Methylphenidate Promotes a Frontoparietal-Dominant Brain State Improving Cognitive Performance: A Randomized Trial

Methylphenidate (MP) is a widely used stimulant medication for the treatment of attention-deficit hyperactivity disorder that enhances brain dopamine signaling and improves attention. However, how dopamine stimulation alters brain state dynamics to support improved attention during task performance is still unclear. To address this, we employed a multimodal neuroimaging approach combining positron emission tomography, functional magnetic resonance imaging, and behavioral tasks, to discover associations between dopamine signaling, brain dynamics, and cognition. Multimodal images were collected from 37 healthy adults under a single-blind, counterbalanced, placebo-controlled crossover study. Dynamic functional analysis was used to compare the alterations in dynamic features of brain states before and after MP. Subsequently, we analyzed the correlation between these brain state changes and baseline striatal D₁ and D₂ dopamine receptor (D₁R, D₂R) availability. We also examined alterations in dynamic brain states and their effects on visuospatial tasks. The results showed that MP primarily affected frontoparietal-dominant activated (FPN+), somatomotor-dominant activated (SOM+), and visual-dominant suppressed (VIS-) brain states. Specifically, the dwell time and fractional occupancy exhibited significant increases within the FPN+ and VIS- and an opposite trend within the SOM+. Furthermore, the increase of dwell time in FPN+, which was positively correlated with baseline striatal D₁R availability, was also associated with quicker response in the 2-ball-track task, but not significantly for the 3-ball-track task. The findings suggest that MP's enhancement of brain states with FPN+ and VIS- while decreasing SOM+, in part through D₁R signaling might underlie MP's improvement of attention for low demanding tasks in healthy populations.