Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands; Turner Institute for Brain and Mental Health, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University, Clayton, Australia
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands
Myrthe Faber
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Communication and Cognition, Tilburg Centre for Cognition and Communication, Tilburg University, Tilburg, Netherlands
Ismael Huertas
Institute of Biomedicine of Seville (IBiS), Seville, Spain
Jan K Buitelaar
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands
Bastiaan R Bloem
Department of Neurology, and Centre of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, Netherlands
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands; Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London, London, United Kingdom
Rick C Helmich
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Neurology, and Centre of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, Netherlands
Koen V Haak
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands
Christian F Beckmann
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands; Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, Netherlands; Wellcome Centre for Integrative Neuroimaging (WIN FMRIB), University of Oxford, Oxford, United Kingdom
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-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.
