Prefronto-Striatal Structural Connectivity Mediates Adult Age Differences in Action Selection.

In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.

Fiber-specific variations in anterior transcallosal white matter structure contribute to age-related differences in motor performance.

Age-related differences in bimanual motor performance have been extensively documented, but their underlying neural mechanisms remain less clear. Studies applying diffusion MRI in the aging population have revealed evidence for age-related white matter variations in the corpus callosum (CC) which are related to bimanual motor performance. However, the diffusion tensor model used in those studies is confounded by partial volume effects in voxels with complex fiber geometries which are present in up to 90% of white matter voxels, including the bilateral projections of the CC. A recently developed whole-brain analysis framework, known as fixel-based analysis (FBA), enables comprehensive statistical analyses of white matter quantitative measures in the presence of such complex fiber geometries. To investigate the contribution of age-related fiber-specific white matter variations to age-related differences in bimanual performance, a cross-sectional lifespan sample of healthy human adults (N â€‹= â€‹95; 20-75 years of age) performed a bimanual tracking task. Furthermore, diffusion MRI data were acquired and the FBA metrics associated with fiber density, cross-section, and combined fiber density and cross-section were estimated. Whole-brain FBA revealed significant negative associations between age and fiber density, cross-section, and combined metrics of multiple white matter tracts, including the bilateral projections of the CC, indicative of white matter micro- and macrostructural degradation with age. More importantly, mediation analyses demonstrated that age-related variations in the combined (fiber density and cross-section) metric of the genu, but not splenium, of the CC contributed to the observed age-related differences in bimanual coordination performance. These findings highlight the contribution of variations in interhemispheric communication between prefrontal (non-motor) cortices to age-related differences in motor performance.