Brain Plasticity Induced by Motor and Cognitive Interventions in Health and Pathology

Plasticity, the way the brain can adapt to environmental or intrinsic changes, is the cornerstone of human behavior. Plasticity does not only harbor the possibility to learn or improve new motor or cognitive skills, but also displays the basis for restoring functioning after brain damage. Brain plasticity can thus be induced by various activities and is most prominently investigated following interventions with the aim to enhance cognition in the healthy population or rehabilitative strategies of motor and cognitive functions in pathological conditions. Although it is widely acknowledged that plastic changes are possible after activitydependent interventions, improvements on untrained functional domains are still not fully comprehended. Furthermore, the previous focus on establishing the efficacy has shifted towards the understanding of behavioral and functional underlying mechanisms of interventions. Three studies presented within the frame of this thesis aimed at investigating mechanisms of brain plasticity in health and pathology induced by rehabilitative, motor and cognitive interventions. In the first study (Zuber et al., 2020), we examined the efficacy in symptom improvement and underlying brain mechanisms of an inpatient personalized multidisciplinary rehabilitation program in patients with multiple sclerosis using functional Magnetic Resonance Imaging (fMRI). The multidisciplinary rehabilitation led to improved fatigue, walking ability as well as quality of life and a more effective recruitment of cerebellar and prefrontal brain regions in patients with multiple sclerosis. Two studies in healthy participants aimed at targeting current challenges in the cognitive training research by studying underlying cognitive and motor mechanisms of working memory training. In study B (Zuber, Geiter, de Quervain, & Magon, 2021), we compared a novel model-based working memory training with and without distractor inhibition to a dual-n-back and active control training in order to study distractor inhibition as a task-related process with the potential to render near and far transfer effects in healthy elderly adults. Working memory capacity was improved only following the model-based training with distractor inhibition, suggesting the novel training to be a promising approach in improving working memory in healthy old adults. In study C (Zuber, Gaetano, et al., 2021), we studied the interactive and additive effects of working memory and motor sequence learning training behaviorally and by resting state functional connectivity. Results indicate a relevance of the sequential order of training performance, with increased functional connectivity between a complex network of parietal, temporal and motor brain regions, specifically when motor training was performed before or combined with working memory training. The results of those three studies indicate plastic changes following rehabilitation in patients with multiple sclerosis and motor and cognitive interventions in healthy people. It can thus be concluded that brain plasticity following interventions in health and pathology is the result of an interplay between various behavioral and functional mechanisms. Hence, this thesis highlights the importance of identifying underlying neural and behavioral processes by theory-driven approaches in methodologically well controlled studies as the basis for translating neuroscientific research into the clinical setting.