Neurobehavioral Domains Research Articles

Impulsivity across reactive, proactive and cognitive domains in Parkinson's disease on dopaminergic medication: Evidence for multiple domain impairment

Impulse control disorders (ICD) may occur in Parkinson’s disease (PD) although it remains to be understood if such deficits may occur even in the absence of a formal ICD diagnosis. Moreover, studies addressing simultaneously distinct neurobehavioral domains, such as cognitive, proactive and reactive motor impulsivity, are still lacking. Here, we aimed to investigate if reactive, proactive and cognitive impulsivity involving risk taking are concomitantly affected in medicated PD patients, and whether deficits were dependent on response strategies, such as speed accuracy tradeoffs, or the proportion of omission vs. commission errors. We assessed three different impulsivity domains in a sample of 21 PD patients and 13 matched controls. We found impaired impulsivity in both reactive (p = 0.042) and cognitive domains (p = 0.015) for the PD patients, irrespective of response strategy. For the latter, effect sizes were larger for the actions related with reward processing (p = 0.017, dCohen = 0.9). In the proactive impulsivity task, PD patients showed significantly increased number of omissions (p = 0.041), a response strategy which was associated with preserved number of commission errors. Moreover, the number of premature and proactive response errors were correlated with disease stage. Our findings suggest that PD ON medication is characterized compared to healthy controls by impairment across several impulsivity domains, which is moderated in the proactive domain by the response strategy.

The effects of roux en y gastric bypass surgery on neurobehavioral symptom domains associated with severe obesity

BackgroundNeurobehavioral symptoms and cognitive dysfunction related to mood disorders are present in individuals with severe obesity. We sought to determine acute improvements in these symptoms and relationships with adiposity, inflammation, and insulin sensitivity after roux-en-y gastric bypass (RYGB) surgery. MethodsThe self-report Zung Depression Rating (ZDRS) and Neurotoxicity Rating (NRS) scales were administered before, and at 6-months after RYGB surgery in severely obese women (body mass index > 35 kg/m2; N = 19). Symptom domains corresponding to depressed mood/suicide ideation, anxiety, cognitive, somatic, and neurovegetative symptoms were assessed. Biologic measures were of adiposity [leptin, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue], inflammation [IL-6, C-reactive protein (CRP)], and insulin sensitivity (Si). Spearman correlations and linear regression (adjusted for biologic measures) assessed relationships between changes in biologic measures and changes in neurobehavioral domains. ResultsBy 6-months after RYGB, VAT, SAT, Si, CRP, and IL-6 had improved (p < .05). Anxiety, somatic, and neurovegetative symptoms domains improved (p < .05), but depressed mood/suicidal ideation and cognitive domains did not. Reductions in VAT were associated with decreases in neurovegetative symptoms (beta = 295 ± 85, p < .01). We also found significant positive longitudinal associations between IL-6 concentrations and minor changes in cognitive symptoms. ConclusionAnxiety, somatic and neurovegetative symptoms, improved within 6 months after RYGB, but depressed mood/suicidal ideation and cognitive symptoms did not improve. Associations between visceral adiposity, IL-6 concentrations and neurovegetative and cognitive symptoms support links between obesity, inflammation and distinct neurobehavioral symptoms.

Working Memory Performance Following Acute Alcohol: Replication and Extension of Dose by Age Interactions

Despite the substantial number of older adult drinkers, few studies have examined acute alcohol effects in aging samples. We have explored these interactions across a variety of neurobehavioral domains and modalities and have consistently observed age-contingent vulnerabilities to alcohol-associated decrements in neurobehavioral functions. However, these studies have not been sufficiently powered to address sex differences, and, thus far, no attempt has been made to replicate results. The current study addresses these gaps. The study used a double-blind, placebo-controlled, factorial design with two age groups (older, 55-70 years; younger, 25-35 years) and three doses (target breath alcohol concentrations: .00, .04, and .065 g/dl). Replication analyses used an independent sample (n = 90) to replicate age-contingent alcohol effects reported by Boissoneault (n = 90). Samples were combined (N = 180; 91 women) to enable sex analyses. The dependent measure was performance efficiency in a visual working memory task. A complex interaction between sex, age, and dose, F(2, 178) = 4.15, p = .02, appeared driven by age-contingent divergence in working memory performance, which was most pronounced between women at the .065 dose, t(28) = 4.61, p < .01, d = 1.68. Replication analyses revealed a pattern of age differences consistent with previous results, although the previously reported age by alcohol interaction failed to reach statistical significance. Results provide further support for the hypothesis that neurobehavioral effects of acute alcohol are age dependent and offer evidence that this interaction may be moderated by sex. Extensions of this work are needed to identify underlying processes and ascertain the functional impact of these effects on the health and well-being of aging adult drinkers.

Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study.

Diagnostic criteria have recently been introduced in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). The purpose of this study is to assess the classification of this condition using the Canadian fetal alcohol spectrum disorder (FASD) multidisciplinary diagnostic guidelines as the standard of comparison. First, classification of ND-PAE was compared with Canadian FASD diagnoses of fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorder. Second, classification of ND-PAE was compared with FAS and pFAS only, a criterion for which includes facial features highly predictive of prenatal alcohol exposure and effects. Eighty-two patients underwent multidisciplinary clinical evaluations using the Canadian FASD diagnostic guidelines between 2011 and 2015. Two clinicians independently reviewed patient files for evidence of diagnostic criteria for ND-PAE when applying an impairment cut-off level of 2 or more standard deviations below the mean, or clinically significant impairment in the absence of standardized norm-referenced measures. Good interrater reliability was established between clinicians (κ = 0.79). Classifications of ND-PAE and Canadian FASD diagnoses, including alcohol-related neurodevelopmental disorder, were moderately correlated (Cramer V [82] = 0.44, p < 0.01). However, ND-PAE possessed low sensitivity in FASD identification. Further, there was no correlation between ND-PAE and FAS/pFAS classifications (Cramer V [82] = 0.05, p > 0.05). Although there is considerable overlap between both sets of criteria, ND-PAE was less likely to identify patients with FASD. Although the neurobehavioral domains assessed by ND-PAE are supported in research, its diagnostic structure restricts the identification of FASD at the impairment threshold of 2 or more standard deviations. A disconnect remains with regard to impairment thresholds between FASD, which relies on neurodevelopmental data, and ND-PAE, which relies on clinical judgment.

Urinary t,t-muconic acid as a proxy-biomarker of car exhaust and neurobehavioral performance in 15-year olds

IntroductionTraffic-related air pollution has been shown to induce neurotoxicity in rodents. Several recent epidemiological studies reported negative associations between residential outdoor air pollution and neurobehavioral performance. We investigated in a population of non-smoker adolescents the associations between the urinary concentration of trans, trans-muconic acid (t,t-MA-U), a metabolite of benzene and used as proxy-biomarker of traffic exposure, and two neurobehavioral domains, i.e. sustained attention and short-term memory. MethodsIn the framework of an environmental health surveillance study in Flanders (Belgium), we examined between 2008 and 2014 grade nine high school students (n=895). We used reaction time, number of omission errors, and number of commission errors in the Continuous Performance Test to evaluate sustained attention, and for the evaluation of short-term memory we used maximum digit span forward and backward of the Digit Span Test. We measured blood lead (PbB) to assess the independent effect of t,t-MA-U on neurobehavioral outcomes. ResultsThis neurobehavioral examination study showed that a ten-fold increase in t,t-MA-U was associated with a 0.14 SD lower sustained attention (95% Confidence Interval: −0.26 to −0.019; p=0.02) and a 0.17 SD diminished short-term memory (95% CI: −0.31 to −0.030; p=0.02). For the same increment in t,t-MA-U, the Continuous Performance Test showed a 12.2ms higher mean reaction time (95% CI: 4.86–19.5; p=0.001) and 0.51 more numbers of errors of omission (95% CI: 0.057–0.97; p=0.028), while no significant association was found with errors of commission. For the Digit Span Tests, the maximum digit span forward was associated with a 0.20 lower number of digits (95% CI: −0.38 to −0.026; p=0.025) and maximum digit span backward with −0.15 digits (95% CI: −0.32 to 0.022; p=0.088). These associations were independent of PbB, parental education and other important covariates including gender, age, passive smoking, ethnicity, urinary creatinine, time of the day, and examination day of the week. For PbB, an independent association was only found with mean reaction time of the Continuous Performance Test (19.1ms, 95% CI: 2.43–35.8; p=0.025). ConclusionsIn adolescents, a ten-fold increase in the concentration of t,t-MA-U, used as a proxy-biomarker for traffic-related exposure, was associated with a significant deficit in sustained attention and short-term memory. The public health implications of this finding cannot be overlooked as the effect-size for these neurobehavioral domains was about 40% of the effect-size of parental education.

Urinary t,t-muconic acid as a proxy-biomarker of car exhaust and neurobehavioral performance in 15-year olds

Introduction: Traffic-related air pollution has been shown to induce neurotoxicity in rodents. Several recent epidemiological studies reported negative associations between residential outdoor air pollution and neurobehavioral performance. We investigated in a population of non-smoker adolescents the associations between the urinary concentration of trans,trans-muconic acid (t,t-MA-U), a metabolite of benzene and used as proxy-biomarker of traffic exposure, and two neurobehavioral domains: sustained attention and short-term memory. Methods: In the framework of an environmental health surveillance study in Flanders (Belgium), we examined between 2008 and 2014 grade nine high school students (n = 895). We used reaction time and number of omission errors in the Continuous Performance Test to evaluate sustained attention, and for the evaluation of short-term memory we used digit span forward and backward of the Digit Span Test. All estimates were adjusted for gender, age, passive smoking, the education level of the parents, time of the day, day of the week, and study period. The models for t,t-MA-U were additionally adjusted for blood lead and vice versa. Results: A ten-fold increase in t,t-MA-U was associated with a 0.22 SD lower sustained attention (95% CI: -0.36 to -0.07) and a 0.17 SD diminished short-term memory (95% CI: -0.32 to -0.03). For the same increment in t,t-MA-U, the Continuous Performance Test showed a 12.2 msec higher mean reaction time (95% CI: 4.85 to 19.5) and 0.51 more numbers of errors of omission (95% CI: 0.055 to 0.97), while for the Digit Span Test the digit span forward decreased by 0.20 digits (95% CI: -0.38 to -0.027) and digit span backward by 0.15 digits (95% CI: -0.32 to 0.022). We found no evidence of effect-modification by education level of the parents. Conclusions: The concentration of t,t-MA-U, used as a proxy for traffic exposure, was associated with a decreased sustained attention and short-term memory in adolescents.

Associations among treatment-related neurological risk factors and neuropsychological functioning in survivors of childhood brain tumor

Adverse neurological side effects associated with childhood brain tumors and their treatments contribute to long-term neurocognitive morbidity. Measures designed to quantify tumor-related risk factors are lacking. The neurological predictor scale (NPS) is designed to assess treatment-related neurological risks. Preliminary validation established associations between the NPS and global cognitive functioning in this population, though its associations with specific neurobehavioral domains has yet to be addressed. Participants referred for outpatient neuropsychological assessment completed performance-based measures of intellectual, attentional, working memory, motor speed, and executive abilities. Caregivers completed ratings of adaptive functioning. Neuropsychological and adaptive data were available for 100 brain tumor survivors (51% female), ages 6 to 22years (M=12.83, SD=4.37). Total NPS scores were generated via retrospective medical record review. Total NPS scores were significantly associated with several neurocognitive composite scores including verbal reasoning and working memory, after controlling for years post-diagnosis (ps<.05). NPS scores also were significantly associated with performance-based measures of attention, executive functioning, and cognitive efficiency (ps<.05). No significant relationship was demonstrated between NPS scores and caregiver-reported adaptive behavior skills (ps>.05). Results indicate that the NPS is associated with performance-based neurocognitive functioning and executive skills but not with functioning in specific caregiver-reported adaptive behavior domains. The NPS offers some value as a resource for understanding associations between treatment-related neurological risks and select aspects of neurocognitive morbidity. Future studies should examine whether the NPS can aid in planning appropriate therapeutic intervention as survivors progress into early adulthood.

Changing the Diagnostic Concept of Schizophrenia: The NIMH Research Domain Criteria Initiative.

Several factors have contributed to a renewed debate in recent years about the nature of schizophrenia. These include discussions about modifications to the diagnostic criteria for the DMS-5 and ICD-11 revisions, increasing data showing that schizophrenia and bipolar disorder do not “breed true,” GWAS findings of shared genetic risk among disorders, and endophenotype-based intermediate phenotypes that show considerable overlap across disorders. These factors accord with proposals that schizophrenia should be thought of not as a specific disease, but rather as a syndrome that represents one segment of a broad spectrum of serious mental illness. Testing such hypotheses requires a different approach to classification that transcends typical “disorder versus control” studies that preclude analysis of cross-cutting mechanisms. The NIMH Research Domain Criteria (RDoC) project was initiated to develop an experimental classification system based upon functional neurobehavioral domains that can be measured at various units of analysis. We provide an overview of the rationale and goals of the RDoC initiative and discuss examples from the recent schizophrenia literature that illustrate RDoC principles. These are intended to illustrate RDoC’s role in facilitating explorations of heterogeneity and co-morbidity that can lead to more precise diagnosis and treatment for psychotic disorders.

The effects of stress during early postnatal periods on behavior and hippocampal neuroplasticity markers in adult male mice

Infancy is a critical period for brain development. Emerging evidence indicates that stress experienced during that period can have long-term programming effects on the brain and behavior. However, whether different time periods represent different vulnerabilities to the programming of different neurobehavioral domains is not yet known. Disrupted maternal care is known to interfere with neurodevelopmental processes and may lead to the manifestation of behavioral abnormalities in adulthood. Mouse dams confronted with insufficient bedding/nesting material have been shown to provide fragmented maternal care to their offspring. Here, we compared the impact of this model of early-life stress (ELS) during different developmental periods comprising either postnatal days (PNDs) 2–9 (ELS-early) or PND 10–17 (ELS-late) on behavior and hippocampal cell adhesion molecules in male mice in adulthood. ELS-early treatment caused a permanent reduction in bodyweight, whereas this reduction only occurred transiently during juvenility in ELS-late mice. Anxiety was only affected in ELS-late mice, while cognition and sociability were equally impaired in both ELS-treated groups. We analyzed hippocampal gene expression of the γ2 subunit of the GABAa receptor (Gabrg2) and of genes encoding cell adhesion molecules. Gabrg2 expression was increased in the ventral hippocampus in ELS-late-treated animals and was correlated with anxiety-like behavior in the open-field (OF) test. ELS-early-treated animals exhibited an increase in nectin-1 expression in the dorsal hippocampus, and this increase was associated with the social deficits seen in these animals. Our findings highlight the relevance of developmental age on stress-induced long-term behavioral alterations. They also suggest potential links between early stress-induced alterations in hippocampal Gabrg2 expression and the developmental programming of anxiety and between changes in hippocampal nectin-1 expression and stress-induced social impairments.

Association of exposure to neighborhood drug activity, neurobehavioral traits, and marijuana use among at-risk African American females

IntroductionTheories of relative deprivation suggest African Americans in disadvantaged communities are at increased risk for drug use. This increased risk may be due, in part, to exposure to drugs and drug subcultures. Given the significance of the prefrontal cortex (PFC) functioning in yielding behavior that is strategically guided rather than reactive to environmental demands, it is important to examine the relationship between PFC functioning, neighborhood drug activity and substance use among African Americans residing in high risk communities. MethodsA sample of 120 young adult African American females was recruited from high-risk neighborhoods. Each completed the modified version of the neighborhood environment scale, a neurobehavioral assessment designed to measure apathy, behavioral disinhibition and executive dysfunction, and provided a urine sample that was tested for the presence of psychoactive drugs. ResultsLogistic regression analyses indicated that females with higher scores on behavioral disinhibition were 2.6 times more likely to test positive for marijuana (95%CI=1.02, 6.57). Neither apathy nor executive dysfunction was related to marijuana use. No relationship emerged between neighborhood drug activity and marijuana use. ConclusionsAmong the neurobehavioral traits considered only behavioral disinhibition was associated with marijuana use, suggesting that different neurobehavioral domains may be uniquely related to marijuana use. For females living in high risk environments, the extent to which they are able to control impulses may provide some protection against marijuana use. Future studies focused on the moderating effects of behavioral disinhibition on the association of exposure to risk environments and marijuana use may prove beneficial. Further, the study adds to the small base of literature supporting the Frontal Systems Behavior Scale as a brief assessment to evaluate frontally-mediated neurobehavioral traits relevant to substance use. However, future studies aimed at examining the influence of neighborhood drug activity might benefit from more precise measures of exposure to neighborhood drug activity. More research to replicate and expand on the present findings is warranted.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning.

Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: A cross-sectional study

Background: Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. Methods: As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH. Results: A two-fold increase of the sum of serum PBDE’s was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE’s on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests. Conclusions: This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.

Psychometric properties of the Penn Computerized Neurocognitive Battery.

The Penn Computerized Neurocognitive Battery (CNB) was designed to measure performance accuracy and speed on specific neurobehavioral domains using tests that were previously validated with functional neuroimaging. The goal of the present study was to evaluate the neuropsychological theory used to construct the CNB by confirming the factor structure of the tests composing it. In a large community sample (N = 9,138; age range 8-21), we performed a correlated-traits confirmatory factor analysis (CFA) and multiple exploratory factor analyses (EFAs) on the 12 CNB measures of Efficiency (which combine Accuracy and Speed). We then performed EFAs of the Accuracy and Speed measures separately. Finally, we performed a confirmatory bifactor analysis of the Efficiency scores. All analyses were performed with Mplus using maximum likelihood estimation. RESULTS strongly support the a priori theory used to construct the CNB, showing that tests designed to measure executive, episodic memory, complex cognition, and social cognition aggregate their loadings within these domains. When Accuracy and Speed were analyzed separately, Accuracy produced 3 reliable factors: executive and complex cognition, episodic memory, and social cognition, while speed produced 2 factors: tests that require fast responses and those where each item requires deliberation. The statistical "Fit" of almost all models described above was acceptable (usually excellent). Based on the analysis from these large-scale data, the CNB offers an effective means for measuring the integrity of intended neurocognitive domains in about 1 hour of testing and is thus suitable for large-scale clinical and genomic studies.

Abnormal movements in first-episode, nonaffective psychosis: Dyskinesias, stereotypies, and catatonic-like signs

Motor abnormalities represent a neurobehavioral domain of signs intrinsic to schizophrenia-spectrum disorders, though they are commonly attributed to medication side effects and remain understudied. Individuals with first-episode psychosis represent an ideal group to study innate movement disorders due to minimal prior antipsychotic exposure. We measured dyskinesias, stereotypies, and catatonic-like signs and examined their associations with: (1) age at onset of psychotic symptoms and duration of untreated psychosis; (2) positive, negative, and disorganized symptoms; (3) neurocognition; and (4) neurological soft signs. Among 47 predominantly African American first-episode psychosis patients in a public-sector hospital, the presence and severity of dyskinesias, stereotypies, and catatonic-like features were assessed using approximately 30-min video recordings. Movement abnormalities were rated utilizing three scales (Dyskinesia Identification System Condensed User Scale, Stereotypy Checklist, and Catatonia Rating Scale). Correlational analyses were conducted. Scores for each of three movement abnormality types were modestly inter-correlated (r=0.29–0.40). Stereotypy score was significantly associated with age at onset of psychotic symptoms (r=0.32) and positive symptom severity scores (r=0.29–0.41). There were no meaningful or consistent associations with negative symptom severity, neurocognition, or neurological soft signs. Abnormal movements appear to represent a relatively distinct phenotypic domain deserving of further research.

Neurobehavioral performance in adolescents is inversely associated with traffic exposure

On the basis of animal research and epidemiological studies in children and elderly there is a growing concern that traffic exposure may affect the brain. The aim of our study was to investigate the association between traffic exposure and neurobehavioral performance in adolescents. We examined 606 adolescents. To model the exposure, we constructed a traffic exposure factor based on a biomarker of benzene (urinary trans,trans-muconic acid) and the amount of contact with traffic preceding the neurobehavioral examination (using distance-weighted traffic density and time spent in traffic). We used a Bayesian structural equation model to investigate the association between traffic exposure and three neurobehavioral domains: sustained attention, short-term memory, and manual motor speed. A one standard deviation increase in traffic exposure was associated with a 0.26 standard deviation decrease in sustained attention (95% credible interval: −0.02 to −0.51), adjusting for gender, age, smoking, passive smoking, level of education of the mother, socioeconomic status, time of the day, and day of the week. The associations between traffic exposure and the other neurobehavioral domains studied had the same direction but did not reach the level of statistical significance. The results remained consistent in the sensitivity analysis excluding smokers and passive smokers. The inverse association between sustained attention and traffic exposure was independent of the blood lead level. Our study in adolescents supports the recent findings in children and elderly suggesting that traffic exposure adversely affects the neurobehavioral function.

The psychosis spectrum in a young U.S. community sample: findings from the Philadelphia Neurodevelopmental Cohort.

Little is known about the occurrence and predictors of the psychosis spectrum in large non-clinical community samples of U.S. youths. We aimed to bridge this gap through assessment of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort, a collaborative investigation of clinical and neurobehavioral phenotypes in a prospectively accrued cohort of youths, funded by the National Institute of Mental Health. Youths (age 11-21; N=7,054) and collateral informants (caregiver/legal guardian) were recruited through the Children's Hospital of Philadelphia and administered structured screens of psychosis spectrum symptoms, other major psychopathology domains, and substance use. Youths were also administered a computerized neurocognitive battery assessing five neurobehavioral domains. Predictors of psychosis spectrum status in physically healthy participants (N=4,848) were examined using logistic regression. Among medically healthy youths, 3.7% reported threshold psychotic symptoms (delusions and/or hallucinations). An additional 12.3% reported significant sub-psychotic positive symptoms, with odd/unusual thoughts and auditory perceptions, followed by reality confusion, being the most discriminating and widely endorsed attenuated symptoms. A minority of youths (2.3%) endorsed subclinical negative/disorganized symptoms in the absence of positive symptoms. Caregivers reported lower symptom levels than their children. Male gender, younger age, and non-European American ethnicity were significant predictors of spectrum status. Youths with spectrum symptoms had reduced accuracy across neurocognitive domains, reduced global functioning, and increased odds of depression, anxiety, behavioral disorders, substance use and suicidal ideation. These findings have public health relevance for prevention and early intervention.

Neurobehavioral function and low-level metal exposure in adolescents.

An excessive metal exposure is harmful to the brain. However, many aspects of metal neurotoxicity remain unclear including the magnitude of the low-level exposure effects and the level of exposure that can be assumed safe. The aim of our study was to investigate the association between a low-level metal exposure and three neurobehavioral domains (sustained attention, short-term memory, and manual motor speed). We measured Cd, Cu, Mn, Pb, and Tl in blood, Cd, Ni, and toxicologically relevant As in urine and methyl Hg in hair in 606 adolescents between 13.6 and 17 years of age. A two-fold increase in blood Cu was associated with a 0.37 standard deviations decrease in sustained attention (95% CI: -0.67 to -0.07, p=0.02) and 0.39 standard deviations decrease in short-term memory (95% CI: -0.70 to -0.07, p=0.02), accounting for gender, age, smoking, passive smoking, household income per capita, occupation of the parents, and education level of the mother. None of the other metals was significantly associated with the neurobehavioral domains that were measured. The observed associations between blood Cu and neurobehavioral performance are in line with recent studies in elderly. However, the relevance of our results for public health remains to be elucidated.

Frontal lobe function and behavioral changes in amyotrophic lateral sclerosis: a study from Southwest China.

Despite growing interest, the frequency and characteristics of frontal lobe functional and behavioral deficits in Chinese people with amyotrophic lateral sclerosis (ALS), as well as their impact on the survival of ALS patients, remain unknown. The Chinese version of the frontal assessment battery (FAB) and frontal behavioral inventory (FBI) were used to evaluate 126 sporadic ALS patients and 50 healthy controls. The prevalence of frontal lobe dysfunction was 32.5%. The most notable impairment domain of the FAB was lexical fluency (30.7%). The binary logistic regression model revealed that an onset age older than 45 years (OR 5.976, P = 0.002) and a lower educational level (OR 0.858, P = 0.002) were potential determinants of an abnormal FAB. Based on the FBI score, 46.0% of patients showed varied degrees of frontal behavioral changes. The most common impaired neurobehavioral domains were irritability (25.4%), logopenia (20.6%) and apathy (19.0%). The binary logistic regression model revealed that the ALS Functional Rating Scale-Revised scale score (OR 0.127, P = 0.001) was a potential determinant of an abnormal FBI. Frontal functional impairment and the severity of frontal behavioral changes were not associated with the survival status or the progression of ALS by the cox proportional hazard model and multivariate regression analyses, respectively. Frontal lobe dysfunction and frontal behavioral changes are common in Chinese ALS patients. Frontal lobe dysfunction may be related to the onset age and educational level. The severity of frontal behavioral changes may be associated with the ALSFRS-R. However, the frontal functional impairment and the frontal behavioral changes do not worsen the progression or survival of ALS.

Insights into Behavioral Vulnerability to Differential Sleep Pressure and Circadian Phase from a Functional ADA Polymorphism

Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss-related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was no longer present when sleep pressure was reduced by the application of multiple naps. Concomitantly, well-being was worse in the G/A genotype under sleep loss when compared to the nap protocol, and n-back working memory performance appeared to be specifically susceptible to sleep-wake manipulation in this genotype. When considering psychomotor vigilance performance, however, a higher sensitivity to sleep-wake manipulation was detected in homozygous participants, but specifically at the end of the night and only for optimal task performance. Although these data are based on a small sample size and hence require replication (12 G/A- and 12 G/G-allele carriers), they confirm the assumption that interindividual differences regarding the effect of sleep manipulation highly depend on the cognitive task and circadian phase, and thus emphasize the necessity of a multimethodological approach. Moreover, they indicate that napping might be suitable to counteract endogenously heightened sleep pressure depending on the neurobehavioral domain.

Effects of occupational exposure to chlorpyrifos on neuropsychological function: A prospective longitudinal study

BackgroundExposure to chlorpyrifos (CPF), an organophosphorus (OP) anticholinesterase insecticide, occurs typically in settings where multiple agents are present (e.g., agriculture) and quantitative dose measures may be absent (e.g., pesticide application). Such exposures allow few opportunities to study potential neurobehavioral effects of CPF alone. We studied the relationship between CPF exposure and behavioral function among CPF manufacturing workers, which allowed identification, measurement, and estimation of exposure and important non-exposure variables that potentially could affect study findings. MethodsA prospective longitudinal study design was used to compare neurobehavioral function over a one-year period among 53 CPF workers and 60 referent workers. Quantitative and qualitative measures were used, and potential confounders were identified and tested for possible inclusion in our statistical models. Neurobehavioral function was assessed by neuropsychological tests covering various behavioral domains that may be adversely affected by exposure to CPF in sufficient amount. ResultsCPF workers had significantly greater CPF exposures during the study period than did referents at levels where physiologic effects on plasma butyrylcholinesterase (BuChE) activity were apparent and with higher 3,5,6-trichloro-2-pyridinol (TCPy/Cr) urinary excretion (p<0.0001) and lower average BuChE activity (p<0.01). No evidence for impaired neurobehavioral domains by either group of workers was observed at baseline, on repeat examination, or between examinations. CPF workers scored higher than referent workers on the verbal memory domain score (p=0.03) at baseline, but there were no significant changes in verbal memory over time and no significant group-by-time interactions. ConclusionsThe study provides important information about CPF exposure in the workplace by not supporting our working hypothesis that CPF exposure associated with various aspects of the manufacturing process would be accompanied by adverse neurobehavioral effects detectable by quantitative neurobehavioral testing. Some aspects making this workplace site attractive for study and also present limitations for the generalization of results to other situations that might have exposures that vary widely between and within different facilities and locations. For example, these results might not apply to occupations such as applicators with higher exposure or to workers with low educational levels.