Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in children with and without ADHD.

Arianna D Cascone, Finnegan Calabro, William Foran, Bart Larsen, Tehila Nugiel, Ashley C Parr, Brenden Tervo-Clemmens, Beatriz Luna, Jessica R Cohen

Journal: Developmental cognitive neuroscience 2023;63():101274

PMID: 37453207

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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.

Address: Neuroscience Curriculum, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: [email protected].; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

DOI: 10.1016/j.dcn.2023.101274

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MeSH Terms: Humans, Child, Attention Deficit Disorder with Hyperactivity, Central Nervous System Stimulants, Dopamine, Neurophysiology, Methylphenidate, Brain, Cognition