Preliminary evidence of the impact of early childhood maltreatment and a preventive intervention on neural patterns of response inhibition in early adolescence.

Maltreated youths in foster care often experience negative developmental and psychological outcomes, which have been linked with poor response inhibition. Recent evidence suggests that childhood maltreatment is also associated with alterations in the neural circuitry underlying response inhibition. However, a burgeoning line of research has begun to explore the mitigating effects of preventive interventions on neural functioning. The current study used event-related functional magnetic resonance imaging to explore the impact of early childhood maltreatment and a preventive intervention on response inhibition in early adolescence. Thirty-six demographically similar adolescents (ages 9-14 years) completed a Go/NoGo task. The sample included nonmaltreated adolescents (n = 14) and maltreated adolescents who were in foster care as preschoolers and randomly assigned to receive services as usual (n = 11) or a preventive intervention, Multidimensional Treatment Foster Care for Preschoolers (n = 11). The groups demonstrated similar behavioral performance but significantly different neural patterns. The maltreated adolescents who received services as usual demonstrated subcortical hypoactivity during successful response inhibition and subcortical hyperactivity during unsuccessful response inhibition. In contrast, the nonmaltreated adolescents and maltreated adolescents who received the intervention exhibited strikingly similar neural patterns during successful response inhibition, but the maltreated adolescents who received the intervention demonstrated prefrontal hypoactivity during unsuccessful response inhibition. These findings offer preliminary evidence that early childhood maltreatment alters the neural patterns underlying response inhibition in early adolescence and that participating in a preventive intervention could mitigate maltreatment-related effects on these neural systems.

Neural Reactivity to Emotional Faces May Mediate the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior.

Reactivity to others' emotions not only can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants (N = 57) provided measures of EC, PD, prosocial behavior, and neural responses to emotional expressions at ages 10 and 13. Initial EC predicted subsequent prosocial behavior. Initial EC and PD predicted subsequent reactivity to emotions in the inferior frontal gyrus (IFG) and inferior parietal lobule, respectively. Activity in the IFG, a region linked to mirror neuron processes, as well as cognitive control and language, mediated the relation between initial EC and subsequent prosocial behavior.

A Physical Activity Intervention and Changes in Body Mass Index at a Middle School With a Large American Indian Population, Oklahoma, 2004-2009.

School-based interventions can reach children and adolescents and aid in reducing the prevalence of childhood obesity. A physical education class that engaged middle school students in a daily 1-mile walk or run and other team sports was developed in a rural school in southwestern Oklahoma with a large American Indian population. Body mass index z scores decreased among boys and were stable among girls in the intervention group compared with students who did not participate in the intervention. A daily required walk or run may help to establish a physical activity habit with all of its associated benefits.

Risk-taking and social exclusion in adolescence: neural mechanisms underlying peer influences on decision-making.

Social exclusion and risk-taking are both common experiences of concern in adolescence, yet little is known about how the two may be related at behavioral or neural levels. In this fMRI study, adolescents (N=27, 14 male, 14-17years-old) completed a series of tasks in the scanner assessing risky decision-making before and after an episode of social exclusion. In this particular context, exclusion was associated with greater behavioral risk-taking among adolescents with low self-reported resistance to peer influence (RPI). When making risky decisions after social exclusion, adolescents who had lower RPI exhibited higher levels of activity in the right temporoparietal junction (rTPJ), and this response in rTPJ was a significant mediator of the relationship between RPI and greater risk-taking after social exclusion. Lower RPI was also associated with lower levels of activity in lPFC during crashes following social exclusion, but unlike rTPJ this response in lPFC was not a significant mediator of the relationship between RPI and greater risk-taking after social exclusion. The results suggest that mentalizing and/or attentional mechanisms have a unique direct effect on adolescents' vulnerability to peer influence on risk-taking.

Patterns of brain activation in foster children and nonmaltreated children during an inhibitory control task.

Children in foster care have often encountered a range of adverse experiences, including neglectful and/or abusive care and multiple caregiver transitions. Prior research findings suggest that such experiences negatively affect inhibitory control and the underlying neural circuitry. In the current study, event-related functional magnetic resonance imaging was employed during a go/no go task that assesses inhibitory control to compare the behavioral performance and brain activation of foster children and nonmaltreated children. The sample included two groups of 9- to 12-year-old children: 11 maltreated foster children and 11 nonmaltreated children living with their biological parents. There were no significant group differences on behavioral performance on the task. In contrast, patterns of brain activation differed by group. The nonmaltreated children demonstrated stronger activation than did the foster children across several regions, including the right anterior cingulate cortex, the middle frontal gyrus, and the right lingual gyrus, during correct no go trials, whereas the foster children displayed stronger activation than the nonmaltreated children in the left inferior parietal lobule and the right superior occipital cortex, including the lingual gyrus and cuneus, during incorrect no go trials. These results provide preliminary evidence that the early adversity experienced by foster children impacts the neural substrates of inhibitory control.

Weight status of American Indian and white elementary school students living in the same rural environment, Oklahoma, 2005-2009.

INTRODUCTION: Studies have assessed rates of childhood obesity in diverse populations, but few have been able to compare the weight status of American Indian and white children living in the same community and attending the same schools. The objective of this study was to measure and compare the weight status of American Indian and white elementary school students (kindergarten through 5th grade) from 2005 through 2009 in an Oklahoma school district. METHODS: We assessed height, weight, age, and sex to calculate body mass index, body mass percentile, and categorical weight status of students, based on the Centers for Disease Control and Prevention 2000 Growth Charts. We used binomial regression to generate risk ratios (RRs) to compare student weight status by race, sex, and age. RESULTS: An average of 753 students was measured in each year; mean age was 8.3 years. From 2005 through 2009, 45.4% of American Indian students and 65.1% of white students were healthy weight or underweight. Greater proportions of American Indian children were very obese (weighted average RR, 2.0); obese (weighted average RR, 1.6), or overweight (weighted average RR, 1.8) compared with white children. The overall prevalence of excess weight changed little during the study period. CONCLUSION: American Indian children had a greater risk of being overweight, obese, or very obese than white children from the same rural environment.

Evaluation of a community-based participatory physical activity promotion project: effect on cardiovascular disease risk profiles of school employees.

BACKGROUND: The efficacy of physical activity in improving cardiovascular disease (CVD) risk profiles has been well established. However, the effectiveness of health promotion programs implemented at the community level remains controversial. This study evaluated a school-based work-site physical activity program. METHODS: Using a community-based participatory research model, a work-site wellness intervention was implemented in a rural public school system in Southwestern Oklahoma. During the 2005-2006 school year, 187 participants (mean age 45 years) completed a pre intervention screening for CVD risk factors followed by a physical activity promotion program. Post intervention screening was conducted after a 6 month period. During both screening sessions, body composition, blood pressure, lipids, glucose and self-reported physical activity levels were assessed. The focus of the intervention was on promoting physical activity. Opportunities for in school physical activity were created by marking hallways, adding a treadmill in each school, and allowing teachers to use planning periods for physical activity. RESULTS: During the post intervention screening, compared to pre intervention levels, participants had lower total, low, and high density lipoprotein-cholesterol (t = 5.9, p < 0.0001, t = 2.6, p = 0.01, and t = 13.2, p < 0.0001 respectively), lower systolic blood pressure (t = 2.9, p = 0.004), and higher self-reported physical activity levels (Sign t = -1.901, p = 0.06). CONCLUSIONS: A successful participatory program was associated with improvements in several CVD risk factors among school employees. Limitations of this study such as seasonal variation in the outcome variables and lack of a control group limit our ability to draw solid conclusions about the effectiveness of the intervention.

Association of HPV16 E6 variants with diagnostic severity in cervical cytology samples of 354 women in a US population.

It has been suggested that DNA sequence variants of HPV16 contribute to differences in the behavior of individual cervical lesions. To address this question, we have analyzed the association of HPV16 variants with diagnostic severity in 354 HPV16-positive Oklahoman women. HPV16 variant status was determined by PCR amplification and DNA sequencing of the E6 open reading frame. European sequences were identified in 86% of samples and 14% were non-European. Of the 51 non-European cases, 61% were Asian-American, 23% African and 16% were Native American variants. European prototype and related variants were present in comparable numbers (43% each) but the relative proportion of each differed with diagnostic category. In general, the proportion of European variants and non-European variants increased with diagnostic severity while the European prototype decreased. When adjusted for age and race (white, black or Hispanic), the increased risk for carcinoma/severe dysplasia for non-European variants was statistically significant with an odds ratio of 3.8 (1.3-10.7). However, the analogous comparison for the European variants, although also showing increased association with carcinoma/severe dysplasia, did not reach statistical significance (OR = 1.6 (95% CI 0.7-3.6). Overall, HPV16 European sequences (both prototype and related variants), were predominant in Oklahoman women including those with cancers. This suggests that while there appear to be differences among the HPV16-variant categories in risk for progression to invasive cancer, all variant categories are associated with the development of invasive cancer.

The Healthy Adults Project in rural Oklahoma.

CONTEXT: Screening to identify individuals at risk for cardiovascular disease is sorely needed in rural areas of Oklahoma. OBJECTIVE: The Healthy Adults Project was started as a screening program for public school employees in a rural school district in southwest Oklahoma. DESIGN, SETTING, AND PARTICIPANTS: The screening project is a collaborative effort between the Anadarko Public School district and the University of Oklahoma Prevention Research Center. Two hundred twenty-four (224) employees participated in the screening in 2004, and 206 employees participated in 2005. FINDINGS: Approximately 50% of females and 80% of males had two or more modifiable risk factors for cardiovascular disease in 2004 and 2005. CONCLUSIONS: Worksite screening is a valuable tool to raise awareness of risk factors for cardiovascular disease, particularly in less densely populated areas where wages are low and few preventive services are available. Knowledge of individual risk is the first step in improving health outcomes.

The Cultivation of Pure Altruism via Gratitude: A Functional MRI Study of Change with Gratitude Practice.

Gratitude is an emotion and a trait linked to well-being and better health, and welcoming benefits to oneself is instrumentally valuable. However, theoretical and empirical work highlights that gratitude is more fully understood as an intrinsically valuable moral emotion. To understand the role of neural reward systems in the association between gratitude and altruistic motivations we tested two hypotheses: First, whether self-reported propensity toward gratitude relates to fMRI-derived indicators of "pure altruism," operationalized as the neural valuation of passive, private transfers to a charity versus to oneself. In young adult female participants, self-reported gratitude and altruism were associated with "neural pure altruism" in ventromedial prefrontal cortex (VMPFC) and nucleus accumbens. Second, whether neural pure altruism can be increased through practicing gratitude. In a double-blind study, we randomly assigned participants to either a gratitude-journal or active-neutral control journal group for 3 weeks. Relative to pre-test levels, gratitude journaling increased the neural pure altruism response in the VMPFC. We posit that as a context-dependent value-sensitive cortical region, the VMPFC supports change with gratitude practice, a change that is larger for benefits to others versus oneself.

Relationship of the 1793G-A and 677C-T polymorphisms of the 5,10-methylenetetrahydrofolate reductase gene to coronary artery disease.

Numerous studies have investigated the relationship between polymorphisms, in particular 677C-T and 1298A-C, of the methylene-tetrahydrofolate reductase (MTHFR) gene and coronary artery disease (CAD) with conflicting results. This study investigates the potential association of two point mutations in MTHFR, 677C-T and 1793G-A, along with other risk factors, with CAD. This is the first hospital-based study to investigate 1793G-A in this context. Genotype analysis was performed on 729 Caucasians and 66 African Americans undergoing coronary angiography using a novel PCR-based assay involving formation of Holliday junctions. Allelic frequencies for 677C-T were 66.2% C and 33.8% T for Caucasians and 90.9% C and 9.1% T for African Americans. With respect to the 1793G-A polymorphism, allelic frequencies were 94.7% G and 5.3% A for Caucasians and 99.2% G and 0.8% A for African Americans. Disease associations were examined in the Caucasian patients due to their greater genotype variability and larger number in the patient cohort. Results suggest that neither 677CT heterozygotes (OR-1.36; 95% CI 0.95 to 1.96) nor mutant homozygotes (OR-0.73; 95% CI 0.44 to 1.20) have either an increased or decreased risk for CAD compared to the 677CC genotype. Likewise, the 1793GA genotype did not demonstrate a statistically significant association with CAD compared to 1793GG patients (OR-0.79; 95% CI 0.47 to 1.33). Mean homocysteine levels (mumol/L) increased from normal to mutant for 677C-T (677CC: 10.2; 677CT: 11.0; 677TT: 11.6) and normal to heterozygous in 1793G-A (1793GG: 10.7; 1793GA: 11.5). These MTHFR polymorphisms did not contribute to the prediction of clinically defined CAD in Caucasians.

Body mass index and blood pressure screening in a rural public school system: the Healthy Kids Project.

INTRODUCTION: All students (N = 2053) in Anadarko public schools, grades kindergarten through 12, were invited to be screened for height, weight, and blood pressure to assess the health status of this multiracial, multiethnic (American Indian, white, African American, and Hispanic) population in southwestern Oklahoma. METHODS: The Centers for Disease Control and Prevention's 2000 growth charts were used to determine body mass index (BMI) percentiles, and standards from the National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents were used to assess blood pressure. RESULTS: Seven hundred sixty-nine students with active consent participated in the screening. Of these, approximately 28% were overweight. American Indians were at significantly greater risk of being overweight or at risk for overweight than whites (relative risk [RR], 1.4; 95% confidence interval [CI], 1.1-1.7) as were African Americans (RR, 1.5; 95% CI, 1.1-2.0), whereas Hispanics (RR, 1.3; 95% CI, 0.9-2.0) did not have a statistically significant increased risk compared with whites. BMI at or above the 95th percentile was strongly associated with elevated blood pressure (> or =90th percentile) (RR, 3.8; 95% CI, 2.6-5.4). CONCLUSION: Students who participated in this BMI screening in the Anadarko public school system evidenced high rates of excess weight, with American Indians and African Americans at greatest risk. Elevated BMI was strongly associated with elevated blood pressure.

Tobacco use among American Indians in Oklahoma: an epidemiologic view.

OBJECTIVES: With the exception of national surveys that sample the entire U.S. population, little information exists on tobacco habits among American Indians. This study is a comparison of tobacco use findings in the 1990s among American Indians in Oklahoma, a state with a large and diverse American Indian population (39 tribes). METHODS: Data on current tobacco use are presented from two statewide surveys, the Oklahoma Youth Tobacco Survey and the Native American Behavioral Risk Factor Survey, as well as two large epidemiologic studies of chronic disease among American Indians-the Cherokee Diabetes Study and the Strong Heart Study. Three of these four sources of data involve research/surveys exclusively about American Indians. RESULTS: Nontraditional use of tobacco by American Indians occurs frequently, according to each instrument. Initiation to this habit begins in middle school and increases dramatically during high school. After age 50, reporting by individuals that they currently smoke declines steadily. CONCLUSIONS: Despite sampling different individuals for the surveys and different tribes for the epidemiologic research, results were comparable in age groups that overlapped. These findings support national data indicating that American Indians have higher prevalence rates of smoking than other racial/ethnic groups. American Indians report smoking on average about a half a pack of cigarettes per day. Individuals reporting using tobacco solely for ceremonial purposes were far fewer than habitual users. Buying tobacco products in American Indian smoke shops helps tribal economies; this fact needs to be considered for prevention programs to succeed.

Neural network predictions of significant coronary artery stenosis in men.

OBJECTIVE: A neural network system was designed to predict whether coronary arteriography on a given patient would reveal any occurrence of significant coronary stenosis (>50%), a degree of stenosis which often leads to coronary intervention. METHODOLOGY: A dataset of 2004 records from male cardiology patients was derived from a national cardiac catheterization database. The catheterizations selected for analysis from the database were first-time and elective, and they were precipitated by chest pain. Eleven patient variables were used as inputs in an artificial neural network system. The network was trained on the earliest 902 records in the dataset. The next 902 records formed a cross-validation file, which was used to optimize the training. A third file composed of the next 100 records facilitated the choice of a cutoff number between 0 and 1. The cutoff number was applied to the last 100 records, which comprised a test file. RESULTS: When a cutoff of 0.25 was compared to the network outputs of all 100 records in the test file, 12 of 46 (specificity=26%) patients without significant stenosis had outputs0.25 (sensitivity=100%). Therefore, the network identified a fraction of the patients in the test file who did not have significant coronary artery stenosis, while at the same time the network identified all of the patients in the test file who had significant stenosis capable of causing chest pain. CONCLUSION: Artificial neural networks may be helpful in reducing unnecessary cardiac catheterizations.

But do you think I'm cool? Developmental differences in striatal recruitment during direct and reflected social self-evaluations.

The current fMRI study investigates the neural foundations of evaluating oneself and others during early adolescence and young adulthood. Eighteen early adolescents (ages 11-14, M=12.6) and 19 young adults (ages 22-31, M=25.6) evaluated whether academic, physical, and social traits described themselves directly (direct self-evaluations), described their best friend directly (direct other-evaluations), described themselves from their best friend's perspective (reflected self-evaluations), or in general could change over time (control malleability-evaluations). Compared to control evaluations, both adolescents and adults recruited cortical midline structures during direct and reflected self-evaluations, as well as during direct other-evaluations, converging with previous research. However, unique to this study was a significant three-way interaction between age group, evaluative perspective, and domain within bilateral ventral striatum. Region of interest analyses demonstrated a significant evaluative perspective by domain interaction within the adolescent sample only. Adolescents recruited greatest bilateral ventral striatum during reflected social self-evaluations, which was positively correlated with age and pubertal development. These findings suggest that reflected social self-evaluations, made from the inferred perspective of a close peer, may be especially self-relevant, salient, or rewarding to adolescent self-processing--particularly during the progression through adolescence - and this feature persists into adulthood.

'Like me?': ventromedial prefrontal cortex is sensitive to both personal relevance and self-similarity during social comparisons.

Social comparisons are an important means by which we gain information about the self, but little is known about the neural mechanisms underlying comparative social judgment, as most prior functional magnetic resonance imaging research on this topic has investigated judgments of self or others in isolation. Ventromedial prefrontal cortex (vmPFC) has routinely been implicated in social cognitive tasks that rely on such absolute judgments about the self or others, but it is unclear whether activity in this region is modulated by personal relevance of social stimuli or self-similarity of judgment targets. Using functional magnetic resonance imaging, we demonstrate that these forces interact to determine vmPFC response during social comparisons, as well as neural activity in the bilateral anterior insulae. Comparisons between the self and similar others exhibit a unique response in this region when compared with other judgment contexts, suggesting that the special psychological status afforded to these social comparisons is indexed by activity in the vmPFC and insula.

Facing puberty: associations between pubertal development and neural responses to affective facial displays.

Adolescence is marked by profound psychosocial and physiological changes. Although investigations into the interactions between these forces have begun to shed light on the neural correlates of affective processing during the transition to adolescence, relatively little is known about the relationship between pubertal development and emotion perception at the neural level. In the current longitudinal study, 45 neurotypical participants were shown affective facial displays while undergoing fMRI, at ages 10 and 13. Neural responses to emotional expressions at both time points were then correlated with a self-report measure of pubertal development, revealing positive associations with activity in amygdala, thalamus and visual cortical areas at age 10 that increased in magnitude and extent by age 13. At the latter time point, pubertal development was additionally correlated with enhanced responses to faces in temporal pole, ventrolateral prefrontal cortex (PFC) and dorsomedial PFC. Longitudinal comparisons revealed that the relationships between pubertal development and activity in the amygdala, hippocampus and temporal pole were significantly stronger during early adolescence than late childhood. These results suggest that pubertal development per se is linked to neural processing of socioemotional stimuli, particularly with respect to the integration of complex perceptual input and higher order cortical processing of affective content.

Entering adolescence: resistance to peer influence, risky behavior, and neural changes in emotion reactivity.

Adolescence is often described as a period of heightened reactivity to emotions paired with reduced regulatory capacities, a combination suggested to contribute to risk-taking and susceptibility to peer influence during puberty. However, no longitudinal research has definitively linked these behavioral changes to underlying neural development. Here, 38 neurotypical participants underwent two fMRI sessions across the transition from late childhood (10 years) to early adolescence (13 years). Responses to affective facial displays exhibited a combination of general and emotion-specific changes in ventral striatum (VS), ventromedial PFC, amygdala, and temporal pole. Furthermore, VS activity increases correlated with decreases in susceptibility to peer influence and risky behavior. VS and amygdala responses were also significantly more negatively coupled in early adolescence than in late childhood while processing sad and happy versus neutral faces. Together, these results suggest that VS responses to viewing emotions may play a regulatory role that is critical to adolescent interpersonal functioning.

Comparison of 2 line blot assays for defining HPV genotypes in oral and oropharyngeal squamous cell carcinomas.

Patients with invasive oral and oropharyngeal squamous cell carcinomas infected with human papillomaviruses (HPV) demonstrate improved survival. HPV detection in tumors may assist in risk stratification of patients and in guiding optimum treatment. Two reverse line blot assays [Linear Array (LA) and INNO-LiPA (LiPA)] were evaluated for detection of HPV genotypes in paraffin-embedded biopsies. Overall, 82.4% of 131 biopsies were HPV+ by LiPA versus 61.1% by LA (κ = 0.32). Completely concordant results were observed in 52.7% of cases: 18 negative and 51 with exactly the same genotype(s). An additional 13 cases had partial agreement. These 82 completely or partially concordant cases revealed a high rate of HPV positivity (78.0%), primarily involving HPV16 (90.6%). HPV+ tumors occurred preferentially in the oropharynx, especially tonsils, with trends for male patients and poor differentiation. Significant differences in these associations were found when LA and LiPA results were analyzed independently. No relationships were found between tumor HPV status and tobacco or alcohol use.

Comparison of molecular methods for detection of HPV in oral and oropharyngeal squamous cell carcinoma.

Substantial molecular evidence exists to implicate human papillomavirus (HPV) in the pathogenesis of a subset of oral and oropharyngeal squamous cell carcinomas. Several studies have shown that HPV-associated oral/oropharyngeal tumors differ etiologically, biologically, and clinically from those that lack the virus. HPV infection confers a significant survival benefit; therefore, HPV detection in tumors could be used to risk-stratify patients and drive optimum treatment strategies. We explored the clinical utility of 6 polymerase chain reaction (PCR)-based or signal amplification-based methods in the detection of HPV in 68 invasive oral/oropharyngeal SSCs and 10 reactive tonsil specimens. Agreement for HPV16 results among the 5 different assays capable of detecting this genotype was substantial (multirater κ=0.72). Only moderate agreement was noted for the 3 assays capable of detecting HPV18 (multirater κ=0.43). HPV results for each assay were evaluated relative to a "majority" HPV result derived from the results of all the detection methods. An HPV16 E6 PCR assay showed the highest concordance with adjudicated consensus HPV16 results (98.7%; κ=0.97), followed by the TaqMan (93.4%; κ=0.87), Linear Array (92.1%; κ=0.84), and E7 PCR (92.1%; κ=0.84) assays, all of which had agreements exceeding 90%, whereas the HPV16/18 Invader assay was lower (85.5%; κ=0.71). The presence of high-risk HPV in a minority of "normal" tonsillar tissues may confound assessment of the virus in oral/oropharyngeal squamous cell carcinoma biopsies using in vitro amplification methods.