Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in
Arianna D Cascone1, Finnegan Calabro2, William Foran3
1Neuroscience Curriculum, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Insights
Children with ADHD show impaired response inhibition, which is improved by dopamine modulation. Higher brain iron, linked to dopamine, predicted better response to methylphenidate in ADHD children.
Area of Science:
- Neuroscience
- Developmental Psychology
- Radiology
Background:
- Children with ADHD often have difficulties with response inhibition.
- Dopamine (DA) modulation, through rewards or medications like methylphenidate (MPH), can improve these deficits.
- The influence of intrinsic dopamine availability on these modulatory effects remains unclear.
Purpose of the Study:
- To investigate the relationship between intrinsic dopamine availability, measured by brain tissue iron, and response inhibition in children.
- To examine how intrinsic dopamine availability affects the response to dopaminergic modulation (MPH) in children with ADHD.
- To clarify the role of subcortical brain iron in cognitive functions related to dopamine.
Main Methods:
- Assessed intrinsic dopamine availability using MRI-based measurements of basal ganglia and thalamic tissue iron.
- Recruited 36 medication-naïve children with ADHD and 29 typically developing (TD) children (ages 8-12).
- Utilized fMRI, standard and rewarded go/no-go tasks, and a double-blind, placebo-controlled MPH challenge in children with ADHD.
Main Results:
- No significant group differences in brain tissue iron were found between children with ADHD and TD children.
- Higher putamen tissue iron correlated with poorer response inhibition across all participants.
- Increased putamen and caudate tissue iron were associated with enhanced task performance following MPH administration in children with ADHD.
Conclusions:
- Subcortical brain tissue iron, a proxy for intrinsic dopamine availability, does not differ between children with ADHD and TD peers.
- Brain iron levels are linked to response inhibition capabilities and predict medication response in ADHD.
- Findings illuminate the role of intrinsic dopamine in cognitive modulation within ADHD and typically developing children.
Abstract:
Children with attention-deficit/hyperactivity disorder (ADHD) exhibit impairments in response inhibition. These impairments are ameliorated by modulating dopamine (DA) via the administration of rewards or stimulant medication like methylphenidate (MPH). It is currently unclear whether intrinsic DA availability impacts these effects of dopaminergic modulation on response inhibition. Thus, we estimated intrinsic DA availability using magnetic resonance-based assessments of basal ganglia and thalamic tissue iron in 36 medication-naïve children with ADHD and 29 typically developing (TD) children (8-12 y) who underwent fMRI scans and completed standard and rewarded go/no-go tasks. Children with ADHD additionally participated in a double-blind, randomized, placebo-controlled, crossover MPH challenge. Using linear regressions covarying for age and sex, we determined there were no group differences in brain tissue iron. We additionally found that higher putamen tissue iron was associated with worse response inhibition performance in all participants. Crucially, we observed that higher putamen and caudate tissue iron was associated with greater responsivity to MPH, as measured by improved task performance, in participants with ADHD. These results begin to clarify the role of subcortical brain tissue iron, a measure associated with intrinsic DA availability, in the cognitive effects of reward- and MPH-related dopaminergic modulation in children with ADHD and TD children.
Related Concept Videos
01:30Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
01:28Disorders of the Nervous Tissue
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...
01:29Drugs Affecting Neurotransmitter Synthesis
01:14Brain Imaging
These technologies include computerized axial tomography (CAT or CT scans), positron-emission tomography (PET scans), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and Transcranial Magnetic...
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
01:30Information Processing Approach