Predicting the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a go/no-go test

Abstract BACKGROUND: We searched for predictors of the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography, event-related potentials (ERPs), and behavioral data from a visual go/no-go test. METHODS: Nineteen-channel electroencephalography (EEG) was recorded during the resting state in eyes-open and eyes-closed conditions and during performance of the cued go/no-go task in 98 medication-naïve ADHD patients aged 7-17 years and in 90 controls with the same age and sex distribution as the patients. For patients, the recording was followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the electrophysiological results independently rated the patients as responders (REs) (N=74) or non-responders (non-REs) (N=24). Using a logistic regression model, comparisons were made between REs and non-REs on the EEG spectra, ERPs (cue P3, contingent negative variation, and P3 no-go of the ERP waves and independent components [ICs] extracted from these waves), reaction time, reaction time variability, number of commission and omission errors, intelligence quotient, age, sex, ADHD subtype, and comorbidities. RESULTS: The two groups differed significantly on eight of the variables, with effect sizes (Cohen's d) ranging from 0.49 to 0.76. In the multivariate logistic regression analysis, only three of these variables were significantly associated with clinical outcome. The amplitude of the IC cue P3, which has a parietal-occipital distribution, was normal in REs but significantly smaller in non-REs, whereas the centrally distributed IC P3 no-go early was smaller in REs than in non-REs and controls. In addition, the REs had more power in the EEG theta band. A quartile-based index was calculated using these three variables. The group with the lowest scores comprised only 36% REs; response rates in the three other groups were 83%, 86%, and 89%. CONCLUSION: The clinical outcome of stimulant medication was best predicted by electrophysiological parameters. The brain dysfunctions of the REs appear to be primarily associated with prefrontal lobe hypoactivation. The non-REs were deviant from the controls in parietal-occipital functions.publishedVersio

Behavioral and Neurophysiological Markers of ADHD in Children, Adolescents, and Adults: A Large-Scale Clinical Study

This study aimed to re-evaluate the possible differences between attention-deficit/hyperactivity disorder (ADHD) subjects and healthy controls in the context of a standard Go/NoGo task (visual continuous performance test [VCPT]), frequently used to measure executive functions. In contrast to many previous studies, our sample comprises children, adolescents, and adults. We analyzed data from 447 ADHD patients and 227 healthy controls. By applying multivariate linear regression analyses, we controlled the group differences between ADHD patients and controls for age and sex. As dependent variables we used behavioral (number of omission and commission errors, reaction time, and reaction time variability) and neurophysiological measures (event-related potentials [ERPs]). In summary, we successfully replicated the deviations of ADHD subjects from healthy controls. The differences are small to moderate when expressed as effect size measures (number of omission errors: d = 0.60, reaction time variability: d = 0.56, contingent negative variation (CNV) and P3 amplitudes: -0.35 < d < -0.47, ERP latencies: 0.21 < d < 0.29). Further analyses revealed no substantial differences between ADHD subtypes (combined, inattentive, and hyperactive/impulsive presentation), subgroups according to high- and low-symptomatic burden or methylphenidate intake for their daily routine. We successfully replicated known differences between ADHD subjects and controls for the behavioral and neurophysiological variables. However, the small-to-moderate effect sizes limit their utility as biomarkers in the diagnostic procedure. The incongruence of self-reported symptomatic burden and clinical diagnosis emphasizes the challenges of the present clinical diagnosis with low reliability, which partially accounts for the low degree of discrimination between ADHD subjects and controls

Attention deficit / hyperactivity ­disorder in Swiss primary care

In 2012, the “Sentinella” survey of Swiss primary care physicians (PCPs) examined the frequency and treatment of attention deficit hyperactivity disorder (ADHD) in Swiss primary care, the differences between pediatricians and general practitioners (GPs) in handling ADHD, as well as the needs of PCPs regarding management of ADHD in practice. An average of 1 out of every 1000 consultations concerned suspected or confirmed ADHD, with pediatricians reporting 18x more consultations per 1000 than GPs. Male patients aged 7–12 represented the majority of consultations. Overall, 54% of pediatricians vs. 17% of GPs diagnosed ADHD themselves, and 88% of pediatricians vs. 40% of GPs treated the condition themselves. Both used medication in almost two-thirds of cases, with no gender-correlated differences observed in stimulant use. A lack of competence for ­diagnosing and treating ADHD was frequently reported, especially among GPs, and a corresponding need for better practical training and education was expressed. The self-reported lack of diagnostic and therapeutic expertise regarding ADHD among Swiss PCPs underscores the need for more training programs, better information on the disorder, and reliable easy-to-use testing aids

Longitudinal investigation in children and adolescents with ADHD and healthy controls: A 2-year ERP study

Cross-sectional group comparisons have shown altered neurocognitive and neurophysiological profiles in individuals with attention-deficit/hyperactivity disorder (ADHD). We report a two-year longitudinal observational study of ADHD children and adolescents (N = 239) regarding ADHD symptoms, behavioral metrics, and event-related potentials (ERP) and compared them to healthy controls (N = 91). The participants were assessed up to five times with a cued Go/NoGo task while ERPs were recorded. We fitted the trajectories of our variables of interest with univariate and bivariate latent growth curve models. At baseline, the ADHD group had increased reaction time variability, higher number of omission and commission errors, and attenuated CNV and P3d amplitudes compared to controls. The task performance in terms of behavioral metrics improved in both groups over two years; however, with differential patterns: the decrease in reaction time and omission errors were stronger in the control group, and the reduction of commission errors was more substantial in the ADHD group. The cueP3, CNV, and N2d amplitudes changed slightly over two years, with negligible differences between both groups. Furthermore, the parent-rated symptom burden in the ADHD group decreased by 22 % (DSM-5-based questionnaire). We did not identify any associations between the changes in symptoms and the changes in the behavioral or neurophysiological metrics. The lack of association between the changes in symptoms and the behavioral or ERP metrics supports the trait liability hypothesis, which claims that the neurocognitive deficits are independent of symptom alleviation. Furthermore, the change in symptom burden was substantial, questioning the stability of the reported ADHD symptoms

Facial emotion recognition deficits in children with and without attention deficit hyperactivity disorder: a behavioral and neurophysiological approach

The current study examined the facial emotion recognition ability with a simultaneous assessment of behavioral and neurophysiological data in children with and without attention deficit hyperactivity disorder (ADHD) aged 7-17 years using a facial emotion matching task and event-related potential measurements (event-related potential components N170 and N250 at T5 and T6) in an emotional continuous performance task. Group differences and interaction effects of children's performance (both behavioral and neurophysiological) were evaluated between children with ADHD and children without ADHD as well as between younger and older children. No deficit in facial emotion recognition was found for children with ADHD compared with children without ADHD even with neurophysiological parameters. However, in terms of developmental differences, the younger children differentiated in their behavioral and neurophysiological performance from the older children. No interaction was detected between the experimental groups and the age groups, indicating that developmental progression in terms of emotional processes did not differ between children with and without ADHD. This study indicates that the facial emotion recognition is above all an age-dependent function with later processing of facial emotion expressions in younger compared with older children and suggests that a facial emotion recognition deficit is secondary in children with ADHD and might occur only with specific emotions or ADHD subtypes, but not in the whole ADHD population