Brain Surface Area Reveals Overlap in Genes, Intelligence, Evolution

“I think it’s a very, very strong work,” says Rachel Brouwer, a neuroscientist at University Medical Center Utrecht in the Netherlands who was not part of the study. The authors pick up which regions of the brain where variability is most explained by genes, but by looking for connections with evolutionary expansion and neurodevelopment, “it is an attempt to link [heritability] to what it actually means in a broader picture,” she says. 

The study’s authors analyzed brain scans captured by MRI from 677 children. The scans let them map the kids’ brains, revealing the layout of their cortical puckers, grooves, and coils. By linking the brains’ features to genetic variations in their sample, the researchers could probe how genes construct the brain during development and through evolution. 

Using image processing tools, the researchers measured the thickness of the cortex and also its surface area. “It’s a measure of if you basically took the cortex and you unfolded it . . . and like, rolled it out like a pizza,” says J. Eric Schmitt, a neurogeneticist at the University of Pennsylvania School of Medicine, and one of the authors of the study. 

The study’s results pointed to the importance of the brain’s surface area in development, which until recently hadn’t received as much attention as total volume or cortical thickness, says Brouwer. 

The researchers also dug into the heritability of these traits by comparing brains in a sample that included a large number of identical and fraternal twins, siblings, and family members. Using correlations to capture the shared fraction of genes based on the family relationship, they could tease out links between genetics and certain features of the brain.  

Surface area and brain structure vary widely in humans and the researchers found that the brain’s total surface area is highly heritable. Genetic factors accounted for 85 percent of the variation, similar to the results of earlier studies. “That’s a huge fraction of the variability. . . . Genes are really, definitely dominant in patterning global surface area,” says Schmitt. 

The scientists also observed that cortical thickness and the brain’s surface area were genetically linked in these kids, contrary to earlier findings in adults that were “interpreted to mean that different genetic factors underlie the development of surface area versus cortical thickness,” says John Gilmore, a psychiatrist at University of North Carolina, Chapel Hill, who was not involved with this work. Previously, Gilmore, Schmitt, and colleagues showed a genetic coupling of cortical thickness and surface area in newborns in a study that inspired this project. 

“If we can find out what are the actual genes that cause this coupling . . .  and why it starts to grow apart when people get older, that would really help in our understanding of the developing brain,” says Brouwer.

Yes, this looks like an important effect . . . [but] if you have a larger or smaller surface area, what does that really mean with reference to IQ?

—David Glahn, Boston Children’s Hospital and Harvard University

The authors also zoomed in on regional differences in the brain. After chopping up the virtual brain surface into roughly 80,000 tiny triangles, they could compare surface areas in different regions of the brain across the study’s subjects. Merging these data with genetic information let the researchers see to what extent variations were connected to heredity at each point. When the scientists accounted for variations in total surface area, their analysis revealed where in the brain surface area was most related to an overall, or global, genetic factor. 

These regions that were most influenced by heredity—large swaths of the frontal and temporal cortex, which are important in language processing and intelligence—overlapped strongly with parts of the brain that expanded during human evolution. These are the areas that are the most different from nonhuman primates, as discovered by other studies. “That led us to hypothesize that perhaps there’s a shared genetic factor that’s influencing all these regions that are evolutionarily novel,” says Schmitt.

These regions are also the ones that change the most rapidly during childhood, which “suggests that maybe some of the genes that cause individual differences within human beings may be the ones that also evolved over time,” says Schmitt. “I find that very interesting. I want to know what genes those are.” This study doesn’t pinpoint the actual genes that control the variations in brain surface area. To find those genes would require an even larger sample size, he says. 

By analyzing their genetically descriptive brain maps alongside results from IQ tests they administered to the kids, the researchers could tease out which areas of the cortex tied to a higher performance on the test may be linked to heredity. 

Their results highlighted a few areas, but one region of the brain really stood out as linking these threads—the supramarginal gyrus on the left side of the brain. “That’s the receptive language center of the brain in almost everybody,” explains Schmitt. The correlations are almost one, basically as high as they can get, which means there’s almost perfect genetic overlap between IQ and surface area in that spot, he says. 

It’s not the first study looking for correlations with intelligence, and Schmitt says that while IQ is a useful and fairly reproducible metric, it’s not a direct measure of intelligence. Even still, “seeing such a strong effect is pretty rare. . . . It’s is a little bit of the holy grail of neuroscience,” he says.

The results are interesting in part because there hasn’t been much work on how surface area relates to intelligence, says Brouwer.  Here, “most of the effects seem to be pretty global, so that means there is some global genetic factor that is good for your brain and your intelligence, for example,” she says. 

Although generally positive about the study’s methods and findings, David Glahn, a psychologist at Boston Children’s Hospital and Harvard University, is skeptical of how important the results regarding intelligence really are. “Yes, this looks like an important effect . . . [but] if you have a larger or smaller surface area, what does that really mean with reference to IQ? Are we talking two-to-three point difference? Or are we talking ten point difference?” he says. It makes sense that the authors see a relationship between the brains’ anatomy and intelligence, but while many papers have also reported such relationships, others haven’t, and the effects observed in adults aren’t very strong, he says. 

Schmitt acknowledges that the underpinnings of intelligence is a sensitive subject in neuroscience but feels comfortable surveying it through population-level studies. It’s also a question he finds fascinating. 

“What drives cognitive skills in humans is, I think, one of the fundamental questions that we have in neuroscience and it’s actually one of the things that got me interested in neuroscience in the first place. Why do we have this thing that sucks up a huge amount of our energy? It’s got to be doing something for us,” says Schmitt. 

J.E. Schmitt et al., “A comprehensive quantitative genetic analysis of cerebral surface area in youth,” J Neurosci, doi:10.1523/JNEUROSCI.2248-18.2019, 2019.