Structural and functional network mechanisms of rescuing cognitive control in aging

Abstract

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.

Keywords: Aging; Cognitive control; Diffusion tractography; EEG; Functional connectivity; tACS.

Fig. 1.

Experimental paradigm. A) Order of tasks from Monday to Friday. The Monday session contained baseline NeuroRacer threshold and MRI measures with no tACS. The following three days contained eight runs of EEG and tACS NeuroRacer multitasking assessments. Friday contained eight runs of NeuroRacer with EEG and no tACS. B) EEG electrode locations marked in black with the tACS stimulation locations highlighted in orange (F3-F4). During non-tACS runs, the stimulating electrodes recorded EEG activity. C) Timeline of tasks within each training session. The Friday session contained only eight runs of NeuroRacer. D) The timing of stimulation during NeuroRacer runs with tACS (top) and with EEG recorded (bottom).

Fig. 2.

A) Data included in stepwise regression model across all participants on the dependent variable of baseline multitasking RT with the significant predictor of baseline theta PLV. P value generated from significant stepwise model. The black trendline represents both groups and participants are color-coded for the tACS treatment that they will later receive (orange, 6 Hz; gray, 1 Hz). B) Cost of multitasking compared to single task on RT at each session. The group that received 6 Hz tACS had faster and overall greater gains than the group that received 1 Hz tACS. P value generated from time × group interaction. Follow-up analyses revealed a significant group difference in RT cost change on tACS 2 (denoted by small asterisk). C) Group change in each PLV frequency band on tACS 2. Theta tACS increased PLV and control tACS decreased PLV. P value generated from main effect of tACS group.

Fig. 3.

Changes in theta, alpha, beta, and gamma PLV as a function of baseline ILF (A) and CCB (B) integrity. P values represent the significance of the predictor of ILF or CCB FA on PLV change in the final model for the 6 Hz group. Insets indicate the tract masks in MNI space, adapted from (Ivanova et al., 2016). Note that the CCB is shown in green.

Fig. 4.

Data included in stepwise regression model across all participants on the dependent variable of RT cost change and PLV change in each frequency predictors. Only alpha PLV was a significant predictor of change in RT cost. The black trendline represents both groups and participants are color-coded for visualization purposes only of the tACS treatment that they received (orange, 6 Hz; gray, 1 Hz). P value listed only for the significant predictor.