As I said a few years ago, I have been persuaded by Suzana Herculano-Houzel's argument that the number and distribution of neurons in our brain largely explain why we have become the dominant animal on planet Earth (Herculano-Houzel 2016). The brain is the organ that organizes our thinking and our behavior. Of the three main components of the brain--neurons, glial cells, and vasculature--neurons are the functional units that integrate synaptic activity and then pass it on. We can infer, therefore, she argues, that the ultimate causes for the flexibility and complexity of cognition and behavior arise from the numbers of neurons in well-defined circuits in the brain.
But now, after reading Alain Goriely's recent article in Brain (2025) criticizing Herculano-Houzel's claim that she has correctly counted the number of neurons in the human brain, I have been reconsidering her whole argument.
Let's begin by reexamining the techniques for counting neurons in the brain.
THE ANSWER IS IN THE BRAIN SOUP
How many neurons are in the human brain? For many years, the answer from many scientists was 100 billion. But, surprisingly, when Herculano-Houzel began some years ago looking for the original scientific research that provided evidence for this number, she found nothing. She discovered that neuroscientists had repeated this number over and over again without realizing that there was no scientific verification for it (Bartheld, Bahney, and Herculano-Houzel 2016).
Moreover, she discovered that scientists had no reliable method for counting brain cells. The most common method for attempting to do this was stereology: virtual three-dimensional probes are placed throughout thin slices of brain tissue from some part of the brain, then the number of cells within the probes are counted, and finally this is extrapolated to the total number of cells in the entire tissue volume. The problem is that this works only for tissues with a relatively homogeneous distribution of cells. In fact, the highly variable density of neurons across different structures of the brain, and even within a single structure, makes stereology impractical for counting the cells in whole brains.
Herculano-Houzel developed a new technique for counting neurons that starts with creating brain soup. She dissects the brain into its anatomically distinct parts--such as the cerebral cortex, the cerebellum, and the olfactory bulbs. She then slices and dices each part into smaller portions. Next, she puts each small part in a tube and uses a detergent that dissolves the cell membranes but leaves the cell nuclei intact. By sliding a piston up and down in the tube, she homogenizes this brain tissue into a soup in which the nuclei are evenly distributed. She stains all the cell nuclei blue so that she can count them under a fluorescent microscope. She then adds an antibody labeled red that binds specifically to a protein expressed in all neuronal cell nuclei, which distinguishes them from other cell nuclei such as glial cells. Going back to the microscope, she can then determine what percentage of all nuclei (stained blue) belong to neurons (now stained red). Finally, she can estimate the number of neurons for each structure of the brain. She has done this in studying the brains of many mammalian animals.
Now she can tell us that the total number of neurons in the whole human brain is not 100 billion but about 86 billion. Of that total, about 16 billion are in the cerebral cortex, which includes about 1.3 billion neurons in the prefrontal cortex. The cerebral cortex is the outer covering of the surfaces of the cerebral hemispheres. The prefrontal cortex covers the front part of the frontal lobe of the cerebral cortex located behind the forehead.
Other animals with larger brains--like elephants, whales, and dolphins--have larger brains with more neurons. But what makes the human brain unique is the large number of neurons in the cerebral cortex, which is the part of the brain responsible for the highest levels of cognition--such as self-consciousness, abstract thinking, social engagement, language, memory, and emotion.
8 BILLION HUMAN BRAINS AND NO TWO ARE THE SAME
Notice that in stating the numbers of neurons, the numbers are qualified by the word "about." That points to the problem identified by Goriely, a mathematician at Oxford University who has noted that if you look at the research of Herculano-Houzel and her colleagues, you will see that the average numbers they give are only rough estimates with a wide range of variation based on a small sample of human brains.
There are two main papers--Von Bartheld et al. (2009) and Andrade-Moraes et al. (2013). The 2009 paper reports an analysis of the brains from four deceased males aged 50, 51, 54, and 71, who had no cognitive impairment when they died. The authors declare that the adult male brain contains an average of 86 billion neurons. But if you look at the numbers for the four brains, you will see that 86 billion is the average of 78.82, 79.72, 90.30, and 95.40 billion. This is a wide range--from 79 billion to 95 billion--and it's based on only four data points.
The 2013 paper reports a counting of the neurons in the brains of five elderly females--between the ages of 71 and 84--who died of non-neurological causes. The numbers for these five brains were 62.1, 63.3, 67.3, 72, and 72.06 billion. This is a wide range, and it's well below the range for the 2009 paper. The average for these women was 67 billion, as opposed to 86 billion for the men.
Goriely suggests that the only statements we can make about these two studies are rather weak:
(i) Experiments have shown variations between 62 and 94 bn neurons in the human brain (n = 9).
(ii) An experimental study on the number of neurons suggests an average between 73 and 99 bn neurons in the healthy male brain (n = 4).
(iii) An experimental study on the number of neurons suggests an average between 61 and 73 bn neurons in the healthy female human brain (n = 5).
Clearly, none of these statements is satisfactory or as catchy as "the human brain has 86 billion neurons" (Goriely 2025, 691).
In a response to Goriely, Christopher von Bartheld (2025) has conceded that, of course, it would be absurd to say that all human brains contain exactly 86 billion neurons. About 8 billion human brains are currently operating in the world today, and because of the biological variability of those individuals, no two brains are exactly alike. But it is still justifiable to look for rough estimates and approximate ranges for the number of neurons in the human brain.
We can expect that the number of neurons in different brains will vary according to the effects of gender, age, brain mass, and variation in life history. For example, people with Down syndrome are thought to have perhaps 40% fewer neurons than a normal brain. People with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and Huntington's disease have fewer neurons in some part of the brain. Malnutrition both in utero and after birth can impede the growth of neurons. Some of the women in the 2013 study were born in World War II or shortly thereafter, and it's possible that they suffered from the malnutrition caused by the war. That or other factors related to their life history might explain why the five women had a lower average number of neurons than the four men.
Actually, the brains of the five women in the 2013 study were used as "controls" in comparison with the brains of five other women with dementia from Alzheimer's disease, and with four women with the neural plaques and neurofibrillary tangles associated with Alzheimer's but without dementia. The study concluded that the five women with dementia had suffered a loss of neurons, while the other nine women had not shown any dementia from loss of neurons.
For a long time it was assumed that dementia and severe mental decline were the inevitable consequence of a normal process of aging with the loss of neurons. What this and other studies have shown is that loss of neurons is not part of the normal aging process, and therefore the neurogenerative diseases of the elderly come from an abnormal loss of neurons.
Hey, this is great news for us old folks--the rotting of our brains is not an unavoidable consequence of our aging!
So what does all of this mean for assessing Herculano-Houzel's argument? This does not refute her claim that she can estimate the number of neurons in human brains. But this does suggest that she needs to qualify her claim by stressing that these numbers are only rough estimates within wide ranges created by the biological variability in individual brains.
I would add that she needs to make a second qualification that has not been brought up by critics like Goriely: although the sheer number of neurons in the human brain is surely a critical factor in explaining the power of the human brain, we also need to recognize the importance of the structural organization of those neurons into complex circuits. Actually, Herculano-Houzel and her colleagues point to this when they stress the importance of how those 86 billion neurons are organized in the human brain, and particularly having 16 billion neurons organized into the circuitry of the neocortex, of which 1.3 billion are in the prefrontal cortex, a structural organization that is unique to the human brain.
At this point, many of you are thinking of questions that I haven't answered. What about those huge cetacean brains? And what about those really smart bird brains that don't even have a cerebral cortex? I'll take up those questions in my next posts.
REFERENCES
Andrade-Moraes, Carlos Humberto, et al. 2013. "Cell Number Changes in Alzheimer's Disease Relate to Dementia, Not to Plaques and Tangles." Brain 136: 3738-3752.
Azevedo, Frederico A. C., et al. 2009. "Equal Numbers of Neuronal and Nonneural Cells Make the Human Brain an Isometrically Scaled-Up Primate Brain." The Journal of Comparative Neurology 513: 532-541.
Goriely, Alain. 2025. "Eighty-Six Billion and Counting: Do We Know the Number of Neurons in the Human Brain?" Brain 148: 689-691.
Herculano-Houzel, Suzana. 2016. The Human Advantage: A New Understanding of How Our Brain Became Remarkable. Cambridge: MIT Press.
von Bartheld, Christopher S. 2025. "Understanding and Misunderstanding Cell Counts of the Human Brain: The Crux of Biological Variation." Brain 148: e72-e74.
von Bartheld, Christopher, Jami Bahney, and Suzana Herculano-Houzel. 2016. "The Search for True Numbers of Neurons and Glial Cells in the Human Brain: A Review of 150 Years of Cell Counting." The Journal of Comparative Neurology 524: 3865-3895.
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