What's so special about the human brain?

There must be something about the human brain that’s different from the brains of other animals — something that enables humans to plan, imagine the future, solve crossword puzzles, tell sarcastic jokes and do the many other things that together make our species unique. And something that explains why humans get devastating conditions that other animals don’t — such as bipolar disorder and schizophrenia.

So, what is that
something?

Illustration of two halves of a human brain made of of different textures.

In the past few years, new methods for studying the human brain — and those of other species — have started to reveal key differences in greater detail than ever before.

Researchers can now snoop on what happens inside millions of brain cells by cataloguing the genes, RNA and proteins they produce. And by studying brain tissue, scientists are learning key lessons about how the organ develops and functions.

One is that the differences between human brain cells and those of other species are often subtle. Another is that the human brain develops slowly compared with other animals. But how these features give rise to our cognitive skills is still a mystery — although researchers have plenty of promising leads.

Illustration of a human figure, chimpanzee and macaque.

Size matters

If there is one thing that stands out about the human brain compared with those of other primates — and even those of some extinct human relatives — it is its size.

A series of graphics that shows the relative sizes of two extinct human species and then the gorilla compared with a modern human brain.

A graphic that shows the comparative sizes of the brains of the mouse, a macaque monkey, a chimpanzee, a human and an African elephant.

A graphic that shows the comparative sizes of the brains of the mouse, a macaque monkey, a chimpanzee, a human and an African elephant, scaled by encephalization quotient.

A series of graphics that shows the comparative sized of the chimpanzee and human cortex, cerebellum and prefrontal cortex.

The human brain is up to three times larger in volume than the brains of chimpanzees, gorillas and many extinct human relatives.

Brain size is tightly correlated with body size in most animals. But humans break the mould. Our brains are much larger than expected given our body size.

Here are some animals’ brains ranked according to size.

Researchers often use a ratio called the encephalization quotient (EQ) to get an idea of how much larger or smaller an animal’s brain is compared with what would be expected given its body size. The EQ is 1.0 if the brain to body mass ratio meets expectations.

Here are their brains scaled according to their EQ, with the actual brain sizes represented by dotted lines. The mouse brain is half as big as expected for its body size. The human brain is more than seven times the expected size.

Although evolution has enlarged the human brain, it hasn’t done so uniformly: some brain areas have ballooned more than others.

One particularly enlarged region is the cortex, an area that carries out planning, reasoning, language and many other behaviours that humans excel at.

Other areas, such as the cerebellum — an area at the back of the brain that is densely populated with neurons, and which helps to conduct movement and planning — have expanded too.

The prefrontal cortex has a similar structure in both chimps and humans, although it takes up much more real estate in the human brain than in the chimp brain.

There is also a big difference between the number of neurons in the human brain compared with those of other animals. The human brain has about 1,000 times more neurons than the mouse brain, for instance, and 13.5 times more than the macaque¹..

But brain size and neuron number aren’t everything; some animals whose brains look and develop differently to mammals — such as ravens and other members of the crow family — can learn or remember impressively. “Brain size alone can’t explain human cognition,” says Chet Sherwood, an anthropologist and neuroscientist at The George Washington University in Washington DC.

Sources: *Brain outlines*: C. C. Sherwood & M. Schumacher (2018); A. M. M. Sousa *et al*. (2017). Brain weights: G. Tartarelli & M. Bisconti (2006). *Brain EQ*: G. Roth & U. Dicke (2005). *Chimpanzee and human*: C. C. Sherwood & M. Schumacher (2018). *Neuron numbers*: Ref. 1; S. Herculano-Houzel (2014); S. Olkowicz *et al*. (2016).

Sources: *Brain outlines*: C. C. Sherwood & M. Schumacher (2018); A. M. M. Sousa *et al*. (2017). Brain weights: G. Tartarelli & M. Bisconti (2006). *Brain EQ*: G. Roth & U. Dicke (2005). *Chimpanzee and human*: C. C. Sherwood & M. Schumacher (2018). *Neuron numbers*: Ref. 1; S. Herculano-Houzel (2014); S. Olkowicz *et al*. (2016).

Special recipe

Looking at brain cells closely has shown some interesting patterns. Over the past five years, techniques that enable scientists to catalogue the genes expressed in a single cell have been revealing the many different types of cell that make up a brain — at a level of detail much higher than anything achieved before.

Last year, a team based at the Allen Institute for Brain Science in Seattle, Washington, reported the most-comprehensive atlases yet of cell types in both the mouse and human brain. As part of an international effort called the BRAIN Initiative Cell Census Network (BICCN), researchers catalogued the whole mouse brain, finding 5,300 cell types²; the human atlas is unfinished but so far includes more than 3,300 types from 100 locations³; researchers expect to find many more.

Some regions do have distinct cell types — for instance, the human visual cortex contained several types of neuron that were exclusive to that area⁴. But in general, human-specific cell types are rare.

The overall impression, when comparing the cell types of the human brain with other species, is one of similarity. “I was expecting bigger differences,” says Ed Lein, a neuroscientist at the Allen Institute, who is involved in efforts to catalogue cells in human, mouse and other brains. “The basic cellular architecture is remarkably conserved until you get down to the finer details”, he says.

Most human brain regions differ from primates and mice in the relative proportions of cell types that appear⁵, and in the ways those cells express their genes: it's not the ingredients that are different, but the recipe.

Take these two comparable regions of the human and mouse cortex, which both process auditory information. The mouse area contains a higher proportion of excitatory neurons, which propagate signals, relative to inhibitory neurons, which dampen activity. The human region had a much greater proportion of non-neuronal cells, such as astrocytes, oligodendrocytes and microglia. These cells support neurons and also help to prune and refine their connections during development. The ratio of these cells to neurons was five times that of mice.

The upshot of the differences still isn’t clear, but the atlases provide a way to study these cells and the genes they express, to better understand their function.

A graphic that compares the shape and density of a neuron in the mouse, chimpanzee and human brain, showing that the human’s are more densely packed and more complex, with more connections.

The same cell types can also look different in different species. This is the same type of neuron — a pyramidal cell — from the cortex of a mouse, chimp and human. The mouse brain has fewer of these cells and they are less well connected compared with the human brain⁶.

Even compared with the chimp, the human neurons are longer and make more connections with each other. The cortical layers they live in are thicker than those of the chimp.

Source: Ref. 6

Making connections

No neuron is an island, and the networks they form could be a huge part of what gives various brains their different functions and specialisms.

A graphic that shows the results of a study that compared the density of interneurons in the brains of mice and humans. Humans were shown to be denser and contain more bipolar interneurons.

One study compared 1.6 million connections between more than 2,000 total brain cells in mouse, macaque and human brain samples taken from the cortex. The human wiring diagram, or ‘connectome’, had 2.5 times more interneurons — a class of cells that dampen neural activity and control excitation, shown here in two colours — than did the mouse, and those cells made ten times more connections between themselves⁷..

A specialized group of interneurons with a preference for connecting to others of the same type (bipolar neurons, in green) were rare in mice but have expanded to be more than half the population in humans. A second class of interneurons, called multipolar neurons, did not expand to the same extent.

Source: Ref. 7; M. Sievers et al. (2024)

The finding was “super surprising”, says study leader Moritz Helmstaedter at the Max Planck Institute for Brain Research in Frankfurt, Germany. He thinks that this expanded network of interneurons might help to solve one major problem in the human brain: neurons operate quickly but thoughts and actions take seconds. Larger networks of interneurons could prolong neuronal activity, allowing the brain to generate more complex thoughts and keep things ‘in mind’ for longer.

The team is now looking at larger segments of the human cortex.

The results of Helmstaedter's connectome study are supported by genetic work. When comparing gene expression across species, many differences turn out to be related to how the connections between neurons — called synapses — connect with and signal to each other.

In a study⁸ led by researchers at the Allen Institute, a few hundred genes showed expression patterns unique to humans. Often, these specializations were related to circuit function — they were involved in synapse-building or signalling. And they were often seen in non-neuronal cells, such as astrocytes and microglia.

Slow to develop

Some scientists think that there is one key pedal that has been pressed in the human brain that can explain many of the differences between us and other species. The brake.

“Whatever you look at, it’s happening more slowly in humans,” says neuroscientist Madeline Lancaster, who studies human brain development at the MRC Laboratory of Molecular Biology in Cambridge, UK.

A bar chart that shows the pace of brain development of the brains of the mouse, macaque monkey, chimpanzee and human. The human brain takes a lot longer to develop, almost half the lifespan.

The pace of brain development varies a lot across species, but it’s incredibly protracted in humans. The mouse brain, for instance, is fully developed just 5% of the way into the animal’s lifespan.

Macaque and chimp brains are fully developed about one-third of the way into theirs.

Human brains take much longer to grow, mature and refine their connections — about 30 years, or almost half our average lifespan.

Source: Ref. 6

This sluggish pace could help humans to grow more neurons, and foster more diversity and complexity. It also gives the brain more time to be shaped by its environment. Research suggests that, in humans, neural progenitors, the cells that give rise to neurons, spend longer in a limbo state before assuming their final identities⁹. Human progenitors also have more potential — they can become more than one broad type of neuron, whereas in rodents one type of progenitor tends to develop into just one type of neuron¹⁰.

A graphic that shows the neuronal development timeline for chimps and humans, showing the human take longer, producing more complex neurons with more synapses.

Here is a typical timeline for chimp neurons — they develop from progenitors, they grow axons and dendrites to reach out to other cells, those outgrowths develop synapses to connect to each other and send signals, and finally they develop a layer of myelin, which insulates neurons and helps signals to travel⁶.

The same process in humans takes longer and results in neurons that grow more dendrites, each with more connections. Axons can be longer than those of chimps because they have further to travel, and the resulting neurons are more complex.

Several gene variants have been linked to this slowdown and elaboration. One is a gene duplication seen only in humans; when mice were engineered to have the same duplication, they grew more synapses and their learning improved¹¹.

Another example is a change in the sequence that codes for a protein called NOTCH, which has been linked to the expansion of the cortex. This change allows human neurons to spend longer proliferating — giving rise to a larger pool of new neurons — than those of non-human primates¹²^,¹³.

Source: Ref. 6

Although some changes to genes and cells undoubtedly make us who we are, it's too early to leap to any conclusions, says Alex Pollen, a geneticist who studies human brain evolution at the University of California San Francisco. Some changes could just be side effects of other adaptations — for example, an increase in certain types of neuron so that brain regions could still communicate when the brain expanded.

There are downsides, too, to our special abilities. Sherwood says that humans undergo more drastic changes than other primates, such as a shrinkage of the cortex, owing to ageing — in part because we live so much longer. But even the oldest great ape brains don’t seem to change as much as human brains do with age, he says. And some conditions that seem specific to humans could be the price we pay for complexity, says Lancaster. “Even a small defect could have more dramatic consequences,” she says.

There’s plenty more to discover about how our brains make us so talkative, sociable and intelligent. Scientists are interested in how gene variants act on neurons and the brain; how neural activity during development influences growth; and how parts of the brain other than the cortex might have changed to endow humans with our unique skills.

The confluence of technologies has energized researchers to look afresh at a classic question, says Lancaster. “I feel lucky to be doing science at this moment.”