Maria Piotrkiewicz

An influence of afterhyperpolarization on the pattern of motoneuronal rhythmic activity.

Motoneuronal spike trains were generated according to a simple model assuming algebraical summation of the afterhyperpolarization (AHP) curve and noisy synaptic inflow. An influence of various model parameters on the relationship between standard deviation (SD), sigma, of interspike intervals (ISIs) and their mean value, Tm, was studied. A typical sigma(Tm) relationship resembled those obtained experimentally and consisted of two parts: a short-interval part with constant sigma and a long-interval part where sigma increased linearly with increasing ISI. It is concluded that the placement of the range of transition between short- and long-interval parts of the plot depends on the properties of the motoneuron and not on those of the synaptic inflow. The break-point interval of the plot is correlated with the AHP duration but is shorter than it. Further, not only are the curves for shorter AHP durations shifted towards shorter ISIs, but they also have lower SDs at their short-interval parts.

Age-related change in duration of afterhyperpolarization of human motoneurones

Motor unit (MU) potentials were recorded from brachial biceps of healthy subjects aged 5.5–79 years. The subjects were subdivided into young (5.5–19 year) and adult (37.5–79 year) groups, between which single MU discharge characteristics were compared. Firing rates were in the ranges of 8.3–21.7 s−1 (mean 12.87 s−1) and 5.9–18.7 s−1 (mean 11.08 s−1) for young and adult groups, respectively. Standard deviations (s.d.) of interspike intervals (ISIs) were in the range 4.84–11.57 ms (mean 8.39 ms) for the young group and 4.26–12.23 ms (mean 7.76 ms) for the adult group. Both differences were statistically significant (P < 0.001). Special attention was paid to the previously developed method of ISI variability analysis, which enabled the comparison of MUs with respect to afterhyperpolarization (AHP) duration of their motoneurones (MNs). The results show that AHP duration increases gradually with increasing age, which is in line with the transformation of muscle properties towards a slower phenotype. This transformation seems to be a continuous process, covering the entire lifespan of a human being, from childhood to senescence. The results presented here are significant for their insight into the ageing process of the neuromuscular system. The age‐related change in AHP duration has not been investigated previously in human studies and has been met with ambiguous results in animal studies.

Time Course Analysis of the Effects of Botulinum Toxin Type A on Elbow Spasticity Based on Biomechanic and Electromyographic Parameters

OBJECTIVE To quantify changes of elbow spasticity over time after botulinum toxin type A (BTX-A) injection in the upper extremity of stroke patients. DESIGN Before-after trial in which the therapeutic effects were followed up at 2, 6, and 9 weeks after the BTX-A injection (Botox). SETTING Hospital. PARTICIPANTS Chronic stroke patients (N=8) with upper-limb spasticity. INTERVENTION BTX-A was injected in upper-limb muscles, including the biceps brachii. MAIN OUTCOME MEASURES Treatment effects were quantified as the changes in the velocity and the length dependence of hyperexcitable stretch reflexes. Manual sinusoid stretches of the elbow joint at 4 frequencies (1/3, 1/2, 1, 3/2Hz) over a movement range of 60 degrees were performed on patients by using a portable device. The Modified Ashworth Scale (MAS), biomechanic viscosity, and the reflexive electromyography threshold (RET) of the biceps brachii were used to evaluate the degree of hypertonia. RESULTS The statistical analyses of the MAS score, biomechanic viscosity, and RET revealed a significant decrease in spasticity after the injection (all P<.05). Moreover, our quantitative parameters (biomechanic viscosity, RET) revealed small changes in spasticity after the BTX-A injection that could not be observed from clinical MAS evaluations. Five of 8 subjects showed a maximal reduction in spasticity (in terms of biomechanic viscosity value) within 6 weeks after the injection, whereas it was notable that all subjects exhibited peak RET values at either 2 or 6 weeks after the injection with variable degrees of relapse of spasticity. CONCLUSIONS Early relapse of spasticity (within 9 weeks of the injection) can be detected from biomechanic and neurophysiologic assessments in a clinical setup. These quantitative indices provide valuable information for clinicians when making decisions to perform additional rehabilitation interventions or another BTX-A injection in the early stages of treatment.

Motoneuron afterhyperpolarisation duration in amyotrophic lateral sclerosis

Non‐technical summary  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of still unknown aetiology, although over 130 years have passed since its first description. Since it is not possible to directly record from motoneurons (MNs) in ALS patients, a significant proportion of the research on ALS takes place in animal models of the disease with specific genetic mutations. However, these results are received with scepticism by many of the clinical researchers, since these mutations are responsible for only about 2% of all human ALS cases. We developed a method to characterise indirectly the human MN afterhyperpolarisation (AHP) duration by analysis of muscular electrical activity. In early stages of ALS muscle impairment we observed substantial shortening of the AHP, which was consistent with the results from acute experiments in ALS animal models. Thus, our study lays a bridge between animal and clinical research that may be relevant for identification of mechanism(s) underlying neurodegeneration in ALS.

Analysis of double discharges in amyotrophic lateral sclerosis

Double discharges of motor units (MUs) occurring during sustained voluntary muscle contractions are observed occasionally in healthy muscles and more frequently in disorders of the neuromuscular system. In healthy subjects, double discharges are generated in motoneurons (MNs) and are considered to be a sign of their increased excitability. Therefore, an analysis of their firing pattern may provide information on the state of MNs in neuromuscular diseases, particularly in amyotrophic lateral sclerosis (ALS), whose etiology remains to be disclosed. Firing patterns of MUs capable of firing double discharges were analyzed in brachial biceps of 14 patients with ALS (184 MUs) and 8 healthy control subjects (102 MUs). The incidence of MUs capable of firing double discharges was significantly higher in ALS patients (28.8%) than in controls (3.9%). The majority of doublet interval durations (range 4–8 ms) as well as firing patterns of doubling MUs did not differ between subject groups. Although our data confirm the hyperexcitability of the MN pool in ALS, analysis of firing characteristics of doubling MUs indicates that doublet generation is governed by the same mechanism as in controls, that is, by delayed depolarization. Our findings may provide insight into MN function in ALS. Muscle Nerve, 2008

Are motoneurons involved in muscular dystrophy

In the early seventies, a suggestion that even in muscular dystrophy a neurogenic factor may be involved, was formulated. The argument which followed this suggestion, resulted in eventual abandoning of this concept even by its author. This discussion however has never been supported by any systematic study of motoneuron activity in muscular dystrophy. We examined an activity of motoneurons supplying brachial biceps in eight controls and 26 patients affected by Duchenne muscular dystrophy by studying single motor unit (MU) potentials picked up by fine wire bipolar electrodes. In the majority of patients, MU firing rates were higher as compared to controls and increased more rapidly with increasing force level. The relationship between standard deviation of interspike intervals and their mean value, SD(x), was shifted towards the shorter intervals and lower SDs. The numerical values describing these changes were correlated with severity of the disease. There is evidence that the break-point of the function SD(x) is correlated with motoneuron properties, in particular with after-hyperpolarization duration. In muscular dystrophy, this break-point corresponds to the shorter interspike intervals. We suggest that the motoneurons in muscular dystrophy are altered either in response to the muscle degeneration, or as a result of the disease itself.

Excitability of single firing human motoneurones to single and repetitive stimulation (experiment and model)

The activity of single motoneurones of m. flexor carpi ulnaris (FCU) was investigated by recording their motor unit (MU) action potentials during weak and moderate voluntary muscle contractions. The MU firing rate range was 4.5–15 imp/s. The excitability of motoneurones was tested with a number of single stimuli eliciting a monosynaptic H-reflex of low amplitude. Two different indices were defined which relate to motoneuronal excitability: the response index — the ratio of the number of responses of a motoneurone to the total number of stimuli, and the response time — the time after the last background MU discharge at which motoneurone is ready to respond to the excitatory volley. Both the response index and the response time were determined for single motoneurones at different levels of background activity. In the lower range of firing rates, the response index for all motoneurones decreased when increasing the firing rate, but it remained constant in the higher rate range. This kind of response seems to be a typical motoneuronal response to the stimulation with single stimuli. The data on the response time were used to study the excitability of the same single motoneurones to computer simulated repetitive stimulation (stimulation rate 40–100 imp/s). In this case, the excitability of each motoneurone was determined as an increment of its firing rate in response to the stimulation. For the lower firing rate range, the excitability for all motoneurones also decreased when the firing rates increased whereas a variety of slopes was obtained in the higher rate range. The results of our experiments and their computer simulation allow us to suggest a possible interrelation between the excitability of firing motoneurones and their interspike membrane potential trajectories.

Double discharges in human soleus muscle

Double discharges (doublets) were recorded from human soleus (SOL), where they have never been reported before. The data analyzed in this study were collected from 12 healthy volunteers. The subjects were recruited for other studies, concerning: (1) estimation of motoneurons’ (MNs) afterhyperpolarization (AHP) duration and (2) analysis of motor unit responses to nerve stimulation, and were not trained to voluntarily evoke doublets. The majority of intradoublet intervals fell into the commonly accepted range 2–20 ms. However, two SOL MNs from one presented exceptional doublets of intradoublet interval about 37 ms. This interval was virtually identical with the interval between second and third discharge in the few triplets recorded from another subject. It is hypothesized that triplets are generated by the delayed depolarization with the second narrow hump, which is the same as the hump responsible for exceptional doublets.

Assessment of Human Motoneuron Afterhyperpolarization Duration in Health and Disease

The results of the investigation of afterhyperpolarization (AHP) duration in normal aging and selected neuromuscular disorders are presented. This investigation yielded unexpected results: the AHP shortening in myogenic disease (DMD) and no significant difference from control values in neurogenic disease (ALS). However, introduction of age factor revealed novel aspects of the human ALS, which can be interpreted on the basis of the results obta-ined in a SOD1 mice, thus confirming usefulness of this animal model of ALS. In spastic patients the AHP was prolonged and the difference from the control AHP duration decre-ased with age and disease duration. Our results suggest that the match between temporal characteristics of the AHP of MN and of the twitch of its muscle unit is preserved during normal aging and in spasticity, but not in the DMD.

Computer simulation study of the relationship between the profile of excitatory postsynaptic potential and stimulus-correlated motoneuron firing

This paper shows the results of computer simulation of changes in motoneuron (MN) firing evoked by a repetitively applied synaptic volley that consists of a single excitatory postsynaptic potential (EPSP). Spike trains produced by the threshold-crossing MN model were analyzed as experimental results. Various output functions were applied for analysis; the most useful was a peristimulus time histogram, a special modification of a raster plot and a peristimulus time frequencygram (PSTF). It has been shown that all functions complement each other in distinguishing between the genuine results evoked by the excitatory volley and the secondary results of the EPSP-evoked synchronization. The EPSP rising edge was best reproduced by the PSTF. However, whereas the EPSP rise time could be estimated quite accurately, especially for high EPSP amplitudes at high MN firing rates, the EPSP amplitude estimate was also influenced by factors unrelated to the synaptic volley, such as the afterhyperpolarization duration of the MN or the amplitude of synaptic noise, which cannot be directly assessed in human experiments. Thus, the attempts to scale any estimate of the EPSP amplitude in millivolts appear to be useless. The decaying phase of the EPSP cannot be reproduced accurately by any of the functions. For the short EPSPs, it is extinguished by the generation of an action potential and a subsequent decrease in the MN excitability. For longer EPSPs, it is inseparable from the secondary effects of synchronization. Thus, the methods aimed at extracting information about long-lasting and complex postsynaptic potentials from stimulus-correlated MN firing, should be refined, and the theoretical considerations checked in computer simulations.