237 research outputs found

    Exploration of peripheral electrical stimulation adapted as a modulation tool for reciprocal inhibition through the activation of afferent fibers during gait

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    The most accessible manner to perform physical activity and allow locomotion in human beings is walking. This activity is allowed thanks to reciprocal Ia inhibition mechanism, controlled by the spinal and supraspinal inhibitory circuits. The idea of this mechanism is to deactivate the antagonist muscle while the agonist is being contracted, allowing the proper muscle coordination necessary to walk. The interruption of spinal fibers produced after Spinal Cord Injury, disrupt this control on reciprocal Ia inhibition. The result of this lack of control is a co-activation of antagonist muscles generating spasticity of lower limbs which induce walking impairments. The importance of walking recovery for the independence and society re-integration of patient, raise the quantity of emerging walking rehabilitation therapies. One of these therapies, the application of peripheral nerve stimulation, has demonstrated promising results although more studies are necessary. This theory is the base of this Master Thesis which aim is to develop and validate a gait neuromodu- lation platform that induce neuroplasticity of spinal circuits, improving reciprocal Ia inhibition. The idea of the platform is to deliver afferent stimulation into the Common Peroneal Nerve innervating Tibialis Anterior muscle, to induce reciprocal Ia inhibition onto the antagonist Soleus muscle. This platform has been validated in 20 healthy volunteers in order to assess its effectiveness. The first part of the experimental protocol is an off-line analysis of Gait Cycle to evaluate the activation of mus- cles during the different phases of this cycle. Then, there is an assessment of the activity of antagonist muscle previous to the stimulation intervention by using the analysis of soleus H-reflex. Posteri- orly, the afferent stimulation is applied during a 10 minutes treadmill training using three different strategies depending on patient: In-phase stimulation during swing phase, Out-of-phase stimulation during stance phase, and Control strategy to check if stimulation has a real effect. The final processes of experimental protocol are two different assessments of the soleus activity, one immediately after the intervention and other 30 minutes after to evaluate the duration of effects. The results obtained demonstrate that afferent electrical stimulation has a real effect on modulation of reciprocal Ia inhibition. On the one hand, when electrical stimulation is applied during the swing phase, there is an improvement of reciprocal Ia inhibition. On the other hand, when stimulation is delivered during the stance phase, there is a worsening of reciprocal Ia inhibition. These results conclude that afferent electrical stimulation, applied at the swing phase of gait cycle, is a promising strategy to induce reciprocal Ia inhibition in Spinal Cord Injury patients. The induc- tion of this inhibitory circuit will lead to the proper activation of muscles during walking, recovering impaired walkingLa forma más accesible de locomoción y actividad física en los seres humanos es caminar. Esta activi- dad se realiza gracias al mecanismo de inhibición recíproca, controlado por los circuitos inhibitorios espinales y supraespinales. La idea de este mecanismo es desactivar el músculo antagonista mientras se contrae el agonista, permitiendo la adecuada coordinación muscular durante la marcha. La interrupción de las fibras espinales tras una Lesión de la Médula Espinal desajusta el control de la inhibition reciprocal. El resultado de esta falta de control es una co-activación de los músculos antago- nistas generando espasticidad en las extremidades inferiores, lo que genera alteraciones en la marcha. La importancia de la recuperación de la marcha para lograr la independencia y la reintegración del paciente en la sociedad, ha incrementado el número de terapias emergentes en rehabilitación de la marcha. Una de estas terapias, la estimulación del nervio periférico, ha demostrado resultados prom- etedores. Esta teoría es la base de esta Tesis de Máster cuyo objetivo es desarrollar y validar una plataforma de neuromodulación de la marcha que induzca la neuroplasticidad de los circuitos espinales, mejorando los valores de inhibición recíproca. La idea es aplicar estimulación aferente en el Nervio Peroneo Común que inerva el músculo Tibial Anterior para inducir la inhibición recíproca en su músculo antagonista Soleo. Esta plataforma ha sido validada en 20 voluntarios sanos con el fin de evaluar su eficacia. La primera parte del protocolo experimental es un análisis del ciclo de la marcha para evaluar la activación de cada músculo durante las diferentes fases de este ciclo. Luego, previo a la intervención de estimu- lación, hay una evaluación de la actividad del músculo antagonista analizando el reflejo H del soleo. La intervención de estimulación aferente se aplica durante un entrenamiento de marcha con una du- ración de 10 minutos, utilizando tres estrategias diferentes dependiendo del paciente: estimulación ’In-phase’ durante la fase de oscilación, estimulación ’Out-of-phase’ durante la fase de postura, y ’Control’ para comprobar si la estimulación tiene un efecto real. Los procesos finales del protocolo son dos evaluaciones de la actividad del soleo, una inmediatamente después de la intervención y otra 30 minutos después para evaluar la duración de los efectos. Los resultados obtenidos demuestran que la estimulación eléctrica aferente tiene un efecto real en la modulación de la inhibición recíproca. Por un lado, cuando la estimulación eléctrica se aplica durante la fase de oscilación, hay una mejora de la inhibición recíproca. Por otro lado, cuando la estimulación se administra durante la fase de postura, hay un empeoramiento de la inhibición recíproca. Estos resultados concluyen que la estimulación eléctrica aferente, administrada en la fase de oscilación del ciclo de la marcha, es una estrategia prometedora para inducir la inhibición recíproca en pacientes con Lesión de la Médula Espinal. La inducción de este circuito inhibidor generará la adecuada acti- vación de los músculos durante la marcha, recuperando el ciclo de marcha normalLa manera més accessible de locomoció i activitat física en els éssers humans és caminar. Aquesta ac- tivitat es realitza gràcies al mecanisme d’inhibició recíproca, controlat pels circuits inhibitoris espinals i supraespinals. La idea d’aquest mecanisme és desactivar el múscul antagonista mentre es contrau l’agonista, permetent la coordinació muscular adequada durant la marxa. La interrupció de les fibres espinals després d’una lesió medul·lar desajusta el control de la inhibició reciprocal. El resultat d’aquesta manca de control és una coactivació dels músculs antagonistes gen- erant espasticitat a les extremitats inferiors, cosa que genera alteracions a la marxa. La importància de la recuperació de la marxa per a la independència i la reintegració del pacient a la societat, ha incrementat el nombre de teràpies emergents de rehabilitació de la marxa. Una daquestes teràpies, lestimulació del nervi perifèric, ha demostrat resultats prometedors. Aquesta teoria és la base dáquesta Tesi de Màster que té com a objectiu desenvolupar una plataforma de neuromodulació de la marxa que indueixi la neuroplasticitat dels circuits espinals, millorant els valors de inhibició recíproca. La idea és aplicar una estimulació aferent al Nervi Peroneal Comú que inerva el múscul Tibial Anterior per induir la inhibició recíproca al múscul antagonista Soli. Aquesta plataforma ha estat validada en 20 voluntaris sans per avaluar-ne l’eficàcia. La primera part del protocol experimental és una anàlisi del cicle de marxa per avaluar l’activació de cada múscul durant les diferents fases del cicle de la marxa. Després, amb la intervenció d’estimulació prèvia, hi ha una avaluació de l’activitat del múscul antagonista analitzant el reflex H del soli. La inter- venció d’estimulació aferent s’aplica durant un entrenament de marxa amb una durada de 10 min- uts, utilitzant tres estratègies diferents depenent del pacient: estimulació ’In-phase’ durant la fase d’oscil·lació, estimulació ’Out-of-phase’ durant la fase de postura, i ’Control’ per comprovar si la es- timulació té un efecte real. Els processos finals del protocol són dues avaluacions de l’activitat de soli, una immediatament després de la intervenció i una altra 30 minuts després per avaluar la durada dels efectes. Els resultats obtinguts demostren que l’estimulació elèctrica aferent té un efecte real en la modulació de la inhibició recíproca. D’una banda, quan s’aplica l’estimulació elèctrica durant la fase d’oscil·lació, hi ha una millora de la inhibició recíproca. D’altra banda, quan s’administra l’estimulació durant la fase de postura, hi ha un empitjorament de la inhibició recíproca. Aquests resultats conclouen que l’estimulació elèctrica aferent, a la fase d’oscil·lació del cicle de la marxa, és una estratègia prometedora per induir la inhibició recíproca en pacients amb lesió medul·lar. La inducció d’aquest circuit inhibidor generarà a l’activació adequada dels músculs durant la marxa, recuperant el cicle de marxa norma

    A novel optogenetics-based therapy for obstructive sleep apnoea

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    Obstructive sleep apnoea (OSA) is characterised by repeat upper airway narrowing and/or collapse during sleep. Many patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel, optogenetics-based therapy, that enables light-stimulation induced upper airway dilator muscle contractions to maintain airway patency. The primary aims of this thesis were to determine feasibility in a rodent model of OSA, and identify effective optogenetic constructs for activating upper airway muscles. Chapters 2 and 3 outline the development of a novel construct for the expression of light-sensitive proteins (opsins) in upper airway muscles, comparing two promotors and two recombinant adeno-associated virus capsids (rAAV) for optogenetic gene transfer. Results show that a muscle-specific promotor (tMCK) was superior to a non-specific promotor (CAG). With tMCK, opsin expression in the tongue was 470% greater (p=0.013, RM-ANOVA), brainstem expression was abolished, and light stimulation facilitated a 66% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA (p<0.001, linear mixed model) (Chapter 2). Moreover, a novel, highly myotropic rAAV serotype, AAVMYO, was superior to a wild-type serotype, AAV9. The AAVMYO serotype driven by tMCK facilitated a further increase in muscle activity with light stimulation to 194% of that recorded during unstimulated breaths (p<0.001, linear mixed model) (Chapter 3). Finally, ultrasound imaging confirmed that the optimised construct was able to generate effective light-induced muscle contractions and airway dilation (Chapter 4). A secondary aim was to advance preclinical trials for the proposed therapy. To this end, a surgical protocol for chronic implantation of light delivery hardware and recording electrodes in rodents was developed (Chapter 5). The final protocol will allow us to determine the effects of acute and chronic light stimulation on opsin-expressing upper airway muscles during natural sleep. In summary, Chapters 2 to 4 provide proof-of-concept for a non-invasive optogenetics-based OSA therapy. The combination of a muscle-specific promotor and a muscle-specific viral vector presents a novel and highly effective method of inducing light sensitivity into skeletal muscle and facilitating light-evoked airway dilation. Finally, Chapter 5 commences the development of a surgical protocol that will aid ongoing preclinical trials

    Protecting the well-being of parents and children during a pandemic

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    BackgroundThe UK was severely affected by the COVID-19 pandemic. Over the course of three years, the disease claimed the lives of over 220,000 people in the UK. To try to control the spread of COVID-19, the UK Government implemented a range of compulsory and recommended non-pharmaceutical interventions to reduce disease transmission. Between 23 March and 1 June 2020, the guidance that was in place was commonly referred to as “lockdown” or “stay-at-home” guidance, because of the stringent restrictions. For example: non-essential shops were closed, people who could had to work from home, only leave the home to shop as infrequently as possible, and to not meet anyone from another household. If people were to go outside of their home, they were advised to keep two meters away from people from other households. One particularly controversial intervention was the closure of schools. However, schools were not fully closed. They were kept open for children who had a parent that was critical to the COVID-19 response and for children who were vulnerable. Schools closing placed a particular strain on families, as parents were required to home-school their children and there were common concerns about children’s education and about the well-being of children and parents as a result of the restrictions.Non-pharmaceutical interventions are not only used for pandemic-related interventions. There are also everyday non-pharmaceutical interventions that are used to reduce disease transmission, one of which is a schools’ sickness policy. It is a legal requirement for schools to have a policy that guides parents, children, and school staff about the procedure to follow if a child is too ill to attend school or becomes ill at school. It is important that this guidance is adhered to, as children can be particularly susceptible to many diseases and are often in close contact with many other children. Nonetheless, it is common for children to attend school whilst they are unwell and “presenteeism,” specifically “school-based presenteeism,” has been used to describe this behaviour. Understanding school-based presenteeism is important to prevent the spread of disease and outbreaks within schools. School-based presenteeism is relatively understudied. However, previous research suggests that the reasons and risk factors for presenteeism are related to perceptions about an illness, attitudes about presenteeism, the financial consequences of staying at home when ill and organisational pressures. Exploration of the connection between presenteeism and perceptions about illness may also be important in relation to adherence to COVID-19 guidance. For about two years during the pandemic, the public were required to self-isolate immediately and seek a COVID-19 test via NHS Test and Trace if they identified any of the Government’s listed symptoms of COVID-19.In this thesis, I investigated the factors that affect (a) the well-being of parents and children during a pandemic and (b) adherence to measures intended to mitigate the spread of disease between families, both in school and during school closures. These aims were investigated under broad objectives, relating to the factors associated with; children attending school whilst unwell; adherence to public health guidance in families; the well-being of children and parents and children’s education during a pandemic; and adherence to NHS Test and Trace guidance in families.MethodsA combination of quantitative and qualitative study designs were used to investigate the thesis’ aims. Study A was a systematic review that was conducted on the 11 July 2022, which included 18 studies concerning factors associated with school-based presenteeism. Study B consisted of one-to-one interviews (n = 5) and two focus groups (n = 5 and n = 7) with a total of 17 parents, that took place between 26 February and 24 March 2020 and asked about parents’ attitudes about presenteeism. Study C was a qualitative study using telephone interviews with parents (n = 30) between 16 and 21 April 2020, which explored families’ experiences of lockdown and about their adherence to the COVID-19 guidance. Study D was a cross-sectional survey (n = 2,010) of a sample of parents in England (8 and 11 June 2020), which assessed the factors associated with children’s school attendance, families’ well-being and children’s non-adherent physical interactions while schools were closed to most children. Study E was a qualitative study with parents (n = 18) interviews were conducted between 30 November and 11 December 2020, which asked about families’ experiences of using and attitudes about NHS Test and Trace. Study F was a cross-sectional survey (n = 941) with UK parents that was conducted between 19 November and 18 December 2021. This final study investigated the risk factors associated with children who continued to socialise and engage in activities when they had signs and symptoms of an infectious disease.ResultsI found that in June 2020, 26% of children and 19% of parents included in my study reported low well-being. Several factors affected the well-being of parents and children. Primarily, responses to the COVID-19 guidance, such as the reduced in-person interactions with non-household members, home-schooling, and concerns about loved ones becoming seriously ill adversely affected family well-being. Moreover, I found that children who had educational difficulties, families with limited resources or a psychological or physical health problems before the pandemic were particularly at risk of low well-being. In contrast, I found that family well-being could be protected by physical exercise, social support, and positive motivations.I found that 15% of children had non-household family interactions in June 2020, in contravention of Government guidance and that, when schools had re-opened, 33% of children attended school, engaged in other activities, or socialised with others when they had symptoms of an infectious disease that should have led them to remain at home. Across multiple studies, I found several risk factors linked with families’ adherence to public health guidance in general, which included national COVID-19 guidance and schools’ sickness policies. These factors included perceptions about the illness; communications about the guidance; and contextual factors, such as financial resources, organisation pressures, social networks, low well-being in children and parents and having special educational needs.ConclusionsOverall, I found surprisingly high numbers of families who reported low well-being and who were non-adherent to the guidance that was in place to prevent disease transmission. I found that adherence was associated with themes about the clarity of the guidance, perceptions about COVID-19, a family’s motivation and attitudes about adherence and other environmental factors that may prevent or encourage adherence. These themes are also relevant to adherence to polices that are used to prevent disease outbreaks in schools outside of a pandemic. Notably, children with special educational needs, families that had fewer resources and parents or children with health problems were at an increased risk of (a) having low family well-being and (b) non-adherence to health guidance. Families that engaged in physical activity, stayed connected with family and friends and had positive motivations were better able to cope with the pandemic. Policymakers need to consider these factors when designing and implementing public health guidance to protect families’ well-being and improve adherence to local and national health guidance.<br/

    Functional network correlates of language and semiology in epilepsy

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    Epilepsy surgery is appropriate for 2-3% of all epilepsy diagnoses. The goal of the presurgical workup is to delineate the seizure network and to identify the risks associated with surgery. While interpretation of functional MRI and results in EEG-fMRI studies have largely focused on anatomical parameters, the focus of this thesis was to investigate canonical intrinsic connectivity networks in language function and seizure semiology. Epilepsy surgery aims to remove brain areas that generate seizures. Language dysfunction is frequently observed after anterior temporal lobe resection (ATLR), and the presurgical workup seeks to identify the risks associated with surgical outcome. The principal aim of experimental studies was to elaborate understanding of language function as expressed in the recruitment of relevant connectivity networks and to evaluate whether it has value in the prediction of language decline after anterior temporal lobe resection. Using cognitive fMRI, we assessed brain areas defined by parameters of anatomy and canonical intrinsic connectivity networks (ICN) that are involved in language function, specifically word retrieval as expressed in naming and fluency. fMRI data was quantified by lateralisation indices and by ICN_atlas metrics in a priori defined ICN and anatomical regions of interest. Reliability of language ICN recruitment was studied in 59 patients and 30 healthy controls who were included in our language experiments. New and established language fMRI paradigms were employed on a three Tesla scanner, while intellectual ability, language performance and emotional status were established for all subjects with standard psychometric assessment. Patients who had surgery were reinvestigated at an early postoperative stage of four months after anterior temporal lobe resection. A major part of the work sought to elucidate the association between fMRI patterns and disease characteristics including features of anxiety and depression, and prediction of postoperative language outcome. We studied the efficiency of reorganisation of language function associated with disease features prior to and following surgery. A further aim of experimental work was to use EEG-fMRI data to investigate the relationship between canonical intrinsic connectivity networks and seizure semiology, potentially providing an avenue for characterising the seizure network in the presurgical workup. The association of clinical signs with the EEG-fMRI informed activation patterns were studied using the data from eighteen patients’ whose seizures and simultaneous EEG-fMRI activations were reported in a previous study. The accuracy of ICN_atlas was validated and the ICN construct upheld in the language maps of TLE patients. The ICN construct was not evident in ictal fMRI maps and simulated ICN_atlas data. Intrinsic connectivity network recruitment was stable between sessions in controls. Amodal linguistic processing and the relevance of temporal intrinsic connectivity networks for naming and that of frontal intrinsic connectivity networks for word retrieval in the context of fluency was evident in intrinsic connectivity networks regions. The relevance of intrinsic connectivity networks in the study of language was further reiterated by significant association between some disease features and language performance, and disease features and activation in intrinsic connectivity networks. However, the anterior temporal lobe (ATL) showed significantly greater activation compared to intrinsic connectivity networks – a result which indicated that ATL functional language networks are better studied in the context of the anatomically demarked ATL, rather than its functionally connected intrinsic connectivity networks. Activation in temporal lobe networks served as a predictor for naming and fluency impairment after ATLR and an increasing likelihood of significant decline with greater magnitude of left lateralisation. Impairment of awareness served as a significant classifying feature of clinical expression and was significantly associated with the inhibition of normal brain functions. Canonical intrinsic connectivity networks including the default mode network were recruited along an anterior-posterior anatomical axis and were not significantly associated with clinical signs

    Towards developing a reliable medical device for automated epileptic seizure detection in the ICU

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    Abstract. Epilepsy is a prevalent neurological disorder that affects millions of people globally, and its diagnosis typically involves laborious manual inspection of electroencephalography (EEG) data. Automated detection of epileptic seizures in EEG signals could potentially improve diagnostic accuracy and reduce diagnosis time, but there should be special attention to the number of false alarms to reduce unnecessary treatments and costs. This research presents a study on the use of machine learning techniques for EEG seizure detection with the aim of investigating the effectiveness of different algorithms in terms of high sensitivity and low false alarm rates for feature extraction, selection, pre-processing, classification, and post-processing in designing a medical device for detecting seizure activity in EEG data. The current state-of-the-art methods which are validated clinically using large amounts of data are introduced. The study focuses on finding potential machine learning methods, considering KNN, SVM, decision trees and, Random forests, and compares their performance on the task of seizure detection using features introduced in the literature. Also using ensemble methods namely, bootstrapping and majority voting techniques we achieved a sensitivity of 0.80 and FAR/h of 2.10, accuracy of 97.1% and specificity of 98.2%. Overall, the findings of this study can be useful for developing more accurate and efficient algorithms for EEG seizure detection medical device, which can contribute to the early diagnosis and treatment of epilepsy in the intensive care unit for critically ill patients

    Proceedings XXII Congresso SIAMOC 2022

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    Il congresso annuale della Società Italiana di Analisi del Movimento in Clinica dà l’occasione a tutti i professionisti, dell’ambito clinico e ingegneristico, di incontrarsi, presentare le proprie ricerche e rimanere aggiornati sulle più recenti innovazioni nell’ambito dell’applicazione clinica dei metodi di analisi del movimento, al fine di promuoverne lo studio e le applicazioni cliniche per migliorare la valutazione dei disordini motori, aumentare l’efficacia dei trattamenti attraverso l’analisi quantitativa dei dati e una più focalizzata pianificazione dei trattamenti, ed inoltre per quantificare i risultati delle terapie correnti

    Spinal Cord Injury and Transcutaneous Spinal Cord Stimulation

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    Recent research of epidural and transcutaneous electrical spinal cord stimulation has demonstrated unprecedented improvements in motor function thought to be irreversibly lost due to chronic, severe spinal cord injury. Studies in parallel assess these methods for spasticity management as an alternative to medications that are often accompanied by deleterious side effects. As a noninvasive intervention, transcutaneous spinal cord stimulation holds the great potential to find its way into wide clinical application. Its firm establishment and lasting acceptance as clinical practice in spinal cord injury will not only hinge on the demonstration of safety and efficacy, but also on the delineation of a conceptual framework of the underlying physiological mechanisms. This will also require advancing our understanding of immediate and temporary effects of transcutaneous spinal cord on neuronal circuits in the intact and injured spinal cord. The purpose of this collection of papers is to bring together peers in the field to share—and eventually fuse—their pertinent research into current neurorehabilitation practice by providing a clinical perspective and novel insights into the underlying mechanisms
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