As a teenager, Chet Sherwood, a biological anthropologist at George Washington University, did not know he was destined to become a scientist. “I wasn’t the kind of kid who collected National Geographic or watched Nova,” he says. During the mid-1990s, Sherwood was a member of Speedking, a Brooklyn punk group described by as “an intense post-hardcore band with thrashing guitar, propulsive synths and vocals traded off between all three members.”

His fascination with the subtleties of human brain anatomy—and ultimately how the human organ compares to that of other animals—came after taking undergraduate courses at Columbia University with the eminent physical anthropologist Ralph Holloway, a time when he was still ensconced in the intense rituals of punk. Sherwood later went on to a doctorate with Holloway and co-advisor Patrick Hof from the Mount Sinai School of Medicine.

He now dedicates his time to exploring what qualities make the human brain special. “When I got started, there were extraordinarily few scientists who considered it their main area of research,” he says. “It seemed like a really opportune subject because there’s a lot we still don’t know. You can make significant discoveries by simply putting some elbow grease into it.” Sherwood talked to me about what we’ve learned about the human organ at various scales, from the molecular to the whole brain. The edited transcript follows:

Is there some general statement you can make about the differences between humans and other animals?

The overall size of the human cerebral cortex, for some reason, has become voluminous to an extreme degree. It’s three or four times bigger than one would expect for a primate of our body size

The primary sensory and motor areas, which are important in the initial processing of incoming inputs for vision, touch and hearing and for motor control, increase in size in the human brain in a manner that keeps pace with body size just like you would expect. But in the human cerebral cortex, there is also a lot of extra neural tissue beyond that.

The extra space is made up of association cortex regions, which are involved in sophisticated cognitive operations. Compared to other species, in humans there are more neurons, the computational units, in the association cortex and more connections among these neurons.

What’s happening at the cellular level?

When you look at the cellular and microstructural makeup of a piece of neocortex in humans as compared to other mammals, what you see overall is extraordinary similarity. There are similar types of neurons arranged in a common pattern into layers. However, the subtle differences at the cellular level between humans and other species make sense in terms of Darwinian “descent with modification.” The makeup of our cerebral cortex most closely resembles that of our closest relatives the great apes and then other primates and so forth.

Humans and chimpanzees share high-density innervation for neurotransmitters serotonin, dopamine acetylcholine in the prefrontal cortex. We share with great apes molecular specializations for the elevated expression of excitatory signaling using the neurotransmitter glutamate, and we have related molecular changes in the neocortex to support the production of aerobic energy.

In addition, humans, chimpanzees and other great apes have a higher density of what are called Von Economo neurons in the anterior cingulate cortex and anterior insular cortex. Von Economo neurons have an elongated spindle shape and have very thick axons that allow them to make high-speed output projections to other parts of brain.

In humans and great apes they are concentrated in parts of the cerebral cortex involved with monitoring body states and integrating that information with decisions in the context of social interactions.

There was a story in a popular science magazine about how these are the neurons that makes us human. That’s just wrong. That conveys the idea that there could be a singular magic bullet that you find in the brain that explains what makes us humans.

Von Economo neurons have now been found in elephants and whales as well as many other species. The Von Economo neurons represent a fascinating question in comparative neuroanatomy and we have only just scratched the surface.

Isn’t it true that we often think we’ve found something that appears unique in humans but those findings are later disproved?

Absolutely. The second edition of Darwin’s Descent of Man reflected the big debates at the time that were taking place between Richard Owen and T.H. Huxley about whether there are distinctive parts of the human brain which would allow us to be set apart as a different order of mammals, as humans. That was the argument extended by Owen.

But T.H. Huxley had made careful dissections of human and ape brains and said the differences are more about degree than overall kind. Charles Darwin thought that this was a prime example of gradualism in evolution and so he had T.H. Huxley write an appendix all about comparisons of human brains to ape brains in the second edition of Descent of Man. Huxley concludes that, yes, human brain are large, but what defines them are differences of degree from the ape brain, rather than any unique individual specialization. Huxley was using tools of gross dissection. But even the modern tools of cellular biology and genomics are bearing that observation out today

Doesn’t some of what distinguishes humans relate to the connections among brain cells.

An interesting story is starting to emerge from a number of different labs that what has been most significantly changed in human brain evolution hasn’t been the distribution of different cell types or even necessarily the expression of neurotransmitters but rather the long-range connectivity.

It’s the wiring diagram of connections that seems to be most significantly modified—for example, the arcuate fasciculus which is an important pathway involved in human language. There are not any new, major white-matter tracts in the human brain as compared to other primates [White matter is the insulating material surrounding neurons’ wirelike extensions that relates to how fast signals travel among neurons.] But what has been shown is that human brains have more promiscuous connectivity along pathways that are also present in our close relatives. These pathways in humans reach out and connect more widespread areas. That means that ultimately the information conveyed is taking in a greater dynamic range of inputs and synthesizing them.

What do you mean by dynamic range?

All of the major highways in the brain in humans are in common with great apes and monkeys. But to use an analogy, think of a highway between Washington and Boston. What humans seem to have done is add more on-ramps. In Philadelphia, you can get on to the highway. In New York, you can get on. The traffic that reaches Boston ultimately originates from a greater diversity of sources. In human brains, this might mean that association regions in our cerebral cortex have the potential to integrate and combine information in new ways that are not possible in other primates.

What about differences at the genetic level?

Many of the genetic changes that have been reported show that there have been modification of cell-cycle dynamics that allow for the expansion of neuron proliferation early in life leading to a large brain size. There have also been changes in the molecular machinery that delivers energy to the brain.

How does all of this neuroanatomy connect with the idea that we are a very social species?

I think the answer has to incorporate information about how our brains develop differently than other species. What it is to be human unfolds in stages of development that allow for interactions with other people and the environment, which serve as a scaffold for development of cognition through the use of language.

If you look broadly at human brain development, it takes course over a longer time and more slowly than in other primate species. We’re born with brains relatively underdeveloped. And so they remain plastic and moldable by social and environmental inputs throughout childhood, probably to a greater extent other species including chimpanzees.

Some of this is probably innate, maybe to guide us to spend more time looking at each other in the eyes, to be more tolerant of one another, not to be aggressive to allow for close social interactions in order to sculpt a highly plastic brain into the wonderful diversity found across humans in cultural attributes, in habits, food and music. All of this is really a testament to the plasticity that defines our species through this differing trajectory of brain development

What’s happening physiologically during development?

We know that in humans, there is a continued maturation of white matter in the cerebral cortex, a continued refinement of connections past adolescence that has an impact on thinking. We also know that in humans, there is an improvement in impulse control and decision making past adolescence. This long period of cognitive development might be important for learning very complicated skills. In non-human primates, we know that white matter does not continue to develop past the time of sexual maturity. This suggests that an extended period of maturation of the long-range association connections in the brain is a distinctive aspect of human brain development. .

Something that’s interesting, though, is that understanding what is distinctive about human brain development can also shed light on vulnerability to neurodegenerative and neuropsychiatric disorders. Adolescence is the time of onset of schizophrenia and bipolar disorders, which are characterized by pathologies in white matter.

Image Source: George Washington University