An integrative framework of cognitive control and reward modulation in children with ADHD: from brain dynamics to clinical symptoms

Project Summary
Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, with
prevalence rates ranging from 5-10% globally. With rising diagnosis rates in the last two decades, childhood
ADHD has become a significant social and financial burden to affected individuals, families, and society at
large. ADHD is characterized by impairments in cognitive control, with adverse life-long consequences for
academic and social functioning. Cognitive control requires dynamic engagement of proactive and reactive
control processes, and aberrancies in these processes underlie behavioral deficits, including elevated
response variability and slow stopping speed. A related line of research suggests that rewards may increase
stopping speed and reduce response variability in ADHD, with some individuals even reaching similar
performance as typically developing children (TDC). However, the cognitive and brain mechanisms underlying
proactive and reactive control, their modulation by reward and relation to clinical symptoms in ADHD are
unknown. Here we develop an innovative multi-componential cognitive, neuroscience, and
computational framework to address this gap and advance fundamental understanding of dysfunctional brain
circuits linking cognitive control and reward systems in children with ADHD. Recent progress in cognitive and
computational neuroscience has demonstrated that cognitive control relies on dynamic brain states
characterized by dynamic interactions in functional brain circuits. The proposed studies will rigorously test
theoretical cognitive and neuroscience models of ADHD by examining reward modulation of proactive and
reactive control as well as dynamic brain circuits involving cognitive control, default mode and reward systems
in children with ADHD. We will integrate multiple high-impact lines of our ongoing research on cognitive
control, children with ADHD, and brain circuit dynamics. Importantly, we will leverage multiple novel
computational models to uncover dynamics of cognitive and brain processes. The proposed studies will: (1)
investigate how reward modulates proactive and reactive control in children with ADHD, (2) determine how
aberrations in reward modulation of proactive and reactive control are related to core clinical symptoms, (3)
characterize dynamic brain circuits underlying reward modulation of proactive and reactive control in children
with ADHD, (4) determine how reward modulation of dynamic brain circuits involving cognitive control and
reward systems are related to core symptoms, (5) identify multivariate cognitive and neurobiological features
for classification of childhood ADHD and prediction of core clinical symptoms of ADHD. The proposed studies
will facilitate a deeper understanding of cognitive and brain mechanisms underlying reward modulation of
cognitive control, which will facilitate developing more effective and precise intervention for childhood ADHD in
the future. Our cognitive, neuroscience and computational framework developed here can be widely applied to
study many psychiatric disorders that manifest similar cognitive deficits, such as schizophrenia and autism.

Grant Number: 5R01MH124816-05
NIH Institute/Center: NIH
Principal Investigator: Weidong Cai