verwarring\ud worden besproken. Het gebruik van concepten die niet goed onderbouwd zijn, zoals\ud ‘hypofunctioneel’ of ‘irritatief’, kan beter vermeden worden. Het woord ‘epileptiform’ wordt\ud zowel beschrijvend gebruikt (‘ziet er scherp uit’) als interpreterend (‘wijst op epilepsie’),\ud wat misverstanden in de hand werkt. De terminologie van het EEG op de Intensive Care\ud vergt standaardisering teneinde klinische consequenties te kunnen onderzoeken. De\ud auteurs roepen op beschrijving en interpretatie volledig te scheide

Stretch Evoked Potentials in Healthy Subjects and After Stroke: A Potential Measure for Proprioceptive Sensorimotor Function

Sensory feedback is of vital importance in motor control, yet rarely assessed in diseases with impaired motor function like stroke. Muscle stretch evoked potentials (StrEPs) may serve as a measure of cortical sensorimotor activation in response to proprioceptive input. The aim of this study is: 1) to determine early and late features of the StrEP and 2) to explore whether StrEP waveform and features can be measured after stroke. Consistency of StrEP waveforms and features was evaluated in 22 normal subjects. StrEP features and similarity between hemispheres were evaluated in eight subacute stroke subjects. StrEPs of normal subjects had a consistent shape across conditions and sessions (mean cross correlation waveforms > 0.75). Stroke subjects showed heterogeneous StrEP waveforms. Stroke subjects presented a normal early peak (40 ms after movement onset) but later peaks had abnormal amplitudes and latencies. No significant differences between stroke subjects with good and poor motor function were found (P > 0.14). With the consistent responses of normal subjects the StrEP meets a prerequisite for potential clinical value. Recording of StrEPs is feasible even in subacute stroke survivors with poor motor function. How StrEP features relate to clinical phenotypes and recovery needs further investigatio