Functional connectivity during tic suppression predicts reductions in vocal tics following behavior therapy in children with Tourette syndrome.

BACKGROUND: Comprehensive Behavioral Intervention for Tics (CBIT) is recommended as a first-line treatment for Tourette syndrome in children and adults. While there is strong evidence proving its efficacy, the mechanisms of reduction in tic severity during CBIT are still poorly understood. In a recent study, our group identified a functional brain network involved in tic suppression in children with TS. We reasoned that voluntary tic suppression and CBIT may share some mechanisms and thus we wanted to assess whether functional connectivity during tic suppression was associated with CBIT outcome. METHODS: Thirty-two children with TS, aged 8 to 13 years old, participated in a randomized controlled trial of CBIT v. a treatment-as-usual control condition. EEG was recorded during tic suppression in all participants at baseline and endpoint. We used a source-reconstructed EEG connectivity pipeline to assess functional connectivity during tic suppression. RESULTS: Functional connectivity during tic suppression did not change from baseline to endpoint. However, baseline tic suppression-related functional connectivity specifically predicted the decrease in vocal tic severity from baseline to endpoint in the CBIT group. Supplementary analyses revealed that the functional connectivity between the right superior frontal gyrus and the right angular gyrus was mainly driving this effect. CONCLUSIONS: This study revealed that functional connectivity during tic suppression at baseline predicted reduction in vocal tic severity. These results suggest probable overlap between the mechanisms of voluntary tic suppression and those of behavior therapy for tics.

Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling.

Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial-frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r = 0.31, RMSE = 9.05, p = 0.005). Out-of-sample replication (p < 0.002) and generalization (p = 0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n = 1791; n = 1701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.

Amygdala-prefrontal connectivity in children with maladaptive aggression is modulated by social impairment.

Aggressive behavior is common across childhood-onset psychiatric disorders and is associated with impairments in social cognition and communication. The present study examined whether amygdala connectivity and reactivity during face emotion processing in children with maladaptive aggression are moderated by social impairment. This cross-sectional study included a well-characterized transdiagnostic sample of 101 children of age 8-16 years old with clinically significant levels of aggressive behavior and 32 typically developing children without aggressive behavior. Children completed a face emotion perception task of fearful and calm faces during functional magnetic resonance imaging. Aggressive behavior and social functioning were measured by standardized parent ratings. Relative to controls, children with aggressive behavior showed reduced connectivity between the amygdala and the dorsolateral prefrontal cortex (PFC) during implicit emotion processing. In children with aggressive behavior, the association between reduced amygdala-ventrolateral PFC connectivity and greater severity of aggression was moderated by greater social impairment. Amygdala reactivity to fearful faces was also associated with severity of aggressive behavior for children without social deficits but not for children with social deficits. Social impairments entail difficulties in interpreting social cues and enacting socially appropriate responses to frustration or provocation, which increase the propensity for an aggressive response via diminished connectivity between the amygdala and the ventral PFC.

Developmental Course and Risk Factors of Physical Aggression in Late Adolescence.

This study examined risk factors of physical aggression during transition from early to late adolescence using a two-wave longitudinal study. Specifically, we examined if risk factors in early adolescence predict physically aggressive behavior starting in late adolescence and why some adolescents desist physical aggressive behavior while others do not. The study sample consisted of 2289 Norwegian adolescents (1235 girls) who participated in the Young-HUNT1 study (mean age 14.5) and the follow-up study 4 years later, Young-HUNT2 study (mean age 18.4). One in six young adolescents reported engaging in physical fights. Moreover, physical aggression in early adolescence was significantly associated with male gender, attention problems, academic problems, being bullied, drinking alcohol, and smoking. Male gender and heavy drinking during early adolescence increased the risk for newly emerging aggressive behavior in late adolescence, whereas heavy drinking during early adolescence was a predictor for persistent versus desisting aggressive behavior in late adolescence.

The Role of Gender in the Associations Among Posttraumatic Stress Symptoms, Anger, and Aggression in Russian Adolescents.

Symptoms of posttraumatic stress disorder (PTSD) have been linked to anger and aggressive behavior in adult and veteran populations. However, research on the associations among anger, aggression, and PTSD in adolescents is lacking, particularly regarding differences between the sexes. To address this research gap, we used self-report data from Russian adolescents (N = 2,810; age range: 13-17 years) to perform a full path analysis examining the associations between PTSD symptoms and the emotional (anger traits) and cognitive (rumination) components of anger as well as physical/verbal and social aggression, after adjusting for depressive symptoms. We also examined the interaction effects between PTSD symptoms and sex on anger and aggression. The results indicated that girls scored higher on measures of anger and PTSD symptoms, ds = 0.20-0.32, whereas boys scored higher on measures of physical and verbal aggression, d = 0.54. Clinical levels of PTSD symptoms were associated with anger rumination, ß = .16, and trait anger, ß = .06, and an interaction effect for PTSD symptoms and sex was found for aggression, whereby boys with clinical levels of PTSD symptoms reported more physical/verbal and social aggression, ßs = .05 and .20, respectively. Our findings suggest that PTSD symptoms may have an important impact on anger, anger rumination, and aggression during adolescence. In particular, boys seem to have an increased risk for aggressive behavior in the presence of PTSD symptoms. The present results highlight the importance of taking anger and aggression into account when evaluating PTSD.

Time course of clinical change following neurofeedback.

Neurofeedback - learning to modulate brain function through real-time monitoring of current brain state - is both a powerful method to perturb and probe brain function and an exciting potential clinical tool. For neurofeedback effects to be useful clinically, they must persist. Here we examine the time course of symptom change following neurofeedback in two clinical populations, combining data from two ongoing neurofeedback studies. This analysis reveals a shared pattern of symptom change, in which symptoms continue to improve for weeks after neurofeedback. This time course has several implications for future neurofeedback studies. Most neurofeedback studies are not designed to test an intervention with this temporal pattern of response. We recommend that new studies incorporate regular follow-up of subjects for weeks or months after the intervention to ensure that the time point of greatest effect is sampled. Furthermore, this time course of continuing clinical change has implications for crossover designs, which may attribute long-term, ongoing effects of real neurofeedback to the control intervention that follows. Finally, interleaving neurofeedback sessions with assessments and examining when clinical improvement peaks may not be an appropriate approach to determine the optimal number of sessions for an application.

A Randomized Controlled Study of Cognitive-Behavioral Therapy for Posttraumatic Stress in Street Children in Mexico City.

The study aimed to evaluate cognitive-behavioral therapy (CBT) for posttraumatic stress (PTS), depression, anxiety, and anger in street children by a randomized controlled trial of CBT versus a waitlist control. It was conducted in 8 residential facilities for street children in Mexico City, with assessments at baseline, posttreatment, and 3 months later. Children who reported at least moderate posttraumatic stress, and fulfilled the study requirement were enrolled in the study (N = 100, 12-18 years old, 36 boys). There were 51 children randomized to CBT and 49 to the waitlist condition. Randomization was stratified by gender. CBT consisted of 12 individual 1-hour sessions administered weekly by 2 trained, master's-level clinicians. Outcome measures included self-reports of PTS, depression, anxiety, and anger; global improvement was assessed by the independent evaluator. Compared to participants in the waitlist condition participants in CBT showed a significant reduction in all symptoms, with effects sizes of 1.73 to 1.75. At follow up there was attrition (n = 36), and no change from posttreatment scores. The study did find statistically significant improvement in symptoms in the CBT group compared to the waitlist condition; symptoms remained stable at 3 months. The study found that CBT for trauma in a sample of street children provided a reduction of a broad range of mental health symptoms.

Cognitive-Behavioral Therapy for a 9-Year-Old Girl With Disruptive Mood Dysregulation Disorder.

Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnosis in the field of childhood onset disorders. Characterized by both behavior and mood disruption, DMDD is a purportedly unique clinical presentation with few relevant treatment studies to date. The current case study presents the application of cognitive-behavioral therapy (CBT) for anger and aggression in a 9-year-old girl with DMDD, co-occurring attention deficit hyperactivity disorder (ADHD), and a history of unspecified anxiety disorder. At the time of intake evaluation, she demonstrated three to four temper outbursts and two to three episodes of aggressive behavior per week, in addition to prolonged displays of non-episodic irritability lasting hours or days at a time. A total of 12 CBT sessions were conducted over 12 weeks and 5 follow-up booster sessions were completed over a subsequent 3-month period. Irritability-related material was specially designed to target the DMDD clinical presentation. Post-treatment and 3-month follow-up assessments, including independent evaluation, demonstrated significant decreases in the target symptoms of anger, aggression, and irritability. Although the complexities of diagnosing and treating DMDD warrant extensive research inquiry, the current case study suggests CBT for anger and aggression as a viable treatment for affected youth.

Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder: a randomized clinical trial.

IMPORTANCE: Disruptive behavior is common in children with autism spectrum disorder. Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale randomized trials. OBJECTIVE: To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior. DESIGN, SETTING, AND PARTICIPANTS: This 24-week randomized trial compared parent training (n = 89) to parent education (n = 91) at 6 centers (Emory University, Indiana University, Ohio State University, University of Pittsburgh, University of Rochester, Yale University). We screened 267 children; 180 children (aged 3-7 years) with autism spectrum disorder and disruptive behaviors were randomly assigned (86% white, 88% male) between September 2010 and February 2014. INTERVENTIONS: Parent training (11 core, 2 optional sessions; 2 telephone boosters; 2 home visits) provided specific strategies to manage disruptive behavior. Parent education (12 core sessions, 1 home visit) provided information about autism but no behavior management strategies. MAIN OUTCOMES AND MEASURES: Parents rated disruptive behavior and noncompliance on co-primary outcomes: the Aberrant Behavior Checklist-Irritability subscale (range, 0-45) and the Home Situations Questionnaire-Autism Spectrum Disorder (range, 0-9). On both measures, higher scores indicate greater severity and a 25% reduction indicates clinical improvement. A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression (range, 1-7), a secondary outcome, with a positive response less than 3. RESULTS: At week 24, the Aberrant Behavior Checklist-Irritability subscale declined 47.7% in parent training (from 23.7 to 12.4) compared with 31.8% for parent education (23.9 to 16.3) (treatment effect, -3.9; 95% CI, -6.2 to -1.7; P < .001, standardized effect size = 0.62). The Home Situations Questionnaire-Autism Spectrum Disorder declined 55% (from 4.0 to 1.8) compared with 34.2% in parent education (3.8 to 2.5) (treatment effect, -0.7; 95% CI, -1.1 to -0.3; P < .001, standardized effect size = 0.45). Neither measure met the prespecified minimal clinically important difference. The proportions with a positive response on the Clinical Global Impression-Improvement scale were 68.5% for parent training vs 39.6% for parent education (P < .001). CONCLUSIONS AND RELEVANCE: For children with autism spectrum disorder, a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes, although the clinical significance of the improvement is unclear. The rate of positive response judged by a blinded clinician was greater for parent training vs parent education. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01233414.

Individualized assessments in treatment research: an examination of parent-nominated target problems in the treatment of disruptive behaviors in youth with Tourette syndrome.

Youth with Tourette syndrome (TS) often exhibit disruptive behaviors. Although improvement data on rating scales support the efficacy of structured psychotherapeutic interventions, there is growing interest in personalized outcome assessments. This report examined parent-nominated target problems (PTPs) as an individualized outcome measure in 48 youth with TS and disruptive behaviors, who participated in one of two randomized psychotherapy trials. At baseline, parents described two primary problems to an independent evaluator who generated a structured narrative for each problem. These narratives were reviewed and updated at endpoint. When rated by five treatment-blind judges, the PTP rating demonstrated excellent reliability and good convergent validity with the Disruptive Behavior Rating Scale (DBRS). The PTP rating exhibited comparable treatment effects to the DBRS, and accounted for additional variance in global treatment outcome. The PTP rating serves a reliable, valid, and sensitive personalized assessment in research trials that provides complementary information to standardized rating scales.

Association of Irritability with Restricted, Repetitive Behaviors and Social Communication Challenges in Autistic Youth.

Although affective irritability is a common and concerning problem for autistic youth, limited research has examined relations among core autism characteristics and irritability. Therefore, this study investigated potential associations among types of restricted/repetitive behaviors (RRBs) and social communication challenges and irritability in autistic children and adolescents. Participants were 107 autistic youth recruited from a university-based autism clinical research program. Two hierarchical multiple regressions were conducted with Affective Reactivity Index as the dependent variable. Covariates were entered at step 1, followed by the independent variables of interest at step 2. For the first model, independent variables of interest were Repetitive Behavior Scale-Revised subscales: stereotyped behavior, self-injurious behavior, compulsive behavior, ritualistic behavior, sameness behavior, and restricted behavior. For the second model, independent variables of interest were Social Responsiveness Scale, Second Edition subscales: social awareness, social cognitive, social communication, and social motivation. Irritability was significantly associated with several categories of RRBs (i.e., insistence on sameness, stereotypic behavior, and restricted interests/activities). Nonetheless, irritability was not associated with categories of social communication and interaction challenges in autistic youth. Results from this study indicated differing associations between core autism characteristics and affective irritability. Findings highlight the importance of differentiating types of restricted, repetitive behaviors and social communication and interaction challenges in conceptualizing mental health concerns in autistic youth.

Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis.

BACKGROUND: Impairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction in these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia. METHODS: Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted. RESULTS: Fifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal and frontotemporal circuitry. CONCLUSION: Alterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia.

Feasibility and preliminary efficacy of behavioral activation for treatment of depression in autistic adolescents.

LAY ABSTRACT: Depression is common among autistic youth and has a significant negative impact on quality of life and day-to-day functioning. Despite great need for efficacious treatments, there are currently limited research-supported interventions for depression symptoms in autistic young people. This study tested a novel, behavior-based approach or psychotherapy for treatment of depression symptoms in autistic adolescents without intellectual disability (i.e. Behavioral Activation for Autistic Adolescents, BA-A) with 15 youth (11-16 years old). BA-A is an individually delivered 12-session therapy that was developed for and to meet the needs of autistic youth with depression. Results found that autistic youth and their caregivers were able to participate in BA-A therapy sessions, and clinicians were able to deliver BA-A in accordance with the treatment manual. Notably, results demonstrated that autistic youth depression symptoms significantly improved after participating in BA-A. Furthermore, anxiety symptoms and social skills significantly improved following BA-A.

Transdiagnostic Symptom Domains are Associated with Head Motion During Multimodal Imaging in Children.

Background: Head motion is a challenge for neuroimaging research in developmental populations. However, it is unclear how transdiagnostic symptom domains including attention, disruptive behavior (e.g., externalizing behavior), and internalizing problems are linked to scanner motion in children, particularly across structural and functional MRI. The current study examined whether transdiagnostic domains of attention, disruptive behavior, and internalizing symptoms are associated with scanner motion in children during multimodal imaging. Methods: In a sample of 9,045 children aged 9-10 years in the Adolescent Brain Cognitive Development (ABCD) Study, logistic regression and linear mixed-effects models were used to examine associations between motion and behavior. Motion was indexed using ABCD Study quality control metrics and mean framewise displacement for the following: T1-weighted structural, resting-state fMRI, diffusion MRI, Stop-Signal Task, Monetary Incentive Delay task, and Emotional n-Back task. The Child Behavior Checklist was used as a continuous measure of symptom severity. Results: Greater attention and disruptive behavior problem severity was associated with a lower likelihood of passing motion quality control across several imaging modalities. In contrast, increased internalizing severity was associated with a higher likelihood of passing motion quality control. Increased attention and disruptive behavior problem severity was also associated with increased mean motion, whereas increased internalizing problem severity was associated with decreased mean motion. Conclusion: Transdiagnostic domains emerged as predictors of motion in youths. These findings have implications for advancing development of generalizable and robust brain-based biomarkers, computational approaches for mitigating motion effects, and enhancing accessibility of imaging protocols for children with varying symptom severities.

Depressive symptoms and anger and aggression in Russian adolescents.

Research among adolescents exploring the association between depressive symptoms and aggression has produced inconsistent findings. This study investigated the prevalence of clinically significant (current major depressive episode) and subthreshold depressive symptoms in a general population sample of adolescents from Northern Russia and explored their association with aggression and anger, while controlling for comorbid mental health problems. The sample consisted of 2600 participants, aged 13-17 years (59.5% female; 95.7% ethnic Russian). Symptoms of a current major depressive episode, types of anger and aggression (anger rumination, trait anger, physical, verbal and social aggression) and comorbid problems (posttraumatic stress, alcohol use, anxiety, and hyperactivity/impulsivity) were assessed by means of self-reports. The prevalence of a clinically significant depressive episode in the past month was 3.5%, while for subthreshold depression it was 21.6%. All anger and aggression variables, as well as comorbid problems increased together with increasing levels of depression. The association between overt aggressive behavior and depression was primarily explained by comorbid mental health problems, whereas anger rumination and social aggression had more direct associations with depression, independent of comorbidity. Among adolescents with depression, boys reported higher levels of social and verbal aggression and of anger rumination than girls. The results of this study suggest that interventions aiming to reduce aggressive behavior in adolescents should consider depression and its comorbid conditions.

Posttraumatic Stress and Perceived Interpersonal Provocation in Adolescents.

Objective: To examine the impact of posttraumatic stress on the choice of responses to and attribution of intentionality in peer provocation in adolescent boys and girls. Methods: A sample of 2678 adolescents from Northern Russia, aged 13-17 years (59.3% female; 95.7% ethnic Russian) completed self-reports on posttraumatic stress and rated hypothetical peer provocation scenarios that teenagers can encounter in their daily lives. Results: Adolescents with clinically significant levels of posttraumatic stress symptoms (n=184 (6.8%)) reported a different pattern of reactions to peer provocation as compared to all other adolescents. Boys and girls with high levels of posttraumatic symptoms reported that they would be less likely to discuss conflict situations and more likely to react with physical aggression. Compared to their male counterparts, girls with high levels of posttraumatic stress symptoms were more likely to endorse hostile intentions, avoid provocations, and were less likely to endorse verbally aggressive responses. In provocation scenarios that involved physical aggression, girls with high levels of posttraumatic stress symptoms were less likely to endorse verbal aggressive responses and more likely to endorse physically aggressive responses than girls without clinically significant levels of posttraumatic symptoms. Girls with high levels of posttraumatic stress symptoms were also more likely to avoid socially aggressive situations than non-traumatized girls, whereas boys had an opposite pattern. Conclusions: High levels of posttraumatic stress symptoms may play a significant role in the endorsement of aggressive reactions in conflicts with peers and patterns of reactions may be gender-specific. A history of posttraumatic stress should be carefully evaluated in children and adolescents seeking treatment for aggressive behavior.

Aggression Is Associated With Social Adaptive Functioning in Children With ASD and Anxiety.

Social adaptive functioning is notably compromised and may be further impaired by aggressive behavior in children with autism spectrum disorder (ASD). This study examined the association between aggressive behavior and social adaptive skills in children with ASD and the contribution of aggressive behavior to social adaptive skills in a combined sample of children with and without ASD. Participants consisted of children, ages 8 to 15 years, with ASD (n = 52) and who were typically developing (n = 29). Results indicate that aggressive behavior is negatively associated with social adaptive skills in children with ASD and that it contributes to reduced social adaptive functioning above and beyond ASD diagnosis. Findings underscore the importance of considering the role of aggressive behavior when evaluating and promoting social functioning in children with ASD.

Protocol description for a randomized controlled trial of fMRI neurofeedback for tics in adolescents with Tourette Syndrome.

This article describes the protocol for a randomized, controlled clinical trial of a neurofeedback (NF) intervention for Tourette Syndrome (TS) and chronic tic disorder. The intervention involves using functional magnetic resonance imaging (fMRI) to provide feedback regarding activity in the supplementary motor area: participants practice controlling this brain area while using the feedback as a training signal. The previous version of this NF protocol was tested in a small study (n = 21) training adolescents with TS that yielded clinically promising results. Therefore, we plan a larger trial. Here we describe the background literature that motivated this work, the design of our original neurofeedback study protocol, and adaptations of the research study protocol for the new trial. We focus on those ideas incorporated into our protocol that may be of interest to others designing and running NF studies. For example, we highlight our approach for defining an unrelated brain region to be trained in the control group that is based on identifying a region with low functional connectivity to the target area. Consistent with a desire for transparency and open science, the new protocol is described in detail here prior to conducting the trial.

Increased Alpha-Band Connectivity During Tic Suppression in Children With Tourette Syndrome Revealed by Source Electroencephalography Analyses.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder involving chronic motor and phonic tics. Most individuals with TS can suppress their tics for at least a short period of time. Yet, the brain correlates of tic suppression are still poorly understood. METHODS: In the current study, high-density electroencephalography was recorded during a resting-state and a tic suppression session in 72 children with TS. Functional connectivity between cortical regions was assessed in the alpha band (8-13 Hz) using an electroencephalography source connectivity method. Graph theory and network-based statistics were used to assess the global network topology and to identify brain regions showing increased connectivity during tic suppression. RESULTS: Graph theoretical analyses revealed distinctive global network topology during tic suppression, relative to rest. Using network-based statistics, we found a subnetwork of increased connectivity during tic suppression (p < .001). That subnetwork encompassed many cortical areas, including the right superior frontal gyrus and the left precuneus, which are involved in the default mode network. We also found a condition-by-age interaction, suggesting age-mediated increases in connectivity during tic suppression. CONCLUSIONS: These results suggest that children with TS suppress their tics through a brain circuit involving distributed cortical regions, many of which are part of the default mode network. Brain connectivity during tic suppression also increases as youths with TS mature. These results highlight a mechanism by which children with TS may control their tics, which could be relevant for future treatment studies.

Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior.

Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8-16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.