Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression

Objectives: Amyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients. / Methods: In two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects. / Results: Compared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 ± 2.6 ms) but not in nonlumbar-affected patients (29.7 ± 12.4 ms, P<0.0001) compared to controls (30.8 ± 7.2 ms, P<0.0001). / Conclusion: The current study revealed that spinal inhibitory circuits are impaired in ALS. / Significance: These findings may provide insight for proposing new therapeutic approaches and following disease progression in humans

Periodontal mechanoreceptors and bruxism at low bite forces

Objective: In this study, we examined if 6–9 Hz jaw tremor, an indirect indicator of Periodontal Mechanoreceptor (PMR) activity, is different in bruxists compared to healthy participants during production of a low-level constant bite force. / Methods: Bite force and surface EMG from the masseter muscle were recorded simultaneously as participants (13 patients, 15 controls) held a force transducer between the upper and lower incisors very gently. / Results: Tremor in 6–9 Hz band for bruxists was greater on average compared to controls, but the difference was not significant, both for force recordings and EMG activity. / Conclusions: The low effect sizes measured with the current protocol contrast highly with those of our previous study, where larger, dynamic bite forces were used, and where jaw tremor was markedly different in bruxists compared with controls. / Significance: We have now gained important insight into the conditions under which abnormal jaw tremor can be elicited in bruxism. From a scientific standpoint, this is critical for understanding the ‘abnormality’ of PMR feedback in bruxism. From a clinical perspective, our results represent progress towards the development of an optimal protocol in which jaw tremor can serve as a biological marker of bruxism

Analysis of motoneuron responses to composite synaptic volleys (computer simulation study)

This paper deals with the analysis of changes in motoneuron (MN) firing evoked by repetitively applied stimuli aimed toward extracting information about the underlying synaptic volleys. Spike trains were obtained from computer simulations based on a threshold-crossing model of tonically firing MN, subjected to stimulation producing postsynaptic potentials (PSPs) of various parameters. These trains were analyzed as experimental results, using the output measures that were previously shown to be most effective for this purpose: peristimulus time histogram, raster plot and peristimulus time intervalgram. The analysis started from the effects of single excitatory and inhibitory PSPs (EPSPs and IPSPs). The conclusions drawn from this analysis allowed the explanation of the results of more complex synaptic volleys, i.e., combinations of EPSPs and IPSPs, and the formulation of directions for decoding the results of human neurophysiological experiments in which the responses of tonically firing MNs to nerve stimulation are analyzed

Post-activation depression of primary afferents reevaluated in humans

Amplitude variation of Hoffmann Reflex (H-reflex) was used as a tool to investigate many neuronal networks. However, H-reflex itself is a subject to intrinsic changes including post-activation depression (P-AD). We aimed to investigate P-AD and its implication on motor control in humans. Upon tibial nerve stimulation in 23 healthy participants, peak-to-peak amplitude change of H-reflex was investigated using surface electromyography (SEMG) of soleus muscle. Variety of stimulus intensities, interstimulus intervals (ISIs), voluntary contraction levels/types and force recording were used to investigate the nature of P-AD. We have shown that P-AD was significantly stronger in the shorter ISIs. The only exception was the ISI of 200 msecs which had a weaker P-AD than some of the longer ISIs. Sudden muscle relaxation, on the other hand, further increased the effectiveness of the ongoing P-AD. Moreover, P-AD displayed its full effect with the first stimulus when there was no muscle contraction and was efficient to reduce the muscle force output by about 30%. These findings provide insight about the variations and mechanism of P-AD and could lead to improvements in diagnostic tools in neurological diseases

Effect of aging on H-reflex response to fatigue

Injury as a result of tripping is relatively common among older people. The risk of falling increases with fatigue and of importance is the ability to dorsiflex the foot through timely activation of the tibialis anterior (TA) muscle to ensure the foot clears the ground, or an obstacle, during the swing phase of walking. We, therefore, questioned whether the muscle spindle input to the motoneurons alters with ongoing fatigue in older people. We electrically stimulated the common peroneal nerve to assess the TA primary afferent efficacy using H-reflex before, immediately following and after a fatiguing maximal isometric contraction. M-response was kept unchanged throughout the experiment to ensure a similar stimulus intensity was delivered across time points. H-reflex increased significantly while the TA muscle was in a state of fatigue for the younger participants but tended to decrease with increasing age. The main contributor to the tonicity of TA muscle, i.e., excitatory synapses of spindle primary endings of motoneurons that innervate TA muscle, tend to lose their efficacy during fatigue in the older individuals but increased efficiency in the majority of the younger people. Since TA muscle is the main dorsiflexor of the foot and it needs to be active during the swing phase of stepping to prevent tripping, older individuals become more susceptible to falling when their muscles are fatigued. This finding may help improve devices/treatments to overcome the problem of tripping among older individuals

Mimicking human neuronal pathways in silico: an emergent model on the effective connectivity

International audienceWe present a novel computational model that detects temporal configurations of a given human neuronal pathway and constructs its artificial replication. This poses a great challenge since direct recordings from individual neurons are impossible in the human central nervous system and therefore the underlying neuronal pathway has to be considered as a black box. For tackling this challenge, we used a branch of complex systems modeling called artificial self-organization in which large sets of software entities interacting locally give rise to bottom-up collective behaviors. The result is an emergent model where each software entity represents an integrate-and-fire neuron. We then applied the model to the reflex responses of single motor units obtained from conscious human subjects. Experimental results show that the model recovers functionality of real human neuronal pathways by comparing it to appropriate surrogate data. What makes the model promising is the fact that, to the best of our knowledge, it is the first realistic model to self-wire an artificial neuronal network by efficiently combining neuroscience with artificial self-organization. Although there is no evidence yet of the model's connectivity mapping onto the human connectivity, we anticipate this model will help neuroscientists to learn much more about human neuronal networks, and could also be used for predicting hypotheses to lead future experiments

Exploring the receptor origin of vibration-induced reflexes

STUDY DESIGN: An experimental design. OBJECTIVES: The aim of this study was to determine the latencies of vibration-induced reflexes in individuals with and without spinal cord injury (SCI), and to compare these latencies to identify differences in reflex circuitries. SETTING: A tertiary rehabilitation center in Istanbul. METHODS: Seventeen individuals with chronic SCI (SCI group) and 23 participants without SCI (Control group) were included in this study. Latency of tonic vibration reflex (TVR) and whole-body vibration-induced muscular reflex (WBV-IMR) of the left soleus muscle was tested for estimating the reflex origins. The local tendon vibration was applied at six different vibration frequencies (50, 85, 140, 185, 235, and 265 Hz), each lasting for 15 s with 3-s rest intervals. The WBV was applied at six different vibration frequencies (35, 37, 39, 41, 43, and 45 Hz), each lasting for 15 s with 3-s rest intervals. RESULTS: Mean (SD) TVR latency was 39.7 (5.3) ms in the SCI group and 35.9 (2.7) ms in the Control group with a mean (95% CI) difference of -3.8 (-6.7 to -0.9) ms. Mean (SD) WBV-IMR latency was 45.8 (7.4) ms in the SCI group and 43.3 (3.0) ms in the Control group with a mean (95% CI) difference of -2.5 (-6.5 to 1.4) ms. There were significant differences between TVR latency and WBV-IMR latency in both the groups (mean (95% CI) difference; -6.2 (-9.3 to -3.0) ms, p = 0.0001 for the SCI group and -7.4 (-9.3 to -5.6) ms, p = 0.011 for Control group). CONCLUSIONS: The results suggest that the receptor of origin of TVR and WBV-IMR may be different