Neuronal Connectivity, Brain Size, & Gender

An article was published just this month in Frontiers by Hänggi et al. titled, “The hypothesis of neuronal interconnectivity as a function of brain size– A general organization principle of the human connectome.” What the team found, in a nutshell, is that the ratio of  interhemispheric (i.e., corpus callosum) versus intrahemispheric (arcuate fibers, fasciculi, etc.) correlates inversely with brain size in humans. Or, to put it more plainly, the larger the brain size, the smaller relative size of the large fiber tracts that connect the two hemispheres.


The team took 138 subjects (69 male, 69 female), with mean age around the mid-20s, no history of neurological, psychiatric, or psychological disorders or drug abuse. The subjects were then divided into two groups using a median split on the measurement of total brain volume (TBV) (small TBV = 55 women, 14 men; large TBV = 55 men, 14 women). Structural MRIs were performed on each subject. These were then subdivided into two separate measures: gray matter (GM) and white matter (WM) volumes.

Ultimately, they also found that intrahemispheric connections shared a strongly positive relationship with TBV (r = 0.765). Although, they did find that interhemispheric WM volumes did modestly increase with TBV, this was small compared to the intrahemispheric WM volumes (r = 0.299).

One of the more interesting findings was were based on sex differences, although they weren’t particularly emphasized in the manuscript. Women, when analyzed separately, appeared to share the same trends as the whole group analysis: large brains linked with massive increase in intrahemispheric connectivity and modest increase in interhemispheric WM volumes. However, males, on the other hand, failed to show any differences in interhemispheric WM volumes according the brain size, suggesting some fundamental sexually dimorphic differences in corpus callosal connectivity in men and women. (Since there were only 14 men in the small TBV group, hopefully the study had enough power to address these smaller effect sizes; there was no mention of a power analysis.)


An illustration from Gray’s Anatomy showing many of the intrahemispheric fibers  of the human brain, shown in red.

Though the overall trend of interhemispheric/intrahemispheric connectivity and TBV were inversely related, this only held true for those brains which fell within the intermediate TBV ranges. Meanwhile, those brains that fell at either end of the spectrum, they instead shared a positive relationship with TBV. (The small brains were all female and the large brains were all male.) Unfortunately, the paper doesn’t indicate whether this is due to higher-than-expected volumes of interhemispheric or intrahemispheric WM. I’ve written a comment on the article regarding this, to which hopefully one of the authors will respond.

The authors state that the “universal scaling law between gray (GM) and white matter (WM) of the cerebral cortex postulates a disproportionally faster increase in WM compared with GM within increasing brain size” (p. 1). These findings have been shown across different species, but until now has not been well addressed within the human species itself. Previous research involving macaque monkeys and modeling systems has spurred on this current work:

“Ringo and colleagues designed a brain model based on an artificial network constrained by well-known macaque anatomical connectivity data. This artificial self-organizing neural network was able to optimize its activation pattern during a simulated pattern discrimination task. Using this network with simulated large and small brains together with their associated transcallosal connectivities they trained the network with the pattern discrimination task. After removing the transcallosal connections from this model it turned out that the performance in the small brain model declined stronger and faster than in the large brain model suggesting that interhemispheric connectivity is more important in small compared to large brains. The authors conclude that in larger brains both hemispheres would work more independently from each other due to longer callosal transmission times than both hemispheres of smaller brains. Therefore, interhemispheric connectivity should be strong in smaller brains while larger brains should show relatively increased intrahemispheric connectivity compared with smaller ones” (p. 2)

Aside from the fact that this study is interesting just in and of itself, it also reminds me of some of the findings in autism about big brains, reduced long-range connectivity, and increased local overconnectivity. It begs the question: How much in autism are we seeing that are developmentally “normal” processes given the constraints of the condition itself? Are some of the variations in connectivity in autism truly “pathological”, particularly when we’re dealing with largescale fiber tracts, or are they a normal adaptation in the face of some other dysfunction? Very interesting stuff.

2 responses to “Neuronal Connectivity, Brain Size, & Gender

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