Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults

Abstract

Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.

Keywords: caffeine; memory; methylphenidate; modafinil; neuroenhancement; neuroimaging; resting state functional connectivity.

FIGURE 1

Marginal means of memory performance in memory tasks with visual and audio material as a function of condition plotted separately for all three stimulant groups. CAF, caffeine; MOD, modafinil; MPH, methylphenidate; error bars represent between‐subject 95% confidence intervals; D_prime, d′ from an implicit memory task; early_audRcall, early recall for memory task with audio material; late_audRecall, late recall for memory task with audio material; early_visRecall, early recall for memory task with visual material; early_false_audRecall, early recall for lures (false memory) in memory task with audio material

FIGURE 2

Effects of caffeine, modafinil, and methylphenidate on functional connectivity. Upper panel: results from hierarchical cluster analysis. Two clusters significantly differed between the stimulant and placebo condition. First and second refer to the first and second resting state scan, respectively. The red lines represent significant correlations of the time series between the regions of interest (gray spheres). Lower panel: change in functional connectivity from the placebo to the stimulant condition correlated significantly negatively with change in latent memory performance from the placebo to the stimulant condition in cluster 1 but not in cluster 2. * indicates significance at a p‐level <.05 (FDR‐corrected)

FIGURE 3

Correlation of stimulant‐induced changes in whole‐brain rs‐FC with changes in latent memory. Left panel: measurement model for latent memory change factor. d′, d prime from implicit memory task; e AR, early recall for memory task with audio material; l AR, late recall for memory task with audio material; e VR, early recall for memory task with visual material; * signifies statistical significance at the p < .05 level. Right panel: results from whole brain hierarchical cluster analysis. Negative correlation of occipital–medial temporal lobe cluster with the latent memory change factor is significantly reduced in the stimulant compared with the placebo condition. First and second refer to the first and second resting state scan, respectively. The red lines represent significant correlations of the time series between the regions of interest (gray spheres)