Estimating the absolute number of axons connecting different cortical areas in humans with diffusion MRI

A simple method is derived for estimating the absolute number of axons linking cortical areas from a whole-cortex diffusion-MRI (dMRI) connectome. We estimate the conversion factor from dMRI tractography to axons using the histologically-measured callosal fiber density, then allocate axons between regions in proportion to dMRI connectivity. Median connectivity is estimated as ~2,700 axons between cortical areas within-hemisphere and ~540 axons interhemispherically, with axons connecting functionally-related areas surprisingly sparse.

Interhemispheric connectivity endures across species: An allometric exposé on the corpus callosum

Rilling & Insel have argued that in primates, bigger brains have proportionally fewer anatomical interhemispheric connections, leading to reduced functional connectivity between the hemispheres (1). They based this on a comparison between surface areas of the corpus callosum and cortex rather than estimating connection counts, while leaving out other quantities also dependent on brain size such as callosal fiber density, neuron density, and number of functional areas.We use data from the literature to directly estimate connection counts. First, we estimate callosal fiber density as a function of brain size. We validate this by comparing out-of-sample human data to our function’s estimate. We then mine the literature to obtain function estimates for all other quantities, and use them to estimate intra- and interhemispheric white matter connection counts as a function of brain size.The results show a much larger decrease in the scaling of interhemispheric to intrahemispheric connections than previously estimated. However, we hypothesize that raw connection counts are the wrong quantity to be estimating when considering functional connectivity. Instead, we hypothesize that functional connectivity is related to connection counts relative to the number of cortical areas.Accordingly, we estimate inter-area connection counts for intra- and interhemispheric connectivity and find no difference in how they scale with brain size. We find that, on average, an interhemispheric inter-area connection contains 3-8x more connections than an intrahemispheric inter-area connection, regardless of brain size. In doing so, we find that the fiber count of the human corpus callosum has been underestimated by 20%.Significance StatementThere are arguments in the literature that larger brains have proportionally fewer interhemispheric connections. We find that the decrease is even larger than previously estimated. However, we argue that this quantity is the wrong thing to measure: Rather, we should measure functional connectivity between cortical areas. We show that the ratio of interhemispheric and intrahemispheric connectivity between cortical areas is constant across mammalian species. These findings are consistent with a growing literature that suggest interhemispheric connectivity is special across all primate species.