Intrinsic amygdala-cortical functional connectivity predicts social network size in humans

Abstract

Using resting-state functional magnetic resonance imaging data from two independent samples of healthy adults, we parsed the amygdala's intrinsic connectivity into three partially distinct large-scale networks that strongly resemble the known anatomical organization of amygdala connectivity in rodents and monkeys. Moreover, in a third independent sample, we discovered that people who fostered and maintained larger and more complex social networks not only had larger amygdala volumes, but also amygdalae with stronger intrinsic connectivity within two of these networks: one putatively subserving perceptual abilities and one subserving affiliative behaviors. Our findings were anatomically specific to amygdalar circuitry in that individual differences in social network size and complexity could not be explained by the strength of intrinsic connectivity between nodes within two networks that do not typically involve the amygdala (i.e., the mentalizing and mirror networks), and were behaviorally specific in that amygdala connectivity did not correlate with other self-report measures of sociality.

Figure 1.

Hypothetical topographic model of amygdala subregions and their affiliated large-scale networks subserving social cognition. A schematic of (a) the amygdala subregions in coronal view that we hypothesize are anchors for (b) three large-scale networks subserving processes important for social cognition. Ins, insula; SS, somatosensory operculum; dTP, dorsal temporal pole; cACC, caudal anterior cingulate cortex; rACC, rostral anterior cingulate cortex; sgACC, subgenual anterior cingulate cortex; MTL, medial temporal lobe; FG, fusiform gyrus; vTP, ventral temporal pole; vlSt, ventrolateral striatum; vmSt, ventromedial striatum.

Figure 2.

Topography of intrinsic connectivity for the whole amygdala in the discovery sample (N = 89). Intrinsic connectivity statistical significance maps are displayed for left and right amygdala seed regions in the discovery sample. Significance maps were thresholded at p < 0.01, averaged across hemisphere for display purposes, and overlaid on Freesurfer's “fsaverage” surface template (a) and a T1 MNI152 2 mm template brain in radiologic convention (b).

Figure 3.

Three connectionally defined subregions of the amygdala. a, A priori seed regions were placed within the vmPFC, cACC, and lOFC. b, c, Each voxel in the amygdala was assigned to the seed region with which it demonstrated the strongest connectivity in the discovery sample (N = 89). Connectivity data are overlaid on a T1 MNI152 2 mm template brain in radiologic convention (b) and depicted in a 3D rendering (C).

Figure 4.

Connectionally defined amygdala subregions from this study and cytoarchitectonically defined amygdala subregions from the Juelich Histological Atlas. Connectionally defined amygdala subregions from our study (a) and cytoarchitectonically defined amygdala subregions obtained from FSL's Juelich Histological Atlas (b) are overlaid on coronal slices of a T1 MNI152 2 mm template brain in radiologic convention. MNI coordinates can be seen in the middle of the figure. The cytoarchitectonically defined subregions are based on probabilistic maps created by Amunts et al. (2005). They include only the voxels that had at least a 50% chance of being assigned to one nuclear group (laterobasal, yellow; superficial, red; centromedial, blue), as used in a previous fcMRI study of these amygdala subregions (Roy et al., 2009).

Figure 5.

Each amygdala subregion anchors one of three distinct large-scale corticolimbic networks. a, Seeds are localized within the connectionally defined amygdala subregions shown in Figure 2. b–d, One sample group mean statistical significance map for each amygdala seed is displayed in standard views (b) as well as views highlighting specific cortical (c) and subcortical brain regions in the discovery sample (N = 89) (d). The maps are binarized at p < 10⁻⁵ and overlaid on a T1 MNI152 0.5 mm template brain in radiologic convention to demonstrate the distinct and shared connectivity across maps. A color key is displayed at the bottom of the figure. cACC, caudal anterior cingulate cortex; Ins, insula; SS, somatosensory operculum; TP, temporal pole; FG, fusiform gyrus; MTL, medial temporal lobe.

Figure 6.

Replication of amygdala subregions and networks in an independent sample (N = 83). a, A priori seed regions were placed within the vmPFC, cACC, and lOFC. b, Each voxel in the amygdala was assigned to the seed region with which it demonstrated the strongest connectivity in the replication sample (N = 83). The cluster maps are overlaid on a T1 MNI152 2 mm template brain in radiologic convention. c, Seeds within the connectionally defined amygdala subregions. d, One sample group mean statistical significance maps for each amygdala seed displayed in standard views. The maps are binarized at p < 10⁻⁵ and overlaid on a MNI152 T1 1.0 mm template brain in radiologic convention. A color key is displayed at the bottom of the figure.

Figure 7.

A larger social network is predicted by stronger connectivity between amygdala subregions and corticolimbic regions important for perception and affiliative behavior. a, Each amygdala subregion and its intrinsic connectivity network were independently defined in the discovery sample (shown here) and then used in the brain-behavior sample to compute the connectivity strength between each amygdala subregion and the rest of the network. b, Scatter plots show that social network size (y-axis) is predicted by the strength of connectivity between two of the three amygdala subregions and their respective networks (x-axis), over and above amygdala volume, in the brain-behavior sample. *p < 0.05; ^†p = 0.06; **the x-axis displays the residual variance in the strength of the resting-state connectivity measure (Fisher's r-to-z) after partialling out its shared variance with amygdala volume.

Figure 8.

Exploratory analyses revealed that the connectivity between the amygdala and specific regions within the networks supporting social perception and affiliation are the best predictors of social network size. a, Brain images show location of voxels within the medial and ventrolateral amygdala's intrinsic connectivity networks (defined in the discovery sample) that correlated with social network size at p < 0.01 in the brain-behavior sample, uncorrected with a cluster size constraint of 10 voxels. Color bars indicate the p values (10⁻²–10⁻⁴) of correlated voxels, which are overlaid on slices of a T1 MNI152 0.5 mm template brain in radiologic convention. b, Scatter plots show the effects for peak voxels with the strength of intrinsic connectivity on the y-axis and social network size on the x-axis; **p < 0.001.