Global comparison between structural and functional connectivities. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-51395-6

Different brain regions are connected by—and interact through—networks of neurons. But the extent to which neuronal wiring drives shared function between these different regions is not well understood. Is this structure-function relationship the same throughout the brain? The same across functions?

Yale researchers have now found that this relationship is variable, which they reported recently in Nature Communications.

For the study, the researchers pulled both structural and functional brain data from large data repositories and calculated how well the coactivation of different brain regions (function) could be explained by the neurons that directly connected them (structure). They evaluated this across brain regions and more than 300 brain functions.

“We found that this relationship exists on a gradient,” said lead author Evan Collins, who is now a graduate student at MIT but who conducted the research as an undergraduate in the Yale Neuroscience Neuroanalytics research group directed by Dennis Spencer and Hitten Zaveri.

“The relationship between structure and function was stronger in the primary sensory and motor cortical areas and for perceptual and motor functions,” Collins said. “It was weakest in the association cortex for complex cognitive functions. Moreover, the way in which humans discern meaning from words mirrors this neural gradient, revealing how our language informs us about our brain organization.”

The evolution of the human brain may help explain this gradient. One possible reason is that while direct connections between brain regions were sufficient for such faculties as vision and movement, as the brain developed more advanced capabilities, like complex cognition, these direct connections had maxed out their usefulness.

“It’s possible that the brain developed more indirect connections between regions in order to establish new, more advanced abilities,” said Zaveri, co-senior author of the study and associate professor of neurology at Yale School of Medicine.