Background

Cognitive control is a quintessential feature of human cognition. Alterations in cognitive control, in ageing and mild cognitive impairment (MCI), relate to microstructure of the cingulum-a white matter tract that connects specific regions involved in control, such as anterior and posterior cingulate cortices. However, the efficiency of the global structural network also correlates with control in MCI. We investigated whether these findings are connected and whether the influence of cingulum microstructure might be mediated by large-scale network properties.

Methods

25 patients with MCI underwent diffusion MRI and cognitive assessment. In each individual, diffusion tensor imaging-based tractography was used to construct whole-brain tractograms, which were represented as network graphs, weighted by the number of reconstructed streamlines between any two nodes. Global efficiency of each network was calculated. Linear regression modelling was used to investigate how global efficiency and microstructure of cingulum portions predict aspects of cognitive control.

Results

When global efficiency was used as a sole predictor, significant relationships were found with Category Fluency (t= 3.25, p=. 004), Digit Symbol Substitution (t= 2.43, p=. 025), and Stroop suppression score (t= 2.26, p=. 035). Category Fluency correlated most strongly with mean diffusivity (MD) of the left posterior cingulum in MCI, while MD of the left parahippocampal and right middle cingulum were the main correlates of Digit Symbol and Stroop suppression scores, respectively. When the relevant microstructural measure from a portion of the cingulum was added to any of the individual regression models for the relevant task, the relationship with global efficiency was no longer significant. In contrast, independent relationship between left posterior cingulum and Category Fluency (t=-2.25, p=. 037) and left parahippocampal cingulum and Digit Symbol Substitution (t=-3.30, p=. 004) remained.

Conclusions

Global efficiency of white matter network structure correlates with cognitive control in MCI. Multivariate analyses suggest that alterations in global efficiency potentially mediate the effect of microstructural variation in specific components of the cingulum. However, for some tasks there was also an association between performance and microstructure of cingulum segments that was independent of global network efficiency. Both global and local network properties are likely to play a role in the status of cognitive control in MCI.