Neurophysiological mechanisms of cognitive and emotional control in ADHD

Project Summary Increasing numbers of children are diagnosed or treated for Attention Deficit Hyperactivity Disorder(ADHD), yet its diagnosis and treatment remain controversial, specific etiologies remain uncertain, and clinicalprediction is poor. The research and training activities proposed in this K23 application advance the PI's long-term career goal of establishing an independent, translational program of research characterizing individualdifferences in the psychological, cognitive, and neurobiological processes contributing to ADHD. The proposedtraining emphasizes skill development in: 1) advanced analysis approaches for electrophysiological data; 2)integrating these analytical approaches in the context of cognitive neuroscience models of attention andworking memory for translational work; 3) learning conceptual and practical tools related to identification ofdevelopmentally-sensitive, multivariate refined phenotypes; and 4) additional training in research ethics andprofessional development. Skills are developed through didactic instruction, hands-on experience in datacollection and analysis, and intensive mentorship related to the closely-linked research and training aims. Consensus is emerging that effective measurement of pathophysiological mechanisms is essential forimprovement of both pharmacological and non-pharmacological treatments of ADHD. Neurocognitivemeasures, broadly defined, are seen as particularly promising for understanding mechanisms of ADHD andcreating alternative phenotypes. They have also been central to efforts at novel treatment development, forexample via computerized cognitive training of working memory and electroencephalogram (EEG)-basedneurofeedback. However, data on efficacy of these new treatments remain unconvincing. This is likely, at leastin part, because the mechanisms of cognitive control being targeted are not adequately specified orcontextualized. In order to move the field forward, at least three issues need to be resolved: 1) the appropriatefractionation of cognitive control deficits needs to be clarified and trial-by-trial neurophysiological predictors ofperformance need to be identified; 2) differences in how control processes are implemented across emotionalcontexts need to be characterized; and 3) cognitive, emotional, and neurophysiological predictors need to berelated to clinical outcomes. EEG measures, including resting and evoked oscillatory activity and evokedresponse potentials (ERPs) are ideal for these purposes because they provide millisecond-level quantificationof the neurophysiological response associated with these psychological processes and thus can help clarifythe neurophysiological bases of impairments. The proposed study applies EEG/ERP methodology to resolve questions related to cognitive andemotional control deficits in a sample of 150 children with and without ADHD, ages 12-16 years, recruited froma larger longitudinal study. Aim 1 tests hypotheses stemming from the adaptive gain theory that ADHD-relateddeficits in working memory and performance variability result from a common problem in attention optimizationand identifies trial-by-trial neurophysiological predictors of performance. Aim 2 integrates the attentiondysregulation described in Aim 1 with two novel ADHD emotion-based types previously identified by the PI.Finally, in Aim 3, cognitive and EEG/ERP markers are incorporated in a recursive decision-making algorithm toidentify multivariate refined phenotype profiles for each emotion-based ADHD type. The potential impact of thiswork over time would be to help sharpen psychiatric nosology and provide improved clinical diagnosis,characterization, and prediction. Ultimately, there is the potential to move psychology and psychiatry towardpersonalized approaches to treatment and spur novel treatment development.