ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting / K. S. ROSCH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 34 p. Titre : ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting Type de document : Texte imprimé et/ou numérique Auteurs : K. S. ROSCH, Auteur ; S. H. MOSTOFSKY, Auteur ; M. B. NEBEL, Auteur Année de publication : 2018 Article en page(s) : 34 p. Langues : Anglais (eng) Mots-clés : Adhd  Delay discounting  Functional connectivity  Ica  Resting-state  Reward  Temporal discounting  fMRI Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1186/s11689-018-9254-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting [Texte imprimé et/ou numérique] / K. S. ROSCH, Auteur ; S. H. MOSTOFSKY, Auteur ; M. B. NEBEL, Auteur . - 2018 . - 34 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 34 p. Mots-clés : Adhd  Delay discounting  Functional connectivity  Ica  Resting-state  Reward  Temporal discounting  fMRI Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1186/s11689-018-9254-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition / L. W. HAWK in Journal of Child Psychology and Psychiatry, 59-12 (December 2018)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 59-12 (December 2018) . - p.1271-1281 Titre : How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition Type de document : Texte imprimé et/ou numérique Auteurs : L. W. HAWK, Auteur ; W. D. FOSCO, Auteur ; Craig R. COLDER, Auteur ; J. G. WAXMONSKY, Auteur ; W. E. PELHAM, Auteur ; K. S. ROSCH, Auteur Article en page(s) : p.1271-1281 Langues : Anglais (eng) Mots-clés : Attention-Deficit/Hyperactivity Disorder  cognition  mediation  methylphenidate Index. décimale : PER Périodiques Résumé : BACKGROUND: Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. METHODS: Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. RESULTS: Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. CONCLUSIONS: These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. En ligne : http://dx.doi.org/10.1111/jcpp.12917 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition [Texte imprimé et/ou numérique] / L. W. HAWK, Auteur ; W. D. FOSCO, Auteur ; Craig R. COLDER, Auteur ; J. G. WAXMONSKY, Auteur ; W. E. PELHAM, Auteur ; K. S. ROSCH, Auteur . - p.1271-1281. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 59-12 (December 2018) . - p.1271-1281 Mots-clés : Attention-Deficit/Hyperactivity Disorder  cognition  mediation  methylphenidate Index. décimale : PER Périodiques Résumé : BACKGROUND: Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. METHODS: Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. RESULTS: Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. CONCLUSIONS: These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. En ligne : http://dx.doi.org/10.1111/jcpp.12917 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

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