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