Avec le besoin de développer un organe artificiel remplaçant le doigt humain dans le cas d'un déficit et la nécessité de comprendre le fonctionnement de ce système physiologique, un modèle physique inverse du système doigt, permettant de chercher les activations neuronales à partir du mouvement, est nécessaire. Malgré le grand nombre d'études dans la modélisation de la main humaine, presque il n'existe aucun modèle physique inverse du système doigt majeur qui s'intéresse à chercher les activations neuronales. Presque tous les modèles existants se sont intéressés à la recherche des forces et des activations musculaires. L'objectif de la thèse est de présenter un modèle neuromusculo-squelettique du système doigt majeur humain permettant d'obtenir les activations neuronales, les activations musculaires et les forces musculaires des tous les muscles agissants sur le système doigt d'après l'analyse du mouvement. Le but de ce type des modèles est de représenter les caractéristiques essentielles du mouvement avec le plus de réalisme possible. Notre travail consiste à étudier, modéliser et à simuler le mouvement du doigt humain. L'innovation du modèle proposé est le couplage entre la biomécanique et les aspects neurophysiologiques afin de simuler la chaine inverse complet du mouvement en allant des données dynamiques du doigt aux intentions neuronales qui contrôlent les activations musculaires. L'autre innovation est la conception d'un protocole expérimental spécifique qui traite à la fois les données sEMG multicanal et les données cinématiques d'après une procédure de capture de mouvement. / With the need to develop an artificial organ replacing the human finger in the case of a deficiency and the need to understand how this physiological system works, an inverse physical model of the finger system for estimating neuronal activations from the movement, is necessary. Despite the large number of studies in the human hand modeling, almost there is no inverse physical model of the middle finger system that focuses on search neuronal activations. Al most all existing models have focused on the research of the muscle forces and muscle activations. The purpose of the manuscript is to present a neuromusculoskeletal model of the human middle finger system for estimating neuronal activations, muscle activations and muscle forces of all the acting muscles after movement analysis. The aim of such models is to represent the essential characteristics of the movement with the best possible realism. Our job is to study, model and simulate the movement of the human finger. The innovation of the proposed model is the coupling between the biomechanical and neurophysiological aspects to simulate the complete inverse movement chain from dynamic finger data to neuronal intents that control muscle activations. Another innovation is the design of a specific experimental protocol that treats both the multichannel sEMG and kinematic data from a data capture procedure of the movement.

By exploiting the concept of emergent network properties and the hierarchical nature of networks, we have constructed several levels of models facilitating the investigations of issues in the area of respiratory neural control. The first of such models is an intracellular second messenger pathway model, which has been shown to be an important contributor to intracellular calcium metabolism and mediate responses to neuromodulators such as serotonin. At the next level, we have constructed new single neuron models of respiratory-related neurons (e.g. the pre-Btzinger complex neuron and the Hypoglossal motoneuron), where the electrical activities of the neurons are linked to intracellular mechanisms responsible for chemical homeostasis. Beyond the level of individual neurons, we have constructed models of neuron populations where the effects of different component neurons, varying strengths and types of inter-neuron couplings, as well as network topology are investigated. Our results from these simulation studies at different structural levels are in line with experiment observations. The small-world topology, as observed in previous anatomical studies, has been shown here to support rhythm generation along with a variety of other network-level phenomena. The interactions between different inter-neuron coupling types simultaneously manifesting at time-scales orders of magnitude apart suggest possible explanations for variations in the outputs measured from the XII rootlet in experiments. In addition, we have demonstrated the significance of pacemakers, along with the importance of considering neuromodulations and second-messenger pathways in an attempt to understand important physiological functions such as breathing activities.

In a school system with fewer teachers, larger groups, and less resources, functionally oriented music therapy (FMT) could be a useful method of helping children function better at school.  In what way can FMT help improve children’s ability to deal with the challenges facing them at school?  During a project that lasted for 26 weeks, two children from a Swedish preschool class were offered individual FMT once a week.  The group as a whole was divided in two and offered group music (according to the Music in preparation for school (MUISC) programme) every second week.  There was an interview with the teacher, along with an assessment of function for the two individuals, at the beginning and at the end of the project.  The two individuals receiving regular FMT functioned better at school at the end of the project.  FMT could be an effective resource to help improve children’s ability to deal with the challenges facing them at school.

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder affecting cognitive control. These functions are important to achieve goals when different actions need to be executed in close succession. This type of multi-component behavior, which often further requires the processing of information from different modalities, is important for everyday activities. Yet, possible changes in neurophysiological mechanisms have not been investigated in adolescent ADHD. We examined N = 31 adolescent ADHD patients and N = 35 healthy controls (HC) in two Stop-Change experiments using either uni-modal or bi-modal stimuli to trigger stop and change processes. These stimuli were either presented together (SCD0) or in close succession of 300 milliseconds (SCD300). Using event-related potentials (ERP), EEG data decomposition and source localization we analyzed neural processes and functional neuroanatomical correlates of multicomponent behavior. Compared to HCs, ADHD patients had longer reaction times and higher error rates when Stop and Change stimuli were presented in close succession (SCD300), but not when presented together (SCD0). This effect was evident in the uni-modal and bi-modal experiment and is reflected by neurophysiological processes reflecting response selection mechanisms in the inferior parietal cortex (BA40). These processes were only detectable after accounting for intra-individual variability in neurophysiological data; i.e. there were no effects in standard ERPs. Multi-component behavior is not always deficient in ADHD. Rather, modulations in multi-component behavior depend on a critical temporal integration window during response selection which is associated with functioning of the inferior parietal cortex. This window is smaller than in HCs and independent of the complexity of sensory input.

Head stabilisation during gait related tasks is thought to be fundamental to whole body stability, but this has received little attention in the older population. There is a need to examine any age related changes in neuromechanical mechanisms underpinning head stabilisation that may challenge the control of head stability, and consequently whole body stability. The present Thesis examined the mechanisms contributing to head stabilisation, and whole body stability during two gait tasks, steady state gait and gait initiation in young and older females, with the overall aim of contributing to negating fall risk. Four studies were designed to examine a) head position and walking speed on gait stability during steady state gait; b) neuromechanical mechanisms underpinning head stabilisation during gait initiation; c) head position on whole body stability during gait initiation; and d) head stabilisation during gait initiation at different speeds. Results showed that a) gait stability, was unaffected by head position and different walking speeds during steady state gait, b) decreased head stability in older individuals during gait initiation can be attributed to a deterioration of the neuromechanical mechanisms relating to head stability, c) free head movement during gait initiation does not affect head stabilisation or whole body stability but it does affect gait parameters, while d) initiating gait at faster than comfortable speeds compromises head stabilisation and reduces whole body stability in older individuals. Collectively, these results demonstrate that older individuals adopt an increased head flexion position when walking, while impaired head stability can be attributed to deterioration of the function of their neuromechanical mechanisms compared to their younger counterparts during gait tasks at comfortable speeds. These findings provide an understanding of the effect head stabilisation can have on older adults’ gait and on their fall risk during gait and gait initiation.

Eye movements are used day-to-day to acquire visual information. Vision is also used for postural control. There are growing indications eye movements can affect postural control. However, this has not been investigated in older adults, which is surprising given the high incidence of falls in older populations. The present thesis aims to address this. The first experimental chapter explores the effects of eye movements on balance during standing in young and older adults. The findings show decreased stability during smooth pursuits, whereas saccades maintained stability to that when fixating a static target. The older adults matched the younger groups performance throughout. The second experimental chapter explores the effects of smooth pursuits and saccades on balance during locomotion in young and older adults. Smooth pursuits were shown to decrease stability, whilst saccades maintained stability compared to fixating a static target. The effects of the eye movements were similar in the older adults. However, the elders exhibited lower baseline stability. The third experimental chapter explores the effects of tracking a real-world stimulus (another person known as `pedestrian') on balance control during locomotion. The pedestrian could be standing still or walking. Fixating the stationary and the walking pedestrian decreased stability similarly when compared to free gaze when the pedestrian was not present. To determine whether these results were transferable to natural gaze rather than instructed gaze, the fourth experimental chapter explores free gaze patterns in a similar real-world environment. Both the young and older adults typically fixated the pedestrian when he was standing still and walking, but began to ignore him once he had walked away from their direction heading. Therefore, experiment 3 behaviour was transferable to natural gaze patterns. The older adults also adopted a more cautious approach by fixating regions on the ground initially, and for longer, before looking to their direction heading.

Introdução: Ativação exacerbada de processos excitatórios mediados por NMDA e excesso de inibição mediada por GABA são descritos, respectivamente, nas fases agudas e subagudas após o traumatismo cranioencefálico (TCE). No entanto, existem poucos estudos a respeito do funcionamento desses circuitos na fase crônica do TCE. Objetivo: Avaliar a excitabilidade cortical (EC) de pacientes em fase crônica que sofreram TCE, especificamente diagnosticados com lesão axonial difusa (LAD). Métodos: Todos os 31 pacientes adultos foram avaliados após 1 ano, pelo menos, do TCE moderado ou grave. Inicialmente, os pacientes foram submetidos à avaliação de funções executivas - atenção, memória, fluência verbal e velocidade de processamento de informação - por meio de bateria neuropsicológica. Em seguida, a avaliação da EC foi realizada utilizando-se uma bobina circular para aplicar pulsos simples e pareados de estimulação magnética transcraniana na região cortical representativa do abdutor curto do polegar (pollicis brevis) na área M1 de ambos hemisférios. Os parâmetros de EC medidos foram: Limiar Motor de Repouso (LMR), Potenciais Evocados Motores (PEM), Inibição Intracortical de Intervalo Curto (IICIC) e Facilitação Intracortical (FIC). Todos os dados foram comparados aos dados normativos de EC já descritos na literatura e também aos de um grupo controle de pessoas saudáveis. Resultados: Não houve diferença significativa entre os hemisférios direto e esquerdo. Desta forma, os dados foram analisados de forma agrupada (\"pooled data\"). Os valores de LMR e FIC dos pacientes com LAD estavam dentro dos valores de normalidade. No entanto, os valores de PEMs a 120% do LMR, a 140% do LMR e IICIC estavam aumentados (respectivamente p=0,013; p=0,012; p < 0,001): PEM-120% LAD 524,95 [365,42 ; 616,66] versus Controles 303,50 [241,49 ; 399,19]; PEM-140% LAD 1150,00 [960,56 ; 1700,00] vs Controles 670,5 [575,43 ; 1122,78] e IICIC LAD 1,09 [0,82 ; 1,35] vs Controles 0,34 [0,28 ; 0,51]; pp02-Rel LAD 0,85 [0,64 ; 1,36] vs Controles 0,28 [0,20 ; 0,37]; pp04-Rel LAD 1,03 [0,88 ; 1,34] vs Controles 0,38 [0,29 ; 0,62] - sugerindo um possível desarranjo no sistema inibitório (p < 0.001). Os achados neuropsicológicos mostraram alterações na memória, atenção e velocidade de processamento de informação, mas possuíam correlação fraca com os dados de EC. Conclusão: Como os processos inibitórios envolvem circuitos mediados por GABA, além de outros, existe a possível inferência de que a própria fisiopatologia do LAD (rompimento de axônios) possa depletar GABA contribuindo com a desinibição do sistema neural na fase crônica do LAD / Background: Overactivation of NMDA-mediated excitatory processes and excess of GABA-mediated inhibition are described after a brain injury on the acute and subacute phases, respectively. Nevertheless, there are few studies regarding the circuitry on the chronic phase of brain injury. Objective: To evaluate the cortical excitability (CE) on the chronic phase of Traumatic Brain Injury (TBI) victims, specifically diagnosed with Diffuse Axonal Injury (DAI). Method: All 31 adult patients were evaluated after one year, at least, from the moderate and severe TBI. First, all patients underwent a broad neuropsychological assessment to evaluate executive functions - attention, memory, verbal fluency and information processing speed. Then, subsequently, the CE assessment was performed with a circular coil applying single-pulse and paired-pulse transcranial magnetic stimulation over the cortical representation of the abductor pollicis brevis muscle on M1 of both hemispheres. The CE parameters measured were: Resting Motor Threshold (RMT), Motor-Evoked Potentials (MEP), Short Interval Intracortical Inhibition (SIICI), and Intracortical Facilitation (ICF). All data were compared to normative data previously described on literature and to a control group that consisted of healthy subjects. Results: No significant difference between Left and Right hemispheres were found on these DAI patients. Therefore, parameters were analyzed as pooled data. Values of RMT and ICF from DAI patients were found within the normality. However, MEPs and SIICI values were higher on DAI patients (respectively p=0,013; p=0,012; p < 0,001): MEP-120% DAI 524,95 [365,42 ; 616,66] versus Control 303,50 [241,49 ; 399,19]; MEP-140% DAI 1150,00 [960,56 ; 1700,00] vs Control 670,5 [575,43 ; 1122,78] and SIICI DAI 1,09 [0,82 ; 1,35] vs Control 0,34 [0,28 ; 0,51]; pp02-Rel DAI 0,85 [0,64 ; 1,36] vs Control 0,28 [0,20 ; 0,37]; pp04-Rel DAI 1,03 [0,88 ; 1,34] vs Control 0,38 [0,29 ; 0,62] - suggesting a disarranged inhibitory system (p < 0.001). The neuropsychological findings had weak correlation with CE data. Conclusion: As inhibition processes also involve GABA-mediated circuitry, it is likely to infer that DAI pathophysiology itself (disruption of axons) may deplete GABA contributing to a disinhibition of the neural system on the chronic phase of DAI

The subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC) in the brain, and plays a major role in the memory consolidation process. It consists of different types of pyramidal neurons. Based on their firing behavior, these excitatory neurons are classified into strong burst firing (SBF), weak burst firing (WBF) and regular firing (RF) neurons. In the first part of the work, morphological differences in the different neuronal subtypes was explored by biocytin staining after classifying the neurons based on the differences in electrophysiological properties. Detailed morphological properties of these three neuronal subtypes were analyzed using Neurolucida neuron reconstruction method. Unlike the differences in their electrophysiological properties, no difference was found in the morphometric properties of these neuronal subtypes. In the second part of the thesis, experimental results on spike- timing- dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of the juvenile (P15-P19) rat are described. The STDP was studied in the WBF and RF neurons. Causal pairing of a single EPSP with a single back propagating action potential (bAP) at a time interval of 10 ms failed to induce plasticity. However, increasing the number of bAPs in such EPSP-bAP pair to three at 50 Hz (bAP burst) induced LTD in both, the RF, as well as the WBF neurons. Increasing the frequency of action potentials to 150 Hz in the bAP burst during causal pairing also induced LTD in both the neuronal subtypes. However, all other STDP related experiments were performed only with the bAP bursts consisting of 3 bAPs evoked at 50 Hz. Amplitude of the causal pairing induced LTD decreased with increasing time interval between EPSP and the bAP burst. Reversing the order of the EPSP and the bAP burst in the pair induced LTP only with a short time interval of 10 ms. This finding is in contrast to most of the reports on excitatory synapses, wherein the pre-before post (causal) pairing induced LTP and vice-versa. The results of causal and anti-causal pairing were used to plot the STDP curve for the WBF neurons. In the STDP curve observed in these synapses, LTD was observed upto a causal time interval of 30 ms, while LTP was limited to 10 ms time interval. Hence, the STDP curve was biased towards LTD. These results reaffirm the earlier observations that the relative timing of the pre- and postsynaptic activities can lead to multiple types of STDP curves. Next, the mechanism of non-Hebbian LTD was studied in both, the RF and WBF neurons. The involvement of calcium in the postsynaptic neuron in plasticity induction was studied by chelating intracellular calcium with BAPTA. The results indicate that the LTD induction in WBF neurons required postsynaptic calcium, while LTD induction in the RF neurons was independent of postsynaptic calcium. Paired pulse ratio (PPR) experiments suggested the involvement of a presynaptic mechanism in the induction of LTD in the RF neurons, and not in the WBF neurons since the PPR was unaffected by the induction protocol only in the WBF neurons. LTD induction in the WBF neurons required activity of the NMDA receptors since LTD was not observed in the presence of the NMDA receptor blocker in the WBF neurons, while it was unaffected in the RF neurons. However, the RF neurons required the activity of L-type calcium channels for plasticity induction, since LTD was affected in the presence of the L-type calcium channel blockers, although the WBF neurons did not require the L-type calcium channel activity for plasticity induction. Hence, in addition to a non-Hebbian STDP curve, a novel mechanism of LTD induction has been reported, where L-type calcium channels are involved in a synaptic plasticity that is expressed via change in the release probability. The findings on the STDP in subicular pyramidal neurons may have strong implications in the memory consolidation process owing to the central role of the subiculum and LTD in it.

Learning and memory consolidation processes in children and adults: a<p>neurophysiological and neuropsychological investigation.<p><p>Sleep is a complex and active state of the brain, associated with essential functional changes<p>[1]. Accumulated evidence in the adult population indicates that sleep participates in the<p>consolidation of declarative (i.e. memory for facts and episodes) and procedural (i.e. skills<p>and habits) memory, allowing novel information to be integrated for the long term in cerebral<p>networks [2]. Whether sleep supports memory consolidation in children likewise and to the<p>same extent than in adults remains disputed. In this framework, I have developed<p>experiments aimed at investigating sleep-dependent consolidation processes both in children<p>and adults, using behavioral and neurophysiological techniques (magneto-encephalography<p>[MEG]; electro-encephalography [EEG]; functional magnetic resonance imaging [fMRI]). To<p>sum up, researches conducted during my PhD thesis have contributed to start unraveling<p>neurophysiological mechanisms participating in sleep-dependent consolidation processes.<p>On the one hand, I report that despite a lack of detectable behavioral differences, posttraining<p>sleep plays a role in reshaping the cerebral networks subtending implicit motor<p>sequence learning in adults [3]. I also showed using a motor adaptation task [4] that sleep<p>contributes to the consolidation of procedural memory in children [5]. On the other hand, I<p>have evidenced neuromagnetic correlates of learning novel semantic representations in<p>children [6-7], and is currently finalizing the analysis of the effect of a post-training nap on the<p>consolidation of these representations. Finally, I showed in epileptic children that interictal<p>epileptic discharges (IED) during sleep impairs declarative memory consolidation processes<p>[8-9], and that this phenomenon is reversible upon pharmacological treatment suppressing<p>IED. Altogether, these findings advocate the need to explore further memory consolidation<p>and its neurophysiological basis in children, both healthy and suffering from various brain<p>pathologies [10].<p>[1] Urbain C. Peigneux, P. & Schmitz R. Sleep and the Brain. (to appear). In The Oxford Handbook of<p>Sleep and Sleep Disorders. C. M. Morin and C. A. Espie (Eds.). Oxford University Press, Oxford, NY.<p>[2] Peigneux P. Schmitz R. & Urbain C. Sleep and Forgetting. In Forgetting. S. Della Sala (Ed.).<p>Psychology Press, Hove, UK. 2010. (pp. 165-184).<p>[3] Urbain C. Schmitz R. Schmidt C. Cleeremans A. Van Bogaert P. Maquet P. and Peigneux P.<p>(submitted). Neuroanatomical Sleep-Dependent Processing in the Probabilistic Serial Reaction Time<p>Task.<p>[4] Huber, R. Ghilardi, M.F. Massimini, M. And Tononi, G. Local sleep and learning. Nature, 2004,<p>430, 78-84.<p>[5] Urbain C. Houyoux E. Albouy G. Peigneux P. (in preparation). Sleep-dependent consolidation of<p>procedural learning in children.<p>[6] Urbain C. Schmitz R. Op De Beeck M. Bourguignon M. Galer S. X. De Tiège, Van Bogaert P.<p>and Peigneux P. (in preparation). How learning new meanings about novel objects modulates cerebral<p>activity in children: A MEG Study.<p>[7] Urbain C. Schmitz R. Bourguignon M. Op De Beeck M. Galer S, De Tiège X. Van Bogaert P.<p>Peigneux P. (2011). Learning and Fast-Mapping Meanings to Novel Object in Children: A MEG Study.<p>17th Annual Meeting of the Organization for Human Brain Mapping [HBM], 26-30 June 2011, Québec<p>City, Canada<p>[8] Urbain C. et al. Is sleep-related consolidation impaired in focal idiopathic epilepsies of childhood?<p>A pilot study, Epilepsy and Behavior, 2011, 22(2), 380-384.<p>[9] Van Bogaert P. Urbain C. Galer S. Ligot N. Peigneux P. and De Tiège X. Impact of focal<p>interictal epileptiform discharges on behaviour and cognition in children. Neurophysiologie<p>Clinique/Clinical Neurophysiology, 2012, 42(1–2), 53-58. / Doctorat en Sciences Psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder affecting cognitive control. These functions are important to achieve goals when different actions need to be executed in close succession. This type of multi-component behavior, which often further requires the processing of information from different modalities, is important for everyday activities. Yet, possible changes in neurophysiological mechanisms have not been investigated in adolescent ADHD. We examined N = 31 adolescent ADHD patients and N = 35 healthy controls (HC) in two Stop-Change experiments using either uni-modal or bi-modal stimuli to trigger stop and change processes. These stimuli were either presented together (SCD0) or in close succession of 300 milliseconds (SCD300). Using event-related potentials (ERP), EEG data decomposition and source localization we analyzed neural processes and functional neuroanatomical correlates of multicomponent behavior. Compared to HCs, ADHD patients had longer reaction times and higher error rates when Stop and Change stimuli were presented in close succession (SCD300), but not when presented together (SCD0). This effect was evident in the uni-modal and bi-modal experiment and is reflected by neurophysiological processes reflecting response selection mechanisms in the inferior parietal cortex (BA40). These processes were only detectable after accounting for intra-individual variability in neurophysiological data; i.e. there were no effects in standard ERPs. Multi-component behavior is not always deficient in ADHD. Rather, modulations in multi-component behavior depend on a critical temporal integration window during response selection which is associated with functioning of the inferior parietal cortex. This window is smaller than in HCs and independent of the complexity of sensory input.