Thalamo-cortical and cerebello-cortical functional connectivity in development.

The thalamus is a critical relay center for neural pathways involving sensory, motor, and cognitive functions, including cortico-striato-thalamo-cortical and cortico-ponto-cerebello-thalamo-cortical loops. Despite the importance of these circuits, their development has been understudied. One way to investigate these pathways in human development in vivo is with functional connectivity MRI, yet few studies have examined thalamo-cortical and cerebello-cortical functional connectivity in development. Here, we used resting-state functional connectivity to measure functional connectivity in the thalamus and cerebellum with previously defined cortical functional networks in 2 separate data sets of children (7-12 years old) and adults (19-40 years old). In both data sets, we found stronger functional connectivity between the ventral thalamus and the somatomotor face cortical functional network in children compared with adults, extending previous cortico-striatal functional connectivity findings. In addition, there was more cortical network integration (i.e. strongest functional connectivity with multiple networks) in the thalamus in children than in adults. We found no developmental differences in cerebello-cortical functional connectivity. Together, these results suggest different maturation patterns in cortico-striato-thalamo-cortical and cortico-ponto-cerebellar-thalamo-cortical pathways.

Pediatric melanoma: Characterizing 256 cases from the Colorado Central Cancer Registry.

BACKGROUND: Melanoma is a rare diagnosis in the pediatric population. Differences in incidence, presentation, and survival distinguish pediatric melanoma from adult melanoma. In order to improve our understanding of pediatric melanoma, our case series investigates differences in incidence, age of onset, and anatomic site between male and female pediatric melanoma patients in Colorado between 1988 and 2015. METHODS: All data were gathered from the Colorado Central Cancer Registry. A request for de-identified data on pediatric melanoma patients between 1988 and 2015 was made by the University of Colorado Department of Dermatology. Chi-square tests were used to compare the differences reported in melanoma between sex, age-groups, and site of lesion. RESULTS: A total of 256 cases of melanoma were reported in Colorado in patients < 20 years of age between 1988 and 2015. Overall incidence of pediatric melanoma in Colorado increased from 1988 to 1999 but declined from 2001 to 2011. There was a significant predominance of female cases in the 10-14 age-group (P = 0.0477) and 15-19 age-group (P = 0.0472). Both groups had increased incidence of melanoma with increasing age. The mean age of onset for both sexes was 16 years old. Boys were more likely to have melanoma of the scalp and neck (P = 0.0523) and less likely to have melanoma of the leg (P = 0.0049). CONCLUSION: Among the pediatric population, girls 10-14 and 15-19 years old are at a significantly increased risk of melanoma compared to boys in these age-groups. Our study found sex-specific differences in anatomic site consistent with prior literature. Further investigations should aim to identify causes for these sex-specific differences in order to better guide public health initiatives.

Clinical correlates of parenting stress in children with Tourette syndrome and in typically developing children.

OBJECTIVE: To determine the impact of tic severity in children with Tourette syndrome on parenting stress and the impact of comorbid attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) symptomatology on parenting stress in both children with Tourette syndrome and typically developing children. STUDY DESIGN: Children with diagnosed Tourette syndrome (n=74) and tic-free typically developing control subjects (n=48) were enrolled in a cross-sectional study. RESULTS: Parenting stress was greater in the group with Tourette syndrome than the typically developing group. Increased levels of parenting stress were related to increased ADHD symptomatology in both children with Tourette syndrome and typically developing children. Symptomatology of OCD was correlated with parenting stress in Tourette syndrome. Parenting stress was independent of tic severity in patients with Tourette syndrome. CONCLUSIONS: For parents of children with Tourette syndrome, parenting stress appears to be related to the child's ADHD and OCD comorbidity and not to the severity of the child's tic. Subthreshold ADHD symptomatology also appears to be related to parenting stress in parents of typically developing children. These findings demonstrate that ADHD symptomatology impacts parental stress both in children with and without a chronic tic disorder.

Association of Marijuana, Mental Health, and Tobacco in Colorado.

OBJECTIVES: Marijuana's evolving legality may change marijuana use patterns in adults. Co-use of marijuana and tobacco are strongly associated, and populations with mental health disorders are disproportionately likely to use either substance, but neither association has been assessed in the context of legal recreational marijuana. We assessed the associations of tobacco smoking with marijuana use and with mental health disorders in Colorado in 2015. METHODS: Data came from a population-based survey of adults (n = 8023). Multiple logistic regressions were used with current tobacco smoking as the primary outcome. Past 30-day marijuana use and mental health status were the independent variables of interest. Covariates included age, sex, ethnicity, poverty level, and education. RESULTS: Adults who used marijuana in the past 30 days had 3.4 (95% confidence interval [CI] 2.7, 4.2) greater odds of currently smoking tobacco compared to adults who had not recently used marijuana, after adjusting for sociodemographic and economic factors. A mental health disorder was independently associated with tobacco smoking (adjusted odds ratio [OR] 1.7, 95% CI 1.4, 2.1). Prevalence of co-use among adults self-reporting a mental health disorder was significantly higher compared those without a mental health disorder (11.1% vs 4.3%; P < 0.0001). CONCLUSIONS: This study examined the associations between mental health, marijuana use, and tobacco smoking after the legalization of recreational marijuana in Colorado. Adults using marijuana and/or self-reporting a mental health disorder were more likely to smoke tobacco and should be targeted for cessation interventions.

Additive global cerebral blood flow normalization in arterial spin labeling perfusion imaging.

To determine how different methods of normalizing for global cerebral blood flow (gCBF) affect image quality and sensitivity to cortical activation, pulsed arterial spin labeling (pASL) scans obtained during a visual task were normalized by either additive or multiplicative normalization of modal gCBF. Normalization by either method increased the statistical significance of cortical activation by a visual stimulus. However, image quality was superior with additive normalization, whether judged by intensity histograms or by reduced variability within gray and white matter.

Arterial spin labeling versus BOLD in direct challenge and drug-task interaction pharmacological fMRI.

A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease. The study compared the effect of drug directly or the interaction of the drug with a cognitive task. Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to the cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.

In vivo evidence of differential impact of typical and atypical antipsychotics on intracortical myelin in adults with schizophrenia.

CONTEXT: Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination. The hypothesis that typical and atypical medications may differentially impact brain myelination in adults with schizophrenia was previously assessed with inversion recovery (IR) images. Increased white matter (WM) volume suggestive of increased myelination was detected in the patient group treated with an atypical antipsychotic compared to a typical one. OBJECTIVE: In a follow-up reanalysis of MRI images from the original study, we used a novel method to assess whether the difference in WM volumes could be caused by a differential effect of medications on the intracortical myelination process. DESIGN, SETTING, AND PARTICIPANTS: Two different male cohorts of healthy controls ranging in age from 18-35 years were compared to cohorts of subjects with schizophrenia who were treated with either oral risperidone (Ris) or fluphenazine decanoate (Fd). MAIN OUTCOME MEASURE: A novel MRI method that combines the distinct tissue contrasts provided by IR and proton density (PD) images was used to estimate intracortical myelin (ICM) volume. RESULTS: When compared with their pooled healthy control comparison group, the two groups of schizophrenic patients differed in the frontal lobe ICM measure with the Ris group having significantly higher volume. CONCLUSIONS: The data suggest that in adults with schizophrenia antipsychotic treatment choice may be specifically and differentially impacting later-myelinating intracortical circuitry. In vivo MRI can be used to dissect subtle differences in brain tissue characteristics and thus help clarify the effect of pharmacologic treatments on developmental and pathologic processes.