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. Our funded project Alpha oscillations and working memory deficits in ADHD: A multimodal imaging investigation (R01MH116268) aims 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 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 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 (14-20 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. Based on recently emerged findings we propose to extend this research to: (i) include neural metrics of anatomical connectivity, thus testing an alternate hypothesis that sources of alpha ERD deficits are anatomical in addition to or underlying functional impairments; and (ii) include a young adult sample (n=90, age=21-26), thus testing two novel hypotheses regarding the association and predictive value of alpha ERD for clinical (co-morbid depression and suicidality) and functional (occupational and financial) outcomes. These additions will significantly increase the impact of the mechanistic, cross-sectional and longitudinal assessment of the project.
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.
