Structural and functional network mechanisms of rescuing cognitive control in aging

Age-related declines in cognitive control, an ability critical in most daily tasks, threaten individual independence. We previously showed in both older and younger adults that transcranial alternating current stimulation (tACS) can improve cognitive control, with effects observed across neural regions distant from the stimulated site and frequencies outside the stimulated range. Here, we assess network-level changes in neural activity that extend beyond the stimulated site and evaluate anatomical pathways that subserve these effects. We investigated the potential to rescue cognitive control in aging using prefrontal (F3-F4) theta (6 Hz) or control (1 Hz) tACS while older adults engaged in a cognitive control video game intervention on three consecutive days. Functional connectivity was assessed with EEG by measuring daily changes in frontal-posterior phase-locking values (PLV) from the tACS-free baseline. Structural connectivity was measured using MRI diffusion tractography data collected at baseline. Theta tACS improved multitasking performance, and individual gains reflected a dissociation in daily PLV changes, where theta tACS strengthened PLV and control tACS reduced PLV. Strengthened alpha-beta PLV in the theta tACS group correlated positively with inferior longitudinal fasciculus and corpus callosum body integrity, and further explained multitasking gains. These results demonstrate that theta tACS can improve cognitive control in aging by strengthening functional connectivity, particularly in higher frequency bands. However, the extent of functional connectivity gains is limited by the integrity of structural white matter tracts. Given that advanced age is associated with decreased white matter integrity, results suggest that the deployment of tACS as a therapeutic is best prior to advanced age.