Elucidation of the neuroanatomical basis of fine motor function across lifespan

Abstract

Fine motor function, the coordinated use of a large number of relatively small arm and hand muscles, is indispensable for performing daily activities and serves as a critical indicator of neurological health. Its decline often accompanies the onset of neurodegenerative diseases like stroke or PD and may even predict cognitive impairment. However, the specific neurobiological pathways linking these together remain poorly understood. A comprehensive understanding requires investigations on how fine motor performance relates to brain structures, white matter health, and disruptions within brain networks that are believed to underpin the parallel decline in both motor and cognitive performances. This critical knowledge gap persists as comprehensive, population-based studies have been lacking. <br /> To address this gap, we used cross-sectional and longitudinal data from the Rhineland Study, a large-scale population-based cohort study. A digital spiral drawing test was utilized to evaluate fine motor skills from three aspects: tracing precision (deviation area), tracing velocity, and frequency of tremor. Brain volumetric and cortical thickness measures were obtained from 3T T1 MRI scans. WMH were obtained from T1, T2 and T2 FLAIR sequences, while white matter integrity was derived from diffusion weighted imaging. Brain functional connectivity was assessed using resting-state functional MRI. Standardized cognitive domain scores were derived from extensive neuropsychological test batteries. <br /> Leveraging data from 8,317 participants of the Rhineland Study, our investigation revealed a multi-faceted relationship between fine motor function and brain health. Firstly, our findings indicate that fine motor function is worse in older adults, and is better in women. Moreover, changes in total brain volume and the thickness of several key motor cortices are robustly related to fine motor function, with the strongest effect for tracing precision. Second, our findings indicate that while a larger WMH burden is associated with worse fine motor control, also changes in the NAWM microstructural integrity of motor and association fibers affect fine motor function. Finally, our findings indicate that fine motor function measured by digital spiral drawing test provides a sensitive, non-invasive and easily administered marker of early cognitive decline and functional brain network disruption, which could be leveraged to identify individuals at increased risk of neurodegenerative diseases. <br /> In summary, this thesis investigated the neuroanatomical basis of fine motor function across lifespan, and explored their associations with cognitive function, using multimodal neuroimaging and large-scale population-based data.