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Background: Cognitive control has been strongly linked to midfrontal theta (4-8 Hz) brain activity. Such control processes are known to be impaired in individuals with psychiatric conditions and neurodevelopmental diagnoses, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Temporal variability in theta, in particular, has been associated with ADHD, with shared genetic variance underlying the relationship. Here, we investigated the phenotypic and genetic relationships between theta phase variability, theta-related signals (the N2, error-related negativity, and error positivity), reaction time, and ADHD and ASD longitudinally in a large twin study of young adults to investigate the stability of the genetic relationships between these measures over time., Methods: Genetic multivariate liability threshold models were run on a longitudinal sample of 566 participants (283 twin pairs). Characteristics of ADHD and ASD were measured in childhood and young adulthood, while an electroencephalogram was recorded in young adulthood during an arrow flanker task., Results: Cross-trial theta phase variability in adulthood showed large positive phenotypic and genetic relationships with reaction time variability and both childhood and adult ADHD characteristics. Error positivity amplitude was negatively related phenotypically and genetically to ADHD and ASD at both time points., Conclusions: We showed significant genetic associations between variability in theta signaling and ADHD. A novel finding from the current study is that these relationships were stable across time, indicating a core dysregulation of the temporal coordination of control processes in ADHD that persists in individuals with childhood symptoms. Error processing, indexed by the error positivity, was altered in both ADHD and ASD, with a strong genetic contribution., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

There is an urgent need to identify the mechanisms that contribute to atypical thinking and behavior associated with psychiatric illness. Behavioral and brain measures of cognitive control are associated with a variety of psychiatric disorders and conditions as well as daily life functioning. Recognition of the importance of cognitive control in human behavior has led to intensive research into behavioral and neurobiological correlates. Oscillations in the theta band (4-8 Hz) over medial frontal recording sites are becoming increasingly established as a direct neural index of certain aspects of cognitive control. In this review, we point toward evidence that theta acts to coordinate multiple neural processes in disparate brain regions during task processing to optimize behavior. Theta-related signals in human electroencephalography include the N2, the error-related negativity, and measures of theta power in the (time-)frequency domain. We investigate how these theta signals are affected in a wide range of psychiatric conditions with known deficiencies in cognitive control: anxiety, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and substance abuse. Theta-related control signals and their temporal consistency were found to differ in most patient groups compared with healthy control subjects, suggesting fundamental deficits in reactive and proactive control. Notably, however, clinical studies directly investigating the role of theta in the coordination of goal-directed processes across different brain regions are uncommon and are encouraged in future research. A finer-grained analysis of flexible, subsecond-scale functional networks in psychiatric disorders could contribute to a dimensional understanding of psychopathology., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The processes underlying persistence and remission of attention-deficit/hyperactivity disorder (ADHD) are poorly understood. We examined whether cognitive and neurophysiological impairments on a performance-monitoring task distinguish between ADHD persisters and remitters., Methods: On average 6 years after initial assessment, 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched control participants were compared on cognitive-performance measures and event-related potentials of conflict monitoring (N2) and error processing (error-related negativity and positivity) from an arrow flanker task with low-conflict and high-conflict conditions. ADHD outcome was examined with parent-reported symptoms and functional impairment measures using a categorical (DSM-IV) and a dimensional approach., Results: ADHD persisters were impaired compared with controls on all cognitive-performance and event-related potential measures (all p < .05). ADHD remitters differed from persisters and were indistinguishable from control participants on the number of congruent (low-conflict) errors, reaction time variability, error-related negativity, and error-related positivity (all p ≤ .05). Remitters did not differ significantly from the other groups on incongruent (high-conflict) errors, mean reaction time, and N2. In dimensional analyses on all participants with childhood ADHD, ADHD symptoms and functional impairment at follow-up were significantly correlated with congruent errors, reaction time variability, and error-related positivity (r = .19-.23, p ≤ .05)., Conclusions: Cognitive and neurophysiological measures of attention-vigilance and error detection distinguished ADHD remitters from persisters. These results extend our previous findings with other tasks and indicate that such measures are markers of remission and candidates for the development of nonpharmacological interventions., (Copyright © 2016 Society of Biological Psychiatry. All rights reserved.)

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., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)