Additive and Interactive Effects of Attention-Deficit/Hyperactivity Disorder and Tic Disorder on Brain Connectivity.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and persistent tic disorder (PTD) are two neurodevelopmental disorders that frequently co-occur. Contributions of each disorder to cognitive and behavioral deficits have been reported. In this paper, we tested 3 models of pathophysiology for the two disorders (additive, interactive, and phenotypic) using resting-state connectivity associated with each disorder separately and together. METHODS: Participants were 148 children (55 with ADHD only, 33 with ADHD and PTD, 27 with PTD only, and 33 healthy control subjects) at ages 8 to 12 years. Following diagnostic interviews and behavioral assessment, participants underwent a 128-channel electroencephalography recording. Resting-state, cortical source-level effective connectivity was analyzed across the 4 groups using a 2 × 2 factorial design with factors of ADHD (with/without) and PTD (with/without). RESULTS: ADHD diagnosis was the primary driver of cognitive and behavioral deficits, while deficits associated with PTD were primarily with thought problems and internalizing problems when compared with controls. Subadditive effects were observed in co-occurring ADHD+PTD for parent-rated behavioral problems and cognitive functions. Aberrant effective connectivity was primarily associated with ADHD, more specifically with lower posterior and occipital-frontal connectivity, while children with PTD exhibited greater left postcentral to precuneus connectivity. Weaker ADHD-related connectivity was associated with more severe behavioral problems, including internalizing behaviors, thought problems, and working memory deficits. CONCLUSIONS: Similar to general behavioral deficits, aberrant resting-state neural connectivity in pediatric ADHD and PTD combines additively in co-occurring cases. The findings of this study support ADHD as a focus of treatment in comorbid cases, given the driving role of ADHD in both behavioral and neurophysiological deficits.

Inhibitory control in children with tic disorder: aberrant fronto-parietal network activity and connectivity.

Chronic tic disorders, including Tourette syndrome, are typically thought to have deficits in cognitive inhibition and top down cognitive control due to the frequent and repetitive occurrence of tics, yet studies reporting task performance results have been equivocal. Despite similar behavioural performance, individuals with chronic tic disorder have exhibited aberrant patterns of neural activation in multiple frontal and parietal regions relative to healthy controls during inhibitory control paradigms. In addition to these top down attentional control regions, widespread alterations in brain activity across multiple neural networks have been reported. There is a dearth, however, of studies examining event-related connectivity during cognitive inhibitory paradigms among affected individuals. The goal of this study was to characterize neural oscillatory activity and effective connectivity, using a case-control design, among children with and without chronic tic disorder during performance of a cognitive inhibition task. Electroencephalogram data were recorded in a cohort of children aged 8-12 years old (60 with chronic tic disorder, 35 typically developing controls) while they performed a flanker task. While task accuracy did not differ by diagnosis, children with chronic tic disorder displayed significant cortical source-level, event-related spectral power differences during incongruent flanker trials, which required inhibitory control. Specifically, attenuated broad band oscillatory power modulation within the anterior cingulate cortex was observed relative to controls. Whole brain effective connectivity analyses indicated that children with chronic tic disorder exhibit greater information flow between the anterior cingulate and other fronto-parietal network hubs (midcingulate cortex and precuneus) relative to controls, who instead showed stronger connectivity between central and posterior nodes. Spectral power within the anterior cingulate was not significantly correlated with any connectivity edges, suggesting lower power and higher connectivity are independent (versus resultant) neural mechanisms. Significant correlations between clinical features, task performance and anterior cingulate spectral power and connectivity suggest this region is associated with tic impairment (r = -0.31, P = 0.03) and flanker task incongruent trial accuracy (r's = -0.27 to -0.42, P's = 0.0008-0.04). Attenuated activation of the anterior cingulate along with dysregulated information flow between and among nodes within the fronto-parietal attention network may be neural adaptations that result from frequent engagement of neural pathways needed for inhibitory control in chronic tic disorder.

The ERN as a neural index of changes in performance monitoring following attention training in pediatric obsessive-compulsive disorder.

Evidence of associations between obsessive compulsive disorder (OCD) and alterations in neural indices of performance monitoring, i.e., elevated neural activity following errors, have accelerated interest in the error-related negativity (ERN) as a biomarker for pediatric OCD. The study investigates the degree to which attention bias training is linked to changes in neural measures of performance monitoring (ERN, correct response negativity or CRN) and whether pre-to-post training changes in these neural indices are associated with symptom changes in youth with OCD. The sample included 36 youth (8-17 years) diagnosed with OCD who completed a 12-session attention training program and pre- and post-training EEG assessment of performance monitoring using cognitive and emotional flanker tasks. The emotional flanker task was individualized to each participant's negative ratings of stimuli at pre-treatment to enhance salience of threat-related stimuli across youth. Results indicated that unlike participants who received attentional control protocol (CON), those who received attentional bias modification protocol (ABM) showed significant attenuations in neural activity following erroneous and correct responses in the emotional flanker task. The ERN amplitude during the cognitive flanker task was unchanged in both ABM and CON groups. Attenuations in the ERN were also linked to decreases in social anxiety and depressive symptoms. Findings highlight the relevance of including emotionally-salient tasks when investigating potential neural mechanisms of treatments and suggest that alterations in neural processes underlying performance monitoring can be targeted via attention training programs in pediatric OCD.

Shared and unique neural mechanisms underlying pediatric trichotillomania and obsessive compulsive disorder.

BACKGROUND: Little is known about the neural underpinnings of pediatric trichotillomania (TTM). We examined error-related negativity (ERN)-amplitude and theta-EEG power differences among youth with TTM, OCD, and healthy controls (HC). METHODS: Forty channel EEG was recorded from 63 pediatric participants (22 with TTM, 22 with OCD, and 19 HC) during the Eriksen Flanker Task. EEG data from inhibitory control were used to derive estimates of ERN amplitude and event-related spectral power associated with motor inhibition. RESULTS: TTM and HC were similar in brain activity patterns in frontal and central regions and TTM and OCD were similar in the parietal region. Frontal ERN-amplitude was significantly larger in OCD relative to TTM and HC, who did not differ from each other. The TTM group had higher theta power compared to OCD in frontal and central regions, and higher theta than both comparison groups in right motor cortex and superior parietal regions. Within TTM, flanker task performance was correlated with EEG activity in frontal, central, and motor cortices whereas global functioning and impairment were associated with EEG power in bilateral motor and parietal cortices. CONCLUSIONS: Findings are discussed in terms of shared and unique neural mechanisms in TTM and OCD and treatment implications.

Modulation of Frontal Oscillatory Power during Blink Suppression in Children: Effects of Premonitory Urge and Reward.

There is a dearth of studies examining the underlying mechanisms of blink suppression and the effects of urge and reward, particularly those measuring subsecond electroencephalogram (EEG) brain dynamics. To address these issues, we designed an EEG study to ask 3 questions: 1) How does urge develop? 2) What are EEG-correlates of blink suppression? 3) How does reward change brain dynamics related to urge suppression? This study examined healthy children (N = 26, age 8-12 years) during blink suppression under 3 conditions: blink freely (i.e., no suppression), blink suppressed, and blink suppressed for reward. During suppression conditions, children used a joystick to indicate their subjective urge to blink. Results showed that 1) half of the trials were associated with clearly defined urge time course of ~7 s, which was accompanied by EEG delta (1-4 Hz) power reduction localized at anterior cingulate cortex (ACC); 2) the EEG correlates of blink suppression were found in left prefrontal theta (4-8 Hz) power elevation; and 3) reward improved blink suppression performance while reducing the EEG delta power observed in ACC. We concluded that the empirically supported urge time course and underlying EEG modulations provide a subsecond chronospatial model of the brain dynamics during urge- and reward-mediated blink suppression.

Atypical functional connectivity in adolescents and adults with persistent and remitted ADHD during a cognitive control task.

We previously provided initial evidence for cognitive and event-related potential markers of persistence/remission of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and adulthood. Here, using a novel brain-network connectivity approach, we aimed to examine whether task-based functional connectivity reflects a marker of ADHD remission or an enduring deficit unrelated to ADHD outcome. High-density EEG was recorded in a follow-up of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 typically developing individuals during an arrow-flanker task, eliciting cognitive control. Functional connectivity was quantified with network-based graph-theory metrics before incongruent (high-conflict) target onset (pre-stimulus), during target processing (post-stimulus) and in the degree of change between pre-stimulus/post-stimulus. ADHD outcome was examined with parent-reported symptoms and impairment using both a categorical (DSM-IV) and a dimensional approach. Graph-theory measures converged in indicating that, compared to controls, ADHD persisters showed increased connectivity in pre-stimulus theta, alpha, and beta and in post-stimulus beta (all p < .01) and reduced pre-stimulus/post-stimulus change in theta connectivity (p < .01). In the majority of indices showing ADHD persister-control differences, ADHD remitters differed from controls (all p < .05) but not from persisters. Similarly, connectivity measures were unrelated to continuous outcome measures of ADHD symptoms and impairment in participants with childhood ADHD. These findings indicate that adolescents and young adults with persistent and remitted ADHD share atypical over-connectivity profiles and reduced ability to modulate connectivity patterns with task demands, compared to controls. Task-based functional connectivity impairments may represent enduring deficits in individuals with childhood ADHD irrespective of diagnostic status in adolescence/young adulthood.