Suzana Herculano-Houzel on cognitive ability and brain size

卢克·穆罕沃斯：你的大部分工作都担心“为什么人类比其他动物更聪明？”在一系列论文中（例如2009那2012), you’ve argued that recent results show that some popular hypotheses are probably wrong. For example, the so-called “overdeveloped” human cerebral cortex contains roughly the percentage of total brain neurons (19%) as do the cerebral cortices of other mammals. Rather, you argue, the human brain may simply be a “linearly scaled-up primate brain”: primate brains seem to have more economical scaling rules than do other mammals, and humans have the largest brain of any primate, and hence the most total neurons.

Your findings were enabled by a new method for neuron quantification developed at your lab, called “isotropic fractionator” (Herculano-Houzel & Lent 2005）。你能描述这种方法如何运作吗？

Suzana Herculano-Houzel：各向同性的分馏器几乎包括将固定的脑组织转化为汤 - 含有自由细胞核的已知体积的汤，这可以很容易地着色（通过染色所有核含有的DNA）并因此在显微镜下可视化和计数。由于大脑中的每个细胞含有一个且只有一个核，因此计数核相当于计数细胞。汤的美丽是它快速（细胞总数可以在几个小时内已知一个小脑，并且在大约一个月内为人类大小的大脑），廉价，非常可靠 - 多或多而不是通常的替代方案，这是立体主义。

体视学,相比之下,包括削减ire brains into a series of very thin slices; processing the slices to allow visualization of the cells (which are otherwise transparent); delineating structures of interest; creating a sampling strategy to account for the heterogeneity in the distribution of cells across brain regions (a problem that is literally dissolved away in the detergent that we use in the isotropic fractionator); acquiring images of these small brain regions to be sampled; and actually counting cells in each of these samples. It is a process that can take a week or more for a single mouse brain. It is more powerful in the sense that spatial information is preserved (while the tissue is necessarily destroyed when turned into soup for our purposes), but on the other hand, it is much more labor-intensive and not appropriate for working on entire brains, because of the heterogeneity across brain parts.

Luke：您自己的工作强调了大脑纯粹的神经元数量的认知能力的重要性。你怎么看待其他最近结果（例如Smaers & Soligo 2013），强调了表观重要性mosaic大脑重组？

Suzana: Mosaic brain organization is a fact. It describes the independent scaling of different parts of the brain across species in evolution, as opposed to every brain part scaling in line with every other part (what Barbara Finlay describes as “linked regularities”). Mosaic scaling in evolution is seen for example in the enormous size that some structures exhibit in some species but not others, relative to the rest of the brain: the common squirrel, for instance, has an enormous superior colliculus, involved in visual processing, that other rodents of a similar brain size do not have; moles and shrews, who rely heavily on olfaction, have even more neurons in the olfactory bulb than in the cerebral cortex – something that is quite different from rodents of a similar brain size (this is work under review).

In the context of our work, mosaic brain evolution means that the numbers of neurons allocated to different brain structures can vary independently across said structures: while, say, the superior colliculus and the visual thalamus tend to gain neurons hand in hand, a particular species can gain neurons much faster in the superior colliculus than in the visual thalamus, for instance. Mosaic brain evolution also refers to the possibility of one system (for instance, vision) expanding faster than another system (say, audition). There is the occasional surprise, however. For instance, we have found that, while primates are highly visual and have a large proportion of the cortex devoted to vision (indeed, much larger than the cortical areas devoted to audition), this proportion (as well as the relative number of cortical neurons devoted to vision) does NOT increase together with increasing brain size. Many more cortical neurons are involved in visual than in auditory processing, yes – but that proportion is stable across primate species. Still, species that rely more heavily on other sensory modalities should have a different distribution of neurons. Indeed, the mouse, contrary to primates, has a far larger percentage of cortical neurons involved in somatosensory processing than primates; and, as I mentioned above, moles and shrews have more neurons in the olfactory bulb than in the whole cortex – a pattern that is not seen in other brains of a similar size.

甚至更有值得注意的是，我们发现哺乳动物进化中脑皮层的表观扩张，从最小哺乳动物中的小于40％的脑大小不同于人类和其他甚至更大的大脑的80％，并不是一个在皮质中的神经元数量的扩张：无论不同物种上皮质的相对大小如何，它均为所有脑神经元的20％ - 即使在人脑中也是如此。这是一个明显的马赛克演化（一个结构接管其他结构）的另一个例子实际上不能成为马赛克演化。这一切都取决于检查的精确变量。

Luke：更具体地说：您认为您的观点是人类大脑基本上是一个“线性扩大的灵长类动物”是具有显着紧张的Smaers＆Soligo（2013）灵长类动物神经结构变异的主要成分分析（PCA）？

Smaers and Soligo claim their PCA shows that while (1) the principal component which accounts for 25.8% of the variance is closely correlated with brain size, it’s also the case that (2) the remaining principal components — which account for a large majority of the variance — are not closely correlated with brain size. In particular, they claim that their phylogenetic analysis shows that “a clade-specific investment in particular brain formations (prefrontal white matter, prefronto-striatal and higher motor control)in combination withincreased absolute brain size differentiates great apes (and humans) from other primates” (emphasis added).

Suzana: No, there is no tension. What we see is that the human cerebral cortex as a whole, like the human cerebellum as a whole, and the remaining areas of the brain as a whole, are linearly scaled-up在他们的神经元数量在其他灵长类动物b相比,相同的结构rains. This means that the relationship between the particular size of a brain structure and its number of neurons is constant and shared across primate species. This does not at all imply or require that all brain areas have the same ratios of numbers of neurons相对彼此那which is what mosaic evolution states: given brain regions can become relatively enlarged or reduced compared to others, and still maintaing the same relationship between their number of neurons and mass as seen across species.

说：是：是的，人类大脑整体做fit the relationship between brain mass and total number of neurons that we found in other primates. As far as I understand, the relative differences that Jeroen Smaers concentrates on are very small – he is looking at the residuals of the relationships, and as many still do, using normalization to external parameters. I believe it is time that we stop assuming that things such as brain mass, or worse, body mass, are true independent parameters (which they very likely aren’t; brain mass, in particular, is the结果大脑及其部分的细胞组成，因此不能确定太多），并开始看看不同参数的绝对值 - 这就是我们在实验室中所做的，试图保持假设的次数最小。

Luke: What are the current estimates of neuron quantities for the largest brains, in elephants and whales? Has you isotropic fractionator process been used on those brains yet, or are their current plans to do so?

Suzana：我们有一篇关于非洲大象大脑中神经元数的审查。大象对我们的假设进行了很大的考验，即神经元的数量是对认知能力的强烈限制因素，这是因为它的大脑，4-5公斤，这是人类大脑的质量约为3倍：我们预测它应该尽管大于我们的大脑，但仍比人类大脑更少。

事实证明，答案更有趣大象小脑，这反过来是脑皮层和小脑中神经元数之间的数值关系中的主要原因。虽然其他哺乳动物（包括人类）在大脑皮质中的每个神经元中有大约4个神经元，但大象在小脑中有45个神经元到脑皮层中的每个神经元。我们现在可以做的就是推测大象小脑中这种非凡的神经元数量的原因，而现在最可能的候选人现在是我对躯干的精细感官电流控制，这是一个令人惊讶的肢体感觉和电动机能力，已知涉及小脑。

Despite the enormous number of neurons in the elephant cerebellum, its cerebral cortex, which is twice the size of ours, has only one third of the neurons in an average human cerebral cortex. Taken together, these results suggest that the limiting factor to cognitive abilities is not the number of neurons in the whole brain, but in the cerebral cortex (to which I would add, “provided that the cerebellum has enough neurons to shape activity in the cerebral cortex”).

We don’t have data on whales yet, but that research is underway in our lab – along with research on carnivores, who we predict to have more neurons than the large artiodactyls that they prey upon.

Luke: What other results in this line of research to you hope to have from your lab or other labs in the next 5 years?

Suzana: We’re extending our analysis to the other mammalian branches — xenarthrans, marsupials, carnivores, chiropterans and perissodactyls — and to non-mammalian vertebrates (birds, reptiles, fish, amphibians) and even some invertebrates. The goal is to achieve a full appreciation and understanding of brain evolution, which will give us, amongst other things, a view into the mechanisms that have led to the generation of brain diversity in evolution. Such a comparative analysis also gives us insights onto the most basic features of the brain: those that are shared by all mammals. As it turns out, there are some, and they are very revealing. One of them, for instance, is the addition of glial cells to the brain, in numbers which seem to be regulated by a self-organized process that is shared across all species examined so far.

We are also focusing our analysis on the prefrontal cortex, that is, the associative areas of the cerebral cortex. While it has been very informative to compare total numbers of neurons in the cerebral cortex across species, it is supposedly those neurons in the associative areas that should really limit the cognitive abilities of the species. This more specific analysis should allow us a new glimpse into the brains of different species and how they compare to the human brain. In this regard, we have a paper in the works comparing the distribution of neurons along the human cerebral cortex with that in other, non-human primate species.

我们还进入了组织的间隔性质：例如，神经元如何分布，以及如何与星形胶质细胞和脉管系统的分布有关。但是一个大问题仍然是跨人类和其他物种的突触数。这也是我们正在努力的东西。

Luke：谢谢，Suzana！