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Stimulant medications affect arousal and reward, not attention networks

Benjamin P. Kay, Muriah D. Wheelock, Joshua S. Siegel, Ryan V. Raut, Roselyne J. Chauvin, Athanasia Metoki, Aishwarya Rajesh, Andrew Eck, Jim Pollaro, Anxu Wang, Vahdeta Suljic, Babatunde Adeyemo, Noah J. Baden, Kristen M. Scheidter, Julia Monk, Forrest I. Whiting, Nadeshka Ramirez-Perez, Samuel R. Krimmel, Russell T. Shinohara, Brenden Tervo‐Clemmens, Robert Hermosillo, Steven M. Nelson, Timothy Hendrickson, Thomas Madison, Lucille A. Moore, Óscar Miranda-Domínguez, Anita Randolph, Eric Feczko, Jarod L. Roland, Ginger E. Nicol, Timothy O. Laumann, Scott Marek, Evan M. Gordon, Marcus E. Raichle, Deanna M. Barch, Damien A. Fair, Nico U.F. Dosenbach

2025Cell7 citationsDOIOpen Access PDF

Abstract

Prescription stimulants (e.g., methylphenidate) are thought to improve attention, but evidence from prior fMRI studies is conflicted. We utilized resting-state fMRI data from the Adolescent Brain Cognitive Development Study (n = 11,875; 8-11 years old) and validated the functional connectivity findings in a precision imaging drug trial with highly sampled (n = 5, 165-210 min each) healthy adults (methylphenidate 40 mg). Stimulant-related connectivity differences in sensorimotor regions matched fMRI patterns of daytime arousal, sleeping longer at night, and norepinephrine transporter expression. Taking stimulants reversed the effects of sleep deprivation on connectivity and school grades. Connectivity was also changed in salience and parietal memory networks, which are important for dopamine-mediated, reward-motivated learning, but not the brain's attention systems (e.g., dorsal attention network). The combined noradrenergic and dopaminergic effects of stimulants may drive brain organization towards a more wakeful and rewarded configuration, improving task effort and persistence without effects on attention networks.

Topics & Concepts

StimulantAffect (linguistics)ArousalNeuroscienceDopaminergicSleep deprivationCognitionSalience (neuroscience)PsychologyMonoaminergicEffects of sleep deprivation on cognitive performanceVigilance (psychology)Brain activity and meditationAddictionDopamineCognitive psychologyBiologyBrain mappingNeuroimagingNorepinephrineWakefulnessNicotineDextroamphetamineFunctional magnetic resonance imagingModafinilDorsumDefault mode networkAttention networkDevelopmental psychologyWorking memoryDisengagement theoryTask (project management)Elementary cognitive taskSleep (system call)Sensory processingAudiologyElectroencephalographyConnectomeReward systemFunctional Brain Connectivity StudiesNeural and Behavioral Psychology StudiesEEG and Brain-Computer Interfaces
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