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.

Vigilance described by the time-on-task effect in EEG activity during a cued Go/NoGo task.

Vigilance refers to the ability to maintain attention and to remain alert to stimuli in prolonged and monotonous tasks. Vigilance decrement describes the decline in performance in the course of such sustained attention tasks. Time-related alterations in attention have been found to be associated with changes in EEG. We investigated these time-on-task effects on the basis of changes in the conventional EEG spectral bands with the aim of finding a compound measure of vigilance. 148 healthy adults performed a cued Go/NoGo task that lasted approximately 21 min. Behavioural performance was examined by comparing the number of errors in the first and last quarters of the task using paired t-test. EEG data were epoched per trial, and time-on-task effects were modelled by using multiple linear regression, with frequency spectra band power values as independent variables and trial number as the dependent variable. Behavioural performance decreased in terms of omission errors only. Performance of the models, expressed by predicted R-squared, was between 0.10 and 0.27, depending on the particular task condition. The time-on-task EEG spectral changes were characterized by broad changes in the alpha and frontal changes in the beta and gamma bands. We were able to identify a set of EEG spectral features that predict time-on-task. Our output is considered to be a measure of vigilance, reflecting the allocation of mental resources for the maintenance of attention.

Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.

Longitudinal Analysis of Self-Reported Symptoms, Behavioral Measures, and Event-Related Potential Components of a Cued Go/NoGo Task in Adults With Attention-Deficit/Hyperactivity Disorder and Controls.

This study characterizes a large sample of adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls regarding their task performance and neurophysiology; cross-sectionally and longitudinally. Self-reported symptoms, behavioral measures, and event-related potentials from a classical cued Go/NoGo task were used to outline the symptom burden, executive function deficits and neurophysiological features, and the associations between these domains. The study participants (N = 210 ADHD, N = 158 controls, age: 18-62 years) were assessed five (ADHD) or three (controls) times over two years. We describe cross-sectional and longitudinal group differences, and associations between symptom burden, and behavioral and event-related potential (ERP) components variables by latent growth curve models, including random slopes and intercepts. The ADHD group showed increased reaction time variability, increased commission and omission errors, and attenuated cueP3, CNV, N2d, and P3d amplitudes. We observed a decrease in self-reported symptoms in the ADHD group over the two years. The behavioral measures (reaction time variability, number of omission, and commission errors) did not change over time, whereas the cueP3, P3d, and N2d amplitude attenuated in both groups. There was no evidence for a robust association between symptom burden and behavioral or ERP measures. The changes in the ERP components with stable task performance, potentially indicate more efficient neuronal processing over the two years. Whether the lack of association between symptom burden and behavioral or ERP measures might be due to the low reliability of the ADHD assessment criteria, or the inappropriateness of the objective measures cannot be inferred.

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.

EEG modulation by different transcranial direct current stimulation (tDCS) montages: a randomized double-blind sham-control mechanistic pilot trial in healthy participants.

Background: Based on our Phantom study on transcranial direct current stimulation (tDCS), we hypothesized that EEG band power and field confinement would be greater following left dorsolateral prefrontal cortex (DLPFC - F3) tDCS using circular vs. rectangular electrodes.Methods: Double-blind-randomized trial comparing tDCS with anode over left DLPFC (groups: rectangular electrodes, circular electrodes, sham) and 2 active subgroup references (right shoulder vs. right DLPFC).Results: Twenty-four randomized participants were assessed. We indeed found higher average EEG power spectral density (PSD) across bands for circular vs. rectangular electrodes, largely confined to F3 and there was a significant increase at AF3 for low alpha (p = 0.037). Significant differences included: increased PSD in low beta (p = 0.024) and theta bands (p = 0.021) at F3, and in theta (p = 0.036) at FC5 for the right DLPFC vs. shoulder with no coherence changes. We found PSD differences between active vs. sham tDCS at Fz for alpha (p = 0.043), delta (p = 0.036), high delta (p = 0.030); and at FC1 for alpha (p = 0.031), with coherence differences for F3-Fz in beta (p = 0.044), theta (p = 0.044), delta (p = 0.037) and high delta (p = 0.009).Conclusion: This pilot study despite low statistical power given its small sample size shows that active left DLPFC tDCS modulates EEG frontocentrally and suggests that electrode shapes/reference locations affect its neurophysiological effects, such as increased low alpha power at AF3 using circular vs. rectangular electrodes. Further research with more participants is warranted.

Protective and Risk Factors for Phantom Limb Pain and Residual Limb Pain Severity.

INTRODUCTION: The exact mechanisms underlying the development and maintenance of phantom limb pain (PLP) are still unclear. This study aimed to identify the factors affecting pain intensity in patients with chronic, lower limb, traumatic PLP. METHODS: This is a cross-sectional analysis of patients with PLP. We assessed amputation-related and pain-related clinical and demographic variables. We used univariate and multivariate models to evaluate the associated factors modulating PLP and residual limb pain (RLP) intensity. RESULTS: We included 71 unilateral traumatic lower limb amputees. Results showed that (1) amputation-related perceptions were experienced by a large majority of the patients with chronic PLP (sensations: 90.1%, n = 64; residual pain: 81.7%, n = 58); (2) PLP intensity has 2 significant protective factors (phantom limb movement and having effective treatment for PLP previously) and 2 significant risk factors (phantom limb sensation intensity and age); and (3) on the other hand, for RLP, risk factors are different: presence of pain before amputation and level of amputation (in addition to the same protective factors). CONCLUSION: These results suggest different neurobiological mechanisms to explain PLP and RLP intensity. While PLP risk factors seem to be related to maladaptive plasticity, since phantom sensation and older age are associated with more pain, RLP risk factors seem to have components leading to neuropathic pain, such as the amount of neural lesion and previous history of chronic pain. Interestingly, the phantom movement appears to be protective for both phenomena.

Real-time Video Projection in an MRI for Characterization of Neural Correlates Associated with Mirror Therapy for Phantom Limb Pain.

Mirror therapy (MT) has been proposed as an effective rehabilitative strategy to alleviate pain symptoms in amputees with phantom limb pain (PLP). However, establishing the neural correlates associated with MT therapy have been challenging given that it is difficult to administer the therapy effectively within a magnetic resonance imaging (MRI) scanner environment. To characterize the functional organization of cortical regions associated with this rehabilitative strategy, we have developed a combined behavioral and functional neuroimaging protocol that can be applied in participants with a leg amputation. This novel approach allows participants to undergo MT within the MRI scanner environment by viewing real-time video images captured by a camera. The images are viewed by the participant through a system of mirrors and a monitor that the participant views while lying on the scanner bed. In this manner, functional changes in cortical areas of interest (e.g., sensorimotor cortex) can be characterized in response to the direct application of MT.