Modeling the impact of lesions in the human brain

Abstract

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous ("resting-state") neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions.

Figure 1. Lesion locations.

Diagrams show a rendering of a standard cortical surface, with ROIs that form part of the DMN indicated in light red. Outlines indicate approximate lesion locations. All lesions are comprised of 50 ROIs. Lesion labels correspond to lesion names in Table 1 and 2.

Figure 2. Structural connectivity, functional connectivity, and measurement of lesion effects.

(A) Top: Intact “unlesioned” structural connectivity (SC). Bottom: lesioned SC. The lesion shown here is L194 and the lesioned portion of the matrix is indicated in light yellow. (B) Top: Unlesioned functional connectivity (FC) matrix, obtained after averaging BOLD cross-correlations from 5 simulation runs. Bottom: lesioned FC matrix (L194), averaged over 5 runs. (C) z-score matrix after subtraction of normalized cross-correlations. (D) Cumulative distribution of z-scores of functional connections after subtraction of lesioned (L194) from unlesioned FC (blue dots) and after subtraction of two sets of 5 unlesioned runs (black dots). The dashed line marks z = 3.3, and the number of functional connections at this threshold was taken as one measure of lesion impact.

Figure 3. Analysis of robustness on the basis of random/targeted node deletions.

The plots show the size of the largest network component (A) and the global efficiency (B) as a function of the number of deleted nodes. The curve for random node deletion is an average of 25 different random sequences. The other three curves represent unique sequences of node deletion determined by node degree (blue) strength (green) or node centrality (red).

Figure 4. Dynamic effects of lesions along the brain's midline.

(A) L194. (B) L821. In this plot, as well as in Figures 5, 6 and S1, a dorsal view of the brain (middle panel) and two lateral views of the left hemisphere (left panels) and the right hemisphere (right panels) are shown. The middle panel plots all significantly different functional connections, while the left and right panels only show significantly different functional connections within the left and right hemispheres, respectively. The 998 ROI z-score FC matrix was aggregated to 66 subregions, and pathways between these 66 subregions are plotted if at least 10% of their constituent connections linking ROI pairs are significantly changed (|z|>3.3) as a result of the lesion. Pathways are plotted in red or blue, if their coupling has been weakened or strengthened, respectively. The approximate lesion center is marked with a green “+”.

Figure 5. Dynamic effects of lesions near the temporo-parietal junction.

(A) L472. (B) L810. For plotting conventions see legend to Figure 4.

Figure 6. Dynamic effects of lesions in frontal cortex.

(A) L86. (B) L555. For plotting conventions see legend to Figure 4.

Figure 7. Summary diagram of relationships between structural lesion measures and dynamic lesion effects.

Structural lesion measures are the sum of the node strengths of the lesion (“lesion strength”), the sum of the node centrality of the lesion (“lesion centrality”) and the extent to which the lesion included nodes within the DMN. Dynamic lesion effects are the number of significantly changed functional connections (outside of the lesioned nodes) and the distance between lesioned and unlesioned FC. Compare r-values to those in Table 3. * = p<0.05, ** = p<0.01, *** = p<0.001.