Brigitta Kakuszi

Electrophysiological indices of aberrant error-processing in adults with ADHD: a new region of interest

Deficits in error-processing are postulated in core symptoms of ADHD. Our goal was to investigate the neurophysiological basis of abnormal error-processing and adaptive adjustments in ADHD, and examine whether error-related alterations extend beyond traditional Regions of Interest (ROIs), particularly to those involved in adaptive adjustments, such as the Salience Network system. We obtained event-related potentials (ERPs) during a Go/NoGo task from 22 adult-ADHD patients and 29 matched healthy controls using a high-density 256-electrode array. Error-related ERPs with error-negativity (ERN) and error-positivity (Pe) served as probes of error-processing. In ADHD patients both ERN and Pe were significantly reduced, and the reduction was associated with core psychopathological symptoms. The ERP-attenuation was prominent not only at traditional ROI-electrodes but across many other brain areas, with a distinctive subset of group-differences and symptom-correlations manifested at temporo-parietal sites, with right-lateralization. Source-localization uncovered two neural-sources for the error-related ERPs: one in the cingulate cortex near midline, which was present in both groups; and one in the right insular cortex, which was present only in the control group. The neural patterns of impairments may be the result of coexisting deficits in the dorsal midline error-processing brain network involved in “error-processing proper” and the right-lateralized temporo-parietal salience network involved in the evaluation of significance of the error-signals. Our source-localization findings potentially identify a missing link between the previously reported structural change, i.e., reduced insular volume, and the well-established behavioral deficits in ADHD.

Altered response-preparation in patients with adult ADHD: A high-density ERP study

Aberrations in early-developing bottom-up processes, such as stimulus-driven response preparation, are thought to play a critical role in the onset of ADHD, and in its persistence over time. Electrophysiology offers a unique tool to gain insight into response preparation, since response preparation has been associated with distinctive ERP changes, including negative potential-shifts which occur predominantly over frontal brain areas. We examined response-preceding negative potential shifts (RPNS) as a probe of response-preparation in adult ADHD patients by obtaining high-density event-related potentials from 33 ADHD and 29 matched healthy subjects during a Go/Nogo task using a 128-channel BioSemi recording-system. Compared to controls, ADHD patients showed enhancement of the RPNS in fronto-central brain regions in the Go condition during correct responses. This change was associated with poor performance in the Stroop incongruency-task: the greater the enhancement, the higher the proportion of errors. Moreover, the ERP-enhancement showed association with the severity of ADHD-symptoms; and with heightened response-variability. Thus, ADHD patients demonstrate neurophysiological alterations in response-preparation and response-preceding brain activity, suggestive of excessive activation of prefrontal neural circuits. Given the correlation with neuropsychological and psychopathological measures, these changes may constitute a pathway for core symptoms of ADHD, including premature and impaired response-preparation and motor-hyperactivity.

Decreased resting gamma activity in adult attention deficit/hyperactivity disorder

Abstract Objectives: To delineate task-free gamma activity in adult ADHD and healthy control subjects based on high-density EEG recordings. Relationship of gamma activity with symptom severity was also examined, since gamma activity is considered to be an index of network functions in the brain that underlie higher-order cognitive processes. Methods: Spontaneous EEG was recorded in adult ADHD subjects (N = 42; 25 methylphenidate-naïve and 17 on methylphenidate treatment) and controls (N = 59) with eyes open. EEG absolute power gamma was investigated in the gamma1 (30.25–39 Hz) and gamma2 (39.25–48 Hz) frequency bands. Results: Gamma1 and gamma2 activity was diminished in ADHD compared with healthy control subjects. The difference between ADHD and controls was the most pronounced in the right centroparietal region for both gamma1 and gamma2. Inverse associations were found between gamma1 and gamma2 activity and ADHD symptoms in centroparietal scalp regions. Conclusions: Gamma activity is reduced in adult ADHD, and the reduction has a predominantly right centroparietal distribution. Our findings are consistent with childhood ADHD literature with respect to diminished posterior gamma activity in patients, which may reflect altered dorsal attention network functions. Gamma abnormalities might provide a link between neurophysiological functioning and neuropsychological deficiencies, thereby offering an opportunity to investigate the neurobiological mechanisms that underlie the clinical symptoms of ADHD.

EPA-0645 – Neural correlates of impairments in conflict monitoring in ADHD: an event related potential (ERP) study

Introduction Major symptoms evidenced by patients with Attention Deficit Hyperactivity Disorder (ADHD) have been linked to deficiencies in cognitive control, especially when conflicts in information processing occur. Objective We wanted to define neural correlates of impairments in conflict monitoring in ADHD using the ERP technique. Unlike previous ERP studies that focused on brain potentials following incorrect responses in ADHD, we investigated a brain potential, the N2, which reflects conflict monitoring before a correct response. Method Participants were 33 adult ADHD subjects, and 29 matched healthy controls. We recorded 128-channel EEGs for ERP responses during a Go/NoGo Task with a prepotent GO response, where subjects had to withhold response to repeated stimuli. Results Using age and gender as covariates in the analyses, subjects with ADHD evidenced significantly larger N2 amplitudes than healthy controls. The extent of N2 enhancement showed a significant association with the number of errors in the incongruent condition of the Stroop Task. With regard to scalp topography, the differences were manifested over the frontal areas, with the most pronounced difference appearing at the midline areas. Conclusions Patients with ADHD evidence a marked enhancement in N2 amplitude in a Go/NoGo task with prepotent response tendency. The fact that N2 enhancement is directly related to incongruent errors in the Stroop task suggests that behavioral deficits in conflict processing in ADHD may be underlied, at least partially, by the ‘hyperreactivity’ of neurobiological processes that generate this brain potential. Supported by the Hungarian Scientific Research Fund (OTKA), Grant NN103325

EPA-0649 – Response inhibition in attention deficit hyperactivity disorder (ADHD): the influence of emotional-valence on the P300 brain potential

Introduction Emerging evidence suggests that disturbances in emotional processing in ADHD may interfere with executive functioning, and account for impairments in life functioning. Objective To investigate whether patients with ADHD evidence deficits in processing emotionally-valenced inputs, and to delineate the neurobiological correlates of these deficits. Methods Using event-related potentials from 128-channels, we tested 33 adult ADHD subjects and 29 individually-matched healthy controls (HC) in a cognitive control task of response inhibition. The task was performed by presenting valenced pictures (positive/negative/neutral) of the International Affective Picture System. The pictures were shown in random sequence, and repeated occasionally. Participants were asked to respond to each stimulus, and to withhold response for the repetition. Results With regard to behavioral measures, ADHD subjects showed more commission and omission errors. In terms of ERPs, both groups displayed a pronounced P300 component for all emotional valences in the frontal regions in the NoGo vs. the Go condition (‘NoGo P300’). However, compared to HCs, ADHD subjects showed a significant P300 reduction for negative, but no reduction for positive, or neutral stimuli. Conclusions Regarding the frontal NoGo P300, HCs were able to overcome the intrusion of negative emotion, and showed the same waveform when presented with negative as they showed with positive or neutral stimuli. By contrast, while ADHD subjects did not differ from HCs regarding positive and neutral inputs, they exhibited a pronounced P300 reduction for negative pictures, which may constitute a neurobiological correlate of emotional dysregulation. Supported by the Hungarian Scientific Research Fund (OTKA), Grant NN103325

Teenage and adult pregnancy: A differential relationship between socio-economic status and smoking

INTRODUCTION Smoking occurs frequently during pregnancy, thereby putting mother and child at health risks. Low socio-economic status is a risk factor for smoking. AIM To investigate the relationship between smoking and low income in teenage and adult pregnancy, which is an important measure of poor socioeconomic status. METHOD The authors used subject-level data from the US NSDUH database, which contains information on pregnancies and smoking. RESULTS Teenage pregnancy is associated with higher, whereas adult pregnancy with lower prevalence of smoking, compared to the age-matched female population. The association between income and smoking is age-dependent. Among adults there is an inverse relationship (high income -- low-risk of smoking), while in teenage pregnancy smoking increases with income. CONCLUSIONS To investigate in teenage and adult pregnancy the relationship between smoking and low income, which is an important measure of poor socio-economic status. Higher socioeconomic status may be associated with risky behaviour, thereby increasing both the risk of smoking and early pregnancy.

P-1108 - Safety data on second-generation antipsychotics: changes from licensing to postmarketing

Background During drug development pharmaceutical manufacturers conduct numerous clinical trials to demonstrate therapeutic efficacy and safety of new antipsychotic drug candidates. However, clinical trials are impacted by the need to comply with scientific standards and regulatory requirements for approval. While supplying information necessary for approval, these trials provide data on a limited sample, obtained under conditions often removed from clinical practice. Drug labeling containing warnings, precautions and adverse events undergo regular revision once the population-based application provides evidence for need to change the information on the safety profiles of drugs. Aims To provide a systematic review of the safety profiles of 9 selected second-generation antipsychotic agents including aripiprazole, asenapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone upon and following FDA approval. Methods To gain access to safety profiles of the selected antipsychotic drugs we investigated the FDAs Summary Basis of Approval Documents. Comparison of safety profiles was made possible via the revisions provided in MedWatch Database. Results Safety data available upon approval fail to provide a full range of emerging side effects. Our results indicate that the labeling of all investigated antipsychotic drugs has been substantially expanded due to safety reasons both with regard to inclusion of adverse reactions (ARs) newly detected in the postmarketing phase and to providing more precise estimates for the incidence of individual ARs already described at the licensing phase. Conclusions Population-based application reveals unforeseeable health risks and additional costs both on manufacturer and patient level, emphasizing the need for novel methods for initial safety evaluation.