Judith Buse

Neuromodulation in Tourette syndrome: dopamine and beyond.

Almost since the beginning of research on Tourette syndrome (TS), tics have been linked to a dysfunction of the dopamine (DA) system. At first, this assumption was mainly based on clinical findings of DA antagonists being the most effective drug in treating tics, but in recent years nuclear imaging has enabled a much deeper understanding of DA neurotransmission in TS. Based on the findings of various PET and SPECT studies the first part of the review discusses four hypotheses on DA dysfunctions in TS: (i) DA hyperinnervation, (ii) supersensitive DA receptors, (iii) pre-synaptic DA abnormality and (iv) DA tonic-phasic dysfunction. According to the latter hypothesis, reduced levels of tonic DA in the extracellular space lead to higher concentrations of DA in the axon terminal and an increase of stimulus-dependent DA release. The second part of the review addresses the modulating role of DA in some major clinical features of TS, like the exacerbation with stress or infection and the association with deficient sensorimotor gating.

Neural correlates of altered sensorimotor gating in boys with Tourette Syndrome: A combined EMG/fMRI study

Abstract Objectives: It has been hypothesised that altered sensorimotor gating might be a core problem in Tourette Syndrome (TS). However, the underlying neurophysiological mechanisms are elusive. Methods: We applied functional magnetic resonance imaging (fMRI) to investigate the neural correlates of altered sensorimotor gating by means of prepulse inhibition (PPI) in 22 boys with TS and 22 healthy boys using tactile PPI. The electromyography of the startle response was recorded simultaneously to the acquisition of the fMRI images. Results: As expected, PPI of the startle response was reduced in boys with TS compared to the healthy boys. We found decreased PPI-related blood oxygen level-dependent (BOLD) activity in boys with TS in the middle frontal gyrus, postcentral gyrus, superior parietal cortex, cingulate gyrus and caudate body. In boys with TS PPI of the startle response was positively correlated to PPI-related BOLD activity in the superior parietal cortex. Conclusions: Our findings indicate that deficient sensorimotor gating in boys with TS is associated with reduced recruitment of brain regions responsible for the higher-order integration of somatosensory stimuli. Due to our strict sample selection we were able to reduce confounding by neural adaptation processes, long-term medication, gender or comorbidities.

The Modulating Role of Stress in the Onset and Course of Tourette’s Syndrome A Review

Accumulating data indicate a common occurrence of tic exacerbations and periods of psychosocial stress. Patients with Tourette’s syndrome (TS) also exhibit aberrant markers of hypothalamic-pituitary-adrenal (HPA) axis activation. Based on these findings, a functional relationship between stress and tic disorders has been suggested, but the underlying mechanism of how stress may affect tic pathology remains to be elucidated. We suggest that dopaminergic and noradrenergic neurotransmission as well as immunology play a crucial role in mediating this relationship. Two possibilities of causal direction might be assumed: (a) psychosocial stress might lead to an exacerbation of tics via activation of HPA axis and subsequent changes in neurotransmission or immunology and (b) TS-related abnormalities in neurotransmission or immunology result in a higher vulnerability of affected patients to respond to psychosocial stress with a strong activation of the HPA axis. It may also be the case that both assumptions hold true and interact with each other.

Clinical pharmacology of dopamine-modulating agents in Tourette's syndrome.

Forty years of research and clinical practice have proved dopamine (DA) receptor antagonists to be effective agents in the treatment of Tourettes syndrome (TS), allowing a significant tic reduction of about 70%. Their main effect seems to be mediated by the blockade of the striatal DA-D2 receptors. Various typical and atypical agents are available and there is still discord between experts about which of them should be considered as first choice. In addition, there are suggestions to use DA receptor agonists such as pergolide or non-DA-modulating agents. The present chapter is focusing on the clinical pharmacology of DA-modulating agents in the treatment of TS. The introduction outlines their clinical relevance and touches on the hypotheses of the role of DA in the pathophysiology of TS. Subsequently, general information about the mechanisms of action and adverse effects are provided. The central part of the chapter forms a systematic review of all DA-modulating agents used in the treatment of TS, including an overview of studies on their effectiveness, and a critical discussion of their specific adverse effects. The present chapter closes with a summary of the body of evidence and a description of the resulting recommendations for the pharmacological treatment of TS.

Fine motor skills and interhemispheric transfer in treatment-naive male children with Tourette syndrome

Aim  This study addressed whether Tourette syndrome is associated with an impairment of fine motor skills or altered interhemispheric transfer. We additionally investigated the association between interhemispheric transfer and size of the corpus callosum.

Accident Proneness in Children and Adolescents Affected by ADHD and the Impact of Medication

Objective: This study aims to ascertain once and for all whether children and adolescents affected by ADHD show a higher risk for accidents, as well as investigating a possible association between the administration of ADHD-specific medication and the occurrence of accidents. Method: Two exceptionally large sets of data were implemented in this analysis. Participants included children and adolescents representative of the entire German population. Data for Survey 1 was collected through extensive administration of questionnaires. Data for Survey 2 stemmed from the records of a leading German health insurance company. In terms of statistical analysis, chi-square tests as well as logistic regression analyses were applied and odds ratios (ORs) were determined. Results: Innovative results are presented showing a significantly higher likelihood for ADHD-affected youngsters to be involved in accidents compared with their nonaffected counterparts (Survey 1: OR = 1.60; Survey 2: OR = 1.89) but lacking an overall significant influence of medication regarding the occurrence of accidents (Survey 1: OR = 1.28; Survey 2: OR = 0.97). Frequency of accidents could be predicted by ADHD, gender, and age in both samples. Medication intake served as a weak predictor only in Survey 2. Conclusion: It has been determined in two representative and independent German samples that youngsters with ADHD are at a significantly higher risk of being involved in accidents. In the future, this should always be considered when setting up a treatment plan to ensure a safer and healthier coming of age without relying solely on specific effects of medication. (J. of Att. Dis. 2016; 20(6) 501-509)

Quality Control of Structural MRI Images Applied Using FreeSurfer-A Hands-On Workflow to Rate Motion Artifacts.

In structural magnetic resonance imaging motion artifacts are common, especially when not scanning healthy young adults. It has been shown that motion affects the analysis with automated image-processing techniques (e.g., FreeSurfer). This can bias results. Several developmental and adult studies have found reduced volume and thickness of gray matter due to motion artifacts. Thus, quality control is necessary in order to ensure an acceptable level of quality and to define exclusion criteria of images (i.e., determine participants with most severe artifacts). However, information about the quality control workflow and image exclusion procedure is largely lacking in the current literature and the existing rating systems differ. Here, we propose a stringent workflow of quality control steps during and after acquisition of T1-weighted images, which enables researchers dealing with populations that are typically affected by motion artifacts to enhance data quality and maximize sample sizes. As an underlying aim we established a thorough quality control rating system for T1-weighted images and applied it to the analysis of developmental clinical data using the automated processing pipeline FreeSurfer. This hands-on workflow and quality control rating system will aid researchers in minimizing motion artifacts in the final data set, and therefore enhance the quality of structural magnetic resonance imaging studies.

Tic Frequency Decreases during Short-term Psychosocial Stress – An Experimental Study on Children with Tic Disorders

It has been suggested that psychosocial stress influences situational fluctuations of tic frequency. However, evidence from experimental studies is lacking. The current study investigated the effects of the Trier Social Stress Test (TSST-C) on tic frequency in 31 children and adolescents with tic disorders. A relaxation and a concentration situation served as control conditions. Patients were asked either to suppress their tics or to “tic freely.” Physiological measures of stress were measured throughout the experiment. The TSST-C elicited a clear stress response with elevated levels of saliva cortisol, increased heart rate, and a larger number of skin conductance responses. During relaxation and concentration, the instruction to suppress tics reduced the number of tics, whereas during stress, the number of tics was low, regardless of the given instruction. Our study suggests that the stress might result in a situational decrease of tic frequency.

Harmonic expectancy violations elicit not-just-right-experiences: A paradigm for investigating obsessive-compulsive characteristics?

Obsessive-compulsive disorder (OCD)-like symptoms are commonly associated with sensations of incompleteness and not-just-right experiences (NJRE). Although NJRE have gained much attention in recent years, most studies have not gone beyond a description of their phenomenology and prevalence also in healthy adults. We applied a validated harmonic expectancy violation paradigm to experimentally investigate NJRE evoked by deviant auditory perceptions. We assessed reaction times (RT) to harmonic and disharmonic chord sequences as well as their emotional appraisal in 64 healthy young adults. The participants clearly indicated disharmonic chord sequences as sounding not-just-right and incomplete and rated them as unpleasant, arousing, and irritating. The RT to disharmonic chord sequences was significantly shorter than the RT to harmonic chord sequences. This effect tended to be greater in those participants who reported stronger general experiences of incompleteness as an underlying core dimension of OCD-like symptoms. In addition, general experience of incompleteness was correlated to the difference between RT to harmonic and that to disharmonic chord sequences, indicating that the intensity of general experience of incompleteness was associated with a more readily activated processing of the deviant auditory perceptions.

The role of obsessive-compulsive symptoms in the psychopathological profile of children with chronic tic disorder and attention-deficit hyperactivity disorder.

OBJECTIVE The study examines the role of obsessive-compulsive symptoms (OCS) as a part of the psychopathology of children with chronic tic disorders (CTD) and/or attention-deficit hyperactivity disorder (ADHD). METHOD We assessed the psychopathology of four large patient groups without further psychiatric disorders: CTD (n = 112), CTD + ADHD (n = 82), ADHD (n = 129), and controls (n = 144)) by implementing the Child Behavior Checklist (CBCL). We compared the main effects for CTD and ADHD with and without including OCS as covariates. RESULTS Including OCS led to substantially different main effects for CTD on seven out of eight CBCL subscales. Slightly different main effects for ADHD were determined with respect to ADHD, mainly on the subscale withdrawn. CONCLUSIONS OCS are closely related to CTD-associated psychopathology and - to a lesser extent, but nevertheless of importance in daily clinical practice - on ADHD-related symptoms. This information can be helpful in implementing more precise diagnostics and treatment in daily routine care.