Age-related differences in response inhibition are mediated by frontoparietal white matter but not functional activity

According to the cortical disconnection hypothesis, age-related changes in white matter may disrupt neural communication, which in turn can impair behavioral performance, including response inhibition and processing speed. In addition, older adults sometimes over-recruit regions of the frontoparietal network as measured using fMRI. To determine whether frontoparietal over-recruitment compensates for white matter dysconnectivity in aging, 145 healthy adults (18-86 years old) underwent a diffusion-weighted imaging scan and completed a response inhibition task (Go/No-go) in the fMRI scanner. Older adults and female participants were slower but equally as accurate compared to younger adults and male participants, respectively. We observed differential frontoparietal recruitment across the cerebral hemispheres, with increasing activity in the right hemisphere in older age. Moreover, frontoparietal white matter mediated the association between age and processing speed (Go reaction times), but not between age and inhibition (No-go accuracy). These results add to the literature on age-related frontoparietal over-recruitment in the domain of response inhibition and suggest that cortical disconnection is an underlying driver of selective age-related differences in behavioral performance.