Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

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.

Is loss avoidance differentially rewarding in adolescents versus adults? Differences in ventral striatum and anterior insula activation during the anticipation of potential monetary losses.

Avoiding loss is a crucial, adaptive guide to human behavior. While previous developmental research has primarily focused on gaining rewards, less attention has been paid to loss processing and its avoidance. In daily life, it is often unknown how likely an action will result in a loss, making the role of uncertainty in loss processing particularly important. By using functional magnetic resonance imaging, we investigated the influence of varying outcome probabilities (12%, 34%, and 67%) on brain regions implicated in loss processing (ventral striatum (VS), anterior insula (AI)) by comparing 28 adolescents (10-18 years) and 24 adults (22-32 years) during the anticipation of potential monetary loss.Overall, results revealed slower RTs in adolescents compared to adults with both groups being faster in the experimental (monetary condition) vs. control trials (verbal condition). Fastest RTs were observed for the 67% outcome probability in both age groups. An age group × outcome probability interaction effect revealed the greatest differences between the groups for the 12% vs. the 67% outcome probability. Neurally, both age groups demonstrated a higher percent signal change in the VS and AI during the anticipation of potential monetary loss versus the verbal condition. However, adults demonstrated an even greater activation of VS and AI than adolescents during the anticipation of potential monetary loss, but not during the verbal condition. This may indicate that adolescents differ from adults regarding their experience of avoiding losing monetary rewards.

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.

Ventral Striatal Activation During Reward Anticipation of Different Reward Probabilities in Adolescents and Adults.

Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior.

Changes in emotions and worries during the Covid-19 pandemic: an online-survey with children and adults with and without mental health conditions.

BACKGROUND: The novel coronavirus disease (Covid-19) has spread quickly worldwide with dramatic consequences on our daily lives. Adverse psychosocial consequences of Covid-19 might be particularly severe for children and adolescents, parents of young children and people with mental health conditions (mhc), who are more prone to the experience of psychosocial stress and who are more dependent on the access to professional psychosocial support. The present survey therefore aimed to explore perceived stress and the emotional responses of children and adolescents as well as adults with and without mhc during the social restrictions due to the Covid-19 pandemic. METHODS: The survey gathered information about 284 children and adolescent (parent-on-child-reports) and 456 adults (including 284 parents, self-reports). The participants were allocated to four groups: children and adolescents with mhc, children and adolescent without mhc, adults with mhc and adults without mhc. The survey included general questions about socio-demographic characteristics and mental health status, the CoRonavIruSHealth Impact Survey and the Perceived Stress Scale (only data on adults). Wilcoxon signed-rank tests were used for comparing the emotional responses during the Covid-19 pandemic with emotions before the Covid-19 pandemic. Independent sample t-test were used to compare the level of perceived stress between the adult groups, linear regression analyses were conducted to examine which variables predicted perceived stress during the Covid-19 restrictions. RESULTS: An increase to the worse during the Covid-19 restrictions was observed for most emotions and worries in all four groups (children and adolescents with mhc, children and adolescents without mhc, adults with mhc, adults without mhc). Contrary to our expectations, a greater number of emotions worsened significantly for children and adolescents as well as adults without mhc as compared to those with mhc. We found higher perceived stress in parents as compared to adults without children in the same household and in adults with mhc as compared to those without mhc. DISCUSSION: Covid-19-related social restrictions and potential health risks seem to affect emotions and perceived stress in children, adolescents and adults. Especially, Covid-19 seems to be have worsened the mental well-being of children and adolescent and their families, who were mentally healthy before the Covid-19 pandemic.

Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling.

An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.

Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder.

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.

Paradoxical response inhibition advantages in adolescent obsessive compulsive disorder result from the interplay of automatic and controlled processes.

Response inhibition deficits have often been described in obsessive compulsive disorder (OCD). Yet, research on response inhibition in OCD focusses on "top-down" controlled mechanisms, and it has been neglected that response inhibition performance depends on the interplay of controlled and automatic processes during response selection. Based on pathophysiological considerations we test the counterintuitive hypothesis that OCD patients show superior inhibitory control when automatic mechanisms govern processes involved in response inhibition. We examined a group of adolescent OCD patients (n = 27) and healthy controls (n = 27) using a combined Simon-Go/NoGo task. This task is able to examine conjoint effects of automatic and controlled processes during response inhibition. EEG and source localization analyses were applied to examine the underlying neural mechanisms. OCD patients committed fewer false alarms than healthy controls (HC) in the congruent Simon-NoGo condition, which is dominated by automatic response selection mechanisms. On a neurophysiological (EEG) level, these effects were reflected by intensified correlates of 'braking' processes associated with modulation of right inferior prefrontal regions. There is no general response inhibition deficit in adolescent OCD. When considering conjoint effects of automatic and controlled processes during the inhibition of responses paradoxical response inhibition advantages can emerge in OCD. This is likely a result of otherwise pathological fronto-striatal hyperactivity and loss of a situation-specific modulation of response selection mechanisms in OCD.

When repetitive mental sets increase cognitive flexibility in adolescent obsessive-compulsive disorder.

BACKGROUND: A major facet of obsessive-compulsive disorder (OCD) is cognitive inflexibility. However, sometimes, cognitive flexibility can be needed to reuse recently abandoned mental sets. Therefore, cognitive flexibility can in certain cases be useful to reinstate some form of rigid, repetitive behavior characterizing OCD. We test the counterintuitive hypothesis that under such circumstances, cognitive flexibility is better in OCD patients than controls. METHODS: We examined N = 20 adolescent OCD patients and N = 22 controls in a backward inhibition (BI) paradigm. This was combined with event-related potential (ERP) recordings and source localization. The BI effect describes the cost of overcoming the inhibition of a recently abandoned mental set that is relevant again. Therefore, a strong BI effect is disadvantageous for cognitive flexibility. RESULTS: Compared to controls, OCD patients revealed a smaller backward inhibition effect. The EEG data revealed larger P1 amplitudes in backward inhibition trials in the OCD group, which was due to activation differences in the inferior frontal gyrus (BA47). The severity of clinical symptoms predicted these neurophysiological modulations. The power of the observed effects was about 95%. CONCLUSIONS: The study shows that cognitive flexibility can be better in OCD than controls. This may be the case in situations where superior abilities in the reactivation of repeating mental sets and difficulties to process new ones coincide. This may be accomplished by intensified inhibitory control mechanisms. The results challenge the view on OCD, since OCD is not generally associated with cognitive inflexibility.

Update on the Pharmacological Treatment of Tics with Dopamine-Modulating Agents.

More than 40 years of research and clinical practice have proven the effectiveness of dopamine receptor antagonists in the pharmacological treatment of tics. A blockade of the striatal dopamine-D2 receptors is mainly responsible for their tic-reducing effect. A broad spectrum of dopamine-modulating agents, such as typical and atypical antipsychotics, but also dopamine receptor agonists are used with an immanent discord between experts about which of them should be considered as first choice. The present Review outlines the state of the art on pharmacological treatment of tics with dopamine-modulating agents by giving an systematic overview of studies on their effectiveness and a critical discussion of their specific adverse effects. It is considered as an update of a previous review of our research group published in 2013. The Review closes with a description of the current resulting treatment recommendations including the results of a first published revised survey on European expert's prescription preferences. Based on the enormously growing evidence on its effectiveness and safety, aripiprazole currently seems to be the most promising agent in the pharmacological treatment of tics. Furthermore, benzamides (especially tiapride), which are commonly used in Europe, have proven their excellent effectiveness-tolerability profile over decades in clinical practice and are therefore also highly recommended for the treatment of tics. Nevertheless, pharmacological treatment of tics remains an indiviual choice depending on each patient's own specific needs.

Anterior insula hyperactivation in ADHD when faced with distracting negative stimuli.

Patients with attention deficit hyperactivity disorder (ADHD) suffer from poor emotion regulation that might arise from problems in the distribution of attentional resources when confronted with emotional distractors. Previous studies investigating the neurocognitive basis of these problems remain inconclusive. Moreover, most of these studies did not exclude participants with comorbidity, particularly of conduct or oppositional defiant disorder. The aim of this study was to assess alterations in fronto-limbic activation in ADHD adolescents specifically during negative distractors in an emotional attention task. For this purpose, we used functional magnetic resonance imaging to assess 25 boys with noncomorbid ADHD and 25 typically developing (TD) boys while they performed an emotional attention task with positive, negative, and neutral emotional distractors. Boys with ADHD had increased activation relative to TD boys specifically during the negative valenced stimuli in an emotional processing network comprising left anterior insula reaching into the inferior frontal gyrus. The findings suggest altered salience processing in ADHD of negative valenced emotional stimuli that may lead to higher distractibility in ADHD specifically when faced with negative emotional distractors.

Neural correlates of prediction violations in boys with Tourette syndrome: Evidence from harmonic expectancy.

OBJECTIVES: It has been suggested that Tourette syndrome (TS) might be associated with alterations of the attention system, but the nature of these alterations and the underlying neuroanatomical network remains elusive. We aimed at investigating the functional neuroanatomical modulators of attention allocation towards predictable versus unpredictable stimuli in boys with TS. METHODS: Using functional magnetic resonance imaging, we ran a harmonic expectancy violation paradigm in 17 boys with TS and 23 matched healthy controls (HCs). We presented chord sequence in which the first four chords induced a strong expectancy for a harmonic chord at the next position. In 70% this expectancy was fulfilled (harmonic), in 30% the expectancy was violated (disharmonic). RESULTS: HCs responded faster to the disharmonic compared to harmonic chords, indicating a stronger attention allocation towards unpredictable stimuli, while this effect was not found in boys with TS. HCs showed stronger anterior cingulate cortex (ACC) activation during disharmonic compared to harmonic chords. Boys with TS showed stronger ACC activation during harmonic chords, which was associated with greater tic severity. CONCLUSIONS: Our findings indicate that boys with TS showed altered reactions towards predictable versus unpredictable stimuli in brain regions playing an important role in attention control. This might indicate altered allocation of attention towards those stimuli.

Modulations of cognitive flexibility in obsessive compulsive disorder reflect dysfunctions of perceptual categorization.

BACKGROUND: Despite cognitive inflexibility is trait like in obsessive compulsive disorder (OCD) patients and underlies clinical symptomatology, it is elusive at what stage of information processing deficits, leading to cognitive inflexibility, emerges. We hypothesize that inhibitory control mechanisms during early stimulus categorization and integration into a knowledge system underlie these deficits. METHODS: We examined N = 25 adolescent OCD patients and matched healthy controls (HC) in a paradigm manipulating the importance of the knowledge system to perform task switching. This was done using a paradigm in which task switches were signaled either by visual stimuli or by working memory processes. This was combined with event-related potential recordings and source localization. RESULTS: Obsessive compulsive disorder patients showed increased switch costs in the memory as compared with the cue-based block, while HC showed similar switch costs in both blocks. At the neurophysiological level, these changes in OCD were not reflected by the N2 and P3 reflecting response-associated processes but by the P1 reflecting inhibitory control during sensory categorization processes. Activation differences in the right inferior frontal gyrus and superior temporal gyrus are associated with the P1 effect. CONCLUSIONS: Cognitive flexibility in adolescent OCD patients is strongly modulated by working memory load. Contrary to common sense, not response-associated processes, but inhibitory control mechanisms during early stimulus categorization processes are likely to underlie cognitive inflexibility in OCD. These processes are associated with right inferior frontal and superior temporal gyrus mechanisms.

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.

Familiality of Co-existing ADHD and Tic Disorders: Evidence from a Large Sibling Study.

BACKGROUND: The association of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is frequent and clinically important. Very few and inconclusive attempts have been made to clarify if and how the combination of ADHD+TD runs in families. AIM: To determine the first time in a large-scale ADHD sample whether ADHD+TD increases the risk of ADHD+TD in siblings and, also the first time, if this is independent of their psychopathological vulnerability in general. METHODS: The study is based on the International Multicenter ADHD Genetics (IMAGE) study. The present sub-sample of 2815 individuals included ADHD-index patients with co-existing TD (ADHD+TD, n = 262) and without TD (ADHD-TD, n = 947) as well as their 1606 full siblings (n = 358 of the ADHD+TD index patients and n = 1248 of the ADHD-TD index patients). We assessed psychopathological symptoms in index patients and siblings by using the Strength and Difficulties Questionnaire (SDQ) and the parent and teacher Conners' long version Rating Scales (CRS). For disorder classification the Parental Account of Childhood Symptoms (PACS-Interview) was applied in n = 271 children. Odds ratio with the GENMOD procedure (PROCGENMOD) was used to test if the risk for ADHD, TD, and ADHD+TD in siblings was associated with the related index patients' diagnoses. In order to get an estimate for specificity we compared the four groups for general psychopathological symptoms. RESULTS: Co-existing ADHD+TD in index patients increased the risk of both comorbid ADHD+TD and TD in the siblings of these index patients. These effects did not extend to general psychopathology. INTERPRETATION: Co-existence of ADHD+TD may segregate in families. The same holds true for TD (without ADHD). Hence, the segregation of TD (included in both groups) seems to be the determining factor, independent of further behavioral problems. This close relationship between ADHD and TD supports the clinical approach to carefully assess ADHD in any case of TD.

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.

Neural correlates of processing harmonic expectancy violations in children and adolescents with OCD.

It has been suggested that patients with obsessive-compulsive disorder (OCD) exhibit enhanced awareness of embedded stimulus patterns as well as enhanced allocation of attention towards unexpected stimuli. Our study aimed at investigating these OCD characteristics by running the harmonic expectancy violation paradigm in 21 boys with OCD and 29 healthy controls matched for age, gender and IQ during a functional magnetic resonance imaging (fMRI) scan. Each trial consisted of a chord sequence in which the first four chords induced a strong expectancy for a harmonic chord at the next position. In 70% of the trials the fifth chord fulfilled this expectancy (harmonic condition), while in 30% the expectancy was violated (disharmonic condition). Overall, the harmonic condition elicited blood-oxygen-level dependent (BOLD) activation in the auditory cortex, while during the disharmonic condition the precuneus, the auditory cortex, the medial frontal gyrus, the premotor cortex, the lingual gyrus, the inferior frontal gyrus and the superior frontal gyrus were activated. In a cluster extending from the right superior temporal gyrus to the inferior frontal gyrus, boys with OCD exhibited increased activation compared to healthy controls in the harmonic condition and decreased activation in the disharmonic condition. Our findings might indicate that patients with OCD are excessively engaged in processing the implicit structure embedded in music stimuli, but they speak against the suggestion that OCD is associated with a misallocation of attention towards the processing of unexpected stimuli.

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

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.

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).