RT Journal Article SR Electronic T1 Contributions of white matter connectivity and BOLD modulation to cognitive aging: A lifespan structure-function association study JF bioRxiv FD Cold Spring Harbor Laboratory SP 620443 DO 10.1101/620443 A1 Christina E. Webb A1 Karen M. Rodrigue A1 David A. Hoagey A1 Chris M. Foster A1 Kristen M. Kennedy YR 2019 UL http://biorxiv.org/content/early/2019/07/02/620443.abstract AB The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent MRI scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered BOLD modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.