Fronto-striatal connectivity patterns account for the impact of methylphenidate on choice impulsivity among healthy adults

Maryana Daood, Leehe Peled-Avron, Rachel Ben-Hayun, Michael Nevat, Judith Aharon-Peretz, Rachel Tomer, Roee Admon

Research output: Contribution to journalArticlepeer-review

Abstract

Choice impulsivity depicts a preference towards smaller-sooner rewards over larger-delayed rewards, and is often assessed using a delay discounting (DD) task. Previous research uncovered the prominent role of dopaminergic signaling within fronto-striatal circuits in mediating choice impulsivity. Administration of methylphenidate (MPH), an indirect dopaminergic agonist, was shown to reduce choice impulsivity in animals and pathological populations, although significant inter-individual variability in these effects was reported. Whether MPH impacts choice impulsivity among healthy individuals, and whether variability in the impact of MPH is related to fronto-striatal activation and connectivity patterns, has yet to be assessed. Here, fifty-seven healthy young adults completed the DD task twice during fMRI scans, after acute administration of either MPH (20 mg) or placebo, in a randomized double-blind placebo-controlled design. Acute MPH administration was found to reduce choice impulsivity at the group level, yet substantial variability in this behavioral response was observed. MPH was also found to increase activation in the bilateral putamen and the right caudate, and to enhance functional connectivity between the left putamen and medial prefrontal cortex (mPFC), particularly during non-impulsive choices. Notably, the more putamen-mPFC functional connectivity increased during non-impulsive choices following MPH administration, the less an individual was likely to make impulsive choices. These findings reveal, for the first time in healthy adults, that acute MPH administration is associated with reduced choice impulsivity and increased striatal activation and fronto-striatal connectivity; and furthermore, that the magnitude of MPH-induced change in fronto-striatal connectivity may account for individual differences in the impact of MPH on impulsive behavior.

Original languageEnglish
Article number109190
JournalNeuropharmacology
Volume216
DOIs
StatePublished - 15 Sep 2022

Bibliographical note

Funding Information:
This research was supported by the Israel Science Foundation (ISF) (grant No. 1806/16 ) awarded to RT.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

  • Delay discounting (DD)
  • Dopamine
  • Functional MRI (fMRI)
  • Methylphenidate (MPH)
  • Prefrontal cortex (PFC)
  • Striatum

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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