Intrinsic connectivity reveals functionally distinct cortico-hippocampal networks in the human brain

Abstract

Episodic memory depends on interactions between the hippocampus and interconnected neocortical regions. Here, using data-driven analyses of resting-state functional magnetic resonance imaging (fMRI) data, we identified the networks that interact with the hippocampus-the default mode network (DMN) and a "medial temporal network" (MTN) that included regions in the medial temporal lobe (MTL) and precuneus. We observed that the MTN plays a critical role in connecting the visual network to the DMN and hippocampus. The DMN could be further divided into 3 subnetworks: a "posterior medial" (PM) subnetwork comprised of posterior cingulate and lateral parietal cortices; an "anterior temporal" (AT) subnetwork comprised of regions in the temporopolar and dorsomedial prefrontal cortex; and a "medial prefrontal" (MP) subnetwork comprised of regions primarily in the medial prefrontal cortex (mPFC). These networks vary in their functional connectivity (FC) along the hippocampal long axis and represent different kinds of information during memory-guided decision-making. Finally, a Neurosynth meta-analysis of fMRI studies suggests new hypotheses regarding the functions of the MTN and DMN subnetworks, providing a framework to guide future research on the neural architecture of episodic memory.

Fig 1. Louvain community detection identifies large-scale resting-state networks.

(A) Inflated cortical surface, colored according to community membership. (B) Connectivity matrix reordered by community to demonstrate the community structure of the group-averaged brain. Colors along the axis demonstrate which rows/columns belong to a given community. Color bar represents Fisher Z-transformed correlation values. (C) Force-directed graph of the group-averaged networks color coded by community membership of the selected partition created using the ForceAtlas2 algorithm [54]. Attn, attention; DMN, default mode network; Front Par, frontoparietal; MTN, medial temporal network; Som-Mot, somatomotor. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 2. Removal of the MTN disproportionately decreases the network connectivity of the DMN and visual network.

(A) Force-directed graph of the group-averaged networks color coded by community membership of the selected partition created using the ForceAtlas2 algorithm [54] with the MTN present (left) and with the MTN excluded (right). (B) Boxplots displaying the path length between the DMN and visual network or the path length between the hippocampi and visual network following removal of each network. *** p < 0.001. Ant, anterior; Attn, attention; AUD, auditory; DAN, dorsal attention network; DMN, default mode network; FP, frontoparietal; LANG, language; MTN, medial temporal network; Post, posterior; SAL, salience; SM, somatomotor; Som-Mot, somatomotor; VIS, visual. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 3. The DMN can be partitioned into 3 interconnected subnetworks.

(A) FC matrix organized by subnetwork. Color bar represents Fisher Z-transformed correlation values. (B) Inflated cortical surface, colored according to community membership of subnetworks. AT, anterior temporal; DMN, default mode network; FC, functional connectivity; MP, medial prefrontal; PM, posterior medial. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 4. DMN subnetworks interact with language, frontoparietal, and MTNs.

(A) Force-directed graph of the group-averaged networks with the DMN relabeled according to subnetwork membership. (B) Boxplots showing participation coefficient for DMN nodes to the rest of the brain (Whole Brain) and participation coefficient for DMN nodes to subnetworks of the DMN (Within DMN). AT, anterior temporal; Attn, attention; DMN, default mode network; Front Par, frontoparietal; MP, medial prefrontal; MTN, medial temporal network; PM, posterior medial; Som-Mot, somatomotor. * indicates significant difference at p < 0.05. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 5. Regions within the MTN and DMN subnetworks exhibit differential FC with the anterior and posterior hippocampus.

(A) Bar graphs of FC from each of the cortical networks to the anterior and posterior hippocampus. Error bars show 95% confidence interval. (B) T-contrast of anterior hippocampal connectivity versus posterior hippocampal connectivity, with warm colors showing regions that had stronger anterior hippocampal connectivity and cool colors showing regions that had stronger posterior hippocampal connectivity. Cortico-hippocampal network boundaries are outlined on the surface of the brain. These results indicate that the temporopolar and mPFC show preferential connectivity with the anterior hippocampus, whereas PM parietal cortex shows preferential connectivity with the posterior hippocampus. Ant, anterior; AT, anterior temporal; DMN, default mode network; FC, functional connectivity; HC, hippocampus; MP, medial prefrontal; mPFC, medial prefrontal cortex; MTN, medial temporal network; PM, posterior medial; Post, posterior. * p < 0.05, *** p < 0.001. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 6. Regions show higher representational profile similarity with community members compared to regions in other communities.

Left: individual subject representational profile similarity of regions within the same network or between network in gray lines with the group average in red, with 95% confidence intervals represented by error bars. Right: boxplot of average region-to-region representational profile similarity between each cortical-hippocampal network (labeled along the x-axis) to itself and every other cortico-hippocampal network (each represented by a colored bar) across the sample (see S6 Fig for the representational profile similarity of the cortico-hippocampal networks compared to every other cortical network). Individual participants represented as dots. AT, anterior temporal; MP, medial prefrontal; MTN, medial temporal network; PM, posterior medial. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 7. Terms associated with activation of each cortico-hippocampal network.

Word clouds are colored according to the network they describe which are displayed on the inflated brain. The size of the terms in the word cloud relates to how strongly the meta-analytic activity of that term correlates with the spatial extent of the network. Red, AT subnetwork; Blue, PM subnetwork; Yellow, MP subnetwork; Green, medial temporal network. Data can be found at https://github.com/ajbarn/hippo_nets.

Fig 8

Left: hypothesized PM/AT divisions with PM nodes as blue and AT nodes as red [29,78]. Right: data-driven network assignments. ANG, angular gyrus; AT, anterior temporal; mPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; PCC, posterior cingulate cortex; PHC, parahippocampal cortex, PM, posterior medial; PRC, perirhinal cortex; PreC, precuneus; RSP, retrosplenial cortex; TP, temporal pole.