Fluid intelligence, the ability to solve novel, complex problems, declines steeply during healthy human aging. Using fMRI, fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and impairment following focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Center for Ageing and Neuroscience data, a large, population-based cohort of healthy males and females across the adult lifespan. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localize the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodeled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of nonphysical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline.SIGNIFICANCE STATEMENTGlobal populations are living longer, driving urgency to understand age-related cognitive declines. Fluid intelligence is of prime importance because it reflects performance across many domains, and declines especially steeply during healthy aging. Despite consensus that fluid intelligence is associated with particular frontoparietal brain regions, little research has investigated suggestions that under-responsiveness of these regions mediates age-related decline. We replicate a recent demonstration of such mediation, showing specific association with brain regions most activated by cognitive demand, and robustness to moderate confounding by unmodeled variables. By showing that this mediation model is moderated by the variety of regular physical activities, more reliably than by their frequency or duration, we identify a potential modifiable lifestyle factor that may help promote successful aging.

Structural brain organization in infancy is associated with later cognitive, behavioral, and educational outcomes. Due to practical limitations, such as poor in-utero imaging, there is a lack of understanding of the early emergence of topological organization. We combine the developing Human Connectome Project’s large infant dataset with generative network modeling to simulate the emergence of network organization over early development. Preterm infants had reduced connectivity, shorter connection lengths and lower network efficiency compared to term-born infants. The models were able to recapitulate the organizational differences between term and preterm networks and revealed that preterm infant networks are better simulated under tighter wiring constraints than term infants. Tighter constraints for preterm models resulted in shorter connection lengths while preserving vital, long-range rich club connections. These simulations suggest that preterm birth is associated with a renegotiation of the cost/value wiring trade-off that may drive the emergence of different network organization.

Fluid intelligence - the ability to solve novel, complex problems - declines steeply during healthy human aging. Using functional magnetic resonance imaging (fMRI), fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data, a large, population-based, healthy, adult lifespan cohort. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localise the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodelled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of non-physical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline.