Network analysis detects changes in the contralesional hemisphere following stroke

Abstract

Changes in brain structure occur in remote regions following focal damage such as stroke. Such changes could disrupt processing of information across widely distributed brain networks. We used diffusion MRI tractography to assess connectivity between brain regions in 9 chronic stroke patients and 18 age-matched controls. We applied complex network analysis to calculate 'communicability', a measure of the ease with which information can travel across a network. Clustering individuals based on communicability separated patient and control groups, not only in the lesioned hemisphere but also in the contralesional hemisphere, despite the absence of gross structural pathology in the latter. In our highly selected patient group, lesions were localised to the left basal ganglia/internal capsule. We found reduced communicability in patients in regions surrounding the lesions in the affected hemisphere. In addition, communicability was reduced in homologous locations in the contralesional hemisphere for a subset of these regions. We interpret this as evidence for secondary degeneration of fibre pathways which occurs in remote regions interconnected, directly or indirectly, with the area of primary damage. We also identified regions with increased communicability in patients that could represent adaptive, plastic changes post-stroke. Network analysis provides new and powerful tools for understanding subtle changes in interactions across widely distributed brain networks following stroke.

Fig. 1

Schematic illustration of the graph theory concepts used in this paper. Figure (a) shows a simple, undirected graph with N = 5 nodes and 7 edges, along with the corresponding adjacency matrix, A. The degree of theith node can be obtained from the adjacency matrix simply by summing the entries in the ith row or column. In (b), we see an example of two different walks between nodes 1 and 9 of a network. The first walk 1 4 5 6 9 (red), of length 4, gives the shortest walk between the two nodes. Whereas the second, longer walk 1 2 3 5 7 8 7 9 (green) illustrates the fact that a walk may use the same link more thanonce; here the edge connecting nodes 7 and 8 is used twice in succession en route to node 9

Fig. 2

Comparison of both connectivity and communicability measures for left (top) and right (bottom) hemispheres. Ordered components of the second right singular vector v[2] of A_deg, C_deg, A_conn and C_conn broadly separated strokes and controls in both left (lesioned) and right hemispheres. Circles denote stroke patients and crosses denote controls.

Fig. 3

u[2] scores for each of the 56 brain regions considered for the left hemisphere (left) and right hemisphere (right). Extreme values of u[2] will drive the separation of individuals into classes. Note that we have enclosed those brain regions returned as significant by our statistical analysis and labelled them accordingly. Red circles denote those brain regions that were found to have diminished communicability scores in strokes, whilst black squares highlight regions showing a relative increase.

Fig. 4

Mean communicability degree scores per brain region for the left (lesioned) hemisphere (top) and the right (contralesional) hemisphere (bottom). White bars show control and black bars show stroke data. Error bars are standard errors. Asterisks indicate significant differences between patients and controls, corrected for multiple comparisons, at corrected p < 0.05 (black asterisks) or trends (corrected p < 0.1, grey asterisks).

Fig. 5

Spatial relationships between stroke lesions, regions associated with reduced communicability degree, and pathways showing reduced FA. Overlap map of stroke lesions is shown in red to white (where colorscale indicates number of patients in whom a lesion is present) in the region of the internal casule/basal ganglia of the left hemisphere. Top row also indicates grey matter regions of interest associated with reduced communicability in patients relative to controls (in blue, where light blue regions are significant (p < 0.05 corrected) and dark blue regions show trends (p < 0.1, corrected). These areas associated with reduced communicability tend to be located around the stroke lesions in the lesioned hemispheres and in homologues locations in the contralesional hemsiphere. Top row also shows narrow pink lines within the white matter that indicate regions of reduced FA on the white matter ‘skeleton’ detected in our previous study of FA in this population (Bosnell et al., submitted for publication). This shows that whereas FA reductions are widespread in the lesioned hemiphere, they are restricted to the corpus callosum of the contralesional hemisphere and do not appear around the regions associated with reduced communicability in this hemisphere. Bottom row indicates grey matter regions of interest associated with increased communicability in patients relative to controls (in green, where light green regions are significant (p < 0.05, corrected) and dark green region shows a trend (p < 0.1, corrected).