Sex differences in atypical fronto-subcortical structural connectivity among children with attention-deficit/hyperactivity disorder: Associations with delay discounting

Keri S Rosch; Mitchell A Batschelett; Deana Crocetti; Stewart H Mostofsky; Karen E Seymour

doi:10.1016/j.bbr.2023.114525

Sex differences in atypical fronto-subcortical structural connectivity among children with attention-deficit/hyperactivity disorder: Associations with delay discounting

Behav Brain Res. 2023 Aug 24:452:114525. doi: 10.1016/j.bbr.2023.114525. Epub 2023 Jun 3.

Authors

Keri S Rosch¹, Mitchell A Batschelett², Deana Crocetti², Stewart H Mostofsky³, Karen E Seymour⁴

Affiliations

¹ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, USA; Neuropsychology Department, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA. Electronic address: rosch@kennedykrieger.org.
² Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, USA.
³ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA; Department of Neurology, Johns Hopkins University, USA.
⁴ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA; Department of Mental Health, Johns Hopkins University, Baltimore, MD, USA.

PMID: 37271314
PMCID: PMC10527538 (available on 2024-08-24)
DOI: 10.1016/j.bbr.2023.114525

Abstract

Purpose: Atypical fronto-subcortical neural circuitry has been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), including connections between prefrontal cortical regions involved in top-down cognitive control and subcortical limbic structures (striatum and amygdala) involved in bottom-up reward and emotional processing. The integrity of fronto-subcortical connections may also relate to interindividual variability in delay discounting, or a preference for smaller, immediate over larger, delayed rewards, which is associated with ADHD, with recent evidence of ADHD-related sex differences.

Methods: We applied diffusion tensor imaging to compare the integrity of the white matter connections within fronto-subcortical tracts among 187 8-12 year-old children either with ADHD ((n = 106; 29 girls) or typically developing (TD) controls ((n = 81; 28 girls). Analyses focused on diagnostic group differences in fractional anisotropy (FA) within fronto-subcortical circuitry implicated in delay discounting, connecting subregions of the striatum (dorsal executive and ventral limbic areas) and amygdala with prefrontal regions of interest (dorsolateral [dlPFC], orbitofrontal [OFC] and anterior cingulate cortex [ACC]), and associations with two behavioral assessments of delay discounting.

Results: Children with ADHD showed reduced FA in tracts connecting OFC with ventral striatum, regardless of sex, whereas reduced FA in the OFC-amygdala and ventral ACC-amygdala tracts were specific to boys with ADHD. Across diagnostic groups and sex, reduced FA in the dorsal ACC-executive striatum tract correlated with greater game time delay discounting.

Conclusions: These results suggest a potential neurobiological substrate of heightened delay discounting in children with ADHD and support the need for additional studies including larger sample sizes of girls with ADHD to further elucidate ADHD-related sex differences in these relationships.

Keywords: Amygdala; DTI; Prefrontal; Reward; Striatum.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / diagnostic imaging
Child
Delay Discounting* / physiology
Diffusion Tensor Imaging
Female
Humans
Magnetic Resonance Imaging
Male
Prefrontal Cortex / diagnostic imaging
Sex Characteristics

Abstract

Publication types

MeSH terms

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