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What's the fuss over human frontal lobe evolution?
Spotlights
Trends in Cognitive Sciences September 2013, Vol. 17, No. 9
What’s the fuss over human frontal lobe evolution? Chet C. Sherwood1 and Jeroen B. Smaers2,3 1
Department of Anthropology, The George Washington University, Washington, DC 20052, USA Department of Anthropology, Stony Brook University, Stony Brook, NY 11794, USA 3 Department of Anthropology, University College London, London, WC1H 0BW, UK 2
Evolutionary neuroscientists seek to understand what makes the human neocortex special aside from its extraordinary expansion. New analyses find that the frontal lobes of humans are not relatively enlarged given our species’ brain size. But are statistical cut-offs masking biologically meaningful changes in the size of the human prefrontal cortex? Over one hundred years ago, shortly after completing his landmark cytoarchitectural mapping of the cerebral cortex, Korbinian Brodmann published measurements of granular prefrontal cortex surface area (i.e., ‘regio frontalis’) in humans and a number of other primates [1]. Although the human neocortex is greatly expanded, it was evident to Brodmann that it possesses essentially the same complement of cytoarchitectural regions as other anthropoid primates (i.e., monkeys and apes). Is the human neocortex just a uniformly scaled up version of the anatomy present in other primates or is it reorganized in association with the evolution of our species’ distinctive cognitive abilities? Brodmann found that granular prefrontal cortex comprised 28% of the neocortical surface in humans, 17% in chimpanzees, and 11% in macaque monkeys. However, because of the infancy of statistics and the limited diversity of species that he measured, the data could only provide a preliminary answer to whether the human prefrontal cortex is relatively enlarged. Given that the prefrontal cortex subserves language, imagination, decision-making, and other executive functions, generations of neurobiologists have asserted that it has surely expanded disproportionately in human evolution. However, the current literature presents contradictory findings. Why the muddle after a century of research? First, it is not obvious how to define the appropriate region of interest for analysis. The frontal lobes may be anatomically subdivided and measured in numerous ways. They contain nearly a dozen distinct areas, including primary motor, premotor, supplemental motor, and cingulate cortex, as well as several granular prefrontal regions. In addition, the white matter tracts of the frontal lobe can be difficult to segment from adjacent regions. Consequently, no two studies have measured the frontal lobes in the same manner. Second, comparing the size of brain structures across species is complicated. Cortical regions scale at different rates with overall brain size, regulated by a combination of factors, including the diffusion gradients of developmental growth cues, functional optimization, and connectivity. The majority of cortical enlargement that Corresponding author: Sherwood, C.C. ([email protected]).
432
accompanies increased brain size in primates is due to the differential elaboration of heteromodal association areas of the frontal, parietal, and temporal lobes [2]. Hence, evaluating the simple percentage of the cerebrum comprised by the frontal lobe or prefrontal cortex might mask the effects of allometric scaling in the human brain. A recent study by Barton and Venditti [3] aimed to examine whether human frontal lobe organization is predictable based on scaling for overall brain size. In this study, the authors re-analyzed five datasets which provide measurements of either the frontal lobe, the prefrontal cortex, or frontopolar area 10 in humans and other primates [4–8]. Each dataset was generated using a different anatomical criterion for delineation of regions of interest using either MRIs or histological sections and each dataset included different nonhuman primate species as a baseline for comparison. Using these data, Barton and Venditti tested whether human frontal lobe (or prefrontal cortex) size falls within the range of values that would be predicted for a typical primate with our brain size. All human values in their analyses fell within the 95% prediction intervals of the nonhuman primate regression lines, leading the authors to conclude that the human brain is not characterized by extraordinary enlargement of frontal lobe or its constituent regions. Instead, they suggest that changes in the network connectivity of prefrontal cortex with other regions, such as the cerebellum, might underlie the evolution of human cognitive abilities. So, do we finally have clarity on this long-standing question? Not exactly. Different analyses of the same data reveal that for several aspects of prefrontal cortex anatomy human values actually do fall outside the 95% prediction intervals (Figure 1). Moreover, by employing a strict 95% prediction cut-off, values that lie just inside this range are disregarded under the assumption that they are not biologically meaningful (e.g. data from [8] indicates that the human prefrontal cortex falls inside the 95% prediction interval relative to the rest of the brain yet is 52% larger than predicted from nonhuman primates, a value that falls outside the 85% prediction interval). In addition, certain datasets were excluded from the Barton and Venditti study, resulting in an incomplete picture (excluded data includes frontal and neocortical volumes [9], and frontal and hemisphere-specific prefrontal volumes [8]). But even deeper problems of interpretation persist. By focusing attention only on the statistical predictability of human frontal lobes from scaling regularities, the nature of the allometric relationship itself is overlooked. In primates, the frontal cortex enlarges relative to the rest of the neocortex to the power of 1.2, resulting in a disproportionately
Spotlights
Trends in Cognitive Sciences September 2013, Vol. 17, No. 9
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TRENDS in Cognitive Sciences
Figure 1. Prefrontal scaling trends. Using the same dataset [8] as Barton and Venditti [3], (A) human right prefrontal cortex is found to be larger than predicted for nonfrontal brain size (this result holds for both gray and white matter and when compared to non-prefrontal brain and cortex size) and (B) human prefrontal white matter is larger than predicted relative to prefrontal gray matter. (C) Data from Smaers et al. [8,9] demonstrating that human prefrontal white matter is larger than predicted relative to non-prefrontal white matter. Axes indicate log volume. Red dots indicate data from monkeys, blue dots indicate data from apes, and green dots indicate data for humans.
bigger frontal cortex in species with larger brains [7]. As a result, both mouse lemurs and humans have frontal cortices that fall close to allometric predictions for their overall brain size [7], yet the human frontal cortex is more than 2,000 times larger and constitutes a much greater fraction of the neocortical surface. Such species differences in cortical organization are not likely to be equivalent in terms of connectivity or executive function. One potential way forward is to combine information on the relative size of brain structures with the overall size of the brain in multivariate analyses [10]. This approach involves considering lineage-specific changes in the relative size of individual cortical areas in tandem with changes in overall brain size, recognizing that both overall and relative size changes in heteromodal association areas, such as the prefrontal cortex, contribute to their computational power. It does not assume that the same residual deviation from allometry in a mouse lemur and a human implies an identical biological system and allows considering evolutionary changes on a continuum rather than based on a truncated 95% prediction interval. Additionally, in order to detect more subtle reorganization of specific circuits within the frontal cortex in human evolution, more data on the size of cytoarchitecturally-defined cortical areas from a diverse representation of primates are sorely needed. We should expect that evolution has tinkered with the organization of the human frontal lobe using the most expedient tools at nature’s disposal, taking advantage of conserved developmental processes that yield predictable
allometric scaling effects and making additional modifications as necessary. References 1 Brodmann, K. (1912) Neue Ergebnisse u¨ber die vergleichende histologische Localisation der Grosshirnrinde mit besonderer Beru¨cksichtigung des Stirnhirns. Suppl. Anat. Anz. 41, 157–216 2 Glasser, M.F. et al. (2013) Trends and properties of human cerebral cortex: correlations with cortical myelin content. Neuroimage http:// dx.doi.org/10.1016/j.neuroimage.2013.03.060 3 Barton, R.A. and Venditti, C. (2013) Human frontal lobes are not relatively large. Proc. Natl. Acad. Sci. U.S.A. 110, 9001–9006 4 Semendeferi, K. et al. (2002) Humans and great apes share a large frontal cortex. Nat. Neurosci. 5, 272–276 5 Semendeferi, K. et al. (2001) Prefrontal cortex in humans and apes: a comparative study of area 10. Am. J. Phys. Anthropol. 114, 224–241 6 Schoenemann, P.T. et al. (2005) Prefrontal white matter volume is disproportionately larger in humans than in other primates. Nat. Neurosci. 8, 242–252 7 Bush, E.C. and Allman, J.M. (2004) The scaling of frontal cortex in primates and carnivores. Proc. Natl. Acad. Sci. U.S.A. 101, 3962–3966 8 Smaers, J.B. et al. (2011) Primate prefrontal cortex evolution: human brains are the extreme of a lateralized ape trend. Brain Behav. Evol. 77, 67–78 9 Smaers, J.B. et al. (2010) Frontal white matter volume is associated with brain enlargement and higher structural connectivity in anthropoid primates. PLoS ONE 5, e9123 10 Smaers, J.B. and Soligo, C. (2013) Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution. Proc. R. Soc. B Biol. Sci. 280, 20130269
1364-6613/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tics.2013.06.008 Trends in Cognitive Sciences, September 2013, Vol. 17, No. 9
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Trends in Cognitive Sciences September 2013, Vol. 17, No. 9
What’s the fuss over human frontal lobe evolution? Chet C. Sherwood1 and Jeroen B. Smaers2,3 1
Department of Anthropology, The George Washington University, Washington, DC 20052, USA Department of Anthropology, Stony Brook University, Stony Brook, NY 11794, USA 3 Department of Anthropology, University College London, London, WC1H 0BW, UK 2
Evolutionary neuroscientists seek to understand what makes the human neocortex special aside from its extraordinary expansion. New analyses find that the frontal lobes of humans are not relatively enlarged given our species’ brain size. But are statistical cut-offs masking biologically meaningful changes in the size of the human prefrontal cortex? Over one hundred years ago, shortly after completing his landmark cytoarchitectural mapping of the cerebral cortex, Korbinian Brodmann published measurements of granular prefrontal cortex surface area (i.e., ‘regio frontalis’) in humans and a number of other primates [1]. Although the human neocortex is greatly expanded, it was evident to Brodmann that it possesses essentially the same complement of cytoarchitectural regions as other anthropoid primates (i.e., monkeys and apes). Is the human neocortex just a uniformly scaled up version of the anatomy present in other primates or is it reorganized in association with the evolution of our species’ distinctive cognitive abilities? Brodmann found that granular prefrontal cortex comprised 28% of the neocortical surface in humans, 17% in chimpanzees, and 11% in macaque monkeys. However, because of the infancy of statistics and the limited diversity of species that he measured, the data could only provide a preliminary answer to whether the human prefrontal cortex is relatively enlarged. Given that the prefrontal cortex subserves language, imagination, decision-making, and other executive functions, generations of neurobiologists have asserted that it has surely expanded disproportionately in human evolution. However, the current literature presents contradictory findings. Why the muddle after a century of research? First, it is not obvious how to define the appropriate region of interest for analysis. The frontal lobes may be anatomically subdivided and measured in numerous ways. They contain nearly a dozen distinct areas, including primary motor, premotor, supplemental motor, and cingulate cortex, as well as several granular prefrontal regions. In addition, the white matter tracts of the frontal lobe can be difficult to segment from adjacent regions. Consequently, no two studies have measured the frontal lobes in the same manner. Second, comparing the size of brain structures across species is complicated. Cortical regions scale at different rates with overall brain size, regulated by a combination of factors, including the diffusion gradients of developmental growth cues, functional optimization, and connectivity. The majority of cortical enlargement that Corresponding author: Sherwood, C.C. ([email protected]).
432
accompanies increased brain size in primates is due to the differential elaboration of heteromodal association areas of the frontal, parietal, and temporal lobes [2]. Hence, evaluating the simple percentage of the cerebrum comprised by the frontal lobe or prefrontal cortex might mask the effects of allometric scaling in the human brain. A recent study by Barton and Venditti [3] aimed to examine whether human frontal lobe organization is predictable based on scaling for overall brain size. In this study, the authors re-analyzed five datasets which provide measurements of either the frontal lobe, the prefrontal cortex, or frontopolar area 10 in humans and other primates [4–8]. Each dataset was generated using a different anatomical criterion for delineation of regions of interest using either MRIs or histological sections and each dataset included different nonhuman primate species as a baseline for comparison. Using these data, Barton and Venditti tested whether human frontal lobe (or prefrontal cortex) size falls within the range of values that would be predicted for a typical primate with our brain size. All human values in their analyses fell within the 95% prediction intervals of the nonhuman primate regression lines, leading the authors to conclude that the human brain is not characterized by extraordinary enlargement of frontal lobe or its constituent regions. Instead, they suggest that changes in the network connectivity of prefrontal cortex with other regions, such as the cerebellum, might underlie the evolution of human cognitive abilities. So, do we finally have clarity on this long-standing question? Not exactly. Different analyses of the same data reveal that for several aspects of prefrontal cortex anatomy human values actually do fall outside the 95% prediction intervals (Figure 1). Moreover, by employing a strict 95% prediction cut-off, values that lie just inside this range are disregarded under the assumption that they are not biologically meaningful (e.g. data from [8] indicates that the human prefrontal cortex falls inside the 95% prediction interval relative to the rest of the brain yet is 52% larger than predicted from nonhuman primates, a value that falls outside the 85% prediction interval). In addition, certain datasets were excluded from the Barton and Venditti study, resulting in an incomplete picture (excluded data includes frontal and neocortical volumes [9], and frontal and hemisphere-specific prefrontal volumes [8]). But even deeper problems of interpretation persist. By focusing attention only on the statistical predictability of human frontal lobes from scaling regularities, the nature of the allometric relationship itself is overlooked. In primates, the frontal cortex enlarges relative to the rest of the neocortex to the power of 1.2, resulting in a disproportionately
Spotlights
Trends in Cognitive Sciences September 2013, Vol. 17, No. 9
(B)
(C)
3.5
4.5 5.5 Non−frontal brain
6.5
Prefrontal white maer −2 −1 0 1 2 3
Right prefrontal cortex 0 1 2 3
Prefrontal white maer −2 −1 0 1 2 3
(A)
0
1 2 3 Prefrontal gray maer
4
2
3 4 5 Non−prefrontal white maer
6
TRENDS in Cognitive Sciences
Figure 1. Prefrontal scaling trends. Using the same dataset [8] as Barton and Venditti [3], (A) human right prefrontal cortex is found to be larger than predicted for nonfrontal brain size (this result holds for both gray and white matter and when compared to non-prefrontal brain and cortex size) and (B) human prefrontal white matter is larger than predicted relative to prefrontal gray matter. (C) Data from Smaers et al. [8,9] demonstrating that human prefrontal white matter is larger than predicted relative to non-prefrontal white matter. Axes indicate log volume. Red dots indicate data from monkeys, blue dots indicate data from apes, and green dots indicate data for humans.
bigger frontal cortex in species with larger brains [7]. As a result, both mouse lemurs and humans have frontal cortices that fall close to allometric predictions for their overall brain size [7], yet the human frontal cortex is more than 2,000 times larger and constitutes a much greater fraction of the neocortical surface. Such species differences in cortical organization are not likely to be equivalent in terms of connectivity or executive function. One potential way forward is to combine information on the relative size of brain structures with the overall size of the brain in multivariate analyses [10]. This approach involves considering lineage-specific changes in the relative size of individual cortical areas in tandem with changes in overall brain size, recognizing that both overall and relative size changes in heteromodal association areas, such as the prefrontal cortex, contribute to their computational power. It does not assume that the same residual deviation from allometry in a mouse lemur and a human implies an identical biological system and allows considering evolutionary changes on a continuum rather than based on a truncated 95% prediction interval. Additionally, in order to detect more subtle reorganization of specific circuits within the frontal cortex in human evolution, more data on the size of cytoarchitecturally-defined cortical areas from a diverse representation of primates are sorely needed. We should expect that evolution has tinkered with the organization of the human frontal lobe using the most expedient tools at nature’s disposal, taking advantage of conserved developmental processes that yield predictable
allometric scaling effects and making additional modifications as necessary. References 1 Brodmann, K. (1912) Neue Ergebnisse u¨ber die vergleichende histologische Localisation der Grosshirnrinde mit besonderer Beru¨cksichtigung des Stirnhirns. Suppl. Anat. Anz. 41, 157–216 2 Glasser, M.F. et al. (2013) Trends and properties of human cerebral cortex: correlations with cortical myelin content. Neuroimage http:// dx.doi.org/10.1016/j.neuroimage.2013.03.060 3 Barton, R.A. and Venditti, C. (2013) Human frontal lobes are not relatively large. Proc. Natl. Acad. Sci. U.S.A. 110, 9001–9006 4 Semendeferi, K. et al. (2002) Humans and great apes share a large frontal cortex. Nat. Neurosci. 5, 272–276 5 Semendeferi, K. et al. (2001) Prefrontal cortex in humans and apes: a comparative study of area 10. Am. J. Phys. Anthropol. 114, 224–241 6 Schoenemann, P.T. et al. (2005) Prefrontal white matter volume is disproportionately larger in humans than in other primates. Nat. Neurosci. 8, 242–252 7 Bush, E.C. and Allman, J.M. (2004) The scaling of frontal cortex in primates and carnivores. Proc. Natl. Acad. Sci. U.S.A. 101, 3962–3966 8 Smaers, J.B. et al. (2011) Primate prefrontal cortex evolution: human brains are the extreme of a lateralized ape trend. Brain Behav. Evol. 77, 67–78 9 Smaers, J.B. et al. (2010) Frontal white matter volume is associated with brain enlargement and higher structural connectivity in anthropoid primates. PLoS ONE 5, e9123 10 Smaers, J.B. and Soligo, C. (2013) Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution. Proc. R. Soc. B Biol. Sci. 280, 20130269
1364-6613/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tics.2013.06.008 Trends in Cognitive Sciences, September 2013, Vol. 17, No. 9
433