Cognitive impairment after focal brain lesions is better predicted by damage to structural than functional network hubs.

Hubs are highly connected brain regions important for coordinating processing in brain networks. It is unclear, however, which measures of network "hubness" are most useful in identifying brain regions critical to human cognition. We tested how closely two measures of hubness-edge density and participation coefficient, derived from white and gray matter, respectively-were associated with general cognitive impairment after brain damage in two large cohorts of patients with focal brain lesions (N = 402 and 102, respectively) using cognitive tests spanning multiple cognitive domains. Lesions disrupting white matter regions with high edge density were associated with cognitive impairment, whereas lesions damaging gray matter regions with high participation coefficient had a weaker, less consistent association with cognitive outcomes. Similar results were observed with six other gray matter hubness measures. This suggests that damage to densely connected white matter regions is more cognitively impairing than similar damage to gray matter hubs, helping to explain interindividual differences in cognitive outcomes after brain damage.