Cognitive stimulation of the default-mode network modulates functional connectivity in healthy aging

• Specific computerised tasks were designed to induce co-activation of target areas.
• A protocol of cognitive stimulation was devised to stimulate the default-mode network.
• Voxel-based correlational methods supported task validity and appropriateness.
• Increases in network connectivity were found in the experimental group.
• Network-based stimulation might be a therapeutical avenue to boost connectivity in neurodegeneration.

A cognitive-stimulation tool was created to regulate functional connectivity within the brain Default-Mode Network (DMN). Computerized exercises were designed based on the hypothesis that repeated task-dependent coactivation of multiple DMN regions would translate into regulation of resting-state network connectivity.Forty seniors (mean age: 65.90 years; SD: 8.53) were recruited and assigned either to an experimental group (n = 21) who received one month of intensive cognitive stimulation, or to a control group (n = 19) who maintained a regime of daily-life activities explicitly focused on social interactions. An MRI protocol and a battery of neuropsychological tests were administered at baseline and at the end of the study. Changes in the DMN (measured via functional connectivity of posterior-cingulate seeds), in brain volumes, and in cognitive performance were measured with mixed models assessing group-by-timepoint interactions. Moreover, regression models were run to test gray-matter correlates of the various stimulation tasks.Significant associations were found between task performance and gray-matter volume of multiple DMN core regions. Training-dependent up-regulation of functional connectivity was found in the posterior DMN component. This interaction was driven by a pattern of increased connectivity in the training group, while little or no up-regulation was seen in the control group. Minimal changes in brain volumes were found, but there was no change in cognitive performance.The training-dependent regulation of functional connectivity within the posterior DMN component suggests that this stimulation program might exert a beneficial impact in the prevention and treatment of early AD neurodegeneration, in which this neurofunctional pathway is progressively affected by the disease.