Differences in Frontal Network Anatomy Across Primate Species

Abstract

The frontal lobe is central to distinctive aspects of human cognition and behavior. Some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. The discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. In this study, we used a novel tractography approach to demonstrate that frontal lobe networks, extending within and beyond the frontal lobes, occupy 66% of total brain white matter in humans and 48% in three monkey species: vervets (Chlorocebus aethiops), rhesus macaque (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis), all male. The simian-human differences in proportional frontal tract volume were significant for projection, commissural, and both intralobar and interlobar association tracts. Among the long association tracts, the greatest difference was found for tracts involved in motor planning, auditory memory, top-down control of sensory information, and visuospatial attention, with no significant differences in frontal limbic tracts important for emotional processing and social behaviour. In addition, we found that a nonfrontal tract, the anterior commissure, had a smaller volume fraction in humans, suggesting that the disproportionally large volume of human frontal lobe connections is accompanied by a reduction in the proportion of some nonfrontal connections. These findings support a hypothesis of an overall rearrangement of brain connections during human evolution.SIGNIFICANCE STATEMENT Tractography is a unique tool to map white matter connections in the brains of different species, including humans. This study shows that humans have a greater proportion of frontal lobe connections compared with monkeys, when normalized by total brain white matter volume. In particular, tracts associated with language and higher cognitive functions are disproportionally larger in humans compared with monkeys, whereas other tracts associated with emotional processing are either the same or disproportionally smaller. This supports the hypothesis that the emergence of higher cognitive functions in humans is associated with increased extended frontal connectivity, allowing human brains more efficient cross talk between frontal and other high-order associative areas of the temporal, parietal, and occipital lobes.

Keywords: comparative anatomy; connectivity; diffusion MRI; evolution; frontal lobe; tractography.

Figure 1.

Pipeline for dissection of the association, commissural, projection, and intrafrontal tracts, illustrated in a single macaque brain. A, An inclusion region of the whole left or right hemisphere was used to extract all hemispheric connections. Exclusion regions (not pictured) were used to remove artifactual streamlines coursing through the contralateral internal, external, and extreme capsules. B, From the set of streamlines in each hemisphere defined in A, an inclusion region of the frontal lobe was used to select only streamlines passing through the frontal lobe, including those extending between frontal and nonfrontal regions. C–F, These frontal lobe connections were then further separated into the following groups: association fibers, using an inclusion region of the frontal lobe (1) and exclusion regions in the midsagittal section (2) and subcortical nuclei (3); C); commissural fibers, using the two frontal lobes (1, 2) as inclusion regions (D); projection fibers, using one inclusion region of the frontal lobe (1) and one in the brainstem, thalamus and internal capsule (2; E); and intrafrontal association fibers (F). Intrafrontal fibers were defined with the condition that both ends of the streamline must be within the frontal lobe region of interest. The same approach was used in all species.

Figure 2.

Regions of interest used to dissect individual tracts in the human (two left columns) and monkey (two right columns) brain. For each example, 3D reconstructions and 2D sections are shown. In addition to the regions depicted here, exclusion regions were used in the midsagittal plane, brainstem, subcortical nuclei, and internal capsule to exclude commissural and projection tracts and remove individual spurious streamlines. A, Uncinate fasciculus (lateral view). Inclusion regions of interest are placed in the anterior temporal lobe (pink) and external/extreme capsules (orange). B, Cingulum (medial view). A single inclusion region (pink) on multiple coronal slices along the cingulate gyrus is used to ensure that all the short projections of the dorsal cingulum are included. C, Frontal aslant tract (anterior view). An inclusion region (light blue) is placed in the white matter medial to the inferior frontal gyrus in the sagittal plane. In humans, a second inclusion region (yellow) is placed in the white matter inferior to the superior frontal gyrus in the axial plane, whereas in monkeys, an atlas-defined region of the superior frontal gyrus is used as the second region to include all streamlines projecting to the medial frontal regions. Exclusion regions were then placed in the frontal pole. D, SLF (lateral view). Posteriorly, one inclusion region (yellow) is placed in the parietal lobe in line with the superior aspect of the central sulcus, whereas anteriorly three separate inclusion regions are used for each of the three branches: SLF I (light blue), II (dark blue), and III (purple), all in a coronal plane passing through the precentral gyrus. Exclusion regions are used in the temporal and occipital lobe in both humans and monkeys. E, Inferior fronto-occipital fasciculus (lateral view). One inclusion region is used in the external/extreme capsules (pink) and one in the anterior border of the occipital lobe (yellow); both are in the coronal plane. F, Arcuate fasciculus, long segment. In the human, one inclusion region (orange) is placed in the coronal plane just anterior to the central sulcus, and one inclusion region in the axial plane inferior to the temporoparietal junction (blue). In the monkey, to be as inclusive as possible, atlas-defined regions of the frontal lobe (pink mask) and superior temporal gyrus (yellow mask) were also used as inclusion regions of interest. In addition to the inclusion regions pictured here, exclusion regions were placed in the external/extreme capsules and the white matter of the superior temporal gyrus to remove the middle longitudinal fasciculus, and in the white matter medial to the supramarginal gyrus to remove SLF fibers. G, Anterior commissure. Two inclusion regions were used to capture the compact bundle of the anterior commissure as it crosses the midline. Each region has two slices in the sagittal plane on either side of the midline, one more medial (green), one placed more laterally (yellow). Exclusion regions were used to remove spurious streamlines forming part of the fornix, anterior thalamic projections, and other projections from the brainstem.

Figure 3.

MRI methods for comparing cortical and white matter volumes across species. Images show the rescaled anatomy of representative cases, and graphs display proportional and absolute volumes. Data points represent individual cases, dashes represent species means. H, Humans (n = 20); V, vervets (n = 4); M, macaques (n = 5). A, Voxel-based measures of frontal cortex volume. B, Voxel-based measures of frontal white matter volume. C, Tractography-based measures of frontal tracts volume. D, Tractography-based measures of anterior commissure (AC) volume. *p < 0.05, **p < 0.01, and ***p < 0.001 when comparing humans with either vervets or macaques. For full statistical results, see Results and Table 3.

Figure 4.

The main frontal tract groups compared among humans, vervets, and macaques. A–D, Images show tractography reconstructions of the frontal association (green; A), commissural (red; B), projection (blue; C), and intralobar frontal (orange; D) networks in single representative brains. Graphs show both proportional volume and absolute volume of each tract group, where data points represent individual brains (H, n = 20; V, n = 4; M, n = 5) and species mean values are indicated by horizontal lines. *p < 0.05 and ***p < 0.001 when comparing humans with either vervets or macaques. For full statistical results, see Results and Table 4.

Figure 5.

Comparison of the major frontal association tracts between humans, vervets, and macaques. Images show tractography reconstructions from individual brains, and graphs show proportional and absolute tract volume measures. Data points represent individual brains (H, n = 20; V, n = 4; M, n = 5). Species means are indicated by horizontal lines. A–E, The tracts shown are the cingulum (burgundy color) and UF (dark green), which represent the major frontolimbic association tracts (A); FAT (pink; B); frontoparietal connections of the superior longitudinal fasciculus (SLF I, light blue; SLF II, dark blue; SLF III, purple; C); IFOF (yellow; D); AF, long segment (light green; E). *p < 0.05, **p < 0.01, and ***p < 0.001 when comparing humans with either vervets or macaques. For full statistical results, see Results and Table 5.

Figure 6.

Comparison of ex vivo and in vivo macaque tractography data. A–E, Images show tractography reconstructions of the cingulum (burgundy) and UF (dark green; A), FAT (pink; B), superior longitudinal fasciculus (SLF I, light blue; SLF II, dark blue; SLF III, purple; C), IFOF (yellow; D), and AF, long segment (light green; E). Data points in the graphs show proportional and absolute tract volumes for individual brains and species mean values are indicated with horizontal lines. There were no significant differences in proportional tract volume between groups, except for the inferior fronto-occipital fasciculus (Welch's F_(1,6.08) = 8.34, *p = 0.027). *p < 0.05, **p < 0.01, and ***p < 0.001 when comparing ex vivo and in vivo macaques with Welch's ANOVA. The AF could not be reconstructed in the in vivo datasets. For full statistical results, see Table 6.

Figure 7.

Comparison of human and macaque in vivo tractography data. A–E, Images show tractography reconstructions of the cingulum (burgundy) and UF (dark green; A), FAT (pink; B), superior longitudinal fasciculus (SLF I, light blue; SLF II, dark blue; SLF III, purple; C), IFOF (yellow; D), and AF, long segment (light green; E). Graphs show proportional and absolute tract volumes for individual brains measured from the in vivo dataset for both humans and monkeys. **p < 0.01 and ***p < 0.001 when comparing humans with either vervets or macaques. Statistics were not calculated for the AF because it was not possible to reconstruct this tract in the macaque in vivo datasets. For full statistical results, see Table 6.