Quantitative assessment of prefrontal cortex in humans relative to nonhuman primates

Abstract

Humans have the largest cerebral cortex among primates. The question of whether association cortex, particularly prefrontal cortex (PFC), is disproportionately larger in humans compared with nonhuman primates is controversial: Some studies report that human PFC is relatively larger, whereas others report a more uniform PFC scaling. We address this controversy using MRI-derived cortical surfaces of many individual humans, chimpanzees, and macaques. We present two parcellation-based PFC delineations based on cytoarchitecture and function and show that a previously used morphological surrogate (cortex anterior to the genu of the corpus callosum) substantially underestimates PFC extent, especially in humans. We find that the proportion of cortical gray matter occupied by PFC in humans is up to 1.9-fold greater than in macaques and 1.2-fold greater than in chimpanzees. The disparity is even more prominent for the proportion of subcortical white matter underlying the PFC, which is 2.4-fold greater in humans than in macaques and 1.7-fold greater than in chimpanzees.

Keywords: chimpanzee; cortical parcellation; evolution; neuroanatomy; prefrontal cortex.

Fig. 1.

Parcellations of prefrontal cortex for human, macaque, and chimpanzee displayed on inflated (unfolded) left hemisphere surfaces cropped to include only anterior regions for lateral (Left) and medial (Right) views of each species. (A) Inflated human cortical surface displaying group-average HCP_MMP1.0 parcellation. Conservative PFC includes red areas. Liberal PFC additionally includes blue areas. (B) Inflated chimpanzee cortical surface displaying a conservative PFC delineation based on the Bailey et al. (42) cytoarchitectonic parcellation and maps/gradients of cortical myelin content. (C) Inflated macaque cortical surface displaying a composite parcellation adapted from three studies (–38) along with conservative and liberal PFC delineations. Figures are not to scale. Data are available at https://balsa.wustl.edu/GrK7 (human), https://balsa.wustl.edu/px4G (chimpanzee), and https://balsa.wustl.edu/k94P (macaque).

Fig. 2.

Structural features of lateral (Top and Second Rows) and medial (Third and Bottom Rows) inflated left hemisphere cortex related to delineations of the PFC. Each primate species cortical surface displays myelin content (Top and Third Rows) and its corresponding spatial gradient (Second and Bottom Rows). The white line overlying each map represents the group-average location of the coronal slice at the corpus callosum genu (see also Fig. 3); pink and blue lines represent group-average conservative and liberal PFC delineations, respectively. Primary motor area 4 and primary visual area V1 are bounded by black contours in the parietal and occipital cortex, respectively. Black bars indicate the relative scale of the group-average inflated surfaces for each species. Data are available at https://balsa.wustl.edu/22XL.

Fig. 3.

PFC border probability maps displayed on inflated left hemisphere atlas surfaces of the frontal lobe (Left, lateral aspect; Right, medial aspect of each pair) overlaid on group-average sulcal depth maps. Human liberal and conservative PFC borders were created using individual subject parcellations, resulting in pronounced intersubject variance on the group-average surface. Corresponding borders in the macaque and chimpanzee were created using a group-average parcellation registered to each individual subject and thus show no such variance. Black bars indicate the relative scale for the group-average inflated surfaces. Data are available at https://balsa.wustl.edu/r7Xw (human), https://balsa.wustl.edu/xMp4 (chimpanzee), and https://balsa.wustl.edu/PMKk (macaque).

Fig. 4.

Log-scale plots comparing PFC gray and white matter volume with reference values across species (macaques, diamonds; chimpanzees, squares; humans, circles). (A) Volumes of conservative PFC (red), non-PFC (black), and area V1 (green) gray matter plotted against total cortical gray matter volume. Volumes of area 4 are plotted with solid magenta markers without a corresponding linear fit. (B) PFC gray matter volume plotted against the volume of the primary visual cortex. Blue, red, and black markers indicate liberal, conservative, and genu-based PFC delineations, respectively. (C) Genu-based PFC white matter volume plotted against total white matter volume. For all panels, solid lines represent the best fit using mean macaque, chimpanzee, and human data points; dotted lines represent 95% CIs.

Fig. 5.

Mapping of surface-based ROI to cortical gray matter ribbon volume. (A) Illustration of human cortical surface ROI mapped to underlying gray matter ribbon volume. (B) Illustration of human genu-based ROI volume anterior to a coronal slice at the genu of the corpus callosum when the image is AC–PC aligned.