Fig. 1: Experimental design.

A Timeline of events. In each session, participants were given an oral dose of methylphenidate (MP) or placebo at time 0; the [¹¹C] Raclopride bolus injection and simultaneous PET-fMRI scanning started at 30 min; an IV dose of MP or placebo was given at 60 min; and throughout the duration of the session participants used a button box in the scanner to self-report their experience of ‘high’ to the drug. B An example subject’s session structure. Participants three separate imaging sessions on different days. Sessions were identical except for drug condition: (Session 1) oral PLA and IV PLA; (Session 2) oral MP (60 mg) and IV PLA (3 cc saline); (Session 3) oral PLA and IV MP (0.25 mg/kg in 3 cc sterile water). The session order was counterbalanced across participants. C Analysis schema. With PET data, minute-to-minute changes in dopamine receptor binding were used to estimate the rate of dopamine increases in response to MP (decreases in D2 receptor binding following MP are a proxy for dopamine increases). With fMRI data, we calculated minute-to-minute changes in global brain connectivity across the scan session. We then performed multiple regression to identify global brain connectivity patterns that were temporally associated with slow and fast dopamine increases. Finally, we parcellated these maps to show how dopamine rate-associated patterns of global brain connectivity were distributed across large-scale brain functional networks.