Dynamics of the Human Structural Connectome Underlying Working Memory Training.

Brain region-specific changes have been demonstrated with a variety of cognitive training interventions. The effect of cognitive training on brain subnetworks in humans, however, remains largely unknown, with studies limited to functional networks. Here, we used a well-established working memory training program and state-of-the art neuroimaging methods in 40 healthy adults (21 females, mean age 26.5 years). Near and far-transfer training effects were assessed using computerized working memory and executive function tasks. Adaptive working memory training led to improvement on (non)trained working memory tasks and generalization to tasks of reasoning and inhibition. Graph theoretical analysis of the structural (white matter) network connectivity ("connectome") revealed increased global integration within a frontoparietal attention network following adaptive working memory training compared with the nonadaptive group. Furthermore, the impact on the outcome of graph theoretical analyses of different white matter metrics to infer "connection strength" was evaluated. Increased efficiency of the frontoparietal network was best captured when using connection strengths derived from MR metrics that are thought to be more sensitive to differences in myelination (putatively indexed by the [quantitative] longitudinal relaxation rate, R1) than previously used diffusion MRI metrics (fractional anisotropy or fiber-tracking recovered streamlines). Our findings emphasize the critical role of specific microstructural markers in providing important hints toward the mechanisms underpinning training-induced plasticity that may drive working memory improvement in clinical populations. SIGNIFICANCE STATEMENT: This is the first study to explore training-induced changes in the structural connectome using a well-controlled design to examine cognitive training with up-to-date neuroimaging methods. We found changes in global integration based on white matter connectivity within a frontoparietal attention network following adaptive working memory training compared with a nonadaptive comparison group. Furthermore, the impact of different diffusion MR metrics and more specific markers of white matter on the graph theoretical findings was evaluated. An increase in network global efficiency following working memory training was best captured when connection strengths were weighted by MR relaxation rates (influenced by myelination). These results are important for the optimization of cognitive training programs for healthy individuals and people with brain disease.