title: Abnormal amygdala functional connectivity associated with emotional lability in children with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD.
  
  
  METHODS
  Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19).
  
  
  RESULTS
  Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups.
  
  
  CONCLUSIONS
  In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala-cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.
authors.affiliation: Indiana University School of Medicine, Riley Hospital for Children; Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center. Electronic address: lhulvers@iupui.edu.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Hulvershorn
authors.affiliation: Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center; Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre.
authors.forename: Maarten
authors.initials: M
authors.lastname: Mennes
authors.affiliation: Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center; Nathan Kline Institute for Psychiatric Research.
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Castellanos
authors.affiliation: Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Martino
authors.affiliation: Nathan Kline Institute for Psychiatric Research; Center for the Developing Brain, Child Mind Institute.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Milham
authors.affiliation: Indiana University School of Medicine, Riley Hospital for Children.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Hummer
authors.affiliation: Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center; Fordham University.
authors.forename: Amy Krain
authors.initials: AK
authors.lastname: Roy
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000503:physiopathology*; D000679:Amygdala / Q000503:physiopathology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology; D002648:Child; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*
keywords: amygdala; attention-deficit/hyperactivity disorder; emotional lability; functional magnetic resonance imaging (fMRI)