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Title: Sensorimotor adaptation : mechanisms, modulation and rehabilitation potential
Author: Petitet, Pierre
ISNI:       0000 0004 7232 838X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Adaptation is a fundamental property of the nervous system that underlies the maintenance of successful actions through flexible reconfiguration of sensorimotor processing. The primary aims of this thesis are 1) to investigate the computational and neural underpinnings of sensorimotor memory formation during prism adaptation (PA) in humans, and 2) how they interact with anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1), in order to 3) improve efficacy of prism therapy for post-stroke spatial neglect. In chapter 4, we modify an influential state-space model of adaptation in order to characterize the contribution of short and long memory timescales to motor behaviour as sensorimotor after-effects (AEs) develop during PA. This enables us, in the multimodal 7 Tesla MRI experiment reported in chapter 5, to demonstrate that the level of M1 excitation:inhibition causally sets the relative contribution of long versus short memory timescales during PA, thus determining behavioural persistence of the AE at retention in young healthy adults. This finding offers a bridge between different levels of investigation by providing a biologically plausible neuro-computational model of how sensorimotor memories are formed and enhanced by a-tDCS. In chapter 6, we use the ageing motor system as a model of reduced GABAergic inhibition and show that the age-related decrease in M1 GABA explains why older adults demonstrate more persistent prism AEs. Taken together, these data indicate that the reduction in M1 GABAergic inhibition via excitatory a-tDCS during PA has the potential to enhance persistence of adaptation memory in both young and older adults. Informed by these results, we subsequently ask whether standard (multi-session) PA therapy combined with left M1 a-tDCS translates to greater and/or longer-lasting clinical improvements in post-stroke spatial neglect patients. In chapter 7, we compare the multimodal neuroimaging data of six neglect patients to normative data of age-matched controls. We show that in all patients, the lesion interrupted long-range frontoparietal connections, and we provide direct evidence for a pathological left dominance of activity within the lateral occipital cortex during deployment of bilateral visuospatial attention. In chapter 8, we present the behavioural performance of these patients throughout the two phases of the clinical study (i.e. before and after either PA + real M1 a-tDCS or PA + sham M1 atDCS). There was no clear effect of a-tDCS on the therapeutic effect of PA in these patients. The results of the studies presented in this thesis provide a novel insight into the neurocomputational mechanisms of sensorimotor memory formation and its modulation by a-tDCS in the healthy brain. Further investigation of how these mechanisms relate to therapeutic improvements following PA in certain neglect patients is needed.
Supervisor: O'Shea, Jacinta ; Johansen-Berg, Heidi Sponsor: European Union FP7 Marie Skłodowska-Curie Initial Training Network
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Clinical Neuroscience ; Sensorimotor adaptation ; Computational neuroscience ; Brain stimulation ; Stroke rehabilitation ; Neuroimaging