Abstract
Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. How dopamine modulates the large-scale brain dynamics during cognitive performance has remained elusive, however. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (L-dopa) on two aspects of brain dynamics, blood oxygen-level-dependent (BOLD) signal variability and the connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in L-dopa-induced behavioral benefits. Relative to placebo, L-dopa increased BOLD signal variability in task-relevant regions within temporal, inferior frontal, parietal and cingulo-opercular cortices. On the connectome level, L-dopa diminished functional integration in a network of temporo-cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity, and occurred concurrent with a relative hyper-connectivity in paracentral lobule and precuneus. Both, L-dopa-induced signal variability modulation and functional connectome modulations proved predictive of an individual’s L-dopa-induced gain in behavioral measures, namely response speed and perceptual sensitivity. Lastly, signal variability modulation correlated positively with modulation of nodal connectivity and network efficiency in distributed cortical regions. In sum, by providing first evidence for a direct link between dopaminergic modulation of brain signal variability and the functional connectome, we conclude that dopamine enhances information-processing capacity in the human cortex during cognitive performance.
Significance Statement How does dopamine shape our cognitive performance? Here we develop and test the hypothesis that enhanced levels of dopamine act upon intra- as well as inter-regional dynamics across the human cortex during a challenging working memory task. We find that, relative to placebo, L-dopa increases signal variability in task-relevant cortical regions, diminishes network integration of temporo-dngulo-opercular regions known to be crucial for sustained attention, and induces hyper-connectivity within the functional connectome. Importantly, the degree of theses modulations explained individuals’ behavioral benefits from L-dopa. Notably, L-dopa-induced modulation of signal variability positively correlated with that of the functional connectome in distributed cortical regions. Our findings shed light on how dopamine modulates dynamic communication in the human cortex during cognitive performance.