High prevalence rates of attention deficit hyperactivity disorder (ADHD) (5-11% of children 4-17 years), combined with its high societal cost, strong persistence and pernicious effects on quality of life, warrant continued efforts to understand its underlying neural mechanisms. Underscoring this need is the increasing recognition that ADHD is clinically and mechanistically heterogeneous, and that this likely degrades the reliability of putative biomarkers of ADHD. Novel, focused studies that aim to reduce such heterogeneity are needed. In this project, we aim to define a robust, relatively unexplored putative biomarker of visual attention deficits, alpha range (8-12Hz) event-related decrease (ERD), which strongly indexes working memory (WM) deficits in ADHD. Using cutting-edge, concurrent EEG-fMRI recordings, we propose to measure event-related alpha ERD and its associated brain activation and network connectivity during WM encoding. The concurrent recordings allow us to directly test if fluctuations in engagement of attention mechanisms captured by the alpha ERD neurophysiological measures predict fluctuations in WM neural processes. Using this methodology, we aim to: (a) identify neural mechanisms underlying alpha ERD deficits and WM performance in ADHD, and (b) define the clinical features of alpha ERD deficits in ADHD, including its effect on real life outcomes such as academic achievement. Unique to this project, we will sample participants who were previously tested in two large ADHD-EEG studies, recruiting them for a longitudinal follow-up experimental session if they are currently in adolescence (14-18 years). By doing so we aim to (c) characterize the developmental trajectory of attention deficits as captured by alpha ERD in ADHD, as well its impact on the trajectory of clinical and real-life outcomes. The adolescent sample will provide new insight into neural and neurophysiological characteristics of ADHD during this developmental period. The outcome of this research is a clearly defined neural mechanism, alpha ERD, that can be targeted in treatment of WM deficits in ADHD, or in other neuropsychiatric disorders.

Public Health Relevance

This project examines a novel putative neurophysiological biomarker, alpha event-related decrease (ERD), of attention mechanisms that directly contribute to deficits of working memory in ADHD. To validate the alpha ERD biomarker, we will characterize the underlying neural mechanisms using concurrent EEG-fMRI, test the clinical correlates, and identify its developmental trajectory into adolescence, which we address through longitudinal follow-up of a large, previously assessed sample. This biomarker will help to identify patients with ADHD whose working memory deficits are due to early attention mechanisms, thus reducing heterogeneity and improving specificity of underlying neural deficits, potentially leading to more targeted, and therefore, more effective treatment approaches for these individuals.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Pacheco, Jenni
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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