Age-related differences in action selection and learning A multimodal brain imaging approach

Recent advancements in medical technologies and services have led to increased life expectancy while age-related declines in cognitive and motor functions place additional pressure on social and healthcare systems. This demographic evolution highlights the critical need to explore the adverse effects of aging on human functioning in everyday life. In particular, the compromised motor control poses a significant threat to functional independence and quality of life. Hence, in the first part of this thesis, we focused on the aging-induced neurodegenerative changes in the brain and their impact on action selection performance as a proxy of motor function.

Accordingly, our investigations revealed that the age-related decline in prefronto- striatal structural connectivity was linked to deficits in action selection performance. This might be due to the reduced information transmission capacity which has negative consequences for action selection performance. Furthermore, we demonstrated that the age-related reduction in concentrations of white matter-related neurometabolites correlates with deteriorations in the microstructural properties of the primary motor cortex, hence it might contribute to the observed slowness in older adults. Lastly, our exploration of the impact of aging on the inhibitory and excitatory brain mechanisms illustrated that older adults exhibited lower concentrations of both GABA and Glx. Our findings also revealed a significant task-induced increase in the SM1 excitability during the performance of the SRT task. Furthermore, we elucidated how task-induced modulations of GABA and Glx were related to action selection performance and learning. The observed effects were driven by YA and the trends were different in YA and OA. We hypothesized that the differential effects between groups could be explained by the age-related structural and functional changes in the CNS of the OA.

In the second part of this thesis, we focused on the role of inhibitory and excitatory neurometabolites in transfer of learning. Accordingly, while we found no significant task- or transfer-induced modulation in the concentrations of GABA and Glx, our findings revealed a significant association between the during-task concentration of S1 Glx and better transfer of learning. This research served as a foundation for extending this paradigm to aging studies.

Consequently, our interest was primarily directed to the investigation of the adverse effects of aging on GABA and Glx concentrations, along with brain structural connectivity, potentially leading to compromised performance and learning in older adults compared to their younger counterparts. Collectively, the studies within this thesis utilized an advanced multimodal neuroimaging approach to investigate the effects of aging on the brain from various perspectives. The basic experimental findings obtained in this thesis may inspire more clinically oriented experiments aimed at developing pharmaceutical, behavioral, and brain stimulation interventions to induce an impact on the metabolites in the human brain. Such interventions have the potential to mitigate, delay, or alleviate the adverse effects of aging, contributing to enhanced cognitive and motor well-being in the aging population and an increase in lifespan and health span.

Functional and structural brain connectivity is an emerging area in neuroscience research with tremendous potential for explaining behavior in normal and disordered conditions. In the present project, we will make use of advanced brain imaging techniques to study the microstructural organization of brain white matter by means of Diffusion Weighted Imaging (DWI), in combination with Constrained Spherical Deconvolution to determine structural brain connectivity. Functional Magnetic Resonance Imaging (fMRI) is used to determine functional interactions in the brain. This will enable us to study the mapping between structural and functional brain connectivity and to investigate their role in the control of movement. Age-related alterations in white matter microstructural organization will be investigated in relation to performance on various motor tasks to investigate the role of age-related changes in structural and functional brain connectivity and how these contribute to the deterioration of fine motor control in older adults.