Stimulant medications affect arousal and reward, not attention networks
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.
Authors
- Kristen M. Scheidter
- Timothy Hendrickson (ORCID: https://orcid.org/0000-0001-6862-6526)
- Benjamin P. Kay (ORCID: https://orcid.org/0000-0003-3628-8029)
- Muriah D. Wheelock (ORCID: https://orcid.org/0000-0002-3409-8777)
- Scott McGill Nelson (ORCID: https://orcid.org/0000-0002-9099-3047)
- Ryan V. Raut (ORCID: https://orcid.org/0000-0002-8761-1431)
- Nico U.F. Dosenbach (ORCID: https://orcid.org/0000-0002-6876-7078)
- Eric Feczko (ORCID: https://orcid.org/0000-0003-1337-5517)
- Lucille A. Moore (ORCID: https://orcid.org/0000-0002-7665-2713)
- Aishwarya Rajesh (ORCID: https://orcid.org/0000-0002-6583-1695)
- Russell Taki Shinohara (ORCID: https://orcid.org/0000-0001-8627-8203)
- Roselyne J. Chauvin (ORCID: https://orcid.org/0000-0001-5786-4705)
- Damien A. Fair (ORCID: https://orcid.org/0000-0001-8602-393X)
- Scott Marek (ORCID: https://orcid.org/0000-0003-0032-9052)
- Brenden Tervo‐Clemmens (ORCID: https://orcid.org/0000-0002-9557-1126)
- Julia Monk
- Evan M. Gordon (ORCID: https://orcid.org/0000-0002-2276-5237)
- Jarod L. Roland (ORCID: https://orcid.org/0000-0002-1312-8826)
- Óscar Miranda-Domínguez (ORCID: https://orcid.org/0000-0002-3622-0166)
- Thomas Madison (ORCID: https://orcid.org/0000-0003-3030-6580)
- Samuel R. Krimmel (ORCID: https://orcid.org/0000-0002-5198-1545)
- Anxu Wang
- Joshua S. Siegel (ORCID: https://orcid.org/0000-0002-5752-3641)
- Timothy O. Laumann
- Robert Hermosillo (ORCID: https://orcid.org/0000-0003-2959-8483)
- Athanasia Metoki (ORCID: https://orcid.org/0000-0002-8945-269X)
- Vahdeta Suljic
- Noah J. Baden
- Nadeshka Ramirez-Perez
- Forrest I. Whiting
- Ginger E. Nicol (ORCID: https://orcid.org/0000-0001-5823-6129)
- Babatunde Adeyemo
- Jim Pollaro
- Deanna M. Barch
- Andrew Eck
- Anita Randolph
- Marcus E. Raichle
Institutions
- University of Minnesota (US)
- NYU Langone Health (US)
- Mallinckrodt (United States) (US)
Publication Details
- Journal
- Cell
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1016/j.cell.2025.11.039
- Citations
- 1
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.43