Methylphenidate enhances a frontoparietal-dominant brain state improving cognitive performance

Background Methylphenidate (MP) is a widely used stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD) 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. Methods We employed a multimodal neuroimaging approach combining positron emission tomography, functional magnetic resonance imaging, and behavioral tests, to discover associations between dopamine signaling, brain activity, 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 then examined alterations in dynamic brain states and their effects on attention performances. Results 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- while 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 significant for the 3-ball-track task. Conclusions The findings suggest that MP’s enhancement of brain states with FPN + and VIS- while decreasing SOM+, in part through D1R signaling might underlie the MP’s improvement of attention for low cognitive effort tasks in healthy populations.