Neural correlates of aggression in medication-naive children with ADHD: multivariate analysis of morphometry and tractography
Open accessAbstract
Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10±2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.
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Such analyses have been applied to study how white matter fiber tracts are affected in individuals with different disease severity, how tracts relate to cognitive and socio-emotional function, and how tracts develop during human neurodevelopment and aging.
“Such analyses have been applied to study, e.g., how white matter fiber tracts are affected in individuals with different disease severity (Cha et al., 2015; Chiang et al., 2016; Price et al., 2007), how tracts relate to cognitive and socio-emotional function (Zekelman et al., 2021), and how tracts are developing during human neurodevelopment and aging (Gertheiss et al., 2013; Hasan et al., 2009a;”
From Quantitative mapping of the brain’s structural connectivity using diffusion MRI tractography: A review (2022) · cites this paper as Cha et al., 2015
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- Authors
- Cha, J., Fekete, T., Siciliano, F., Biezonski, D., Greenhill, L., Pliszka, S. R., Blader, J. C., Krain Roy, A., Leibenluft, E., & Posner, J.
- Affiliations
- New York State Psychiatric Institute (US)
- KU Leuven (BE)
- The University of Texas at San Antonio Health Science Center (US)
- National Institute of Mental Health (US)
- Corresponding author
- Cha, Jiook
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2015-02-03
- Volume
- 40
- Issue
- 7
- Pages
- 1717-1725
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4915254
- OpenAlex
- W1987128048
- Cited by
- 75
- References
- 7
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 8 · 2021: 11 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 5
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Shire
- National Institute of Mental Health (R01MH101172, K23MH091249)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, aggression, nucleus accumbens, impulsivity, white matter connectivity, orbitofrontal cortex, cortical thickness, reward processing, frustration, structural MRI, diffusion MRI
- MeSH terms
- Adolescent, Aggression, Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Child, Female, Humans, Image Processing, Computer-Assisted, Impulsive Behavior, Magnetic Resonance Imaging, Male, Neural Pathways, Statistics as Topic, Multivariate Analysis, White Matter
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