Focal brain lesions to critical locations cause widespread disruption of the modular organization of the brain

Abstract

Although it is generally assumed that brain damage predominantly affects only the function of the damaged region, here we show that focal damage to critical locations causes disruption of network organization throughout the brain. Using resting state fMRI, we assessed whole-brain network structure in patients with focal brain lesions. Only damage to those brain regions important for communication between subnetworks (e.g., "connectors")--but not to those brain regions important for communication within sub-networks (e.g., "hubs")--led to decreases in modularity, a measure of the integrity of network organization. Critically, this network dysfunction extended into the structurally intact hemisphere. Thus, focal brain damage can have a widespread, nonlocal impact on brain network organization when there is damage to regions important for the communication between networks. These findings fundamentally revise our understanding of the remote effects of focal brain damage and may explain numerous puzzling cases of functional deficits that are observed following brain injury.

Figure 1

Schematic of nodal roles. Schematic illustrating the role of connectors (black circles) and hubs (white squares) in modular organization. Hubs have many within-module connections, and connectors have many between-module connections. Note that any brain region may have both connector- and hub-like properties and can have continuous values for hubness and connectorness (see Figure 5).

Figure 2

Overlap of individual patient lesions. An overlap plot of the location of brain damage in 35 patients with focal lesions. The color designates the number of patients with damage to a particular brain region. On this and subsequent figures: R = right hemisphere; L = left hemisphere.

Figure 3

Modular organization of the healthy control template. Top (left) and lateral (right) views of the control template graph created from averaged rs-fMRI data from 24 healthy participants. Brain regions (nodes) are represented by squares (hubs, WD > 1) or circles (nonhubs, WD ≤ 1), and node size represents connectorness (PC). The modularity-optimized partition of the graph resulted in four modules: fronto-parietal (FP), centro-temporal (C), medial-temporal (MT), and occipito-parietal (OP). Within-module edges match module color and between-module edges are black. This partitioning scheme was consistent across thresholds and present in both hemispheres when analyzed separately (see Figure 8). R = right hemisphere; L = left hemisphere.

Figure 4

Damage to each module. Patients had focal brain damage to a heterogeneous set of cortical regions that overlapped with multiple modules. Color indicates percentage of damage to the module, and patients are sorted based on their modularity scores, ranging from low (top) to high (bottom) levels of modularity. FP = fronto-parietal; C = centro-temporal; MT = medial-temporal; OP = occipito-parietal.

Figure 5

Nodal roles. Nodes in the control template were characterized based on their PC (left), a measure of the number of intermodule connections, and WD (right), a measure of the number of intramodule connections. Individual nodes from different modules had a wide range of values, providing a continuum over which patient damage could be assessed. In the figure, AAL region names correspond to abbreviations reported in the AAL atlas (Tzourio-Mazoyer et al., 2002); R = right hemisphere; L = left hemisphere.

Figure 6

PC and WD damage score correlations with modularity across the whole brain. (Left) PC damage score was negatively correlated with the modularity of individual participants, across the whole brain (cost = 0.15, r = −.41, p = .02). (Right) WD damage score was not related to modularity, and the correlation between PC and modularity was more negative than the correlation between WD and modularity. These relationships were consistent across a range of cost thresholds.

Figure 7

PC and WD damage score correlations with modularity for each hemisphere. (Left) PC damage score was negatively correlated with the modularity of individual participants in the (top) lesioned (cost = 0.15, r = −.41, p = .02) and (bottom) nonlesioned hemisphere (cost = 0.20, r = −.44, p = .01). (Right) WD damage score was not related to modularity in either hemisphere. The correlation between PC and modularity was more negative than the correlation between WD and modularity in both hemispheres and these relationships were consistent across a range of cost thresholds.

Figure 8

Examples of individual patients with low and high PC damage scores. (A) Control template graphs from the average of the healthy control participants across (top) the whole brain and (bottom) each hemisphere separately. (B) Patients with low connector damage tended to have preserved modular structure across the whole brain (top; Q = 0.48) and both hemispheres (bottom; lesioned: Q = 0.36, nonlesioned: Q = 0.41). (C) Patients with high connector damage, however, had highly disrupted modular organization across the whole brain (top; Q = 0.21) and both hemispheres (bottom; lesioned: Q = 0.20; nonlesioned Q = 0.19). Plotting conventions follow Figure 3. Module colors are assigned to match control template modules with the highest number of overlapping nodes. Yellow stars represent lesioned nodes, with size of the star proportional to the percent damage to that node (these two patients were approximately matched for the sizes of their lesions).