Abstract
BACKGROUND: Identifying neural markers of clinical symptom fluctuations is prerequisite to developing more precise brain-targeted treatments in psychiatry. We have recently shown that working memory (WM) in healthy adults is dependent on the rise and fall interplay between alpha (8-12 Hz)/beta (15-29 Hz) and high-frequency activity (HFA; 55-80 Hz) bursts within frontoparietal regions, and that deviations in these patterns lead to WM performance errors. However, it is not known whether such bursting deviations correlate to clinically relevant WM-related symptoms or clinical status in individuals with WM deficits. METHODS: We utilized trial-by-trial burst characterization and source localization approaches collected during a Sternberg WM paradigm within our magnetic resonance imaging/electroencephalography dataset of 27 adolescents with attention deficit hyperactivity disorder (ADHD) who completed the EEG procedures regularly during their participation in intermittent theta burst stimulation research studies, including an intermittent theta burst stimulation clinical trial (for a total of n = 180 participant/sessions). Source localizing electroencephalography data to each participant's structural MRI, the rate and volume of alpha, beta, and HFA bursts were examined within the dorsolateral prefrontal cortex and posterior parietal cortex. RESULTS: Alpha/beta bursting decreased during stimuli encoding and increased during the delay, while HFA bursting was elevated during encoding and decreased during the delay. Deviations in bursting patterns were associated with WM errors and clinical symptoms. CONCLUSIONS: Dysfunctional alpha/beta and HFA burst dynamics within the frontoparietal region underlie both intra-individual WM performance and WM symptom fluctuations in adolescents with ADHD. Such burst dynamics reflect a novel target and biomarker for WM-related treatment development.