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ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting.
J Neurodev Disord. 2018 12 13; 10(1):34.JN

Abstract

BACKGROUND

Attention-deficit/hyperactivity disorder (ADHD) is associated with atypical fronto-subcortical neural circuitry and heightened delay discounting, or a stronger preference for smaller, immediate rewards over larger, delayed rewards. Recent evidence of ADHD-related sex differences in brain structure and function suggests anomalies in fronto-subcortical circuitry may differ among girls and boys with ADHD. The current study examined whether the functional connectivity (FC) within fronto-subcortical neural circuitry differs among girls and boys with ADHD compared to same-sex typically developing (TD) controls and relates to delay discounting.

METHODS

Participants include 8-12-year-old children with ADHD (n = 72, 20 girls) and TD controls (n = 75, 21 girls). Fronto-subcortical regions of interest were functionally defined by applying independent component analysis to resting-state fMRI data. Intrinsic FC between subcortical components, including the striatum and amygdala, and prefrontal components, including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and anterior dorsolateral prefrontal cortex (dlPFC), was compared across diagnostic groups overall and within sex. Correlations between intrinsic FC of the six fronto-subcortical pairs and delay discounting were also examined.

RESULTS

Both girls and boys with ADHD show atypical FC between vmPFC and subcortical regions including the striatum (stronger positive FC in ADHD) and amygdala (weaker negative FC in ADHD), with the greatest diagnostic effects among girls. In addition, girls with ADHD show atypical intrinsic FC between the striatum and dlPFC components, including stronger positive FC with ACC and stronger negative FC with dlPFC. Further, girls but not boys, with ADHD, show heightened real-time delay discounting. Brain-behavior correlations suggest (1) stronger negative FC between the striatal and dlPFC components correlated with greater money delay discounting across all participants and (2) stronger FC between the amygdala with both the dlPFC and ACC components was differentially related to heightened real-time discounting among girls and boys with and without ADHD.

CONCLUSIONS

Our findings suggest fronto-subcortical functional networks are affected in children with ADHD, particularly girls, and relate to delay discounting. These results also provide preliminary evidence of greater disruptions in fronto-subcortical FC among girls with ADHD that is not due to elevated inattention symptom severity, intellectual reasoning ability, age, or head motion.

Authors+Show Affiliations

Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, 21205, USA. rosch@kennedykrieger.org. Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, MD, 21205, USA. rosch@kennedykrieger.org. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. rosch@kennedykrieger.org.Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, 21205, USA. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, 21205, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Pub Type(s)

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

Language

eng

PubMed ID

30541434

Citation

Rosch, Keri S., et al. "ADHD-related Sex Differences in Fronto-subcortical Intrinsic Functional Connectivity and Associations With Delay Discounting." Journal of Neurodevelopmental Disorders, vol. 10, no. 1, 2018, p. 34.
Rosch KS, Mostofsky SH, Nebel MB. ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting. J Neurodev Disord. 2018;10(1):34.
Rosch, K. S., Mostofsky, S. H., & Nebel, M. B. (2018). ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting. Journal of Neurodevelopmental Disorders, 10(1), 34. https://doi.org/10.1186/s11689-018-9254-9
Rosch KS, Mostofsky SH, Nebel MB. ADHD-related Sex Differences in Fronto-subcortical Intrinsic Functional Connectivity and Associations With Delay Discounting. J Neurodev Disord. 2018 12 13;10(1):34. PubMed PMID: 30541434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting. AU - Rosch,Keri S, AU - Mostofsky,Stewart H, AU - Nebel,Mary Beth, Y1 - 2018/12/13/ PY - 2018/02/08/received PY - 2018/11/14/accepted PY - 2018/12/14/entrez PY - 2018/12/14/pubmed PY - 2019/10/8/medline KW - ADHD KW - Delay discounting KW - Functional connectivity KW - ICA KW - Resting-state KW - Reward KW - Temporal discounting KW - fMRI SP - 34 EP - 34 JF - Journal of neurodevelopmental disorders JO - J Neurodev Disord VL - 10 IS - 1 N2 - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with atypical fronto-subcortical neural circuitry and heightened delay discounting, or a stronger preference for smaller, immediate rewards over larger, delayed rewards. Recent evidence of ADHD-related sex differences in brain structure and function suggests anomalies in fronto-subcortical circuitry may differ among girls and boys with ADHD. The current study examined whether the functional connectivity (FC) within fronto-subcortical neural circuitry differs among girls and boys with ADHD compared to same-sex typically developing (TD) controls and relates to delay discounting. METHODS: Participants include 8-12-year-old children with ADHD (n = 72, 20 girls) and TD controls (n = 75, 21 girls). Fronto-subcortical regions of interest were functionally defined by applying independent component analysis to resting-state fMRI data. Intrinsic FC between subcortical components, including the striatum and amygdala, and prefrontal components, including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and anterior dorsolateral prefrontal cortex (dlPFC), was compared across diagnostic groups overall and within sex. Correlations between intrinsic FC of the six fronto-subcortical pairs and delay discounting were also examined. RESULTS: Both girls and boys with ADHD show atypical FC between vmPFC and subcortical regions including the striatum (stronger positive FC in ADHD) and amygdala (weaker negative FC in ADHD), with the greatest diagnostic effects among girls. In addition, girls with ADHD show atypical intrinsic FC between the striatum and dlPFC components, including stronger positive FC with ACC and stronger negative FC with dlPFC. Further, girls but not boys, with ADHD, show heightened real-time delay discounting. Brain-behavior correlations suggest (1) stronger negative FC between the striatal and dlPFC components correlated with greater money delay discounting across all participants and (2) stronger FC between the amygdala with both the dlPFC and ACC components was differentially related to heightened real-time discounting among girls and boys with and without ADHD. CONCLUSIONS: Our findings suggest fronto-subcortical functional networks are affected in children with ADHD, particularly girls, and relate to delay discounting. These results also provide preliminary evidence of greater disruptions in fronto-subcortical FC among girls with ADHD that is not due to elevated inattention symptom severity, intellectual reasoning ability, age, or head motion. SN - 1866-1955 UR - https://www.unboundmedicine.com/medline/citation/30541434/ADHD_related_sex_differences_in_fronto_subcortical_intrinsic_functional_connectivity_and_associations_with_delay_discounting_ L2 - https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-018-9254-9 DB - PRIME DP - Unbound Medicine ER -