Age-Related Changes in Frontal Network Structural and Functional Connectivity in Relation to Bimanual Movement Control

Changes in both brain structure and neurophysiological function regulating homotopic as well as heterotopic interhemispheric interactions (IHIs) are assumed to be responsible for the bimanual performance deficits in older adults. However, how the structural and functional networks regulating bimanual performance decline in older adults, as well as the interplay between brain structure and function remain largely unclear. Using a dual-site transcranial magnetic stimulation paradigm, we examined the age-related changes in the interhemispheric effects from the dorsolateral prefrontal cortex and dorsal premotor cortex onto the contralateral primary motor cortex (M1) during the preparation of a complex bimanual coordination task in human. Structural properties of these interactions were assessed with diffusion-based fiber tractography. Compared with young adults, older adults showed performance declines in the more difficult bimanual conditions, less optimal brain white matter (WM) microstructure, and a decreased ability to regulate the interaction between dorsolateral prefrontal cortex and M1. Importantly, we found that WM microstructure, neurophysiological function, and bimanual performance were interrelated in older adults, whereas only the task-related changes in IHI predicted bimanual performance in young adults. These results reflect unique interactions between structure and function in the aging brain, such that declines in WM microstructural organization likely lead to dysfunctional regulation of IHI, ultimately accounting for bimanual performance deficits.