Genetic Overlap between Evoked Frontocentral Theta-Band Phase Variability, Reaction Time Variability, and Attention-Deficit/Hyperactivity Disorder Symptoms in a Twin Study

Background Electrophysiological and hemodynamic activity is altered in attention-deficit/hyperactivity disorder (ADHD) during tasks requiring cognitive control. Frontal midline theta oscillations are a cortical correlate of cognitive control influencing behavioral outcomes including reaction times. Reaction time variability (RTV) is consistently increased in ADHD and is known to share genetic effects with the disorder. The etiological relationship between the cognitive control system, RTV, and ADHD is unknown. In a sample of twins selected for ADHD and matched control subjects, we aimed to quantify the strength of the phenotypic, genetic, and environmental relationships between event-related midline theta oscillations, RTV, and ADHD. Methods Our sample included 134 participants aged 12 to 15 years: 67 twin pairs (34 monozygotic; 33 dizygotic) with concordance or discordance for ADHD symptomatology assessed at 8, 10, and 12 years of age. Our main outcome measures were frontal midline theta activity, derived from both channel and source decomposed electroencephalographic data, and behavioral performance on a response-choice arrow flanker task known to elicit theta activity. Results Variability in stimulus event-related theta phase from frontal midline cortex is strongly related to both RTV and ADHD, both phenotypically and genetically. Conclusions This is the first finding to confirm the genetic link between the frontal midline cognitive control system and ADHD and the first to identify a genetically related neurophysiological marker of RTV in ADHD. Variability in the timing of the theta signal in ADHD may be part of a dysfunctional brain network that impairs regulation of task-relevant responses in the disorder.