Weidong Cai1, Tianwen Chen2, Luca Szegletes3, Kaustubh Supekar2, Vinod Menon4. 1. Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California. Electronic address: wdcai@stanford.edu. 2. Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California. 3. Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California; Department of Automation and Applied Informatics, Budapest University of Technology and Economics, Budapest, Hungary. 4. Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California; Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California; Stanford Neurosciences Institute, Stanford University School of Medicine, Stanford, California.
Abstract
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is thought to stem from aberrancies in large-scale cognitive control networks. However, the exact nature of aberrant brain circuit dynamics involving these control networks is poorly understood. Using a saliency-based triple-network model of cognitive control, we tested the hypothesis that dynamic cross-network interactions among the salience, central executive, and default mode networks are dysregulated in children with ADHD, and we investigated how these dysregulations contribute to inattention. METHODS: Using functional magnetic resonance imaging data from 140 children with ADHD and typically developing children from two cohorts (primary cohort = 80 children, replication cohort = 60 children) in a case-control design, we examined both time-averaged and dynamic time-varying cross-network interactions in each cohort separately. RESULTS: Time-averaged measures of salience network-centered cross-network interactions were significantly lower in children with ADHD compared with typically developing children and were correlated with severity of inattention symptoms. Children with ADHD displayed more variable dynamic cross-network interaction patterns, including less persistent brain states, significantly shorter mean lifetimes of brain states, and intermittently weaker cross-network interactions. Importantly, dynamic time-varying measures of cross-network interactions were more strongly correlated with inattention symptoms than with time-averaged measures of functional connectivity. Crucially, we replicated these findings in the two independent cohorts of children with ADHD and typically developing children. CONCLUSIONS: Aberrancies in time-varying engagement of the salience network with the central executive network and default mode network are a robust and clinically relevant neurobiological signature of childhood ADHD symptoms. The triple-network neurocognitive model provides a novel, replicable, and parsimonious dynamical systems neuroscience framework for characterizing childhood ADHD and inattention.
BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) is thought to stem from aberrancies in large-scale cognitive control networks. However, the exact nature of aberrant brain circuit dynamics involving these control networks is poorly understood. Using a saliency-based triple-network model of cognitive control, we tested the hypothesis that dynamic cross-network interactions among the salience, central executive, and default mode networks are dysregulated in children with ADHD, and we investigated how these dysregulations contribute to inattention. METHODS: Using functional magnetic resonance imaging data from 140 children with ADHD and typically developing children from two cohorts (primary cohort = 80 children, replication cohort = 60 children) in a case-control design, we examined both time-averaged and dynamic time-varying cross-network interactions in each cohort separately. RESULTS: Time-averaged measures of salience network-centered cross-network interactions were significantly lower in children with ADHD compared with typically developing children and were correlated with severity of inattention symptoms. Children with ADHD displayed more variable dynamic cross-network interaction patterns, including less persistent brain states, significantly shorter mean lifetimes of brain states, and intermittently weaker cross-network interactions. Importantly, dynamic time-varying measures of cross-network interactions were more strongly correlated with inattention symptoms than with time-averaged measures of functional connectivity. Crucially, we replicated these findings in the two independent cohorts of children with ADHD and typically developing children. CONCLUSIONS: Aberrancies in time-varying engagement of the salience network with the central executive network and default mode network are a robust and clinically relevant neurobiological signature of childhood ADHD symptoms. The triple-network neurocognitive model provides a novel, replicable, and parsimonious dynamical systems neuroscience framework for characterizing childhood ADHD and inattention.
Authors: Thomas Insel; Bruce Cuthbert; Marjorie Garvey; Robert Heinssen; Daniel S Pine; Kevin Quinn; Charles Sanislow; Philip Wang Journal: Am J Psychiatry Date: 2010-07 Impact factor: 18.112
Authors: Heather M Shappell; Kelly A Duffy; Keri S Rosch; James J Pekar; Stewart H Mostofsky; Martin A Lindquist; Jessica R Cohen Journal: Neuroimage Date: 2021-01-14 Impact factor: 6.556