Ectopic Motor Unit Activity in Motor Neuron Disease

__Abstract__ Motor neuron disease (MND) is characterized by the progressive loss of motor neurons that control voluntary muscles. Due to its progressive nature, the muscles gradually lose their function leading to paralysis and, ultimately, death. The most common variant of MND is amyotrophic lateral sclerosis (ALS). Of all the people diagnosed with ALS, 50% die within approximately two to three years after their first symptoms arise and only about 20% live longer than 5 years [1]. Onset is typically around 50 - 70 years of age, but in some patients the onset may be much earlier, around the age of 20 - 30 years. Incidence is higher among men than women, estimated at 2:1 [2-4]. The first symptoms usually occur in the limbs, but muscle weakness may also begin in the bulbar region. Progressive weakness of the respiratory muscles leading to respiratory failure is the most common cause of death. Before the first clinical signs of muscle weakness become apparent, more than 50% of the motor neurons innervating a muscle may already be lost [5]. In the Netherlands, approximately 1,700 people (prevalence 10.3 per 100,000) suffer from ALS [2]. Every year, approximately 500 people (incidence 2.8 per 100,000) in the Netherlands are diagnosed with ALS [2], and about the same number of persons dies every year. In comparison, approximately 570 people in the Netherlands died in traffic accidents in 2013 [6]. The term ALS was first described in 1874 by Jean-Martin Charcot [7]. Despite the tremendous technological progress that has been made in the last 140 years and despite numerous studies that have been conducted to unravel the mechanisms that may cause this deadly disease, relatively little is known about the mechanisms that cause ALS and the progressive degeneration of motor neurons is often unpredictable. The great majority of patients is classified as having sporadic ALS, and only 5 - 10% of the patients have a familial history of this disease. A complex interaction between genetic and environmental factors is believed to contribute to the development of the disease. Several genes have been identified and their discovery gave new insights into the underlying pathophysiological mechanisms. At present, no cure is available, and the only approved and widely used medication (Riluzole) can only marginally slow down the progression of the disease by approximately 3 months [8]. In this section, first the concept of a motor unit as a crucial component being affected by MND will be introduced, together with some basics on how motor units are affected in this condition. Next, one of the most obvious clinical signs, fasciculations, will be discussed, followed by the varying clinical phenotypes. Subsequently, the difficulties in the diagnostic process and the prognosis will be described. Currently, both can be very difficult, especially in the early stages of the disease, even with a thorough clinical and electrodiagnostic examination

EEG-based investigation of cortical activity during Postural Control

The postural control system regulates the ability to maintain a stable upright stance and to react to changes in the external environment. Although once believed to be dominated by low-level reflexive mechanisms, mounting evidence has highlighted a prominent role of the cortex in this process. Nevertheless, the high-level cortical mechanisms involved in postural control are still largely unexplored. The aim of this thesis is to use electroencephalography, a widely used and non-invasive neuroimaging tool, to shed light on the cortical mechanisms which regulate postural control and allow balance to be preserved in the wake of external disruptions to one’s quiet stance. EEG activity has been initially analysed during a well-established postural task - a sequence of proprioceptive stimulations applied to the calf muscles to induce postural instability – traditionally used to examine the posturographic response. Preliminary results, obtained through a spectral power analysis of the data, highlighted an increased activation in several cortical areas, as well as different activation patterns in the two tested experimental conditions: open and closed eyes. An improved experimental protocol has then been developed, allowing a more advanced data analysis based on source reconstruction and brain network analysis techniques. Using this new approach, it was possible to characterise with greater detail the topological structure of cortical functional connections during the postural task, as well as to draw a connection between quantitative network metrics and measures of postural performance. Finally, with the integration of electromyography in the experimental protocol, we were able to gain new insights into the cortico-muscular interactions which direct the muscular response to a postural challenge. Overall, the findings presented in this thesis provide further evidence of the prominent role played by the cortex in postural control. They also prove how novel EEG-based brain network analysis techniques can be a valid tool in postural research and offer promising perspectives for the integration of quantitative cortical network metrics into clinical evaluation of postural impairment.Kerfi stöðustjórnunar er afturvirkt stýrikerfi sem vinnur stöðugt að því að viðhalda uppréttri stöðu líkamans og bregðast við ójafnvægi. Vaxandi þekking á undanförnum árum hefur lýst því að úrvinnsla þessara upplýsinga á sér stað á öllum stigum miðtaugakerfisins, þá sérstaklega barkarsvæði heilahvela. Engu að síður, er nákvæmu hlutverk heilabarkar við stöðustjórnun enn óljóst að mörgu leyti. Tilgangur þessa verkefnis var að rannsaka nánar hlutverk heilabarkar við truflun og áreiti á kerfi stöðustjórnarinnar, með notkun hágæða heilarafrits (EEG). Við byrjuðum á því að mæla heilarit einstaklinga meðan á þekktri líkamsstöðu-æfingu stóð, til þess að skoða svörun líkamans við röð titringsáreita sem beitt var á kálfavöðvana til að framkalla óstöðugleika. Bráðabirgðaniðurstöður fengnar með PSD-aðferð (power spectral analysis) leiddu í ljós aukna virkni á ákveðnum svæðum í heilaberki og sérstakt viðbragðsmynstur við að framkvæma æfinguna, annars vegar með lokuð augu og hins vegar opin augu. Rannsókn okkar hélt áfram með nýrri og þróaðari tækni sem gerði okkur kleift að framkvæma fullkomnari greiningaraðferðir til að túlka, greina og skilja merki frá heilaritnu. Með fullkomnari greiningaraðferðum var hægt að lýsa með nákvæmari hætti staðfræðilega uppbyggingu starfrænna tenginga í heilaberki meðan á líkamsstöðu æfingunni stóð, sem og að draga tengsl á milli megindlegra netmælinga og mælinga á líkamsstöðu. Að lokum bætist við vöðvarafritsmæling við aðferðafræðina, sem gaf okkur innsýn inn í samskipti heilabarka og vöðvana sem stýra vöðvaviðbrögðum og viðhalda líkamsstöðu við utanaðkomandi áreiti. Á heildina litið gefa niðurstöðurnar sem settar eru fram í þessari ritgerð enn sterkari vísbendingar um það áberandi hlutverk sem heilabörkurinn gegnir við stjórnun líkamsstöðu. Niðurstöðurnar sanna einnig hvernig ný aðferð á greiningu á tengslaneti heilans sem byggir á heilariti getur verið gilt tæki í líkamsstöðu rannsóknum og er nytsamlegt tól fyrir mælingar á heilakerfisneti í klínískt mat á skerðingu líkamsstöðu

EEG-based investigation of cortical activity during Postural Control

The postural control system regulates the ability to maintain a stable upright stance and to react to changes in the external environment. Although once believed to be dominated by low-level reflexive mechanisms, mounting evidence has highlighted a prominent role of the cortex in this process. Nevertheless, the high-level cortical mechanisms involved in postural control are still largely unexplored. The aim of this thesis is to use electroencephalography, a widely used and non-invasive neuroimaging tool, to shed light on the cortical mechanisms which regulate postural control and allow balance to be preserved in the wake of external disruptions to one’s quiet stance. EEG activity has been initially analysed during a well-established postural task - a sequence of proprioceptive stimulations applied to the calf muscles to induce postural instability – traditionally used to examine the posturographic response. Preliminary results, obtained through a spectral power analysis of the data, highlighted an increased activation in several cortical areas, as well as different activation patterns in the two tested experimental conditions: open and closed eyes. An improved experimental protocol has then been developed, allowing a more advanced data analysis based on source reconstruction and brain network analysis techniques. Using this new approach, it was possible to characterise with greater detail the topological structure of cortical functional connections during the postural task, as well as to draw a connection between quantitative network metrics and measures of postural performance. Finally, with the integration of electromyography in the experimental protocol, we were able to gain new insights into the cortico-muscular interactions which direct the muscular response to a postural challenge. Overall, the findings presented in this thesis provide further evidence of the prominent role played by the cortex in postural control. They also prove how novel EEG-based brain network analysis techniques can be a valid tool in postural research and offer promising perspectives for the integration of quantitative cortical network metrics into clinical evaluation of postural impairment

Muscle activation patterns in shoulder impingement patients

Introduction: Shoulder impingement is one of the most common presentations of shoulder joint problems 1. It appears to be caused by a reduction in the sub-acromial space as the humerus abducts between 60o -120o – the 'painful arc'. Structures between the humeral head and the acromion are thus pinched causing pain and further pathology 2. Shoulder muscle activity can influence this joint space but it is unclear whether this is a cause or effect in impingement patients. This study aimed to observe muscle activation patterns in normal and impingement shoulder patients and determine if there were any significant differences. Method: 19 adult subjects were asked to perform shoulder abduction in their symptomatic arm and non-symptomatic. 10 of these subjects (age 47.9 ± 11.2) were screened for shoulder impingement, and 9 subjects (age 38.9 ± 14.3) had no history of shoulder pathology. Surface EMG was used to collect data for 6 shoulder muscles (Upper, middle and lower trapezius, serratus anterior, infraspinatus, middle deltoids) which was then filtered and fully rectified. Subjects performed 3 smooth unilateral abduction movements at a cadence of 16 beats of a metronome set at 60bpm, and the mean of their results was recorded. T-tests were used to indicate any statistical significance in the data sets. Significance was set at P<0.05. Results: There was a significant difference in muscle activation with serratus anterior in particular showing a very low level of activation throughout the range when compared to normal shoulder activation patterns (<30%). Middle deltoid recruitment was significantly reduced between 60-90o in the impingement group (30:58%).Trends were noted in other muscles with upper trapezius and infraspinatus activating more rapidly and erratically (63:25%; 60:27% respectively), and lower trapezius with less recruitment (13:30%) in the patient group, although these did not quite reach significance. Conclusion: There appears to be some interesting alterations in muscle recruitment patterns in impingement shoulder patients when compared against their own unaffected shoulders and the control group. In particular changes in scapula control (serratus anterior and trapezius) and lateral rotation (infraspinatus), which have direct influence on the sub-acromial space, should be noted. It is still not clear whether these alterations are causative or reactionary, but this finding gives a clear indication to the importance of addressing muscle reeducation as part of a rehabilitation programme in shoulder impingement patients

Epidemiology of Injury in English Women's Super league Football: A Cohort Study

INTRODUCTION: The epidemiology of injury in male professional football has been well documented (Ekstrand, Hägglund, & Waldén, 2011) and used as a basis to understand injury trends for a number of years. The prevalence and incidence of injuries occurring in womens super league football is unknown. The aim of this study is to estimate the prevalence and incidence of injury in an English Super League Women’s Football squad. METHODS: Following ethical approval from Leeds Beckett University, players (n = 25) signed to a Women’s Super League Football club provided written informed consent to complete a self-administered injury survey. Measures of exposure, injury and performance over a 12-month period was gathered. Participants were classified as injured if they reported a football injury that required medical attention or withdrawal from participation for one day or more. Injuries were categorised as either traumatic or overuse and whether the injury was a new injury and/or re-injury of the same anatomical site RESULTS: 43 injuries, including re-injury were reported by the 25 participants providing a clinical incidence of 1.72 injuries per player. Total incidence of injury was 10.8/1000 h (95% CI: 7.5 to 14.03). Participants were at higher risk of injury during a match compared with training (32.4 (95% CI: 15.6 to 48.4) vs 8.0 (95% CI: 5.0 to 10.85)/1000 hours, p 28 days) of which there were three non-contact anterior cruciate ligament (ACL) injuries. The epidemiological incidence proportion was 0.80 (95% CI: 0.64 to 0.95) and the average probability that any player on this team will sustain at least one injury was 80.0% (95% CI: 64.3% to 95.6%) CONCLUSION: This is the first report capturing exposure and injury incidence by anatomical site from a cohort of English players and is comparable to that found in Europe (6.3/1000 h (95% CI 5.4 to 7.36) Larruskain et al 2017). The number of ACL injuries highlights a potential injury burden for a squad of this size. Multi-site prospective investigations into the incidence and prevalence of injury in women’s football are require

The new technique for accurate estimation of the spinal cord circuitry:recording reflex responses of large motor unit populations

We propose and validate a non-invasive method that enables accurate detection of the discharge times of a relatively large number of motor units during excitatory and inhibitory reflex stimulations. HDsEMG and intramuscular EMG (iEMG) were recorded from the tibialis anterior muscle during ankle dorsiflexions performed at 5%, 10%, and 20% of the maximum voluntary contraction (MVC) force, in 9 healthy subjects. The tibial nerve (inhibitory reflex) and the peroneal nerve (excitatory reflex) were stimulated with constant current stimuli. In total, 416 motor units were identified from the automatic decomposition of the HDsEMG. The iEMG was decomposed using a state-of-the-art decomposition tool and provided 84 motor units (average of two recording sites). The reflex responses of the detected motor units were analyzed using the peri-stimulus time histogram (PSTH) and the peri-stimulus frequencygram (PSF). The reflex responses of the common motor units identified concurrently from the HDsEMG and the iEMG signals showed an average disagreement (the difference between number of observed spikes in each bin relative to the mean) of 8.2±2.2% (5% MVC), 6.8±1.0% (10% MVC), and 7.5±2.2% (20% MVC), for reflex inhibition, and 6.5±4.1%, 12.0±1.8%, 13.9±2.4%, for reflex excitation. There was no significant difference between the characteristics of the reflex responses, such as latency, amplitude and duration, for the motor units identified by both techniques. Finally, reflex responses could be identified at higher force (four of the nine subjects performed contraction up to 50% MVC) using HDsEMG but not iEMG, because of the difficulty in decomposing the iEMG at high forces. In conclusion, single motor unit reflex responses can be estimated accurately and non-invasively in relatively large populations of motor units using HDsEMG. This non-invasive approach may enable a more thorough investigation of the synaptic input distribution on active motor units at various force levels

A Systematic Review and Meta-Analysis of the Incidence of Injury in Professional Female Soccer

The epidemiology of injury in male professional football is well documented and has been used as a basis to monitor injury trends and implement injury prevention strategies. There are no systematic reviews that have investigated injury incidence in women’s professional football. Therefore, the extent of injury burden in women’s professional football remains unknown. PURPOSE: The primary aim of this study was to calculate an overall incidence rate of injury in senior female professional soccer. The secondary aims were to provide an incidence rate for training and match play. METHODS: PubMed, Discover, EBSCO, Embase and ScienceDirect electronic databases were searched from inception to September 2018. Two reviewers independently assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement using a 22-item STROBE checklist. Seven prospective studies (n=1137 professional players) were combined in a pooled analysis of injury incidence using a mixed effects model. Heterogeneity was evaluated using the Cochrane Q statistic and I2. RESULTS: The epidemiological incidence proportion over one season was 0.62 (95% CI 0.59 - 0.64). Mean total incidence of injury was 3.15 (95% CI 1.54 - 4.75) injuries per 1000 hours. The mean incidence of injury during match play was 10.72 (95% CI 9.11 - 12.33) and during training was 2.21 (95% CI 0.96 - 3.45). Data analysis found a significant level of heterogeneity (total Incidence, X2 = 16.57 P < 0.05; I2 = 63.8%) and during subsequent sub group analyses in those studies reviewed (match incidence, X2 = 76.4 (d.f. = 7), P <0.05; I2 = 90.8%, training incidence, X2 = 16.97 (d.f. = 7), P < 0.05; I2 = 58.8%). Appraisal of the study methodologies revealed inconsistency in the use of injury terminology, data collection procedures and calculation of exposure by researchers. Such inconsistencies likely contribute to the large variance in the incidence and prevalence of injury reported. CONCLUSIONS: The estimated risk of sustaining at least one injury over one football season is 62%. Continued reporting of heterogeneous results in population samples limits meaningful comparison of studies. Standardising the criteria used to attribute injury and activity coupled with more accurate methods of calculating exposure will overcome such limitations