Cited by 57Functional Brain Connectivity StudiesNeurotransmitter Receptor Influence on BehaviorAttention Deficit Hyperactivity Disorder

The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults

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Farr, Olivia M., Zhang, Sheng, Hu, Sien, Matuskey, David, Abdelghany, Osama, Malison, Robert T., Li, Chiang-shan R.·2014·The International Journal of Neuropsychopharmacology

Abstract

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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  1. Ashburner J Friston KJ Nonlinear spatial normalization using basis functions Hum Brain Mapp 1999 7 254 266 10408769 PMC6873340
  2. Casanova C Merabet L Desautels A Minville K Higher-order motion processing in the pulvinar Prog Brain Res 2001 134 71 82 11702564
  3. Talley EM Rosin DL Lee A Guyenet PG Lynch KR Distribution of alpha 2A–adrenergic receptor-like immunoreactivity in the rat central nervous system J Comp Neurol 1996 372 111 134 8841924

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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
Published
2014-05-13
Volume
17
Issue
08
Pages
1177-1191
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
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
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

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