Parallel Interdigitated Distributed Networks within the Individual Estimated by Intrinsic Functional Connectivity

Abstract

Certain organizational features of brain networks present in the individual are lost when central tendencies are examined in the group. Here we investigated the detailed network organization of four individuals each scanned 24 times using MRI. We discovered that the distributed network known as the default network is comprised of two separate networks possessing adjacent regions in eight or more cortical zones. A distinction between the networks is that one is coupled to the hippocampal formation while the other is not. Further exploration revealed that these two networks were juxtaposed with additional networks that themselves fractionate group-defined networks. The collective networks display a repeating spatial progression in multiple cortical zones, suggesting that they are embedded within a broad macroscale gradient. Regions contributing to the newly defined networks are spatially variable across individuals and adjacent to distinct networks, raising issues for network estimation in group-averaged data and applied endeavors, including targeted neuromodulation.

Keywords: association cortex; brain systems; default network; dorsal attention network; frontoparietal network; hippocampus; memory.

Figure 1

Two Parallel Interdigitated Distributed Networks at or near the Canonical Default Network Are Revealed by Functional Connectivity within Individuals Each row illustrates functional connectivity (FC) maps from a single subject (S1–S4). Two networks were observed in each individual. Subject-specific seed regions were placed in the left lateral PFC of the discovery dataset (white filled-in circle). The seed region labeled A^∗ yielded Hypothesized Network A (left) and the seed region labeled B^∗ yielded Hypothesized Network B (right). Note that throughout the cortex, Networks A and B are adjacent to one another with slightly varied positions from individual to individual. Hypothesized Network A includes posterior inferior parietal lobule, lateral temporal cortex, ventromedial PFC, retrosplenial/ventral posteromedial cortex, and parahippocampal cortex. Hypothesized Network B includes the temporoparietal junction, lateral temporal cortex, an inferior region of ventromedial PFC, a dorsal region of anteromedial PFC, and posterior cingulate cortex. Regions (hollow circles A and B) were selected to formally test the distinction between the two networks in independent data. The surfaces are rotated by 19° along the y plane to better show the ventromedial PFC and intraparietal sulcus. The same views are used in accompanying figures.

Figure 2

Parallel Distributed Networks Are Statistically Dissociated Using Independent Data Functional correlation strength was computed between the two PFC seed regions yielding Network A and Network B and the pairs of adjacent seed regions in lateral temporal (Temporal), inferior parietal (Parietal), Posteromedial, and Medial PFC cortices (regions shown in Figure 1). This yielded a 2 × 2 contrast for each zone of cortex (e.g., Networks A and B’s PFC regions against Networks A and B’s Temporal regions). An additional seed region in PHC was grouped with Network B’s posteromedial region. Correlations with Network A’s PFC region are shown in yellow and Network B’s in red. Bars represent the mean from the 12 sessions of the hypothesis-testing dataset with SEM. All 20 2 × 2 ANOVA tests were significant (^∗∗p < 0.01), with most showing a cross-over interaction.

Figure 3

Parallel Distributed Networks Contain Juxtaposed Regions in Numerous Cortical Zones The two dissociated networks near the canonical default network, Network A and Network B, are shown for two subjects (S1 and S4) in a schematic form on the same cortical surface representation. The dashed boxes highlight nine cortical zones where neighboring representations of the two networks were found including: (1) dorsolateral PFC, (2) inferior PFC, (3) lateral temporal cortex, (4) inferior parietal lobule extending into the temporoparietal junction, (5) posteromedial cortex, (6) midcingulate cortex, (7) dorsomedial PFC, (8) ventromedial PFC, and (9) anteromedial PFC. Some zones, including the dorsal region along the PFC (labeled 7), are subtle, but consistent, in all subjects, suggesting that there exists small, closely juxtaposed components of the two dissociated networks.

Figure 4

Multiple Parallel Interdigitated Distributed Networks at or near the Canonical Frontoparietal Control and Dorsal Attention Networks Estimated by Functional Connectivity within Individuals Best estimate maps (using all 24 sessions in each individual) of Networks A and B that fractionate the default network are illustrated (top). Maps from two subjects (S1 and S4) are displayed. The canonical Frontoparietal Network (middle) and Dorsal Attention Network (bottom) also each fractionate into two juxtaposed networks. Seed regions are illustrated by filled white circles.

Figure 5

Relationship of Parallel Interdigitated Networks to Canonical Networks from Group-Averaged Data Each row illustrates how the networks identified in two individuals (S1 and S4) correspond to the well-characterized topography of group-derived networks. The black border represents the outline of the canonical default, frontoparietal control, and dorsal attention networks (top to bottom) calculated using data from 1,000 subjects that were parcellated into seven networks (from Yeo et al., 2011). The correlation maps from each seed (white filled circle) are shown in color. Broadly, the networks can be seen to occupy separate, closely juxtaposed regions that fall within the canonical network borders in most cases. Exceptions can also be found, such as in the inferior frontal cortex in Default Network A and in the parietal lobe in Frontoparietal Control Network B, where the individual’s connectivity map strays outside the group network borders.

Figure 6

Detailed Anatomy of Six Distinct Networks: Parietal and Medial Prefrontal Cortices The fine-scale interdigitation of the six identified networks is highlighted in regions where the macroscale organization is evident. White lines serve as landmarks so that the relative position of each network can be appreciated across panels: Networks A and B of the Default Network (DN-A, DN-B), Frontoparietal Control Network (FPN-A, FPN-B), and Dorsal Attention Network (dATN-A, dATN-B). In each row, FC maps from an individual are displayed for either medial frontal cortex (top two rows) or lateral parietal cortex (bottom two rows).

Figure 7

Detailed Anatomy of Six Distinct Networks: Lateral Temporal Cortex In a similar format to Figure 6, each column displays FC maps from an individual to illustrate the fine-scale interdigitation in the lateral temporal cortex.

Figure 8

Diagrammatic Representation of Six Parallel Distributed Networks within One Individual The central figure shows an illustration of the six networks overlaid on the same cortical surface. The top panel shows the lateral view, and the lower panel shows the medial view. The different colors correspond to the canonical network that each network resembles (red, Default Network, DN-A and DN-B; blue, Frontoparietal Network, FPN-A and FPN-B; green, Dorsal Attention Network, dATN-A and dATN-B). The names of the networks are based on prior literature, recognizing that the novel organization identified here may lead to a reconsideration of the functional domains. Data shown are from S4 (see also Figure S6).