Mapping dopaminergic projections in the human brain with resting-state fMRI

Marianne Oldehinkel*, Alberto Llera, Myrthe Faber, Ismael Huertas, Jan K. Buitelaar, Bastiaan R. Bloem, Andre F. Marquand, Rick C. Helmich, Koen Haak, Christian F. Beckmann

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)


The striatum receives dense dopaminergic projections, making it a key region of the dopaminergic system. Its dysfunction has been implicated in various conditions including Parkinson’s disease (PD) and substance use disorder. However, the investigation of dopamine-specific functioning in humans is problematic as current MRI approaches are unable to differentiate between dopaminergic and other projections. Here, we demonstrate that ‘connectopic mapping’-a novel approach for characterizing fine-grained, overlapping modes of functional connectivity-can be used to map dopaminergic projections in striatum. We applied connectopic mapping to resting-state functional MRI data of the Human Connectome Project (population cohort; N=839) and selected the second-order striatal connectivity mode for further analyses. We first validated its specificity to dopaminergic projections by demonstrating a high spatial correlation (r=0.884) with dopamine transporter availability-a marker of dopaminergic projections-derived from DaT SPECT scans of 209 healthy controls. Next, we obtained the subject-specific second-order modes from 20 controls and 39 PD patients scanned under placebo and under dopamine replacement therapy (L-ÐOPA), and show that our proposed dopaminergic marker tracks PD diagnosis, symptom severity, and sensitivity to L-ÐOPA. Finally, across 30 daily alcohol users and 38 daily smokers, we establish strong associations with self-reported alcohol and nicotine use. Our findings provide evidence that the second-order mode of functional connectivity in striatum maps onto dopaminergic projections, tracks inter-individual differences in PD symptom severity and L-ÐOPA sensitivity, and exhibits strong associations with levels of nicotine and alcohol use, thereby offering a new biomarker for dopamine-­ related (dys)function in the human brain.

Original languageEnglish
Article numbere71846
Pages (from-to)1-37
Publication statusPublished - 3 Feb 2022


  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers/analysis
  • Brain/diagnostic imaging
  • Cohort Studies
  • Corpus Striatum/diagnostic imaging
  • Dopamine Plasma Membrane Transport Proteins/physiology
  • Dopamine/metabolism
  • Female
  • Humans
  • Levodopa/therapeutic use
  • Magnetic Resonance Imaging/methods
  • Male
  • Middle Aged
  • Neural Pathways/physiopathology
  • Parkinson Disease/diagnostic imaging


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