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This thesis investigates sensorimotor adaptive mechanisms that maintain the accuracy of goal-directed saccades in amblyopia, a developmental disorder characterized by impairment of spatiotemporal visual processing. Saccadic adaptation was induced by displacing the visual target toward initial fixation during the saccade. Eleven visually normal controls and seven patients with amblyopia were tested binocularly and monocularly with the amblyopic and fellow eye (non-dominant and dominant eye in controls) in three separate sessions. Patients with amblyopia exhibited reduced adaptation of saccadic gain compared to controls when viewing with the amblyopic eye and binocularly. Initiation of saccades was also delayed in patients when viewing with the amblyopic eye. It is proposed that the adaptive ability to modify the initial saccadic motor commands for maintaining short-term saccadic accuracy is impaired in amblyopia due to imprecise error signals. Moreover, this thesis reaffirms the notion that the error signals driving saccadic adaptation are visual in nature.

This thesis investigates sensorimotor adaptive mechanisms that maintain the accuracy of goal-directed saccades in amblyopia, a developmental disorder characterized by impairment of spatiotemporal visual processing. Saccadic adaptation was induced by displacing the visual target toward initial fixation during the saccade. Eleven visually normal controls and seven patients with amblyopia were tested binocularly and monocularly with the amblyopic and fellow eye (non-dominant and dominant eye in controls) in three separate sessions. Patients with amblyopia exhibited reduced adaptation of saccadic gain compared to controls when viewing with the amblyopic eye and binocularly. Initiation of saccades was also delayed in patients when viewing with the amblyopic eye. It is proposed that the adaptive ability to modify the initial saccadic motor commands for maintaining short-term saccadic accuracy is impaired in amblyopia due to imprecise error signals. Moreover, this thesis reaffirms the notion that the error signals driving saccadic adaptation are visual in nature.

Our walking patterns must be adjusted continuously in everyday living, whether for maneuvering on slippery surfaces or stepping over cracks on the street. Walking becomes more challenging as it requires more energy to lift and accelerate the body due to additional loads on the body as we move through space. This dissertation investigates gait, stability, and adaptation in adults with range of adiposity. First, we studied how people with obesity adapt to spatial (obstacle crossing) and temporal (metronome walking) task constraints during walking over-ground. Results indicated that people prioritized a spatial over temporal constraint when attempting to meet both constraints at the same time. Second, we tested how massive weight loss affects gait and stability. We measured how bariatric surgery patients walked and crossed obstacles before and one year after surgery. Findings indicated that massive weight loss improved not only gait but also postural stability during gait. Third, we quantified whole-body rotational characteristics in adults with obesity through changes in angular momentum quantities during steady-state walking. I found that angular momentum (1) was greater in adults with higher BMI, (2) was highly regulated by foot placement, and (3) did not change with walking speed. Taken together these results suggest that gait and stability can be adapted. These findings may help to develop interventions to target specific walking deficits in patients with mobility limitations such as obesity.

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<p>Children with myelomeningocele (MMC) usually have problems with daily life activities, but the background to their problems is not altogether obvious. An understanding of the possible causes of activity problems is a prerequisite for the effectiveness of physical therapy. The overall aim of the present studies was to identify impairments above the cele level, which might influence mobility in children with MMC (study I) and to analyse sitting posture (study II) and the movement characteristics of reaching movements (study III and IV). </p><p>In total, 41 children and young adults with MMC and without mental retardation were investigated. Study I comprised 32 children, 6-11 years. Mobility and the caregiver assistance required for mobility were quantified according to the Paediatric Evaluation of Disability Inventory (PEDI) and correlation between mobility and neurological impairment, hand function and cognitive function were calculated. The results showed that nine children achieved independent mobility and that there was a moderate and significant correlation between the need for physical assistance and high cele level, impaired hand function and impaired cognitive function. In those children who used a wheelchair, only poor hand strength was significantly correlated with the need for caregiver assistance.</p><p>Study II comprised 11 children, 10-13 years, and a control group of 20 healthy children. Sitting posture was investigated by using a force plate and analysed from the frequency and the amplitude of the postural sway. The reaction forces before and during rapid arm lift were also analysed. The result showed that children with MMC had significantly lower sway frequency compared to the controls. In both groups, the ground reaction forces were registered before the children lifted their arms. Study III and IV comprised 31 children and young adults, 9-19 years and 31 matched controls. Reaching movements were investigated with a digitising tablet, linked to a computer. The ability to program and execute reaching movements was analysed and also the ability to adapt reaching to new visuomotor conditions. The results showed that the MMC group had poorer precision, less straight movements and shorter deceleration phases as compared to the controls. In both groups the movements were pre-programmed. In addition, adaptation of reaching to new visuomotor conditions was poor in the MMC group as compared to the controls. </p><p>In conclusion we found that impairments above the cele level influenced mobility and the control of sitting posture in children with MMC. Reduced precision and co-ordination of reaching, and also difficulties with motor adaptation, could partly explain thier problems with hand activities. These findings need to be considered in therapy programs for children and young adults with MMC.</p>

Children with myelomeningocele (MMC) usually have problems with daily life activities, but the background to their problems is not altogether obvious. An understanding of the possible causes of activity problems is a prerequisite for the effectiveness of physical therapy. The overall aim of the present studies was to identify impairments above the cele level, which might influence mobility in children with MMC (study I) and to analyse sitting posture (study II) and the movement characteristics of reaching movements (study III and IV). In total, 41 children and young adults with MMC and without mental retardation were investigated. Study I comprised 32 children, 6-11 years. Mobility and the caregiver assistance required for mobility were quantified according to the Paediatric Evaluation of Disability Inventory (PEDI) and correlation between mobility and neurological impairment, hand function and cognitive function were calculated. The results showed that nine children achieved independent mobility and that there was a moderate and significant correlation between the need for physical assistance and high cele level, impaired hand function and impaired cognitive function. In those children who used a wheelchair, only poor hand strength was significantly correlated with the need for caregiver assistance. Study II comprised 11 children, 10-13 years, and a control group of 20 healthy children. Sitting posture was investigated by using a force plate and analysed from the frequency and the amplitude of the postural sway. The reaction forces before and during rapid arm lift were also analysed. The result showed that children with MMC had significantly lower sway frequency compared to the controls. In both groups, the ground reaction forces were registered before the children lifted their arms. Study III and IV comprised 31 children and young adults, 9-19 years and 31 matched controls. Reaching movements were investigated with a digitising tablet, linked to a computer. The ability to program and execute reaching movements was analysed and also the ability to adapt reaching to new visuomotor conditions. The results showed that the MMC group had poorer precision, less straight movements and shorter deceleration phases as compared to the controls. In both groups the movements were pre-programmed. In addition, adaptation of reaching to new visuomotor conditions was poor in the MMC group as compared to the controls. In conclusion we found that impairments above the cele level influenced mobility and the control of sitting posture in children with MMC. Reduced precision and co-ordination of reaching, and also difficulties with motor adaptation, could partly explain thier problems with hand activities. These findings need to be considered in therapy programs for children and young adults with MMC.

Movement is essential to human life because it provides us with the freedom of mobility and the power to affect our surroundings. Moreover, movements are vital to communication: from hand and finger movements when writing, mouth and throat movements when speaking, to painting, dancing, and other forms of artistic self expression. As people grow and experience new environments, adaptively maintaining the accuracy of movements is a critical function of the motor system. In this dissertation, I explore the key mechanisms that underlie the adaptability of simple visually guided reaching movements. I specifically focus on two key facets of this adaptability: how motor learning rate can be predicted by motor variability and how motor learning affects the mechanisms which underlie movement planning. Inspired by reinforcement learning, I hypothesized that greater amounts of motor variability aligned with a task will produce more effective exploration, leading to faster learning rates. I discovered that this relationship predicts person-to-person and task-to-task differences in learning rate for both reward-based and error-based learning tasks. Moreover, I found that the motor system actively and enduringly reshapes motor output variability, aligning it with a task to improve learning. These results indicate that the structure of motor variability is an activelyregulated, critical feature of the motor system which plays a fundamental role in determining motor learning ability. Combining prominent theories in motor control, I created a model which describes the planning of visually guided reaching movements. This model computes a weighted average of two independent feature-based motor plans: one based on the goal location of a movement, and the other based on an intended movement vector. Employing this model to characterize the generalization of adaptation to movements and movement sequences, I find that both features, movement vector and goal location, contribute significantly to movement planning, and that each feature is remapped by motor adaptation. My results show that multiple features contribute to the planning of both point-to-point and sequential reaching movements. Moreover, a computational model which is based on the remapping of multiple features accurately predicts how visuomotor adaptation affects the planning of movement sequences. / Engineering and Applied Sciences

abstract: Brain-machine interfaces (BMIs) were first imagined as a technology that would allow subjects to have direct communication with prosthetics and external devices (e.g. control over a computer cursor or robotic arm movement). Operation of these devices was not automatic, and subjects needed calibration and training in order to master this control. In short, learning became a key component in controlling these systems. As a result, BMIs have become ideal tools to probe and explore brain activity, since they allow the isolation of neural inputs and systematic altering of the relationships between the neural signals and output. I have used BMIs to explore the process of brain adaptability in a motor-like task. To this end, I trained non-human primates to control a 3D cursor and adapt to two different perturbations: a visuomotor rotation, uniform across the neural ensemble, and a decorrelation task, which non-uniformly altered the relationship between the activity of particular neurons in an ensemble and movement output. I measured individual and population level changes in the neural ensemble as subjects honed their skills over the span of several days. I found some similarities in the adaptation process elicited by these two tasks. On one hand, individual neurons displayed tuning changes across the entire ensemble after task adaptation: most neurons displayed transient changes in their preferred directions, and most neuron pairs showed changes in their cross-correlations during the learning process. On the other hand, I also measured population level adaptation in the neural ensemble: the underlying neural manifolds that control these neural signals also had dynamic changes during adaptation. I have found that the neural circuits seem to apply an exploratory strategy when adapting to new tasks. Our results suggest that information and trajectories in the neural space increase after initially introducing the perturbations, and before the subject settles into workable solutions. These results provide new insights into both the underlying population level processes in motor learning, and the changes in neural coding which are necessary for subjects to learn to control neuroprosthetics. Understanding of these mechanisms can help us create better control algorithms, and design training paradigms that will take advantage of these processes. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2015

L'adaptation motrice permet d'ajuster la sortie motrice en réponse à des perturbations de l'environnement. Au début de l'adaptation, un processus stratégique conscient appelé recalibration a lieu. Ce processus implique le cervelet et le cortex pariétal postérieur. Il permet de réduire les erreurs motrices en se basant sur le retour sensoriel. Les patients dystoniques ont des altérations du traitement de l'information somatosensorielle. Nous avons fait l'hypothèse que cela devait entrainer des anomalies d'adaptation au cours de la phase de recalibration. En utilisant l'imagerie par résonnance magnétique (IRMf) et la magnétoencéphalographie (MEG), nous avons enregistré l'activité cérébrale chez des patients ayant une crampe de l'écrivain et chez des volontaires sains, alors qu'ils réalisaient une tâche de pointage avec ou sans perturbation visuelle associée. L'étude en IRMf a révélé l'implication d'un réseau cérébello-pariétal postérieur dans la détection des erreurs motrices. Ce réseau était hypoactif chez les patients qui compensaient en recrutant un réseau alternatif plus cognitif mettant en jeu la mémoire visuo-spatiale et la représentation cognitive de la main. La MEG nous a permis d'analyser la dynamique temporelle des activations et de montrer en particulier que la préparation du mouvement est déjà anormale chez les patients; de réaliser une analyse fréquentielle de la communication cérébello-corticale. Cette analyse a révélé un défaut de cohérence dans la bande gamma, entre le cervelet et le cortex moteur et prémoteur ainsi qu'avec le cortex pariétal postérieur. L'ensemble de nos résultats suggère un désordre constitutionnel de ce réseau dans la dystonie. / Dystonia is a movement disorder characterized by prolonged muscle contractions causing involuntary repetitive twisting movements and abnormal postures. Motor adaptation shapes the motor output according to the changes in the environment. At its early stage, motor adaptation involves a strategic conscious process called “recalibration” that minimizes the perturbation and reduces the motor error based on online integration of sensory feedback. Sensorimotor processing is impaired in dystonia and we hypothesized that this may lead to deficits of the “recalibration” phase during motor adaptation. We used magnetoencephalography (MEG) and functional magnetic resonance imagery (fMRI) to record brain activation in patients with writer’s cramp and healthy volunteers using a classical rotation learning task. The fMRI study revealed that the cerebello-parietal network was directly implicated in motor error detection. In writer’s cramp, this network was underactivacted and patients relied more on cognitive networks based on visuospatial memory and cognitive representations of the hand. With MEG, (1) we reconstructed the temporal dynamic of activations in the cerebello-parietal network and demonstrated abnormal movement preparation in writer’s cramp patients; (2) we realized a spectral analysis of the cerebello-parietal communication. This analysis revealed decreased gamma coherence between the cerebellum, and the premotor and motor cortices and with posterior parietal cortex. All of our data suggest an underlying disorder of this network in dystonia.