Scientists have shed new light on how our brains developed differently from those of other primates and gave rise to human culture, language and tool use, discovering that the cerebellum may have played a greater role in the evolution of the human brain than previously thought.

For the study, published Thursday in PLOS Genetics, researchers looked at the roles of the cerebellum and the prefrontal cortex in our brain's evolution by comparing epigenetic differences in brain tissue from humans, chimpanzees and rhesus macaque monkeys. "It's pretty obvious that humans are different from other species in terms of cognition, but we really don't know the biological, neurochemical basis for that," Elaine Guevara, an assistant research professor at Duke University and the study's lead author, told The Academic Times. 

The prefrontal cortex is the "usual subject" when it comes to studying human brain evolution and what makes us stand out in the animal kingdom, Guevara said. The region of the brain directly behind the forehead, it is conspicuously large in humans and plays an important role in controlling behavior. Neuroscientists have long debated whether our special cognitive abilities are attributable to longer prefrontal cortex development periods in humans relative to other primates, though recent research suggests that human brain circuitry matures much like that of chimpanzees and macaques. 

Evidence increasingly suggests that the cerebellum — an area of the hindbrain that, while most closely linked to motor function, also has powerful processing capabilities — could also help coordinate complex behavior in humans. 

"The cerebral cortex is the big, fancy part of the brain in humans and it's where the language centers are," Guevara said. "But these parts of the brain also interconnect with the cerebellum, which seems to be doing some heavy lifting on processing information and allowing humans to automate complex behaviors. If you think about the really complex things we learn to do in a given culture during our long development period that become second nature or muscle memory — tool use, writing, playing an instrument, riding a bike — they require a lot of learning but become very easy for us."

The researchers examined postmortem brains of seven humans, seven rhesus macaques and eight chimpanzees, selecting a mix of relatively young and older adult subjects from each species. Specifically, they examined tissue samples from the cerebellum and the prefrontal cortex, looking for unique patterns of methylation. Methylation is a chemical modification to DNA that does not change the underlying genetic code but can reflect whether a gene is turned on or off, providing researchers with a telltale sign of epigenetic differences, including those between species.

"Methylation is a really great source of information about development," Guevara said. "It's really crucial in development and can really reflect species-specific developmental programs. All our cells have the same genome, but it's the differences in which genes are turned on that make our liver, for example, different from our eye. That's established during development, and methylation kind of records that. 

"We found more places in the genome that showed a unique pattern of methylation in the human cerebellum than in the prefrontal cortex," she continued. "Even though [the cerebellum] has a conserved role across many species, in human evolution, it may have been co-opted to receive a lot of input from the cerebral cortex to process all that information in order to support the execution of really complex behavior that we see in humans — including culture and learned behavior."

Therein may lie the answer to one of neuroscience's biggest questions: What sets us apart from other primates? How did we come to build the Louvre and the Library of Congress, while our closest relatives stayed in the trees? Guevara believes that our sharing of cultural knowledge across generations could be part of what has distinguished us. We have the longest lifespans of any primate, with our life expectancy even in preindustrial times estimated to have been twice as high as that of today's apes, giving us more time to learn and teach others. "That's one hypothesis: Our species just lives long enough to accumulate a lot of knowledge and pass it down," she said. 

The new study adds a piece to the puzzle as the field of neuroscience enters a new stage: Rather than studying regions in isolation, researchers can build more complex models that more accurately reflect the brain's connectivity. The research team's next steps will involve examining molecular differences between more regions of the brain and across a wider variety of primate species. "It's one small step at a time, but it's starting to contribute to an emerging picture of what combinations of things set the human brain apart," Guevara said. "We're really excited about what's coming." 

The study, "Comparative analysis reveals distinctive epigenetic features of the human cerebellum," published May 6 in PLOS Genetics, was authored by Elaine E. Guevara, Duke University and The George Washington University; William D. Hopkins, University of Texas MD Anderson Cancer Center; Patrick R. Hof, Icahn School of Medicine at Mount Sinai and New York Consortium in Evolutionary Biology; John J. Ely, MAEBIOS; and Brenda J. Bradley and Chet C. Sherwood, The George Washington University.