Neuromelanin-Sensitive MRI to Investigate Dopamine in Adolescents with ADHD
Poster No:
1930
Submission Type:
Abstract Submission
Authors:
Ryan Verbitsky1, Bevin Wiley1, Marilena DeMayo1, Clifford Cassidy2, Kara Murias1
Institutions:
1University of Calgary, Calgary, Canada, 2SUNY Stony brook, New York, NY
First Author:
Co-Author(s):
Introduction:
Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder marked by deficits in executive functioning (EF), including working memory, cognitive flexibility, selective attention, and response inhibition. These deficits are partly attributed to disruptions in dopamine signaling in the prefrontal cortex from the ventral tegmental area (VTA) and substantia nigra (SN). Neuromelanin is a paramagnetic byproduct of dopamine and noradrenaline synthesis that is localized to site of production and accumulates throughout the lifespan. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) provides a non-invasive proxy for dopamine function by detecting neuromelanin. This study aims to explore neuromelanin signal in the VTA-SN region of a adolescents with ADHD and neurotypical individuals to assess the relationship of EF performance and stimulant medication effect.
Methods:
A total of 30 adolescents (mean age = 12.44 years, sd = 1.92y, 13 females) comprised of adolescents both with and without ADHD aged 10–16 years were recruited. NM-MRI was conducted using a 3T MRI scanner. NM-MRI preprocessing involved co-registration, bias correction, and normalization to calculate contrast-to-noise ratio (CNR) values for the VTA-SN region. EF tasks, including Flanker (test of inhibition), List Sorting (working memory), Dimension Change Card Sort (cognitive flexibility), and Stop Signal Reaction Task (response inhibition) were administered. Robust linear regression was used to analyze relationships between NM-MRI signal and EF performance. An additional robust linear regression analysis was performed examining the relationship between NM-MRI signal and stimulant medication historical dose and duration in the ADHD group.
Results:
Preliminary data from 30 participants was used for voxelwise analyses, which identified clusters of significant neuromelanin signal variation correlating with EF task performance. There was a negative association between NM-MRI signal in the substantia nigra and working memory (p=0.0006). Associations with other EF tasks were not significant. There was a negative association between NM-MRI signal in the substantia nigra and duration of medication (p= 0.0064). However, association with the dose (mg) of medication was not significant.
Conclusions:
These preliminary findings support the use of NM-MRI to neuromelanin content in adolescents with a non-neurodegenerative disorder, demonstrating its potential as a non-invasive marker for dopamine function and metabolism. Variations in NM-MRI signals were associated with differences in EF task performance and stimulant medication exposure, highlighting its promise as an imaging tool for assessing other neurodevelopmental disorders or conditions associated with attention dysregulation or catecholamine synthesis. Further validation studies are required to confirm its utility and reproducibility, especially in pediatric populations.
Modeling and Analysis Methods:
Image Registration and Computational Anatomy
Motion Correction and Preprocessing
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Neuroanatomy Other 2
Novel Imaging Acquisition Methods:
Anatomical MRI
Imaging Methods Other 1
Keywords:
Attention Deficit Disorder
Dopamine
MRI
Neurotransmitter
PEDIATRIC
Other - Neuromelanin; Executive control; Stimulant medication
1|2Indicates the priority used for review
·NM average CNR scan at x = 90, y =112, z = 59, containing voxels with a relationship where p<0.05 in MNI space using MATLAB
Abstract Information
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Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Cassidy, C. M., Zucca, F. A., Girgis, R. R., Baker, S. C., Weinstein, J. J., Sharp, M. E., Bellei, C., Valmadre, A., Vanegas, N., Kegeles, L. S., Brucato, G., Kang, U. J., Sulzer, D., Zecca, L., Abi-Dargham, A., & Horga, G. (2019a). Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. Proceedings of the National Academy of Sciences of the United States of America, 116(11), 5108–5117. https://doi.org/10.1073/pnas.1807983116