Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 11, Pages 5108-5117Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1807983116
Keywords
magnetic resonance imaging; dopamine; neuromelanin; schizophrenia; Parkinson's disease
Categories
Funding
- NYSPI MRI unit
- David Mahoney Neuroimaging Grant from The Dana Foundation
- Parkinson's Disease Foundation
- Fonds de Recherche du Quebec-Sante
- Quebec Research Fund on Parkinson's
- NIH [NS101982, NS096494]
- Italian Ministry of Education, University, and Research (MIUR)-National Research Programme (PNR)-National Research Council of Italy (CNR) Flagship InterOmics Project [PB.P05]
- MIURPNR-CNR Aging Program
- MIUR Research Projects of National Interest [2015T778JW]
- Grigioni Foundation for Parkinson's Disease (Milan, Italy)
- NIH National Institute on Drug Abuse Grant [DA04718]
- Parkinson's, Richter
- JPB Foundations
- Parkinson's Foundation
Ask authors/readers for more resources
Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in non-neurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN sub-regions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available