Bridging the gap between the human and macaque connectome: a quantitative comparison of global interspecies structure-function relationships and network topology

Abstract

Resting state functional connectivity MRI (rs-fcMRI) may provide a powerful and noninvasive "bridge" for comparing brain function between patients and experimental animal models; however, the relationship between human and macaque rs-fcMRI remains poorly understood. Here, using a novel surface deformation process for species comparisons in the same anatomical space (Van Essen, 2004, 2005), we found high correspondence, but also unique hub topology, between human and macaque functional connectomes. The global functional connectivity match between species was moderate to strong (r = 0.41) and increased when considering the top 15% strongest connections (r = 0.54). Analysis of the match between functional connectivity and the underlying anatomical connectivity, derived from a previous retrograde tracer study done in macaques (Markov et al., 2012), showed impressive structure-function correspondence in both the macaque and human. When examining the strongest structural connections, we found a 70-80% match between structural and functional connectivity matrices in both species. Finally, we compare species on two widely used metrics for studying hub topology: degree and betweenness centrality. The data showed topological agreement across the species, with nodes of the posterior cingulate showing high degree and betweenness centrality. In contrast, nodes in medial frontal and parietal cortices were identified as having high degree and betweenness in the human as opposed to the macaque. Our results provide: (1) a thorough examination and validation for a surface-based interspecies deformation process, (2) a strong theoretical foundation for making interspecies comparisons of rs-fcMRI, and (3) a unique look at topological distinctions between the species.

Keywords: graph theory; macaque functional connectivity; network topology; resting state functional connectivity MRI; structure function relationships.

Figure 1.

a, Functional connectivity matrix using the Markov atlas in the group of human subjects. b, Anatomical connectivity matrix derived from a recent retrograde tracer study (Markov et al., 2012). For ease of visual comparison, we rearranged the ROI order for both matrices by community assignment. That is, community detection was run on the anatomical matrix using a method by Bullmore and Sporns (2009). Visually, one can see similarities in the functional and structural matrices. The family of ROC curves and regression analyses outlined in the Materials and Methods quantifies this relationship.

Figure 2.

Qualitative interspecies comparisons of motor connectivity. Motor cortex resting state networks in the human and the macaque. The red regions with arrows pointing to them are the right motor cortex seed region. Resting state time series in this seed region were correlated with time series in each remaining ROI. Correlation coefficients between this seed region and each other ROI are indicated by the color scale. Macaque connectivity is visualized on the human brain for comparison.

Figure 3.

Qualitative interspecies comparisons of default mode connectivity. Functional connectivity is shown between a right anterior node of the default network, area 10 (shown in red), and the rest of the cortex in the human and the macaque. Correlation coefficients between the seed region and each other ROI are indicated by the color scale. Macaque connectivity is visualized on the human brain for comparison.

Figure 4.

Interspecies functional connectivity match. Scatter plot and regression line show the relationship between human and macaque functional connectivity considering all functional connections in both species (a) and the top 15% human functional connections plotted against all corresponding macaque functional connections (b). All values are considered after Fisher's r to z transformation and are based on the Markov atlas.

Figure 5.

Human and macaque functional connectivity match using various parcellation schemes. a, The top 15% of connections from the human functional connectivity matrix are compared with each corresponding connection in the macaque. b, The relationship between human and macaque functional connectivity compared across the cortex. All comparisons shown are made after whole-brain regression and Fisher's z transformation.

Figure 6.

Match between functional and anatomical connectivity. Linear regression shows the relationship between functional and structural connectivity in regions that are anatomically connected. All values are Fisher's z transformed; functional connectivity values were then log transformed where applicable. Comparisons are performed both with and without whole-brain regression (WBR).

Figure 7.

Family of ROC curves showing the match between human and macaque functional connectivity to the anatomical connectivity measured in the macaque. Each line represents an individual ROC curve for a given threshold. The diagonal line represents what would be expected by chance. The greater the area under the curve, the greater the proportion of matches between structural and functional matrices. Comparisons are performed both with and without whole-brain regression (WBR). The structure–function relationship is nonrandom, highest for the strongest structural connections, and slightly improved with whole-brain regression.

Figure 8.

Effect of whole-brain regression on strength and distribution of correlation coefficients for each human participant. Correlation coefficients strengths were rank ordered and placed into 10% bins. The number of connections that remained in the same bin before and after whole-brain regression were quantified and plotted at the top. Approximately 80% of connections remain in the top 10% (1–10% bin) after whole-brain regression. Importantly, similar correspondence is identified for the bottom bins.

Figure 9.

Interspecies comparison of node degree. a, b, Node degree, or the number of functional connections each ROI has to all other regions, is visualized in both species. For all analyses, both human and macaque matrices were thresholded to include only the top 15% of the strongest functional connections. Macaque connectivity is visualized on the human brain and scales are identical between species, allowing for direct comparison. Statistical comparison of human and macaque node degree are based on 10,000 permutations for 15% (c), 10% (e), and 20% (f) connection density. Blue colors represent regions where macaques have higher node degree and red colors represent areas where humans have higher node degree than macaques (p < 0.05, corrected). Notice that high degree nodes are clustered in the posterior cingulate in the macaque, whereas in humans, connections are spread to other networks such as the frontoparietal system. d, Nodes have been reordered according to the number of connections to allow for comparison of degree distributions. Highly connected hubs in the macaques are clustered in only a few select regions that also have a greater number of max connections than humans (i.e., more “scale free”). Conversely, humans show a more distributed pattern in which highly connected hubs are spread throughout the cortex (i.e., less “scale free”).

Figure 10.

Interspecies comparison of betweeness centrality. a, b, Betweenness centrality, or the fraction of shortest paths that pass through a given ROI, is visualized in humans and macaques. Both human and macaque matrices were thresholded to include only the top 15% of the strongest functional connections. Macaque connectivity is visualized on the human brain and scales are identical between species, allowing for direct comparison. Statistical comparison of group differences in betweenness centrality based on 10,000 permutations for the 15% (c), 10% (d), and 20% (e) strongest functional connections. Blue colors represent areas where macaques have higher betweenness centrality and red colors represent areas where humans have stronger centrality than macaques (p < 0.05, corrected). Notice that humans have stronger centrality in frontoparietal regions, whereas macaque hubs are again centered preferentially in and around the posterior cingulate.