Mal-Adaptation of Event-Related EEG Responses Preceding Performance Errors

Recent EEG and fMRI evidence suggests that behavioral errors are foreshadowed by systematic changes in brain activity preceding the outcome by seconds. In order to further characterize this type of error precursor activity, we investigated single-trial event-related EEG activity from 70 participants performing a modified Eriksen flanker task, in particular focusing on the trial-by-trial dynamics of a fronto-central independent component that previously has been associated with error and feedback processing. The stimulus-locked peaks in the N2 and P3 latency range in the event-related averages showed expected compatibility and error-related modulations. In addition, a small pre-stimulus negative slow wave was present at erroneous trials. Significant error-preceding activity was found in local stimulus sequences with decreased conflict in the form of less negativity at the N2 latency (310–350 ms) accumulating across five trials before errors; concomitantly response times were speeding across trials. These results illustrate that error-preceding activity in event-related EEG is associated with the performance monitoring system and we conclude that the dynamics of performance monitoring contribute to the generation of error-prone states in addition to the more remote and indirect effects in ongoing activity such as posterior alpha power in EEG and default mode drifts in fMRI

Neural plasticity in functional and anatomical MRI studies of children with Tourette syndrome

Background: Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by chronic motor and vocal tics. The typical clinical course of an attenuation of symptoms during adolescence in parallel with the emerging self-regulatory control during development suggests that plastic processes may play an important role in the development of tic symptoms. Methods: We conducted a systematic search to identify existing imaging studies (both anatomical and functional magnetic resonance imaging [fMRI]) in young persons under the age of 19 years with TS. Results: The final search resulted in 13 original studies, which were reviewed with a focus on findings suggesting adaptive processes (using fMRI) and plasticity (using anatomical MRI). Differences in brain activation compared to healthy controls during tasks that require overriding of prepotent responses help to understand compensatory pathways in children with TS. Along with alterations in regions putatively representing the origin of tics, deviations in several other regions most likely represent an activity-dependent neural plasticity that help to modulate tic severity, such as the prefrontal cortex, but also in the corpus callosum and the limbic system. Discussion: Factors that potentially influence the development of adaptive changes in the brain of children with TS are age, comorbidity with other developmental disorders, medication use, IQ along with study-design or MRI techniques for acquisition, and analysis of data. The most prominent limitation of all studies is their cross-sectional design. Longitudinal studies extending to younger age groups and to children at risk for developing TS hopefully will confirm findings of neural plasticity in future investigations.publishedVersio

Lower Cardiac Vagal Activity Predicts Self-Reported Difficulties With Emotion Regulation in Adolescents With ADHD

Objective: To investigate the relation between cardiac vagal activity (CVA), a measure of autonomic nervous system (ANS) flexibility, and self-reported emotion regulation (ER) difficulties in adolescents with attention-deficit/hyperactivity disorder (ADHD) and controls. Methods: The sample comprised 11-17-year-old adolescents with ADHD (n=34) and controls (n = 33). Multiple linear regression analyses investigated the relation between CVA, as indexed by high frequency heart rate variability (HF-HRV), and ER difficulties as assessed by the Difficulties in Emotion Regulation Scale (DERS). Supplemental analyses were performed in ADHD and control groups separately. Analyses assessed effects of body mass index (BMI), physical activity levels, and HF peak as a surrogate of respiration on CVA. Results: Lower CVA was associated with ER difficulties, and specifically with limited access to effective ER strategies. When investigating the relation between CVA and ER in the ADHD and control groups separately, there was a tendency of lower CVA predicting limited access to effective ER strategies in the ADHD group, and not in the control group. Conclusion: The results suggest that lower CVA, i.e., reduced ANS flexibility, in adolescents with ADHD and controls is associated with self-reported ER difficulties, and specifically with limited access to effective ER strategies. There was a tendency for lower CVA to predict limited ER strategies only in the adolescents with ADHD and not controls. Keywords: attention-deficit/hyperactivity disorder; autonomic nervous system; cardiac vagal activity; difficulties in emotion regulation scale; emotion regulation; heart rate variability

Development of Performance and ERPs in a Flanker Task in Children and Adolescents with Tourette Syndrome—A Follow-Up Study

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder with childhood-onset, with a typical decline in tic severity, as well as an increasing ability to suppress tics in late childhood and adolescence. These processes develop in parallel with general improvement of self-regulatory abilities, and performance monitoring during this age-span. Hence, changes in performance monitoring over time might provide insight into the regulation of tics in children and adolescents with TS.Method: We measured reaction time, reaction time variability, accuracy, and event-related potentials (ERP) in 17 children with TS, including 10 children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), 24 children with ADHD, and 29 typically developing children, using a modified Eriksen Flanker task in two testing sessions administered on average 4.5 years apart. We then compared task performance, as well as ERP components across groups, and over time using regression models.Results: Task performance improved in all groups with age, and behavioral differences between children with TS and controls diminished at second assessment, while differences between controls and children with ADHD largely persisted. In terms of ERP, the early P3 developed earlier in children with TS compared with controls at the first assessment, but trajectories converged with maturation. ERP component amplitudes correlated with worst-ever tic scores.Conclusions: Merging trajectories between children with TS and controls are consistent with the development of compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression, in contrast to children with ADHD. Correlations between ERP amplitudes and tic scores also support this notion

European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part III: pharmacological treatment

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients’ self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient’s needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician’s preferences, experience, and local regulatory requirements.publishedVersio

Electrophysiological Correlates of Performance Monitoring in Children with Tourette Syndrome. A developmental perspective

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset, characterized by chronic motor and vocal tics. Typically, tic symptoms attenuate during adolescence in parallel with the emerging self-regulatory control during brain development. The voluntary control over thought and action provides the ability to withhold unwanted behaviour and an association between cognitive control and tic control has been suggested. This attenuation of tic symptoms also suggests that neuroplasticity may play an important role in this process. The work discussed herein is centred on how compensatory mechanisms may affect dysfunctional neurocognitive processes, specifically performance monitoring deficits in children and adolescents with TS. In paper I, we have summarized current knowledge on neural plasticity in children and adolescence with TS. To present the current understanding of dysfunctional neurocognitive processes seen in functional magnetic resonance imaging and possible compensatory effects seen in anatomical magnetic resonance imaging in TS, we conducted an overview of data from studies comparing children with TS to healthy peers. In order to assess the importance of possible adaptive effects in paediatric TS, we reviewed with special attention to covariation with tic severity. The summary revealed differences in brain regions representing the tic origin along with deviations in other regions that might represent activity-dependent activation that help to modulate tic severity in TS compared with controls. Age, comorbidity with other developmental disorders, especially with attention deficit/hyperactivity disorder (ADHD), medication use, and intelligence were identified as factors that potentially influence the development of adaptive changes. Comparative analyses or meta-analytic approaches are thus far difficult due to inherent differences in study-design, magnetic resonance imaging techniques for acquisition, and analysis of primary data. The paper highlights the importance of studying cognitive control and adaptive effects in TS, while also revealing the scarcity of studies with longitudinal design and other modalities, as e.g. electrophysiology. The two next papers are based on the electrophysiological data collected to better understand the origins of cognitive control and performance monitoring deficits in TS. The main aim of paper II was to test an established experimental setup of performance monitoring in order to identify if behavioural and electrophysiological performance monitoring differences occur in children with TS when compared to controls and a contrast group with children with ADHD at the age of 8-12 years. We employed event-related potentials (ERP) in order to monitor stimulus-related and response-related components elicited during a flanker task. The main findings of this investigation indicate that the children with TS and children with ADHD and healthy controls behaviourally performed much the same regarding reaction times, accuracy and response variability when controlling for covariates. However, when not controlling for relevant covariates, children with TS and children with ADHD performed on a slightly lower level. ERP results showed higher amplitudes of an early P3 component of the stimulus-locked potentials in ensemble averages and in separate trial outcomes, as well as a slightly higher positive complex before the motor response, likely reflecting a late P3 in children with TS when compared to controls and children with ADHD. We interpreted the differences as mainly caused by heightened attentional resource allocation during stimulus evaluation. Groups did not differ in post-response components. These findings thus suggest that children with TS may employ additional attentional resources as a compensatory mechanism to maintain equal behavioural performance. While paper II focused on disentangling the role of sub-processes of performance monitoring in children with TS, paper III was more focused on the developmental changes in performance monitoring which might help the understanding of tic regulation and attenuation over time in children and adolescents with TS. To this end, we compared task performance and ERP components from the first assessment with a follow-up ERP study administered on average 4.5 years later in the same population using regression models. The results from this investigation indicated that cognitive measures of children with TS approached the values found in controls at the second assessment while differences between children with ADHD and controls largely persisted. ERP measures related to orienting and sustained attention, that developed earlier in children with TS compared with controls at the first assessment converged with maturation and correlated with worst-ever tic scores. In summary, the research described in this thesis contributes to the further understanding of electrophysiological correlates of performance monitoring in children with Tourette syndrome in several ways. In paper I, we found the current literature to implicate dysfunctional neurocognitive processes and possible compensatory effects in children with TS. The use of a neurocognitive model of performance monitoring in paper II suggested heightened orienting and/or attention requirements during stimulus evaluation as a compensatory mechanism to maintain equal behavioural performance. The developmental approach in paper III allowed us to find evidence of converging cognitive and electrophysiological measures over time in children with TS when compared with controls as well as correlation between ERPs and worst-ever tic scores. The main results from each of the papers presented continue to implicate compensatory self-regulation mechanisms during early adolescence, probably facilitating tic suppression. Correlations between ERP amplitudes and tic scores also support this notion

Go/NoGo Performance in Boys with Tourette Syndrome

Tourette syndrome has been associated with impairments of performance monitoring and alterations of attentional and executive functions. This impairment has been linked to fronto-striatal dysfunctions, which comprise the same braincircuits that are actively engaged in the suppression of tics. We compared behavioral performance and performance monitoring in nineteen boys with Tourette syndrome (TS) (mean age 12.64 years, ± 2.05) and nineteen age-matched controls (mean age 13.16 years, ± 2.29) in a Go/NoGo paradigm. This paradigm was designed to test for problems with inhibition and attention when withholding the response to NoGo targets following repetitive Go targets. The results indicated similar performance accuracy in the TS group and the control group. TS participants showed the expected pattern of Post-Error Slowing, but responded significantly also slower to correct Go trials than the controls. The reaction times (RT) to NoGo targets in commission errors, however, did not differ between the groups. The results suggest that boys with TS develop inhibitory adaptive strategies (overall slower reaction times) to maintain high performance accuracy. These effects may be suspended prior to and during NoGo commission errors.Tourette Syndrom (TS) wurde mit Beeinträchtigungen des Handlungsüberwachungs-Systems und mit Veränderungen von Aufmerksamkeit und exekutiven Funktionen assoziiert. Diese Beeinträchtigungen mögen mit einer fronto-striatalen Dysfunktion in Verbindung stehen, die dieselben Gehirnbahnen betreffen, die zur aktiven Unterdrückung von Tics benutzt werden. Wir verglichen Leistungsgenauigkeit und Reaktionszeiten von 19 Jungs mit TS (Durchschnittsalter 12.64 Jahre, ± 2.05) mit 19 gleichaltrigen Jungs einer Kontrollgruppe (Durchschnittsalter 13.16 Jahre, ± 2.29) in einem Go/NoGo-Experiment. Dieses Experiment testet Probleme mit Inhibition und Aufmerksamkeit, wenn ein Teilnehmer seine Antwort auf einen NoGo-Zielreiz unterdrücken soll. Die Resultate wiesen auf eine ähnliche Leistungsgenauigkeit der TS-Gruppe und der Kontrollgruppe hin. Die Kinder mit TS zeigten das erwartete Muster einer Verlangsamung nach einer fehlerhaften Antwort, aber antworteten auch signifikant langsamer auf die korrekten Go-Zielreize als die Kontrollgruppe. Die Reaktionszeiten auf die falsch beantworteten inhibitorischen Zielreize unterschieden sich jedoch nicht in beiden Gruppen. Diese Resultate lassen vermuten, dass die Kinder mit TS inhibitorische adaptive Strategien (insgesamt langsamere Reaktionszeiten) entwickelt haben, um eine hohe Leistungsgenauigkeit aufrecht zu erhalten. Diese Effekte schienen vorübergehend aufgehoben zu sein vor und während falsch beantworteter NoGo-Zielreize

Neural plasticity in functional and anatomical MRI studies of children with Tourette syndrome

Background: Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by chronic motor and vocal tics. The typical clinical course of an attenuation of symptoms during adolescence in parallel with the emerging self-regulatory control during development suggests that plastic processes may play an important role in the development of tic symptoms. Methods: We conducted a systematic search to identify existing imaging studies (both anatomical and functional magnetic resonance imaging [fMRI]) in young persons under the age of 19 years with TS. Results: The final search resulted in 13 original studies, which were reviewed with a focus on findings suggesting adaptive processes (using fMRI) and plasticity (using anatomical MRI). Differences in brain activation compared to healthy controls during tasks that require overriding of prepotent responses help to understand compensatory pathways in children with TS. Along with alterations in regions putatively representing the origin of tics, deviations in several other regions most likely represent an activity-dependent neural plasticity that help to modulate tic severity, such as the prefrontal cortex, but also in the corpus callosum and the limbic system. Discussion: Factors that potentially influence the development of adaptive changes in the brain of children with TS are age, comorbidity with other developmental disorders, medication use, IQ along with study-design or MRI techniques for acquisition, and analysis of data. The most prominent limitation of all studies is their cross-sectional design. Longitudinal studies extending to younger age groups and to children at risk for developing TS hopefully will confirm findings of neural plasticity in future investigations

Event-Related-Potential (ERP) Correlates of Performance Monitoring in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

Introduction: Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in children and tends to persist into adulthood. Evidence from neuropsychological, neuroimaging, and electrophysiological studies indicates that alterations of error processing are core symptoms in children and adolescents with ADHD. To test whether adults with ADHD show persisting deficits and compensatory processes, we investigated performance monitoring during stimulus-evaluation and response-selection, with a focus on errors, as well as within-group correlations with symptom scores. Methods: Fifty-five participants (27 ADHD and 28 controls) aged 19–55 years performed a modified flanker task during EEG recording with 64 electrodes, and the ADHD and control groups were compared on measures of behavioral task performance, event-related potentials of performance monitoring (N2, P3), and error processing (ERN, Pe). Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptom load. Results: Adults with ADHD showed higher error rates in incompatible trials, and these error rates correlated positively with the ASRS scores. Also, we observed lower P3 amplitudes in incompatible trials, which were inversely correlated with symptom load in the ADHD group. Adults with ADHD also displayed reduced error-related ERN and Pe amplitudes. There were no significant differences in reaction time (RT) and RT variability between the two groups. Conclusion: Our findings show deviations of electrophysiological measures, suggesting reduced effortful engagement of attentional and error-monitoring processes in adults with ADHD. Associations between ADHD symptom scores, event-related potential amplitudes, and poorer task performance in the ADHD group further support this notion.publishedVersio