Details of how deficits are tested are likely a large contributor. That said, I will end this review by offering an alternative thought—not because it is likely to be correct, but because it emphasizes a dimension to the complexity of the problem that has received little consideration to date. The thought is this: what if the increased size of the cerebellum and the extensive projections to association cortex are a spandrel or an unavoidable byproduct of

coordinated evolution? Evolution of brain structures is powerfully limited by rules of embryonic development, birth orders of neurons, and size scaling relations among brain regions. In considering Neratinib molecular weight the large size

of the cerebellum in primates and humans, adaptive arguments have been put forward in the context of motor function leaning on the dexterous hands of primates and consequences of full bipedalism in humans (e.g., Holmes, 1939 and Glickstein, 2007) or, in the context of cognitive function, the extraordinary mental abilities of apes and humans (Leiner et al., 1986). These notions assume that there has been direct selection for an increase in the size of the cerebellum. An alternative is that the selection has been for an overall increase in brain size and the cerebellum comes along as a byproduct. As overall brain size enlarges across diverse mammalian species, the sizes of component brain structures scale predictably but at different rates (Finlay and Darlington, 1995). The relation is far from perfect in that exceptions can occur (e.g., Barton and Harvey, http://www.selleckchem.com/products/ch5424802.html 2000) but the overall trend is nonetheless compelling. For example, the cerebral cortex scales with the largest rate of growth as overall brain size increases between species (Finlay and Darlington, 1995). Mammals with big brains will have very big cerebrums. One likely reason for this regularity is constraints of embryonic development. The progenitor pool that gives rise to the cerebral cortex is large as the process of neurogenesis begins relatively late. Thus, as brain size

is enlarged, the cerebral cortex disproportionately scales in relation to 4��8C other structures such as the brain stem, which emerge relatively early in the developmental sequence. Mosaic evolutionary events are not needed to drive relative overexpansion of the cerebral cortex—in fact, an exceptional evolutionary event shifting neuronal birth order, progenitor pool size, or a related factor would be required to modify the rate of scaling. Relevant here is that the next fastest scaling brain structure is the cerebellum (Finlay and Darlington, 1995). As brain size increases from a mouse to a monkey to a human, the cerebellum’s size scales at a rate second only to that of the cerebral cortex.