The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults
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By blocking dopamine and norepinephrine transporters, methylphenidate affects cognitive performance and regional brain activation in healthy individuals as well as those with neuropsychiatric disorders. Resting-state connectivity evaluates the functional integrity of a network of brain regions. Here, we examined how methylphenidate effects resting-state functional connectivity of the dorsal striatum and thalamus, areas each with dense dopaminergic and noradrenergic innervations, as well as global cerebral connectivity. We administered a single, oral dose (45 mg) to 24 healthy adults and compared resting-state connectivity to 24 demographically matched adults who did not receive any medication. The results showed that methylphenidate alters seed-based and global connectivity between the thalamus/dorsal striatum with primary motor cortex, amygdala/hippocampus and frontal executive areas (p < 0.05, corrected). Specifically, while methylphenidate at this dosage enhances connectivity to the motor cortex and memory circuits, it dampens prefrontal cortical connectivity perhaps by increasing catecholaminergic signalling past the 'optimal' level. These findings advance our understanding of a critical aspect of the multifaceted effects of methylphenidate on brain functions. The results may also facilitate future studies of the aetiology and treatment of neurological and psychiatric disorders that implicate catecholaminergic dysfunction.
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Nonstimulants have downstream effects that modulate activation patterns of frontoparietal regions through extracellular catecholamine and indirect effects that regulate brain connectivity patterns of the central executive network and default mode network.
“Besides, they also have downstream effects that modulate the activation patterns of frontoparietal regions through extracellular catecholamine and indirect effects that regulate the brain connectivity patterns of the central executive network and default mode network (Borchert et al., 2019; Farr et al., 2014; Lin & Gau, 2015; Schulz et al., 2012; Shafritz et al., 2004).”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Farr et al., 2014
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- Authors
- Farr, O. M., Zhang, S., Hu, S., Matuskey, D., Abdelghany, O., Malison, R. T., & Li, C.-S. R.
- Affiliations
- Yale University (US)
- Yale New Haven Hospital (US)
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-13
- Volume
- 17
- Issue
- 08
- Pages
- 1177-1191
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC4506752
- OpenAlex
- W2103784428
- Cited by
- 57
- References
- 133
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 1 · 2014: 1
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Alliance for Research on Schizophrenia and Depression (P20DA027844)
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R21AA018004, R01AA021449)
- National Institute on Drug Abuse (R21DA026998, K24DA017899, R01DA023248, P20DA027844, K02DA026990)
- National Institute of Neurological Disorders and Stroke (T32 NS07224, T32NS007224)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- methylphenidate, resting-state functional connectivity, dorsal striatum, thalamus, seed-based functional connectivity, primary motor cortex, amygdala, hippocampus, prefrontal cortex, dopamine transporter, norepinephrine transporter, healthy adults
- MeSH terms
- Adult, Central Nervous System Stimulants, Corpus Striatum, Female, Humans, Magnetic Resonance Imaging, Male, Methylphenidate, Neural Pathways, Rest, Thalamus, Young Adult, Functional Neuroimaging, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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