Brain size varies by over 100,000 times - and that's across mammals alone. How does diversity in brain size come about in evolution? Are there any regularities across species, that is, characteristics that are shared by all mammalian brains, whatever their size or the species to which they belong? Conversely, are there characteristics that are particular to some mammalian groups, but not others? What are the rules that govern how brains are built?
Most of our studies apply the Isotropic Fractionator, a non-stereological method developed in the lab in 2005 that allows the fast, simple and reliable determination of numbers of neuronal and non-neuronal cells in any dissectable brain structure, and has been shown to be as reliable as stereology.
Here's Suzana Herculano-Houzel's talk at TEDGlobal 2013 about how the human brain is remarkable - but not special, compared to others:
And here are some of our main findings so far:
Not all brains are created equal
Brain size can no longer be considered a proxy for numbers of neurons in the brain across species, contrary to what has been common practice so far under the assumption that different brains followed the same scaling rules (reviewed in Herculano-Houzel, 2011, 2011, 2012 and Herculano-Houzel et al., 2014). By comparing rodents, more rodents, primates, more primates, insectivores, afrotherians (including the elephant) and artiodactyls, we have been able to infer the ancestral neuronal scaling rules - that is, those that applied to the original mammals - and to deduce the changes that led to how the brain is put together in the different lineages, reviewed here. In contrast, the relationship between brain structure size and number of other cells (glial and endothelial cells) is shared across all orders and brain structures analyzed so far.
The human brain is not special
The human brain is remarkable, yes - but turns out not to be special, at least not in its number of neurons, compared to other primates, and also not in its size, as long as great apes are left out of the comparison (and great apes, by the way, also have just as many neurons as a generic primate of their brain size would have). The usual way to phrase that comparison is by stating that the human brain is larger than expected for its body size. The reasoning here is that if humans are smaller than great apes, then our brain should be smaller than theirs. But the argument can be turned around: If great apes are larger than humans, why don't THEY have larger brains than we do?
The metabolic cost of being human - and how cooking got us here
The human brain costs about 500 kCal per day, which is 20-25% of the energy consumed by the entire body. We have shown, however, that this seemingly extraordinary metabolic cost is actually just the expected amount of calories for the number of neurons in the human brain, given our finding that the metabolic cost of a brain is a simple linear function of its number of neurons, irrespective of brain size, at an average cost of 6 kCal per billion neurons per day.
The large metabolic cost of neurons shines new light on the humans vs. great apes paradox: We propose that great apes cannot afford a brain that is any bigger than it already is, due to a metabolic limitation imposed by their diet, which doesn't offer enough calories to support both a huge body and the huge number of neurons that a larger brain would have. This metabolic limitation must also have applied to our ancestors, who we propose that were also limited by their diet to having about the same number of neurons that modern great apes have. We suggest that the evolution of modern humans, with the very fast increase in brain size in less than 2 million years since Homo erectus, was made possible by the invention of cooking, which made more calories available in less time per day, thus allowing large brains to go from being a major liability to being a major asset, subject to strong positive selection in evolution.
Larger brains for larger bodies?
Larger species tend to have larger brains - though brain size increases at a smaller rate than body size, as power functions of exponents between 0.6 and 1.0 across species of different orders. It is usually assumed that the relationship is due to a requirement of larger bodies for more neurons to operate them. However, we have found that while larger primates do have more neurons in the spinal cord, the rate at which these neurons become more numerous is small, with an exponent of only 0.3. Likewise, the number of facial motor neurons increases very slowly with body size, with an exponent of only 0.2, across marsupials and primates alike. In the crocodile, which has continued growth through life, the increase in body mass is similarly accompanied by only a very small rate of increase in brain mass. These findings, together with the very small number of neurons found in the spinal cord and brainstem in comparison to the brain, suggest that while larger bodies do tend to require more neurons, the pressure for more neurons is very small and explains only a small part of the increase in brain mass or number of neurons across species. Hence our proposition that body mass is actually not that relevant and should not be used as a normalizing parameter in comparative studies.
Dogmas that are no more
Examining some of the most basic issues in neuroanatomy have allowed us to overthrow dogmas that have been repeated in textbooks and in the news far too often, with no experimental basis until then:
- The human brain does not have 100 billion neurons (which we believe was meant to be simply an estimate of order of magnitude, and not as an actual count), but an average of 86 billion neurons;
- there are not 10 times more glial cells than neurons in the human brain, but at most 1 glial cell to every neuron in the whole brain;
- The ratio of glial cells to neurons does not increase with brain size, but rather with decreasing neuronal density (and thus presumably with increasing average neuronal size);
- The percentage of neurons in the cerebral cortex that are connected through the white matter, which had been considered to be constant across species, actually decreases across primate species of increasing brain size (but does remain fairly stable across rodents of larger brain size);
- The number of neurons underneath a mm2 of cortical surface is not uniform across primate nor rodent species, nor across the surface of a single cortex, be it mouse or human;
- As a consequence, the number of neurons in the cortex of a species is not a simple function of its surface area, and the degree of gyrification is neither a function of number of neurons nor of surface area, within the human cerebral cortex or across species. Rather, we propose that cortical folding occurs as the expanding cortex settles into the most stable conformation, that is, the one of least effective free energy, depending simply on the combination of its total surface area and average thickness;
- This means that cortical folding can no longer be considered a means to allow larger numbers of neurons to fit in the cortex, nor the result of expanding numbers of neurons;
- Contrary to the former notion that neurogenesis is over by birth, so that all neurons found in adult cortex are already present at birth, we found that there actually is massive cortical neurogenesis in the rat after birth - and throughout the brain;
- Cortical expansion, which has been equated with "brain evolution", whereby the relative size of the cerebral cortex increases while the relative size of the cerebellum remains fairly constant, is not accompanied by an expansion of the relative number of cortical neurons. Rather, the cerebral cortex and cerebellum gain neurons coordinately across species, humans included, despite the faster increase in cerebral cortical size;
- Primates are not the only species to undergo a faster addition of neurons to the cerebral cortex and cerebellum than to the rest of brain; artiodactyls also show this pattern.
Totally unexpected findings
Once we had enough data on the numbers of neurons and other cells that compose different brains, unexpected findings started to turn out, against our expectations:
- What makes the cerebral cortex fold? It is not increasing numbers of neurons, but deformation that allows it to settle into the (folded) conformation of least effective free energy, depending simply on the combination of total surface area and cortical thickness. Even more unexpected: the variation in the degree of folding behaves in exactly the same way as crumpled sheets of paper. You can reproduce Figure 2 of our Science paper in your own home, with just a stack of office paper and a ruler!
- If larger brains across species of a same order have more neurons, do larger brains across individuals of a same species also have more neurons? As it turns out, not at all - which means that the evolution of species with larger brains cannot be explained simply as the result of selection for individuals that have more neurons and larger brains along a continuum.
- While there is a tremendous amount of variability in neuronal cell size across species and structures, it turns out that the neuronal mass fraction of any brain structure is always close to 2/3, while non-neuronal cells occupy the other 1/3 of the mass of the structure. That's right: this means that if any brain, any brain structure, were passed through a magic sieve that separated neurons to one side and all other cells to the other side, the pile of neurons would always have about 2x the mass of the pile of other cells. This seems to be one of the most basic features of the mammalian brain, and we propose that it results from the very conserved mechanism through which glial cells are added to the tissue.