The present study demonstrates individual and inter-species variations in SC in macaques and humans. We used multi-size hierarchical ROIs and two types of ROIs gave the different information about the inter-species variation of SC. Remarkably, the temporal lobe showed high individual variation in both species and high inter-species variation. In contrast, several brain regions, such as the PFC, Sensory, and PVA, show low individual and inter-species variability. Furthermore, LASSO regression analysis showed a unique SC that differentiates the white matter structure between macaques and humans in several brain regions, such as the TAC, AGC, SVA, Sensory, and Motor regions. These results indicate that these key connections contribute to determine the inter-species variation between macaques and humans, as well as to the characteristics of individuals.
The individual variations of SC in macaques and humans
The current study showed a high similarity of SC in the whole brain among human individuals (Fig. 1B). This corresponds to a previous study that quantified the population probability of a white matter tract innervating a cortical region and reported 85% similarity between individuals in humans 22. Macaques also showed high individual similarities in the white matter structure of the whole brain (Fig. 1B). In contrast to humans, a few studies have reported inter-individual similarities among macaques in several brain regions 23,24. The similarity of fiber shapes in neural fiber patterns obtained through DTI is high at the global level, while their differences are greater at the local level in macaques and humans 23. The SC in areas 44, 45A, and 45 B in macaques, homologs of Broca’s area in humans, show individual variability, while human JBA44 and JBA45 also show individual variability 24. In the present study, we did not compare these brain regions because of the difficulty in identifying whether 44, 45A, and 45B in macaques have functions similar to those of Broca’s area in humans. Instead, we used the PFC, including these regions. Individual variations were observed in the PFC, but the temporal lobes, including the MTL, TAC, auditory cortex, and insular cortex, showed higher variations than the PFC in macaques and humans (Fig. 2 and Fig. 3). Previous studies have revealed that individual variations in the temporal lobe morphology are related to individual variations in cognitive function. The thickness of the gyri in the transverse temporal gyrus is proportional to language experiences 25. Individual variability in sulcal depth and cortical thickness was estimated vertex-wise using intraclass correlation and intrasubject variance regression. Functional and anatomical variabilities across the auditory cortex have also been observed in macaques and humans 18,26,27. The individual differences in white matter organization in the insular cortex is linked to a salience network, which is important for cognitive control systems in humans and macaques 28. The TAC is essential for integrating information from various sensory sources for cognitive processing in macaques and humans 29,30. These studies indicate that high individual variations of SC with TAC and insular cortex in macaques and humans may be linked to individual variations in cognitive performance.
The inter-species variation of SC regions between macaques and humans.
High inter-species similarity with level 1 ROIs indicated that the global structure of the SC was similar between macaques and humans (Fig. 4). The modules estimated using graph theory were similar between macaques and humans, corresponding to the global similarity of the SC (Fig. 6). The decreased similarity of SC with level 2 ROIs (Figs. 2 and 3) indicates inter-species variation in SC in local regions. Remarkably, 11 of 13 ROIs showed similar pattern of individual and inter-species variations in macaques and humans, (1) low individual variation and low inter-species variation (PFC, Sensory, and PVA); (2) high individual variation and high inter-species variation (IPL and temporal lobe, including the Auditory and IC); (3) low individual variation and high inter-species variation (Motor, ACG, and SVA); and (4) high individual variation and low inter-species variation (SPL and MTL) (Fig. 8). Individual variations can be linked to the distinct characteristics of behavioral/cognitive performance. Additionally, inter-species variation indicates differences in anatomical connections related to distinct functions between macaques and humans. Previous study reveals that Architectonic subdivisions in the parietal-occipital cortices of macaque monkeys have been explored and have considerable cortical expansion and sub-divisions like humans 8, consistent with the current results.
In this study, we applied LASSO regression to compare the SC between macaques and humans. When using a high-dimensional regression model, we must select many potential covariates. LASSO regression analyses the properties of dimensionality reduction under a sparsity assumption when the number of possible covariates is larger than the sample size 31. Therefore, the LASSO regression has an advantage for SC analysis, which generally uses a lot of ROIs. The features extracted by LASSO regression provide insights into the key regions that distinguish macaque from human cognitive behavior. Remarkably, TAC was associated with 10 connections, and Motor was associated with 5 connections from the extracted 20 features. Furthermore, half of the 20 connections were between the temporal and frontal lobes, as well as between the temporal and parietal lobes. The temporal lobe is involved in many high-level cognitive functions that are particularly well-developed in humans. These include conceptual categorization, semantic processing, and language processing 32,33. Previous MRI studies have shown that the SC in areas 44, 45A, and 45B in macaques and the Broca’s area in humans show low similarity 24. Whole-brain morphological comparisons of human and non-human primate brains have shown that the temporal lobe is a major hotspot of expansion and reorganization 34,35. Another study revealed that each part of the cortical gray matter in both macaques and humans is connected to major white matter fiber pathways 16, and the most important differences among the species were found in the middle temporal gyrus 16. Previous studies also showed that association fibers, such as the arcuate fasciculus, a dorsal association tract connecting the perisylvian regions of the frontal, parietal, and temporal lobes, are different between macaques and humans 36, while the results from LASSO regression in this study highlight that the most explanatory feature for the differences between macaques and humans is the interhemispheric TAC-TAC connection. The temporal cortex in primates is a unique specialization that differs from the lateral expansions of other species 37. Its constituent areas link the visual association cortex and auditory primary cortex to multimodal areas responsible for high-level behaviors, including categorization, semantic processing, and social cognition 38,39. The TAC connects to the fronto-occipital lobe in humans, whereas it mainly connects to the occipital lobe in macaques (Fig. 6). This difference can be linked to evolutionary features in the higher order of cognition between macaques and humans. In contrast, the SC related to motor and sensory functions in macaques were higher than those in humans. This suggests that macaques may allocate more brain resources to regions associated with body function than humans.
Limitations of study
In this study, we investigated the SC in ten macaques and ten humans. Although we could have increased the human sample size in order to better validate the results, we chose to match the sample size to that of the macaques. This is because it is difficult to increase the sample size in animal studies.
This study compared the similarities from the perspective of SC and did not account for differences in brain size. Nevertheless, given that the number of tracts was fixed, and the comparison was conducted as a proportion of the total SC, the findings of this study are crucial in the context of translational research.