Hair Cortisol and Perceived Stress-Predictors for the Onset of Tics? A European Longitudinal Study on High-Risk Children.

Some retrospective studies suggest that psychosocial stressors trigger the onset of tics. This study examined prospective hypothalamic-pituitary-adrenal (HPA) axis activity and perceived stress prior to tic onset. In the present study, 259 children at high risk for developing tics were assessed for hair cortisol concentration (HCC) and parent-on-child-reported perceived stress four-monthly over a three-year period. We used (i) generalised additive modelling (GAM) to investigate the time effects on HCC (hair samples n = 765) and perceived stress (questionnaires n = 1019) prior to tic onset and (ii) binary logistic regression to predict tic onset in a smaller subsample with at least three consecutive assessments (six to nine months before, two to five months before, and at tic onset). GAM results indicated a non-linear increasing course of HCC in children who developed tics, and a steady HCC course in those without tics, as well as a linear-increasing course of perceived stress in both groups. Logistic regression showed that with a higher HCC in hair samples collected in a range of two to five months before tic onset (which refers to cortisol exposure in a range of four to eight months), the relative likelihood of tic onset rose. Our study suggests increased stress prior to tic onset, as evidenced by higher HCC several months before tic onset.

Hair cortisol-a stress marker in children and adolescents with chronic tic disorders? A large European cross-sectional study.

BACKGROUND: There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. METHODS: Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3-16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3-10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. RESULTS: There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. CONCLUSION: A link between HCC and TDs is not supported by the present results.

Comprehensive Behavioral Intervention for Tics reduces perception-action binding during inhibitory control in Gilles de la Tourette syndrome.

Gilles de la Tourette Syndrome (GTS) is a developmental disorder. Empirical studies and an emerging cognitive framework on GTS suggest that GTS is a disorder of abnormally strong 'perception-action binding'. Theoretical considerations imply that the effectiveness of long-established behavioral interventions might be related to a normalization of increased binding in GTS. This has not been tested yet. We examined the effect of a standardized Comprehensive Behavior Intervention for Tics (CBIT) in N = 21 adolescent GTS patients and N = 21 healthy controls on perception-action binding in an inhibitory control paradigm. Prior to CBIT, GTS patients showed compromised performance compared to controls, specifically when inhibitory control was triggered by uni-modal visual compared to bi-modal stimuli. After CBIT intervention, GTS patient's performance was at the same level as healthy controls. This is supported by a Bayesian data analysis. CBIT specifically affected inhibitory control in a condition where reconfigurations of perception-action bindings are necessary to perform inhibitory control. A power of 95% was evident for these effects. CBIT reduces increased 'binding' between perception and action in GTS and thereby increases the ability to perform response inhibition. The results are the first to provide insights as to why CBIT is effective by relating elements of this intervention to overarching cognitive theoretical frameworks on perception-action bindings.

Evidence for an altered architecture and a hierarchical modulation of inhibitory control processes in ADHD.

Inhibitory control deficits are a hallmark in ADHD. Yet, inhibitory control includes a multitude of entities (e.g. 'inhibition of interferences' and 'action inhibition'). Examining the interplay between these kinds of inhibitory control provides insights into the architecture of inhibitory control in ADHD. Combining a Simon task and a Go/Nogo task, we assessed the interplay of 'inhibition of interferences' and 'action inhibition'. This was combined with EEG recordings, EEG data decomposition and source localization. Simon interference effects in Go trials were larger in ADHD. At the neurophysiological level, this insufficient inhibition of interferences in ADHD related to the superior parietal cortex. Simon interference effects were absent in action inhibition (Nogo) trials in ADHD, compared to controls. This was supported by bayesian statistics. The power of effects was higher than 95%. The differential effects between the groups were associated with modulations of neurophysiological response selection processes in the superior frontal gyrus. ADHD is not only associated with deficits in inhibitory control. Rather, the organization and architecture of the inhibitory control system is different in ADHD. Distinguishable inhibitory control processes operate on a hierarchical 'first come, first serve' basis and are not integrated in ADHD. This is a new facet of ADHD.

Altered perception-action binding modulates inhibitory control in Gilles de la Tourette syndrome.

BACKGROUND: Gilles de la Tourette Syndrome (GTS) is a multifaceted neuropsychiatric developmental disorder with onset in childhood or adolescence and frequent remissions in early adulthood. A rather new emerging concept of this syndrome suggests that it is a disorder of purposeful actions, in which sensory processes and their relation to motor responses (actions) play a particularly important role. Thus, this syndrome might be conceived as a condition of altered 'perception-action binding'. In the current study, we test this novel concept in the context of inhibitory control. METHODS: We examined N = 35 adolescent GTS patients and N = 39 healthy controls in a Go/Nogo-task manipulating the complexity of sensory information triggering identical actions; i.e. to inhibit a motor response. This was combined with event-related potential recordings, EEG data decomposition and source localization. RESULTS: GTS patients showed worse performance compared to controls and larger performance differences when inhibitory control had to be exerted using unimodal visual compared to bimodal auditory-visual stimuli. This suggests increased binding between bimodal stimuli and responses leading to increased costs of switching between responses instructed by bimodal and those instructed by unimodal stimuli. The neurophysiological data showed that this was related to mechanisms mediating between stimulus evaluation and response selection; i.e. perception-action binding processes in the right inferior parietal cortex (BA40). CONCLUSIONS: Stimulus-action inhibition binding is stronger in GTS patients than healthy controls and affects inhibitory control corroborating the concept suggesting that GTS might be a condition of altered perception-action integration (binding); i.e. a disorder of purposeful actions.

Differences in response inhibition processes between adolescents and adults are modulated by sensory processes.

Response inhibition processes undergo strong developmental changes. The same is true for sensory processes, and recent evidence shows that there also within-modality differences in the efficacy to trigger motor response inhibition. Yet, modulatory effects of within-modality differences during age-related changes in response inhibition between adolescence and adulthood are still indeterminate. We investigated this question in a system neurophysiological approach combining analysis of event-related potentials (ERPs) with temporal EEG signal decomposition and source localization processes. We used the somatosensory system to examine possible within-modality differences. The study shows that differences in response inhibition processes between adolescents and adults are modulated by sensory processes. Adolescents show deficient response inhibition when stimuli triggering these mechanisms are processed via SI somatosensory areas, compared to SII somatosensory areas. Opposed to this, no differences between adolescents and adults are evident, when response inhibition processes are triggered via SII cortical regions. The EEG data suggests that specific neurophysiological subprocesses are associated with this. Adolescents seem to encounter problems assigning processing resources to integrate motor with tactile information in posterior parietal areas when this information is processed via SI. Thus, basic perceptual and age-related processes interactively modulate response inhibition as an important instance of cognitive control.

Neurophysiological variability masks differences in functional neuroanatomical networks and their effectiveness to modulate response inhibition between children and adults.

Executive functions are well-known to undergo developmental changes from childhood to adulthood. Considerable efforts have been made to elucidate the affected system neurophysiological mechanisms. But while it is well-known that developmental changes affect intra-individual variability, this potential bias has largely been neglected when investigating the neurophysiology underlying developmental differences between children and adults. We hypothesize that due to differences in intra-individual variability of neural processes between children and adults, reliable group differences will only be evident after accounting for intra-individual variability in neurophysiological processes. We, therefore, investigate response-inhibition processes as an important instance of executive control in children (between 10 and 14 years) and adults (between 20 and 29 years) and decompose EEG data on the basis of the latency and temporal variability. This was combined with source localization. Children showed more impulsive behavior than adults. Importantly, a reliable match between the neurophysiological and behavioral data could only be found when accounting for intra-individual variability in the EEG data. These decomposed data showed that children and adults use similar neurophysiological mechanisms at the response selection level to accomplish inhibitory control, but seem to engage different neuroanatomical structures to do so according to source localization results: In adults, these processes were related to the medial frontal cortex. In children, the same processes were reflected in a shift of the scalp topography and related to the superior parietal cortex. These shifts in neural networks were associated with lower effectiveness in exerting inhibitory control. However, these differences in the functional neuroanatomical architecture can only be seen when intra-individual variability is taken into account.

On the dependence of response inhibition processes on sensory modality.

The ability to inhibit responses is a central sensorimotor function but only recently the importance of sensory processes for motor inhibition mechanisms went more into the research focus. In this regard it is elusive, whether there are differences between sensory modalities to trigger response inhibition processes. Due to functional neuroanatomical considerations strong differences may exist, for example, between the visual and the tactile modality. In the current study we examine what neurophysiological mechanisms as well as functional neuroanatomical networks are modulated during response inhibition. Therefore, a Go/NoGo-paradigm employing a novel combination of visual, tactile, and visuotactile stimuli was used. The data show that the tactile modality is more powerful than the visual modality to trigger response inhibition processes. However, the tactile modality loses its efficacy to trigger response inhibition processes when being combined with the visual modality. This may be due to competitive mechanisms leading to a suppression of certain sensory stimuli and the response selection level. Variations in sensory modalities specifically affected conflict monitoring processes during response inhibition by modulating activity in a frontal parietal network including the right inferior frontal gyrus, anterior cingulate cortex and the temporoparietal junction. Attentional selection processes are not modulated. The results suggest that the functional neuroanatomical networks involved in response inhibition critically depends on the nature of the sensory input. Hum Brain Mapp 38:1941-1951, 2017. © 2017 Wiley Periodicals, Inc.