Over the last decades, robotic devices for neurorehabilitation have been developed with the aim of providing better and faster improvement of motor performance. These devices are being used to help patients repeat movements and (re)learn different dynamic tasks. Over the years, these devices have become bigger and more complex, so as to provide the end user with a more realistic and sophisticated stimuli while still allowing the experimenter to have control over the interaction forces that can potentially shape the motor behaviour. However, experimental results have shown no clear advantage of these complex devices over simpler versions. In this context, this thesis investigates sensory-motor processes of human interaction, which can help us understand the main issues for rehabilitation devices and how to overcome the limitations of simple devices to train particular motor behaviours. Conventional neurorehabilitation of motor function relies on haptic interaction between the patient and physiotherapist. However, how humans deal with human-human interactions is largely unknown, and has been little studied. In this regard, experiments of the first section of the thesis investigate the mechanisms of interaction during human-human collaborative tasks. It goes from identifying the different strategies that dyads can take to proposing methods to measure and understand redundancy and synchrony in haptic interactions. It also shows that one can shape the interaction between partners by modifying only the visual information provided to each agent. Learning a novel skill requires integration of different sensory modalities, in particular vision and proprioception. Hence, one can expect that learning will depend on the mechanical characteristics of the device. For instance, a device with limited degrees of freedom will reduce the amount of information about the environment, modify the dynamics of the task and prevent certain error-based corrections. To investigate this, the second section of the thesis examines whether the lack of proprioceptive feedback that is created due to mechanical constraints or haptic guidance can be substituted with visual information. Psychophysical experiments with healthy subjects and some preliminary experiments with stroke patients presented in this thesis support the idea that by incorporating task-relevant visual feedback into simple devices, one could deliver effective neurorehabilitation protocols. The contributions of the thesis are not limited to the role of visual feedback to shape motor behaviour, but also advance our understanding on the mechanisms of learning and human-human interaction.

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Examining 20 human wound bed biopsies (pilonidal sinus and venous leg ulcers), significant differences were observed between the subpopulations of wound macrophages in acute healing and chronic non-healing wounds. The results exhibit that within the acute wound there is an accumulation of early stage macrophages (mean 20.8, SD 8.6) differentiating from monocytes which become activated and contribute to the wound healing process. There being few early stage macrophages within the chronic wound (mean 10.4, SD 6.7) (p≤0.01). Chronic wounds in comparison demonstrated a significant accumulation of tissue macrophages (mean 34.0, SD 10.5) when compared to acute wounds (mean 10.9, SD 4.4) with limited wound healing (p≤0.01). The dermagraft (DG) study comprising of 53 patients, showed that applying a biologically active dressing (1-12 dressings over 12 weeks) and compression to the wound bed, exhibited complete closure (76%) or reduction in the size of the wounds at 12 weeks, compared to compression alone. Changes in the extracellular components and an array of inflammatory cells and cytokines in fifty three paired wound bed biopsies (106) with and without DG were examined at week 0 and week 6 of treatment. On histological investigation, DG exhibited an increase in the amount of collagen present and angiogenesis in the wound at week 6 of treatment. Although there were no significant changes in the lymphocyte counts in response to the application of DG, it was possible to demonstrate a significant increase in the number of stage macrophages at week 6 of treatment (p≤0.05) and a significant reduction in the tissue macrophage counts, at week 6 of treatment (p≤0.05) in patients treated with 4 pieces of DG. The levels of different cytokine expression within the wound bed at week 6 exhibited some changes but this was not significant, in response to DG treatment. This could be to the possible presence of proteinases within the chronic wound bed hydrolysing the cytokines produced by DG. From the results attained, it was able to conclude, for clinical use 4 pieces of DG at regular dosing intervals were sufficient to achieve wound contraction or closure. This dose regimen has not been taken forward for further pivotal studies. This thesis thus represents some of the first evidence in human tissue that macrophages may play role in wound healing, and in chronic wounds, a subpopulation of macrophages can be modified to stimulate these wounds towards healing.

Introduction : Les troubles cognitifs et comportementaux après une lésion cérébrale peuvent entraîner des limitations d’activités et des restrictions de participation. Un programme de réadaptation, pluridisciplinaire et holistique a été développé à la Pitié Salpêtrière. D’une durée de 7 semaines, il vise l’amélioration de la participation en associant des rééducations individuelles et des mises en situation écologiques (ex : préparation de repas, reprise des transports en commun...). Les effets du programme n’ont jamais été investigués. Objectif : 1) définir et valider le programme de réadaptation par l’équipe multidisciplinaire à l’aide d’un modèle logique et 2) documenter l’effet du programme sur l’activité «préparer les repas». Méthode : Mesures répétées pré (T1 et T2) et post programme (T3, T4, T5 jusqu’ à 6 mois) avec 7 sujets uniques. Outil de mesure : Cooking Task (CT) (Chevignard, 2000), Profil des Activités Instrumentales (PAI) (Bottari, 2009) et Mesure des Habitudes de Vie (MHAVIE) (Noreau, 2002). Résultats : Objectif 1 : la documentation de chaque activité du programme est validée par des groupes d’experts. Objectif 2 : Les méthodes « two standard deviation band» et “non-overlap of all pairs” (NAP) pour cas unique démontrent des différences significatives entre les périodes pré et post programme au nombre total d’erreurs au CT (6/7 sujets), en besoin en aide (PAI). L’item préparation de repas de la MHAVIE suggère une amélioration pour 4/7 sujets. Discussion : L’ensemble des résultats du CT (diminution des erreurs), du PAI et de la MHAVIE suggère une amélioration globale de l’activité « préparer un repas » à la suite du programme de réadaptation. / Background: Cognitive and behavioural difficulties following acquired brain injury (ABI) may lead to severe limitations in activities and restrictions in participation. A specific ABI, holistic and multidisciplinary rehabilitation program was developed at the Salpêtrière hospital (Paris, France). Over a 7-week period, the program aims to improve participants’ participation by combining individual rehabilitation and environmental scenarios such as meal preparation, transportation etc. Program effects have never been investigated. Objectives: 1) to define and validate the rehabilitation program by a multidisciplinary team using a logic model and 2) to document the program's effect on the activity "prepare meals." Method: Repeated measurements pre-program (T1 and T2) and post-program (T3, T4, T5 up to 6 months) with 7 subjects using the Cooking Task (CT) (Chevignard, 2000), Instrumental Activities of Daily Living (IADL) (Bottari, 2009), and Measure of Life Habits (LIFE-H) (Noreau, 2002). Results: Using the two standard deviation band method and “non-overlap of all pairs” (NAP) methods for small n design, significant differences in pre and post program measures were found for the total number of errors in CT (6/7 subjects), the need of assistance (IADL). The results of the LIFE-H suggest an effect of improving the preparation of meals for 4/7 subjects. Discussion: The combined results from the CT (fewer errors), IADL and LIFE-H suggest an overall improvement in the activity "preparing a meal" after the rehabilitation program.