Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a "small-world" organization following traumatic brain injury (TBI). Methods:We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging.Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions:We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. Neurology Traumatic brain injury (TBI) frequently produces cognitive deficits.1 Patients often show persistent impairments in information processing speed, memory, and executive function, which limit recovery.1-3 The pathophysiologic basis for these problems remain incompletely understood. 4 However, the presence of traumatic axonal injury (TAI) appears to be particularly important in determining the pattern of cognitive problems. [5][6][7][8] Cognitive functions are dependent on the efficient functioning of distributed brain networks, which consist of spatially separated brain regions connected by white matter tracts. TAI can disrupt these connections, 9,10 and can impair network functioning.6,11 A detailed description of brain network function is likely to be important for understanding how TBI affects high-level cognitive processes.Graph theory allows a quantitative analysis of network organization and has recently found application in the study of brain function.12,13 Graph theory describes brain networks as sets of interacting nodes (distinct brain regions or groups of neurons) connected by edges (white matter tracts). Networks with high levels of local node clustering and relatively few connecting edges strike an optimal balance between the demands of specialized processing in local modules and the need for integrated processing across the whole network, and are said to have a small-world architecture. 13 The disruption of small-worldness has been observed in a number of neurologic conditions. 14,15 As TAI disrupts the connections of distributed brain networks, graph theoretical analysis is likely to offer insights into the dysfunction of these networks following TBI.
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