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Its dysfunction has been implicated in various conditions including Parkinson\u2019s 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 \u2018connectopic mapping\u2019 \u2013 a novel approach for characterizing fine-grained, overlapping modes of functional connectivity \u2013 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 (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.884) with dopamine transporter availability \u2013 a marker of dopaminergic projections \u2013 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-DOPA), and show that our proposed dopaminergic marker tracks PD diagnosis, symptom severity, and sensitivity to L-DOPA. 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-DOPA 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.\n                  <\/jats:p>","DOI":"10.7554\/elife.71846","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T13:15:19Z","timestamp":1643289319000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.71846","source":"Crossref","is-referenced-by-count":47,"title":["Mapping dopaminergic projections in the human brain with resting-state fMRI"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-0548","authenticated-orcid":true,"given":"Marianne","family":"Oldehinkel","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05wg1m734","id-type":"ROR","asserted-by":"publisher"}],"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre","place":["Nijmegen, Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/05wg1m734","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cognitive Neuroscience, Radboud University Medical Centre","place":["Nijmegen, Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Turner Institute for Brain and Mental Health, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University","place":["Clayton, 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