Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring.

PubMed

Huizink, Anja C; Mulder, Eduard J H

2006-01-01

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.

Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

PubMed Central

Kundakovic, Marija; Lim, Sean; Gudsnuk, Kathryn; Champagne, Frances A.

2013-01-01

Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder. PMID:23914177

Neurobehavioral Outcomes 11 Years After Neonatal Caffeine Therapy for Apnea of Prematurity.

PubMed

Mürner-Lavanchy, Ines M; Doyle, Lex W; Schmidt, Barbara; Roberts, Robin S; Asztalos, Elizabeth V; Costantini, Lorrie; Davis, Peter G; Dewey, Deborah; D'Ilario, Judy; Grunau, Ruth E; Moddemann, Diane; Nelson, Harvey; Ohlsson, Arne; Solimano, Alfonso; Tin, Win; Anderson, Peter J

2018-05-01

Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate effects of neonatal caffeine therapy in very low birth weight (500-1250 g) infants on neurobehavioral outcomes in 11-year-old participants of the Caffeine for Apnea of Prematurity trial. Thirteen academic hospitals in Canada, Australia, Great Britain, and Sweden participated in this part of the 11-year follow-up of the double-blind, randomized, placebo-controlled trial. Measures of general intelligence, attention, executive function, visuomotor integration and perception, and behavior were obtained in up to 870 children. The effects of caffeine therapy were assessed by using regression models. Neurobehavioral outcomes were generally similar for both the caffeine and placebo group. The caffeine group performed better than the placebo group in fine motor coordination (mean difference [MD] = 2.9; 95% confidence interval [CI]: 0.7 to 5.1; P = .01), visuomotor integration (MD = 1.8; 95% CI: 0.0 to 3.7; P < .05), visual perception (MD = 2.0; 95% CI: 0.3 to 3.8; P = .02), and visuospatial organization (MD = 1.2; 95% CI: 0.4 to 2.0; P = .003). Neonatal caffeine therapy for apnea of prematurity improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. General intelligence, attention, and behavior were not adversely affected by caffeine, which highlights the long-term safety of caffeine therapy for apnea of prematurity in very low birth weight neonates. Copyright © 2018 by the American Academy of Pediatrics.

Epidemiological evidence for a health risk from mobile phone base stations.

PubMed

Khurana, Vini G; Hardell, Lennart; Everaert, Joris; Bortkiewicz, Alicja; Carlberg, Michael; Ahonen, Mikko

2010-01-01

Human populations are increasingly exposed to microwave/radiofrequency (RF) emissions from wireless communication technology, including mobile phones and their base stations. By searching PubMed, we identified a total of 10 epidemiological studies that assessed for putative health effects of mobile phone base stations. Seven of these studies explored the association between base station proximity and neurobehavioral effects and three investigated cancer. We found that eight of the 10 studies reported increased prevalence of adverse neurobehavioral symptoms or cancer in populations living at distances < 500 meters from base stations. None of the studies reported exposure above accepted international guidelines, suggesting that current guidelines may be inadequate in protecting the health of human populations. We believe that comprehensive epidemiological studies of long-term mobile phone base station exposure are urgently required to more definitively understand its health impact.

Effects of methanol vapor on human neurobehavioral measures. Research report, Jul 88-Oct 90

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, M.R.; Bergman, F.J.; Cohen, H.D.

1991-01-01

Methanol may become an important alternative fuel for vehicles in the near future. The objective of the preliminary study was to determine if inhalation exposure to methanol, near the maximum concentration allowed for an eight-hour average exposure in the workplace (200 ppm), would have adverse effects on human neurobehavioral functions. Twelve healthy young men were exposed twice to filtered air and twice to 192 ppm methanol vapors for 75 minutes on different days under double-blind conditions. Twenty-two neurobehavioral and neurophysiological tests were administered before, during, and after exposure to measure visual, behavioral, reasoning, and hearing functions. Exposure to methanol producedmore » significant increases in blood and urine methanol concentration at the end of the exposure period. As expected, no changes in plasma formate were observed. Methanol exposure had no effect on the subjects' performance on most of the tests. However, some methanol-exposed subjects reported more fatigue and lack of concentration. Performance was also slightly impaired on the Sternberg memory task. There were also changes in the latency of the P200 component of the visual- and auditory-event related potential. These effects were small and did not exceed the range of results measured in filtered air-exposed subjects.« less

Neurologic outcomes of toxic oil syndrome patients 18 years after the epidemic.

PubMed Central

de la Paz, Manuel Posada; Philen, Rossanne M; Gerr, Fredric; Letz, Richard; Ferrari Arroyo, Maria José; Vela, Lydia; Izquierdo, Maravillas; Arribas, Concepción Martín; Borda, Ignacio Abaitua; Ramos, Alejandro; Mora, Cristina; Matesanz, Gloria; Roldán, Maria Teresa; Pareja, Juan

2003-01-01

Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women. PMID:12896854

Neurologic outcomes of toxic oil syndrome patients 18 years after the epidemic.

PubMed

de la Paz, Manuel Posada; Philen, Rossanne M; Gerr, Fredric; Letz, Richard; Ferrari Arroyo, Maria José; Vela, Lydia; Izquierdo, Maravillas; Arribas, Concepción Martín; Borda, Ignacio Abaitua; Ramos, Alejandro; Mora, Cristina; Matesanz, Gloria; Roldán, Maria Teresa; Pareja, Juan

2003-08-01

Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women.

Prospective Assessment of Neurocognition in Future Gulf-deployed and Gulf-nondeployed Military Personnel: A Pilot Study

DTIC Science & Technology

2007-02-01

increased emotional distress but with advantaged simple reactiontime. Unit cohesion buffers the adverse effects of early life events on PTSD prior to...motor speed), and emotional (e.g., mood) behaviors thought to reflect neural integrity. Unresolved issues include whether subjective...including neurobehavioral and emotional functioning, (b) examine the impact of deployment-related stress and environmental exposures on

Assessment and evaluation of the high risk neonate: the NICU Network Neurobehavioral Scale.

PubMed

Lester, Barry M; Andreozzi-Fontaine, Lynne; Tronick, Edward; Bigsby, Rosemarie

2014-08-25

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

PubMed

2005-07-01

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based on evidence from studies in experimental animals that prenatal and postnatal exposures to methamphetamine produce neurobehavioral alterations, small litter size, and low birth weight. Results from studies in humans suggest that methamphetamine may cause low birth weight and shortened gestation, but study confounders such as possible multiple drug usage prevent a definite conclusion. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

The neurobehavioral teratology of retinoids: a 50-year history.

PubMed

Adams, Jane

2010-10-01

This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

PubMed Central

Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

2012-01-01

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

Neurobehavioral performance in adolescents is inversely associated with traffic exposure.

PubMed

Kicinski, Michal; Vermeir, Griet; Van Larebeke, Nicolas; Den Hond, Elly; Schoeters, Greet; Bruckers, Liesbeth; Sioen, Isabelle; Bijnens, Esmée; Roels, Harry A; Baeyens, Willy; Viaene, Mineke K; Nawrot, Tim S

2015-02-01

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Meta-Analysis of the Efficacy and Safety of Using Oil Massage to Promote Infant Growth.

PubMed

Li, Xiwen; Zhong, Qingling; Tang, Longhua

2016-01-01

The synthesizing evidence on the effectiveness of using oil massage to promote the growth of infants is still lacking. This paper aims to determine whether oil massage can promote the physical and neurobehavioral growth of infants according to variables and to evaluate whether oil massage is safe for infant skin. The randomized controlled trials, clinical controlled trials and quasi-experimentally designed trials published prior to or in 2014 were searched according to predetermined inclusion criteria and exclusion criteria in Medline, PubMed, Ovid, the Cochran Library, and Chinese databases, including the China National Knowledge Infrastructure, Wan Fang database and VIP journal integration platform. Besides, the grey lectures were searched as well through Open Grey, GrayLIT Network and Clinical Trials.gov. Eight studies out of 625 retrieved articles were eligible for inclusion. Oil massage increased the infant weights, lengths and head circumferences. However, it did not promote a significant advantage in neurobehavioral scores or cause a significant risk of adverse skin reactions. The core mechanisms and standard procedures of oil massage as well as the preferred oil type should be the focus of future nursing practice and research. Oil massage may effectively improve the physical growth of infants, and it presents a limited risk of adverse skin reactions. However, the relationship between neurodevelopment and oil massage requires further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurobehavioral Manifestations of HIV/AIDS: Diagnosis and Treatment

PubMed Central

Singer, Elyse J.; Thames, April D.

2015-01-01

Synopsis Behavioral disorders are common in HIV-infected (HIV+) persons. The differential includes pre-existing psychiatric diseases, substance abuse, direct effects of HIV infection, opportunistic infection (OI), and the adverse effects of medical therapies. Many patients have more than one contributing or co-morbid problem to explain these behavioral changes. The differential should always include consideration of psychosocial, genetic, and medical causes of disease. Treatment strategies must take into account the co-administration of antiretroviral therapy and the specific neurological problems common in the HIV+ population. PMID:26613994

Past, present and emerging toxicity issues for jet fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mattie, David R., E-mail: david.mattie@wpafb.af.mil; Sterner, Teresa R.

2011-07-15

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8more » and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.« less

Past, present and emerging toxicity issues for jet fuel.

PubMed

Mattie, David R; Sterner, Teresa R

2011-07-15

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

Neurobehavioral effects of ambient air pollution on cognitive performance in US adults.

PubMed

Chen, Jiu-Chiuan; Schwartz, Joel

2009-03-01

In vivo animal experiments demonstrate neurotoxicity of exposures to particulate matter (PM) and ozone, but only one small epidemiological study had linked ambient air pollution with central nervous system (CNS) functions in children. To examine the neurobehavioral effects associated with long-term exposure to ambient PM and ozone in adults. We conducted a secondary analysis of the Neurobehavioral Evaluation System-2 (NES2) data (including a simple reaction time test [SRTT] measuring motor response speed to a visual stimulus; a symbol-digit substitution test [SDST] for coding ability; and a serial-digit learning test [SDLT] for attention and short-term memory) from 1764 adult participants (aged 37.5+/-10.9 years) of the Third National Health and Nutrition Examination Survey in 1988-1991. Based on ambient PM(10) (PM with aerodynamic diameter <10microm) and ozone data from the EPA Aerometric Information Retrieval System database, estimated annual exposure prior to the examination were aggregated at the centroid of each census-block group of geocoded residences, using distance-weighted averages from all monitors in the residing and adjoining counties. Generalized linear models were constructed to examine the associations, adjusting for potential confounders. In age- and sex-adjusted models, PM(10) predicted reduced CNS functions, but the association disappeared after adjustment for sociodemographic factors. There were consistent associations between ozone and reduced performance in NES2. In models adjusting for demographics, socioeconomic status, lifestyle, household and neighborhood characteristics, and cardiovascular risk factors, ozone predicted high scores in SDST and SDLT, but not in SRTT. Each 10-ppb increase in annual ozone was associated with increased SDST and SDLT scores by 0.16 (95%CI: 0.01, 0.23) and 0.56 (95%CI: 0.07, 1.05), equivalent to 3.5 and 5.3 years of aging-related decline in cognitive performance. Our study provides the first epidemiological data supporting the adverse neurobehavioral effects of ambient air pollutants in adults.

Neurobehavioral, autonomic nervous function and lymphocyte subsets among aluminum electrolytic workers.

PubMed

He, S C; Qiao, N; Sheng, W

2003-01-01

The purpose of our study is to determine the alteration of neurobehavioral parameters, autonomic nervous function and lymphocyte subsets in aluminum electrolytic workers of long-term aluminum exposure. 33 men who were 35.16 +/- 2.95 (mean +/- S.D) years old occupationally exposed to aluminum for 14.91 +/- 6.31 (mean +/- S.D) years. Air Al level and urinary aluminum concentration was measured by means of graphite furnace atomic absorption spectrophotometer. Normal reference group were selected from a flour plant. Neurobehavioral core test battery (NCTB) recommended by WHO was utilized. Autonomic nervous function test battery recommended by Ewing DJ was conducted on subjects. FAC SCAN was used to measure the lymphocyte subsets of peripheral blood. The mean air aluminum level in the workshop was 6.36 mg/m3, ranged from 2.90 to 11.38 mg/m3. Urinary aluminum of the Al electrolytic workers (40.08 +/- 9.36 microgram/mg.cre) was obviously higher than that of control group (26.84 +/- 8.93 m/mg.cre). Neurobehavioral results showed that the scores of DSY, PAC and PA in Al electrolytic workers were significantly lower than those of control group, The score of POMSC, POMSF and SRT among Al exposed workers were significantly augmented in relation to those of control group. Autonomic nervous function test results showed that R-R interval variability of maximum ratio of immediately standing up in Al electrolytic workers were decreased compare with the control group, while the BP-IS, HR-V, HR-DB, R30:15 had no significant change. Peripheral blood lymphocyte subsets test showed that CD4-CD8+ T lymphocyte in Al electrolytic workers increased. This study suggests that Al exposure exerts adverse effects on neurobehavioral performance, especially movement coordination and negative mood, and parasympathetic nervous function; moreover it increase CD4-CD8+ T lymphocyte subsets.

Neuromotor function in ship welders after cessation of manganese exposure.

PubMed

Wastensson, Gunilla; Sallsten, Gerd; Bast-Pettersen, Rita; Barregard, Lars

2012-08-01

The aim of the present study was to investigate whether previous long-term exposure to manganese (Mn) via inhalation of welding fumes can cause persistent impairment in neuromotor function even long after cessation of exposure. Quantitative tests of tremor, motor speed, manual dexterity, diadochokinesis, eye-hand coordination and postural stability were administered to 17 retired ship welders (mean age 69 years), with mean exposure time 28 years. The welders' exposure had ceased on average 18 years before the study. A cumulative exposure index (CEI) was calculated for each of the former welders. The welders were compared with 21 referents from the same shipyards (mean age was 66 years). Former welders performed less well than referents in the grooved pegboard test, and poorer performance was associated with CEI. The performance in most of the other neurobehavioral tests was similar between groups, but the welders tended to perform slightly better than the referents in tests demanding hand steadiness. The latter finding may be due to a training effect from their former working tasks or selection bias into or out of this occupation. In the present study of welders with previous welding fume exposure, former welders and referents performed similarly in most of the neurobehavioral tests. Previous adverse effects on the neuromotor system might have ceased, and decreased neuromotor function due to normal aging processes in both groups might have disguised any slight effect of previous Mn exposure. The poorer performance in the grooved pegboard test among welders may indicate an adverse effect on motor function of long-term exposure to Mn, but this finding has to be confirmed by other studies.

Reconsideration of the WHO NCTB Strategy and Test Selection

PubMed Central

Anger, W. Kent

2014-01-01

The World Health Organization-recommended Neurobehavioral Core Test Battery (NCTB) became the international standard for identifying adverse human behavioral effects due to neurotoxic chemical exposure when it was first proposed in 1983. Since then the WHO NCTB has been repeatedly cited as the basis for test selection in human neurotoxicology research. A Discussion Group was held before the International Symposium on Neurobehavioral Methods and effects in Occupational and Environmental Health to review the NCTB and reconsider it’s tests. The workshop made three consensus recommendations to the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP): a ‘screening’ battery of broadly sensitive tests is needed as guidance to the field of human neurotoxicologythe SCNP should convene a panel to reconsider the functions measured and the tests in the WHO NCTBThree disciplines should be represented in the panel recommending a revised NCTB: Neuropsychology; Experimental Psychology; Neurology This recommendation will be pursued at the next meeting of the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP). PMID:25172409

Environmental lead toxicity: Nutrition as a component of intervention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahaffey, K.R.

The influence of nutritional status on susceptibility to the toxicity of lead is discussed. Emphasis is given to dietary factors of substantial clinical importance. Subtle changes in susceptibility are difficult to evaluate under conditions of overwhelming lead exposure. It is clear that subtle effects of lead exposure on neurobehavioral and cognitive development are a major concern. The role of nutrition is considered to be an adjunct to reduction of environmental lead exposure, which is the primary means of reducing adverse health effects of lead. Nutrition should be evaluated as a component of strategies to address this broad societal issue.

The contributions of early adverse experiences and trajectories of respiratory sinus arrhythmia on the development of neurobehavioral disinhibition among children with prenatal substance exposure

PubMed Central

Conradt, Elisabeth; Degarmo, David; Fisher, Phil; Abar, Beau; Lester, Barry M.; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

2015-01-01

Neurobehavioral disinhibition (ND) is a complex condition reflecting a wide range of problems involving difficulties with emotion regulation and behavior control. Respiratory sinus arrhythmia (RSA) is a physiological correlate of emotion regulation that has been studied in a variety of at-risk populations; however, there are no studies of RSA in children with ND. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,073 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. ND was assessed at ages 8/9, 11, and 13/14 years via behavioral dysregulation and executive dysfunction composite measures. Greater exposure to early adversity was related to less RSA reactivity at 3 years, increases in RSA reactivity from ages 3 to 6 years, and increased behavioral dysregulation from ages 8/9 to 13/14. RSA reactivity was examined as a moderator of the association between early adversity and changes in ND. A significant Early Adversity × RSA Reactivity quadratic interaction revealed that children with decelerations in RSA reactivity exhibited increases in behavioral dysregulation, regardless of their exposure to early adversity. However, greater exposure to early adversity was related to greater increases in behavioral dysregulation, but only if children exhibited accelerations in RSA reactivity from ages 3 to 6 years. The results contribute to our understanding of how interactions across multiple levels of analysis contribute to the development of ND. PMID:24909973

Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment

PubMed Central

Braun, Joseph M.

2017-01-01

Endocrine disrupting chemicals (EDCs) may increase the risk of childhood diseases by disrupting hormonally mediated processes critical for growth and development during gestation, infancy, or childhood. The fetus, infant, and child may have enhanced sensitivity to environmental stressors like EDCs due to rapid development and greater exposure to some EDCs that results from their developmentally appropriate behavior, anatomy, and physiology. This review summarizes epidemiological studies examining the relations of early-life exposure to bisphenol A (BPA), phthalates, triclosan, and perfluoroalkyl substance (PFAS) with childhood neurobehavioral disorders and obesity. The available epidemiological evidence suggests that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehavior (BPA and phthalates) and excess adiposity or increased risk of obesity/overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability, and elucidating the presence and nature of sexually dimorphic EDC effects would result in stronger inferences from epidemiological studies. Ultimately, better estimates of the causal effects of EDC exposures on child health could help identify susceptible sub-populations and lead to public health interventions to reduce these exposures. PMID:27857130

Development of Translational Methods in Spectral Analysis of Human Infant Crying and Rat Pup Ultrasonic Vocalizations for Early Neurobehavioral Assessment

PubMed Central

Zeskind, Philip Sanford; McMurray, Matthew S.; Garber, Kristin A.; Neuspiel, Juliana M.; Cox, Elizabeth T.; Grewen, Karen M.; Mayes, Linda C.; Johns, Josephine M.

2011-01-01

The purpose of this article is to describe the development of translational methods by which spectrum analysis of human infant crying and rat pup ultrasonic vocalizations (USVs) can be used to assess potentially adverse effects of various prenatal conditions on early neurobehavioral development. The study of human infant crying has resulted in a rich set of measures that has long been used to assess early neurobehavioral insult due to non-optimal prenatal environments, even among seemingly healthy newborn and young infants. In another domain of study, the analysis of rat put USVs has been conducted via paradigms that allow for better experimental control over correlated prenatal conditions that may confound findings and conclusions regarding the effects of specific prenatal experiences. The development of translational methods by which cry vocalizations of both species can be analyzed may provide the opportunity for findings from the two approaches of inquiry to inform one another through their respective strengths. To this end, we present an enhanced taxonomy of a novel set of common measures of cry vocalizations of both human infants and rat pups based on a conceptual framework that emphasizes infant crying as a graded and dynamic acoustic signal. This set includes latency to vocalization onset, duration and repetition rate of expiratory components, duration of inter-vocalization-intervals and spectral features of the sound, including the frequency and amplitude of the fundamental and dominant frequencies. We also present a new set of classifications of rat pup USV waveforms that include qualitative shifts in fundamental frequency, similar to the presence of qualitative shifts in fundamental frequency that have previously been related to insults to neurobehavioral integrity in human infants. Challenges to the development of translational analyses, including the use of different terminologies, methods of recording, and spectral analyses are discussed, as well as descriptions of automated processes, software solutions, and pitfalls. PMID:22028695

Advancing Clinical Outcomes, Biomarkers and Treatments for Severe TBI

DTIC Science & Technology

2017-08-01

determining the neurobehavioral and neural effects of repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive technique to stimulate the...examined to determine effectiveness in inducing structural and functional neural plasticity and improving neurobehavioral recovery after severe TBI...Specific Aims: Aim I will determine presence, direction and sustainability of rTMS-induced neurobehavioral effects measured with the Disability Rating

Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV.

PubMed

Chiò, A; Ilardi, A; Cammarosano, S; Moglia, C; Montuschi, A; Calvo, A

2012-04-03

To assess the effect of neurobehavioral dysfunction on amyotrophic lateral sclerosis (ALS) survival and on the use of life-prolonging therapies in a population-based setting. Of the 132 patients diagnosed with ALS in the province of Torino, Italy, between January 1, 2007, and June 30, 2008, 128 participated in the study. Neurobehavioral dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), using the Family Rating forms, administered within 4 months from diagnosis. The 128 patients included 71 men and 57 women, with a mean age at onset of 64.7 (SD 11) years. Forty-one patients (32.0%) had a neurobehavioral dysfunction and 9 (7.0%) an isolated dysexecutive behavior. Enteral nutrition (EN) and noninvasive ventilation (NIV) were performed with similar frequencies in patients with and without neurobehavioral dysfunction. Patients with neurobehavioral dysfunction had a significantly shorter survival than those with a normal FrSBe score (median survival, 3.3 vs 4.3 years; p = 0.02). Patients with isolated dysexecutive behavior had a shorter survival than those without neurobehavioral dysfunction (median survival, 2.5 vs 4.5 years; p = 0.03). Patients with neurobehavioral dysfunction had a shorter survival after EN and NIV, while patients with isolated dysexecutive behavior had a shorter survival after NIV but not after EN. The negative effect of comorbid neurobehavioral dysfunction and of isolated dysexecutive behavior on survival persisted under the Cox multivariate model. The presence of neurobehavioral dysfunction or of isolate dysexecutive behavior in ALS at diagnosis is a strong predictor of a poor outcome, partially related to a reduced efficacy of life-prolonging therapies.

Apartment residents' and day care workers' exposures to tetrachloroethylene and deficits in visual contrast sensitivity.

PubMed Central

Schreiber, Judith S; Hudnell, H Kenneth; Geller, Andrew M; House, Dennis E; Aldous, Kenneth M; Force, Michael S; Langguth, Karyn; Prohonic, Elizabeth J; Parker, Jean C

2002-01-01

Tetrachloroethylene (also called perchloroethylene, or perc), a volatile organic compound, has been the predominant solvent used by the dry-cleaning industry for many years. The U.S. Environmental Protection Agency (EPA) classified perc as a hazardous air pollutant because of its potential adverse impact on human health. Several occupational studies have indicated that chronic, airborne perc exposure adversely affects neurobehavioral functions in workers, particularly visual color discrimination and tasks dependent on rapid visual-information processing. A 1995 study by Altmann and colleagues extended these findings, indicating that environmental perc exposure at a mean level of 4,980 microg/m(3) (median=1,360 microg/m(3)) alters neurobehavioral functions in residents living near dry-cleaning facilities. Although the U.S. EPA has not yet set a reference concentration guideline level for environmental exposure to airborne perc, the New York State Department of Health set an air quality guideline of 100 microg/m(3). In the current residential study, we investigated the potential for perc exposure and neurologic effects, using a battery of visual-system function tests, among healthy members of six families living in two apartment buildings in New York City that contained dry-cleaning facilities on the ground floors. In addition, a day care investigation assessed the potential for perc exposure and effects among workers at a day care center located in the same one-story building as a dry-cleaning facility. Results from the residential study showed a mean exposure level of 778 microg/m(3) perc in indoor air for a mean of 5.8 years, and that perc levels in breath, blood, and urine were 1-2 orders of magnitude in excess of background values. Group-mean visual contrast sensitivity (VCS), a measure of the ability to detect visual patterns, was significantly reduced in the 17 exposed study participants relative to unexposed matched-control participants. The groups did not differ in visual acuity, suggesting that the VCS deficit was of neurologic origin. Healthy workers in the day care investigation were chronically exposed to airborne perc at a mean of 2,150 microg/m(3) for a mean of 4.0 years. Again, group-mean VCS, measured 6 weeks after exposure cessation, was significantly reduced in the nine exposed workers relative to matched controls, and the groups did not differ significantly in visual acuity. These results suggested that chronic, environmental exposure to airborne perc adversely affects neurobehavioral function in healthy individuals. Further research is needed to assess the susceptibility of the young and elderly to perc-induced effects, to determine whether persistent solvent-induced VCS deficits are a risk factor for the development of neurologic disease, and to identify the no observable adverse effect level for chronic, environmental, perc exposure in humans. PMID:12117642

Appraisal of neurobehavioral methods in environmental health research: the developing brain as a target for neurotoxic chemicals.

PubMed

Winneke, Gerhard

2007-10-01

Psychological tests as developed and validated in the field of differential psychology have a longstanding tradition as tools to study individual differences. In clinical neuropsychology, global or more specific tests are used as neuropsychological tools in the differential diagnosis of various forms of brain damage or neurobehavioral dysfunction following chemical insults, such as mental sequelae of prenatal alcohol consumption by pregnant mothers (fetal alcohol syndrome) or of maternal thyroid deficiency during pregnancy. Psychometric tests are constructed to fulfill basic quality criteria, namely objectivity, reliability and validity. For strictly diagnostic purposes in individual cases they must also possess normative values based on representative reference groups. Intelligence tests or their developmental variants are often used as endpoints in environmental health research for studying neurodevelopmental adversity due to early exposure to neurotoxic chemicals in the environment. Intelligence as treated in psychology is a complex construct made up of specific cognitive functions which usually cover verbal, numerical and spatial skills, as well as perceptual speed, memory and reasoning. In this paper, case studies covering neurodevelopmental adversity of inorganic lead, of methylmercury and of polychlorinated biphenyls (PCBs) are reviewed, and the issue of postnatal behavioral sequelae of prenatal exposure is covered. In such observational studies precautions must be taken in order to avoid pitfalls of causative interpretation of associations between exposure and neurobehavioral outcome. This requires consideration of co-exposure and confounding. Important confounders considered in most modern developmental cohort studies are maternal intelligence and quality of the home environment.

Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides

PubMed Central

Harari, Raul; Julvez, Jordi; Murata, Katsuyuki; Barr, Dana; Bellinger, David C.; Debes, Frodi; Grandjean, Philippe

2010-01-01

Background The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable. Objectives In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children’s neurobehavioral functions at 6–8 years of age. Methods We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children’s current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity. Results Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5–2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results. Conclusions These findings support the notion that prenatal exposure to pesticides—at levels not producing adverse health outcomes in the mother—can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a “silent pandemic” of developmental neurotoxicity. PMID:20185383

Neurobehavioral deficits and increased blood pressure in school-age children prenatally exposed to pesticides.

PubMed

Harari, Raul; Julvez, Jordi; Murata, Katsuyuki; Barr, Dana; Bellinger, David C; Debes, Frodi; Grandjean, Philippe

2010-06-01

The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable. In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children's neurobehavioral functions at 6-8 years of age. We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children's current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity. Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with pre-natal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5-2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results. These findings support the notion that prenatal exposure to pesticides-at levels not producing adverse health outcomes in the mother-can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a "silent pandemic" of developmental neurotoxicity.

Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: II. Prenatal and Postnatal Developmental Toxicity and Maternal Function Study.

PubMed

Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

2016-09-01

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes. © The Author(s) 2016.

Trace elements as paradigms of developmental neurotoxicants: lead, methylmercury and arsenic

PubMed Central

Grandjean, Philippe; Herz, Katherine T.

2014-01-01

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available several decades ago so that past and cumulated exposures could be easily characterized through analysis of biological samples, e.g. blood and urine. The first compelling evidence resulted from unfortunate poisoning events that allowed scrutiny of long-term outcomes of acute exposures that occurred during early development. Pursuant to this documentation, prospective studies of children's cohorts that applied sensitive neurobehavioral methods supported the notion that the brain is uniquely vulnerable to toxic damage during early development. Lead, methylmercury, and arsenic thereby serve as paradigm neurotoxicants that provide a reference for other substances that may have similar adverse effects. Less evidence is available on manganese, fluoride, and cadmium, but experience from the former trace elements suggest that, with time, adverse effects are likely to be documented at exposures previously thought to be low and safe. PMID:25175507

Trace elements as paradigms of developmental neurotoxicants: Lead, methylmercury and arsenic.

PubMed

Grandjean, Philippe; Herz, Katherine T

2015-01-01

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available several decades ago so that past and cumulated exposures could be easily characterized through analysis of biological samples, e.g. blood and urine. The first compelling evidence resulted from unfortunate poisoning events that allowed scrutiny of long-term outcomes of acute exposures that occurred during early development. Pursuant to this documentation, prospective studies of children's cohorts that applied sensitive neurobehavioral methods supported the notion that the brain is uniquely vulnerable to toxic damage during early development. Lead, methylmercury, and arsenic thereby serve as paradigm neurotoxicants that provide a reference for other substances that may have similar adverse effects. Less evidence is available on manganese, fluoride, and cadmium, but experience from the former trace elements suggest that, with time, adverse effects are likely to be documented at exposures previously thought to be low and safe. Copyright © 2014 Elsevier GmbH. All rights reserved.

Neurobehavior related to epigenetic differences in preterm infants

PubMed Central

Lester, Barry M; Marsit, Carmen J; Giarraputo, James; Hawes, Katheleen; LaGasse, Linda L; Padbury, James F

2015-01-01

Preterm birth is associated with medical problems affecting the neuroendocrine system, altering cortisol levels resulting in negative effects on newborn neurobehavior. Newborn neurobehavior is regulated by DNA methylation of NR3C1 and HSD11B2. Aim: Determine if methylation of HSD11B2 and NR3C1 is associated with neurobehavioral profiles in preterm infants. Patients & methods: Neurobehavior was measured before discharge from the hospital in 67 preterm infants. Cheek swabs were collected for DNA extraction. Results: Infants with the high-risk neurobehavioral profile showed more methylation than infants with the low-risk neurobehavioral profile at CpG3 for NR3C1 and less methylation of CpG3 for HSD11B2. Infants with these profiles were more likely to have increased methylation of NR3C1 and decreased methylation of HSD11B2 at these CpG sites. Conclusion: Preterm birth is associated with epigenetic differences in genes that regulate cortisol levels related to high-risk neurobehavioral profiles. PMID:26585459

Infant Neurobehavioral Development

PubMed Central

Lester, Barry M.; Miller, Robin J.; Hawes, Katheleen; Salisbury, Amy; Bigsby, Rosemarie; Sullivan, Mary C.; Padbury, James F.

2011-01-01

The trend toward single-room neonatal intensive care units (NICUs) is increasing; however scientific evidence is, at this point, mostly anecdotal. This is a critical time to assess the impact of the single-room NICU on improving medical and neurobehavioral outcomes of the preterm infant. We have developed a theoretical model that may be useful in studying how the change from an open-bay NICU to a single-room NICU could affect infant medical and neurobehavioral outcome. The model identifies mediating factors that are likely to accompany the change to a single-room NICU. These mediating factors include family centered care, developmental care, parenting and family factors, staff behavior and attitudes, and medical practices. Medical outcomes that plan to be measured are sepsis, length of stay, gestational age at discharge, weight gain, illness severity, gestational age at enteral feeding, and necrotizing enterocolitis (NEC). Neurobehavioral outcomes include the NICU Network Neurobehavioral Scale (NNNS) scores, sleep state organization and sleep physiology, infant mother feeding interaction scores, and pain scores. Preliminary findings on the sample of 150 patients in the open-bay NICU showed a “baseline” of effects of family centered care, developmental care, parent satisfaction, maternal depression, and parenting stress on the neurobehavioral outcomes of the newborn. The single-room NICU has the potential to improve the neurobehavioral status of the infant at discharge. Neurobehavioral assessment can assist with early detection and therefore preventative intervention to maximize developmental outcome. We also present an epigenetic model of the potential effects of maternal care on improving infant neurobehavioral status. PMID:21255702

Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury

PubMed Central

Hellmich, Helen L.; Eidson, Kristine; Cowart, Jeremy; Crookshanks, Jeanna; Boone, Deborah K.; Shah, Syed; Uchida, Tatsuo; DeWitt, Douglas S.; Prough, Donald S.

2008-01-01

Increases of synaptically released zinc and intracellular accumulation of zinc in hippocampal neurons after traumatic or ischemic brain injury is neurotoxic and chelation of zinc has been shown to reduce neurodegeneration. Although our previous studies showed that zinc chelation in traumatically brain-injured rats correlated with an increase in whole-brain expression of several neuroprotective genes and reduced numbers of apoptotic neurons, the effect on functional outcome has not been determined, and the question of whether this treatment may actually be clinically relevant has not been answered. In the present study, we show that treatment of TBI rats with the zinc chelator calcium EDTA reduces the numbers of injured, Fluoro-Jade- positive neurons in the rat hippocampus 24 hours after injury but does not improve neurobehavioral outcome (spatial memory deficits) two weeks post-injury. Our data suggest that zinc chelation, despite providing short-term histological neuroprotection, fails to improve long-term functional outcome, perhaps because long-term disruptions in homeostatic levels of zinc adversely influence hippocampus-dependent spatial memory. PMID:18556117

Methylphenidate therapy improves cognition, mood, and function of brain tumor patients.

PubMed

Meyers, C A; Weitzner, M A; Valentine, A D; Levin, V A

1998-07-01

Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness. These are caused both by the effects of the disease and the effects of radiation and chemotherapy. We sought to determine whether methylphenidate treatment would improve these patients' neurobehavioral functioning despite their expected neurologic deterioration. Thirty patients with primary brain tumors underwent neuropsychologic assessment before and during treatment with methylphenidate. Ability to function in activities of daily living and magnetic resonance imaging (MRI) findings were also documented. Patients were assessed on 10, 20, and 30 mg of methylphenidate twice daily. Significant improvements in cognitive function were observed on the 10-mg twice-daily dose. Functional improvements included improved gait, increased stamina and motivation to perform activities, and in one case, increased bladder control. Adverse effects were minimal and immediately resolved when treatment was discontinued. There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose. Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects. This study demonstrated improved patient function in the setting of a progressive neurologic illness. Methylphenidate should be more widely considered as adjuvant brain tumor therapy.

rTMS: A Treatment to Restore Function After Severe TBI

DTIC Science & Technology

2016-10-01

of rTMS-induced neurobehavioral effects measured with the Disability Rating Scale. Aim II will determine the presence, direction and sustainability...Aim IV addresses the need to confirm rTMS safety for severe TBI. 15. SUBJECT TERMS Disability Rating Scale (DRS), Neurobehavioral, Repetitive...rTMS sessions. The Disability Rating Scale (DRS) will be used at four time points to measure neurobehavioral recovery slopes. Net neural effects

Health-hazard evaluation report HETA-83-085-1757, Everglades National Park, Everglades, Florida

DOE Office of Scientific and Technical Information (OSTI.GOV)

McConnell, R.; Fidler, A.T.; Chrislip, D.

1986-12-01

Adverse health effects from exposure to N,N-diethyl-m-toluamide (DEET), and insect repellant, in employees of Everglades National Park, Florida were investigated in response to a request from the National Park Service. Neurobehavioral analysis showed significant correlations between DEET exposure and affective symptoms, insomnia, muscle cramps, and urinary hesitation. The authors conclude that skin rashes, daytime sleepiness, and impaired cognitive function are significantly associated with DEET exposure. Since a safe alternative is not available, it is recommended that exposure be minimized by using lower concentrations and making use of protective clothing.

[Prospective study of ketogenic diet in treatment of children with global developmental delay].

PubMed

Zhu, Deng-Na; Li, Ping; Wang, Jun; Yuan, Jun-Ying; Zhang, Guang-Yu; Liang, Jiang-Fang; Wang, Ming-Mei; Zhao, Yun-Xia; An, Shuang; Ma, Na; Ma, Dan-Dan

2017-10-01

To study the effect of ketogenic diet (KD) on neurobehavioral development, emotional and social behaviors, and life ability in children with global developmental delay (GDD). A prospective case-control study was performed for hospitalized children with GDD, who were randomly divided into KD treatment group (n=40) and conventional treatment group (n=37). The children in both groups were given comprehensive rehabilitation training, and those in the KD treatment group were given modified Atkins diet in addition to the comprehensive rehabilitation training. The children in both groups were assessed with the Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and Infants-Junior High School Students' Social Life Abilities Scale (S-M scale) before treatment and after 3, 6, and 9 months of treatment. The two groups were compared in terms of the improvements in neurobehavioral development, emotional and social behaviors, and social life ability. After 3, 6, and 9 months of treatment, the KD treatment group had significantly greater improvements in the scores of the adaptive, fine motor, and language quotients of the Gesell Developmental Scale compared with the conventional treatment group (P<0.05); the KD treatment group had significantly greater improvements in CITSEA/CBCL scores than the conventional treatment group (P<0.05). The KD treatment group had a greater improvement in the score of the S-M scale after 9 months of treatment (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1 experienced mild urinary stones. KD can improve the neurobehavioral development and behavioral and emotional behaviors in children with GDD, and it has few adverse effects.

NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a novel environment.

PubMed

Hirano, Tetsushi; Yanai, Shogo; Takada, Tadashi; Yoneda, Naoki; Omotehara, Takuya; Kubota, Naoto; Minami, Kiichi; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

2018-01-05

Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain. A single-administration of 5 or 50mg/kg CTD to male C57BL/6N mice at or below the no-observed-adverse-effect level (NOAEL) induced an acute increase in anxiety during the elevated plus-maze test. In addition, mice in the CTD-administered group spontaneously emitted human-audible vocalizations (4-16kHz), which are behavioral signs of aversive emotions, and showed increased numbers of c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be rendered vulnerable to a novel environment via the activation of thalamic and hippocampal regions related to stress responses. These findings should provide critical insight into the neurobehavioral effects of neonicotinoids on mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

Developmental Exposure to a Commercial PBDE mixture, DE·71: Neurobehavioral, Hormonal, and Reproductive Effects

EPA Science Inventory

Developmental effects of PBDEs have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial m...

Neurobehavioral, Hormonal, and Reproductive Effects following Developmental Exposure to a Commercial PBDE Mixture, DE-71

EPA Science Inventory

Developmental effects caused by PBDEs have been suspected due to their chemically structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabromi...

Zebrafish model systems for developmental neurobehavioral toxicology.

PubMed

Bailey, Jordan; Oliveri, Anthony; Levin, Edward D

2013-03-01

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. Copyright © 2013 Wiley Periodicals, Inc.

Resilience among children and adolescents at risk for depression: Mediation and moderation across social and neurobiological contexts.

PubMed

Silk, Jennifer S; Vanderbilt-Adriance, Ella; Shaw, Daniel S; Forbes, Erika E; Whalen, Diana J; Ryan, Neal D; Dahl, Ronald E

2007-01-01

This article offers a multilevel perspective on resilience to depression, with a focus on interactions among social and neurobehavioral systems involved in emotional reactivity and regulation. We discuss models of cross-contextual mediation and moderation by which the social context influences or modifies the effects of resilience processes at the biological level, or the biological context influences or modifies the effects of resilience processes at the social level. We highlight the socialization of emotion regulation as a candidate process contributing to resilience against depression at the social context level. We discuss several factors and their interactions across levels-including genetic factors, stress reactivity, positive affect, neural systems of reward, and sleep-as candidate processes contributing to resilience against depression at the neurobehavioral level. We then present some preliminary supportive findings from two studies of children and adolescents at high risk for depression. Study 1 shows that elevated neighborhood level adversity has the potential to constrain or limit the benefits of protective factors at other levels. Study 2 indicates that ease and quickness in falling asleep and a greater amount of time in deep Stage 4 sleep may be protective against the development of depressive disorders for children. The paper concludes with a discussion of clinical implications of this approach.

Effects of tartrazine on exploratory behavior in a three-generation toxicity study in mice.

PubMed

Tanaka, Toyohito; Takahashi, Osamu; Oishi, Shinshi; Ogata, Akio

2008-10-01

Tartrazine was given to mice in the diet at levels of 0 (control), 0.05%, 0.15%, and 0.45% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(2) generation, and selected reproductive and neurobehavioral parameters were measured. In the F(1) generation, the development of swimming direction at postnatal day (PND) 7 was accelerated significantly in male offspring in a dose-related manner. Surface righting at PND 7 was affected significantly in female offspring in dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age. In the F(2) generation, the development of swimming direction at PND 7 was accelerated significantly in the high-dosed group in male offspring. Time taken of olfactory orientation at PND 14 was accelerated significantly in male offspring in a dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age, and in males at 8 weeks of age. The dose levels of tartrazine in the present study produced a few adverse effects on neurobehavioral parameters throughout generations in mice.

Zebrafish Model Systems for Developmental Neurobehavioral Toxicology

PubMed Central

Bailey, Jordan; Oliveri, Anthony; Levin, Edward D.

2014-01-01

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. PMID:23723169

Chronic hypoxia-induced alteration of presynaptic protein profiles and neurobehavioral dysfunction are averted by supplemental oxygen in Lymnaea stagnalis.

PubMed

Fei, G-H; Feng, Z-P

2008-04-22

Chronic hypoxia causes neural dysfunction. Oxygen (O(2)) supplements have been commonly used to increase the O(2) supply, yet the therapeutic benefit of this treatment remains controversial due to a lack of cellular and molecular evidence. In this study, we examined the effects of short-burst O(2) supplementation on neural behavior and presynaptic protein expression profiles in a simple chronic hypoxia model of snail Lymnaea stagnalis. We reported that hypoxia delayed the animal response to light stimuli, suppressed locomotory activity, induced expression of stress-response proteins, hypoxia inducible factor-1alpha (HIF-1alpha) and heat shock protein 70 (HSP70), repressed syntaxin-1 (a membrane-bound presynaptic protein) and elevated vesicle-associated membrane protein-1 (VAMP-1) (a vesicle-bound presynaptic protein) level. O(2) supplements relieved suppression of neural behaviors, and corrected hypoxia-induced protein alterations in a dose-dependent manner. The effectiveness of supplemental O(2) was further evaluated by determining time courses for recovery of neural behaviors and expression of stress response proteins and presynaptic proteins after relief from hypoxia conditions. Our findings suggest that O(2) supplement improves hypoxia-induced adverse alterations of presynaptic protein expression and neurobehaviors, however, the optimal level of O(2) required for improvement is protein specific and system specific.

Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

PubMed

Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

2016-10-01

Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m(2)), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comorbidities and risk factors associated with newly diagnosed epilepsy in the U.S. pediatric population.

PubMed

Oh, Ahyuda; Thurman, David J; Kim, Hyunmi

2017-10-01

Neurobehavioral comorbidities can be related to underlying etiology of epilepsy, epilepsy itself, and adverse effects of antiepileptic drugs. We examined the relationship between neurobehavioral comorbidities and putative risk factors for epilepsy in children with newly diagnosed epilepsy. We conducted a retrospective analysis of children aged ≤18years in 50 states and the District of Columbia, using the Truven Health MarketScan® commercial claims and encounters database from January 1, 2009 to December 31, 2013. The eligible study cohort was continuously enrolled throughout 2013 as well as enrolled for any days during a baseline period of at least the prior 2years. Newly diagnosed cases of epilepsy were defined by International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or recurrent seizures and evidence of prescribed antiepileptic drugs during 2013, when neither seizure codes nor seizure medication claims were recorded during baseline periods. Twelve neurobehavioral comorbidities and eleven putative risk factors for epilepsy were measured. More than 6 million children were analyzed (male, 51%; mean age, 8.8years). A total of 7654 children were identified as having newly diagnosed epilepsy (125 per 100,000, 99% CI=122-129). Neurobehavioral comorbidities were more prevalent in children with epilepsy than children without epilepsy (60%, 99% CI=58.1-61.0 vs. 23%, CI=23.1-23.2). Children with epilepsy were far more likely to have multiple comorbidities (36%, 99% CI=34.3-37.1) than those without epilepsy (8%, 99% CI=7.45-7.51, P<0.001). Preexisting putative risk factors for epilepsy were detected in 28% (99% CI=26.9-29.6) of children with epilepsy. After controlling for demographics, neurobehavioral comorbidities, family history of epilepsy, and other risk factors than primary interest, neonatal seizures had the strongest independent association with the development of epilepsy (OR=29.8, 99% CI=23.7-37.3, P<0.001). Compared with children with risk factors but no epilepsy, those with both epilepsy and risk factors were more likely to have intellectual disabilities (OR=13.4, 99% CI=11.9-15.0, P<0.001). The epilepsy and intellectual disabilities could share the common pathophysiology in the neuronal network. Copyright © 2017 Elsevier Inc. All rights reserved.

[Adverse birth outcomes of maternal smoking during pregnancy and genetic polymorphisms: exploiting gene-environment interaction].

PubMed

Sasaki, Seiko; Kishi, Reiko

2009-09-01

It has been recognized that metabolic enzymes mediating genetic susceptibility to environmental chemicals such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls might be related to adverse human health. Recent studies, including the Hokkaido Study of Environmental and Children's Health, have shown that metabolic enzymes mediating genetic susceptibility to environmental chemicals including tobacco smoke might be related to adverse birth outcomes. Certain maternal genetic polymorphisms in the polycyclic aromatic hydrocarbons (PAHs)-metabolizing enzymes have been shown to enhance the association between maternal smoking and infant birth weight in both Caucasians and Japanese. For maternal genetic polymorphisms encoding the N-nitrosamine-metabolizing enzymes, we found that infant birth weight, birth length and birth head circumference were significantly smaller among infants of smokers than among those of nonsmokers and quitters. The adverse effects of maternal smoking on infant birth size may be modified by maternal genetic polymorphisms. Further study is required to clarify the potential association between genetic polymorphisms and cognitive function in childhood, becauae it has been reported that a small birth length or a small head circumference at birth might affect neurobehavioral development during early childhood. It is necessary to elucidate additive impacts of genetic factors on adverse effects of various chemicals commonly encountered in our daily lives, follow up the development of children, and carry out longitudinal observation.

COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

EPA Science Inventory

The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution

PubMed Central

Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

2016-01-01

There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

[Assessment for effect of low level lead-exposure on neurobehavior in workers of printing house].

PubMed

Niu, Q; Dai, F; Chen, Y

1998-11-30

WHO Neurobehavioral Core Test Battery (NCTB) was conducted among 28 lead-exposed workers (mean age 24.84, SD2.85) in printing house and 46 controls (mean age 22.78, SD1.45), in order to assess whether low level lead exposure may be related to neurobehavioral dysfunction. The items of test were: 1. Profile of mood state(POMS), (2) Simple reaction time, (3) Digit span, (4) Santa Anna manual dexterity, (5) Digit simbol, (6) Benton visual retention; and Prusuit aiming test. In all the NCTB test values, there was no significant difference between two groups. Multiple stepwise regression analysis shows that exposure duration is related to neurobehavior scores. Mild lead exposure may affect neurobehavior in some degree but not significant.

Pesticide poisoning in a preschool child: a case study examining neurocognitive and neurobehavioral effects.

PubMed

Riccio, Cynthia A; Avila, Leonor; Ash, Michael J

2010-04-01

Exposure to environmental toxins, such as pesticides, has been shown to have adverse effects in humans, particularly neurological effects. Cases of acute pesticide poisoning occur less frequently and are less well documented; specific deficits (e.g., in processing speed, working memory) have not consistently been discussed. This is a case study of a preschooler who underwent a neuropsychological assessment due to a pesticide poisoning. His parents reported attention, speech, social, and gross and fine motor concerns after the poisoning. A number of methods and measures were used, including observational data, neuropsychological, and behavioral and social-emotional measures. Consistent with past research, results from the assessment demonstrated the subtle and not-so-subtle effects of acute pesticide poisoning. Implications of the findings are discussed.

Neurodevelopmental Low-dose Bisphenol A Exposure Leads to Early Life-stage Hyperactivity and Learning Deficits in Adult Zebrafish

PubMed Central

Saili, Katerine S.; Corvi, Margaret M.; Weber, Daniel N.; Patel, Ami U.; Das, Siba R.; Przybyla, Jennifer; Anderson, Kim A.; Tanguay, Robert L.

2011-01-01

Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The zebrafish model was employed to investigate the neurobehavioral effects of developmental bisphenol A (BPA) exposure. The objectives of this study were to identify whether low-dose, developmental BPA exposure affects larval zebrafish locomotor behavior and whether learning deficits occur in adults exposed during development. Two control compounds, 17β-estradiol (an estrogen receptor ligand) and GSK4716 (a synthetic estrogen related receptor gamma ligand), were included. Larval toxicity assays were used to determine appropriate BPA, 17β-estradiol, and GSK4716 concentrations for behavior testing. BPA tissue uptake was analyzed using HPLC and lower doses were extrapolated using a linear regression analysis. Larval behavior tests were conducted using a ViewPoint Zebrabox. Adult learning tests were conducted using a custom-built T-maze. BPA exposure to ≤30 μM was nonteratogenic in zebrafish. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1 μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1 μM 17β-estradiol or GSK4716 also led to larval hyperactivity. This study demonstrates the efficacy of using the larval zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure. PMID:22108044

A clinical study of the effects of lead poisoning on the intelligence and neurobehavioral abilities of children.

PubMed

Hou, Shuangxing; Yuan, Lianfang; Jin, Pengpeng; Ding, Bojun; Qin, Na; Li, Li; Liu, Xuedong; Wu, Zhongliang; Zhao, Gang; Deng, Yanchun

2013-02-18

Lead is a heavy metal and important environmental toxicant and nerve poison that can destruction many functions of the nervous system. Lead poisoning is a medical condition caused by increased levels of lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and issues, including the central nervous system. It interferes with the development of the nervous system, and is therefore particularly toxic to children, causing potentially permanent neural and cognitive impairments. In this study, we investigated the relationship between lead poisoning and the intellectual and neurobehavioral capabilities of children. The background characteristics of the research subjects were collected by questionnaire survey. Blood lead levels were detected by differential potentiometric stripping analysis (DPSA). Intelligence was assessed using the Gesell Developmental Scale. The Achenbach Child Behavior Checklist (CBCL) was used to evaluate each child's behavior. Blood lead levels were significantly negatively correlated with the developmental quotients of adaptive behavior, gross motor performance, fine motor performance, language development, and individual social behavior (P < 0.01). Compared with healthy children, more children with lead poisoning had abnormal behaviors, especially social withdrawal, depression, and atypical body movements, aggressions and destruction. Lead poisoning has adverse effects on the behavior and mental development of 2-4-year-old children, prescribing positive and effective precautionary measures.

Pesticide exposure and stunting as independent predictors of neurobehavioral deficits in Ecuadorian school children.

PubMed

Grandjean, Philippe; Harari, Raul; Barr, Dana B; Debes, Frodi

2006-03-01

To examine possible effects on blood pressure, neurological function, and neurobehavioral tests in school-aged children with and without prenatal pesticide exposure in an area where stunting is common. In a community of Northern Ecuador with intensive floriculture and a high female employment rate, we invited 79 children attending the 2 lowest grades of a public school for clinical examinations. In addition to a thorough physical examination, we administered simple reaction time, Santa Ana dexterity test, Stanford-Binet copying, and Wechsler Intelligence Scale for Children-Revised Digit Spans forward. Maternal interview included detailed assessment of occupational history to determine pesticide exposure during pregnancy. Recent and current pesticide exposure was assessed by erythrocyte acetylcholine esterase activity and urinary excretion of organophosphate metabolites. All eligible children participated in the study, but 7 children were excluded from data analysis due to other disease or age >9 years. A total of 31 of the remaining 72 children were classified as stunted based on their height for age. Maternal occupational history revealed that 37 children had been exposed to pesticides during development. After confounder adjustment, prenatal pesticide exposure was associated with a higher systolic blood pressure than in the controls. On neurological examination, 14 exposed children and 9 controls showed > or =1 abnormalities. Of 5 neurobehavioral tests, the Stanford-Binet copying test showed a lower drawing score for copying designs in exposed children than in controls. Stunting was associated with a lower score on this test only, and both risk factors remained statistically significant in a multiple regression analysis with adjustment for demographic and social confounders. Increased excretion of dimethyl and diethyl metabolites of organophosphates was associated with increased reaction time and no other outcomes. Prenatal pesticide exposure may cause lasting neurotoxic damage and add to the adverse effects of malnutrition in developing countries. The effects differ from those due to acute pesticide exposure.

Neurocognitive and Behavioral Outcomes in Latino Childhood Cancer Survivors

PubMed Central

Patel, Sunita K.; Lo, Tracy T. Y.; Dennis, Jessica M.; Bhatia, Smita

2013-01-01

Background Children with brain tumors and leukemia are at risk for neurocognitive and behavioral late effects due to central nervous system-directed therapies. Few studies have examined these outcomes in ethnic minority samples, despite speculation that socio-demographic factors may increase vulnerability for adverse neurobehavioral outcomes. We evaluated the neurocognitive and behavioral outcomes and their impact on the health-related quality of life in survivors of childhood cancer drawn from Latino families in the Los Angeles region. Procedure Using culturally-relevant recruitment strategies, 73 predominantly Spanish-speaking parents of pediatric brain tumor or leukemia survivors completed standardized questionnaires, including the Conners Parent-Report and the Bidimensional Acculturation Scales. Clinical and socio-demographic factors influencing the development of neurocognitive and behavioral dysfunction were examined. Results Approximately 50% of the children placed at or above the “elevated” level for difficulties with attention, school-based learning, and peer relations. Younger age at diagnosis significantly predicted dysfunction in inattention, learning problems, and hyperactivity/impulsivity. Children whose parents were less adherent to the non-Hispanic white culture were more likely to have problems with peer relations and executive functioning. HRQL was significantly lower in survivors with neurocognitive and behavioral dysfunction relative to those with normal range scores on the Conners scale. Conclusions In addition to the child’s age at diagnosis, acculturation appears to predict select neurocognitive and behavioral outcomes in this socio-demographically homogeneous sample of Latino families. Further research is needed to understand the interaction of ethnic and cultural factors with therapeutic exposures in determining the adverse neurobehavioral outcomes, so as to optimally design interventions. PMID:23733619

Neurocognitive and behavioral outcomes in Latino childhood cancer survivors.

PubMed

Patel, Sunita K; Lo, Tracy T Y; Dennis, Jessica M; Bhatia, Smita

2013-10-01

Children with brain tumors and leukemia are at risk for neurocognitive and behavioral late effects due to central nervous system-directed therapies. Few studies have examined these outcomes in ethnic minority samples, despite speculation that socio-demographic factors may increase vulnerability for adverse neurobehavioral outcomes. We evaluated the neurocognitive and behavioral outcomes and their impact on the health-related quality of life in survivors of childhood cancer drawn from Latino families in the Los Angeles region. Using culturally-relevant recruitment strategies, 73 predominantly Spanish-speaking parents of pediatric brain tumor or leukemia survivors completed standardized questionnaires, including the Conners parent-report and the Bidimensional Acculturation Scales. Clinical and socio-demographic factors influencing the development of neurocognitive and behavioral dysfunction were examined. Approximately 50% of the children placed at or above the "elevated" level for difficulties with attention, school-based learning, and peer relations. Younger age at diagnosis significantly predicted dysfunction in inattention, learning problems, and hyperactivity/impulsivity. Children whose parents were less adherent to the non-Hispanic white culture were more likely to have problems with peer relations and executive functioning. HRQL was significantly lower in survivors with neurocognitive and behavioral dysfunction relative to those with normal range scores on the Conners scale. In addition to the child's age at diagnosis, acculturation appears to predict select neurocognitive and behavioral outcomes in this socio-demographically homogeneous sample of Latino families. Further research is needed to understand the interaction of ethnic and cultural factors with therapeutic exposures in determining the adverse neurobehavioral outcomes, so as to optimally design interventions. Copyright © 2013 Wiley Periodicals, Inc.

No effects of power line frequency extremely low frequency electromagnetic field exposure on selected neurobehavior tests of workers inspecting transformers and distribution line stations versus controls.

PubMed

Li, Li; Xiong, De-fu; Liu, Jia-wen; Li, Zi-xin; Zeng, Guang-cheng; Li, Hua-liang

2014-03-01

We aimed to evaluate the interference of 50 Hz extremely low frequency electromagnetic field (ELF-EMF) occupational exposure on the neurobehavior tests of workers performing tour-inspection close to transformers and distribution power lines. Occupational short-term "spot" measurements were carried out. 310 inspection workers and 300 logistics staff were selected as exposure and control. The neurobehavior tests were performed through computer-based neurobehavior evaluation system, including mental arithmetic, curve coincide, simple visual reaction time, visual retention, auditory digit span and pursuit aiming. In 500 kV areas electric field intensity at 71.98% of total measured 590 spots were above 5 kV/m (national occupational standard), while in 220 kV areas electric field intensity at 15.69% of total 701 spots were above 5 kV/m. Magnetic field flux density at all the spots was below 1,000 μT (ICNIRP occupational standard). The neurobehavior score changes showed no statistical significance. Results of neurobehavior tests among different age, seniority groups showed no significant changes. Neurobehavior changes caused by daily repeated ELF-EMF exposure were not observed in the current study.

Recent versus chronic exposure to particulate matter air pollution in association with neurobehavioral performance in a panel study of primary schoolchildren.

PubMed

Saenen, Nelly D; Provost, Eline B; Viaene, Mineke K; Vanpoucke, Charlotte; Lefebvre, Wouter; Vrijens, Karen; Roels, Harry A; Nawrot, Tim S

2016-10-01

Children's neuropsychological abilities are in a developmental stage. Recent air pollution exposure and neurobehavioral performance are scarcely studied. In a panel study, we repeatedly administered to each child the following neurobehavioral tests: Stroop Test (selective attention) and Continuous Performance Test (sustained attention), Digit Span Forward and Backward Tests (short-term memory), and Digit-Symbol and Pattern Comparison Tests (visual information processing speed). At school, recent inside classroom particulate matter ≤2.5 or 10μm exposure (PM2.5, PM10) was monitored on each examination day. At the child's residence, recent (same day up to 2days before) and chronic (365days before examination) exposures to PM2.5, PM10 and black carbon (BC) were modeled. Repeated neurobehavioral test performances (n=894) of the children (n=310) reflected slower Stroop Test (p=0.05) and Digit-Symbol Test (p=0.01) performances with increasing recent inside classroom PM2.5 exposure. An interquartile range (IQR) increment in recent residential outdoor PM2.5 exposure was associated with an increase in average latency of 0.087s (SE: ±0.034; p=0.01) in the Pattern Comparison Test. Regarding chronic exposure at residence, an IQR increment of PM2.5 exposure was associated with slower performances in the Continuous Performance (9.45±3.47msec; p=0.007) and Stroop Tests (59.9±26.5msec; p=0.02). Similar results were obtained for PM10 exposure. In essence, we showed differential neurobehavioral changes robustly and adversely associated with recent or chronic ambient exposure to PM air pollution at residence, i.e., with recent exposure for visual information processing speed (Pattern Comparison Test) and with chronic exposure for sustained and selective attention. Copyright © 2016. Published by Elsevier Ltd.

NEUROBEHAVIORAL EFFECTS OF EXPOSURE TO ENVIRONMENTAL POLLUTANTS IN CZECH CHILDREN

EPA Science Inventory

Ambient levels of SO2, NOx, PAHs and heavy metals are elevated in Northern Bohemia as a result of intensive mining and combustion of brown coal. To assess the neurotoxicological effects of exposure to these chemicals, tests from the Neurobehavioral Evaluation System (NES2) we...

Influence of Study Design on Developmental and Reproductive Toxicology Study Outcomes.

PubMed

Foster, Paul M D

2017-01-01

Regulatory studies of developmental and reproductive toxicity (DART) studies have remained largely unchanged for decades, with exposures occurring at various phases of the reproductive cycle and toxicity evaluations at different ages/times depending on the study purpose. The National Toxicology Program has conducted studies examining the power to detect adverse effects where there is a prenatal exposure, but evaluations occur postnatally. In these studies, examination is required of only 1 male and female pup from each litter beyond weaning. This provides poor resolving power to detect rare events (e.g., reproductive tract malformations). If an adverse effect is detected, there is little confidence in the shape of the dose-response curve (and the Benchmark Dose or No Observed Adverse Effect Level [NOAEL]). We have developed a new protocol to evaluate DART, the modified one generation study, with exposure commencing with pregnant animals and retention of 4 males and females from each litter beyond weaning to improve statistical power. These animals can be allocated to specific cohorts that examine subchronic toxicity, teratology, littering, and neurobehavioral toxicity in the same study. This approach also results in a reduction in animal numbers used, compared with individual stand-alone studies, and offers increased numbers of end points evaluated compared with recent Organization for Economic Cooperation and Development proposals.

Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vibol, Sao; Faculty of Agricultural Technology and Management, Royal University of Agriculture, Phnom Penh; Hashim, Jamal Hisham, E-mail: jamalhas@hotmail.com

The research was carried out at 3 study sites with varying groundwater arsenic (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen as a highly contaminated site (300–500 μg/L), Svay Romiet Commune was chosen as a moderately contaminated site (50–300 μg/L) and Anlong Romiet Commune was chosen as a control site. Neurobehavioral tests on the 3 exposure groups were conducted using a modified WHO neurobehavioral core test battery. Seven neurobehavioral tests including digit symbol, digit span, Santa Ana manual dexterity, Benton visual retention, pursuit aiming, trail making and simple reaction time were applied. Children's hair samplesmore » were also collected to investigate the influence of hair As levels on the neurobehavioral test scores. The results from the inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples showed that hair As levels at the 3 study sites were significantly different (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a median hair As level of 0.93 μg/g, while the moderately contaminated site (n=151) had a median hair As level of 0.22 μg/g, and the control site (n=214) had a median hair As level of 0.08 μg/g. There were significant differences among the 3 study sites for all the neurobehavioral tests scores, except for digit span (backward) test. Multiple linear regression clearly shows a positive significant influence of hair As levels on all the neurobehavioral test scores, except for digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn) and cadmium (Cd). Children with high hair As levels experienced 1.57–4.67 times greater risk of having lower neurobehavioral test scores compared to those with low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status. In conclusion, arsenic-exposed school children from the Kandal Province of Cambodia with a median hair As level of 0.93 µg/g among those from the highly contaminated study site, showed clear evidence of neurobehavioral effects. - Highlights: • We measured the level of arsenic concentration in school secondary school children's hair. • As contamination in groundwater is the major source effect on the neurobehavioral performance of school children. • School children in highly and moderately contaminated sites are at risk of As exposure.« less

rTMS: A Treatment to Restore Function After Severe TBI

DTIC Science & Technology

2017-10-01

rTMS- induced changes in functional neural activation and whether or not these changes correlate with improving neurobehavioral function. Aim III...will examine the effect of rTMS on white fiber tracts and whether or not the rTMS-related effects correlate with improving neurobehavioral function

Neurobehavioral Assessment from Fetus to Infant: The NICU Network Neurobehavioral Scale and the Fetal Neurobehavior Coding Scale

ERIC Educational Resources Information Center

Salisbury, Amy L.; Fallone, Melissa Duncan; Lester, Barry

2005-01-01

This review provides an overview and definition of the concept of neurobehavior in human development. Two neurobehavioral assessments used by the authors in current fetal and infant research are discussed: the NICU Network Neurobehavioral Assessment Scale and the Fetal Neurobehavior Coding System. This review will present how the two assessments…

Association between Exposure to Electromagnetic Fields from High Voltage Transmission Lines and Neurobehavioral Function in Children

PubMed Central

Huang, Jiongli; Tang, Tiantong; Hu, Guocheng; Zheng, Jing; Wang, Yuyu; Wang, Qiang; Su, Jing; Zou, Yunfeng; Peng, Xiaowu

2013-01-01

Background Evidence for a possible causal relationship between exposure to electromagnetic fields (EMF) emitted by high voltage transmission (HVT) lines and neurobehavioral dysfunction in children is insufficient. The present study aims to investigate the association between EMF exposure from HVT lines and neurobehavioral function in children. Methods Two primary schools were chosen based on monitoring data of ambient electromagnetic radiation. A cross-sectional study with 437 children (9 to 13 years old) was conducted. Exposure to EMF from HVT lines was monitored at each school. Information was collected on possible confounders and relevant exposure predictors using standardized questionnaires. Neurobehavioral function in children was evaluated using established computerized neurobehavioral tests. Data was analyzed using multivariable regression models adjusted for relevant confounders. Results After controlling for potential confounding factors, multivariable regression revealed that children attending a school near 500 kV HVT lines had poorer performance on the computerized neurobehavioral tests for Visual Retention and Pursuit Aiming compared to children attending a school that was not in close proximity to HVT lines. Conclusions The results suggest long-term low-level exposure to EMF from HVT lines might have a negative impact on neurobehavioral function in children. However, because of differences in results only for two of four tests achieved statistical significance and potential limitations, more studies are needed to explore the effects of exposure to extremely low frequency EMF on neurobehavioral function and development in children. PMID:23843999

Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

PubMed Central

Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

2014-01-01

Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

Potential short-term neurobehavioral alterations in children associated with a peak pesticide spray season: The Mother's Day flower harvest in Ecuador

PubMed Central

Suarez-Lopez, Jose R.; Checkoway, Harvey; Jacobs, David R.; Al-Delaimy, Wael K.; Gahagan, Sheila

2017-01-01

Background Exposures to cholinesterase inhibitor pesticides (e.g. organophosphates) have been associated with children's neurobehavioral alterations, including attention deficit and impulsivity. Animal studies have observed transient alterations in neurobehavioral performance in relation to cholinesterase inhibitor pesticide exposures; however, limited evidence exists regarding transient effects in humans. Methods We estimated the associations between neurobehavioral performance and time after Mother's Day flower harvest (the end of a heightened pesticide usage period) among 308 4-to 9-year-old children living in floricultural communities in Ecuador in 2008 who participated in the ESPINA study. Children's neurobehavior was examined once (NEPSY-II: 11 subtests covering 5 domains), between 63-100 days (SD: 10.8 days) after Mother's Day harvest (blood acetylcholinesterase activity levels can take 82 days to normalize after irreversible inhibition with organophosphates). Results The mean (SD) neurobehavioral scaled scores across domains ranged from 6.6 (2.4) to 9.9 (3.3); higher values reflect greater performance. Children examined sooner after Mother's Day had lower neurobehavioral scores than children examined later, in the domains of (score difference per 10.8 days, 95%CI): Attention/Inhibitory Control (0.38, 0.10-0.65), Visuospatial Processing (0.60, 0.25-0.95) and Sensorimotor (0.43, 0.10-0.77). Scores were higher with longer time post-harvest among girls (vs. boys) in Attention/Inhibitory Control. Conclusions Our findings, although cross-sectional, are among the first in non-worker children to suggest that a peak pesticide use period may transiently affect neurobehavioral performance, as children examined sooner after the flower harvest had lower neurobehavioral performance than children examined later. Studies assessing pre- and post-exposure measures are needed. PMID:28188819

Prenatal drug exposure: infant and toddler outcomes.

PubMed

Bandstra, Emmalee S; Morrow, Connie E; Mansoor, Elana; Accornero, Veronica H

2010-04-01

This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may herald more significant learning and behavioral problems during school-age and adolescence when the child is inevitably confronted with increasing social and academic challenges is the subject of ongoing longitudinal research.

Neuromodulation and Neurorehabilitation for Treatment of Functional Deficits after TBI Plus PTSD

DTIC Science & Technology

2017-10-01

or not these changes correlate with improving neurobehavioral function. Aim III will examine the effect of rTMS on white fiber tracts and whether or...not the rTMS-related effects correlate with improving neurobehavioral function. Aim IV addresses the need to confirm rTMS safety for severe TBI. 15

Neurobehavioral Syndromes in Cocaine-Exposed Newborn Infants.

ERIC Educational Resources Information Center

Lester, Barry M.; And Others

1991-01-01

The effects of fetal cocaine exposure on newborn cry characteristics were studied in 80 cocaine-exposed and 80 control infants. Findings were consistent with the notion that two neurobehavioral syndromes, excitable and depressed, can be described in cocaine-exposed infants and that these two syndromes are a result of direct neurotoxic effects and…

Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

PubMed

Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

2016-06-01

The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

Differential modulatory effects of morphine on acute and chronic stress induced neurobehavioral and cellular markers in rats.

PubMed

Joshi, Jagdish C; Ray, Arunabha; Gulati, Kavita

2014-04-15

The present study evaluated the effects of morphine treatments on elevated plus maze test parameters, oxidative stress markers and Hsp70 expression in normal and stressed rats. Acute and chronic stress caused neurobehavioral suppression, altered prooxidant-antioxidant balance and increased Hsp70 expression in brain homogenates in a differential manner. Morphine (1 and 5mg/kg) attenuated RS induced anxiogenesis, changes in MDA and GSH but further enhanced Hsp70 expression. Similar anxiolytic and Hsp70 enhancing effects were seen after morphine in normal rats (no RS). Exposure to chronic RS did not elicit any appreciable neurobehavioral response in EPM but enhanced MDA, lowered GSH and exaggerated the Hsp70 expression. Pretreatment with morphine did not affect the neurobehavioral response to chronic RS, but reverted the GSH and Hsp70 expression. The results suggest that morphine differentially influences acute and chronic stress induced changes in anxiety behavior and complex interactions between oxidative stress markers and Hsp70 expression which may contribute to these effects. Copyright © 2014 Elsevier B.V. All rights reserved.

APPLICATIONS OF A NEUROBEHAVIORAL SCREENING BATTERY

EPA Science Inventory

With the growing awareness of the neurological effects of many environmental chemicals there is considerable emphasis being placed on the detection of neurotoxic potential at the screening, or first-tier, level of testing. e have developed a neurobehavioral screening battery cons...

Cross-cultural comparison of neurobehavioral performance in Asian workers.

PubMed

Chung, Jong-Hak; Sakong, Joon; Kang, Pock-Soo; Kim, Chang-Yoon; Lee, Kyeong-Soo; Jeon, Man-Joong; Sung, Nak-Jung; Ahn, Sang-Ho; Won, Kyu-Chang

2003-08-01

Widely-used neurobehavioral tests have been developed and standardized on Western populations, but studies on subject factors for Asian populations have been very limited. For the effective application and interpretation of neurobehavioral tests in Asian populations, an evaluation of the effects of subject factors, including cultural background, is necessary. A cross-cultural study was conducted to evaluate the effects of cultural background and the interaction between cultural background and education on neurobehavioral tests in Asian populations. The Korean version of the Swedish Performance Evaluation System (Simple Reaction Time, Symbol Digit, and Finger Tapping Speed) and a pegboard test were administered to 537 workers who were not exposed to chemicals at work from Fareast (Korea and Chinese), Central (Uzbekistan and Tajikistan), and South Asia (Sri Lanka and Indonesia). The Fareast Asian group exhibited better performance in adjusted test scores than other Asian groups, achieving significance for Symbol Digit and Finger Tapping Speed in both genders. The magnitude of the effect of cultural background on Symbol Digit was comparable to the effect of about 10 years of education. Cultural background did not modify the relation between years of education and Symbol Digit in either males or females. This study may provide the first evidence that cultural background has a large impact on neurobehavioral test performance, even within Asian populations, and suggests that cultural background is a critical confounding factor that must be controlled in epidemiologic studies which include Asian populations in the sample.

Saturnine curse: a history of lead poisoning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, D.W.

1985-01-01

Over the past ten years there has been increasing recognition of subacute and chronic lead poisoning and a growing awareness of its pathophysiology and clinical effects. Besides the classic manifestations of abdominal colic, seizures, and anemia progressing to gout, renal disease, and neuropathy, more subtle manifestations are now being increasingly recognized, such as the development of hypertension, neurobehavioral changes, reproductive and endocrine abnormalities, a possible role in carcinogenesis, and an overall increase in morbidity and mortality. Lead was one of the seven metals of antiquity, and it has accompanied the Eurasian and American civilizations since their beginnings. Lead is anmore » extremely pernicious metal with a multitude of adverse effects. The recurring nature of lead poisoning throughout the development of civilization can truly be referred to as the saturnine curse. 16 references.« less

High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders.

PubMed

Chang, Yongmin; Kim, Yangho; Woo, Seung-Tae; Song, Hui-Jin; Kim, Suk Hwan; Lee, Hun; Kwon, Young Joo; Ahn, Joon-Ho; Park, Sin-Jae; Chung, In-Sung; Jeong, Kyoung Sook

2009-07-01

The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology. A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations. Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results. The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

PubMed Central

Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C.

2017-01-01

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance. PMID:28620347

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

PubMed

Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C

2017-01-01

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance.

Neurobehavioral epidemiology: application in risk assessment.

PubMed Central

Grandjean, P; White, R F; Weihe, P

1996-01-01

Neurobehavioral epidemiology may contribute information to risk assessment in relation to a) characterization of neurotoxicity and its time course; b) the dose-effect relationship; c) the dose-response relationship; and d) predisposing factors. The quality of this information relies on the validity of the exposure data, the validity and sensitivity of neurobehavioral function tests, and the degree to which sources of bias are controlled. With epidemiologic studies of methylmercury-associated neurotoxicity as an example, the field of research involves numerous uncertainties that should be taken into account in the risk assessment process. PMID:9182047

A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in rats.

PubMed

Breglia, Rudolph; Bui, Quang; Burnett, Donald; Koschier, Francis; Lapadula, Elizabeth; Podhasky, Paula; Schreiner, Ceinwen; White, Russell

2014-01-01

A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

The Effect of One Night's Sleep Deprivation on Adolescent Neurobehavioral Performance

PubMed Central

Louca, Mia; Short, Michelle A.

2014-01-01

Study Objectives: To investigate the effects of one night's sleep deprivation on neurobehavioral functioning in adolescents. Design: Participants completed a neurobehavioral test battery measuring sustained attention, reaction speed, cognitive processing speed, sleepiness, and fatigue every 2 h during wakefulness. Baseline performance (defined as those test bouts between 09:00 and 19:00 on days 2 and 3, following two 10-h sleep opportunities) were compared to performance at the same clock time the day following total sleep deprivation. Setting: The sleep laboratory at the Centre for Sleep Research. Participants: Twelve healthy adolescents (6 male), aged 14-18 years (mean = 16.17, standard deviation = 0.83). Measurements and Results: Sustained attention, reaction speed, cognitive processing speed, and subjective sleepiness were all significantly worse following one night without sleep than following 10-h sleep opportunities (all main effects of day, P < 0.05). Sleep deprivation led to increased variability on objective performance measures. There were between-subjects differences in response to sleep loss that were task-specific, suggesting that adolescents may not only vary in terms of the degree to which they are affected by sleep loss but also the domains in which they are affected. Conclusions: These findings suggest that one night of total sleep deprivation has significant deleterious effects upon neurobehavioral performance and subjective sleepiness. These factors impair daytime functioning in adolescents, leaving them at greater risk of poor academic and social functioning and accidents and injuries. Citation: Louca M, Short MA. The effect of one night's sleep deprivation on adolescent neurobehavioral performance. SLEEP 2014;37(11):1799-1807. PMID:25364075

Neurobehavioral Impairments Caused by Developmental Imidacloprid Exposure in Zebrafish

PubMed Central

Crosby, Emily B.; Bailey, Jordan M.; Oliveri, Anthony N.; Levin, Edward D.

2015-01-01

BACKGROUND Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. METHODS Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4 h to 5 d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. RESULTS In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strain of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. DISCUSSION Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. PMID:25944383

[Effects of aluminum on neurobehavioral function and metabolism of monoamine neurotransmitter].

PubMed

Yang, H; Zheng, Y; Liang, Y

1998-03-01

To evaluate the effects of occupational exposure to aluminum on neurobahavioral function and metabolism of monoamine neurotransmitter. Thirty-three workers exposed to aluminum and 40 controls were studied. Air aluminum concentrations in workplace environment were detected with an atomic absorption spectrophotometer, homovanillic acid (HVA) and vanilylmandellic acid (VMA) in urine and aluminum in serum and urine were detected with high perfolmance liquid chromatography. Neurobehavioral function was tested with Neurobehavioral Core Test Battery recommended by WHO. Geometric time-weighted average of aluminum in workplace environment was 0.95 mg/m3, ranging from 0.31 to 4.12 mg/m3, and urine aluminum levels in workers exposed to aluminum averaged 12.25 micrograms/L, significantly higher than that in controls (5.78 micrograms/L). There was no significant difference in serum aluminum between the exposed and controls. Both urine VMA and HVA levels were higher in the workers exposed to aluminum, and urine VMA level in the exposed was significantly higher than that in controls. There was significant difference in neurobehavioral test, including Santa Ana, digit symbol and Benton tests between the exposed and control workers. It suggests that occupational exposure to low level of aluminum can affect the neurobehavioral function and metabolism of monoamine neurotransmitter.

Persistent organochlorinated pesticides and mechanisms of their toxicity.

PubMed

Mrema, Ezra J; Rubino, Federico M; Brambilla, Gabri; Moretto, Angelo; Tsatsakis, Aristidis M; Colosio, Claudio

2013-05-10

Persistent organic pollutants comprised of organic chemicals like polychlorinated biphenyls, dibenzo-p-dioxins, dibenzofurans and organochlorinated pesticides which have many characteristics in common. Once released in the environment they resist physical, biological, chemical and photochemical breakdown processes and thus persist in the environment. They are subject to long transboundary air pollution transport. They accumulate in the food chain due to their lipophilicity, bioaccumulation and biomagnification properties. Human exposure occurs through inhalation of air, ingestion of food and skin contact. Because most of them bioaccumulate and remain preferentially in fat, their long-term effects are still a matter of public health concern. They are condemned for health adverse effects such as cancer, reproductive defects, neurobehavioral abnormalities, endocrine and immunological toxicity. These effects can be elicited via a number of mechanisms among others include disruption of endocrine system, oxidation stress and epigenetic. However most of the mechanisms are not clear thus a number of studies are ongoing trying to elucidate them. In this review, the underlying possible mechanisms of action and their possible roles in adverse developmental and reproductive processes are discussed and where possible a linkage is made to some existing epidemiological data. Both genomic and nongenomic pathways are used to describe these effects. Understanding of these mechanisms will enable development of strategies to protect the public by reducing these adverse effects. This review is limited to persistent organochlorinated pesticides (OCPs) such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), beta-hexachlorocyclohexane (β-HCH) and endosulfan. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neurobehavioral assessment of rats exposed to pristine polystyrene nanoplastics upon oral exposure.

PubMed

Rafiee, Mohammad; Dargahi, Leila; Eslami, Akbar; Beirami, Elmira; Jahangiri-Rad, Mahsa; Sabour, Siamak; Amereh, Fatemeh

2018-02-01

The increasing use of plastics has raised concerns about pollution of freshwater by these polymeric materials. Knowledge about their potential effects on environmental and public health is limited. Recent publications have suggested that the degradation of plastics will result in the release of nano-sized plastic particles to the environment. Therefore, it is of utmost importance to gain knowledge about whether and how nanoplastics affect living organisms. The present study aimed to analyse potential neurobehavioral effects of polystyrene nanoparticles (PS-NPs) after long-term exposure on rat. Potential effects of PS-NPs were investigated using four test dosages (1, 3, 6, and 10 mg PS-NPs/kg of body weight/day) administrated orally with adult Wistar male rats for five weeks. Neurobehavioral tests were chosen to assess a variety of behavioral domains. Particle diameters in test suspensions were determined through dynamic light scattering and showed an average hydrodynamic diameter of approximately 38.92 nm. No statistically significant behavioral effects were observed in all tests performed (p > 0.05). In the elevated plus maze, PS-NPs-exposed rats showed greater number of entries into open arms compared to controls. Also, PS-NPs had no significant influence on body weight of animals. Taking into account the subtle and transient nature of neurobehavioral consequences, however, these results underline the possibility of even pristine plastic nanoparticles to induce behavioral alteration in the rest of the food web, including for marine biota and humans. Indeed even though studied neurobehavioral effects in our study was not statistically significant, the observed subtle effects may be clinically considerable. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Interaction Between Occupational Vanadium Exposure and hsp70-hom on Neurobehavioral Function].

PubMed

Zhang, Qin; Liu, Yun-xing; Cui, Li; Li, Shun-pin; Gao, Wei; Hu, Gao-lin; Zhang, Zu-hui; Lan, Ya-jia

2016-01-01

In determine the effect of heat shock protein 70-hom gene (hsp70-hom) polymorphism on the neurobehavioral function of workers exposed to vanadium. Workers from the vanadium products and chemical industry were recruited by cluster sampling. Demographic data and exposure information were collected using a questionnaire. Neurobehavioral function was assessed by Neurobehavioral Core Test Battery. The hsp70-hom genotype was detected by restricted fragment length polymorphism-polymerase chain reaction (RFLP-PCR). A neurobehavioral index (NBI) was formulated through principal component analysis. Workers with a T/C genotype had worse performance in average reaction time, visual retention, digital span (backward), Santa Ana aiming (non-habitual hand), pursuit aiming (right points, total points), digit symbol and NBI score than others (P < 0.05). The relative risk of abnormal NBI score of the workers with a T/C genotype was 1.748 fold of those with a T/T genotype. The relative risk of abnormal.NBI score of the workers exposed to vanadium was 3.048 fold of controls (P < 0.05). But after adjustment with age and education, only vanadium exposure appeared with a significant effect on NBI score. When gene polymorphism and vanadium exposure coexisted, the effect of vanadium on neurobehavioral function was attenuated, but the influence of T/C genotype increased Codds ratio (OR = 4.577, P < 0.05). After adjustment with age and education, the OR of T/C genotype further increased to 7.777 (P < 0.05). Vanadium exposure and T/C genotype had.a bio-interaction effect on NBI score Crelative excess risk due to interaction (RERI) = 4.12, attributable proportion (AP) = 0.7, synergy index (S) = 6.45]. After adjustment with age and education, the RERI became 2.49 and the AP became 0.75, but no coefficient of interaction was produced. Priorities of occupational protection should be given to vanadium-exposed workers with a hsp70-hom T/C genotype and low education level.

The politics of plastics: the making and unmaking of bisphenol a "safety".

PubMed

Vogel, Sarah A

2009-11-01

Bisphenol A (BPA), a synthetic chemical used in the production of plastics since the 1950s and a known endocrine disruptor, is a ubiquitous component of the material environment and human body. New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities. These findings challenge the long-standing scientific and legal presumption of BPA's safety. The history of how BPA's safety was defined and defended provides critical insight into the questions now facing lawmakers and regulators: is BPA safe, and if not, what steps must be taken to protect the public's health? Answers to both questions involve reforms in chemical policy, with implications beyond BPA.

DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS.

EPA Science Inventory

The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus pesticides, fenamiphos and profenophos. Both pesticides inhibit blood ChE, yet brain ChE is relatively spared (little to no inhibition up t...

Pediatric Oncology Branch - Neurobehavioral Assessments | Center for Cancer Research

Cancer.gov

Neurobehavioral Research Assessments As part of the clinical trials investigating new treatments or natural history studies exploring the effects of diseases, such as cancer and neurofibromatosis type 1, we conduct comprehensive assessments of children, adolescents, and adults to identify strengths and weaknesses in neuropsychological functioning and to monitor changes in

Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid

PubMed Central

Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel CT; Li, Rui; Yang, Xu

2014-01-01

Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish.

PubMed

Crosby, Emily B; Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

2015-01-01

Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4h to 5d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strains of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. Copyright © 2015 Elsevier Inc. All rights reserved.

Physiological correlates of neurobehavioral disinhibition that relate to drug use and risky sexual behavior in adolescents with prenatal substance exposure.

PubMed

Conradt, Elisabeth; Lagasse, Linda L; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R; Whitaker, Toni M; Hammond, Jane A; Lester, Barry M

2014-01-01

Physiological correlates of behavioral and emotional problems, substance use onset and initiation of risky sexual behavior have not been studied in adolescents with prenatal drug exposure. We studied the concordance between baseline respiratory sinus arrhythmia (RSA) at age 3 and baseline cortisol levels at age 11. We hypothesized that children who showed concordance between RSA and cortisol would have lower neurobehavioral disinhibition scores which would in turn predict age of substance use onset and first sexual intercourse. The sample included 860 children aged 16 years participating in the Maternal Lifestyle Study, a multisite longitudinal study of children with prenatal exposure to cocaine and other substances. Structural equation modeling was used to test pathways between prenatal substance exposure, early adversity, baseline RSA, baseline cortisol, neurobehavioral disinhibition, drug use, and sexual behavior outcomes. Concordance was studied by examining separate male and female models in which there were statistically significant interactions between baseline RSA and cortisol. Prenatal substance exposure was operationalized as the number of substances to which the child was exposed. An adversity score was computed based on caregiver postnatal substance use, depression and psychological distress, number of caregiver changes, socioeconomic and poverty status, quality of the home environment, and child history of protective service involvement, abuse and neglect. RSA and cortisol were measured during a baseline period prior to the beginning of a task. Neurobehavioral disinhibition, based on composite scores of behavioral dysregulation and executive dysfunction, substance use and sexual behavior were derived from questionnaires and cognitive tests administered to the child. Findings were sex specific. In females, those with discordance between RSA and cortisol (high RSA and low cortisol or low RSA and high cortisol) had the most executive dysfunction which, in turn, predicted earlier initiation of alcohol by age 16. Among boys, there also existed a significant baseline RSA by baseline cortisol interaction. Boys with low baseline RSA and high baseline cortisol had the highest levels of behavioral dysregulation. This increase in behavioral dysregulation was in turn related to initiation of alcohol use by age 16 and lower age of first sexual intercourse. We found sex-specific pathways to the initiation of alcohol use and risky sexual behavior through the combined activity of parasympathetic and neuroendocrine functioning. The study of multiple physiological systems may suggest new pathways to the study of age of onset of substance use and engagement in risky sexual behavior in adolescents. © 2014 S. Karger AG, Basel.

Physiological Correlates of Neurobehavioral Disinhibition that Relate to Drug Use and Risky Sexual Behavior in Adolescents with Prenatal Substance Exposure

PubMed Central

Conradt, Elisabeth; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.; Lester, Barry M.

2015-01-01

Physiological correlates of behavioral and emotional problems, substance use onset and initiation of risky sexual behavior have not been studied in adolescents with prenatal drug exposure. We studied the concordance between baseline respiratory sinus arrhythmia (RSA) at age 3 and baseline Cortisol levels at age 11. We hypothesized that children who showed concordance between RSA and Cortisol would have lower neurobehavioral disinhibition scores which would in turn predict age of substance use onset and first sexual intercourse. The sample included 860 children aged 16 years participating in the Maternal Lifestyle Study, a multisite longitudinal study of children with prenatal exposure to cocaine and other substances. Structural equation modeling was used to test pathways between prenatal substance exposure, early adversity, baseline RSA, baseline Cortisol, neurobehavioral disinhibition, drug use, and sexual behavior outcomes. Concordance was studied by examining separate male and female models in which there were statistically significant interactions between baseline RSA and Cortisol. Prenatal substance exposure was operationalized as the number of substances to which the child was exposed. An adversity score was computed based on caregiver postnatal substance use, depression and psychological distress, number of caregiver changes, socioeconomic and poverty status, quality of the home environment, and child history of protective service involvement, abuse and neglect. RSA and Cortisol were measured during a baseline period prior to the beginning of a task. Neurobehavioral disinhibition, based on composite scores of behavioral dysregulation and executive dysfunction, substance use and sexual behavior were derived from questionnaires and cognitive tests administered to the child. Findings were sex specific. In females, those with discordance between RSA and Cortisol (high RSA and low Cortisol or low RSA and high Cortisol) had the most executive dysfunction which, in turn, predicted earlier initiation of alcohol by age 16. Among boys, there also existed a significant baseline RSA by baseline Cortisol interaction. Boys with low baseline RSA and high baseline Cortisol had the highest levels of behavioral dysregulation. This increase in behavioral dysregulation was in turn related to initiation of alcohol use by age 16 and lower age of first sexual intercourse. We found sex-specific pathways to the initiation of alcohol use and risky sexual behavior through the combined activity of parasympathetic and neuroendocrine functioning. The study of multiple physiological systems may suggest new pathways to the study of age of onset of substance use and engagement in risky sexual behavior in adolescents. PMID:25033835

Developmental fluoride neurotoxicity: a systematic review and meta-analysis.

PubMed

Choi, Anna L; Sun, Guifan; Zhang, Ying; Grandjean, Philippe

2012-10-01

Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children's neurodevelopment. We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development. We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg's funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies. The standardized weighted mean difference in IQ score between exposed and reference populations was -0.45 (95% confidence interval: -0.56, -0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease. The results support the possibility of an adverse effect of high fluoride exposure on children's neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.

Cognitive and Behavioral Impairments Evoked by Low-Level Exposure to Tobacco Smoke Components: Comparison with Nicotine Alone.

PubMed

Hall, Brandon J; Cauley, Marty; Burke, Dennis A; Kiany, Abtin; Slotkin, Theodore A; Levin, Edward D

2016-06-01

Active maternal smoking has adverse effects on neurobehavioral development of the offspring, with nicotine (Nic) providing much of the underlying causative mechanism. To determine whether the lower exposures caused by second-hand smoke are deleterious, we administered tobacco smoke extract (TSE) to pregnant rats starting preconception and continued through the second postnatal week, corresponding to all 3 trimesters of fetal brain development. Dosing was adjusted to produce maternal plasma Nic concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers. We then compared TSE effects to those of an equivalent dose of Nic alone, and to a 10-fold higher Nic dose. Gestational exposure to TSE and Nic significantly disrupted cognitive and behavioral function in behavioral tests given during adolescence and adulthood (postnatal weeks 4-40), producing hyperactivity, working memory deficits, and impairments in emotional processing, even at the low exposure levels corresponding to second-hand smoke. Although TSE effects were highly correlated with those of Nic, the effects of TSE were much larger than could be attributed to just the Nic in the mixture. Indeed, TSE effects more closely resembled those of the 10-fold higher Nic levels, but still exceeded their magnitude. In combination with our earlier findings, this study thus completes the chain of causation to prove that second-hand smoke exposure causes neurodevelopmental deficits, originating in disruption of neurodifferentiation, leading to miswiring of neuronal circuits, and as shown here, culminating in behavioral dysfunction. As low level exposure to Nic alone produced neurobehavioral teratology, 'harm reduction' Nic products do not abolish the potential for neurodevelopmental damage. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Vanadium Exposure-Induced Neurobehavioral Alterations among Chinese Workers

PubMed Central

Li, Hong; Zhou, Dinglun; Zhang, Qin; Feng, Chengyong; Zheng, Wei; He, Keping; Lan, Yajia

2014-01-01

Vanadium-containing products are manufactured and widely used in the modern industry. Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive. This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure. A total of 463 vanadium-exposed workers (exposed group) and 251 non-exposed workers (control group) were recruited from a Steel and Iron Group in Sichuan, China. A WHO-recommended neurobehavioral core test battery (NCTB) and event-related auditory evoked potentials test (P300) were used to assess the neurobehavioral functions of all study subjects. A general linear model was used to compare outcome scores between the two groups while controlling for possible confounders. The exposed group showed a statistically significant neurobehavioral alteration more than the control group in the NCTB tests. The exposed workers also exhibited an increased anger-hostility, depression-dejection and fatigue-inertia on the profile of mood states (p<0.05). Performances in the Simple Reaction Time, Digit Span, Benton Visual Retention and Pursuit Aiming were also poorer among exposed workers as compared to unexposed control workers(p<0.05). Some of these poor performances in tests were also significantly related to workers’ exposure duration. P300 latencies were longer in the exposed group than in the control (p<0.05). Longer mean reaction times and more counting errors were also found in the exposed workers (p<0.05). Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of altered neurobehavioral outcomes by occupational exposure to vanadium. PMID:23500660

Early Malnutrition and Child Neurobehavioral Development: Insights from the Study of Children of Diabetic Mothers.

ERIC Educational Resources Information Center

Rizzo, Thomas A.; And Others

1997-01-01

Studied whether disturbances in mothers' metabolism (N=139) during pregnancy may exert long-range effects on neurobehavioral development of singleton progeny. Examined detailed pregnancy and perinatal records of mothers who experienced diabetes in pregnancy and intelligence tests of their offspring, administered at ages 7 to 11 years. All…

Sleep disturbance and neurobehavioral performance among postpartum women.

PubMed

Insana, Salvatore P; Williams, Kayla B; Montgomery-Downs, Hawley E

2013-01-01

Sleep disturbances cause neurobehavioral performance and daytime functioning impairments. Postpartum women experience high levels of sleep disturbance. Thus, the study objective was to describe and explore the relation between neurobehavioral performance and sleep among women during the early postpartum period. Longitudinal field-based study. There were 70 primiparous women and nine nulliparous women in a control group. None. During their first 12 postpartum weeks, 70 primiparous women wore continuous wrist actigraphy to objectively monitor their sleep. Each morning they self-administered the psychomotor vigilance test (PVT) to index their neurobehavioral performance. Nine nulliparous women in a control group underwent the same protocol for 12 continuous weeks. Postpartum PVT mean reciprocal (1/RT) reaction time did not differ from that of women in the control group at postpartum week 2, but then worsened over time. Postpartum slowest 10% 1/RT PVT reaction time was significantly worse than that of women in the control group at all weeks. Despite improvements in postpartum sleep, neurobehavioral performance continued to worsen from week 2 through the end of the study. Across the first 12 postpartum weeks, PVT measures were more frequently associated with percent sleep compared with total sleep time, highlighting the deleterious consequences of sleep disruption on maternal daytime functioning throughout the early postpartum period. Worsened maternal neurobehavioral performance across the first 12 postpartum weeks may have been influenced by the cumulative effects of sleep disturbance. These results can inform future work to identify the particular sleep profiles that could be primary intervention targets to improve daytime functioning among postpartum women, and indicate need for further research on the effectiveness of family leave policies. The time when postpartum women return to control-level daytime functioning is unknown.

Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

PubMed

Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

2015-03-01

The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

Reliability of Neurobehavioral Assessments from Birth to Term Equivalent Age in Preterm and Term Born Infants.

PubMed

Eeles, Abbey L; Olsen, Joy E; Walsh, Jennifer M; McInnes, Emma K; Molesworth, Charlotte M L; Cheong, Jeanie L Y; Doyle, Lex W; Spittle, Alicia J

2017-02-01

Neurobehavioral assessments provide insight into the functional integrity of the developing brain and help guide early intervention for preterm (<37 weeks' gestation) infants. In the context of shorter hospital stays, clinicians often need to assess preterm infants prior to term equivalent age. Few neurobehavioral assessments used in the preterm period have established interrater reliability. To evaluate the interrater reliability of the Hammersmith Neonatal Neurological Examination (HNNE) and the NICU Network Neurobehavioral Scale (NNNS), when used both preterm and at term (>36 weeks). Thirty-five preterm infants and 11 term controls were recruited. Five assessors double-scored the HNNE and NNNS administered either preterm or at term. A one-way random effects, absolute, single-measures interclass correlation coefficient (ICC) was calculated to determine interrater reliability. Interrater reliability for the HNNE was excellent (ICC > 0.74) for optimality scores, and good (ICC 0.60-0.74) to excellent for subtotal scores, except for 'Tone Patterns' (ICC 0.54). On the NNNS, interrater reliability was predominantly excellent for all items. Interrater agreement was generally excellent at both time points. Overall, the HNNE and NNNS neurobehavioral assessments demonstrated mostly excellent interrater reliability when used prior to term and at term.

Neurobehavioral Assessment before Birth

ERIC Educational Resources Information Center

DiPietro, Janet A.

2005-01-01

The complexities of neurobehavioral assessment of the fetus, which can be neither directly viewed nor manipulated, cannot be understated. Impetus to develop methods for measuring fetal neurobehavioral development has been provided by the recognition that individual differences in neurobehavioral functioning do not originate with birth and…

The Politics of Plastics: The Making and Unmaking of Bisphenol A “Safety”

PubMed Central

2009-01-01

Bisphenol A (BPA), a synthetic chemical used in the production of plastics since the 1950s and a known endocrine disruptor, is a ubiquitous component of the material environment and human body. New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities. These findings challenge the long-standing scientific and legal presumption of BPA's safety. The history of how BPA's safety was defined and defended provides critical insight into the questions now facing lawmakers and regulators: is BPA safe, and if not, what steps must be taken to protect the public's health? Answers to both questions involve reforms in chemical policy, with implications beyond BPA. PMID:19890158

Associations Between the Self-Reported Frequency of Hearing Chemical Alarms in Theater and Visuospatial Function in Gulf War Veterans.

PubMed

Chao, Linda L

2016-10-01

The aim of this study was to examine the relationship between the self-reported frequencies of hearing chemical alarms during deployment and visuospatial function in Gulf War (GW) veterans. The relationship between the self-reported frequency of hearing chemical alarms, neurobehavioral, and volumetric brain imaging data was examined with correlational, regression, and mediation analyses. The self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on a visuospatial task (ie, Block Design) over and above potentially confounding variables, including concurrent, correlated GW-related exposures. This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume. Exposure to substances that triggered chemical alarms during GW deployment likely had adverse effects on veterans' brain structure and function, warranting further investigation of whether these GW veterans are at an increased risk for dementia.

The accumulation of brain injury leads to severe neuropathological and neurobehavioral changes after repetitive mild traumatic brain injury.

PubMed

Gao, Huabin; Han, Zhaoli; Bai, Ruojing; Huang, Shan; Ge, Xintong; Chen, Fanglian; Lei, Ping

2017-02-15

Traumatic brain injury (TBI) is a major public health problem with long-term neurobehavioral sequela. The evidences have revealed that TBI is a risk factor for later development of neurodegenerative disease and both the single and repetitive brain injury can lead to the neurodegeneration. But whether the effects of accumulation play an important role in the neurodegenerative disease is still unknown. We utilized the Sprague Dawley (SD) rats to develop the animal models of repetitive mild TBI and single mild TBI in order to detect the neurobehavioral changes. The results of neurobehavioral test revealed that the repetitive mild TBI led to more severe behavioral injuries than the single TBI. There were more activated microglia cells and astrocytes in the repetitive mild TBI group than the single TBI group. In consistent with this, the levels of TNF-α and IL-6 were higher and the expression of IL-10 was lower in the repetitive mild TBI group compared with the single TBI group. The expression of amyloid precursor protein (APP) increased in the repetitive TBI group detected by ELISA and western blot. But the levels of total tau (Tau-5) and P-tau (ser202) seem no different between the two groups in most time point. In conclusion, repetitive mild TBI could lead to more severe neurobehavioral impairments and the effects of accumulation may be associated with the increased inflammation in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Patterned feeding experience for preterm infants: study protocol for a randomized controlled trial.

PubMed

Pickler, Rita H; Wetzel, Paul A; Meinzen-Derr, Jareen; Tubbs-Cooley, Heather L; Moore, Margo

2015-06-04

Neurobehavioral disabilities occur in 5-15% of preterm infants with an estimated 50-70% of very low birth weight preterm infants experiencing later dysfunction, including cognitive, behavioral, and social delays that often persist into adulthood. Factors implicated in poor neurobehavioral and developmental outcomes are hospitalization in the neonatal intensive care unit (NICU) and inconsistent caregiving patterns. Although much underlying brain damage occurs in utero or shortly after birth, neuroprotective strategies can stop lesions from progressing, particularly when these strategies are used during the most sensitive periods of neural plasticity occurring months before term age. The purpose of this randomized trial is to test the effect of a patterned feeding experience on preterm infants' neurobehavioral organization and development, cognitive function, and clinical outcomes. This trial uses an experimental, longitudinal, 2-group design with 120 preterm infants. Infants are enrolled within the first week of life and randomized to an experimental group receiving a patterned feeding experience from the first gavage feeding through discharge or to a control group receiving usual feeding care experience. The intervention involves a continuity of tactile experiences associated with feeding to train and build neuronal networks supportive of normal infant feeding experience. Primary outcomes are neurobehavioral organization as measured by Neurobehavioral Assessment of the Preterm Infant at 3 time points: the transition to oral feedings, NICU discharge, and 2 months corrected age. Secondary aims are cognitive function measured using the Bayley Scales of Infant and Toddler Development, Third Edition at 6 months corrected age, neurobehavioral development (sucking organization, feeding performance, and heart rate variability), and clinical outcomes (length of NICU stay and time to full oral feeding). The potential effects of demographic and biobehavioral factors (perinatal events and conditions of maternal or fetal/newborn origin and immunologic and genetic biomarkers) on the outcome variables will also be considered. Theoretically, the intervention provided at a critical time in neurologic system development and associated with a recurring event (feeding) should enhance neural connections that may be important for later development, particularly language and other cognitive and neurobehavioral organization skills. NCT01577615 11 April 2012.

The effect of one night's sleep deprivation on adolescent neurobehavioral performance.

PubMed

Louca, Mia; Short, Michelle A

2014-11-01

To investigate the effects of one night's sleep deprivation on neurobehavioral functioning in adolescents. Participants completed a neurobehavioral test battery measuring sustained attention, reaction speed, cognitive processing speed, sleepiness, and fatigue every 2 h during wakefulness. Baseline performance (defined as those test bouts between 09:00 and 19:00 on days 2 and 3, following two 10-h sleep opportunities) were compared to performance at the same clock time the day following total sleep deprivation. The sleep laboratory at the Centre for Sleep Research. Twelve healthy adolescents (6 male), aged 14-18 years (mean = 16.17, standard deviation = 0.83). Sustained attention, reaction speed, cognitive processing speed, and subjective sleepiness were all significantly worse following one night without sleep than following 10-h sleep opportunities (all main effects of day, P < 0.05). Sleep deprivation led to increased variability on objective performance measures. There were between-subjects differences in response to sleep loss that were task-specific, suggesting that adolescents may not only vary in terms of the degree to which they are affected by sleep loss but also the domains in which they are affected. These findings suggest that one night of total sleep deprivation has significant deleterious effects upon neurobehavioral performance and subjective sleepiness. These factors impair daytime functioning in adolescents, leaving them at greater risk of poor academic and social functioning and accidents and injuries.

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

PubMed

Kiciński, Michał; Viaene, Mineke K; Den Hond, Elly; Schoeters, Greet; Covaci, Adrian; Dirtu, Alin C; Nelen, Vera; Bruckers, Liesbeth; Croes, Kim; Sioen, Isabelle; Baeyens, Willy; Van Larebeke, Nicolas; Nawrot, Tim S

2012-11-14

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. 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. 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. 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.

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

PubMed Central

2012-01-01

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. PMID:23151181

Comprehensive assessment of a chlorinated drinking water concentrate in a rat multigenerational reproductive toxicity study.

PubMed

Narotsky, Michael G; Klinefelter, Gary R; Goldman, Jerome M; Best, Deborah S; McDonald, Anthony; Strader, Lillian F; Suarez, Juan D; Murr, Ashley S; Thillainadarajah, Inthirany; Hunter, E Sidney; Richardson, Susan D; Speth, Thomas F; Miltner, Richard J; Pressman, Jonathan G; Teuschler, Linda K; Rice, Glenn E; Moser, Virginia C; Luebke, Robert W; Simmons, Jane Ellen

2013-09-17

Some epidemiological studies report associations between drinking water disinfection byproducts (DBPs) and adverse reproductive/developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. Using a multigenerational rat bioassay, we evaluated an environmentally relevant "whole" mixture of DBPs representative of chlorinated drinking water, including unidentified DBPs as well as realistic proportions of known DBPs at low-toxicity concentrations. Source water from a water utility was concentrated 136-fold, chlorinated, and provided as drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) continued exposures and were bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight and prenatal loss. No adverse effects were observed for pup weight, prenatal loss, pregnancy rate, gestation length, puberty onset in males, growth, estrous cycles, hormone levels, immunological end points, and most neurobehavioral end points. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These results highlight areas for future research, while the largely negative findings, particularly for pup weight and prenatal loss, are notable.

The Observer Effect and Its Impact on Staff Behavior in an Acquired Brain Injury Neurobehavioral Treatment Setting

ERIC Educational Resources Information Center

Guercio, John M.; Dixon, Mark R.

2011-01-01

Staff in three neurobehavioral residential settings (5 in each residence for a total of 15 staff) were trained on specific positive interaction behaviors in a multiple baseline design. Staff in each of the residences were provided with recommended behaviors for interacting with residents through an observational procedure where they observed and…

Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results

PubMed Central

Himes, Sarah K.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Smith, Lynne M.; Arria, Amelia M.; Grotta, Sheri A. Della; Dansereau, Lynne M.; Abar, Beau; Neal, Charles R.; Lester, Barry M.; Huestis, Marilyn A.

2014-01-01

Background The objective was to evaluate effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Methods Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child’s neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared to child hair results. Results A total of 264 children were evaluated. Significantly more PME children (n=133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n=131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared to PME children without postnatal exposure. Conclusions Child hair testing offered a non-invasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years. PMID:24518561

Risk of neurobehavioral disinhibition in prenatal methamphetamine-exposed young children with positive hair toxicology results.

PubMed

Himes, Sarah K; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Smith, Lynne M; Arria, Amelia M; Della Grotta, Sheri A; Dansereau, Lynne M; Abar, Beau; Neal, Charles R; Lester, Barry M; Huestis, Marilyn A

2014-08-01

The objective was to evaluate the effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa, and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child's neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared with child hair results. A total of 264 children were evaluated. Significantly more PME children (n = 133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n = 131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared with PME children without postnatal exposure. Child hair testing offered a noninvasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years.

Research needs for assessing iodine intake, iodine status, and the effects of maternal iodine supplementation12

PubMed Central

Ershow, Abby G; Coates, Paul M; Swanson, Christine A

2016-01-01

The Office of Dietary Supplements of the NIH convened 3 workshops on iodine nutrition in Rockville, Maryland, in 2014. The purpose of the current article is to summarize and briefly discuss a list of research and resource needs developed with the input of workshop participants. This list is composed of the basic, clinical, translational, and population studies required for characterizing the benefits and risks of iodine supplementation, along with related data, analyses, evaluations, methods development, and supporting activities. Ancillary studies designed to use the participant, biological sample, and data resources of ongoing and completed studies (including those not originally concerned with iodine) may provide an efficient, cost-effective means to address some of these research and resource needs. In the United States, the foremost question is whether neurobehavioral development in the offspring of mildly to moderately iodine-deficient women is improved by maternal iodine supplementation during pregnancy. It is important to identify the benefits and risks of iodine supplementation in all population subgroups so that supplementation can be targeted, if necessary, to avoid increasing the risk of thyroid dysfunction and related adverse health effects in those with high iodine intakes. Ultimately, there will be a need for well-designed trials and other studies to assess the impact of maternal supplementation on neurodevelopmental outcomes in the offspring. However, 2 basic information gaps loom ahead of such a study: the development of robust, valid, and convenient biomarkers of individual iodine status and the identification of infant and toddler neurobehavioral development endpoints that are sensitive to mild maternal iodine deficiency during pregnancy and its reversal by supplementation. PMID:27534640

Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes.

PubMed

Brunssen, Susan H; Moy, Sheryl S; Toews, Arrel D; McPherson, Christopher A; Harry, G Jean

2013-01-01

Adverse neurodevelopmental outcomes are linked to perinatal production of inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for maternal elevation in IL-6 has been established in determining neurobehavioral outcomes in the offspring and considered the primary target mediating the fetal inflammatory response, questions remain as to the specific actions of IL-6 on the developing brain. CD-1 male mice received a subdural injection of the bioactive fusion protein, hyper IL-6 (HIL-6) on postnatal-day (PND)4 and assessed from preweaning until adulthood. Immunohistochemical evaluation of astrocytes and microglia and mRNA levels for pro-inflammatory cytokines and host response genes indicated no evidence of an acute neuroinflammatory injury response. HIL-6 accelerated motor development and increased reactivity to stimulation and number of entries in a light/dark chamber, decreased ability to learn to withhold a response in passive avoidance, and effected deficits in social novelty behavior. No changes were observed in motor activity, pre-pulse startle inhibition, or learning and memory in the Morris water maze or radial arm maze, as have been reported for models of more severe developmental neuroinflammation. In young animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP processes in the cortex was evident by immunohistochemistry. The non-hydroxy cerebroside fraction of cerebral lipids was increased. These results provide evidence for selective effects of IL-6 signaling, particularly trans-signaling, in the developing brain in the absence of a general neuroinflammatory response. These data contribute to our further understanding of the multiple aspects of IL-6 signaling in the developing brain. Published by Elsevier Inc.

The effect of occupational exposure to benzo[a]pyrene on neurobehavioral function in coke oven workers.

PubMed

Qiu, Chongying; Peng, Bin; Cheng, Shuqun; Xia, Yinyin; Tu, Baijie

2013-03-01

Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (B[a]P), known as an indicator species for PAH contamination, is a neurobehavioral toxicant. The purpose of the study was to evaluate the relationship between B[a]P exposure, a B[a]P-related urinary metabolite and neurobehavioral function among coke oven workers. Coke oven workers and oxygen factory workers participated in this study. B[a]P exposure was monitored by air sampling pump, and urinary 1-hydroxypyrene (1-OHP) level was detected with high performance liquid chromatography (HPLC). A questionnaire and the neurobehavioral core test battery (NCTB) were administered to all subjects. B[a]P-exposed workers were found to have higher urinary 1-OHP levels and worse NCTB performances on eight items than control workers. B[a]P concentrations were higher in the coke oven plant than that in the controls' workplace. The performances on simple reaction time, correct pursuit aiming, and error pursuit aiming decreased with increasing airborne B[a]P in coke oven workers. There were significant correlations between urinary 1-OHP level and six items of the NCTB. Occupational exposure to B[a]P is associated with neurobehavioral function impairment in coke oven workers. Copyright © 2012 Wiley Periodicals, Inc.

δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 (ALAD2) and Peptide Transporter 2*2 Haplotype (hPEPT2*2) Differently Influence Neurobehavior in Low-Level Lead Exposed Children

PubMed Central

Sobin, Christina; Gisel Flores-Montoya, Mayra; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2014-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1 to 11.8 years. Ninety-six percent of children had BLLs < 5.0 µg/dL. After adjusting for covariates (sex, age and mother’s level of education) and sibling exclusion (N = 252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. PMID:25514583

δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter 2*2 haplotype (hPEPT2*2) differently influence neurobehavior in low-level lead exposed children.

PubMed

Sobin, Christina; Flores-Montoya, Mayra Gisel; Gutierrez, Marisela; Parisi, Natali; Schaub, Tanner

2015-01-01

Delta-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter haplotype 2*2 (hPEPT2*2) through different pathways can increase brain levels of delta-aminolevulinic acid and are associated with higher blood lead burden in young children. Past child and adult findings regarding ALAD2 and neurobehavior have been inconsistent, and the possible association of hPEPT2*2 and neurobehavior has not yet been examined. Mean blood lead level (BLL), genotype, and neurobehavioral function (fine motor dexterity, working memory, visual attention and short-term memory) were assessed in 206 males and 215 females ages 5.1-11.8years. Ninety-six percent of children had BLLs<5.0μg/dl. After adjusting for covariates (sex, age and mother's level of education) and sibling exclusion (N=252), generalized linear mixed model analyses showed opposite effects for the ALAD2 and hPEPT2*2 genetic variants. Significant effects for ALAD2 were observed only as interactions with BLL and the results suggested that ALAD2 was neuroprotective. As BLL increased, ALAD2 was associated with enhanced visual attention and enhanced working memory (fewer commission errors). Independent of BLL, hPEPT2*2 predicted poorer motor dexterity and poorer working memory (more commission errors). BLL alone predicted poorer working memory from increased omission errors. The findings provided further substantiation that (independent of the genetic variants examined) lowest-level lead exposure disrupted early neurobehavioral function, and suggested that common genetic variants alter the neurotoxic potential of low-level lead. ALAD2 and hPEPT2*2 may be valuable markers of risk, and indicate novel mechanisms of lead-induced neurotoxicity. Longitudinal studies are needed to examine long-term influences of these genetic variants on neurobehavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Late Dose-Response Effects of Prenatal Cocaine Exposure on Newborn Neurobehavioral Performance

PubMed Central

Tronick, Edward Z.; Frank, Deborah A.; Cabral, Howard; Mirochnick, Mark; Zuckerman, Barry

2008-01-01

Objective To determine in a representative sample of full-term urban newborns of English-speaking mothers whether an immediate or late dose-response effect could be demonstrated between prenatal cocaine exposure and newborn neurobehavioral performance, controlling for confounding factors. Methods The Neonatal Behavioral Assessment Scale (NBAS) was administered by masked examiners to a total sample of 251 clinically healthy, full-term infants at 2 days and/or 17 days. Three in utero cocaine exposure groups were defined: heavily exposed (n = 44, >75th percentile self-reported days of use during pregnancy and/or >75th percentile of meconium benzoylecognine concentration); lightly exposed (n = 79, less than both 75th percentiles); and unexposed (n = 101, no positive biological or self-report marker). At the 3-week examination there were 38 heavily exposed, 73 lightly exposed, and 94 unexposed infants. Controlling for infant birth weight, gestational age, infant age at the time of examination, mothers’ age, perinatal risk, obstetric medication, and alcohol, marijuana, and cigarette use, a regression analysis evaluated the effects of levels of cocaine exposure on NBAS performance. Results No neurobehavioral effects of exposure on the newborn NBAS cluster scores or on the qualifier scores were found when confounders were controlled for at 2 to 3 days of age. At 3 weeks, after controlling for covariates, a significant dose effect was observed, with heavily exposed infants showing poorer state regulation and greater excitability. Conclusions These findings demonstrate specific dose-related effects of cocaine on 3-week neurobehavioral performance, particularly for the regulation of arousal, which was not observed in the first few days of life. PMID:8668416

NEUROBEHAVIORAL TERATOGENICITY OF SARIN IN AN AVIAN MODEL

PubMed Central

Yanai, Joseph; Pinkas, Adi; Seidler, Frederic J.; Ryde, Ian T.; Van der Zee, Eddy A.; Slotkin, Theodore A.

2009-01-01

Nerve gas organophosphates like sarin are likely to be used in urban terrorism, leading to widespread exposures of pregnant women and young children. Here, we established a model for sarin neurobehavioral teratogenicity in the developing chick so as to explore the consequences of apparently subtoxic sarin exposure and the mechanisms underlying synaptic and behavioral deficits. Chicken eggs were injected with sarin (2, 6 and 12 μg/kg) on incubation days 2 and 6, treatments that did not decrease hatching and did not evoke dysmorphology. After hatching the chicks were tested for filial imprinting and neurochemical markers known to be critical for imprinting. Imprinting was reduced at 2 and 6 μg/kg but not at the highest dose. Acetylcholinesterase and choline acetyltransferase were unaffected but sarin reduced the concentration of the high-affinity choline transporter, the rate-limiting factor in acetylcholine utilization. The concentration of PKC isoforms was assessed in the imprinting-related intermediate part of the medial hyperstriatum ventrale, the region most closely associated with cholinergic function in imprinting behavior. Sarin reduced the concentration of all isoforms (α, β, γ) with a similar, biphasic dose-response curve to that seen for behavioral performance, a relationship noted in previous work with organophosphate pesticides. Our results indicate that otherwise subtoxic exposures to sarin produce neurodevelopmental deficits; since we utilized a chick model, which is devoid of maternal confounds that are present in mammalian development, the adverse effects of sarin are mediated directly in the developing organism. PMID:19660543

Neurobehavioral assessment of children and adolescents attending a developmental disabilities clinic.

PubMed

Brasić, James Robert; Barnett, Jacqueline Y; Kowalik, S; Tsaltas, Margaret Owen; Ahmad, Raheela

2004-12-01

Although the risk of the eventual development of tardive dyskinesia and other persistent adverse effects of neuroleptics is high, among adults with mental retardation and other developmental disabilities, neuroleptics may ameliorate dyskinesias, aggression, and inattention. The effects of traditional neuroleptics on a comparable population of children and adolescents with mental retardation and other developmental disabilities are unknown. The objective of this study was to develop an assessment battery to describe the effects of traditional neuroleptics on the behavior and movements of a small sample of children and adolescents with mental retardation and other developmental disabilities. 13 children and adolescents aged 6 to 16 years attending a developmental disabilities clinic were evaluated utilizing a Movement Assessment Battery to measure behavior and motions. Five subjects took traditional neuroleptic medications. Trained raters can reliably assess the movements and behaviors of children and adolescents with multiple handicaps. Children and adolescents with developmental disabilities may be vulnerable to experience functional impairment and akathisia, tics, and other dyskinesias when administered traditional neuroleptic medications.

Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

NASA Technical Reports Server (NTRS)

Dijk, Derk-Jan

1999-01-01

Total sleep deprivation leads to decrements in neurobehavioral performance and changes in electroencephalographic (EEG) oscillations as well as the incidence of slow eye movements ad detected in the electro-oculogram (EOG) during wakefulness. Although total sleep deprivation is a powerful tool to investigate the association of EEG/EOG and neurobehavioral decrements, sleep loss during space flight is usual only partial. Furthermore exposure to the microgravity environment leads to changes in sodium and volume homeostasis and associated renal and cardio-endocrine responses. Some of these changes can be induced in head down tilt bedrest studies. We integrate research tools and research projects to enhance the fidelity of the simulated conditions of space flight which are characterized by complexity and mutual interactions. The effectiveness of countermeasures and physiologic mechanisms underlying neurobehavioral changes and renal-cardio endocrine changes are investigated in Project 3 of the Human Performance Team and Project 3 of the Cardiovascular Alterations Team respectively. Although the. specific aims of these two projects are very different, they employ very similar research protocols. Thus, both projects investigate the effects of posture/bedrest and sleep deprivation (total or partial) on outcome measures relevant to their specific aims. The main aim of this enhancement grant is to exploit the similarities in research protocols by including the assessment of outcome variables relevant to the Renal-Cardio project in the research protocol of Project 3 of the Human Performance Team and by including the assessment of outcome variables relevant to the Quantitative EEG and Sleep Deprivation Project in the research protocols of Project 3 of the Cardiovascular Alterations team. In particular we will assess Neurobehavioral Function and Waking EEG in the research protocols of the renal-cardio endocrine project and renin-angiotensin and cardiac function in the research protocol of the Quantitative EEG and Waking Neurobehavioral Function project. This will allow us to investigate two additional specific aims: 1) Test the hypothesis that chronic partial sleep deprivation during a 17 day bed rest experiment results in deterioration of neurobehavioral function during waking and increases in EEG power density in the theta frequencies, especially in frontal areas of the brain, as well as the nonREM- REM cycle dependent modulation of heart-rate variability. 2) Test the hypothesis that acute total sleep deprivation modifies the circadian rhythm of the renin-angiotensin system, changes the acute responsiveness of this system to posture beyond what a microgravity environment alone does and affects the nonREM-REM cycle dependent modulation of heart-rate variability.

Placebo-Controlled Trial of Familiar Auditory Sensory Training for Acute Severe Traumatic Brain Injury: A Preliminary Report.

PubMed

Pape, Theresa Louise-Bender; Rosenow, Joshua M; Steiner, Monica; Parrish, Todd; Guernon, Ann; Harton, Brett; Patil, Vijaya; Bhaumik, Dulal K; McNamee, Shane; Walker, Matthew; Froehlich, Kathleen; Burress, Catherine; Odle, Cheryl; Wang, Xue; Herrold, Amy A; Zhao, Weihan; Reda, Domenic; Mallinson, Trudy; Conneely, Mark; Nemeth, Alexander J

2015-07-01

Sensory stimulation is often provided to persons incurring severe traumatic brain injury (TBI), but therapeutic effects are unclear. This preliminary study investigated neurobehavioral and neurophysiological effects related to sensory stimulation on global neurobehavioral functioning, arousal, and awareness. A double-blind randomized placebo-controlled trial where 15 participants in states of disordered consciousness (DOC), an average of 70 days after TBI, were provided either the Familiar Auditory Sensory Training (FAST) or Placebo of silence. Global neurobehavioral functioning was measured with the Disorders of Consciousness Scale (DOCS). Arousal and awareness were measured with the Coma-Near-Coma (CNC) scale. Neurophysiological effect was measured using functional magnetic resonance imaging (fMRI). FAST (n = 8) and Placebo (n = 7) groups each showed neurobehavioral improvement. Mean DOCS change (FAST = 13.5, SD = 8.2; Placebo = 18.9, SD = 15.6) was not different, but FAST patients had significantly (P = .049; 95% confidence interval [CI] = -1.51, -.005) more CNC gains (FAST = 1.01, SD = 0.60; Placebo = 0.25, SD = 0.70). Mixed-effects models confirm CNC findings (P = .002). Treatment effect, based on CNC, is large (d = 1.88, 95% CI = 0.77, 3.00). Number needed to treat is 2. FAST patients had more fMRI activation in language regions and whole brain (P values <.05) resembling healthy controls' activation. For persons with DOC 29 to 170 days after TBI, FAST resulted in CNC gains and increased neural responsivity to vocal stimuli in language regions. Clinicians should consider providing the FAST to support patient engagement in neurorehabilitation. © The Author(s) 2015.

Neurobehavioral Integrity of Chimpanzee Newborns: Comparisons across groups and across species reveal gene-environment interaction effects

PubMed Central

Bard, Kim A.; Brent, Linda; Lester, Barry; Worobey, John; Suomi, Stephen J.

2014-01-01

The aims of this article are to describe the neurobehavioral integrity of chimpanzee newborns, to investigate how early experiences affect the neurobehavioral organization of chimpanzees, and to explore species differences by comparing chimpanzee newborns to a group of typically developing human newborns. Neurobehavioral integrity related to orientation, motor performance, arousal, and state regulation of 55 chimpanzee (raised in four different settings) and 42 human newborns was measured with the Neonatal Behavioral Assessment Scale (NBAS) a semi-structured 25-minute interactive assessment. Thirty-eight chimpanzees were tested every other day from birth, and analyses revealed significant developmental changes in 19 of 27 NBAS scores. The cross-group and cross-species comparisons were conducted at 2 and 30 days of age. Among the 4 chimpanzee groups, significant differences were found in 23 of 24 NBAS scores. Surprisingly, the cross-species comparisons revealed that the human group was distinct in only 1 of 25 NBAS scores (the human group had significantly less muscle tone than all the chimpanzee groups). The human group was indistinguishable from at least one of the chimpanzee groups in the remaining 24 of 25 NBAS scores. The results of this study support the conclusion that the interplay between genes and environment, rather than genes alone or environment alone, accounts for phenotypic expressions of newborn neurobehavioral integrity in hominids. PMID:25110465

[Psychological and neurobehavioral effects of aluminum on exposed workers].

PubMed

Guo, G; Ma, H; Wang, X

1998-09-01

To explore neurotoxicity and the changes in psychological and neurobehavioral functions in workers exposed to aluminum. Psychological status and neurobehavioral functions of 103 exposed workers and 64 controls were examined with Neurobehavioral Core Test Battery recommended by World Health Organization (WHO), and meanwhile, air concentrations of aluminum in the workplaces and urine levels of aluminum in the exposed workers were determined. Urine levels of aluminum in the exposed workers were markedly higher than those in non-exposed controls, with a statistical significance. Scores for tension, depression, anger, fatigue and confusion in the workers exposed to aluminum for more than ten years were significantly more than those in non-exposed controls. Scores of the performance of Santa Ana, digit symbol and pursuit aiming in the former were significantly lower, and no other changes in psychological and behavioral functions was found in workers exposed for less than ten years, except for their scores of pursuit aiming. Obvious changes in psychological status, neuromotor speed and their accuracy were observed in workers exposed to aluminum for a long term.

Neurobehavioural and neurodevelopmental effects of pesticide exposures

PubMed Central

London, Leslie; Beseler, Cheryl; Bouchard, Maryse F.; Bellinger, David C.; Colosio, Claudio; Grandjean, Philippe; Harari, Raul; Kootbodien, Tahira; Kromhout, Hans; Little, Francesca; Meijster, Tim; Moretto, Angelo; Rohlman, Diane S.; Stallones, Lorann

2012-01-01

The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes amongst occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or pre-natal exposure. PMID:22269431

Dynamic Circadian Modulation in a Biomathematical Model for the Effects of Sleep and Sleep Loss on Waking Neurobehavioral Performance

PubMed Central

McCauley, Peter; Kalachev, Leonid V.; Mollicone, Daniel J.; Banks, Siobhan; Dinges, David F.; Van Dongen, Hans P. A.

2013-01-01

Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation—and thereby sensitivity to neurobehavioral impairment from sleep loss—is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation—and thus sensitivity to sleep loss—depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work. Citation: McCauley P; Kalachev LV; Mollicone DJ; Banks S; Dinges DF; Van Dongen HPA. Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance. SLEEP 2013;36(12):1987-1997. PMID:24293775

Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis

PubMed Central

Sun, Guifan; Zhang, Ying; Grandjean, Philippe

2012-01-01

Background: Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children’s neurodevelopment. Objective: We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development. Methods: We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg’s funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies. Results: The standardized weighted mean difference in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease. Conclusions: The results support the possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment. PMID:22820538

Neurobehavior disinhibition, parental substance use disorder, neighborhood quality and development of cannabis use disorder in boys☆

PubMed Central

Ridenour, Ty A.; Tarter, Ralph E.; Reynolds, Maureen; Mezzich, Ada; Kirisci, Levent; Vanyukov, Michael

2009-01-01

This prospective investigation examined the contribution of neighborhood context and neurobehavior disinhibition to the association between substance use disorder (SUD) in parents and cannabis use disorder in their sons. It was hypothesized that both neighborhood context and son’s neurobehavior disinhibition mediate this association. Two hundred and sixteen boys were tracked from ages 10–12 to age 22. The extent to which neighborhood context and neurobehavior disinhibition mediate the association between parental SUD and son’s cannabis use disorder was evaluated using structural equation modeling. The best fitting model positioned neighborhood context and neurobehavior disinhibition as mediators of the association between parental SUD and cannabis use disorder in sons. Neurobehavior disinhibition also was a mediator of the association between neighborhood context and son’s cannabis use. The implications of this pattern of association between parental SUD, neighborhood context and individual risk for SUD for improving prevention are discussed. PMID:19268495

Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid.

PubMed

Kim, Pitna; Park, Jin Hee; Kwon, Kyoung Ja; Kim, Ki Chan; Kim, Hee Jin; Lee, Jong Min; Kim, Hahn Young; Han, Seol-Heui; Shin, Chan Young

2013-01-01

Ginseng is one of the most widely used medicinal plants, which belongs to the genus Panax. Compared to uncured white ginseng, red ginseng has been generally regarded to produce superior pharmacological effects with lesser side/adverse effects, which made it popular in a variety of formulation from tea to oriental medicine. Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring. VPA-induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng (KRG) in a dose dependent manner. Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open-field test. KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level. These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

PubMed Central

Soontornniyomkij, Virawudh; Kesby, James P.; Morgan, Erin E.; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G.; Grant, Igor

2016-01-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value. PMID:27484318

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models.

PubMed

Soontornniyomkij, Virawudh; Kesby, James P; Morgan, Erin E; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G; Grant, Igor

2016-09-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.

Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.

PubMed

Crouse, Lee C B; Lent, Emily May; Leach, Glenn J

2015-01-01

3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d. © The Author(s) 2015.

Neurobehavioral effects of aspartame consumption.

PubMed

Lindseth, Glenda N; Coolahan, Sonya E; Petros, Thomas V; Lindseth, Paul D

2014-06-01

Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40-50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health. © 2014 Wiley Periodicals, Inc.

Neurobehavioral Effects of Aspartame Consumption

PubMed Central

Lindseth, Glenda N.; Coolahan, Sonya E.; Petros, Thomas V.; Lindseth, Paul D.

2017-01-01

Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40–50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health. PMID:24700203

Uncovering Physiologic Mechanisms of Circadian Rhythms and Sleep/Wake Regulation Through Mathematical Modeling

DTIC Science & Technology

2007-06-01

the effects of rest -activity-work schedules and interventions on neurobehavioral function. In a symposium titled “Modeling Human Neurobehavioral...physio- logic basis of Process S. The mutually inhibitory neu- ronal populations, together with the surrogate Process S, have the potential to serve...as a function of both ta and φ (Czeisler et al., 1999). Briefly, by imposing a cyclic pattern of bed rest and wake time at a period, T, sufficiently

Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.

PubMed

Boschen, K E; Keller, S M; Roth, T L; Klintsova, A Y

The long-term effects of developmental alcohol and stress exposure are well documented in both humans and non-human animal models. Damage to the brain and attendant life-long impairments in cognition and increased risk for psychiatric disorders are debilitating consequences of developmental exposure to alcohol and/or psychological stress. Here we discuss evidence for a role of epigenetic mechanisms in mediating these consequences. While we highlight some of the common ways in which stress or alcohol impact the epigenome, we point out that little is understood of the epigenome's response to experiencing both stress and alcohol exposure, though stress is a contributing factor as to why women drink during pregnancy. Advancing our understanding of this relationship is of critical concern not just for the health and well-being of individuals directly exposed to these teratogens, but for generations to come. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative EEG Monitoring of Vigilance: Effects of Sleep Deprivation, Circadian Phase and Sympathetic Activation

NASA Technical Reports Server (NTRS)

Dijk, Derk-Jan

1999-01-01

Shuttle astronauts typically sleep only 6 to 6.5 hours per day while in orbit. This sleep loss is related to recurrent sleep cycle shifting--due to mission-dependent orbital mechanics and mission duration requirements-- and associated circadian displacement of sleep, the operational demands of space flight, noise and space motion sickness. Such sleep schedules are known to produce poor subjective sleep quality, daytime sleepiness, reduced attention, negative mood, slower reaction times, and impaired daytime alertness. Countermeasures to allow crew members to obtain an adequate amount of sleep and maintain adequate levels of neurobehavioral performance are being developed and investigated. However, it is necessary to develop methods that allow effective and attainable in-flight monitoring of vigilance to evaluate the effectiveness of these countermeasures and to detect and predict online critical decrements in alertness/performance. There is growing evidence to indicate that sleep loss and associated decrements in neurobehavioral function are reflected in the spectral composition of the electroencephalogram (EEG) during wakefulness as well as in the incidence of slow eye movements recorded by the electro-oculogram (EOG). Further-more, our preliminary data indicated that these changes in the EEG during wakefulness are more pronounced when subjects are in a supine posture, which mimics some of the physiologic effects of microgravity. Therefore, we evaluate the following hypotheses: (1) that during a 40-hour period of wakefulness (i.e., one night of total sleep deprivation) neurobehavioral function deteriorates, the incidence of slow eye-movements and EEG power density in the theta frequencies increases especially in frontal areas of the brain; (2) that the sleep deprivation induced deterioration of neurobehavioral function and changes in the incidence of slow eye movements and the spectral composition of the EEG are more pronounced when subjects are in a supine position; and (3) that based on assessment of slow-eye movements and quantitative on-line topographical analyses of EEG during wakefulness an EEG and or EOG parameter can be derived/constructed which accurately predicts changes in neurobehavioral function.

Transplacental Exposure to AZT Induces Adverse Neurochemical and Behavioral Effects in a Mouse Model: Protection by L-Acetylcarnitine

PubMed Central

Venerosi Pesciolini, Aldina; Tramutola, Antonella; Ajmone-Cat, Maria Antonietta; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giovine, Angela; Peluso, Gianfranco; Minghetti, Luisa; Nicolai, Raffaella; Calamandrei, Gemma; Casolini, Paola

2013-01-01

Maternal-fetal HIV-1 transmission can be prevented by administration of AZT, alone or in combination with other antiretroviral drugs to pregnant HIV-1-infected women and their newborns. In spite of the benefits deriving from this life-saving prophylactic therapy, there is still considerable uncertainty on the potential long-term adverse effects of antiretroviral drugs on exposed children. Clinical and experimental studies have consistently shown the occurrence of mitochondrial dysfunction and increased oxidative stress following prenatal treatment with antiretroviral drugs, and clinical evidence suggests that the developing brain is one of the targets of the toxic action of these compounds possibly resulting in behavioral problems. We intended to verify the effects on brain and behavior of mice exposed during gestation to AZT, the backbone of antiretroviral therapy during human pregnancy. We hypothesized that glutamate, a neurotransmitter involved in excitotoxicity and behavioral plasticity, could be one of the major actors in AZT-induced neurochemical and behavioral alterations. We also assessed the antioxidant and neuroprotective effect of L-acetylcarnitine, a compound that improves mitochondrial function and is successfully used to treat antiretroviral-induced polyneuropathy in HIV-1 patients. We found that transplacental exposure to AZT given per os to pregnant mice from day 10 of pregnancy to delivery impaired in the adult offspring spatial learning and memory, enhanced corticosterone release in response to acute stress, increased brain oxidative stress also at birth and markedly reduced expression of mGluR1 and mGluR5 subtypes and GluR1 subunit of AMPA receptors in the hippocampus. Notably, administration during the entire pregnancy of L-acetylcarnitine was effective in preventing/ameliorating the neurochemical, neuroendocrine and behavioral adverse effects induced by AZT in the offspring. The present preclinical findings provide a mechanistic hypothesis for the neurobehavioral effects of AZT and strongly suggest that preventive administration of L-acetylcarnitine might be effective in reducing the neurological side-effects of antiretroviral therapy in fetus/newborn. PMID:23409035

NICU Network Neurobehavioral Profiles Predict Developmental Outcomes in a Low Risk Sample

PubMed Central

Sucharew, Heidi; Khoury, Jane C.; Xu, Yingying; Succop, Paul; Yolton, Kimberly

2012-01-01

Summary Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. In conclusion, three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations. PMID:22686386

Three Scoring Approaches to the Neurobehavioral Symptom Inventory for Measuring Clinical Change in Service Members Receiving Intensive Treatment for Combat-Related mTBI.

PubMed

Dretsch, Michael; Bleiberg, Joseph; Williams, Kathy; Caban, Jesus; Kelly, James; Grammer, Geoffrey; DeGraba, Thomas

2016-01-01

To examine the use of the Neurobehavioral Symptom Inventory to measure clinical changes over time in a population of US service members undergoing treatment of mild traumatic brain injury and comorbid psychological health conditions. A 4-week, 8-hour per day, intensive, outpatient, interdisciplinary, comprehensive treatment program at the National Intrepid Center of Excellence in Bethesda, Maryland. Three hundred fourteen active-duty service members being treated for combat-related comorbid mild traumatic brain injury and psychological health conditions. Repeated-measures, retrospective analysis of a single-group using a pretest-posttest treatment design. Three Neurobehavioral Symptom Inventory scoring methods: (1) a total summated score, (2) the 3-factor method, and (3) the 4-factor method (with and without orphan items). All 3 scoring methods yielded statistically significant within-subject changes between admission and discharge. The evaluation of effect sizes indicated that the 3 different Neurobehavioral Symptom Inventory scoring methods were comparable. Findings indicate that the different scoring methods all have potential for assessing clinical changes in symptoms for groups of patients undergoing treatment, with no clear advantage with any one method.

Neurobehavioral effects of transportation noise in primary schoolchildren: a cross-sectional study

PubMed Central

2010-01-01

Background Due to shortcomings in the design, no source-specific exposure-effect relations are as yet available describing the effects of noise on children's cognitive performance. This paper reports on a study investigating the effects of aircraft and road traffic noise exposure on the cognitive performance of primary schoolchildren in both the home and the school setting. Methods Participants were 553 children (age 9-11 years) attending 24 primary schools around Schiphol Amsterdam Airport. Cognitive performance was measured by the Neurobehavioral Evaluation System (NES), and a set of paper-and-pencil tests. Multilevel regression analyses were applied to estimate the association between noise exposure and cognitive performance, accounting for demographic and school related confounders. Results Effects of school noise exposure were observed in the more difficult parts of the Switching Attention Test (SAT): children attending schools with higher road or aircraft noise levels made significantly more errors. The correlational pattern and factor structure of the data indicate that the coherence between the neurobehavioral tests and paper-and-pencil tests is high. Conclusions Based on this study and previous scientific literature it can be concluded that performance on simple tasks is less susceptible to the effects of noise than performance on more complex tasks. PMID:20515466

Nursing care of the brain injury patient on a locked neurobehavioral unit.

PubMed

Becker, Christine

2012-01-01

Behavioral problems after a brain injury can be extremely challenging for those working with brain injured people. Nursing staff must be familiar with commonly used post brain injury medications and their effects, behavioral management plans, appropriate use of restrictive devices, and verbal or physical crisis intervention techniques when necessary. Rehabilitation nurses caring for brain injured patients on a locked neurobehavioral unit must maintain continual training and specific competence in this environment to ensure patient and staff safety. © 2012 Association of Rehabilitation Nurses.

Ambient Light Intensity, Actigraphy, Sleep and Respiration, Circadian Temperature and Melatonin Rhythms and Daytime Performance of Crew Members During Space Flight on STS-90 and STS-95 Missions

NASA Technical Reports Server (NTRS)

Czeisler, Charles A.; Dijk, D.-J.; Neri, D. F.; Hughes, R. J.; Ronda, J. M.; Wyatt, J. K.; West, J. B.; Prisk, G. K.; Elliott, A. R.; Young, L. R.

1999-01-01

Sleep disruption and associated waking sleepiness and fatigue are common during space flight. A survey of 58 crew members from nine space shuttle missions revealed that most suffered from sleep disruption, and reportedly slept an average of only 6.1 hours per day of flight as compared to an average of 7.9 hours per day on the ground. Nineteen percent of crewmembers on single shift missions and 50 percent of the crewmembers in dual shift operations reported sleeping pill usage (benzodiazepines) during their missions. Benzodiazepines are effective as hypnotics, however, not without adverse side effects including carryover sedation and performance impairment, anterograde amnesia, and alterations in sleep EEG. Our preliminary ground-based data suggest that pre-sleep administration of 0.3 mg of the pineal hormone melatonin may have the acute hypnotic properties needed for treating the sleep disruption of space flight without producing the adverse side effects associated with benzodiazepines. We hypothesize that pre-sleep administration of melatonin will result in decreased sleep latency, reduced nocturnal sleep disruption, improved sleep efficiency, and enhanced next-day alertness and cognitive performance both in ground-based simulations and during the space shuttle missions. Specifically, we have carried out experiments in which: (1) ambient light intensity aboard the space shuttle is assessed during flight; (2) the impact of space flight on sleep (assessed polysomnographically and actigraphically), respiration during sleep, circadian temperature and melatonin rhythms, waking neurobehavioral alertness and performance is assessed in crew members of the Neurolab and STS-95 missions; (3) the effectiveness of melatonin as a hypnotic is assessed independently of its effects on the phase of the endogenous circadian pacemaker in ground-based studies, using a powerful experimental model of the dyssomnia of space flight; (4) the effectiveness of melatonin as a hypnotic is assessed during the STS-90 (Neurolab) and STS-95 missions in a double-blind placebo-controlled trial. In both flight-based experiments, the effects of melatonin on sleep stages and spectral composition of the EEG during sleep will be determined as well as its effects on daytime alertness and performance; (5) the impact of space flight on sleep and waking neurobehavioral alertness and performance in 30-45-year-old astronauts is compared with its impact in a 77-year-old astronaut. This case study is the first to assess the effects of space flight on an older individual. Because the investigators are still blind to the treatment in this double-blind, placebo-controlled trial, preliminary results will be presented independent of the drug condition.

2B-Alert Web: An Open-Access Tool for Predicting the Effects of Sleep/Wake Schedules and Caffeine Consumption on Neurobehavioral Performance.

PubMed

Reifman, Jaques; Kumar, Kamal; Wesensten, Nancy J; Tountas, Nikolaos A; Balkin, Thomas J; Ramakrishnan, Sridhar

2016-12-01

Computational tools that predict the effects of daily sleep/wake amounts on neurobehavioral performance are critical components of fatigue management systems, allowing for the identification of periods during which individuals are at increased risk for performance errors. However, none of the existing computational tools is publicly available, and the commercially available tools do not account for the beneficial effects of caffeine on performance, limiting their practical utility. Here, we introduce 2B-Alert Web, an open-access tool for predicting neurobehavioral performance, which accounts for the effects of sleep/wake schedules, time of day, and caffeine consumption, while incorporating the latest scientific findings in sleep restriction, sleep extension, and recovery sleep. We combined our validated Unified Model of Performance and our validated caffeine model to form a single, integrated modeling framework instantiated as a Web-enabled tool. 2B-Alert Web allows users to input daily sleep/wake schedules and caffeine consumption (dosage and time) to obtain group-average predictions of neurobehavioral performance based on psychomotor vigilance tasks. 2B-Alert Web is accessible at: https://2b-alert-web.bhsai.org. The 2B-Alert Web tool allows users to obtain predictions for mean response time, mean reciprocal response time, and number of lapses. The graphing tool allows for simultaneous display of up to seven different sleep/wake and caffeine schedules. The schedules and corresponding predicted outputs can be saved as a Microsoft Excel file; the corresponding plots can be saved as an image file. The schedules and predictions are erased when the user logs off, thereby maintaining privacy and confidentiality. The publicly accessible 2B-Alert Web tool is available for operators, schedulers, and neurobehavioral scientists as well as the general public to determine the impact of any given sleep/wake schedule, caffeine consumption, and time of day on performance of a group of individuals. This evidence-based tool can be used as a decision aid to design effective work schedules, guide the design of future sleep restriction and caffeine studies, and increase public awareness of the effects of sleep amounts, time of day, and caffeine on alertness. © 2016 Associated Professional Sleep Societies, LLC.

Evaluation of uncontrolled confounding in studies of environmental exposures and neurobehavioral testing in children.

PubMed

Mink, Pamela J; Goodman, Michael; Barraj, Leila M; Imrey, Harriet; Kelsh, Michael A; Yager, Janice

2004-07-01

Neurobehavioral tests are commonly used in studies of children exposed to low-level environmental concentrations of compounds known to be neurotoxic at higher levels. However, uncontrolled or incomplete control for confounding makes interpretation of results problematic because effects of confounders are often stronger than the effects of primary interest. We examined a priori the potential impact of confounding in a hypothetical study evaluating the association of a potentially neurotoxic environmental exposure with neurobehavioral function in children. We used 2 outcome measures: the Bayley Scales of Infant Development Mental Development Index and the Stanford-Binet Intelligence Scale Composite Score. We selected 3 potential confounders: maternal intelligence, home environment, and socioeconomic status as measured by years of parental education. We conducted 3 sets of analyses measuring the effect of each of the 3 confounding factors alone, 2 confounders acting simultaneously, and all 3 confounders acting simultaneously. Relatively small differences (0.5 standard deviations) in confounding variables between "exposed" and "unexposed" groups, if unmeasured and unaccounted for in the analysis, could produce spurious differences in cognitive test scores. The magnitude of this difference (3-10 points) has been suggested to have a meaningful impact in populations. The method of measuring confounders (eg, maternal intelligence) could also substantially affect the results. It is important to carefully consider the impact of potential confounders during the planning stages of an observational study. Study-to-study differences in neurobehavioral outcomes with similar environmental exposures could be partially explained by differences in the adjustment for confounding variables. Copyright 2004 Lippincott Williams and Wilkins

Neurobehavioral effects during experimental exposure to 1-octanol and isopropanol.

PubMed

van Thriel, Christoph; Kiesswetter, Erns; Blaszkewicz, Meinolf; Golka, Klaus; Seeber, Andreas

2003-04-01

The study examined acute neurobehavioral effects provoked by controlled exposure to 1-octanol and isopropanol among male volunteers. In a 29-m3 exposure laboratory, 24 male students (mean age 25.8 years) were exposed to 1-octanol and isopropanol. Each substance was used in two concentrations (0.1 and 6.4 ppm for 1-octanol; 34.9 and 189.9 ppm for isopropanol:). In a crossover design, each subject was exposed for 4 hours to the conditions. Twelve subjects reported enhanced chemical sensitivity; the other 12 were age-matched controls. At the onset and end of the exposures neurobehavioral tests were administered and symptoms were rated. At the end of the high and low isopropanol exposures the tiredness ratings were elevated, but no dose-dependence could be confirmed. For both substances and concentrations, the annoyance ratings increased during the exposure, but only for isopropanol did the increase show a dose-response relation. The subjects reported olfactory symptoms during the exposure to the high isopropanol and both 1-octanol concentrations. Isopropanol provoked no sensory irritation, whereas high 1-octanol exposure slightly enhanced it. Only among the subjects with enhanced chemical sensitivity were both 1-octanol concentrations associated with a stronger increase in annoyance, and lower detection rates were observed in a divided attention task. Previous studies reporting no neurobehavioral effects for isopropanol (up to 400 ppm) were confirmed. The results obtained for 1-octanol lacked dose-dependency, and their evaluation, is difficult. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task.

Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice.

PubMed

Sugawara, Norio; Nakai, Kunihiko; Nakamura, Tomoyuki; Ohba, Takashi; Suzuki, Keita; Kameo, Satomi; Satoh, Chieko; Satoh, Hiroshi

2006-05-01

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.

Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age.

PubMed

Boucher, Olivier; Burden, Matthew J; Muckle, Gina; Saint-Amour, Dave; Ayotte, Pierre; Dewailly, Eric; Nelson, Charles A; Jacobson, Sandra W; Jacobson, Joseph L

2011-05-01

The beneficial effects of prenatal and early postnatal intakes of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. The aim of this study was to examine the relation of n-3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test-Children's Version. Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n-3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA-related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n-3 PUFA intake in utero on memory function in school-age children.

Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age123

PubMed Central

Boucher, Olivier; Burden, Matthew J; Muckle, Gina; Saint-Amour, Dave; Ayotte, Pierre; Dewailly, Eric; Nelson, Charles A; Jacobson, Sandra W

2011-01-01

Background: The beneficial effects of prenatal and early postnatal intakes of omega-3 (n−3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. Objective: The aim of this study was to examine the relation of n−3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. Design: In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test–Children's Version. Results: Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n−3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA–related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. Conclusion: To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n−3 PUFA intake in utero on memory function in school-age children. PMID:21389181

Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodavanti, Prasada; Coburn, Cary; Moser, Virginia

2010-06-01

Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.7, 10.2, or 30.6 mg/kg/day DE-71 in corn oil by oral gavage from gestational day 6 to weaning. DE-71 did not alter maternal or male offspring body weights. However, female offspring were smaller compared with controls from postnatal days (PNDs) 35-60. Although several neurobehavioral endpoints were assessed, the only statistically significant behavioral findingmore » was a dose-by-age interaction in the number of rears in an open-field test. Developmental exposure to DE-71 caused severe hypothyroxinemia in the dams and early postnatal offspring. DE-71 also affected anogenital distance and preputial separation in male pups. Body weight gain over time, reproductive tissue weights, and serum testosterone concentrations at PND 60 were not altered. Mammary gland development of female offspring was significantly affected at PND 21. Congener-specific analysis of PBDEs indicated accumulation in all tissues examined. Highest PBDE concentrations were found in fat including milk, whereas blood had the lowest concentrations on a wet weight basis. PBDE concentrations were comparable among various brain regions. Thus, perinatal exposure to DE-71 leads to accumulation of PBDE congeners in various tissues crossing blood-placenta and blood-brain barriers, causing subtle changes in some parameters of neurobehavior and dramatic changes in circulating thyroid hormone levels, as well as changes in both male and female reproductive endpoints. Some of these effects are similar to those seen with PCBs, and the persistence of these changes requires further investigation.« less

Level of NICU Quality of Developmental Care and Neurobehavioral Performance in Very Preterm Infants

PubMed Central

Del Prete, Alberto; Bellù, Roberto; Tronick, Ed; Borgatti, Renato

2012-01-01

OBJECTIVE: To examine the relation between the neurobehavior of very preterm infants and the level of NICU quality of developmental care. METHODS: The neurobehavior of 178 very preterm infants (gestational age ≤29 weeks and/or birth weight ≤1500 g) from 25 NICUs participating in a large multicenter, longitudinal study (Neonatal Adequate Care for Quality of Life, NEO-ACQUA) was examined with a standardized neurobehavioral assessment, the NICU Network Neurobehavioral Scale (NNNS). A questionnaire, the NEO-ACQUA Quality of Care Checklist was used to evaluate the level of developmental care in each of the NICUs. A factor analyses applied to NEO-ACQUA Quality of Care Checklist produced 2 main factors: (1) the infant-centered care (ICC) index, which measures parents’ involvement in the care of their infant and other developmentally oriented care interventions, and (2) the infant pain management (IPM) index, which measures the NICU approach to and the procedures used for reducing infant pain. The relations between NNNS neurobehavioral scores and the 2 indexes were evaluated. RESULTS: Infants from NICUs with high scores on the ICC evidenced higher attention and regulation, less excitability and hypotonicity, and lower stress/abstinence NNNS scores than infants from low-care units. Infants from NICUs with high scores on the IPM evidenced higher attention and arousal, lower lethargy and nonoptimal reflexes NNNS scores than preterm infants from low-scoring NICUs. CONCLUSIONS: Very preterm infant neurobehavior was associated with higher levels of developmental care both in ICC and in IPM, suggesting that these practices support better neurobehavioral stability. PMID:22492762

Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.

PubMed

Turan, Nefize; Miller, Brandon A; Heider, Robert A; Nadeem, Maheen; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2017-11-01

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

Changing delay discounting in the light of the competing neurobehavioral decision systems theory: a review.

PubMed

Koffarnus, Mikhail N; Jarmolowicz, David P; Mueller, E Terry; Bickel, Warren K

2013-01-01

Excessively devaluing delayed reinforcers co-occurs with a wide variety of clinical conditions such as drug dependence, obesity, and excessive gambling. If excessive delay discounting is a trans-disease process that underlies the choice behavior leading to these and other negative health conditions, efforts to change an individual's discount rate are arguably important. Although discount rate is often regarded as a relatively stable trait, descriptions of interventions and environmental manipulations that successfully alter discount rate have begun to appear in the literature. In this review, we compare published examples of procedures that change discount rate and classify them into categories of procedures, including therapeutic interventions, direct manipulation of the executive decision-making system, framing effects, physiological state effects, and acute drug effects. These changes in discount rate are interpreted from the perspective of the competing neurobehavioral decision systems theory, which describes a combination of neurological and behavioral processes that account for delay discounting. We also suggest future directions that researchers could take to identify the mechanistic processes that allow for changes in discount rate and to test whether the competing neurobehavioral decision systems view of delay discounting is correct. © Society for the Experimental Analysis of Behavior.

Changing Delay Discounting in the Light of the Competing Neurobehavioral Decision Systems Theory: a Review

PubMed Central

Koffarnus, Mikhail N.; Jarmolowicz, David P.; Mueller, E. Terry; Bickel, Warren K.

2014-01-01

Excessively devaluing delayed reinforcers co-occurs with a wide variety of clinical conditions such as drug dependence, obesity, and excessive gambling. If excessive delay discounting is a trans-disease process that underlies the choice behavior leading to these and other negative health conditions, efforts to change an individual’s discount rate are arguably important. Although discount rate is often regarded as a relatively stable trait, descriptions of interventions and environmental manipulations that successfully alter discount rate have begun to appear in the literature. In this review, we compare published examples of procedures that change discount rate and classify them into categories of procedures, including therapeutic interventions, direct manipulation of the executive decision-making system, framing effects, physiological state effects, and acute drug effects. These changes in discount rate are interpreted from the perspective of the competing neurobehavioral decision systems theory, which describes a combination of neurological and behavioral processes that account for delay discounting. We also suggest future directions that researchers could take to identify the mechanistic processes that allow for changes in discount rate and to test whether the competing neurobehavioral decision systems view of delay discounting is correct. PMID:23344987

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

PubMed

Chervin, Ronald D; Garetz, Susan L; Ruzicka, Deborah L; Hodges, Elise K; Giordani, Bruno J; Dillon, James E; Felt, Barbara T; Hoban, Timothy F; Guire, Kenneth E; O'Brien, Louise M; Burns, Joseph W

2014-08-15

Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. ClinicalTrials.gov, ID: NCT00233194.

NTP technical report on the toxicity studies of Pesticide/Fertilizer Mixtures Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.

PubMed

Yang, R.

1993-08-01

Toxicity studies were performed with pesticide and fertilizer mixtures representative of groundwater contamination found in California and Iowa. The California mixture was composed of aldicarb, atrazine, 1,2-dibromo-3-chloropropane, 1,2- dichloropropane, ethylene dibromide, simazine, and ammonium nitrate. The Iowa mixture contained alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate. The mixtures were administered in drinking water (with 512 ppm propylene glycol) to F344/N rats and B6C3F1 mice of each sex at concentrations ranging from 0.1x to 100x, where 1x represented the median concentrations of the individual chemicals found in studies of groundwater contamination from normal agricultural activities. This report focuses primarily on 26-week toxicity studies describing histopathology, clinical pathology, neurobehavior/neuropathology, and reproductive system effects. The genetic toxicity of the mixtures was assessed by determining the frequency of micronuclei in peripheral blood of mice and evaluating micronuclei and sister chromatid exchanges in splenocytes from female mice and male rats. Additional studies with these mixtures that are briefly reviewed in this report include teratology studies with Sprague-Dawley rats and continuous breeding studies with CD-1 Swiss mice. In 26-week drinking water studies of the California and the Iowa mixtures, all rats (10 per sex and group) survived to the end of the studies, and there were no significant effects on body weight gains. Water consumption was not affected by the pesticide/fertilizer contaminants, and there were no clinical signs of toxicity or neurobehavioral effects as measured by a functional observational battery, motor activity evaluations, thermal sensitivity evaluations, and startle response. There were no clear adverse effects noted in clinical pathology (including serum cholinesterase activity), organ weight, reproductive system, or histopathologic evaluations, although absolute and relative liver weights were marginally increased with increasing exposure concentration in both male and female rats consuming the Iowa mixture. In 26-week drinking water studies in mice, one male receiving the California mixture at 100x died during the study, and one control female and one female in the 100x group in the Iowa mixture study also died early. It could not be determined if the death of either of the mice in the 100x groups was related to consumption of the pesticide/fertilizer mixtures. Water consumption and body weight gains were not affected in these studies, and no signs of toxicity were noted in clinical observations or in neurobehavioral assessments. No clear adverse effects were noted in clinical pathology, reproductive system, organ weight, or histopathologic evaluations of exposed mice. The pesticide/fertilizer mixtures, when tested over a concentration range similar to that used in the 26-week studies, were found to have no effects in teratology studies or in a continuous breeding assay examining reproductive and developmental toxicity. The California and Iowa pesticide mixtures were tested for induction of micronuclei in peripheral blood erythrocytes of female mice. Results of tests with the California mixture were negative. Significant increases in micronucleated normochromatic erythrocytes were seen at the two-highest concentrations (10x and 100x) of the Iowa mixture, but the increases were within the normal range of micronuclei in historical control animals. Splenocytes of male rats and female mice exposed to these mixtures were examined for micronucleus and sister chromatid exchange frequencies. Sister chromatid exchange frequencies were marginally increased in rats and mice receiving the California mixture, but neither species exhibited increased frequencies of micronucleated splenocytes. None of these changes were considered to have biological importance. In summary, studies of potential toxicity associated with the consumption of mixtures of pesticides and a fertilizer representative of groundwater contamination in agriculturative of groundwater contamination in agricultural areas of Iowa and California failed to demonstrate any significant adverse effects in rats or mice receiving the mixtures in drinking water at concentrations as high as 100 times the median concentrations of the individual chemicals determined by groundwater surveys. NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.

Advances in family-based interventions in the neonatal ICU.

PubMed

Welch, Martha G; Myers, Michael M

2016-04-01

Despite advances in medical care, preterm infants remain at risk for many adverse outcomes. This article reviews findings from several recent neonatal ICU (NICU) interventions and a trial of a novel nurture-based approach, Family Nurture Intervention (FNI). Recent trials reviewed here find positive effects of a variety of family-related interventions focused on parental guidance. These interventions target prescribed physical activities with infants, parents' stress, and the parents' ability to recognize their positive and negative behaviors with their infants. Beneficial effects include reductions in parenting stress, maternal anxiety, and depression. A different approach, FNI, is aimed at establishing mother-infant emotional connection. As in other trials, FNI also decreased maternal symptoms of anxiety and depression, and increased maternal sensitivity. Additionally, FNI led to positive short and long-term effects on infant neurobehavioral outcomes at term and 18 months. A number of recent parent-based NICU interventions have been effective at reducing preterm parent stress. Another, FNI, has positive effects on both maternal and infant outcomes and promises to be cost-effective. Future decreases in long-term morbidity in preterm infants will increasingly rely on nonmedical interventions. Therefore, the rigorous development and testing of such interventions should be a high priority in perinatology research.

Developmental toxicity of prenatal exposure to toluene.

PubMed

Bowen, Scott E; Hannigan, John H

2006-01-01

Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are increasingly exposed to solvents such as toluene in occupational settings (ie, long-term, low-concentration exposures) or through inhalant abuse (eg, episodic, binge exposures to high concentrations). The risk for teratogenic outcome is much less with low to moderate occupational solvent exposure compared with the greater potential for adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in children born to women exposed to high concentrations of abused organic solvents such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the teratogenic effects of abuse patterns of exposure to toluene and other inhalants remain understudied. We briefly review how animal models can aid substantially in clarifying the developmental risk of exposure to solvents for adverse biobehavioral outcomes following abuse patterns of use and in the absence of associated health problems and co-drug abuse (eg, alcohol). Our studies also begin to establish the importance of dose (concentration) and critical perinatal periods of exposure to specific outcomes. The present results with our clinically relevant animal model of repeated, brief, high-concentration binge prenatal toluene exposure demonstrate the dose-dependent effect of toluene on prenatal development, early postnatal maturation, spontaneous exploration, and amphetamine-induced locomotor activity. The results imply that abuse patterns of toluene exposure may be more deleterious than typical occupational exposure on fetal development and suggest that animal models are effective in studying the mechanisms and risk factors of organic solvent teratogenicity.

Association among parental substance use disorder, p300 amplitude, and neurobehavioral disinhibition in preteen boys at high risk for substance use disorder.

PubMed

Habeych, Miguel E; Sclabassi, Robert J; Charles, Prophete J; Kirisci, Levent; Tarter, Ralph E

2005-06-01

The P300 amplitude of the event-related potential as a mediator of the association between parental substance use disorder (SUD) and child's neurobehavioral disinhibition was assessed. The P300 amplitude was recorded using an oddball task in sons of fathers having either lifetime SUD (n = 105) or no psychiatric disorder (n = 160). Neurobehavioral disinhibition was assessed using measures of affect regulation, behavior control, and executive cognitive function. Parental SUD and child's P300 amplitude accounted for, respectively, 16.6% and 16.8% of neurobehavioral disinhibition variance. Controlling for parental and child psychopathology, an association between parental SUD and child's P300 amplitude was not observed. It was concluded that the P300 amplitude does not mediate the association between parental SUD and child's neurobehavioral disinhibition. Copyright 2005 APA, all rights reserved.

Placental epigenetic patterning of glucocorticoid response genes is associated with infant neurodevelopment

PubMed Central

Paquette, Alison G; Lester, Barry M; Lesseur, Corina; Armstrong, David A; Guerin, Dylan J; Appleton, Allison A; Marsit, Carmen J

2015-01-01

Aim: To determine associations between methylation of NR3C1, HSD11B2, FKBP5 and ADCYAP1R1 and newborn neurobehavioral outcomes. Methods: In 537 newborns, placental methylation was quantified using bisulfite pyrosequencing. Profiles of neurobehavior were derived via the Neonatal Intensive Care Unit Network Neurobehavioral Scales. Using exploratory factor analysis, the relationships between methylation factor scores and neurobehavioral profiles were examined. Results: Increased scores of the factor characterized by NR3C1 methylation were associated with membership in a reactive, poorly regulated profile (odds ratio: 1.47; 95% CI: 1.00–2.18), while increased scores of the factor characterized by HSD11B2 methylation reduced this risk. Conclusion: These results suggest that coordinated regulation of these genes influences neurobehavior and demonstrates the importance of examining these alterations in a harmonized fashion. PMID:26343289

Propofol improved neurobehavioral outcome of cerebral ischemia-reperfusion rats by regulating Bcl-2 and Bax expression.

PubMed

Xi, Hong-Jie; Zhang, Tian-Hua; Tao, Tao; Song, Chun-Yu; Lu, Shu-Jun; Cui, Xiao-Guang; Yue, Zi-Yong

2011-09-02

Propofol is an intravenous anesthetic with neuroprotective effects against cerebral ischemia-reperfusion (I/R) injury. Few studies regarding the neuroprotective and neurobehavioral effects of propofol have been conducted, and the underlying mechanisms are still unclear. Because I/R may result in neuronal apoptosis, the apoptosis regulatory genes B-cell leukemia-2 (Bcl-2) and Bcl-2-associated X protein (Bax) may be involved in the neuroprotective process. In this study, 120 Wistar rats were randomly divided into three groups (sham, I/R-induced, and propofol-treated). Cerebral ischemia was induced by clamping the bilateral common carotid arteries for 10min. Propofol (1.0mg/kg/min) was administered intravenously for 1h before the induction of ischemia. Neuronal damage was evaluated by neurobehavioral scores and histological examination of the brain sections at the level of the dorsal hippocampus at 6h, 24h, 48h, 72h, 4days, 5days, 6days, and 7days after I/R. The apoptotic rate of hippocampal neurons was detected by flow cytometry. The expression of Bcl-2 and Bax was evaluated using immunohistochemical and Western blot methods. The results of this study showed that neurobehavioral scores were higher in propofol-treated rats compared with I/R-induced rats with no propofol treatment. Moreover, the hippocampal expression of Bcl-2 was significantly higher, while the expression of Bax was significantly lower in propofol-treated rats compared with I/R-induced rats at 24h after ischemia. Hence, this study suggests that the neuroprotective effects of propofol against neuronal apoptosis may be a consequence of the regulation of Bcl-2 and Bax. Copyright © 2011 Elsevier B.V. All rights reserved.

Fetal Growth and Neurobehavioral Outcomes in Childhood

PubMed Central

Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

2014-01-01

Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

Neurobehavioral Impact of Successive Cycles of Sleep Restriction With and Without Naps in Adolescents

PubMed Central

Lo, June C.; Lee, Su Mei; Teo, Lydia M.; Lim, Julian; Gooley, Joshua J.

2017-01-01

Abstract Study Objectives: To characterize adolescents’ neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction. Methods: Fifty-seven healthy adolescents (aged 15–19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00–06:00) and recovery (9-hr TIB for two nights per cycle; 23:00–08:00) intended to simulate the weekday sleep loss and weekend attempt to “catch up” on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day. Results: Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study. Conclusions: Adolescents’ neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend “catch-up sleep,” even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night. PMID:28364507

Neurobehavioral Impact of Successive Cycles of Sleep Restriction With and Without Naps in Adolescents.

PubMed

Lo, June C; Lee, Su Mei; Teo, Lydia M; Lim, Julian; Gooley, Joshua J; Chee, Michael W L

2017-02-01

To characterize adolescents' neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction. Fifty-seven healthy adolescents (aged 15-19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00-06:00) and recovery (9-hr TIB for two nights per cycle; 23:00-08:00) intended to simulate the weekday sleep loss and weekend attempt to "catch up" on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day. Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study. Adolescents' neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend "catch-up sleep," even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night. © Sleep Research Society 2016. Published by Oxford University Press [on behalf of the Sleep Research Society].

Adversity and Resilience Are Associated with Outcome after Mild Traumatic Brain Injury in Military Service Members.

PubMed

Reid, Matthew W; Cooper, Douglas B; Lu, Lisa H; Iverson, Grant L; Kennedy, Jan E

2018-05-15

The objective of this study was to assess the associations between resilience, adversity, post-concussion symptoms, and post-traumatic stress symptom reporting after mild traumatic brain injury (mTBI). We hypothesized that resilience would be associated with less symptom reporting, and adversity would be associated with greater symptom reporting. This was a cross-sectional study of retrospective data collected for an ongoing TBI repository. United States military service members who screened positive for mTBI during a primary care visit completed the Trauma History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were used for the present study. Only participants with complete data for the above measures were included, yielding a sample size of 165 participants. Adversity (THS) and resilience (CD-RISC) scores were each correlated significantly with post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in the hypothesized direction. Interactions between adversity and resilience were absent for all measures except the NSI sensory subscale. Four traumatic event types were significantly associated positively with most NSI and PCL-C total and subscale scores, but the age at which traumatic events were first experienced showed few and mixed significant associations. In conclusion, resilience and adversity were significantly associated with symptom endorsement after mTBI. Screening for cumulative adversity may identify individuals at greater risk of developing persistent post-concussion symptoms and/or PTSD, and interventions that increase resilience may reduce symptom severity.

The effect of hypocalcemia in early childhood on autism-related social and communication skills in patients with 22q11 deletion syndrome.

PubMed

Muldoon, Meghan; Ousley, Opal Y; Kobrynski, Lisa J; Patel, Sheena; Oster, Matthew E; Fernandez-Carriba, Samuel; Cubells, Joseph F; Coleman, Karlene; Pearce, Bradley D

2015-09-01

22q11 deletion syndrome (22qDS), also known as DiGeorge syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months, whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p < 0.05), Speech (p < 0.01), and Symbolic domains (p < 0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes.

The effect of hypocalcemia in early childhood on autism-related social and communication skills in patients with 22q11 deletion syndrome

PubMed Central

Muldoon, Meghan; Ousley, Opal Y.; Kobrynski, Lisa J.; Patel, Sheena; Oster, Matthew E.; Fernandez-Carriba, Samuel; Cubells, Joseph F.; Coleman, Karlene; Pearce, Bradley D.

2014-01-01

22q11 deletion syndrome (22qDS), also known as DiGeorge Syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p<0.05), Speech (p<0.01), and Symbolic domains (p<0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes. PMID:25267002

Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus.

PubMed

Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Ahmed, Sahabuddin; Dwivedi, Durgesh; Saroha, Babita; Lahkar, Mangala

2016-11-15

Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-κB activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-κB activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the Neurobehavioral Properties of Naringin in Swiss Mice.

PubMed

Ben-Azu, Benneth; Nwoke, Ekene Enekabokom; Umukoro, Solomon; Aderibigbe, Adegbuyi Oladele; Ajayi, Abayomi Mayowa; Iwalewa, Ezekiel O

2018-03-12

This study was carried out to investigate the neurobehavioral properties of naringin, a flavonoid compound formed from naringenin on behavioral models in mice. The neurobehavioral property of naringin (2.5, 5 and 10 mg/kg) administered intraperitoneally (i.p.) was assessed on novelty-induced rearing, locomotor behavior using open field test; anxiolytic effect was evaluated using hole-board, light and dark box, and elevated-plus maze paradigms. The anti-depressant-like property was also assessed using forced swim test (FST), tail suspension test (TST) and social interaction test (SIT). The cognitive enhancing effect of naringin was evaluated using Y-maze test. Intraperitoneal administration of naringin (2.5 and 5 mg/kg) demonstrated significant (p<0.05) increase in rearing behavior but not the spontaneous motor activity in comparison to control. In the anti-depressant test, naringin (2.5, 5 and 10 mg/kg, i.p.) significantly decreased the duration of immobility in the FST and TST, and increased the % social interaction preference in the SIT relative to controls, suggesting anti-depressant-like and increased social behaviors. Moreover, naringin also exhibited anxiolytic and memory enhancing properties in mice. These findings suggest that naringin possesses anti-depressant- and anxiolytic-like activities as well as memory enhancing effect in mice. © Georg Thieme Verlag KG Stuttgart · New York.

Longitudinal associations from neurobehavioral disinhibition to adolescent risky sexual behavior in boys: direct and mediated effects through moderate alcohol consumption.

PubMed

Riggs, Nathaniel R; Tate, Eleanor B; Ridenour, Ty A; Reynolds, Maureen D; Zhai, Zu W; Vanyukov, Michael M; Tarter, Ralph E

2013-10-01

This longitudinal study tested the hypothesis that neurobehavioral disinhibition (ND) in childhood, mediated by alcohol use, portends risky sexual behavior (number of sexual partners) in midadolescence. Participants were 410 adolescent boys. Neurobehavioral disinhibition was assessed at 11.3 years of age. Frequency and quantity of alcohol use on a typical drinking occasion were assessed at 13.4 years of age at first follow-up, and sexual behavior at 16.0 years at second follow-up. Quantity of alcohol consumed on a typical drinking occasion, but not frequency of alcohol use, mediated the relation between ND and number of sexual partners. These findings indicate that number of sexual partners in midadolescence is predicted by individual differences in boys' psychological self-regulation during childhood and moderate alcohol consumption in early adolescence, and that ND may be a potential target for multi-outcome public health interventions. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Effects of onboard insecticide use on airline flight attendants.

PubMed

Kilburn, Kaye H

2004-06-01

Flight attendants (FAs) exposed to insecticide spray in an aircraft were compared with unexposed subjects for neurobehavioral function, pulmonary function, mood states, and symptoms. The 33 symptomatic FAs were self-selected, and 5 had retired for disability. Testing procedures included balance, reaction time, color discrimination, visual fields, grip strength, verbal recall, problem solving, attention and discrimination functions, and long-term memory functions. Measurements were expressed as a percentage of their predicted values (derived from unexposed controls), and the author compared the means of the percentage predicted values by analysis of variance. Symptom frequencies and Profile of Mood States (POMS) scores were assessed. FAs were significantly more impaired than controls with respect to balance with eyes closed, grip strength, and color discrimination. Nearly half had 3 or more abnormal neurobehavioral functions, after adjustment was made for age, sex, and education level. Neither elevated POMS scores nor frequencies of average symptoms correlated with their numbers of abnormal measurements. Occupational exposure to synthetic pyrethrin insecticides on airliners was associated with neurobehavioral impairment and disability retirement.

Brain imaging and behavioral outcome in traumatic brain injury.

PubMed

Bigler, E D

1996-09-01

Brain imaging studies have become an essential diagnostic assessment procedure in evaluating the effects of traumatic brain injury (TBI). Such imaging studies provide a wealth of information about structural and functional deficits following TBI. But how pathologic changes identified by brain imaging methods relate to neurobehavioral outcome is not as well known. Thus, the focus of this article is on brain imaging findings and outcome following TBI. The article starts with an overview of current research dealing with the cellular pathology associated with TBI. Understanding the cellular elements of pathology permits extrapolation to what is observed with brain imaging. Next, this article reviews the relationship of brain imaging findings to underlying pathology and how that pathology relates to neurobehavioral outcome. The brain imaging techniques of magnetic resonance imaging, computerized tomography, and single photon emission computed tomography are reviewed. Various image analysis procedures, and how such findings relate to neuropsychological testing, are discussed. The importance of brain imaging in evaluating neurobehavioral deficits following brain injury is stressed.

Longitudinal Associations from Neurobehavioral Disinhibition to Adolescent Risky Sexual Behavior in Boys: Direct and Mediated Effects through Moderate Alcohol Consumption

PubMed Central

Riggs, Nathaniel R.; Tate, Eleanor B.; Ridenour, Ty A.; Reynolds, Maureen D.; Zhai, Zu W.; Vanyukov, Michael M.; Tarter, Ralph E.

2013-01-01

Purpose This longitudinal study tested the hypothesis that neurobehavioral disinhibition (ND) in childhood, mediated by alcohol use, portends risky sexual behavior (number of sexual partners) in mid-adolescence. Methods Participants were 410 adolescent boys. Neurobehavioral disinhibition was assessed at 11.3 years of age. Frequency and quantity of alcohol use on a typical drinking occasion were assessed at 13.4 years of age at first follow-up and sexual behavior at 16.0 years at second follow-up. Results Quantity of alcohol consumed on a typical drinking occasion, but not frequency of alcohol use, mediated the relation between ND and number of sexual partners. Conclusions These findings indicate that number of sexual partners in mid-adolescence is predicted by individual differences in boys’ psychological self-regulation during childhood and moderate alcohol consumption in early adolescence, and that ND may be a potential target for multi-outcome public health interventions. PMID:23876782

The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.

PubMed

Tsai, Song-Yen; Chou, Hung-Yi; The, Hee-Wen; Chen, Chao-Meei; Chen, Chien-Jen

2003-08-01

This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.

Neurobehavioral consequences of prenatal alcohol exposure: an international perspective.

PubMed

Riley, Edward P; Mattson, Sarah N; Li, Ting-Kai; Jacobson, Sandra W; Coles, Claire D; Kodituwakku, P W; Adnams, Colleen M; Korkman, Marit I

2003-02-01

This article represents the proceedings of a symposium at the 2002 Research Society on Alcoholism/International Society for Biomedical Research on Alcoholism meeting in San Francisco, CA. The organizers were Edward P. Riley and Sarah N. Mattson, and the chairperson was Edward P. Riley. The presentations were (1) Neurobehavioral deficits in alcohol-exposed South African infants: preliminary findings, by Sandra W. Jacobson, Christopher D. Molteno, Denis Viljoen, and Joseph L. Jacobson; (2) A pilot study of classroom intervention for learners with fetal alcohol syndrome in South Africa, by Colleen Adnams, M. W. Rossouw, M. D. Perold, P. W. Kodituwakku, and W. Kalberg; (3) Differential effects of prenatal alcohol exposure on fluid versus crystallized intelligence, by P. W. Kodituwakku, W. Kalberg, L. Robinson, and P. A. May; (4) Neurobehavioral outcomes of prenatal alcohol exposure: early identification of alcohol effects, by Claire D. Coles; (5) Fetal alcohol syndrome in Moscow, Russia: neuropsychology test performance, by Sarah N. Mattson, E. P. Riley, A. Matveeva, and G. Marintcheva; and (6) Long-term follow-up of Finnish children exposed to alcohol in utero in various durations, by Marit I. Korkman and I. Autti-Rämö. The discussant was Ting-Kai Li.

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice.

PubMed

Onaolapo, Olakunle James; Onaolapo, Adejoke Yetunde

2013-01-01

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

Maternal depression and neurobehavior in newborns prenatally exposed to methamphetamine.

PubMed

Paz, Monica S; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Della Grotta, Sheri; Liu, Jing; Lester, Barry M

2009-01-01

The effects of maternal depression on neonatal neurodevelopment in MA exposed neonates have not been well characterized. To determine the neurobehavioral effects of maternal depressive symptoms on neonates exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS). The purpose of the IDEAL study is to determine the effects of prenatal MA exposure on child outcome. IDEAL screened 13,808 subjects, 1632 were eligible and consented and 176 mothers were enrolled. Only biological mothers with custody of their child at the one-month visit (n=50 MA; n=86 comparison) had the Addiction Severity Index (ASI) administered. The NNNS was administered to the neonate by an examiner blinded to MA exposure within the first five days of life. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS outcomes, with and without covariates. Significance was accepted at p<.05. After adjusting for covariates, regardless of exposure status, maternal depressive symptoms were associated with lower handling and arousal scores, elevated physiological stress scores and an increased incidence of hypotonicity. When adjusting for covariates, MA exposure was associated with lower arousal and higher lethargy scores. Maternal depressive symptoms are associated with neurodevelopmental patterns of decreased arousal and increased stress. Prenatal MA exposure combined with maternal depression was not associated with any additional neonatal neurodevelopmental differences.

Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance.

PubMed

McCauley, Peter; Kalachev, Leonid V; Mollicone, Daniel J; Banks, Siobhan; Dinges, David F; Van Dongen, Hans P A

2013-12-01

Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation--and thereby sensitivity to neurobehavioral impairment from sleep loss--is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation--and thus sensitivity to sleep loss--depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work.

BDE 49 and developmental toxicity in zebrafish

PubMed Central

McClain, Valerie; Stapleton, Heather M.; Gallagher, Evan

2011-01-01

The polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants. Human health concerns of these agents have largely centered upon their potential to elicit reproductive and developmental effects. Of the various congeners, BDE 49 (2,2’,4,5’-tetrabromodiphenyl ether) has been poorly studied, despite the fact that it is often detected in the tissues of fish and wildlife species. Furthermore, we have previously shown that BDE 49 is a metabolic debromination product of BDE 99 hepatic metabolism in salmon, carp and trout, underscoring the need for a better understanding of biological effects. In the current study, we investigated the developmental toxicity of BDE 49 using the zebrafish (Danio rerio) embryo larval model. Embryo and larval zebrafish were exposed to BDE 49 at either 5 hours post fertilization (hpf) or 24 hpf and monitored for developmental and neurotoxicity. Exposure to BDE 49 at concentrations of 4 µM- 32 µM caused a dose-dependent loss in survivorship at 6 days post fertilization (dpf). Morphological impairments were observed prior to the onset of mortality, the most striking of which included severe dorsal curvatures of the tail. The incidence of dorsal tail curvatures was dose and time dependent. Exposure to BDE 49 caused cardiac toxicity as evidenced by a significant reduction in zebrafish heart rates at 6 dpf but not earlier, suggesting that cardiac toxicity was non-specific and associated with physiological stress. Neurobehavioral injury from BDE 49 was evidenced by an impairment of touch-escape responses observed at 5 dpf. Our results indicate that BDE 49 is a developmental toxicant in larval zebrafish that can cause morphological abnormalities and adversely affect neurobehavior. The observed toxicities from BDE 49 were similar in scope to those previously reported for the more common tetrabrominated congener, BDE 47, and also for other lower brominated PBDEs, suggest that these compounds may share similarities in risk to aquatic species. PMID:21951712

Does Growth Impairment Underlie the Adverse Effects of Dexamethasone on Development of Noradrenergic Systems?

PubMed

Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J

2018-06-20

Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth. Somatic growth was reduced with exposure in all three stages, with greater sensitivity for the postnatal regimens; brain region growth was impaired to a lesser extent. Norepinephrine content and concentration were reduced depending on the treatment regimen, with a rank order of deficits of PN7-9 > PN1-3 > GD17-19. However, brain growth impairment did not parallel reduced norepinephrine content in magnitude, dose threshold, sex or regional selectivity, or temporal pattern, and even when corrected for reduced brain region weights (norepinephrine per g tissue), the dexamethasone-exposed animals showed subnormal values. Regression analysis showed that somatic growth impairment accounted for an insubstantial amount of the reduction in norepinephrine content, and brain growth impairment accounted for only 12%, whereas specific effects on norepinephrine accounted for most of the effect. The adverse effects of dexamethasone on noradrenergic system development are not simply related to impaired somatic or brain region growth, but rather include specific targeting of neurodifferentiation. Copyright © 2018. Published by Elsevier B.V.

Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?

PubMed

Slotkin, Theodore A; Stadler, Ashley; Skavicus, Samantha; Card, Jennifer; Ruff, Jonathan; Levin, Edward D; Seidler, Frederic J

2017-01-01

Secondhand tobacco smoke exposure in pregnancy increases the risk of neurodevelopmental disorders. We evaluated in rats whether there is a critical period during which tobacco smoke extract (TSE) affects the development of acetylcholine and serotonin systems, prominent targets for adverse effects of nicotine and tobacco smoke. We simulated secondhand smoke exposure by administering TSE so as to produce nicotine concentrations one-tenth those in active smoking, with 3 distinct, 10-day windows: premating, early gestation or late gestation. We conducted longitudinal evaluations in multiple brain regions, starting in early adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure in any of the 3 windows impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although the adverse effects were seen for all 3 treatment windows, there was a distinct progression, with lowest sensitivity for premating exposure and higher sensitivity for gestational exposures. Serotonin receptors were also reduced by TSE exposure with the same profile: little effect with premating exposure, intermediate effect with early gestational exposure and large effect with late gestational exposure. As serotonergic circuits can offset the neurobehavioral impact of cholinergic deficits, these receptor changes were maladaptive. Thus, there is no single 'critical period' for effects of low-level tobacco smoke but there is differential sensitivity dependent upon the developmental stage at the time of exposure. Our findings reinforce the need to avoid secondhand smoke exposure not only during pregnancy, but also in the period prior to conception, or generally for women of childbearing age. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development.

PubMed

Schambra, Uta B; Goldsmith, Jeff; Nunley, Kevin; Liu, Yali; Harirforoosh, Sam; Schambra, Heidi M

2015-01-01

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about alcohol consumption during the 3rd and 4th weeks of human pregnancy to include occasional light to moderate drinking. Copyright © 2015 Elsevier Inc. All rights reserved.

Behavorial effects of subchronic inhalation of toluene in adult rats

EPA Science Inventory

Whereas the acute neurobehavioral effects oftoluene are robust and well characterized, evidence for persistent effects ofrepeated exposure to this industrial solvent is less compelling. The present studies sought to determine whether repeated inhalation oftoluene caused persist...

Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits, Neuroinflammation, and Hippocampal Injury in the Juvenile Rat

PubMed Central

Lan, Kuo-Mao; Tien, Lu-Tai; Cai, Zhengwei; Lin, Shuying; Pang, Yi; Tanaka, Sachiko; Rhodes, Philip G.; Bhatt, Abhay J.; Savich, Renate D.; Fan, Lir-Wan

2016-01-01

The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)–P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.5 h. Human recombinant EPO (rEPO, at a dose of 5 units/g) was administered intraperitoneally one hour before or immediately after insult, followed by additional injections at 24 and 48 h post-insult. The control rats were injected with normal saline following HI. Neurobehavioral tests were performed on P8 and P20, and brain injury was examined on P21. HI insult significantly impaired neurobehavioral performance including sensorimotor, locomotor activity and cognitive ability on the P8 and P20 rats. HI insult also resulted in brain inflammation (as indicated by microglia activation) and neuronal death (as indicated by Jade B positive staining) in the white matter, striatum, cortex, and hippocampal areas of the P21 rat. Both pre- and post-treatment with rEPO significantly improved neurobehavioral performance and protected against the HI-induced neuronal death, microglia activation (OX42+) as well as loss of mature oligodendrocytes (APC-CC1+) and hippocampal neurons (Nissl+). The long-lasting protective effects of rEPO in the neonatal rat HI model suggest that to exert neurotrophic activity in the brain might be an effective approach for therapeutic treatment of neonatal brain injury induced by hypoxia-ischemia. PMID:26927081

Short-term high-altitude pre-exposure improves neurobehavioral ability

PubMed Central

Guo, Wenyun; Chen, Guozhu; Qin, Jun; Zhang, Jihang; Guo, Xubin; Yu, Jie; Song, Pan; Lu, Wei; Xu, Baida; Li, Jiabei; Ding, Xiaohan

2016-01-01

This study aims to evaluate the effect of the duration of high-altitude (HA) pre-exposure on human neurobehavioral parameters including mood states and cognitive performance at HA. One hundred and eleven healthy individuals (ranging in age from 18 to 35 years) were recruited to participate in this study. They were divided into two groups: a 4-day short-term HA pre-exposure group (n=57) and a 3-month long-term HA pre-exposure group (n=54). All participants lived in the area at 400 m altitude above sea level before pre-exposure to HA. They were then transported to 3700 m plateau for either a 4-day or a 3-month HA pre-exposure, and finally delivered to 4400 m plateau. On the last day of pre-exposure at 3700 m and on the 10th day at 4400 m, neurobehavioral parameters of the participants in the two groups were evaluated. At the end of pre-exposure and on the 10th day of HA exposure, participants in the short-term group had significantly lower negative mood states, better cognitive performance with higher sensorimotor, attention, and psychomotor abilities, and less acute mountain sickness in comparison with the participants in the long-term pre-exposure group. Our field study with large samples showed that in comparison with 3-month long-term pre-exposure, 4-day short-term HA pre-exposure at 3700 m has a better effect in improving human neurobehavioral parameters including mood states and cognitive performance and reducing acute mountain sickness when exposed to a HA at 4400 m. PMID:26966781

Kangaroo-mother care method and neurobehavior of preterm infants.

PubMed

Silva, Margareth Gurgel de Castro; Barros, Marina Carvalho de Moraes; Pessoa, Úrsula Maria Lima; Guinsburg, Ruth

2016-04-01

To evaluate the effect of kangaroo-mother care (KMC) in preterm (PT) neurobehavior between 36 and 41 weeks post-conceptual age (PCA). A prospective cohort of 61 preterm infants with gestational age (GA) of 28-32 w evaluated by the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS), with 36-41 w PCA. Infants with clinical instability were excluded. They were analyzed in 2 groups: - Kangaroo (KAN): KMC for 7 or more days; Conventional (CON): did not receive KMC. Scores of the 13 NNNS variables were compared between groups and the effect of KMC in the scores of the variables of NNNS were evaluated by multiple linear regression, controlling for confounders. The KAN groups (n=24) and CON (n=37) were similar regarding main demographic and clinical maternal and neonatal characteristics. Mean GA was 30.3 w; and birth weight was 1170 g for both groups. PT of KAN group were admitted in KMC with PCA of 35.8 w (38.5 days of life) and remained with this care for 14.3 days. The NNNS was applied 13 days after the start of KMC. PT submitted to KMC showed higher quality of movements (KAN: 4.98 ± 0.53 vs CON: 4.53 ± 0.47; p=0.001) and lower scores on Signs of stress and abstinence (KAN: 0.03 ± 0.03 vs CON: 0.05 ± 0.03; p=0.001). Controlling for confounders, the KMC was associated with higher scores on the variables Attention, Quality of movements, and lower scores on Asymmetry and Signs of stress and abstinence. PT submitted to the KMC, compared to those non-submitted, have better neurobehavior performance between 36 and 41 weeks of post-conceptual age. Copyright © 2016. Published by Elsevier Ireland Ltd.

Prevalence of Neurobehavioral, Social, and Emotional Dysfunction in Patients Treated for Childhood Craniopharyngioma: A Systematic Literature Review

PubMed Central

Zada, Gabriel; Kintz, Natalie; Pulido, Mario; Amezcua, Lilyana

2013-01-01

Background Craniopharyngiomas (CP) are locally invasive and frequently recurring neoplasms often resulting in neurological and endocrinological dysfunction in children. In addition, social-behavioral impairment is commonly reported following treatment for childhood CP, yet remains to be fully understood. The authors aimed to further characterize the prevalence of neurobehavioral, social, and emotional dysfunction in survivors of childhood craniopharyngiomas. Materials and Methods A systematic literature review was conducted in PubMed to identify studies formally assessing neurobehavioral, social, and emotional outcomes in patients treated for CP prior to 18 years of age. Studies published between the years 1990-2012 that reported the primary outcome (prevalence of neurobehavioral, social, emotional/affective dysfunction, and/or impaired quality of life (QoL)) in ≥10 patients were included. Results Of the 471 studies screened, 11 met inclusion criteria. Overall neurobehavioral dysfunction was reported in 51 of 90 patients (57%) with available data. Social impairment (i.e. withdrawal, internalizing behavior) was reported in 91 of 222 cases (41%). School dysfunction was reported in 48 of 136 patients (35%). Emotional/affective dysfunction was reported in 58 of 146 patients (40%), primarily consisting of depressive symptoms. Health related quality of life was affected in 49 of 95 patients (52%). Common descriptors of behavior in affected children included irritability, impulsivity, aggressiveness, and emotional outbursts. Conclusions Neurobehavioral, social, and emotional impairment is highly prevalent in survivors of childhood craniopharyngioma, and often affects quality of life. Thorough neurobehavioral/emotional screening and appropriate counseling is recommended in this population. Additional research is warranted to identify risk factors and treatment strategies for these disorders. PMID:24223703

Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day

NASA Technical Reports Server (NTRS)

Wyatt, J. K.; Ritz-De Cecco, A.; Czeisler, C. A.; Dijk, D. J.

1999-01-01

The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15-24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

The effect of ambient cadmium air pollution on the hair mineral content of children.

PubMed

Stewart-Pinkham, S M

1989-01-01

Hair analyses of 80 children with learning and behavioral problems were assessed by age, sex, season, place of residence, exposure to passive smoke and excess contact with known cadmium air pollutant sources. All children had been exposed for at least 2 years to air pollution from a refuse-derived fuel incineration plant. All of the patients had increased hair cadmium compared with a control group, but there was a strong seasonal influence on hair cadmium. Exposure to cadmium was ubiquitous. A neurobehavioral toxic effect was found in children who showed evidence of inhibition of pyrimidine-5'-nucleotidase by low hair phosphorus levels and low zinc levels in whom there was enhanced lead absorption. Hair analyses appear to be a useful biological monitor for detecting toxic effects from ambient air cadmium levels in subsets of the population at risk for heavy metal toxicity. Air filter measurements appear worthless for detecting environmental contamination with cadmium in air with low levels of lead. Trees, on the other hand, which are more adversely affected by cadmium than other heavy metals, show evidence of inhibition of pyrimidine-5'-nucleosidase by excess seeding.

Exposure to Enriched Environment Decreases Neurobehavioral Deficits Induced by Neonatal Glutamate Toxicity

PubMed Central

Horvath, Gabor; Reglodi, Dora; Vadasz, Gyongyver; Farkas, Jozsef; Kiss, Peter

2013-01-01

Environmental enrichment is a popular strategy to enhance motor and cognitive performance and to counteract the effects of various harmful stimuli. The protective effects of enriched environment have been shown in traumatic, ischemic and toxic nervous system lesions. Monosodium glutamate (MSG) is a commonly used taste enhancer causing excitotoxic effects when given in newborn animals. We have previously demonstrated that MSG leads to a delay in neurobehavioral development, as shown by the delayed appearance of neurological reflexes and maturation of motor coordination. In the present study we aimed at investigating whether environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal MSG treatment. Newborn pups were treated with MSG subcutaneously on postnatal days 1, 5 and 9. For environmental enrichment, we placed rats in larger cages, supplemented with different toys that were altered daily. Normal control and enriched control rats received saline treatment only. Physical parameters such as weight, day of eye opening, incisor eruption and ear unfolding were recorded. Animals were observed for appearance of reflexes such as negative geotaxis, righting reflexes, fore- and hindlimb grasp, fore- and hindlimb placing, sensory reflexes and gait. In cases of negative geotaxis, surface righting and gait, the time to perform the reflex was also recorded daily. For examining motor coordination, we performed grid walking, footfault, rope suspension, rota-rod, inclined board and walk initiation tests. We found that enriched environment alone did not lead to marked alterations in the course of development. On the other hand, MSG treatment caused a slight delay in reflex development and a pronounced delay in weight gain and motor coordination maturation. This delay in most signs and tests could be reversed by enriched environment: MSG-treated pups kept under enriched conditions showed no weight retardation, no reflex delay in some signs and performed better in most coordination tests. These results show that environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal excitotoxicity. PMID:24065102

Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

PubMed

Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

2014-08-01

This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody.

PubMed

Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Newcomb, Deanna L; Chellman, Gary J

2015-06-01

Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and infants included clinical signs, body weight, toxicokinetics, blood lymphocyte phenotyping, T-cell-dependent antibody response (infants only), antitherapeutic antibody (ATA), organ weights (infants only), and gross and microscopic histopathology. Infants were also examined for external and visceral morphologic and neurobehavioral development. There were no adverse tabalumab-related effects on maternal or infant endpoints. An expected pharmacological decrease in peripheral blood B-lymphocytes occurred in adults and infants; however, B-cell recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204 in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary immunization. Following secondary KLH immunization, all infants in both dose groups mounted anti-KLH IgM and IgG antibody responses similar to control. Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the no-observed-adverse-effect level for maternal and developmental toxicity was 30 mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety of 16× the anticipated clinical exposure. © 2015 Wiley Periodicals, Inc.

Circadian Rhythms, Sleep Deprivation, and Human Performance

PubMed Central

Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

2014-01-01

Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats.

PubMed

Kiss, Peter; Szogyi, Donat; Reglodi, Dora; Horvath, Gabor; Farkas, Jozsef; Lubics, Andrea; Tamas, Andrea; Atlasz, Tamas; Szabadfi, Krisztina; Babai, Norbert; Gabriel, Robert; Koppan, Miklos

2009-02-19

Perinatal asphyxia during delivery produces long-term deficits and represents a major problem in both neonatal and pediatric care. Several morphological, biochemical and behavioral changes have been described in rats exposed to perinatal asphyxia. The aim of the present study was to evaluate how perinatal asphyxia affects the complex early neurobehavioral development and retinal structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by cesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily during the first 3 weeks, and motor coordination tests were performed on postnatal weeks 3-5. After completion of the testing procedure, retinas were removed for histological analysis. We found that in spite of the fast catch-up-growth of asphyctic pups, nearly all examined reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting reflexes, development of fore- and hindlimb grasp and placing, gait and auditory startle reflexes. Time to perform negative geotaxis, surface righting and gait reflexes was significantly longer during the first few weeks in asphyctic pups. Among the motor coordination tests, a markedly weaker performance was observed in the grid walking and footfault test and in the walk initiation test. Retinal structure showed severe degeneration in the layer of the photoreceptor and bipolar cell bodies. In summary, our present study provided a detailed description of reflex and motor development following perinatal asphyxia, showing that asphyxia led to a marked delay in neurobehavioral development and a severe retinal degeneration.

Pathophysiological and neurobehavioral injuries in mice experimentally envenomed with Androctonus liouvillei (Pallary, 1928) scorpion venom.

PubMed

El Hidan, Moulay Abdelmonaim; Touloun, Oulaid; El Hiba, Omar; Boumezzough, Ali

2016-01-01

The genus Androctonus is represented by 7 scorpion species in Morocco. All studies conducted on the characterization of Androctonus species venom are limited to Androctonus mauritanicus. However, there is other species which arouses also interest of scientists due to their high toxicity. Thus, we chose to assess the toxic effect of Androctonus liouvillei venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. In addition, we aimed to characterize the neurobehavioral impairments, in Swiss mice, 3h, 6h and 12h following envenomation. The LD50 of A. liouvillei scorpion venom was found to be 0.29mg/kg by subcutaneous injection route. Venom administration induced glomerular destruction and disorganization in the Bowman's spac. Examination of lungs showed a remarkable focal rupture of the alveolar structure and intra-alveolar hemorrhage. Concurrently, there was a significant enhancement in the serum enzymes levels of AST, ALT, CPK and LDH, and a high level of glucose and creatinine. Proteinuria was also observed. Regarding the behavioral effects we noted a hypoactivity and anxiogenic-like effect, manifested by an increased time spent in the open arms in groups tested 30min and 12h after the injection. Concomitantly with an increased immobility time in the tail suspension test. The present finding show an obvious profound neuromodulatory effect of A. liouvillei venom manifested by an impaired neurobehavioral and physiological patterns in mice that may in part explain the toxic effect of the venom in human as one of the potent death agents. Copyright © 2015 Elsevier GmbH. All rights reserved.

Current pharmacotherapy of attention deficit hyperactivity disorder.

PubMed

Reddy, D S

2013-10-01

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder in children and adults characterized by a persistent pattern of impulsiveness, inattention and hyperactivity. It affects about 3-10% of children and 2-5% of adolescents and adults and occurs about four times more commonly in boys than girls. The cause of ADHD is unknown, but it has strong genetic and environment components. The first-line treatment options for ADHD include behavioral therapy, pharmacotherapy with stimulants or both. Methylphenidate and amphetamine salts are the stimulant drugs of choice for ADHD treatment. Amphetamines act by increasing presynaptic release of dopamine and other biogenic amines in the brain. Methylphenidate inhibits the reuptake of dopamine and norepinephrine and therefore its pharmacology is identical to that of amphetamines. Lisdex-amfetamine is a prodrug of dextroamphetamine with low feasibility for abuse. Atomoxetine, a selective norepinephrine reuptake inhibitor, is an alternative, non-stimulant drug for ADHD but it is less efficacious than stimulants. Stimulants are generally safe but are associated with adverse effects including headache, insomnia, anorexia and weight loss. There is increased awareness about serious cardiovascular and psychiatric adverse events with ADHD drugs including concern for growth suppression in children. Stimulants have a high potential for abuse and dependence, and should be handled safely to prevent misuse and abuse. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical.

PubMed

Bhatt, Prakash Chandra; Pathak, Shruti; Kumar, Vikas; Panda, Bibhu Prasad

2018-02-01

The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE). NN treatment led to a significant increase in TLT in the retention trials as compared to acquisition trial TLT suggesting an improved learning and memory in rats. Further, treatment of NN caused an increase in the activity of AChE (42%), accompanied with a reduced activity of glutathione (42%), superoxide dismutase (43%) and catalase (41%). It also decreased the level of lipid peroxidation (28%) and protein carbonyl contents (30%) in hippocampus as compared to those treated with colchicine alone, suggesting a possible neuroprotective efficacy of NN. Interestingly, in silico studies also demonstrated an effective amyloid-β and BACE-1 inhibition activity. These findings clearly indicated that NN reversed colchicine-induced behavioral and neurochemical alterations through potent antioxidant activity and could possibly impart beneficial effects in cognitive defects associated with Alzheimer's disease.

Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

PubMed Central

Kiss, Peter; Vadasz, Gyongyver; Kiss-Illes, Blanka; Horvath, Gabor; Tamas, Andrea; Reglodi, Dora; Koppan, Miklos

2013-01-01

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia. PMID:24232451

Environmental enrichment decreases asphyxia-induced neurobehavioral developmental delay in neonatal rats.

PubMed

Kiss, Peter; Vadasz, Gyongyver; Kiss-Illes, Blanka; Horvath, Gabor; Tamas, Andrea; Reglodi, Dora; Koppan, Miklos

2013-11-13

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.

Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage.

PubMed

Zhu, Yan; Deng, Li; Tang, Huajun; Gao, Xiaoqing; Wang, Youhua; Guo, Kan; Kong, Jiming; Yang, Chaoxian

2017-05-01

Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of Bcl-2 protein increased and expressions of Caspase-3 and Bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

PubMed Central

Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2016-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to cover the lifespan of the laboratory mouse using a battery of neurobehavioral techniques. PMID:26793076

The medical consultation viewed as a value chain: a neurobehavioral approach to emotion regulation in doctor-patient interaction.

PubMed

Finset, Arnstein; Mjaaland, Trond A

2009-03-01

To present a model of the medical consultation as a value chain, and to apply a neurobehavioral perspective to analyze each element in the chain with relevance for emotion regulation. Current knowledge on four elements in medical consultations and neuroscientific evidence on corresponding basic processes are selectively reviewed. The four elements of communication behaviours presented as steps in a value chain model are: (1) establishing rapport, (2) patient disclosure of emotional cues and concerns, (3) the doctor's expression of empathy, and (4) positive reappraisal of concerns. The metaphor of the value chain, with emphasis on goal orientation, helps to understand the impact of each communicative element on the outcome of the consultation. Added value at each step is proposed in terms of effects on outcome indicators; in this case patients affect regulation. Neurobehavioral mechanisms are suggested to explain the association between communication behaviour and affect regulation outcome. The value chain metaphor and the emphasis on behaviour-outcome-mechanisms associations may be of interest as conceptualizations for communications skills training.

The relationships between pesticide metabolites and neurobehavioral test performance in the third National Health and Nutrition Examination Survey.

PubMed

Krieg, Edward F

2013-01-01

Regression analysis was used to estimate and test for relationships between urinary pesticide metabolites and neurobehavioral test performance in adults, 20 to 59 years old, participating in the third National Health and Nutrition Examination Survey. The 12 pesticide metabolites included 2 naphthols, 8 phenols, a phenoxyacetic acid, and a pyridinol. The 3 neurobehavioral tests included in the survey were simple reaction time, symbol-digit substitution, and serial digit learning. As the 2,4-dichlorophenol, 2,5-dichlorophenol, and the pentachlorophenol concentrations increased, performance on the serial digit learning test improved. As the 2,5-dichlorophenol concentration increased, performance on the symbol-digit substitution test improved. At low concentrations, the parent compounds of these metabolites may act at acetylcholine and γ-aminobutyric acid synapses in the central nervous system to improve neurobehavioral test performance.

Principal components analysis of the Neurobehavioral Symptom Inventory in a nonclinical civilian sample.

PubMed

Sullivan, Karen A; Lurie, Janine K

2017-01-01

The study examined the component structure of the Neurobehavioral Symptom Inventory (NSI) under five different models. The evaluated models comprised the full NSI (NSI-22) and the NSI-20 (NSI minus two orphan items). A civilian nonclinical sample was used. The 575 volunteers were predominantly university students who screened negative for mild TBI. The study design was cross-sectional, with questionnaires administered online. The main measure was the Neurobehavioral Symptom Inventory. Subscale, total and embedded validity scores were derived (the Validity-10, the LOW6, and the NIM5). In both models, the principal components analysis yielded two intercorrelated components (psychological and somatic/sensory) with acceptable internal consistency (alphas > 0.80). In this civilian nonclinical sample, the NSI had two underlying components. These components represent psychological and somatic/sensory neurobehavioral symptoms.

Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function in lead-exposed workers from lead-acid battery manufacturing process.

PubMed

Ravibabu, K; Barman, T; Rajmohan, H R

2015-01-01

The interaction between serum neuron-specific enolase (NSE), biogenic amino-acids and neurobehavioral function with blood lead levels in workers exposed to lead form lead-acid battery manufacturing process was not studied. To evaluate serum NSE and biogenic amino-acids (dopamine and serotonin) levels, and neurobehavioral performance among workers exposed to lead from lead-acid storage battery plant, and its relation with blood lead levels (BLLs). In a cross-sectional study, we performed biochemical and neurobehavioral function tests on 146 workers exposed to lead from lead-acid battery manufacturing process. BLLs were assessed by an atomic absorption spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA. Neurobehavioral functions were assessed by CDC-recommended tests---simple reaction time (SRT), symbol digit substitution test (SDST), and serial digit learning test (SDLT). There was a significant correlation (r 0.199, p<0.05) between SDST and BLL. SDLT and SRT had also a significant positive correlation (r 0.238, p<0.01). NSE had a negative correlation (r -0.194, p<0.05) with serotonin level. Multiple linear regression analysis revealed that both SRT and SDST had positive significant associations with BLL. SRT also had a positive significant association with age. Serum NSE cannot be used as a marker for BLL. The only domain of neurobehavioral function tests that is affected by increased BLL in workers of lead-acid battery manufacturing process is that of the "attention and perception" (SDST).

Assessment of learning, memory and attention in developmental neurotoxicity regulatory studies: Introduction.

PubMed

Makris, Susan L; Vorhees, Charles V

2015-01-01

There are a variety of chemicals, including pharmaceuticals, that alter neurobehavior following developmental exposure and guidelines for the conduct of studies to detect such effects by statute in the United States and Europe. Guidelines for Developmental Neurotoxicity Testing (DNT) studies issued by the U.S. Environmental Protection Agency (EPA) under prevailing law and European Organization for Economic Cooperation and Development (OECD) recommendations to member countries provide that such studies include a series of neurobehavioral and neuropathological assessments. Among these are assessment of cognitive function, specifically learning and memory. After reviewing 69 DNT studies submitted to the EPA, tests of learning and memory were noted to have detected the lowest observed adverse effect level (LOAELs) less frequently than behavioral tests of locomotor activity and acoustic/auditory startle, but slightly more than for the developmental Functional Observational Battery (devFOB; which is less extensive than the full FOB), but the reasons for the lower LOAEL detection rate for learning and memory assessment could not be determined. A major concern identified in the review, however, was the adequacy of the methods employed in these studies rather than on the importance of learning and memory to the proper assessment of brain function. Accordingly, a symposium was conducted to consider how the guidelines for tests of learning and memory might be improved. Four laboratories with established histories investigating the effects of chemical exposures during development on learning, memory, and attention, were invited to review the topic and offer recommendations, both theoretical and practical, on approaches to improve the assessment of these vital CNS functions. Reviewers were asked to recommend methods that are grounded in functional importance to CNS integrity, well-validated, reliable, and amenable to the context of regulatory studies as well as to basic research on the underlying processes they measure. This Introduction sets the stage for the reviews by providing the background and regulatory context for improved tests for learning and memory in DNT and other regulatory studies, such as single- or multi-generational studies where similar methods are incorporated. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurobehavioral presentations of brain neoplasms.

PubMed Central

Filley, C M; Kleinschmidt-DeMasters, B K

1995-01-01

We studied 8 patients with frontal or temporolimbic neoplasms who had psychiatric presentations to clarify diagnostic criteria for distinguishing psychiatric disease from structural brain lesions and to examine brain-behavior relationships associated with cerebral neoplasms using modern neuroimaging techniques. Medical records were retrospectively reviewed for evidence of neurobehavioral and neurologic manifestations, tumor histologic features, and the results of treatment. Clinical presentations were correlated with tumor location as determined by computed tomography and magnetic resonance imaging. Patients with frontal lobe tumors presented with abulia, personality change, or depression, whereas those with temporolimbic tumors had auditory and visual hallucinations, mania, panic attacks, or amnesia. After treatment, neurobehavioral syndromes abated or resolved in 7 of 8 patients. We recommend that any patient 40 years of age or older with a change in mental state, cognitive or emotional, should have neuroimaging of the brain. Any patient with a psychiatric presentation who has specific neurobehavioral or neurologic findings or an unexpectedly poor response to psychopharmacologic treatment should also have brain imaging. These case reports extend and update observations on the importance of frontal and temporolimbic systems in the pathogenesis of neurobehavioral disorders. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. PMID:7667978

OVERVIEW AND EVALUATION OF NEUROBEHAVIORAL EFFECTS OF FLAME RETARDANTS IN LABORATORY ANIMALS.

EPA Science Inventory

Polybrominated diphenyl ether (PBDE) flame retardants are used worldwide and have been detected in numerous environmental, including human, samples. Concern has been raised regarding their potential developmental neurotoxic effects. There is an emerging literature on behavioral...

Cerebral oxygenation in patients undergoing shoulder surgery in beach chair position: comparing general to regional anesthesia and the impact on neurobehavioral outcome.

PubMed

Aguirre, J; Borgeat, A; Trachsel, T; Cobo Del Prado, I; De Andrés, J; Bühler, P

2014-02-01

Ischemic brain damage has been reported in healthy patients after beach chair position for surgery due to cerebral hypoperfusion. Near-infrared spectroscopy has been described as a non-invasive, continuous method to monitor cerebral oxygen saturation. However, its impact on neurobehavioral outcome comparing different anesthesia regimens has been poorly described. In this prospective, assessor-blinded study, 90 patients undergoing shoulder surgery in beach chair position following general (G-group, n=45) or regional anesthesia (R-group; n=45) were enrolled to assess the prevalence of cerebral desaturation events comparing anesthesia regimens and their impact on neurobehavioral and neurological outcome. Anesthesiologists were blinded to regional cerebral oxygen saturation values. Baseline data assessed the day before surgery included neurological and neurobehavioral tests, which were repeated the day after surgery. The baseline data for regional cerebral oxygen saturation/bispectral index and invasive blood pressure both at heart and auditory meatus levels were taken prior to anesthesia, 5 min after induction of anesthesia, 5 min after beach chair positioning, after skin incision and thereafter all 20 min until discharge. Patients in the R-group showed significantly less cerebral desaturation events (p<0.001), drops in regional cerebral oxygen saturation values (p<0.001), significantly better neurobehavioral test results the day after surgery (p<0.001) and showed a greater hemodynamic stability in the beach chair position compared to patients in the G-group. The incidence of regional cerebral oxygen desaturations seems to influence the neurobehavioral outcome. Regional anesthesia offers more stable cardiovascular conditions for shoulder surgery in beach chair position influencing neurobehavioral test results at 24h. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Neurobehavioral toxicity testing for risk assessment.

EPA Science Inventory

Neurobehavioral evaluations are key components in neurotoxicity testing. In the realm of regulatory testing, these evaluations range from a functional observational battery (FOB) and an Irwin’s screen, which assess the neurological, motor, and functional integrity of the subject...

Evidence for non-acetylcholinesterase mechanisms in ...

EPA Pesticide Factsheets

Acetyicholinesterase inhibition is a well-established mode of action for adverse effects of organophosphorus and carbamate pesticides, and the use of this endpoint in regulatory considerations has been assumed to be protective of downstream cholinergic effects. It has been questioned whether neurodevelopmental outcomes are also a consequence of this enzyme inhibition, or whether there are alternative non-cholinesterase mechanisms by which these chemicals alter key events in nervous system development. There is a growing body of literature in laboratory animals indicating that gestational and/or postnatal exposure may cause persistent behavioral effects into adulthood, as well as emerging epidemiological reports of neurodevelopmental outcomes in children. Common experimental findings are alterations in motor activity, cognitive function, and affective and social behaviors in rats or mice, as well as disrupted neuromotor and cognitive development in children. However, the data do not provide evidence for a characteristic pattern of effects. This may suggest nonspecific alterations in neurobehavioral function, but it may also be the result of considerable differences in exposure parameters, experimental designs, test methods and equipment, populations and animal models, and a host of other variables. A number of pesticides have been implicated, but the database for chiorpyrifos is the largest and thus those studies influence any evaluations of trend. Specific attri

Evidence for non-acetylcholinesterase mechanisms in ...

EPA Pesticide Factsheets

Acetylcholinesterase inhibition is a well-established mode of action for adverse effects of organophosphorus and carbamate pesticides, and the use of this endpoint in regulatory considerations has been assumed to be protective of downstream cholinergic effects. It has been questioned whether neurodevelopmental outcomes are also a consequence of this enzyme inhibition, or whether there are alternative non-cholinesterase mechanisms by which these chemicals alter key events in nervous system development. There is a growing body of literature in laboratory animals indicating that gestational and/or postnatal exposure may cause persistent behavioral effects into adulthood, as well as emerging epidemiological reports of neurodevelopmental outcomes in children. Common experimental findings are alterations in motor activity, cognitive function, and affective and social behaviors in rats or mice, as well as disrupted neuromotor and cognitive development in children. However, the data do not provide evidence for a characteristic pattern of effects. This may suggest nonspecific alterations in neurobehavioral function, but it may also be the result of considerable differences in exposure parameters, experimental designs, test methods and equipment, populations and animal models, and a host of other variables. A number of pesticides have been implicated, but the database for chlorpyrifos is the largest and thus those studies influence any evaluations of trend. Specific attri

Toward an understanding of violence: neurobehavioral aspects of unwarranted physical aggression: Aspen Neurobehavioral Conference consensus statement.

PubMed

Filley, C M; Price, B H; Nell, V; Antoinette, T; Morgan, A S; Bresnahan, J F; Pincus, J H; Gelbort, M M; Weissberg, M; Kelly, J P

2001-01-01

Violence is a global problem that poses a major challenge to individuals and society. This document is a consensus statement on neurobehavioral aspects of violence as one approach to its understanding and control. This consensus group was convened under the auspices of the Aspen Neurobehavioral Conference, an annual consensus conference devoted to the understanding of issues related to mind and brain. The conference is supported by the Brain Injury Association and by individual philanthropic contributions. Participants were selected by conference organizers to represent leading opinion in neurology, neuropsychology, psychiatry, trauma surgery, nursing, evolutionary psychology, medical ethics, and law. A literature review of the role of the brain in violent behavior was conducted and combined with expert opinion from the group. The major goal was to survey this field so as to identify major areas of interest that could be targeted for further research. Additional review was secured from the other attendees at the Aspen Neurobehavioral Conference. The group met in the spring of 1998 and 1999 for two 5-day sessions, between which individual assignments were carried out. The consensus statement was prepared after the second meeting, and agreement on the statement was reached by participants after final review of the document. Violence can result from brain dysfunction, although social and evolutionary factors also contribute. Study of the neurobehavioral aspects of violence, particularly frontal lobe dysfunction, altered serotonin metabolism, and the influence of heredity, promises to lead to a deeper understanding of the causes and solution of this urgent problem.

Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease: Clinical correlations With Neurobehavioral Data in Cross-Sectional and After 18 Months Follow-ups.

PubMed

Wu, Ming-Kung; Lu, Yan-Ting; Huang, Chi-Wei; Lin, Pin-Hsuan; Chen, Nai-Ching; Lui, Chun-Chung; Chang, Wen-Neng; Lee, Chen-Chang; Chang, Ya-Ting; Chen, Sz-Fan; Chang, Chiung-Chih

2015-07-01

Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to fiber tract integrity, we predefined 11 major association tracts and calculated tract specific fractional anisotropy (FA) values. Eighty-five patients with AD underwent neurobehavioral assessments including the minimental state examination (MMSE) and 12-item neuropsychiatric inventory twice with a 1.5-year interval to represent major outcome factors. In the cross-sectional data, total cholesterol, low-density lipoprotein, vitamin B12, and homocysteine levels correlated variably with WM FA values. After entering the biomarkers and WM FA into a regression model to predict neurobehavioral outcomes, only fiber tract FA or homocysteine level predicted the MMSE score, and fiber tract FA or age predicted the neuropsychiatric inventory total scores and subdomains of apathy, disinhibition, and aberrant motor behavior. In the follow-up neurobehavioral data, the mean global FA value predicted the MMSE and aberrant motor behavior subdomain, while age predicted the anxiety and elation subdomains. Cerebrovascular risk biomarkers may modify WM microstructural organization, while the association with fiber integrity showed greater clinical significance to the prediction of neurobehavioral outcomes both cross-sectionally and longitudinally.

AGE-RELATED, MULTIPLE-SYSTEM EFFECTS FROM ENVIRONMENTAL EXPOSURE TO AIRBORNE MANGANESE (MN)

EPA Science Inventory

Past research has tentatively associated excessive manganese (Mn) exposure with Parkinson-like effects in older adults, violent and aggressive behavior in young adults, and learning and neurobehavioral deficits in elementary school children. Our recent EPA/University of Quebec at...

Microbial colonization is required for normal neurobehavioral development in zebrafish..

EPA Science Inventory

Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we ex...

Microbial colonization is required for normal neurobehavioral development in zebrafish.

EPA Science Inventory

Host-associated microbiota are a dynamic system that shapes organismal development. There is growing evidence that microbiota modify the toxicokinetics and/or toxicodynamics of environmental chemicals. To delineate the neurobehavioral consequences of microbial colonization, we ex...

Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals.

PubMed

Portella, André Krumel; Silveira, Patrícia Pelufo

2014-12-01

Fetal growth restriction results from a failure to achieve a higher growth potential and has been associated with many maternal conditions, such as chronic diseases (infections, hypertension, and some cases of diabetes and obesity), exposures (tobacco smoke, drugs), and malnutrition. This early adversity induces a series of adaptive physiological responses aimed at improving survival, but imposing increased risk for developing chronic nontransmittable diseases (obesity, type II diabetes, cardiovascular disease) in the long term. Recently, mounting evidence has shown that fetal growth impairment is related to altered feeding behavior and preferences through the life course. When living in countries undergoing nutritional transition, in which individuals experience the coexistence of underweight and overweight problems (the "double burden of malnutrition"), fetal growth-restricted children can be simultaneously growth restricted and overweight-a double burden of malnutrition at the individual level. Considering food preferences as an important aspect of nutrition security, we will summarize the putative neurobiological mechanisms at the core of the relationship between fetal growth and nutrition security over the life course and the evidence linking early life adversity to later food preferences. © 2014 New York Academy of Sciences.

Blast overpressure in rats: recreating a battlefield injury in the laboratory.

PubMed

Long, Joseph B; Bentley, Timothy L; Wessner, Keith A; Cerone, Carolyn; Sweeney, Sheena; Bauman, Richard A

2009-06-01

Blast injury to the brain is the predominant cause of neurotrauma in current military conflicts, and its etiology is largely undefined. Using a compression-driven shock tube to simulate blast effects, we assessed the physiological, neuropathological, and neurobehavioral consequences of airblast exposure, and also evaluated the effect of a Kevlar protective vest on acute mortality in rats and on the occurrence of traumatic brain injury (TBI) in those that survived. This approach provides survivable blast conditions under which TBI can be studied. Striking neuropathological changes were caused by both 126- and 147-kPa airblast exposures. The Kevlar vest, which encased the thorax and part of the abdomen, greatly reduced airblast mortality, and also ameliorated the widespread fiber degeneration that was prominent in brains of rats not protected by a vest during exposure to a 126-kPa airblast. This finding points to a significant contribution of the systemic effects of airblast to its brain injury pathophysiology. Airblast of this intensity also disrupted neurologic and neurobehavioral performance (e.g., beam walking and spatial navigation acquisition in the Morris water maze). When immediately followed by hemorrhagic hypotension, with MAP maintained at 30 mm Hg, airblast disrupted cardiocompensatory resilience, as reflected by reduced peak shed blood volume, time to peak shed blood volume, and time to death. These findings demonstrate that shock tube-generated airblast can cause TBI in rats, in part through systemic mediation, and that the resulting brain injury significantly impacts acute cardiovascular homeostatic mechanisms as well as neurobehavioral function.

The intersection of stress, drug abuse and development.

PubMed

Thadani, Pushpa V

2002-01-01

Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

Sleep deprivation reduces perceived emotional intelligence and constructive thinking skills.

PubMed

Killgore, William D S; Kahn-Greene, Ellen T; Lipizzi, Erica L; Newman, Rachel A; Kamimori, Gary H; Balkin, Thomas J

2008-07-01

Insufficient sleep can adversely affect a variety of cognitive abilities, ranging from simple alertness to higher-order executive functions. Although the effects of sleep loss on mood and cognition are well documented, there have been no controlled studies examining its effects on perceived emotional intelligence (EQ) and constructive thinking, abilities that require the integration of affect and cognition and are central to adaptive functioning. Twenty-six healthy volunteers completed the Bar-On Emotional Quotient Inventory (EQi) and the Constructive Thinking Inventory (CTI) at rested baseline and again after 55.5 and 58 h of continuous wakefulness, respectively. Relative to baseline, sleep deprivation was associated with lower scores on Total EQ (decreased global emotional intelligence), Intrapersonal functioning (reduced self-regard, assertiveness, sense of independence, and self-actualization), Interpersonal functioning (reduced empathy toward others and quality of interpersonal relationships), Stress Management skills (reduced impulse control and difficulty with delay of gratification), and Behavioral Coping (reduced positive thinking and action orientation). Esoteric Thinking (greater reliance on formal superstitions and magical thinking processes) was increased. These findings are consistent with the neurobehavioral model suggesting that sleep loss produces temporary changes in cerebral metabolism, cognition, emotion, and behavior consistent with mild prefrontal lobe dysfunction.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

PubMed

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

2016-11-02

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period.

PubMed

Philippot, Gaëtan; Gordh, Torsten; Fredriksson, Anders; Viberg, Henrik

2017-10-01

Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg -1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Experimental exposure to methylformate and its neurobehavioral effects.

PubMed

Sethre, T; Läubli, T; Berode, M; Hangartner, M; Krueger, H

2000-08-01

The aim of the study was to investigate the acute effects of experimental methylformate exposure on the nervous system. In an exposure chamber, 20 subjects were exposed to methylformate at 100 ppm [Swiss maximum allowable concentration (MAC)] for 8 h. The same number of subjects with the same ages (between 20 and 30 years), gender and education level (university) were examined by the same procedure as a control group. The subjects did not know if they were exposed or not. Three times (morning, noon, evening) during these 8 h, mood [Profile of Mood States (POMS)], neurobehavioral performance (reaction, Stroop, nonverbal learning, determination, tracking; Wiener Test System), vision (visual acuity, contrast sensitivity, color sensitivity) and postural sway were tested. During an undemanding test (POMS) and a demanding performance task (determination test), pulse, electromyography (EMG) of the forehead and of the neck were recorded. In the morning and evening spirometry [forced vital capacity (FVC), forced one-second expiration volume (FEV), medium expiration flow (MEF) and peak expiration flow (PEF)] and the odor perception threshold were measured. In the evening, in the exposed group, fatigue was significantly increased and the EMG of the forehead during a demanding task showed a different development during exposure. The other tests showed no significant solvent effect, but 16 of 43 test parameters showed a significant effect of time. The results of this study indicate a possible effect of methylformate exposure on the subjective feeling of fatigue after 8 h exposure at 100 ppm in young and healthy subjects, without measurable impairment of neurobehavioral performance. We assume that a similar effect in normal work, combined with a heavy workload and shift work, can lead to an impairment of productivity, and increase the risk of accidents.

Further characterization of the GlyT-1 inhibitor Org25935: anti-alcohol, neurobehavioral, and gene expression effects.

PubMed

Lidö, Helga Höifödt; Jonsson, Susanne; Hyytiä, Petri; Ericson, Mia; Söderpalm, Bo

2017-05-01

The glycine transporter-1 inhibitor Org25935 is a promising candidate in a treatment concept for alcohol use disorder targeting the glycine system. Org25935 inhibits ethanol-induced dopamine elevation in brain reward regions and reduces ethanol intake in Wistar rats. This study aimed to further characterise the compound and used ethanol consumption, behavioral measures, and gene expression as parameters to investigate the effects in Wistar rats and, as pharmacogenetic comparison, Alko-Alcohol (AA) rats. Animals were provided limited access to ethanol in a two-bottle free-choice paradigm with daily drug administration. Acute effects of Org25935 were estimated using locomotor activity and neurobehavioral status. Effects on gene expression in Wistar rats were measured with qPCR. The higher but not the lower dose of Org25935 reduced alcohol intake in Wistar rats. Unexpectedly, Org25935 reduced both ethanol and water intake and induced strong CNS-depressive effects in AA-rats (withdrawn from further studies). Neurobehavioral effects by Org25935 differed between the strains (AA-rats towards sedation). Org25935 did not affect gene expression at the mRNA level in the glycine system of Wistar rats. The data indicate a small therapeutic range for the anti-alcohol properties of Org25935, a finding that may guide further evaluations of the clinical utility of GlyT-1 inhibitors. The results point to the importance of pharmacogenetic considerations when developing drugs for alcohol-related medical concerns. Despite the lack of successful clinical outcomes, to date, the heterogeneity of drug action of Org25935 and similar agents and the unmet medical need justify further studies of glycinergic compounds in alcohol use disorder.

Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish.

PubMed

Knecht, Andrea L; Truong, Lisa; Marvel, Skylar W; Reif, David M; Garcia, Abraham; Lu, Catherine; Simonich, Michael T; Teeguarden, Justin G; Tanguay, Robert L

2017-08-15

Benzo[a]pyrene (B[a]P) is a well-known genotoxic polycylic aromatic compound whose toxicity is dependent on signaling via the aryl hydrocarbon receptor (AHR). It is unclear to what extent detrimental effects of B[a]P exposures might impact future generations and whether transgenerational effects might be AHR-dependent. This study examined the effects of developmental B[a]P exposure on 3 generations of zebrafish. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to 5 and 10μM B[a]P and raised in chemical-free water until adulthood (F0). Two generations were raised from F0 fish to evaluate transgenerational inheritance. Morphological, physiological and neurobehavioral parameters were measured at two life stages. Juveniles of the F0 and F2 exhibited hyper locomotor activity, decreased heartbeat and mitochondrial function. B[a]P exposure during development resulted in decreased global DNA methylation levels and generally reduced expression of DNA methyltransferases in wild type zebrafish, with the latter effect largely reversed in an AHR2-null background. Adults from the F0 B[a]P exposed lineage displayed social anxiety-like behavior. Adults in the F2 transgeneration manifested gender-specific increased body mass index (BMI), increased oxygen consumption and hyper-avoidance behavior. Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies. Indirect evidence suggested the potential for an AHR2-dependent epigenetic route. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prenatal Dexamethasone Augments the Neurobehavioral Teratology of Chlorpyrifos: Significance for Maternal Stress and Preterm Labor

PubMed Central

Levin, Edward D.; Cauley, Marty; Johnson, Joshua E.; Cooper, Ellen M.; Stapleton, Heather M.; Ferguson, P. Lee; Seidler, Frederic J.; Slotkin, Theodore A.

2014-01-01

Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. We administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure-8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos’ effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants. PMID:24177596

COMPUTERIZED ASSESSMENT OF HUMAN NEUROTOXICITY: SENSITIVITY TO NITROUS OXIDE EXPOSURE

EPA Science Inventory

The authors recently developed a flexible, portable, computer based neurobehavioral evaluation system (NES) to standardize data collection in epidemiologic field studies of individuals at risk for neurobehavioral toxicity. The current study was performed to examine the system's s...

APPROACHES TO ASSESSING THE VALIDITY OF A FUNCTIONAL OBSERVATIONAL BATTERY

EPA Science Inventory

With the growing importance of neurobehavioral assessments at the preliminary stage of chemical testing, it is critical that the screening procedures utilized be valid indicators of neurobehavioral dysfunction in addition to being sensitive, specific, and reliable. fforts in this...

Neurobehavioral toxicity of cadmium sulfate to the planarian Dugesia dorotocephala

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grebe, E.; Schaeffer, D.J.

1991-05-01

The authors are developing bioassays which use planarians (free-living platyhelminthes) for the rapid determination of various types of toxicity, including acute mortality, tumorigenicity, and short-term neurobehavioral responses. Their motivation for using these animals is due to their importance as components of the aquatic ecology of unpolluted streams their sensitivity to low concentrations of environmental toxicants and the presence of a sensitive neurological system with a true brain which allows for complex social behavior. A previous paper described the results of a neurobehavioral bioassay using phenol in a crossover study. This paper reports a similar crossover study using cadmium sulfate.

Workshop on perinatal exposure to dioxin-like compounds. VI. Role of biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooper, K.; Clark, C.G.

1995-03-01

Studies of perinatal exposures to dioxin-like compounds (DLCs), coplanar polycyclic halogenated aromatics whose prototype is 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), have employed a variety of outcome measures to investigate effects on the reproductive/developmental, endocrine, immune, and neurobehavioral systems. The effects include infertility, growth retardation, fetal loss, changed sexual differentiation, reduced cognitive/motor function, dermatologic and other ectodermal effects, and decreased immune response. Significant biomarkers have included sperm count; CD4/CD8 ratio; and levels of testosterone, T4, and clopamine. Using specific dioxin or PCB congeners, these and other markers were used to investigate the mechanisms of the observed effects. The DLCs, which include some PCB congeners,more » are characterized by high-affinity binding to the Ah receptor; most biological effects are thought to be mediated by the ligand-Ah receptor complex. Other PCB congeners have low affinity for the Ah receptor, and operate by non-Ah receptor mechanisms. The biologic activity of a PCB mixture is the sum of the agonist and antagonist activities of the different constituents in the mixture. Animal studies with specific PCB congeners can help to clarify these activities. With similar approaches, biologic markers of effect can be developed and applied in epidemiologic studies to monitor for, and predict, adverse effects in humans. 52 refs., 2 figs., 1 tab.« less

DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENSMIPHOS OR PROFENOPHOS.

EPA Science Inventory

This manuscript examines the relationship between cholinesterase inhibition and behavioral effects produced by two pesticides, fenamiphos and profenophos. Both pesticides greatly inhibit blood cholinesterase but the brain is relatively spared up to lethal doses. Despite the sim...

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

EPA Science Inventory

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metric...

Some Clinically Useful Information that Neuropsychology Provides Patients, Carepartners, Neurologists, and Neurosurgeons About Deep Brain Stimulation for Parkinson's Disease

PubMed Central

Tröster, Alexander I

2017-01-01

Abstract Deep brain stimulation (DBS) is an effective (but non-curative) treatment for some of the motor symptoms and treatment complications associated with dopaminergic agents in Parkinson's disease (PD). DBS can be done relatively safely and is associated with quality of life gains. In most DBS centers, neuropsychological evaluations are performed routinely before surgery, and sometimes after surgery. The purpose of such evaluation is not to decide solely on its results whether or not to offer DBS to a given candidate, but to provide the patient and treatment team with the best available information to make reasonable risk-benefit assessments. This review provides information relevant to the questions often asked by patients and their carepartners, neurologists, and neurosurgeons about neuropsychological outcomes of DBS, including neuropsychological adverse event rates, magnitude of cognitive changes, outcomes after unilateral versus bilateral surgery directed at various targets, impact of mild cognitive impairment (MCI) on outcome, factors implicated in neurobehavioral outcomes, and safety of newer interventions or techniques such as asleep surgery and current steering. PMID:29077802

NEUROBEHAVIORAL TESTING IN ANIMALS AND THE APPLICATION TO RISK ASSESSMENT.

EPA Science Inventory

Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...

Neurobehavioral foundation of environmental reactivity.

PubMed

Moore, Sarah R; Depue, Richard A

2016-02-01

Sensitivity to environmental context has been of interest for many years, but the nature of individual differences in environmental sensitivity has become of particular focus over the past 2 decades. What is particularly uncertain are the neural variables and processes that mediate the effects of environment on developmental outcomes. Accordingly, we provide a neurobehavioral foundation of reactivity to the environment in several steps. First, the different patterns of environmental sensitivity are defined to identify the significant factors involved in the manifestation of these patterns. Second, we focus on neurobiological reactivity as the construct underlying variation in sensitivity to the environment by (a) providing an organizing threshold model of elicitation of neurobiology by environmental context; and (b) integrating the literature on 2 sets of neuromodulators in terms of each modulator's (a) contribution to neural and behavioral reactivity to stimulation, and (b) relation to emotional-motivational systems (dopamine, opiates and oxytocin, corticotropin-releasing hormone) or the general modulation of those systems (serotonin, norepinephrine, and GABA). Discussion concludes with (a) a comprehensive neurobehavioral framework of environmental reactivity based on a combinatorial model of a supertrait, (b) methodological implications of the model, and (c) a developmental perspective on environmental reactivity. (c) 2016 APA, all rights reserved).

Neurobehavioral Performance Impairment in Insomnia: Relationships with Self-Reported Sleep and Daytime Functioning

PubMed Central

Shekleton, Julia A.; Flynn-Evans, Erin E.; Miller, Belinda; Epstein, Lawrence J.; Kirsch, Douglas; Brogna, Lauren A.; Burke, Liza M.; Bremer, Erin; Murray, Jade M.; Gehrman, Philip; Lockley, Steven W.; Rajaratnam, Shantha M. W.

2014-01-01

Study Objectives: Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction. Design: Cross-sectional, multicenter study. Setting: Three sleep laboratories in the USA and Australia. Patients: Seventy-six individuals who met the Research Diagnostic Criteria (RDC) for Primary Insomnia, Psychophysiological Insomnia, Paradoxical Insomnia, and/or Idiopathic Childhood Insomnia (44F, 35.8 ± 12.0 years [mean ± SD]) and 20 healthy controls (14F, 34.8 ± 12.1 years). Interventions: N/A. Measurements and Results: Participants completed a 7-day sleep-wake diary, questionnaires assessing daytime dysfunction, and a neurobehavioral test battery every 60-180 minutes during an afternoon/evening sleep laboratory visit. Included were tasks assessing sustained and switching attention, working memory, subjective sleepiness, and effort. Switching attention and working memory were significantly worse in insomnia patients than controls, while no differences were found for simple or complex sustained attention tasks. Poorer sustained attention in the control, but not the insomnia group, was significantly associated with increased subjective sleepiness. In insomnia patients, poorer sustained attention performance was associated with reduced health-related quality of life and increased insomnia severity. Conclusions: We found that insomnia patients exhibit deficits in higher level neurobehavioral functioning, but not in basic attention. The findings indicate that neurobehavioral deficits in insomnia are due to neurobiological alterations, rather than sleepiness resulting from chronic sleep deficiency. Citation: Shekleton JA; Flynn-Evans EE; Miller B; Epstein LJ; Kirsch D; Brogna LA; Burke LM; Cremer E; Murray JM; Gehrman P; Lockley SW; Rajaratnam SMW. Neurobehavioral performance impairment in insomnia: relationships with self-reported sleep and daytime functioning. SLEEP 2014;37(1):107-116. PMID:24470700

Organophosphorus pesticide exposure and neurobehavioral performance in Latino children living in an orchard community.

PubMed

Butler-Dawson, Jaime; Galvin, Kit; Thorne, Peter S; Rohlman, Diane S

2016-03-01

Children living in agricultural communities have a greater risk from pesticides due to para-occupational pathways. The goal of this study was to assess the impact of exposure to organophosphorus pesticides on the neurobehavioral performance of school-aged Latino children over time. Two exposure measures were used to estimate children's pesticide exposure: parent's occupation (agricultural or non-agricultural) and organophosphate residues in home carpet dust samples. During 2008-2011, 206 school-aged children completed a battery of neurobehavioral tests two times, approximately one year apart. The associations between both exposure measures and neurobehavioral performance were examined. Pesticide residues were detected in dust samples from both agricultural and non-agricultural homes, however, pesticides were detected more frequently and in higher concentrations in agricultural homes compared to non-agricultural homes. Although few differences were found between agricultural and non-agricultural children at both visits, deficits in learning from the first visit to the second visit, or less improvement, was found in agricultural children relative to non-agricultural children. These differences were significant for the Divided Attention and Purdue Pegboard tests. These findings are consistent with previous research showing deficits in motor function. A summary measure of organophosphate residues was not associated with neurobehavioral performance. Results from this study indicate that children in agricultural communities are at increased risk from pesticides as a result of a parent working in agricultural. Our findings suggest that organophosphate exposure may be associated with deficits in learning on neurobehavioral performance, particularly in tests of with motor function. In spite of regulatory phasing out of organophosphates in the U.S., we still see elevated levels and higher detection rates of several organophosphates in agricultural households than non-agricultural households, albeit lower levels than prior studies. Copyright © 2016. Published by Elsevier B.V.

Neurobehavioral changes in response to alterations in gene expression profiles in the brains of mice exposed to low and high levels of mercury vapor during postnatal development.

PubMed

Yoshida, Minoru; Honda, Akiko; Watanabe, Chiho; Satoh, Masahiko; Yasutake, Akira

2014-08-01

This study examined the relationship between neurobehavioral changes and alterations in gene expression profiles in the brains of mice exposed to different levels of Hg(0) during postnatal development. Neonatal mice were repeatedly exposed to mercury vapor (Hg(0)) at a concentration of 0.057 mg/m(3) (low level), which was close to the current threshold value (TLV), and 0.197 mg/m(3) (high level) for 24 hr until the 20(th) day postpartum. Behavioral responses were evaluated based on changes in locomotor activity in the open field test (OPF), learning ability in the passive avoidance response test (PA), and spatial learning ability in the Morris water maze (MM) at 12 weeks of age. No significant differences were observed in the three behavioral measurements between mice exposed to the low level of Hg(0) and control mice. On the other hand, total locomotive activity in mice exposed to the high level of Hg(0) was significantly decreased and central locomotion was reduced in the OPF task. Mercury concentrations were approximately 0.4 μg/g and 1.9 μg/g in the brains of mice exposed to the low and high levels of Hg(0), respectively. Genomic analysis revealed that the expression of 2 genes was up-regulated and 18 genes was down-regulated in the low-level exposure group, while the expression of 3 genes was up-regulated and 70 genes was down-regulated in the high-level exposure group. Similar alterations in the expression of seven genes, six down-regulated genes and one up-regulated gene, were observed in both groups. The results indicate that an increase in the number of altered genes in the brain may be involved in the emergence of neurobehavioral effects, which may be associated with the concentration of mercury in the brain. Moreover, some of the commonly altered genes following exposure to both concentrations of Hg(0) with and without neurobehavioral effects may be candidates as sensitive biomarker genes for assessing behavioral effects in the early stages of development.

Neurobehavioral effects among inhabitants around mobile phone base stations.

PubMed

Abdel-Rassoul, G; El-Fateh, O Abou; Salem, M Abou; Michael, A; Farahat, F; El-Batanouny, M; Salem, E

2007-03-01

There is a general concern on the possible hazardous health effects of exposure to radiofrequency electromagnetic radiations (RFR) emitted from mobile phone base station antennas on the human nervous system. To identify the possible neurobehavioral deficits among inhabitants living nearby mobile phone base stations. A cross-sectional study was conducted on (85) inhabitants living nearby the first mobile phone station antenna in Menoufiya governorate, Egypt, 37 are living in a building under the station antenna while 48 opposite the station. A control group (80) participants were matched with the exposed for age, sex, occupation and educational level. All participants completed a structured questionnaire containing: personal, educational and medical histories; general and neurological examinations; neurobehavioral test battery (NBTB) [involving tests for visuomotor speed, problem solving, attention and memory]; in addition to Eysenck personality questionnaire (EPQ). The prevalence of neuropsychiatric complaints as headache (23.5%), memory changes (28.2%), dizziness (18.8%), tremors (9.4%), depressive symptoms (21.7%), and sleep disturbance (23.5%) were significantly higher among exposed inhabitants than controls: (10%), (5%), (5%), (0%), (8.8%) and (10%), respectively (P<0.05). The NBTB indicated that the exposed inhabitants exhibited a significantly lower performance than controls in one of the tests of attention and short-term auditory memory [Paced Auditory Serial Addition Test (PASAT)]. Also, the inhabitants opposite the station exhibited a lower performance in the problem solving test (block design) than those under the station. All inhabitants exhibited a better performance in the two tests of visuomotor speed (Digit symbol and Trailmaking B) and one test of attention (Trailmaking A) than controls. The last available measures of RFR emitted from the first mobile phone base station antennas in Menoufiya governorate were less than the allowable standard level. Inhabitants living nearby mobile phone base stations are at risk for developing neuropsychiatric problems and some changes in the performance of neurobehavioral functions either by facilitation or inhibition. So, revision of standard guidelines for public exposure to RER from mobile phone base station antennas and using of NBTB for regular assessment and early detection of biological effects among inhabitants around the stations are recommended.

Both physiology and epidemiology support zero tolerable blood lead levels.

PubMed

Shefa, Syeda T; Héroux, Paul

2017-10-05

Inorganic lead is one of the most common causes of environmental metal poisonings, and its adverse effects on multiple body systems are of great concern. The brain, along with the kidneys, are critically susceptible to lead toxicity for their hosting of high affinity lead binding proteins, and very sensitive physiology. Prolonged low-lead exposure frequently remains unrecognized, causes subtle changes in these organ systems, and manifests later at an irreversible stage. With the repeated documentation of "no safe blood lead level", the pernicious effects of lead at any measurable concentration need to be emphasized. In this review, we surveyed articles on chronic low-level lead exposures with a blood lead concentrations <10μg/dL and the development of neurobehavioral or renal disorders. The negative impacts of lead on both nervous and renal systems were obvious at a blood lead concentration of 2μg/dL, with the absence of any detectable threshold. The deleterious effect of lead on two different organ systems at such low concentrations drew our attention to the various extracellular and intracellular events that might be affected by minimal concentration of body lead, especially blood lead. Is there a true common ground between low-level lead toxicity in both the nervous system and the kidney? Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal Antecedents of Newborn Neurological Maturation

ERIC Educational Resources Information Center

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

2010-01-01

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24 to 38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the first weeks after birth…

NEUROBEHAVIORAL DATA INTERPRETATION IN NEUROTOXICITY STUDIES: FOB, MOTOR ACTIVITY AND FUNCTION

EPA Science Inventory

Neurobehavioral evaluations are emerging as a key component in neurotoxicity testing. The tests most often used for screening are the functional observational battery (FOB) and motor activity. The FOB is a series of non-invasive observational and manipulative measures which ass...

Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

PubMed

Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

2015-10-01

Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy. © The Author(s) 2015.

Effects of neurobehavioral assessment on feeding and weight gain in preterm neonates.

PubMed

Senn, Theresa E; Espy, Kimberly Andrews

2003-04-01

Neonatal intensive care unit personnel and parents often are concerned that developmental assessment will tire preterm neonates and impair their feeding ability and subsequent weight gain. Therefore, the amount of fluid consumed by 108 preterm neonates (

[The peptide correction of neurotic disorders among professional truck-drivers].

PubMed

Bashkireva, A S; Artamonova, V G

2012-01-01

This study was designed to estimate the neurobehavioral status and to compare the prevalence of psychoadaptive disorders among lorry-drivers (experimental group) and metal craftsmen (control group) in connection with their age, length of service, occupational hazards, work schedule and sociodemographic characteristics. 150 male lorry-drivers (mean age 43.3 +/- 0.9) and 150 male metal craftsmen (mean age 42.8 +/- 0.9) were examined using a clinical questionnaire to identify, estimate and compare neurotic states. The study comprised 3 groups: 1st--subjects with stable psychic adaptation, 2nd--subjects with unstable psychic adaptation, a risk group, 3rd--subjects with stable psychic disadaptation, i.e. with some borderline mental disorders (BMD). Significant differences in the prevalence of psychic adaptation and disadaptation among groups under study were found. The predominance of the 2nd and 3rd groups among lorry-drivers in comparison with control group was found. The results showed that social and demographic characteristics had no significant influence neither in experimental nor in control groups (p > 0.1). Variability of psychoemotional imbalance levels among lorry-drivers was found to be due to a combination of the following factors: occupational exposure and their work schedule, while in control group--to the age of metal craftsmen. Comparative analysis of neurobehavioral disorders revealed the predominance of the asthenic symptoms, anxious and depressive manifestations, hysterical reactions among lorry-drivers, and the vegetative disorders only in control group. The results thus obtained support the hypothesis of occupational hazards and long driving experience being the risk factors for the development of BMD. The application of bioregulating peptides was found to restore the organism adaptive potential, improved psychoemotional indices, intensified resistance to work stress and reduced occupational risk of borderline mental disorders (p < 0.001-0.05). The best effect was obtained in case of combined application of several cytogens (pinealon and vezugen), which were optimally selected regarding the effect of each adverse occupational factor on a target organ or system. The employed parameters of psychoemotional state were rather informative for assessing the peptidergic properties of cytogens in occupational medicine and geriatrics.

A Brief History of INA and ICOH SCNP: International Neurotoxicology Association and International Congress on Occupational Health Scientific Committee on Neurotoxicology and Psychophysiology

EPA Science Inventory

Two international scientific societies dedicated to research in neurotoxicology and neurobehavioral toxicology are the International Neurotoxicology Association (INA) and the International Congress on Occupational Health International Symposium on Neurobehavioral Methods and Effe...

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

PubMed Central

Garry, Vincent F; Harkins, Mary E; Erickson, Leanna L; Long-Simpson, Leslie K; Holland, Seth E; Burroughs, Barbara L

2002-01-01

We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed. PMID:12060842

NICU Network Neurobehavioral Scale: 1-month normative data and variation from birth to 1 month.

PubMed

Provenzi, Livio; Olson, Karen; Giusti, Lorenzo; Montirosso, Rosario; DeSantis, Andrea; Tronick, Ed

2018-06-01

BackgroundThe Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized method for infant neurobehavioral assessment. Normative values are available for newborns, but the NNNS is not always feasible at birth. Unfortunately, 1-month NNNS normative data are lacking.AimsTo provide normative data for the NNNS examination at 1 month and to assess birth-to-one-month changes in NNNS summary scores.Study designThe NNNS was administered at birth and at 1 month within a longitudinal prospective study design.SubjectsA cohort of 99 clinically healthy full-term infants were recruited from a well-child nursery.Outcome measuresBirth-to-1-month NNNS variations were evaluated and the association of neonatal and sociodemographic variables with the rate of change of NNNS summary scores were investigated.Results and conclusionsNNNS scores from the 10th to the 90th percentile represent a range of normative performance at 1 month. A complex pattern of stability and change emerged comparing NNNS summary scores from birth to 1 month. Orienting, Regulation, and Quality of movements significantly increased, whereas Lethargy and Hypotonicity significantly decreased. Birth-to-1-month changes in NNNS performance suggest improvements in neurobehavioral organization. These data are useful for research purposes and for clinical evaluation of neurobehavioral performance in both healthy and at-risk 1-month-old infants.

Familiar auditory sensory training in chronic traumatic brain injury: a case study.

PubMed

Sullivan, Emily Galassi; Guernon, Ann; Blabas, Brett; Herrold, Amy A; Pape, Theresa L-B

2018-04-01

The evaluation and treatment for patients with prolonged periods of seriously impaired consciousness following traumatic brain injury (TBI), such as a vegetative or minimally conscious state, poses considerable challenges, particularly in the chronic phases of recovery. This blinded crossover study explored the effects of familiar auditory sensory training (FAST) compared with a sham stimulation in a patient seven years post severe TBI. Baseline data were collected over 4 weeks to account for variability in status with neurobehavioral measures, including the Disorders of Consciousness scale (DOCS), Coma Near Coma scale (CNC), and Consciousness Screening Algorithm. Pre-stimulation neurophysiological assessments were completed as well, namely Brainstem Auditory Evoked Potentials (BAEP) and Somatosensory Evoked Potentials (SSEP). Results revealed that a significant improvement in the DOCS neurobehavioral findings after FAST, which was not maintained during the sham. BAEP findings also improved with maintenance of these improvements following sham stimulation as evidenced by repeat testing. The results emphasize the importance for continued evaluation and treatment of individuals in chronic states of seriously impaired consciousness with a variety of tools. Further study of auditory stimulation as a passive treatment paradigm for this population is warranted. Implications for Rehabilitation Clinicians should be equipped with treatment options to enhance neurobehavioral improvements when traditional treatment methods fail to deliver or maintain functional behavioral changes. Routine assessment is crucial to detect subtle changes in neurobehavioral function even in chronic states of disordered consciousness and determine potential preserved cognitive abilities that may not be evident due to unreliable motor responses given motoric impairments. Familiar Auditory Stimulation Training (FAST) is an ideal passive stimulation that can be supplied by families, allied health clinicians and nursing staff of all levels.

CHARACTERIZATION OF THE EFFECTS OF INHALED PERCHLOROETHYLENE ON SUSTAINED ATTENTION IN RATS PERFORMING A VISUAL SIGNAL DETECTION TASK

EPA Science Inventory

The aliphatic hydrocarbon perchloroethyelene (PCE) has been associated with neurobehavioral dysfunction including reduced attention in humans. The current study sought to assess the effects of inhaled PCE on sustained attention in rats performing a visual signal detection task (S...

Neurobehavorial effects of acute exposure to four solvents: meta-abalyses

EPA Science Inventory

Meta-and re-analyses of the available data for the neurobehavioral effects of acute inhalation exposure to toluene were reported by Benignus et al. (2007). The present study was designed to test the generality of the toluene results in as many other solvents as possible by furthe...

Neurobehavioral effects of combined prenatal exposure to low-level mercury vapor and methylmercury.

PubMed

Yoshida, Minoru; Suzuki, Megumi; Satoh, Masahiko; Yasutake, Akira; Watanabe, Chiho

2011-01-01

We evaluated the effects of prenatal exposure to low-level mercury (Hg(0)) or methylmercury (MeHg) as well as combined exposure (Hg(0) + MeHg exposure) on the neurobehavioral function of mice. The Hg(0) exposure group was exposed to Hg(0) at a mean concentration of 0.030 mg/m(3) for 6 hr/day during gestation period. The MeHg exposure was supplied with food containing 5 ppm of MeHg from gestational day 1 to postnatal day 10. The combined exposure group was exposed to both Hg(0) vapor and MeHg according to above described procedure. After delivery, when their offspring reached the age of 8 weeks, behavioral analysis was performed. Open field (OPF) tests of the offspring showed an increase and decrease in voluntary activity in male and female mice, respectively, in the MeHg exposure group. In addition, the rate of central entries was significantly higher in this group than in the control group. The results of OPF tests in the Hg(0) + MeHg exposure group were similar to those in the MeHg exposure group in both males and females. The results in the Hg(0) exposure group did not significantly differ from those in the control group in males or females. Passive avoidance response (PA) tests revealed no significant differences in avoidance latency in the retention trial between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in males or females. Morris water maze tests showed a delay in the latency to reach the platform in the MeHg and Hg(0) + MeHg exposure groups compared with the control group in males but no significant differences between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in females. The results of OPF tests revealed only slight effects of prenatal low-level Hg(0) exposure (0.03 mg/m(3)), close to the no-observable-effect level (NOEL) stated by the WHO (0.025 mg/m(3)), on the subsequent neurobehavioral function. However, prenatal exposure to 5 ppm of MeHg affected exploratory activity in the OPF test, and, in particular, male mice were highly sensitive to MeHg. The MeHg and Hg(0) + MeHg exposure groups showed similar neurobehavioral effects. Concerning the effects of prenatal mercury exposure under the conditions of this study, the effects of MeHg exposure may be more marked than those of Hg(0) exposure.

Energy drink enhances the behavioral effects of alcohol in adolescent mice.

PubMed

Krahe, Thomas E; Filgueiras, Cláudio C; da Silva Quaresma, Renata; Schibuola, Helen Gomes; Abreu-Villaça, Yael; Manhães, Alex C; Ribeiro-Carvalho, Anderson

2017-06-09

Mixing alcohol with energy drinks has become increasingly popular among teenagers and young adults due to the prevailing view that the stimulant properties of energy drinks decrease the depressant effects of alcohol. Surprisingly, in spite of energy drinks being heavily marketed to and consumed by adolescents, there is scarcely available preclinical data on the neurobehavioral effects of energy drinks mixed with alcohol during adolescence. Thus, here we examine the effects of the combined exposure to alcohol and energy drink on adolescent mice using a variety of behavioral tasks to assess locomotor activity, righting reflex and motor coordination. At postnatal day 40, male and female Swiss mice were assigned to the following experimental groups: alcohol diluted in energy drink (Ed+Etoh), alcohol diluted in water (Etoh) or controls (Ctrl: energy drink or water). Alcohol and energy drink (Red Bull) concentrations were 4g/kg and 8ml/kg, respectively, and all solutions were administered via oral gavage. When compared to Etoh mice, Ed+Etoh animals displayed greater locomotor activity and increased anxiety-like behaviors in the open-field, lost their righting reflexes sooner and displayed poorer motor coordination in the rotarod. Collectively, our findings indicate that alcohol-induced deficits in adolescent mice are worsened by energy drink and go against the view that the stimulant properties of energy drinks can antagonize the adverse effects of alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

From lead to manganese through mercury: mythology, science, and lessons for prevention.

PubMed

Alessio, Lorenzo; Campagna, Marcello; Lucchini, Roberto

2007-11-01

Lead (Pb), mercury (Hg), and manganese (Mn) are well-known neurotoxic metals. The knowledge of toxicity was developed through an extensive amount of research, starting with lead and mercury and proceeding today with manganese. Unfortunately, the consequent implementation of preventive measures was generally delayed, causing important negative effects to the exposed populations. A review and historical reconstruction of the research development that yielded modern understanding of lead and mercury neurotoxicity was conducted to derive useful lessons for the prevention of manganese neurotoxicity. Medieval alchemists named planets and metals from gods since they were already aware of the toxicity and the adverse effects caused by lead and mercury. Historical lessons learned from these two metals may help to avoid the repetition of further mistakes regarding other neurotoxic metals like manganese. The knowledge and experience on the toxicokinetics and toxicodynamics of lead and mercury is useful and valuable to identify a proper approach to "safe" exposure levels for manganese. Further information is still needed on the early neurotoxic and neurobehavioral effects after prolonged exposure to very low doses of lead, mercury, and manganese. Nevertheless, according to the precautionary principle, effective preventive measures should be already undertaken to prevent the onset of more severe health effects in the population. This is the most important lesson to be learned and applied from more than 30 years of occupational and environmental neurotoxicology of metals. (c) 2007 Wiley-Liss, Inc.

Organizational topology of brain and its relationship to ADHD in adolescents with d-transposition of the great arteries.

PubMed

Schmithorst, Vincent J; Panigrahy, Ashok; Gaynor, J William; Watson, Christopher G; Lee, Vince; Bellinger, David C; Rivkin, Michael J; Newburger, Jane W

2016-08-01

Little is currently known about the impact of congenital heart disease (CHD) on the organization of large-scale brain networks in relation to neurobehavioral outcome. We investigated whether CHD might impact ADHD symptoms via changes in brain structural network topology in a cohort of adolescents with d-transposition of the great arteries (d-TGA) repaired with the arterial switch operation in early infancy and referent subjects. We also explored whether these effects might be modified by apolipoprotein E (APOE) genotype, as the APOE ε2 allele has been associated with worse neurodevelopmental outcomes after repair of d-TGA in infancy. We applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 47 d-TGA adolescents and 29 healthy referents to construct measures of structural topology at the global and regional levels. We developed statistical mediation models revealing the respective contributions of d-TGA, APOE genotype, and structural network topology on ADHD outcome as measured by the Connors ADHD/DSM-IV Scales (CADS). Changes in overall network connectivity, integration, and segregation mediated worse ADHD outcomes in d-TGA patients compared to healthy referents; these changes were predominantly in the left and right intrahemispheric regional subnetworks. Exploratory analysis revealed that network topology also mediated detrimental effects of the APOE ε4 allele but improved neurobehavioral outcomes for the APOE ε2 allele. Our results suggest that disruption of organization of large-scale networks may contribute to neurobehavioral dysfunction in adolescents with CHD and that this effect may interact with APOE genotype.

The effect of claustrum lesions on human consciousness and recovery of function.

PubMed

Chau, Aileen; Salazar, Andres M; Krueger, Frank; Cristofori, Irene; Grafman, Jordan

2015-11-01

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal Stress and Affect Influence Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Hilton, Sterling C.; Hawkins, Melissa; Costigan, Kathleen A.; Pressman, Eva K.

2002-01-01

Investigated associations between maternal psychological and fetal neurobehavioral functioning with data provided at 24, 30, and 36 weeks gestation. Found that fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more pregnancy-specific hassles were more active across gestation. Fetuses of women…

Fetal Neurobehavioral Development and the Role of Maternal Nutrient Intake and Psychological Health

ERIC Educational Resources Information Center

Spann, Marisa; Smerling, Jennifer; Gustafsson, Hanna C.; Foss, Sophie; Monk, Catherine

2014-01-01

Measuring and understanding fetal neurodevelopment provides insight regarding the developing brain. Maternal nutrient intake and psychological stress during pregnancy each impact fetal neurodevelopment and influence childhood outcomes and are thus important factors to consider when studying fetal neurobehavioral development. The authors provide an…

Childhood Fears, Neurobehavioral Functioning and Behavior Problems in School-Age Children

ERIC Educational Resources Information Center

Kushnir, Jonathan; Sadeh, Avi

2010-01-01

The objective is to examine underlying associations between childhood fears, behavior problems and neurobehavioral functioning (NBF) in school-age children. Healthy, regular school children (N = 135), from second, fourth and sixth grade classes were assessed. Data regarding children's fears and behavioral problems were obtained with the Revised…

Neurobehavioral effects of postnatal exposure to low-level mercury vapor and/or methylmercury in mice.

PubMed

Yoshida, Minoru; Lee, Jin-Yong; Satoh, Masahiko; Watanabe, Chiho

2018-01-01

This study examined the effects on neurobehavioral function of exposure to low-level mercury vapor (Hg 0 ), methylmercury (MeHg) in female mice and the combination of Hg 0 and MeHg during postnatal development. Postnatal mice were exposed to Hg 0 at a mean concentration of 0.188 mg/m 3 Hg 0 and supplied with food containing 3.85 μg/g of MeHg from day 2 to day 28 after delivery. The combined exposure group was exposed to both Hg 0 and MeHg, using the same procedure. When their offspring reached the age of 11 weeks, behavioral analyses were performed. The behavioral effects in mice were evaluated based on locomotive activity and rate of center entries in the open field (OPF), learning activity in the passive avoidance response (PA) and spatial learning ability in the radial maze (RM). Total locomotive activity in the OPF significantly decreased in the Hg 0 , MeHg and combined exposure groups compared with the control group. The proportion of entries to central area in the OPF was significantly higher in the combined exposure group than in the control group, while those in the Hg 0 or MeHg exposure group did not differ from the control group. Other behavioral tests did not reveal significant differences among the groups. Behavioral anomalies were more distinctive after combined exposure compared to Hg 0 or MeHg exposure alone. The brain Hg concentration of offspring, immediately after exposure, was highest in the combined exposure group, exceeding 2 μg/g, followed by the MeHg and Hg 0 exposure groups. Thus, the enhancement of neurobehavioral effects in the combined exposure group was associated with higher brain mercury concentration.

DETERMINATION OF PYRETHROID PESTICIDE RESIDUES FROM RAT TISSUE USING TWO-DIMENSIONAL LCMS

EPA Science Inventory

Pyrethroids are a synthetic class of pesticides that elicit neurobehavioral effects in mammals. They are applied occupationally and residentially creating the potential for human exposure. Determining relationships between parent pyrethroid tissue concentrations and neurotoxic ...

Long-Term Cognitive and Neuropsychiatric Consequences of Repetitive Concussion and Head-Impact Exposure.

PubMed

McAllister, Thomas; McCrea, Michael

2017-03-01

Initially, interest in sport-related concussion arose from the premise that the study of athletes engaged in sports associated with high rates of concussion could provide insight into the mechanisms, phenomenology, and recovery from mild traumatic brain injury. Over the last decade, concerns have focused on the possibility that, for some athletes, repetitive concussions may raise the long-term risk for cognitive decline, neurobehavioral changes, and neurodegenerative disease. First conceptualized as a discrete event with variable recovery trajectories, concussion is now viewed by some as a trigger of neurobiological events that may influence neurobehavioral function over the course of the life span. Furthermore, advances in technology now permit us to gain a detailed understanding of the frequency and intensity of repetitive head impacts associated with contact sports (eg, football, ice hockey). Helmet-based sensors can be used to characterize the kinematic features of concussive impacts, as well as the profiles of typical head-impact exposures experienced by athletes in routine sport participation. Many large-magnitude impacts are not associated with diagnosed concussions, whereas many diagnosed concussions are associated with more modest impacts. Therefore, a full understanding of this topic requires attention to not only the effects of repetitive concussions but also overall exposure to repetitive head impacts. This article is a review of the current state of the science on the long-term neurocognitive and neurobehavioral effects of repetitive concussion and head-impact exposure in contact sports.

Long-Term Cognitive and Neuropsychiatric Consequences of Repetitive Concussion and Head-Impact Exposure

PubMed Central

McAllister, Thomas; McCrea, Michael

2017-01-01

Initially, interest in sport-related concussion arose from the premise that the study of athletes engaged in sports associated with high rates of concussion could provide insight into the mechanisms, phenomenology, and recovery from mild traumatic brain injury. Over the last decade, concerns have focused on the possibility that, for some athletes, repetitive concussions may raise the long-term risk for cognitive decline, neurobehavioral changes, and neurodegenerative disease. First conceptualized as a discrete event with variable recovery trajectories, concussion is now viewed by some as a trigger of neurobiological events that may influence neurobehavioral function over the course of the life span. Furthermore, advances in technology now permit us to gain a detailed understanding of the frequency and intensity of repetitive head impacts associated with contact sports (eg, football, ice hockey). Helmet-based sensors can be used to characterize the kinematic features of concussive impacts, as well as the profiles of typical head-impact exposures experienced by athletes in routine sport participation. Many large-magnitude impacts are not associated with diagnosed concussions, whereas many diagnosed concussions are associated with more modest impacts. Therefore, a full understanding of this topic requires attention to not only the effects of repetitive concussions but also overall exposure to repetitive head impacts. This article is a review of the current state of the science on the long-term neurocognitive and neurobehavioral effects of repetitive concussion and head-impact exposure in contact sports. PMID:28387556

Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage.

PubMed

Turan, Nefize; Miller, Brandon A; Huie, J Russell; Heider, Robert A; Wang, Jun; Wali, Bushra; Yousuf, Seema; Ferguson, Adam R; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2018-02-01

Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH. We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically. PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days. PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure

PubMed Central

Panczakiewicz, Amy L.; Glass, Leila; Coles, Claire D.; Kable, Julie A.; Sowell, Elizabeth R.; Wozniak, Jeffrey R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

2016-01-01

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented, however the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure (n=192) and controls (n=215). Two age groups [child (5–7y) or adolescent (10–16y)] and both sexes were included. All subjects completed standardized neuropsychological testing and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) MANOVAs. Significant effects were followed by univariate analyses. Results No three-way or two-way interactions were significant. The main effect of group was significant in all three MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on three measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual-spatial scores and fewer somatic complaints than females. Conclusion Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for non-exposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the two age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. PMID:27430360

CORRELATIONS OF PESTICIDE-INDUCED CHOLINESTERASE INHIBITION AND MOTOR ACTIVITY CHANGES IN ADULT RATS.

EPA Science Inventory

The acute neurobehavioral effects of acetylcholinesterase-inhibiting pesticides are primarily due to overstimulation of the cholinergic system. Lowered motor activity levels represent a sensitive endpoint with which to monitor functional changes in laboratory animals exposed to ...

Fetal Neurobehavioral Development: A Tale of Two Cities.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Caulfield, Laura; Costigan, Kathleen A.; Merialdi, Mario; Nguyen, Ruby H. N.; Zavaleta, Nelly; Gurewitsch, Edith D.

2004-01-01

Longitudinal neurobehavioral development was examined in 237 fetuses of low-risk pregnancies from 2 distinct populations-Baltimore, Maryland, and Lima, Peru-at 20, 24, 28, 32, 36, and 38 weeks gestation. Data were based on digitized Doppler-based fetal heart rate (FHR) and fetal movement (FM). In both groups, FHR declined while variability,…

Bisphenol A in Relation to Behavior and Learning of School-Age Children

ERIC Educational Resources Information Center

Hong, Soon-Beom; Hong, Yun-Chul; Kim, Jae-Won; Park, Eun-Jin; Shin, Min-Sup; Kim, Boong-Nyun; Yoo, Hee-Jeong; Cho, In-Hee; Bhang, Soo-Young; Cho, Soo-Churl

2013-01-01

Bisphenol A (BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior. Methods: Urinary BPA concentrations and behavioral and learning…

Neurobehaviors of Japanese Newborns in Relation to the Characteristics of Early Mother-Infant Interaction

ERIC Educational Resources Information Center

Loo, Kek Khee; Ohgi, Shohei; Howard, Judy; Tyler, Rachelle; Hirose, Taiko

2005-01-01

The authors examined the relationship between newborn neurobehavioral profiles and the characteristics of early mother-infant interaction in Nagasaki, Japan. The authors administered the Brazelton Neonatal Behavioral Assessment Scale (NBAS; T. B. Brazelton & J. K. Nugent, 1995) in the newborn period and the Nursing Child Assessment Teaching…

Impact of Tactile Stimulation on Neurobehavioral Development of Premature Infants in Assiut City

ERIC Educational Resources Information Center

Sayed, Atyat Mohammed Hassan; Youssef, Magda Mohamed E.; Hassanein, Farouk El-Sayed; Mobarak, Amal Ahmed

2015-01-01

Objective: To assess impact of tactile stimulation on neurobehavioral development of premature infants in Assiut City. Design: Quasi-experimental research design. Setting: The study was conducted in the Neonatal Intensive Care Unit at Assiut University Children Hospital, Assiut General Hospital, Health Insurance Hospital (ElMabarah Hospital) and…

MRI Features in a Canine Model of Ischemic Stroke: Correlation between Lesion Volume and Neurobehavioral Status during the Subacute Stage

PubMed Central

Kang, Byeong-Teck; Jang, Dong-Pyo; Gu, Su-Hyun; Lee, Jong-Hwan; Jung, Dong-In; Lim, Chae-Young; Kim, Ha-Jung; Kim, Young-Bo; Kim, Hyung-Joong; Woo, Eung-Je; Cho, Zang-Hee; Park, Hee-Myung

2009-01-01

The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI) and assess the correlation between the volume of the ischemic lesion and neurobehavioral status during the subacute stage of ischemic stroke. Ischemic stroke was induced in 6 healthy laboratory beagles through permanent occlusion of the middle cerebral artery (MCAO). T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), measurement of the apparent diffusion coefficient (ADC) ratio, and neurobehavioral evaluation were performed 3 times serially by using a 1.5-T MR system: before and 3 and 10 d after MCAO. Ischemic lesions demonstrated T2 hyperintensity, FLAIR hyperintensity, and DWI hyperintensity. The ADC ratio was decreased initially but then was increased at 10 d after MCAO. Ischemic lesion volumes on T2-weighted and FLAIR imaging were not significantly different from those on DWI. The lesion volume and neurobehavioral score showed strong correlation. Our results suggest that conventional MRI may be a reliable diagnostic tool during the subacute stage of canine ischemic stroke. PMID:19887030

EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss

NASA Technical Reports Server (NTRS)

Cajochen, C.; Khalsa, S. B.; Wyatt, J. K.; Czeisler, C. A.; Dijk, D. J.

1999-01-01

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1-7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.

Neurobehavioral development in Joubert syndrome.

PubMed

Gitten, J; Dede, D; Fennell, E; Quisling, R; Maria, B L

1998-08-01

Research on children with Joubert syndrome has focused on brain structural abnormalities and associated clinical symptoms. The degree of developmental delay has not been objectively reported. We investigated the neurobehavioral development of children with Joubert syndrome through neurobehavioral assessment in the largest sample to date. Thirty-two parents of children with Joubert syndrome completed the Child Development Inventory and magnetic resonance imaging (MRI) data was gathered on 17 of these children. Results indicate that 94% were severely impaired according to the Child Development Inventory, with age being positively correlated with degree of neurobehavioral impairment. The average developmental age of our sample was 19 months (63% below chronological age). Severity of illness as measured by the General Development scale of the Child Development Inventory and severity of illness as measured by MRI (overall severity rating) did not yield consistent data regarding severity of the midbrain and cerebellar malformations. Similarly, markers of abnormal cerebral development such as cortical atrophy and delayed myelination were independent of severity of illness ratings on the Child Development Inventory. The degree of developmental delay in Joubert syndrome and the severity of gross central nervous system malformations appear independent.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

PubMed Central

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

2016-01-01

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

Family Nurture Intervention in the Neonatal Intensive Care Unit improves social-relatedness, attention, and neurodevelopment of preterm infants at 18 months in a randomized controlled trial.

PubMed

Welch, Martha G; Firestein, Morgan R; Austin, Judy; Hane, Amie A; Stark, Raymond I; Hofer, Myron A; Garland, Marianne; Glickstein, Sara B; Brunelli, Susan A; Ludwig, Robert J; Myers, Michael M

2015-11-01

Preterm infants are at high risk for adverse neurodevelopmental and behavioral outcomes. Family Nurture Intervention (FNI) in the Neonatal Intensive Care Unit (NICU) is designed to counteract adverse effects of separation of mothers and their preterm infants. Here, we evaluate effects of FNI on neurobehavioral outcomes. Data were collected at 18 months corrected age from preterm infants. Infants were assigned at birth to FNI or standard care (SC). Bayley Scales of Infant Development III (Bayley-III) were assessed for 76 infants (SC, n = 31; FNI, n = 45); the Child Behavior Checklist (CBCL) for 57 infants (SC, n = 31; FNI, n = 26); and the Modified Checklist for Autism in Toddlers (M-CHAT) was obtained for 59 infants (SC, n = 33; FNI, n = 26). Family Nurture Intervention significantly improved Bayley-III cognitive (p = .039) and language (p = .008) scores for infants whose scores were greater than 85. FNI infants had fewer attention problems on the CBCL (p < .02). FNI improved total M-CHAT scores (p < .02). Seventy-six percent of SC infants failed at least one of the M-CHAT items, compared to 27% of FNI infants (p < .001). In addition, 36% of SC infants versus 0% of FNI infants failed at least one social-relatedness M-CHAT item (p < .001). Family Nurture Intervention is the first NICU intervention to show significant improvements in preterm infants across multiple domains of neurodevelopment, social-relatedness, and attention problems. These gains suggest that an intervention that facilitates emotional interactions between mothers and infants in the NICU may be key to altering developmental trajectories of preterm infants. © 2015 Association for Child and Adolescent Mental Health.

Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders

PubMed Central

Lemonnier, E; Villeneuve, N; Sonie, S; Serret, S; Rosier, A; Roue, M; Brosset, P; Viellard, M; Bernoux, D; Rondeau, S; Thummler, S; Ravel, D; Ben-Ari, Y

2017-01-01

In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl−)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3–11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2–18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily. PMID:28291262

Sleep in infants and children with prenatal alcohol exposure.

PubMed

Inkelis, Sarah M; Thomas, Jennifer D

2018-05-31

Prenatal exposure to alcohol can result in a range of neurobehavioral impairments and physical abnormalities. The term fetal alcohol spectrum disorders (FASD) encompasses the outcomes of prenatal alcohol exposure (PAE), the most severe of which is fetal alcohol syndrome (FAS). These effects have lifelong consequences, placing a significant burden on affected individuals, caregivers, and communities. Caregivers of affected children often report that their child has sleep problems, and many symptoms of sleep deprivation overlap with the cognitive and behavioral deficits characteristic of FASD. Alcohol-exposed infants and children demonstrate poor sleep quality based on measures of electroencephalography (EEG), actigraphy, and questionnaires. These sleep studies indicate a common theme of disrupted sleep pattern, more frequent awakenings, and reduced total sleep time. However, relatively little is known about circadian rhythm disruption, and the neurobehavioral correlates of sleep disturbance in individuals with PAE. Furthermore, there is limited information available to healthcare providers about identification and treatment of sleep disorders in patients with FASD. This review consolidates the findings from studies of infant and pediatric sleep in this population, providing an overview of typical sleep characteristics, neurobehavioral correlates of sleep disruption, and potential avenues for intervention in the context of PAE. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

BDE99 (2,2',4,4',5-pentabromodiphenyl ether) suppresses differentiation into neurotransmitter phenotypes in PC12 cells.

PubMed

Slotkin, Theodore A; Card, Jennifer; Infante, Alice; Seidler, Frederic J

2013-01-01

Early-life exposures to brominated diphenyl ethers (BDEs) lead to neurobehavioral abnormalities later in life. Although these agents are thyroid disruptors, it is not clear whether this mechanism alone accounts for the adverse effects. We evaluated the impact of 2,2',4,4',5-pentabromodiphenyl ether (BDE99) on PC12 cells undergoing neurodifferentiation, contrasting the effects with chlorpyrifos, a known developmental neurotoxicant. BDE99 elicited decrements in the number of cells, evidenced by a reduction in DNA levels, to a lesser extent than did chlorpyrifos. This did not reflect cytotoxicity from oxidative stress, since cell enlargement, monitored by the total protein/DNA ratio, was not only unimpaired by BDE99, but was actually enhanced. Importantly, BDE99 impaired neurodifferentiation into both the dopamine and acetylcholine neurotransmitter phenotypes. The cholinergic phenotype was affected to a greater extent, so that neurotransmitter fate was diverted away from acetylcholine and toward dopamine. Chlorpyrifos produced the same imbalance, but through a different underlying mechanism, promoting dopaminergic development at the expense of cholinergic development. In our earlier work, we did not find these effects with BDE47, a BDE that has greater endocrine disrupting and cytotoxic effects than BDE99. Thus, our results point to interference with neurodifferentiation by specific BDE congeners, distinct from cytotoxic or endocrine mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

Neurobehavioral performance impairment in insomnia: relationships with self-reported sleep and daytime functioning.

PubMed

Shekleton, Julia A; Flynn-Evans, Erin E; Miller, Belinda; Epstein, Lawrence J; Kirsch, Douglas; Brogna, Lauren A; Burke, Liza M; Bremer, Erin; Murray, Jade M; Gehrman, Philip; Lockley, Steven W; Rajaratnam, Shantha M W

2014-01-01

Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction. Cross-sectional, multicenter study. Three sleep laboratories in the USA and Australia. Seventy-six individuals who met the Research Diagnostic Criteria (RDC) for Primary Insomnia, Psychophysiological Insomnia, Paradoxical Insomnia, and/or Idiopathic Childhood Insomnia (44F, 35.8 ± 12.0 years [mean ± SD]) and 20 healthy controls (14F, 34.8 ± 12.1 years). N/A. Participants completed a 7-day sleep-wake diary, questionnaires assessing daytime dysfunction, and a neurobehavioral test battery every 60-180 minutes during an afternoon/evening sleep laboratory visit. Included were tasks assessing sustained and switching attention, working memory, subjective sleepiness, and effort. Switching attention and working memory were significantly worse in insomnia patients than controls, while no differences were found for simple or complex sustained attention tasks. Poorer sustained attention in the control, but not the insomnia group, was significantly associated with increased subjective sleepiness. In insomnia patients, poorer sustained attention performance was associated with reduced health-related quality of life and increased insomnia severity. We found that insomnia patients exhibit deficits in higher level neurobehavioral functioning, but not in basic attention. The findings indicate that neurobehavioral deficits in insomnia are due to neurobiological alterations, rather than sleepiness resulting from chronic sleep deficiency.

The Effects of Maternal Alcohol Consumption and Cigarette Smoking during Pregnancy on Acoustic Cry Analysis.

ERIC Educational Resources Information Center

Nugent, J. Kevin; And Others

1996-01-01

Measured the neurobehavioral integrity of Irish infants and maternal alcohol consumption and cigarette smoking. Subjects were 127 primiparous mothers. Results demonstrated significant cry effects on infants of heavily drinking mothers, supporting the conclusion that newborn infants show functional disturbances in the nervous system resulting from…

Influence of Dopamine-Related Genes on Neurobehavioral Recovery after Traumatic Brain Injury during Early Childhood.

PubMed

Treble-Barna, Amery; Wade, Shari L; Martin, Lisa J; Pilipenko, Valentina; Yeates, Keith Owen; Taylor, H Gerry; Kurowski, Brad G

2017-06-01

The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3.5 and 7 years after injury. Thirty-two single nucleotide polymorphisms (SNPs) in dopamine-related genes (dopamine receptor D2 [DRD2], solute carrier family 6 member 3 [SLC6A3], solute carrier family 18 member A2 [SLC18A2], catechol-o-methyltransferase [COMT], and ankyrin repeat and kinase domain containing 1 [ANKK1]) were examined in association with short- and long-term executive function and behavioral adjustment, as well as their trajectories over time. After controlling for premorbid child functioning, genetic variation within the SLC6A3 (rs464049 and rs460000) gene was differentially associated with neurobehavioral recovery trajectories over time following TBI relative to OI, with rs464049 surviving multiple testing corrections. In addition, genetic variation within the ANKK1 (rs1800497 and rs2734849) and SLC6A3 (rs464049, rs460000, and rs1042098) genes was differentially associated with short- and long-term neurobehavioral recovery following TBI, with rs460000 and rs464049 surviving multiple testing corrections. The findings provide preliminary evidence that genetic variation in genes involved in DRD2 expression and density (ANKK1) and dopamine transport (SLC6A3) plays a role in neurobehavioral recovery following pediatric TBI.

Are there gender differences in cognitive function, chronic stress, and neurobehavioral symptoms after mild-to-moderate traumatic brain injury?

PubMed

Covassin, Tracey; Bay, Esther

2012-06-01

Research is inconclusive on whether gender differences exist in cognitive function in persons who sustain a mild-to-moderate traumatic brain injury (TBI). Furthermore, it is also unclear whether there is a relationship between chronic stress and cognitive function in these persons. The purpose of this integrative review is to determine whether gender differences exist in cognitive function, neurobehavioral symptoms, and chronic stress levels after a mild-to-moderate TBI. Participants (n = 72) were recruited from eight outpatient rehabilitation centers. Participants completed the demographic questions, the Immediate Postconcussion Assessment Cognitive Testing neurocognitive test battery, the Perceived Stress Scale-14, and the Neurobehavioral Functioning Inventory (NFI). Gender differences were present on verbal memory composite scores (p = .033), with women performing worse than men. There were no other between-gender differences on cognitive tasks, neurobehavioral symptoms, or chronic stress. Higher chronic stress levels result in a decrease in verbal memory (p = .015) and motor processing speed (p = .006) and slower reaction time (p = .007) for women. As male NFI cognition scores increased, motor processing speed scores decreased (p = .012) and reaction time got slower (p = .019), whereas women exhibited decreased verbal memory (p = .017) and slower reaction time (p = .034). As NFI motor symptoms increased, men exhibited decreased verbal memory (p = .005), visual memory (p = .002), and motor processing speed (p = .002) and slower reaction time (p = .002). Overall, this study only found gender differences on verbal memory composite scores, whereas the remaining cognitive tasks, neurobehavioral symptoms, and chronic stress did not indicate gender differences. Correlations between chronic stress, neurobehavioral symptoms, and cognitive function differed in both men and women with TBI. Persons in the chronic phase of recovery from a TBI may benefit from training in compensatory strategies for verbal memory deficits and stress management.

Sex differences in disinhibition and its relationship to physical abuse in a sample of stimulant-dependent patients.

PubMed

Winhusen, Theresa; Lewis, Daniel

2013-04-01

Research suggests that impulsivity is a vulnerability factor for developing stimulant dependence, that women develop dependence more quickly than men, and that physical abuse can increase impulsivity and may have greater adverse health consequences in women. This study sought to tie these findings together by evaluating: (1) sex differences in disinhibition prior to lifetime initiation of stimulant abuse and (2) the relationship between physical abuse and disinhibition in stimulant-dependent patients. The Frontal Systems Behavior Scale (FrSBe) is a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses pre-morbid functioning and has a specific cutoff for defining clinically significant abnormalities. Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 118 methamphetamine- and/or cocaine-dependent participants. Lifetime physical abuse was measured by the Addiction Severity Index (ASI). The proportion reporting clinically significant disinhibition was significantly higher in women (64.9%) than in men (45.0%, p=0.04), with no significant difference on the other FrSBe scales. Physical abuse in women, but not men, was associated with worse functioning, with physically abused, relative to non-abused, women having a significantly greater proportion with clinically significant disinhibition (p<0.01) and total neurobehavioral abnormalities (p<0.01). These findings suggest that women may have significantly greater disinhibition than men prior to lifetime initiation of stimulant abuse and that physical abuse in women is associated with greater disinhibition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Current Topics in Postnatal Behavioral Testing.

PubMed

Henck, Judith W; Elayan, Ikram; Vorhees, Charles; Fisher, J Edward; Morford, LaRonda L

2016-09-01

The study of developmental neurotoxicity (DNT) continues to be an important component of safety evaluation of candidate therapeutic agents and of industrial and environmental chemicals. Developmental neurotoxicity is considered to be an adverse change in the central and/or peripheral nervous system during development of an organism and has been primarily evaluated by studying functional outcomes, such as changes in behavior, neuropathology, neurochemistry, and/or neurophysiology. Neurobehavioral evaluations are a component of a wide range of toxicology studies in laboratory animal models, whereas neurochemistry and neurophysiology are less commonly employed. Although the primary focus of this article is on neurobehavioral evaluation in pre- and postnatal development and juvenile toxicology studies used in pharmaceutical development, concepts may also apply to adult nonclinical safety studies and Environmental Protection Agency/chemical assessments. This article summarizes the proceedings of a symposium held during the 2015 American College of Toxicology annual meeting and includes a discussion of the current status of DNT testing as well as potential issues and recommendations. Topics include the regulatory context for DNT testing; study design and interpretation; behavioral test selection, including a comparison of core learning and memory systems; age of testing; repeated testing of the same animals; use of alternative animal models; impact of findings; and extrapolation of animal results to humans. Integration of the regulatory experience and scientific concepts presented during this symposium, as well as from subsequent discussion and input, provides a synopsis of the current state of DNT testing in safety assessment, as well as a potential roadmap for future advancement. © The Author(s) 2016.

Maternal smoking during pregnancy and risk of alcohol use disorders among adult offspring.

PubMed

Nomura, Yoko; Gilman, Stephen E; Buka, Stephen L

2011-03-01

The aim of this study was to evaluate the association between maternal smoking during pregnancy (MSP) and lifetime risk for alcohol use disorder (AUD) and to explore possible mechanisms through which MSP may be related to neurobehavioral conditions during infancy and childhood, which could, in turn, lead to increased risk for AUD. A sample of 1,625 individuals was followed from pregnancy for more than 40 years. Capitalizing on the long follow-up time, we used survival analysis to examine lifetime risks of AUD (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) in relation to levels of MSP (none, <20 cigarettes/day, and ≥20 cigarettes/day). We then used structural equation modeling to test hypotheses regarding potential mechanisms, including lower birth weight, neurological abnormalities, poorer academic functioning, and behavioral dysregulation. Relative to unexposed offspring, offspring of mothers who smoked 20 cigarettes per day or more exhibited greater risks for AUD (hazard ratio = 1.31, 95% CI [1.08, 1.59]). However, no differences were observed among offspring exposed to fewer than 20 cigarettes per day. In structural equation models, MSP was associated with neurobehavioral problems during infancy and childhood, which, in turn, were associated with an increased risk for adult AUD. MSP was associated with an increased lifetime risk for AUD. Adverse consequences were evident from birth to adulthood. A two-pronged remedial intervention targeted at both the mother (to reduce smoking during pregnancy) and child (to improve academic functioning) may reduce the risk for subsequent AUD.

On-Line Analysis of Physiologic and Neurobehavioral Variables During Long-Duration Space Missions

NASA Technical Reports Server (NTRS)

Brown, Emery N.

1999-01-01

The goal of this project is to develop reliable statistical algorithms for on-line analysis of physiologic and neurobehavioral variables monitored during long-duration space missions. Maintenance of physiologic and neurobehavioral homeostasis during long-duration space missions is crucial for ensuring optimal crew performance. If countermeasures are not applied, alterations in homeostasis will occur in nearly all-physiologic systems. During such missions data from most of these systems will be either continually and/or continuously monitored. Therefore, if these data can be analyzed as they are acquired and the status of these systems can be continually assessed, then once alterations are detected, appropriate countermeasures can be applied to correct them. One of the most important physiologic systems in which to maintain homeostasis during long-duration missions is the circadian system. To detect and treat alterations in circadian physiology during long duration space missions requires development of: 1) a ground-based protocol to assess the status of the circadian system under the light-dark environment in which crews in space will typically work; and 2) appropriate statistical methods to make this assessment. The protocol in Project 1, Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral will study human volunteers under the simulated light-dark environment of long-duration space missions. Therefore, we propose to develop statistical models to characterize in near real time circadian and neurobehavioral physiology under these conditions. The specific aims of this project are to test the hypotheses that: 1) Dynamic statistical methods based on the Kronauer model of the human circadian system can be developed to estimate circadian phase, period, amplitude from core-temperature data collected under simulated light- dark conditions of long-duration space missions. 2) Analytic formulae and numerical algorithms can be developed to compute the error in the estimates of circadian phase, period and amplitude determined from the data in Specific Aim 1. 3) Statistical models can detect reliably in near real- time (daily) significant alternations in the circadian physiology of individual subjects by analyzing the circadian and neurobehavioral data collected in Project 1. 4) Criteria can be developed using the Kronauer model and the recently developed Jewett model of cognitive -performance and subjective alertness to define altered circadian and neurobehavioral physiology and to set conditions for immediate administration of countermeasures.

Assessment of neurotoxic effects of mercury in beluga whales (Delphinapterus leucas), ringed seals (Pusa hispida), and polar bears (Ursus maritimus) from the Canadian Arctic.

PubMed

Krey, Anke; Ostertag, Sonja K; Chan, Hing Man

2015-03-15

Marine mammals are indicator species of the Arctic ecosystem and an integral component of the traditional Inuit diet. The potential neurotoxic effects of increased mercury (Hg) in beluga whales (Delphinapterus leucas), ringed seals (Pusa hispida), and polar bears (Ursus maritimus) are not clear. We assessed the risk of Hg-associated neurotoxicity to these species by comparing their brain Hg concentrations with threshold concentrations for toxic endpoints detected in laboratory animals and field observations: clinical symptoms (>6.75 mg/kg wet weight (ww)), neuropathological signs (>4 mg/kg ww), neurochemical changes (>0.4 mg/kg ww), and neurobehavioral changes (>0.1mg/kg ww). The total Hg (THg) concentrations in the cerebellum and frontal lobe of ringed seals and polar bears were <0.5mg/kg ww, whereas the average concentration in beluga whale brain was >3mg/kg ww. Our results suggest that brain THg levels in polar bears are below levels that induce neurobehavioral effects as reported in the literature, while THg concentrations in ringed seals are within the range that elicit neurobehavioral effects and individual ringed seals exceed the threshold for neurochemical changes. The relatively high THg concentration in beluga whales exceeds all of the neurotoxicity thresholds assessed. High brain selenium (Se):Hg molar ratios were observed in all three species, suggesting that Se could protect the animals from Hg-associated neurotoxicity. This assessment was limited by several factors that influence neurotoxic effects in animals, including: animal species; form of Hg in the brain; and interactions with modifiers of Hg-associated toxicity, such as Se. Comparing brain Hg concentrations in wildlife with concentrations of appropriate laboratory studies can be used as a tool for risk characterization of the neurotoxic effects of Hg in Arctic marine mammals. Copyright © 2014 Elsevier B.V. All rights reserved.

NEUROBEHAVIORAL EFFECTS OF GESTATIONAL AND PERINATAL EXPOSURE TO HEPTACHLOR IN RATS.

EPA Science Inventory

In nervous system development, GABA serves as a trophic signal which influences the development of almost all neurotransmitter systems, and is the earliest neurotransmitter detected in fetal rat brain. Since cyclodiene pesticides block GABAergic neurotransmission they may have pr...

Exposure to radio-frequency electromagnetic waves alters acetylcholinesterase gene expression, exploratory and motor coordination-linked behaviour in male rats.

PubMed

Obajuluwa, Adejoke Olukayode; Akinyemi, Ayodele Jacob; Afolabi, Olakunle Bamikole; Adekoya, Khalid; Sanya, Joseph Olurotimi; Ishola, Azeez Olakunle

2017-01-01

Humans in modern society are exposed to an ever-increasing number of electromagnetic fields (EMFs) and some studies have demonstrated that these waves can alter brain function but the mechanism still remains unclear. Hence, this study sought to investigate the effect of 2.5 Ghz band radio-frequency electromagnetic waves (RF-EMF) exposure on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA expression level as well as locomotor function and anxiety-linked behaviour in male rats. Animals were divided into four groups namely; group 1 was control (without exposure), group 2-4 were exposed to 2.5 Ghz radiofrequency waves from an installed WI-FI device for a period of 4, 6 and 8 weeks respectively. The results revealed that WiFi exposure caused a significant increase in anxiety level and affect locomotor function. Furthermore, there was a significant decrease in AChE activity with a concomitant increase in AChE mRNA expression level in WiFi exposed rats when compared with control. In conclusions, these data showed that long term exposure to WiFi may lead to adverse effects such as neurodegenerative diseases as observed by a significant alteration on AChE gene expression and some neurobehavioral parameters associated with brain damage.

ROLE OF CENTRAL NERVOUS SYSTEM INSULIN RESISTANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

de la Monte, Suzanne M; Wands, Jack R

2011-01-01

Fetal alcohol spectrum disorder (FASD) is the most common preventable cause of mental retardation in the USA. Ethanol impairs neuronal survival and function by two major mechanisms: 1) it inhibits insulin signaling required for viability, metabolism, synapse formation, and acetylcholine production; and 2) it functions as a neurotoxicant, causing oxidative stress, DNA damage and mitochondrial dysfunction. Ethanol inhibition of insulin signaling is mediated at the insulin receptor (IR) level and caused by both impaired receptor binding and increased activation of phosphatases that reverse IR tyrosine kinase activity. As a result, insulin activation of PI3K-Akt, which mediates neuronal survival, motility, energy metabolism, and plasticity, is impaired. The neurotoxicant effects of ethanol promote DNA damage, which could contribute to mitochondrial dysfunction and oxidative stress. Therefore, chronic in utero ethanol exposure produces a dual state of CNS insulin resistance and oxidative stress, which we postulate plays a major role in ethanol neurobehavioral teratogenesis. We propose that many of the prominent adverse effects of chronic prenatal exposure to ethanol on CNS development and function may be prevented or reduced by treatment with peroxisome-proliferated activated receptor (PPAR) agonists which enhance insulin sensitivity by increasing expression and function of insulin-responsive genes, and reducing cellular oxidative stress. PMID:21063035

Neurobehavioral and Psychosocial Issues in Klinefelter Syndrome

ERIC Educational Resources Information Center

Geschwind, Daniel H.; Dykens, Elisabeth

2004-01-01

Klinefelter Syndrome (KS) is a relatively common (1/500 to 1/1,000) genetic syndrome caused by an extra X chromosome in males, leading to an XXY karyotype. In most cases, the physical and neurobehavioral characteristics of KS are relatively mild, and KS is not usually associated with moderate or severe mental retardation. However, KS is often…

Neurobehavioral Consequences of Prenatal Exposure to Smoking at 6 to 8 Months of Age

ERIC Educational Resources Information Center

Willoughby, Michael; Greenberg, Mark; Blair, Clancy; Stifter, Cynthia

2007-01-01

Between 400,000 and 800,000 infants are born in the United States each year to women who smoked cigarettes during their pregnancy. Whereas the physical health consequences to infants of prenatal exposure to smoking are well established, the early neurobehavioral consequences are less well understood. This study investigated the neurobehavioral…

Epigenetic Regulation of Placental "NR3C1": Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking?

ERIC Educational Resources Information Center

Stroud, Laura R.; Papandonatos, George D.; Salisbury, Amy L.; Phipps, Maureen G.; Huestis, Marilyn A.; Niaura, Raymond; Padbury, James F.; Marsit, Carmen J.; Lester, Barry M.

2016-01-01

Epigenetic regulation of the placental glucocorticoid receptor gene ("NR3C1") was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP-exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral…

Sleep Deprivation and Neurobehavioral Dynamics

PubMed Central

Basner, Mathias; Rao, Hengyi; Goel, Namni; Dinges, David F.

2013-01-01

Lifestyles involving sleep deprivation are common, despite mounting evidence that both acute total sleep deprivation and chronically restricted sleep degrade neurobehavioral functions associated with arousal, attention, memory and state stability. Current research suggests dynamic differences in the way the central nervous system responds to acute versus chronic sleep restriction, which is reflected in new models of sleep-wake regulation. Chronic sleep restriction likely induces long-term neuromodulatory changes in brain physiology that could explain why recovery from it may require more time than from acute sleep loss. High intraclass correlations in neurobehavioral responses to sleep loss suggest that these trait-like differences are phenotypic and may include genetic components. Sleep deprivation induces changes in brain metabolism and neural activation that involve distributed networks and connectivity. PMID:23523374

Neurobehavioral Disorder Associated With Prenatal Alcohol Exposure

PubMed Central

Hagan, Joseph F.; Balachova, Tatiana; Bertrand, Jacquelyn; Chasnoff, Ira; Dang, Elizabeth; Fernandez-Baca, Daniel; Kable, Julie; Kosofsky, Barry; Senturias, Yasmin N.; Singh, Natasha; Sloane, Mark; Weitzman, Carol; Zubler, Jennifer

2017-01-01

Children and adolescents affected by prenatal exposure to alcohol who have brain damage that is manifested in functional impairments of neurocognition, self-regulation, and adaptive functioning may most appropriately be diagnosed with neurobehavioral disorder associated with prenatal exposure. This Special Article outlines clinical implications and guidelines for pediatric medical home clinicians to identify, diagnose, and refer children regarding neurobehavioral disorder associated with prenatal exposure. Emphasis is given to reported or observable behaviors that can be identified as part of care in pediatric medical homes, differential diagnosis, and potential comorbidities. In addition, brief guidance is provided on the management of affected children in the pediatric medical home. Finally, suggestions are given for obtaining prenatal history of in utero exposure to alcohol for the pediatric patient. PMID:27677572

Overlapping neurobehavioral circuits in ADHD, obesity, and binge eating: Evidence from Neuroimaging Research

PubMed Central

Seymour, Karen E.; Reinblatt, Shauna P.; Benson, Leora; Carnell, Susan

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (e.g. obesity, binge / loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, e.g. functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing i) reward processing, ii) response inhibition, and iii) emotional processing and regulation, and outline three specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research. PMID:26098969

Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

PubMed

Singh, K P; Tripathi, Nidhi

2015-05-01

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute and Developmental Behavioral Effects of Flame ...

EPA Pesticide Factsheets

As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4’-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n≈24 per dose per compound) were exposed to test compounds (0.4 - 120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system. This study

Poisoning Young Minds.

ERIC Educational Resources Information Center

Schmidt, Charles W.

1999-01-01

Notes that neurobehavioral problems from exposure to lead and other toxins can be observed at doses far below those that cause more obvious signs of exposure. Calls for refining tests of cognitive and developmental skills in exposed children, identifying additional contaminants and mechanisms for behavioral effects, and improving dose- repose…

Acute and Developmental Behavioral Effects of Flame Retardants and Related Chemicals in Zebrafish

EPA Science Inventory

As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the ne...

Effects of in utero and lactational exposure to SbV on rat neurobehavioral development and fertility.

PubMed

Coelho, Deise R; De-Carvalho, Rosangela R; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Paumgartten, Francisco J R

2014-12-01

Meglumine antimoniate (MA) is a pentavalent antimony drug used to treat leishmaniases. We investigated the neurobehavioral development, sexual maturation and fertility of the offspring of MA-treated rats. Dams were administered MA (0, 75, 150, 300 mg Sb(V)/kg body wt/d, sc) from gestation day 0, throughout parturition and lactation, until weaning. At the highest dose, MA reduced the birth weight and the number of viable newborns. In the male offspring, MA did not impair development (somatic, reflex maturation, weight gain, puberty onset, open field test), sperm count, or reproductive performance. Except for a minor effect on body weight gain and vertical exploration in the open field, MA also did not affect the development of female offspring. Measurements of the Sb levels (ICP-MS) in the blood of MA-treated female rats and their offspring demonstrated that Sb is transferred to the fetuses via the placenta and to the suckling pups via milk. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of cumulative pain/stress on neurobehavioral development of preterm infants in the NICU.

PubMed

Cong, Xiaomei; Wu, Jing; Vittner, Dorothy; Xu, Wanli; Hussain, Naveed; Galvin, Shari; Fitzsimons, Megan; McGrath, Jacqueline M; Henderson, Wendy A

2017-05-01

Vulnerable preterm infants experience repeated and prolonged pain/stress stimulation during a critical period in their development while in the neonatal intensive care unit (NICU). The contribution of cumulative pain/stressors to altered neurodevelopment remains unclear. The study purpose was to investigate the impact of early life painful/stressful experiences on neurobehavioral outcomes of preterm infants in the NICU. A prospective exploratory study was conducted with fifty preterm infants (28 0/7-32 6/7weeks gestational age) recruited at birth and followed for four weeks. Cumulative pain/stressors (NICU Infant Stressor Scale) were measured daily and neurodevelopmental outcomes (NICU Network Neurobehavioral Scale) were examined at 36-37weeks post-menstrual age. Data analyses were conducted on the distribution of pain/stressors experienced over time and the linkages among pain/stressors and neurobehavioral outcomes. Preterm infants experienced a high degree of pain/stressors in the NICU, both in numbers of daily acute events (22.97±2.30 procedures) and cumulative times of chronic/stressful exposure (42.59±15.02h). Both acute and chronic pain/stress experienced during early life significantly contributed to the neurobehavioral outcomes, particularly in stress/abstinence (p<0.05) and habituation responses (p<0.01), meanwhile, direct breastfeeding and skin-to-skin holding were also significantly associated with habituation (p<0.01-0.05). Understanding mechanisms by which early life experience alters neurodevelopment will assist clinicians in developing targeted neuroprotective strategies and individualized interventions to improve infant developmental outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting risk in space: Genetic markers for differential vulnerability to sleep restriction

NASA Astrophysics Data System (ADS)

Goel, Namni; Dinges, David F.

2012-08-01

Several laboratories have found large, highly reliable individual differences in the magnitude of cognitive performance, fatigue and sleepiness, and sleep homeostatic vulnerability to acute total sleep deprivation and to chronic sleep restriction in healthy adults. Such individual differences in neurobehavioral performance are also observed in space flight as a result of sleep loss. The reasons for these stable phenotypic differential vulnerabilities are unknown: such differences are not yet accounted for by demographic factors, IQ or sleep need, and moreover, psychometric scales do not predict those individuals cognitively vulnerable to sleep loss. The stable, trait-like (phenotypic) inter-individual differences observed in response to sleep loss—with intraclass correlation coefficients accounting for 58-92% of the variance in neurobehavioral measures—point to an underlying genetic component. To this end, we utilized multi-day highly controlled laboratory studies to investigate the role of various common candidate gene variants—each independently—in relation to cumulative neurobehavioral and sleep homeostatic responses to sleep restriction. These data suggest that common genetic variations (polymorphisms) involved in sleep-wake, circadian, and cognitive regulation may serve as markers for prediction of inter-individual differences in sleep homeostatic and neurobehavioral vulnerability to sleep restriction in healthy adults. Identification of genetic predictors of differential vulnerability to sleep restriction—as determined from candidate gene studies—will help identify astronauts most in need of fatigue countermeasures in space flight and inform medical standards for obtaining adequate sleep in space. This review summarizes individual differences in neurobehavioral vulnerability to sleep deprivation and ongoing genetic efforts to identify markers of such differences.

The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

McInturf, S.M.; Bekkedal, M.Y.V.; Wilfong, E.

2011-07-15

The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distressmore » vocalizations were elevated in F{sub 1} offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F{sub 1} females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P{sub 0} animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.« less

Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

PubMed

Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

2016-03-01

The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2015-09-01

for public release; distribution unlimited Autism spectrum disorder (ASD); biomarker; early brain development; intrinsic functional brain networks...three large neuroimaging/neurobehavioral datasets to identify brain-imaging based biomarkers for Autism Spectrum Disorders (ASD). At Yale, we focus...neurobehavioral!datasets!in!order!to!identify! brainFimaging!based!biomarkers!for! Autism ! Spectrum ! Disorders !(ASD),!including!1)!BrainMap,! developed!and

Distal 10q monosomy: new evidence for a neurobehavioral condition?

PubMed

Plaisancié, Julie; Bouneau, Laurence; Cances, Claude; Garnier, Christelle; Benesteau, Jacques; Leonard, Samantha; Bourrouillou, Georges; Calvas, Patrick; Vigouroux, Adeline; Julia, Sophie; Bieth, Eric

2014-01-01

Pure distal monosomy of the long arm of chromosome 10 is a rare cytogenetic abnormality. The location and size of the deletions described in this region are variable. Nevertheless, the patients share characteristic facial appearance, variable cognitive impairment and neurobehavioral manifestations. A Minimal Critical Region corresponding to a 600 kb Smallest Region of deletion Overlap (SRO) has been proposed. In this report, we describe four patients with a distal 10q26 deletion, who displayed attention-deficit/hyperactivity disorders (ADHD). One of them had a marked behavioral profile and relatively preserved cognitive functions. Interestingly, the SRO was not included in the deleted segment of this patient suggesting that this deletion could contain candidate genes involved in the control of neurobehavioral functions. One of these candidates was the CALY gene, known for its association with ADHD patients and whose expression level was shown to be correlated with neurobehavioral disturbances in varying animal models. This report emphasizes the importance of the behavioral problems as a cardinal feature of the 10q microdeletion syndrome. Haploinsufficiency of CALY could play a crucial role in the development of the behavioral troubles within these patients. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Impact of hospital-based environmental exposures on neurodevelopmental outcomes of preterm infants.

PubMed

Santos, Janelle; Pearce, Sarah E; Stroustrup, Annemarie

2015-04-01

Over 300,000 infants are hospitalized in a neonatal intensive care unit (NICU) in the United States annually during a developmental period critical to later neurobehavioral function. Environmental exposures during the fetal period and infancy have been shown to impact long-term neurobehavioral outcomes. This review summarizes evidence linking NICU-based environmental exposures to neurodevelopmental outcomes of children born preterm. Preterm infants experience multiple exposures important to neurodevelopment during the NICU hospitalization. The physical layout of the NICU, management of light and sound, social interactions with parents and NICU staff, and chemical exposures via medical equipment are important to long-term neurobehavioral outcomes in this highly vulnerable population. Existing research documents NICU-based exposure to neurotoxic chemicals, aberrant light, excess sound, and restricted social interaction. In total, this creates an environment of co-existing excesses (chemicals, light, sound) and deprivation (touch, speech). The full impact of these co-exposures on the long-term neurodevelopment of preterm infants has not been adequately elucidated. Research into the importance of the NICU from an environmental health perspective is in its infancy, but could provide understanding about critical modifiable factors impacting the neurobehavioral health of hundreds of thousands of children each year.

Studying Health Outcomes in Farmworker Populations Exposed to Pesticides

PubMed Central

McCauley, Linda A.; Anger, W. Kent; Keifer, Matthew; Langley, Rick; Robson, Mark G.; Rohlman, Diane

2006-01-01

A major goal of studying farmworkers is to better understand how their work environment, including exposure to pesticides, affects their health. Although a number of health conditions have been associated with pesticide exposure, clear linkages have yet to be made between exposure and health effects except in cases of acute pesticide exposure. In this article, we review the most common health end points that have been studied and describe the epidemiologic challenges encountered in studying these health effects of pesticides among farmworkers, including the difficulties in accessing the population and challenges associated with obtaining health end point data. The assessment of neurobehavioral health effects serves as one of the most common and best examples of an approach used to study health outcomes in farmworkers and other populations exposed to pesticides. We review the current limitations in neurobehavioral assessment and strategies to improve these analytical methods. Emerging techniques to improve our assessment of health effects associated with pesticide exposure are reviewed. These techniques, which in most cases have not been applied to farmworker populations, hold promise in our ability to study and understand the relationship between pesticide exposure and a variety of health effects in this population. PMID:16760000

Is the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) effective for preterm infants with intrauterine growth restriction?

PubMed Central

Als, H; Duffy, FH; McAnulty, GB; Fischer, CB; Kosta, S; Butler, SC; Parad, RB; Blickman, JG; Zurakowski, D; Ringer, SA

2014-01-01

Objective This study investigates the effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) on neurobehavioral and electrophysiological functioning of preterm infants with severe intrauterine growth restriction (IUGR). Study Design Thirty IUGR infants, 28 to 33 weeks gestational age, randomized to standard care (control/C = 18), or NIDCAP (experimental/E = 12), were assessed at 2 weeks corrected age (2wCA) and 9 months corrected age (9mCA) in regard to health, anthropometrics, and neurobehavior, and additionally at 2wCA in regard to electrophysiology (EEG). Result The two groups were comparable in health and anthropometrics at 2wCA and 9mCA. The E-group at 2wCA showed significantly better autonomic, motor, and self-regulation functioning, improved motility, intensity and response thresholds, and reduced EEG connectivity among several adjacent brain regions. At 9mCA, the E-group showed significantly better mental performance. Conclusion This is the first study to show NIDCAP effectiveness for IUGR preterm infants. PMID:20651694

Medical management of children with epilepsy.

PubMed

Ackermann, S; Wilmshurst, J M

2015-02-01

Epilepsy is a common neurological condition presenting to the pediatrician. There are many seizure mimics and the differential diagnosis of paroxysmal events is wide which may make a definitive diagnosis challenging. Epilepsy is a heterogeneous condition with marked variability in presentation, underlying etiologies, associated comorbidities and outcomes. The reorganization of epilepsies in 2010 reflects an increasing understanding of the neuropathological and etiological mechanisms as a result of rapid technological advances in neuroimaging techniques and molecular genetics in particular. An increasing number of treatment options are available although high quality evidence, applicable to children, is lacking. Choices should be tailored to the individual patient applying knowledge of adverse drug effects, including the potential for seizure exacerbation in certain syndromes. Neurobehavioral and psychiatric comorbidities occur in up to 80% of children and frequently remain unrecognized. Screening for these conditions should form part of holistic management, along with awareness of the psychosocial and educational needs of the child from the time of initial diagnosis. The management of individual children with epilepsy therefore presents a myriad challenges. Early referral to a specialist with expertise in the management of pediatric epilepsy should be sought whenever there is diagnostic uncertainty or a poor response to therapy.

Infant malnutrition predicts conduct problems in adolescents

PubMed Central

Galler, Janina R.; Bryce, Cyralene P.; Waber, Deborah P.; Hock, Rebecca S.; Harrison, Robert; Eaglesfield, G. David; Fitzmaurice, Garret

2013-01-01

Objectives The purpose of this study was to compare the prevalence of conduct problems in a well-documented sample of Barbadian adolescents malnourished as infants and a demographic comparison group and to determine the extent to which cognitive impairment and environmental factors account for this association. Methods Behavioral symptoms were assessed using a 76-item self-report scale in 56 Barbadian youth (11–17 years of age) with histories of protein–energy malnutrition (PEM) limited to the first year of life and 60 healthy classmates. Group comparisons were carried out by longitudinal and cross-sectional multiple regression analyses at 3 time points in childhood and adolescence. Results Self-reported conduct problems were more prevalent among previously malnourished youth (P < 0.01). Childhood IQ and home environmental circumstances partially mediated the association with malnutrition. Teacher-reported classroom behaviors at earlier ages were significantly correlated with youth conduct problems, confirming the continuity of conduct problems through childhood and adolescence. Discussion Self-reported conduct problems are elevated in children and adolescents with histories of early childhood malnutrition. Later vulnerability to increased conduct problems appears to be mediated by the more proximal neurobehavioral effects of the malnutrition on cognitive function and by adverse conditions in the early home environment. PMID:22584048

Infant malnutrition predicts conduct problems in adolescents.

PubMed

Galler, Janina R; Bryce, Cyralene P; Waber, Deborah P; Hock, Rebecca S; Harrison, Robert; Eaglesfield, G David; Fitzmaurice, Garret

2012-07-01

The purpose of this study was to compare the prevalence of conduct problems in a well-documented sample of Barbadian adolescents malnourished as infants and a demographic comparison group and to determine the extent to which cognitive impairment and environmental factors account for this association. Behavioral symptoms were assessed using a 76-item self-report scale in 56 Barbadian youth (11-17 years of age) with histories of protein-energy malnutrition (PEM) limited to the first year of life and 60 healthy classmates. Group comparisons were carried out by longitudinal and cross-sectional multiple regression analyses at 3 time points in childhood and adolescence. Self-reported conduct problems were more prevalent among previously malnourished youth (P < 0.01). Childhood IQ and home environmental circumstances partially mediated the association with malnutrition. Teacher-reported classroom behaviors at earlier ages were significantly correlated with youth conduct problems, confirming the continuity of conduct problems through childhood and adolescence. Self-reported conduct problems are elevated in children and adolescents with histories of early childhood malnutrition. Later vulnerability to increased conduct problems appears to be mediated by the more proximal neurobehavioral effects of the malnutrition on cognitive function and by adverse conditions in the early home environment.

Development of allosteric modulators of GPCRs for treatment of CNS disorders.

PubMed

Nickols, Hilary Highfield; Conn, P Jeffrey

2014-01-01

The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as "bitopic" ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction. © 2013.

Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

PubMed

Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

2010-01-01

Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

Evaluating and treating neurobehavioral symptoms in professional American football players

PubMed Central

Possin, Katherine L.; Hess, Christopher P.; Huang, Eric J.; Grinberg, Lea T.; Nolan, Amber L.; Cohn-Sheehy, Brendan I.; Ghosh, Pia M.; Lanata, Serggio; Merrilees, Jennifer; Kramer, Joel H.; Berger, Mitchel S.; Miller, Bruce L.; Yaffe, Kristine; Rabinovici, Gil D.

2015-01-01

Summary In the aftermath of multiple high-profile cases of chronic traumatic encephalopathy (CTE) in professional American football players, physicians in clinical practice are likely to face an increasing number of retired football players seeking evaluation for chronic neurobehavioral symptoms. Guidelines for the evaluation and treatment of these patients are sparse. Clinical criteria for a diagnosis of CTE are under development. The contribution of CTE vs other neuropathologies to neurobehavioral symptoms in these players remains unclear. Here we describe the experience of our academic memory clinic in evaluating and treating a series of 14 self-referred symptomatic players. Our aim is to raise awareness in the neurology community regarding the different clinical phenotypes, idiosyncratic but potentially treatable symptoms, and the spectrum of underlying neuropathologies in these players. PMID:26336629

Long-term perchloroethylene exposure: a limited meta-analysis of neurobehavorial deficits in occupationally and residentially exposed groups

EPA Science Inventory

The literature concerning the neurobehavioral and neurophysiological effects of long-term exposure to perchloroethylene (PERC) in humans was meta-analyzed to provide a quantitative review and synthesis. The useable data base from this literature comprised studies reporting effec...

METHODOLOGICAL ISSUES IN HUMAN EXPOSURE STUDIES OF LOW LEVEL SOLVENT MIXTURES

EPA Science Inventory

The design of appropriate studies to assess the sensory irritant and neurobehavioral-effects of exposure to complex VOC mixtures poses a variety of methodological challenges, particularly at the low levels found in new buildings. or instance, Otto et al (1989) exposed subjects to...

EXPERIMENTAL DESIGN AND INSTRUMENTATION FOR A FIELD EXPERIMENT

EPA Science Inventory

This report concerns the design of a field experiment for a military setting in which the effects of carbon monoxide on neurobehavioral variables are to be studied. ield experiment is distinguished from a survey by the fact that independent variables are manipulated, just as in t...

Neurobehavioral evaluations of rats gestationally exposed to gasoline vapors

EPA Science Inventory

As the US fuel supply is moving towards blends with higher ethanol levels, there are questions regarding effects of these fuel vapors in the developing fetus. As part of a project evaluating gasoline-ethanol blends of different proportions. we included an evaluation of inhaled pu...

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

DTIC Science & Technology

2015-10-01

characterization of the mouse model of repeated blast also found no cumula- tive effect of repeated blast on cortical levels of reactive oxygen species [39]. C...overpressure in rats to investigate the cumulative effects of multiple blast exposures on neurologic status, neurobehavioral function, and brain...preclinical model of blast overpressure in rats to investigate the cumulative effects of multiple blast exposures using neurological, neurochemical

Marijuana and Breastfeeding: Applicability of the Current Literature to Clinical Practice.

PubMed

Mourh, Jasminder; Rowe, Hilary

2017-12-01

With recent legalization of marijuana in numerous U.S. states, the risk of marijuana exposure via breast milk is a rising concern. This review analyzes the available human and animal literature regarding maternal use of marijuana during lactation. The findings can be categorized into four areas of analysis: effects of marijuana on the mother, transfer into milk, transfer to the offspring, and effects on the offspring. Human and animal data have reported decreased prolactin levels as well as potential maternal psychological changes. Animal and human studies have reported transfer into milk; levels were detected in animal offspring, and metabolites were excreted by both human and animal offspring. Further, animal data have predominately displayed motor, neurobehavioral, and developmental effects, whereas human data suggested possible psychomotor outcomes; however, some studies reported no effect. Despite these results, many human studies were marred by limitations, including small sample sizes and confounding variables. Also, the applicability of animal data to the human population is questionable and the true risk of adverse effects is not entirely known. There are large gaps in the literature that need to be addressed; in particular, studies need to focus on evaluating the short- and long-term consequences of maternal marijuana use for the infant and the potential for different risks based on the frequency of maternal use. Until further evidence becomes available, practitioners need to weigh the benefits of breastfeeding for mother and child, with the potential influence of marijuana on infant development when determining the infant's most suitable form of nutrition.

The interaction between manganese exposure and alcohol on neurobehavioral outcomes in welders.

PubMed

Ellingsen, Dag G; Kusraeva, Zarina; Bast-Pettersen, Rita; Zibarev, Evgenij; Chashchin, Maxim; Thomassen, Yngvar; Chashchin, Valery

2014-01-01

Neurobehavioral functions were studied in 137 welders exposed to the geometric mean (GM) air concentration of 214 μg/m(3) (range 1-3230) of manganese (Mn) based on the individual mean from two days of air sampling. Only 22 μg/m(3) (GM) was soluble in the artificial lung fluid Hatch solution. The welders were compared to 137 referents (turner/fitters) recruited from the same plants. The GM concentrations of Mn in whole blood (B-Mn) and urine (U-Mn) were 12.8 μg/L and 0.36 μg/g creatinine versus 8.0 μg/L and 0.07 μg/g creatinine in the referents. Alcohol consumption was assessed by measuring carbohydrate deficient transferrin in serum (sCDT). The welders had poorer performance than the referents on the Grooved Pegboard, Finger Tapping, Simple Reaction Time (SRT) and possibly the Maximum Frequency tests. They also reported more subjective symptoms. Welders with sCDT above the upper reference limit had substantially poorer performances on the Grooved Pegboard test, Finger Tapping test and SRT than welders with sCDT below this level. No effect of high sCDT was observed in the referents, indicating an interaction between high sCDT and exposure to Mn for these tests. Self-reported alcohol consumption had no impact on these neurobehavioral test results. A statistically significant difference in the SRT and Grooved Pegboard test results remained after excluding all subjects with sCDT above the normal level, but the difference in test scores between the groups was smaller. These welders also reported more subjective symptoms than the referents. The results suggest that sCDT should be measured in neurobehavioral studies of occupationally Mn exposed populations for a more precise estimation of high alcohol consumption. Copyright © 2013 Elsevier Inc. All rights reserved.

Prenatal Exposure to Organophosphate Pesticides and Neurobehavioral Development of Neonates: A Birth Cohort Study in Shenyang, China

PubMed Central

Zhang, Ying; Han, Song; Liang, Duohong; Shi, Xinzhu; Wang, Fengzhi; Liu, Wei; Zhang, Li; Chen, Lixin; Gu, Yingzi; Tian, Ying

2014-01-01

Background A large amount of organophosphate pesticides (OPs) are used in agriculture in China every year, contributing to exposure of OPs through dietary consumption among the general population. However, the level of exposure to OPs in China is still uncertain. Objective To investigate the effect of the exposure to OPs on the neonatal neurodevelopment during pregnancy in Shenyang, China. Methods 249 pregnant women enrolled in the Central Hospital Affiliated to Shenyang Medical College from February 2011 to August 2012. A cohort of the mothers and their neonates participated in the study and information on each subject was obtained by questionnaire. Dialkyl phosphate (DAP) metabolites were detected in the urine of mothers during pregnancy to evaluate the exposure level to OPs. Neonate neurobehavioral developmental levels were assessed according to the standards of the Neonatal Behavioral Neurological Assessment (NBNA). Multiple linear regressions were utilized to analyze the association between pregnancy exposure to OPs and neonatal neurobehavioral development. Results The geometric means (GM) of urinary metabolites for dimethyl phosphate (DMP), dimethyl thiophosphate (DMTP), diethyl phosphate (DEP), and diethyl thiophosphate (DETP) in pregnant women were 18.03, 8.53, 7.14, and 5.64 µg/L, respectively. Results from multiple linear regressions showed that prenatal OP exposure was one of the most important factors affecting NBNA scores. Prenatal total DAP concentrations were inversely associated with scores on the NBNA scales.?Additionally, a 10-fold increase in DAP concentrations was associated with a decrease of 1.78 regarding the Summary NBNA (95% CI, −2.12 to −1.45). And there was an estimated 2.11-point difference in summary NBNA scores between neonates in the highest quintile of prenatal OP exposure and the lowest quintile group. Conclusion The high exposure of pregnant women to OPs in Shenyang, China was the predominant risk factor for neonatal neurobehavioral development. PMID:24551109

Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand

PubMed Central

LaGasse, Linda L.; Wouldes, Trecia; Newman, Elana; Smith, Lynne M.; Shah, Rizwan Z.; Derauf, Chris; Huestis, Marilyn A.; Arria, Amelia M.; Grotta, Sheri Della; Wilcox, Tara; Lester, Barry M.

2010-01-01

Background Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants. Design The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte. Results MA Exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress. Conclusion Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress. PMID:20615464

Chlorpyrifos exposures in Egyptian cotton field workers.

PubMed

Farahat, Fayssal M; Fenske, Richard A; Olson, James R; Galvin, Kit; Bonner, Matthew R; Rohlman, Diane S; Farahat, Taghreed M; Lein, Pamela J; Anger, W Kent

2010-06-01

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers. Copyright 2010 Elsevier Inc. All rights reserved.

Chlorpyrifos Exposures in Egyptian Cotton Field Workers

PubMed Central

Farahat, Fayssal M.; Fenske, Richard A.; Olson, James R.; Galvin, Kit; Bonner, Matthew R.; Rohlman, Diane S.; Lein, Pamela J.; Anger, W. Kent

2013-01-01

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: 1) dermal exposure was an important contributor to internal dose and varied across body regions; and 2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers. PMID:20193710

Tourette Syndrome: Overview and Classroom Interventions. A Complex Neurobehavioral Disorder Which May Involve Learning Problems, Attention Deficit Hyperactivity Disorder, Obsessive Compulsive Symptoms, and Stereotypical Behaviors.

ERIC Educational Resources Information Center

Fisher, Ramona A.; Collins, Edward C.

Tourette Syndrome is conceptualized as a neurobehavioral disorder, with behavioral aspects that are sometimes difficult for teachers to understand and deal with. The disorder has five layers of complexity: (1) observable multiple motor, vocal, and cognitive tics and sensory involvement; (2) Attention Deficit Hyperactivity Disorder; (3)…

Neuroprotective Effects of Sevoflurane against Electromagnetic Pulse-Induced Brain Injury through Inhibition of Neuronal Oxidative Stress and Apoptosis

PubMed Central

Wang, Jin; Han, Li-Chun; Li, Li-Ya; Wu, Guang-Li; Hou, Yan-Ning; Guo, Guo-Zhen; Wang, Qiang; Sang, Han-Fei; Xu, Li-Xian

2014-01-01

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis. PMID:24614080

Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

NASA Astrophysics Data System (ADS)

Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

2016-04-01

Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

Neuroprotective effects of sevoflurane against electromagnetic pulse-induced brain injury through inhibition of neuronal oxidative stress and apoptosis.

PubMed

Deng, Bin; Xu, Hao; Zhang, Jin; Wang, Jin; Han, Li-Chun; Li, Li-Ya; Wu, Guang-Li; Hou, Yan-Ning; Guo, Guo-Zhen; Wang, Qiang; Sang, Han-Fei; Xu, Li-Xian

2014-01-01

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis.

The Effects of Sleep Restriction and Extension on School-Age Children: What a Difference an Hour Makes.

ERIC Educational Resources Information Center

Sadeh, Avi; Gruber, Reut; Raviv, Amiram

2003-01-01

Assessed effects of sleep restriction and extension on 9- to 12-year-olds' neurobehavioral functioning. Found that modest sleep restriction led to improved sleep quality but to reduced reported alertness. Children who extended sleep improved significantly from baseline their performance on the digit forward memory test and reaction time on the…

EFFECT OF 3,3'-IMINODIPROPIONITRILE ON THE PERIPHERAL STRUCTURES OF THE RATVISUAL SYSTEM

EPA Science Inventory

Short-term repeated administration of 3,3'-iminodiproprionitrile (IDPN) results in a complex neurobehavioral syndrome that has been previously described (Thuiller and Burger, 1954). dult male Long-Evans rats received IDPN (400 mg/kg i.p.) and were killed, 1 day after one dose, or...

The Effects of Low Level Prenatal Carbon Monoxide on Neocortical Development

DTIC Science & Technology

2010-06-02

amount of NO available, which may have formed free radicals damaging the tissue and resulting in cell death. Treatment with a synthetic cGMP also failed...Watkinson B (36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana , cigarettes, and alcohol. J Dev Behav Pediatr

COMPARISON OF ACUTE NEUROBEHAVIORAL AND CHOLINESTERASE INHIBITORY EFFECTS OF N-METHYL CARBAMATES IN RAT

EPA Science Inventory

There are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (R...

Reply to Cicchetti, Kaufman, and Sparrow

ERIC Educational Resources Information Center

Weisglas-Kuperus, Nynke; Vreugdenhil, Hestien J. I.; Mulder, Paul G. H.

2004-01-01

The aim of the review of D.V. Cicchetti, A.S. Kaufman, and S.S. Sparrow (funded by the General Electric Company; this issue) is to "evaluate [the] literature relating the effects of prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) upon neurobehavioral, health-related, and cognitive deficits in neonates, developing infants,…

Arousal, Attention, and Neurobehavioral Assessment in the Neonatal Period: Implications for Intervention and Policy

ERIC Educational Resources Information Center

Gardner, Judith M.; Karmel, Bernard Z.; Freedland, Robert L.; Lennon, Elizabeth M.; Flory, Michael J.; Miroshnichenko, Inna; Phan, Ha T. T.; Barone, Anthony; Harin, Anantham

2006-01-01

Neonatal assessments should provide valid estimates of behavior and neurological status, reflect recovery from acute effects, predict subsequent outcome, and point to specific intervention strategies for any problems noted. The authors report relations among measures designed to evaluate early behavioral capabilities and dysfunctions in areas…

NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult rats were maintained on a chlorpyrifos-containing diet to p...

The Effect of Early Deprivation on Executive Attention in Middle Childhood

ERIC Educational Resources Information Center

Loman, Michelle M.; Johnson, Anna E.; Westerlund, Alissa; Pollak, Seth D.; Nelson, Charles A.; Gunnar, Megan R.

2013-01-01

Background: Children reared in deprived environments, such as institutions for the care of orphaned or abandoned children, are at increased risk for attention and behavior regulation difficulties. This study examined the neurobehavioral correlates of executive attention in post institutionalized (PI) children. Methods: The performance and…

DEVELOPMENT AND PEER REVIEW OF TIME-TO-EFFECT MODELS FOR THE ANALYSIS OF NEUROTOXICITY AND OTHER TIME DEPENDENT DATA

EPA Science Inventory

Neurobehavioral studies pose unique challenges for dose-response modeling, including small sample size and relatively large intra-subject variation, repeated measurements over time, multiple endpoints with both continuous and ordinal scales, and time dependence of risk characteri...

Polybrominated Diphenyl Ether (DE-71)Interferes with Thyroid Hormone Action Independent Of Effects On Circulating Levels of Thyroid Hormone in Male Rats

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) are routinely found in human tissues including cord blood and breast milk. PBDEs may interfere with thyroid hormone (TH) during development, which could produce neurobehavioral deficits. An assumption in experimental and epidemiological stud...

NEUROBEHAVIORAL ASSESSMENT USING A FUNCTIONAL OBSERVATIONAL BATTERY AND MOTOR ACTIVITY IN RATS PERINATALLY EXPOSED TO DE-71.

EPA Science Inventory

Polybrominated Diphenyl ethers (PBDEs) have been widely used as flame retardants in a variety of commercial products. Their persistence in the environment and detection in populations throughout the world has raised concern about their toxic effects. Developmental Neurotoxic ef...

Assessment of bioaccumulation and neurotoxicity in rats with portacaval anastomosis and exposed to manganese phosphate: a pilot study.

PubMed

Salehi, F; Carrier, G; Normandin, L; Kennedy, G; Butterworth, R F; Hazell, A; Therrien, G; Mergler, D; Philippe, S; Zayed, J

2001-12-01

The use of the additive methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline has resulted in increased attention to the potential toxic effects of manganese (Mn). Hypothetically, people with chronic liver disease may be more sensitive to the adverse neurotoxic effects of Mn. In this work, bioaccumulation of Mn, as well as histopathology and neurobehavioral damage, in end-to-side portacaval anastomosis (PCA) rats exposed to Mn phosphate via inhalation was investigated. During the week before the PCA operation, 4 wk after the PCA operation, and at the end of exposure, the rats were subjected to a locomotor evaluation (day-night activities) using a computerized autotrack system. Then a group of 6 PCA rats (EXP) was exposed to 3050 microg m(-3) (Mn phosphate) for 8 h/day, 5 days/wk for 4 consecutive weeks and compared to a control group (CON), 7 PCA rats exposed to 0.03 microg m(-3). After exposure, the rats were euthanized and Mn content in tissues and organs was determined by neutron activation analysis. The manganese concentrations in blood (0.05 microg/g vs. 0.02 microg/g), lung (1.32 microg/g vs. 0.24 microg/g), cerebellum (0.85 microg/g vs. 0.64 microg/g), frontal cortex (0.87 microg/g vs. 0.61 microg/g), and globus pallidus (3.56 microg/g vs. 1.33 microg/g) were significantly higher in the exposed group compared to the control group (p <.05). No difference was observed in liver, kidney, testes, and caudate putamen between the two groups. Neuronal cell loss was assessed by neuronal cell counts. The loss of cells in globus pallidus and caudate putamen as well as in frontal cortex was significantly higher (p <.05) for the EXP group. Assessment of the locomotor activities did not reveal any significant difference. This study constitutes a first step toward our understanding of the potential adverse effects of Mn in sensitive populations.

Sequential multiple-assignment randomized trial design of neurobehavioral treatment for patients with metastatic malignant melanoma undergoing high-dose interferon-alpha therapy.

PubMed

Auyeung, S Freda; Long, Qi; Royster, Erica Bruce; Murthy, Smitha; McNutt, Marcia D; Lawson, David; Miller, Andrew; Manatunga, Amita; Musselman, Dominique L

2009-10-01

Interferon-alpha therapy, which is used to treat metastatic malignant melanoma, can cause patients to develop two distinct neurobehavioral symptom complexes: a mood syndrome and a neurovegetative syndrome. Interferon-alpha effects on serotonin metabolism appear to contribute to the mood and anxiety syndrome, while the neurovegetative syndrome appears to be related to interferon-alpha effects on dopamine. Our goal is to propose a design for utilizing a sequential, multiple assignment, randomized trial design for patients with malignant melanoma to test the relative efficacy of drugs that target serotonin versus dopamine metabolism during 4 weeks of intravenous, then 8 weeks of subcutaneous, interferon-alpha therapy. Patients will be offered participation in a double-blinded, randomized, controlled, 14-week trial involving two treatment phases. During the first month of intravenous interferon-alpha therapy, we will test the hypotheses that escitalopram will be more effective in reducing depressed mood, anxiety, and irritability, whereas methylphenidate will be more effective in diminishing interferon-alpha-induced neurovegetative symptoms, such as fatigue and psychomotor slowing. During the next 8 weeks of subcutaneous interferon therapy, participants whose symptoms do not improve significantly will be randomized to the alternate agent alone versus escitalopram and methylphenidate together. We present a prototype for a single-center, sequential, multiple assignment, randomized trial, which seeks to determine the efficacy of sequenced and targeted treatment for the two distinct symptom complexes suffered by patients treated with interferon-alpha. Because we cannot completely control for external factors, a relevant question is whether or not 'short-term' neuropsychiatric interventions can increase the number of interferon-alpha doses tolerated and improve long-term survival. This sequential, multiple assignment, randomized trial proposes a framework for developing optimal treatment strategies; however, additional studies are needed to determine the best strategy for treating or preventing neurobehavioral symptoms induced by the immunotherapy interferon-alpha.

Cognitive requirements of competing neuro-behavioral decision systems: some implications of temporal horizon for managerial behavior in organizations

PubMed Central

Foxall, Gordon R.

2014-01-01

Interpretation of managerial activity in terms of neuroscience is typically concerned with extreme behaviors such as corporate fraud or reckless investment (Peterson, 2007; Wargo et al., 2010a). This paper is concerned to map out the neurophysiological and cognitive mechanisms at work across the spectrum of managerial behaviors encountered in more day-to-day contexts. It proposes that the competing neuro-behavioral decisions systems (CNBDS) hypothesis (Bickel et al., 2012b) captures well the range of managerial behaviors that can be characterized as hyper- or hypo-activity in either the limbically-based impulsive system or the frontal-cortically based executive system with the corresponding level of activity encountered in the alternative brain region. This pattern of neurophysiological responding also features in the Somatic Marker Hypothesis (Damasio, 1994) and in Reinforcement Sensitivity Theory (RST; Gray and McNaughton, 2000; McNaughton and Corr, 2004), which usefully extend the thesis, for example in the direction of personality. In discussing these theories, the paper has three purposes: to clarify the role of cognitive explanation in neuro-behavioral decision theory, to propose picoeconomics (Ainslie, 1992) as the cognitive component of competing neuro-behavioral decision systems theory and to suggest solutions to the problems of imbalanced neurophysiological activity in managerial behavior. The first is accomplished through discussion of the role of picoeconomics in neuro-behavioral decision theory; the second, by consideration of adaptive-innovative cognitive styles (Kirton, 2003) in the construction of managerial teams, a theme that can now be investigated by a dedicated research program that incorporates psychometric analysis of personality types and cognitive styles involved in managerial decision-making and the underlying neurophysiological bases of such decision-making. PMID:24744719

Cognition and behavior in pre-pubertal children with Prader-Willi syndrome and associations with sleep-related breathing disorders.

PubMed

Festen, Dederieke A M; Wevers, Maaike; de Weerd, Al W; van den Bossche, Renilde A S; Duivenvoorden, Hugo J; Hokken-Koelega, Anita C S

2008-12-01

Prader-Willi syndrome (PWS) is characterized by hypotonia, hypogonadism, obesity, and short stature. Neurobehavioral abnormalities, cognitive impairment, and sleep-related breathing disorders (SRBD) are common. In the general population associations between neurobehavioral and cognitive abnormalities and SRBD have been found. We investigated cognition, behavior, and SRBD in children with PWS. Thirty-one pre-pubertal PWS children were evaluated (5 with paternal deletion, 14 with maternal disomy, 4 with imprinting-center mutation, and in 8 the defect was not specified). Cognition was assessed by Wechsler scale subtests, and behavior by parent-questionnaires. Polysomnography was performed. Cognition, behavior, and associations with SRBD were evaluated. All cognitive subtests were significantly below O SDS, with the lowest median (interquartile range) scores for the Block design subtest (-2.7 SDS (-3.0 to -0.3)). In 60%, verbal subtests were less affected than performance subtests. Parents reported problem behavior related to "emotions/behavior not adapted to the social situation" and "insensitivity to social information." All children had SRBD, with an Apnea Hypopnea Index of 4.1/hr (2.6-7.9). One performance subtest score was significantly higher in children with better sleep efficiency, and daytime sleepiness was associated with more autistic-like social impairment. In contrast to our expectations, behavior was worse in children with better sleep-related breathing. In pre-pubertal PWS children, cognition is impaired. Neurobehavioral abnormalities are common, particularly autistic-like social impairment. Sleep efficiency was associated with better performance on one of the performance subtests, and neurobehavioral abnormalities were associated with daytime sleepiness. In contrast, we could not confirm a positive association of neurobehavioral abnormalities with SRBD in PWS. Copyright (c) 2008 Wiley-Liss, Inc.

Indoor mold exposure associated with neurobehavioral and pulmonary impairment: a preliminary report.

PubMed

Kilburn, Kaye H

2003-07-01

Recently, patients who have been exposed indoors to mixed molds, spores, and mycotoxins have reported asthma, airway irritation and bleeding, dizziness, and impaired memory and concentration, all of which suggest the presence of pulmonary and neurobehavioral problems. The author evaluated whether such patients had measurable pulmonary and neurobehavioral impairments by comparing consecutive cases in a series vs. a referent group. Sixty-five consecutive outpatients exposed to mold in their respective homes in Arizona, California, and Texas were compared with 202 community subjects who had no known mold or chemical exposures. Balance, choice reaction time, color discrimination, blink reflex, visual fields, grip, hearing, problem-solving, verbal recall, perceptual motor speed, and memory were measured. Medical histories, mood states, and symptom frequencies were recorded with checklists, and spirometry was used to measure various pulmonary volumes and flows. Neurobehavioral comparisons were made after individual measurements were adjusted for age, educational attainment, and sex. Significant differences between groups were assessed by analysis of variance; a p value of less than 0.05 was used for all statistical tests. The mold-exposed group exhibited decreased function for balance, reaction time, blink-reflex latency, color discrimination, visual fields, and grip, compared with referents. The exposed group's scores were reduced for the following tests: digit-symbol substitution, peg placement, trail making, verbal recall, and picture completion. Twenty-one of 26 functions tested were abnormal. Airway obstructions were found, and vital capacities were reduced. Mood state scores and symptom frequencies were elevated. The author concluded that indoor mold exposures were associated with neurobehavioral and pulmonary impairments that likely resulted from the presence of mycotoxins, such as trichothecenes.

Racial and ethnic disparities in functional, psychosocial, and neurobehavioral outcomes after brain injury.

PubMed

Arango-Lasprilla, Juan Carlos; Kreutzer, Jeffrey S

2010-01-01

Because of the growing minority population in the past 3 decades in the United States and the increasing numbers of individuals who sustain a traumatic brain injury (TBI), researchers and clinicians have started to pay more attention to the role of race and ethnicity in outcomes after TBI, with the goal of better serving this population. The aim of this article is to review the literature on the influence of race/ethnicity on functional, psychosocial, and neurobehavioral outcomes after TBI. Specifically, the following 8 areas of outcomes will be examined: (1) treatment outcomes, (2) neuropsychological outcomes, (3) employment/productivity, (4) functional outcomes, (5) community integration, (6) marital status, (7) quality of life/life satisfaction, and (8) emotional/neurobehavioral outcomes. To conclude this review, suggestions for improvements in professional competency, research, systems of care, and training are proposed.

Chitosan nanoparticles and their Tween 80 modified counterparts disrupt the developmental profile of zebrafish embryos.

PubMed

Yuan, Zhongyue; Li, Ying; Hu, Yulan; You, Jian; Higashisaka, Kazuma; Nagano, Kazuya; Tsutsumi, Yasuo; Gao, Jianqing

2016-12-30

Chitosan nanoparticles (CS-NPs) and their Tween 80 modified counterparts (TmCS-NPs) are among the most commonly used brain-targeted vehicles. However, their potential developmental toxicity is poorly understood. In this study, zebrafish embryos are introduced as an in vivo platform. Both NPs showed a dose-dependent increase in developmental toxicity (decreased hatching rate, increased mortality and incidences of malformation). Neurobehavioral changes included decreased spontaneous movement in TmCS-NP treated embryos and hyperactive effect in CS-NP treated larvae. Both NPs remarkably inhibited axonal development of primary and secondary motor neurons, and affected the muscle structure. Overall, this study demonstrated that CS-NPs and TmCS-NPs could affect embryonic development, disrupt neurobehavior of zebrafish larvae and affect muscle and neuron development, suggesting more attention on biodegradable chitosan nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulation of stress-induced neurobehavioral changes and brain oxidative injury by nitric oxide (NO) mimetics in rats.

PubMed

Gulati, Kavita; Chakraborti, Ayanabha; Ray, Arunabha

2007-11-02

The present study evaluated the effects of NO mimetics on stress-induced neurobehavioral changes and the possible involvement of ROS-RNS interactions in rats. Restraint stress (RS) suppressed both percent open arm entries and time spent in the open arms in the elevated plus maze (EPM) test. These RS-induced changes in EPM activity were attenuated by the NO mimetics, l-arginine, isosorbide dinitrate and molsidomine, in a differential manner. RS-exposed rats showed (a) increased lipid peroxidation (MDA) and (b) lowered reduced glutathione (GSH) and NO metabolites (NOx), in brain homogenates of these animals. Pretreatment with the NO mimetics also differentially influenced RS-induced changes in brain oxidative stress markers. The results suggest that NO may protect against stress-induced anxiogenic behavior and oxidative injury in the brain and highlight the significance of ROS-RNS interactions.

Medicinal Cannabis in California: An Interview with Igor Grant, MD.

PubMed

Piomelli, Daniele; Grant, Igor

2016-01-01

Dr. Igor Grant, MD, is distinguished professor and chair of psychiatry and director of the HIV Neurobehavioral Research Program and the Center for Medicinal Cannabis Research at the University of California, San Diego. Dr. Grant is a neuropsychiatrist who graduated from the University of British Columbia School of Medicine (1966), and received specialty training in psychiatry at the University of Pennsylvania (1967-1971), and additional training in neurology at the Institute of Neurology (1980-1981), London, U.K. Dr. Grant's academic interests focus on the effects of various diseases on brain and behavior, with an emphasis on translational studies in HIV, and drugs of abuse. He has contributed to ∼700 scholarly publications and is principal investigator of several NIH studies, including an NIDA P50 (Translational Methamphetamine AIDS Research Center-TMARC), and is codirector of the HIV Neurobehavioral Research Center (HNRC).

Human Impairment from Living near Confined Animal (Hog) Feeding Operations

PubMed Central

Kilburn, Kaye H.

2012-01-01

Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure.

PubMed

Panczakiewicz, Amy L; Glass, Leila; Coles, Claire D; Kable, Julie A; Sowell, Elizabeth R; Wozniak, Jeffrey R; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

2016-09-01

Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Subjects were 407 youth with prenatal alcohol exposure (n = 192) and controls (n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. Copyright © 2016 by the Research Society on Alcoholism.

Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests

NASA Astrophysics Data System (ADS)

Hienz, Robert; Davis, Catherine; Weed, Michael; Guida, Peter; Gooden, Virginia; Brady, Joseph; Roma, Peter

Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests INTRODUCTION Risk assessment of the biological consequences of living in the space radiation environment represents one of the highest priority areas of NASA radiation research. Of critical importance is the need for a risk assessment of damage to the central nervous system (CNS) leading to functional cognitive/behavioral changes during long-term space missions, and the development of effective shielding or biological countermeasures to such risks. The present research focuses on the use of an animal model that employs neurobehavioral tests identical or homologous to those currently in use in human models of risk assessment by U.S. agencies such as the Depart-ment of Defense and Federal Aviation and Federal Railroad Administrations for monitoring performance and estimating accident risks associated with such variables as fatigue and/or alcohol or drug abuse. As a first approximation for establishing human risk assessments due to exposure to space radiation, the present work provides animal performance data obtained with the rPVT (rat Psychomotor Vigilance Test), an animal analog of the human PVT that is currently employed for human risk assessments via quantification of sustained attention (e.g., 'vigilance' or 'readiness to perform' tasks). Ground-based studies indicate that radiation can induce neurobehavioral changes in rodents, including impaired performance on motor tasks and deficits in spatial learning and memory. The present study is testing the hypothesis that radiation exposure impairs motor function, performance accuracy, vigilance, motivation, and memory in adult male rats. METHODS The psychomotor vigilance test (PVT) was originally developed as a human cognitive neurobe-havioral assay for tracking the temporally dynamic changes in sustained attention, and has also been used to track changes in circadian rhythm. In humans the test requires responding to a small, bright-red-light stimulus (LED-digital counter) as soon as the stimulus appears, which stops the stimulus counter and displays the reaction time for each trial in milliseconds for a 1-sec period. Simple to perform, the PVT has only very minor learning effects, is widely used in human risk assessments in operational environments, and has been recently developed and adopted for use on the ISS for astronauts as a "self test" to provide performance feedback, detect changes in alertness, prevent errors, and manage fatigue from sleep loss, circadian dis-ruption, and high workload requirements. A rodent version of the PVT, the rPVT, has been developed and demonstrated to track the same types of performance variables as the human PVT -i.e., general motor function and speed, fine motor control, inhibitory control ("impul-sivity"), timing, selective attention, motivation, and basic sensory function. Five cohorts of 16 rats each (total N = 80) were trained on the rPVT, exported to BNL for head-only radiation exposure (0, 25, 50, 100, and 200 cGy protons @ 150 MeV/n), then returned to Johns Hopkins for follow-up testing. RESULTS The rPVT was readily learned by all rats and required as little as 5-7 days of training to acquire baseline performance levels. Following irradiation, performances in the rPVT were disrupted at exposure levels of 50, 100, and 200 cGy, showing a consistent, significant increase (i.e., slowing) in reaction times and increased lapses in responding, both indicative of a decrease in sustained attention. Additionally, premature responses showed consistent increases at the higher radiation levels. None of these changes were observed in the non-exposed control animals. Over this same time period, no significant changes were observed in discrimination accuracy, motivation (as indicated by trials completed), or food intake. SUMMARY AND CONCLUSIONS The results of these experiments demonstrate the sensitivity of tests such as the rPVT for assessing the effects of head-only space radiation on cognitive neurobehavioral function. Expo-sure to protons at as little as 50 cGy produce highly specific effects on vigilance that include impaired attention and motor function (i.e., slowed reaction times, increased lapses in atten-tion, and increased premature responding). Such deficits could significantly impact routine performances in operational environments during lunar and Mars missions, and also negatively affect post-mission adjustment upon return to Earth.

90-Day Inhalation Toxicity Study of Bio-Derived Gevo Alcohol-to-Jet (ATJ) Synthetic Paraffinic Kerosene (SPK) in Rats with Neurotoxicity Testing and Genotoxicity Assay

DTIC Science & Technology

2015-05-31

body weights, food consumption , and reproductive indices (vaginal cytology, sperm cell parameters). Neurobehavioral effects , evaluated by motor...Human Performance Wing Human Effectiveness Directorate Bioeffects Division Molecular Bioeffects Branch Wright-Patterson AFB OH 45433-5707...IV, DAF Chief, Bioeffects Division Human Effectiveness Directorate 711 th Human Perfmmance Wing Air Force Research Laboratmy This repmi is

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study

PubMed Central

Kiblawi, Zeina N.; Smith, Lynne M.; Diaz, Sabrina D.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry

2013-01-01

Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How MA use during pregnancy affects neonatal and infant neurobehavior is unknown. Methods The Infant Development, Environment, and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. 17,961 were eligible and 3,705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or GC/MS confirmation of amphetamine and metabolites in meconium. Comparison subjects were matched (race, birth weight, maternal education, insurance), denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, or phencyclidine. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life and again at one month to 380 enrollees (185 exposed, 195 comparison). ANOVA tested exposure effects on NNNS summary scores at birth and one month. GLM repeated measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates. Results By one month of age, both groups demonstrated higher quality of movement (P=.029), less lethargy (P=.001), and fewer asymmetric reflexes (P=.012), with no significant differences in NNNS scores between the exposed and comparison groups. Over the first month of life, arousal increased in exposed infants but decreased in comparison infants (p=.031) and total stress was decreased in exposed infants with no change in comparison infants (p=.026). Conclusions Improvement in total stress and arousal were observed in MA-exposed newborns by one month of age relative to the newborn period. PMID:24588296

Environmental enrichment synergistically improves functional recovery by transplanted adipose stem cells in chronic hypoxic-ischemic brain injury.

PubMed

Seo, Jung Hwa; Kim, Hyongbum; Park, Eun Sook; Lee, Jong Eun; Kim, Dong Wook; Kim, Hyun Ok; Im, Sang Hee; Yu, Ji Hea; Kim, Ji Yeon; Lee, Min-Young; Kim, Chul Hoon; Cho, Sung-Rae

2013-01-01

We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASC-SC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin(+) neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU(+)βIII-tubulin(+) neurons, GFAP(+) astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56(+) glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.

Effects of anemia at different stages of gestation on infant outcomes.

PubMed

Menon, Kavitha C; Ferguson, Elaine L; Thomson, Christine D; Gray, Andrew R; Zodpey, Sanjay; Saraf, Abhay; Das, Prabir Kumar; Skeaff, Sheila A

2016-01-01

Maternal anemia is a public health challenge worldwide. The present study aims to explore the effects of maternal anemia at different stages of gestation on postnatal growth and neurobehavioral development in infants. A cohort of pregnant Indian women were followed from 13 to 22 wk gestation (i.e., second trimester; n = 211), 29 to 42 wk gestation (i.e., third trimester; n = 178); their infants were followed to ∼3 wk (n = 147) postpartum. Data collected included information on sociodemographic and health-related factors, including anemia (i.e., low hemoglobin status), maternal and infant anthropometric data, and infant neurobehavioral data. A mixed logistic regression model was used to examine the impact of anemia during pregnancy on maternal and infant outcomes (i.e., anthropometric growth parameters and infant neurobehavioral development). The prevalence of maternal anemia was 41% and 55% (P < 0.001), and iron deficiency anemia was 3.6% and 5.6%, respectively, in the second trimester and third trimester. Infants of pregnant women who were not anemic in the second trimester were 0.26 standard deviations (SD) heavier (P = 0.029), 0.50 SD taller (P = 0.001), and had 0.26 SD larger head circumference (P = 0.029) compared with infants of anemic pregnant women. Infants of pregnant women who were not anemic in the third trimester had orientation scores 3.88 higher (P = 0.004) than infants of women who were anemic. Our findings indicate that maternal anemia in the second trimester of gestation influences postnatal infant growth and underscores the necessity of alleviating anemia in young women in the early stages of gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Signs of neurobehavioral dysfunction in a sample of learning disabled children: stability and concurrent validity.

PubMed

Morrison, D C; Hinshaw, S P; Carte, E T

1985-12-01

Of 270 learning disabled children with average intelligence and significant delays in reading comprehension a sample of 37 were evaluated for signs of neurobehavioral dysfunction. All such signs--primitive reflexes, equilibrium reactions, and postrotary nystagmus--were reliably assessed. A subsample of 19 children was compared with developmentally normal and mentally retarded samples for the occurrence of tonic neck reflexes and equilibrium reactions. The learning disabled children consistently showed deviancies like those of the retarded children; both of these groups differed from the normal children on most measures. These deviant responses persisted over a 9-mo. period for the learning disabled group. Compared with norms, the total learning disabled sample displayed hyponystagmus, and this depressed nystagmus persisted for 11 mo. Results are discussed in relation to the lack of correlation among the various signs of neurobehavioral dysfunction in the learning disabled children.

Neurobehavioral phenotype in Prader-Willi syndrome.

PubMed

Whittington, Joyce; Holland, Anthony

2010-11-15

The focus of this article is on the lifetime development of people with Prader-Willi syndrome (PWS) and specifically on the neurobehavioral phenotype. We consider studies of this aspect of the phenotype (the "behavioral phenotype" of the syndrome) that have confirmed that there are specific behaviors and psychiatric disorders, the propensities to which are increased in those with PWS, and cannot be accounted for by other variables such as IQ or adaptive behavior. Beginning with a description of what is observed in people with PWS, we review the evolving PWS phenotype and consider how some aspects of the phenotype might be best explained, and how this complex phenotype may relate to the equally complex genotype. We then consider in more detail some of the neurobehavioral aspects of the phenotype listed above that raise the greatest management problems for parents and carers. © 2010 Wiley-Liss, Inc.

Developmental Dyslexia: Early Precursors, Neurobehavioral Markers, and Biological Substrates

ERIC Educational Resources Information Center

Benasich, April A., Ed.; Fitch, R. Holly, Ed.

2012-01-01

Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…

The Effects of the Newborn Behavioral Observations (NBO) System on Sensitivity in Mother-Infant Interactions

ERIC Educational Resources Information Center

Nugent, J. Kevin; Bartlett, Jessica Dym; Von Ende, Adam; Valim, Clarissa

2017-01-01

The Newborn Behavioral Observations (NBO) system is a neurobehavioral observation tool designed to sensitize parents to infants' capacities and individuality and to enhance the parent-infant relationship by strengthening parents' confidence and practical skills in caring for their children. The NBO's focus on relationship building is intended for…

Biologic and plastic effects of experimental traumatic brain injury treatment paradigms and their relevance to clinical rehabilitation

PubMed Central

Garcia, Alexandra N.; Shah, Mansi A.; Dixon, C. Edward; Wagner, Amy K.; Kline, Anthony E.

2011-01-01

Neuroplastic changes, whether induced by traumatic brain injury (TBI) or therapeutic interventions, alter neurobehavioral outcome. Here we present several treatment strategies that have been evaluated using experimental TBI models and discuss potential mechanisms of action (i.e., plasticity) and how such changes affect function. PMID:21703575

A New Neurobehavioral Model of Autism in Mice: Pre-and Postnatal Exposure to Sodium Valproate

ERIC Educational Resources Information Center

Wagner, George C.; Reuhl, Kenneth R.; Cheh, Michelle; McRae, Paulette; Halladay, Alycia K.

2006-01-01

Autism symptoms, including impairments in language development, social interactions, and motor skills, have been difficult to model in rodents. Since children exposed in utero to sodium valproate (VPA) demonstrate behavioral and neuroanatomical abnormalities similar to those seen in autism, the neurodevelopmental effects of this antiepileptic…

NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350g body weight by...

[Short- and long-term consequences of prenatal exposure to cannabis].

PubMed

Karila, L; Cazas, O; Danel, T; Reynaud, M

2006-02-01

Cannabis is one of the most commonly used drugs by pregnant women. The objective of this review of literature was to examine the association between cannabis use during pregnancy and effects upon growth, cognitive development (memory, attention, executive functions...) and behavior of newborns, children and teenagers. We searched for articles indexed in the medline database from 1970 to 2005. The following terms were used in the literature search: cannabis/marijuana, pregnancy, fetal development, newborn, prenatal exposure, neurobehavioral deficits, cognitive deficits, executive functions, cannabinoids, reproduction. Most of the articles were published in English. Cannabis use during pregnancy is related to diverse neurobehavioral and cognitive outcomes, including symptoms of inattention, impulsivity, deficits in learning and memory, and a deficiency in aspects of executive functions. It seems difficult to identify complications, such as lower birth weight, only attributable to cannabis as opposed to the multiple perinatal complications associated with tobacco smoking. In addition to alcohol and cigarettes, information should be given to women about the potentially harmful effects on fetal development, newborns, children and teenagers of smoking cannabis. Therefore, it seems necessary to develop prevention programs on this subject.

The Cumulative Neurobehavioral and Physiological Effects of Chronic Caffeine Intake: Individual Differences and Implications for the Use of Caffeinated Energy Products

PubMed Central

Spaeth, Andrea M; Goel, Namni; Dinges, David F

2014-01-01

The use of caffeine-containing energy products (CCEP) has increased worldwide in recent years and research shows that CCEP can improve cognitive and physical performance. All of the top-selling energy drinks contain caffeine, which is likely to be the primary psychoactive ingredient in CCEP. Presumably, individuals consume CCEP to counteract feelings of ‘low-energy’ in situations causing tiredness, fatigue, and/or reduced alertness. This review discusses the scientific evidence for sleep loss, circadian phase, sleep inertia and the time-on-task effect as causes of ‘low energy’ and summarizes research assessing the efficacy of caffeine to counteract decreased alertness and increased fatigue in such situations. The results of a placebo-controlled experiment on healthy adults undergoing three nights of total sleep deprivation (with or without 2 hour naps every 12 hours) are presented to illustrate the physiological and neurobehavioral effects of sustained low-dose caffeine. Individual differences, including genetic factors, in the response to caffeine and to sleep loss are discussed. We conclude with future directions for research on this important and evolving topic. PMID:25293542

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

PubMed Central

Gong, Linji; Ma, Yuanyuan; Xu, Haiwei; Gu, Zhanjun; Zhu, Jingci; Fan, Xiaotang

2018-01-01

Introduction Silica nanoparticles (SiO2-NPs) are currently among the most widely used nanomaterials, but their potentially adverse effects on brain development remain unknown. The developing brain is extremely sensitive to NP neurotoxicity during the early postnatal period. Materials and methods Herein, we investigated the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3, respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor proliferation at P8 and long-term neurobehavior in adults. Results SiO2-NP exposure resulted in inflammatory cell infiltration in lung tissue, microglia over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal precursor proliferation in the DG-subgranular zone at P8. Moreover, after exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and slight anxiety-like behaviors in adulthood, but this exposure did not induce locomotor activity impairment, depression-like behavior, or short-term memory impairment. Discussion These findings suggest that early-age SiO2-NP exposure induced inflammation and inhibited precursor proliferation in the DG in a dose-dependent manner, which might be related to the social dysfunction observed in adulthood.

Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

PubMed

Shibasaki, Y; Hayata-Takano, A; Hazama, K; Nakazawa, T; Shintani, N; Kasai, A; Nagayasu, K; Hashimoto, R; Tanida, M; Katayama, T; Matsuzaki, S; Yamada, K; Taniike, M; Onaka, Y; Ago, Y; Waschek, J A; Köves, K; Reglődi, D; Tamas, A; Matsuda, T; Baba, A; Hashimoto, H

2015-06-25

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Reproductive disorders associated with pesticide exposure.

PubMed

Frazier, Linda M

2007-01-01

Exposure of men or women to certain pesticides at sufficient doses may increase the risk for sperm abnormalities, decreased fertility, a deficit of male children, spontaneous abortion, birth defects or fetal growth retardation. Pesticides from workplace or environmental exposures enter breast milk. Certain pesticides have been linked to developmental neurobehavioral problems, altered function of immune cells and possibly childhood leukemia. In well-designed epidemiologic studies, adverse reproductive or developmental effects have been associated with mixed pesticide exposure in occupational settings, particularly when personal protective equipment is not used. Every class of pesticides has at least one agent capable of affecting a reproductive or developmental endpoint in laboratory animals or people, including organophosphates, carbamates, pyrethroids, herbicides, fungicides, fumigants and especially organochlorines. Many of the most toxic pesticides have been banned or restricted in developed nations, but high exposures to these agents are still occurring in the most impoverished countries around the globe. Protective clothing, masks and gloves are more difficult to tolerate in hot, humid weather, or may be unavailable or unaffordable. Counseling patients who are concerned about reproductive and developmental effects of pesticides often involves helping them assess their exposure levels, weigh risks and benefits, and adopt practices to reduce or eliminate their absorbed dose. Patients may not realize that by the first prenatal care visit, most disruptions of organogenesis have already occurred. Planning ahead provides the best chance of lowering risk from pesticides and remediating other risk factors before conception.

Environmental factors associated with a spectrum of neurodevelopmental deficits.

PubMed

Mendola, Pauline; Selevan, Sherry G; Gutter, Suzanne; Rice, Deborah

2002-01-01

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively unique in that different parts are responsible for different functional domains, and these develop at different times (e.g., motor control, sensory, intelligence and attention). In addition, the many cell types in the brain have different windows of vulnerability with varying sensitivities to environmental agents. This review focuses on two environmental agents, lead and methylmercury, to illustrate the neurobehavioral and cognitive effects that can result from early life exposures. Special attention is paid to distinguishing between the effects detected following episodes of poisoning and those detected following lower dose exposures. Perinatal and childhood exposure to high doses of lead results in encephalopathy and convulsions. Lower-dose lead exposures have been associated with impairment in intellectual function and attention. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. At lower levels of methylmercury exposure, the effects in children have been more subtle. Other environmental neurotoxicants that have been shown to produce developmental neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides, ionizing radiation, environmental tobacco smoke, and maternal use of alcohol, tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent. Copyright 2002 Wiley-Liss, Inc.

Managing temptation in obesity treatment: a neurobehavioral model of intervention strategies

PubMed Central

Appelhans, Bradley M; French, Simone A; Pagoto, Sherry L; Sherwood, Nancy E

2015-01-01

Weight loss outcomes in lifestyle interventions for obesity are primarily a function of sustained adherence to a reduced-energy diet, and most lapses in diet adherence are precipitated by temptation from palatable food. The high nonresponse and relapse rates of lifestyle interventions suggest that current temptation management approaches may be insufficient for most participants. In this conceptual review, we discuss three neurobehavioral processes (attentional bias, temporal discounting, and the cold-hot empathy gap) that emerge during temptation and contribute to lapses in diet adherence. Characterizing the neurobehavioral profile of temptation highlights an important distinction between temptation resistance strategies aimed at overcoming temptation while it is experienced, and temptation prevention strategies that seek to avoid or minimize exposure to tempting stimuli. Many temptation resistance and temptation prevention strategies heavily rely on executive functions mediated by prefrontal systems that are prone to disruption by common occurrences such as stress, insufficient sleep, and even exposure to tempting stimuli. In contrast, commitment strategies are a set of devices that enable individuals to manage temptation by constraining their future choices, without placing heavy demands on executive functions. These concepts are synthesized in a conceptual model that categorizes temptation management approaches based on their intended effects on reward processing and degree of reliance on executive functions. We conclude by discussing the implications of our model for strengthening temptation management approaches in future lifestyle interventions, tailoring these approaches based on key individual difference variables, and suggesting high-priority topics for future research. PMID:26431681

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury

PubMed Central

Cohen-Yeshurun, Ayelet; Willner, Dafna; Trembovler, Victoria; Alexandrovich, Alexander; Mechoulam, Raphael; Shohami, Esther; Leker, Ronen R

2013-01-01

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions. PMID:23695434

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury.

PubMed

Cohen-Yeshurun, Ayelet; Willner, Dafna; Trembovler, Victoria; Alexandrovich, Alexander; Mechoulam, Raphael; Shohami, Esther; Leker, Ronen R

2013-08-01

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions.

The efficacy of objective and subjective predictors of driving performance during sleep restriction and circadian misalignment.

PubMed

Kosmadopoulos, Anastasi; Sargent, Charli; Zhou, Xuan; Darwent, David; Matthews, Raymond W; Dawson, Drew; Roach, Gregory D

2017-02-01

Fatigue is a significant contributor to motor-vehicle accidents and fatalities. Shift workers are particularly susceptible to fatigue-related risks as they are often sleep-restricted and required to commute around the clock. Simple assays of performance could provide useful indications of risk in fatigue management, but their effectiveness may be influenced by changes in their sensitivity to sleep loss across the day. The aim of this study was to evaluate the sensitivity of several neurobehavioral and subjective tasks to sleep restriction (SR) at different circadian phases and their efficacy as predictors of performance during a simulated driving task. Thirty-two volunteers (M±SD; 22.8±2.9 years) were time-isolated for 13-days and participated in one of two 14-h forced desynchrony protocols with sleep opportunities equivalent to 8h/24h (control) or 4h/24h (SR). At regular intervals during wake periods, participants completed a simulated driving task, several neurobehavioral tasks, including the psychomotor vigilance task (PVT), and subjective ratings, including a self-assessment measure of ability to perform. Scores transformed into standardized units relative to baseline were folded into circadian phase bins based on core body temperature. Sleep dose and circadian phase effect sizes were derived via mixed models analyses. Predictors of driving were identified with regressions. Performance was most sensitive to sleep restriction around the circadian nadir. The effects of sleep restriction around the circadian nadir were larger for simulated driving and neurobehavioral tasks than for subjective ratings. Tasks did not significantly predict driving performance during the control condition or around the acrophase during the SR condition. The PVT and self-assessed ability were the best predictors of simulated driving across circadian phases during SR. These results show that simple performance measures and self-monitoring explain a large proportion of the variance in driving when fatigue-risk is high. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methyl mercury exposure and neurodevelopmental outcomes in the Seychelles Child Development Study Main cohort at age 22 and 24years.

PubMed

van Wijngaarden, Edwin; Thurston, Sally W; Myers, Gary J; Harrington, Donald; Cory-Slechta, Deborah A; Strain, J J; Watson, Gene E; Zareba, Grazyna; Love, Tanzy; Henderson, Juliette; Shamlaye, Conrad F; Davidson, Philip W

All fish contain methyl mercury (MeHg), a known neurotoxicant at adequate dosage. There is still substantial scientific uncertainty about the consequences, if any, of mothers consuming fish with naturally-acquired levels of MeHg contamination. In 1989-1990, we recruited the Main Cohort of the Seychelles Child Development Study to assess the potential developmental effects of prenatal MeHg exposure. We report here on associations with neurodevelopmental outcomes obtained at 22 and 24years of age. Neurodevelopmental tests at 22years included the Boston Naming Test, Cambridge Neuropsychological Test Automated Battery (CANTAB), and the Profile of Mood States. At 24years, we administered the Stroop Word-Color Test, the Barkley Adult ADHD Rating Scale, the Test of Variables of Attention, and the Finger Tapping test. We also administered a healthy behaviors survey at both ages. Primary analyses examined covariate-adjusted associations in multiple linear regression models with prenatal MeHg exposure. In secondary analyses we also examined associations with recent postnatal MeHg exposure. We did not observe adverse associations between prenatal MeHg exposure and any of the measured endpoints. Some measures of attention, executive function, and delayed recall showed improved performance with increasing exposure. Secondary analysis did not show consistent patterns of association with postnatal exposure. Our cohort has been examined at ten different ages over 24years of follow-up. Findings suggest that prenatal and recent postnatal MeHg exposure from ocean fish consumption is not adversely associated with neurobehavioral development at levels that are about ten times higher than typical U.S. exposures. Copyright © 2016 Elsevier Inc. All rights reserved.

Prenatal exposure to dental amalgam: evidence from the Seychelles Child Development Study main cohort.

PubMed

Watson, Gene E; Lynch, Miranda; Myers, Gary J; Shamlaye, Conrad F; Thurston, Sally W; Zareba, Grazyna; Clarkson, Thomas W; Davidson, Philip W

2011-11-01

Dental amalgams contain approximately 50 percent metallic mercury and emit mercury vapor during the life of the restoration. Controversy surrounds whether fetal exposure to mercury vapor resulting from maternal dental amalgam restorations has neurodevelopmental consequences. The authors determined maternal amalgam restoration status during gestation (prenatal exposure to mercury vapor [Hg(0)]) retrospectively in 587 mother-child pairs enrolled in the Seychelles Child Development Study, a prospective longitudinal cohort study of the effects of prenatal and recent postnatal methylmercury (MeHg) exposure on neurodevelopment. They examined covariate-adjusted associations between prenatal maternal amalgam restoration status and the results of six age-appropriate neurodevelopmental tests administered at age 66 months. The authors fit the models without and with adjustment for prenatal and recent postnatal MeHg exposure metrics. The mean number of maternal amalgam restorations present during gestation was 5.1 surfaces (range, 1-22) in the 42.4 percent of mothers who had amalgam restorations. The authors found no significant adverse associations between the number of amalgam surfaces present during gestation and any of the six outcomes, with or without adjustment for prenatal and postnatal MeHg exposure. Results of analyses with the secondary metric, prenatal amalgam occlusal point scores, showed an adverse association in boys only on a letter- and word-identification subtest of a frequently used test of scholastic achievement, whereas girls scored better on several other tests with increasing exposure. This study's results provide no support for the hypothesis that prenatal Hg(0) exposure arising from maternal dental amalgam restorations results in neurobehavioral consequences in the child. These findings require confirmation from a prospective study of coexposure to MeHg and Hg(0).

Comparison at 32-37 Weeks Postconception of Infants Born 1983-1989 and 1995-2004 on the Neurobehavioral Assessment of the Preterm Infant

ERIC Educational Resources Information Center

Brown, Josephine V.; Bakeman, Roger; Sampers, Jackie S.; Korner, Anneliese F.; Constantinou, Janet C.; Anand, K. J. S.

2008-01-01

In spite of numerous recent outcome studies of extremely low birth weight (ELBW) infants, no data exist on their development prior to term. In this study we traced and compared the neurobehavioral development of 251 ELBW (less than 1,000 g) and 240 low birth weight (LBW; 1,000 g-2,500 g) preterms born between 1995 and 2004 from 32 to 37 weeks…

Corpus callosum differences assessed by fetal MRI in late-onset intrauterine growth restriction and its association with neurobehavior.

PubMed

Egaña-Ugrinovic, Gabriela; Sanz-Cortés, Magdalena; Couve-Pérez, Constanza; Figueras, Francesc; Gratacós, Eduard

2014-09-01

The aim of this study is to evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriate for gestational age and its association with neurobehavioral outcome. One hundred and seventeen late-onset IUGR and 73 control fetuses were imaged using a 3T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale test was performed on IUGR newborns at 42 ± 1 weeks. IUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and/or abnormal brain and/or abnormal uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases. CC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk. © 2014 John Wiley & Sons, Ltd.

Rehabilitation following pediatric traumatic brain injury: variability in adherence to psychosocial quality-of-care indicators.

PubMed

Ennis, Stephanie K; Jaffe, Kenneth M; Mangione-Smith, Rita; Konodi, Mark A; MacKenzie, Ellen J; Rivara, Frederick P

2014-01-01

To examine variations in processes of pediatric inpatient rehabilitation care related to family-centered care, management of neurobehavioral and psychosocial needs, and community reintegration after traumatic brain injury. Nine acute rehabilitation facilities from geographically diverse areas of the United States. A total of 174 children with traumatic brain injury. Retrospective chart review. Adherence to care indicators (the number of times recommended care was delivered or attempted divided by the number of times care was indicated). Across facilities, adherence rates (adjusted for difficulty of delivery) ranged from 33.6% to 73.1% (95% confidence interval, 13.4-53.9, 58.7-87.4) for family-centered processes, 21.3% to 82.5% (95% confidence interval, 6.6-36.1, 67.6-97.4) for neurobehavioral and psychosocial processes, and 22.7% to 80.3% (95% confidence interval, 5.3-40.1, 68.1-92.5) for community integration processes. Within facilities, standard deviations for adherence rates were large (24.3-34.9, family-centered domain; 22.6-34.2, neurobehavioral and psychosocial domain; and 21.6-40.5, community reintegration domain). The current state of acute rehabilitation care for children with traumatic brain injury is variable across different quality-of-care indicators addressing neurobehavioral and psychosocial needs and facilitating community reintegration of the patient and the family. Individual rehabilitation facilities demonstrate inconsistent adherence to different indicators and inconsistent performance across different care domains.

Do all roads lead to Rome? The role of neuro-immune interactions before birth in the programming of offspring obesity

PubMed Central

Jasoni, Christine L.; Sanders, Tessa R.; Kim, Dong Won

2015-01-01

The functions of the nervous system can be powerfully modulated by the immune system. Although traditionally considered to be quite separate, neuro-immune interactions are increasingly recognized as critical for both normal and pathological nervous system function in the adult. However, a growing body of information supports a critical role for neuro-immune interactions before birth, particularly in the prenatal programming of later-life neurobehavioral disease risk. This review will focus on maternal obesity, as it represents an environment of pathological immune system function during pregnancy that elevates offspring neurobehavioral disease risk. We will first delineate the normal role of the immune system during pregnancy, including the role of the placenta as both a barrier and relayer of inflammatory information between the maternal and fetal environments. This will be followed by the current exciting findings of how immuno-modulatory molecules may elevate offspring risk of neurobehavioral disease by altering brain development and, consequently, later life function. Finally, by drawing parallels with pregnancy complications other than obesity, we will suggest that aberrant immune activation, irrespective of its origin, may lead to neuro-immune interactions that otherwise would not exist in the developing brain. These interactions could conceivably derail normal brain development and/or later life function, and thereby elevate risk for obesity and other neurobehavioral disorders later in the offspring's life. PMID:25691854

Cerebral oxygenation in the beach chair position for shoulder surgery in regional anesthesia: impact on cerebral blood flow and neurobehavioral outcome.

PubMed

Aguirre, José A; Märzendorfer, Olivia; Brada, Muriel; Saporito, Andrea; Borgeat, Alain; Bühler, Philipp

2016-12-01

Beach chair position is considered a potential risk factor for central neurological events particularly if combined with low blood pressure. The aim of this study was to assess the impact of regional anesthesia on cerebral blood flow and neurobehavioral outcome. This is a prospective, assessor-blinded observational study evaluating patients in the beach chair position undergoing shoulder surgery under regional anesthesia. University hospital operating room. Forty patients with American Society of Anesthesiologists classes I-II physical status scheduled for elective shoulder surgery. Cerebral saturation and blood flow of the middle cerebral artery were measured prior to anesthesia and continued after beach chair positioning until discharge to the postanesthesia care unit. The anesthesiologist was blinded for these values. Controlled hypotension with systolic blood pressure≤100mm Hg was maintained during surgery. Neurobehavioral tests and values of regional cerebral saturation, bispectral index, the mean maximal blood flow of the middle cerebral artery, and invasive blood pressure were measured prior to regional anesthesia, and measurements were repeated after placement of the patient on the beach chair position and every 20 minutes thereafter until discharge to postanesthesia care unit. The neurobehavioral tests were repeated the day after surgery. The incidence of cerebral desaturation events was 5%. All patients had a significant blood pressure drop 5 minutes after beach chair positioning, measured at the heart as well as the acoustic meatus levels, when compared with baseline values (P<.05). There was no decrease in either the regional cerebral saturation (P=.136) or the maximal blood flow of the middle cerebral artery (P=.212) at the same time points. Some neurocognitive tests showed an impairment 24 hours after surgery (P<.001 for 2 of 3 tests). Beach chair position in patients undergoing regional anesthesia for shoulder surgery had no major impact on cerebral blood flow and cerebral oxygenation. However, some impact on neurobehavioral outcome 24 hours after surgery was observed. Copyright © 2016 Elsevier Inc. All rights reserved.

Exploiting Redundant Measurement of Dose and Developmental Outcome: New Methods from the Behavioral Teratology of Alcohol.

ERIC Educational Resources Information Center

Bookstein, Fred L.; And Others

1996-01-01

Discusses the use of new statistical procedures in a study of the enduring effects of prenatal alcohol exposure upon the neurobehavioral development of some 500 children born in 1975-76. Explains how the Partial Least Squares (PLS) methodology can summarize the data powerfully while avoiding familiar inferential pitfalls. (MDM)

Individual Differences in Neurobehavioral Effects of Pyridostigmine

DTIC Science & Technology

2001-02-01

Combat Casualty Care Course, Brooke Army Medical Center, Ft. Sam Houston, TX, 1982. Forensic Accident Investigation, Armed Forces Institute of...Occupational Medicine-Diplomate January 31,1989 Medical Review Officer Certification Council-June 13,1993 American Board of Forensic Examiners-Sept, 1996...Medicine Fellow, Aerospace Medical Association Fellow, International Association of Aviation and Space Medicine Fellow, American College of Forensic

Reliability of concentrations of organophosphate pesticide metabolites in serial urine specimens from pregnancy in the Generation R Study.

PubMed

Spaan, Suzanne; Pronk, Anjoeka; Koch, Holger M; Jusko, Todd A; Jaddoe, Vincent W V; Shaw, Pamela A; Tiemeier, Henning M; Hofman, Albert; Pierik, Frank H; Longnecker, Matthew P

2015-05-01

The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the present study, urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined in 120 pregnant women participating in the Generation R Study in Rotterdam. Intra-class correlation coefficients (ICCs) across serial urine specimens taken at <18, 18-25, and >25 weeks of pregnancy were determined to assess reliability. Geometric mean total DAP metabolite concentrations were 229 (GSD 2.2), 240 (GSD 2.1), and 224 (GSD 2.2) nmol/g creatinine across the three periods of gestation. Metabolite concentrations from the serial urine specimens in general correlated moderately. The ICCs for the six DAP metabolites ranged from 0.14 to 0.38 (0.30 for total DAPs), indicating weak to moderate reliability. Although the DAP metabolite levels observed in this study are slightly higher and slightly more correlated than in previous studies, the low to moderate reliability indicates a high degree of within-person variability, which presents challenges for designing well-powered epidemiological studies.

Development of allosteric modulators of GPCRs for treatment of CNS disorders

PubMed Central

Nickols, Hilary Highfield; Conn, P. Jeffrey

2013-01-01

The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than do orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as “bitopic” ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction. PMID:24076101

Real-world implications of apathy among older adults: Independent associations with activities of daily living and quality of life.

PubMed

Tierney, Savanna M; Woods, Steven Paul; Weinborn, Michael; Bucks, Romola S

2018-03-13

Apathy is common in older adults and has been linked to adverse health outcomes. The current study examined whether apathy contributes to problems managing activities of daily living (ADLs) and lower quality of life (QoL) in older adults. Participants included 83 community-dwelling older adults. Apathy was assessed using a composite of the self and family-rating scales from the Frontal Systems Behavioral Scale (FrSBe). A knowledgeable informant completed the Activities of Daily Living Questionnaire (ADLQ), and participants completed the World Health Organization Quality of Life (WHOQol) scale. Nominal logistic regressions controlling for age, anxiety and depression symptoms, chronic medical conditions, and global cognition revealed that higher levels of apathy were significantly associated with a wide range of mild ADL problems. In parallel, a multiple linear regression indicated that greater apathy was significantly associated with lower QoL independent of ADL problems, anxious and depressive symptomology, chronic medical conditions, global cognition and age. Findings suggest that apathy confers an increased risk of problems in the independent management of daily activities and poorer well-being among community-dwelling older adults. Neurobehavioral and pharmacological interventions to improve apathy may have beneficial effects on the daily lives of older adults.

Methylphenidate Disrupts Social Play Behavior in Adolescent Rats

PubMed Central

Vanderschuren, Louk JMJ; Trezza, Viviana; Griffioen-Roose, Sanne; Schiepers, Olga JG; Van Leeuwen, Natascha; De Vries, Taco J; Schoffelmeer, Anton NM

2008-01-01

Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3-3.0 mg/kg, s.c. or p.o.) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an α-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of α-1 adrenoceptors, β-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. These data show that methylphenidate selectively blocks the most vigorous part of the behavioral repertoire of adolescent rats through a noradrenergic mechanism. We suggest that the effect of methylphenidate on social play is a reflection of its therapeutic effect in ADHD, that is, improved behavioral inhibition. However, given the importance of social play for development, these findings may also indicate an adverse side effect of methylphenidate. PMID:18305462

Methylphenidate disrupts social play behavior in adolescent rats.

PubMed

Vanderschuren, Louk J M J; Trezza, Viviana; Griffioen-Roose, Sanne; Schiepers, Olga J G; Van Leeuwen, Natascha; De Vries, Taco J; Schoffelmeer, Anton N M

2008-11-01

Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3-3.0 mg/kg, s.c. or p.o.) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an alpha-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of alpha-1 adrenoceptors, beta-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. These data show that methylphenidate selectively blocks the most vigorous part of the behavioral repertoire of adolescent rats through a noradrenergic mechanism. We suggest that the effect of methylphenidate on social play is a reflection of its therapeutic effect in ADHD, that is, improved behavioral inhibition. However, given the importance of social play for development, these findings may also indicate an adverse side effect of methylphenidate.

Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight

NASA Technical Reports Server (NTRS)

Dinges, David F.

1999-01-01

This project is concerned with identifying ways to prevent neurobehavioral and physical deterioration due to inadequate sleep in astronauts during long-duration manned space flight. The performance capability of astronauts during extended-duration space flight depends heavily on achieving recovery through adequate sleep. Even with appropriate circadian alignment, sleep loss can erode fundamental elements of human performance capability including vigilance, cognitive speed and accuracy, working memory, reaction time, and physiological alertness. Adequate sleep is essential during manned space flight not only to ensure high levels of safe and effective human performance, but also as a basic regulatory biology critical to healthy human functioning. There is now extensive objective evidence that astronaut sleep is frequently restricted in space flight to averages between 4 hr and 6.5 hr/day. Chronic sleep restriction during manned space flight can occur in response to endogenous disturbances of sleep (motion sickness, stress, circadian rhythms), environmental disruptions of sleep (noise, temperature, light), and curtailment of sleep due to the work demands and other activities that accompany extended space flight operations. The mechanism through which this risk emerges is the development of cumulative homeostatic pressure for sleep across consecutive days of inadequate sleep. Research has shown that the physiological sleepiness and performance deficits engendered by sleep debt can progressively worsen (i.e., accumulate) over consecutive days of sleep restriction, and that sleep limited to levels commonly experienced by astronauts (i.e., 4 - 6 hr per night) for as little as 1 week, can result in increased lapses of attention, degradation of response times, deficits in complex problem solving, reduced learning, mood disturbance, disruption of essential neuroendocrine, metabolic, and neuroimmune responses, and in some vulnerable persons, the emergence of uncontrolled sleep attacks. The prevention of cumulative performance deficits and neuroendocrine disruption from sleep restriction during extended duration space flight involves finding the most effective ways to obtain sleep in order to maintain the high-level cognitive and physical performance functions required for manned space flight. There is currently a critical deficiency in knowledge of the effects of how variations in sleep duration and timing relate to the most efficient return of performance per unit time invested in sleep during long-duration missions, and how the nature of sleep physiology (i.e., sleep stages, sleep electroencephalographic [EEG] power spectral analyses) change as a function of sleep restriction and performance degradation. The primary aim of this project is to meet these critical deficiencies through utilization of a response surface experimental paradigm, testing in a dose-response manner, varying combinations of sleep duration and timing, for the purpose of establishing how to most effectively limit the cumulative adverse effects on human performance and physiology of chronic sleep restriction in space operations.

A Neurobehavioral Study of Rats Using a Model Perfluorinated Acid, NDFDA.

DTIC Science & Technology

1982-07-13

1 AD-Alla 560 DISTICT OFVCOLUMBIAUUNIV WASHIrGTON, DEPT OF BIOLOGY F662 NEUROEHA IORAL STUDY OF RATS USING A MODEL PERFLUORINATEO AC--ETCU U JUL A2 I...S. TYPE OF REPORT & PERIOD COVERED A NEUROBEHAVIORAL STUDY OF RATS USING A MODEL Final Report PERFLUORINATED ACID, NDFDA ___nu; 6. PERFORMING O IG...OPT0 Y&’ A@E(ben Des Btntete AFOSR-TR" FINAL RPORT A NEUROBUEIAVIORAL STUDY ON RATS USING A MODEL PERFLUORINATED ACID , NDFDA Prepared by: Inez R

Parent observed neuro-behavioral and pro-social improvements with oxytocin following surgical resection of craniopharyngioma.

PubMed

Cook, Naomi; Miller, Jennifer; Hart, John

2016-08-01

Social and emotional impairment, school dysfunction, and neurobehavioral impairment are highly prevalent in survivors of childhood craniopharyngioma and negatively affect quality of life. As surgical resection of craniopharyngioma typically impairs hypothalamic/pituitary function, it has been postulated that perhaps post-operative deficiency of the hormone oxytocin may be the etiology of social/emotional impairment. Research on the benefits of oxytocin treatment as a hormone facilitating social interaction is well established. However, no research has yet been conducted on patients with known pituitary/hypothalamic dysfunction due to structural lesions or surgery. This case report investigates the effects of oxytocin therapy on a youngster with pituitary/hypothalamic dysfunction after craniopharyngioma removal. In this individual, treatment with low dose intranasal oxytocin resulted in increased desire for socialization and improvement in affection towards family. In light of these findings, the authors believe that further research into the potential benefits of intranasal oxytocin therapy for patients with panhypopituitarism is necessary to determine whether a broader population may also benefit from intranasal oxytocin therapy.

Sleep and Sleepiness among First-Time Postpartum Parents: A Field- and Laboratory-Based Multimethod Assessment

PubMed Central

Insana, Salvatore P.; Montgomery-Downs, Hawley E.

2012-01-01

The study aim was to compare sleep, sleepiness, fatigue, and neurobehavioral performance among first-time mothers and fathers during their early postpartum period. Participants were 21 first-time postpartum mother-father dyads (N=42) and seven childless control dyads (N=14). Within their natural environment, participants completed one week of wrist actigraphy monitoring, along with multi-day self-administered sleepiness, fatigue, and neurobehavioral performance measures. The assessment week was followed by an objective laboratory based test of sleepiness. Mothers obtained more sleep compared to fathers, but mothers’ sleep was more disturbed by awakenings. Fathers had greater objectively measured sleepiness than mothers. Mothers and fathers did not differ on subjectively measured sleep quality, sleepiness, or fatigue; however, mothers had worse neurobehavioral performance than fathers. Compared to control dyads, postpartum parents experienced greater sleep disturbance, sleepiness, and sleepiness associated impairments. Study results inform social policy, postpartum sleep interventions, and research on postpartum family systems and mechanisms that propagate sleepiness. PMID:22553114

Psychopathology in children of schizophrenics

PubMed Central

Shah, Sharita; Kamat, Sanjeev; Sawant, Urmila; Dhavale, H.S.

2003-01-01

The higher prevalence of schizophrenia in children of schizophrenics than in the general population has generated an interest in pinpointing those behaviors that may precede the disorder and serve as an index of vulnerability to the disorder. Signs of neurobehavioral dysfunction in areas of neurocognitive functioning and social behavior have been found in school-age children of schizophrenic parents. This study assessed the neurobehavioral functioning, social behavior, cognitive functioning, attention and intelligence in children with a schizophrenic parent and compared the same parameters with children of mentally healthy parents. The children aged 12-15 years, were assessed with a battery of neurobehavioral tests. The children with a schizophrenic parent performed more poorly on the tests as compared to the children of mentally healthy parents. The children with a schizophrenic parent were seen to have more behavioral problems, especially withdrawn behavior and more social problems when compared to the other children in the study. Poor attention, disordered thoughts and lower intelligence were also observed to be more in the children of the schizophrenic parent PMID:21206831

The Hokkaido Birth Cohort Study on Environment and Children's Health: cohort profile-updated 2017.

PubMed

Kishi, Reiko; Araki, Atsuko; Minatoya, Machiko; Hanaoka, Tomoyuki; Miyashita, Chihiro; Itoh, Sachiko; Kobayashi, Sumitaka; Ait Bamai, Yu; Yamazaki, Keiko; Miura, Ryu; Tamura, Naomi; Ito, Kumiko; Goudarzi, Houman

2017-05-18

The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

Proceedings of the Annual Chemical Defense Bioscience Review (5th) Held at Columbia, Maryland on 29-31 May 1985. Appendix 2

DTIC Science & Technology

1985-06-01

biocompatible enzyme-like catalyst for the rapid and specific deactivation of sys- temically sorbed nerve agents . We plan to introduce catalytic groups (thiol...mustard, seizures, respiratory failure, atropine, 2-PAM chloride, neurobehavioral effects, nerve agents , soman, cyanide, animal models, chemical casualties...Animal Model ........ .. A-541 Dr. H.L. Williams Effects of Nerve Agents on the Respiratory and e Cardiovascular Systems

Estimation of health effects of prenatal methylmercury exposure using structural equation models.

PubMed

Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe; Weihe, Pal

2002-10-14

Observational studies in epidemiology always involve concerns regarding validity, especially measurement error, confounding, missing data, and other problems that may affect the study outcomes. Widely used standard statistical techniques, such as multiple regression analysis, may to some extent adjust for these shortcomings. However, structural equations may incorporate most of these considerations, thereby providing overall adjusted estimations of associations. This approach was used in a large epidemiological data set from a prospective study of developmental methyl-mercury toxicity. Structural equation models were developed for assessment of the association between biomarkers of prenatal mercury exposure and neuropsychological test scores in 7 year old children. Eleven neurobehavioral outcomes were grouped into motor function and verbally mediated function. Adjustment for local dependence and item bias was necessary for a satisfactory fit of the model, but had little impact on the estimated mercury effects. The mercury effect on the two latent neurobehavioral functions was similar to the strongest effects seen for individual test scores of motor function and verbal skills. Adjustment for contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates only marginally, but the mercury effect could be reduced to non-significance by assuming a large measurement error for the PCB biomarker. The structural equation analysis allows correction for measurement error in exposure variables, incorporation of multiple outcomes and incomplete cases. This approach therefore deserves to be applied more frequently in the analysis of complex epidemiological data sets.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Needleman, H.L.; Schell, A.; Bellinger, D.

To determine whether the effects of low-level lead exposure persist, we reexamined 132 of 270 young adults who had initially been studied as primary school-children in 1975 through 1978. In the earlier study, neurobehavioral functioning was found to be inversely related to dentin lead levels. As compared with those we restudied, the other 138 subjects had had somewhat higher lead levels on earlier analysis, as well as significantly lower IQ scores and poorer teachers' ratings of classroom behavior. When the 132 subjects were reexamined in 1988, impairment in neurobehavioral function was still found to be related to the lead contentmore » of teeth shed at the ages of six and seven. The young people with dentin lead levels greater than 20 ppm had a markedly higher risk of dropping out of high school (adjusted odds ratio, 7.4; 95 percent confidence interval, 1.4 to 40.7) and of having a reading disability (odds ratio, 5.8; 95 percent confidence interval, 1.7 to 19.7) as compared with those with dentin lead levels less than 10 ppm. Higher lead levels in childhood were also significantly associated with lower class standing in high school, increased absenteeism, lower vocabulary and grammatical-reasoning scores, poorer hand-eye coordination, longer reaction times, and slower finger tapping. No significant associations were found with the results of 10 other tests of neurobehavioral functioning. Lead levels were inversely related to self-reports of minor delinquent activity. We conclude that exposure to lead in childhood is associated with deficits in central nervous system functioning that persist into young adulthood.« less

Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

PubMed

Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

2016-08-01

Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.

Neurobehavioral performance and work experience in Florida farmworkers.

PubMed

Kamel, Freya; Rowland, Andrew S; Park, Lawrence P; Anger, W Kent; Baird, Donna D; Gladen, Beth C; Moreno, Tirso; Stallone, Lillian; Sandler, Dale P

2003-11-01

Farmworkers experience many work-related hazards, including exposure to neurotoxicants. We compared neurobehavioral performance of 288 farmworkers in central Florida who had done farm work for at least 1 month with 51 controls who had not. Most of the farmworkers had worked in one or more of three types of agriculture: ornamental ferns, nurseries, or citrus fruit. We collected information on farm work history in a structured interview and evaluated neurobehavioral performance using a battery of eight tests. Analyses were adjusted for established confounders including age, sex, education, and acculturation. Ever having done farm work was associated with poor performance on four tests--digit span [odds ratio (OR) = 1.90; 95% confidence interval (CI), 1.02-3.53], tapping (coefficient = 4.13; 95% CI, 0.00-8.27), Santa Ana test (coefficient = 1.34; 95% CI, 0.29-2.39), and postural sway (coefficient = 4.74; 95% CI, -2.20 to 11.7)--but had little effect on four others: symbol digit latency, vibrotactile threshold, visual contrast sensitivity, and grip strength. Associations with farm work were similar in magnitude to associations with personal characteristics such as age and sex. Longer duration of farm work was associated with worse performance. Associations with fern work were more consistent than associations with nursery or citrus work. Deficits related to the duration of work experience were seen in former as well as current farmworkers, and decreased performance was related to chronic exposure even in the absence of a history of pesticide poisoning. We conclude that long-term experience of farm work is associated with measurable deficits in cognitive and psychomotor function.

Division III Collision Sports Are Not Associated with Neurobehavioral Quality of Life.

PubMed

Meehan, William P; Taylor, Alex M; Berkner, Paul; Sandstrom, Noah J; Peluso, Mark W; Kurtz, Matthew M; Pascual-Leone, Alvaro; Mannix, Rebekah

2016-01-15

We sought to determine whether the exposure to the sub-concussive blows that occur during division III collegiate collision sports affect later life neurobehavioral quality-of-life measures. We conducted a cross-sectional study of alumni from four division III colleges, targeting those between the ages of 40-70 years, using several well-validated quality-of-life measures for executive function, general concerns, anxiety, depression, emotional and behavior dyscontrol, fatigue, positive affect, sleep disturbance, and negative consequences of alcohol use. We used multivariable linear regression to assess for associations between collision sport participation and quality-of-life measures while adjusting for covariates including age, gender, race, annual income, highest educational degree, college grades, exercise frequency, and common medical conditions. We obtained data from 3702 alumni, more than half of whom (2132) had participated in collegiate sports, 23% in collision sports, 23% in non-contact sports. Respondents with a history of concussion had worse self-reported health on several measures. When subjects with a history of concussion were removed from the analyses in order to assess for any potential effect of sub-concussive blows alone, negative consequences of alcohol use remained higher among collision sport athletes (β-coefficient 1.957, 95% CI 0.827-3.086). There were, however, no other significant associations between exposure to collision sports during college and any other quality-of-life measures. Our results suggest that, in the absence of a history of concussions, participation in collision sports at the Division III collegiate level is not a risk factor for worse long-term neurobehavioral outcomes, despite exposure to repeated sub-concussive blows.

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

PubMed Central

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.

PubMed

McHill, Andrew W; Hull, Joseph T; Wang, Wei; Czeisler, Charles A; Klerman, Elizabeth B

2018-06-05

Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.

The effect of indoor office environment on the work performance, health and well-being of office workers.

PubMed

Vimalanathan, Komalanathan; Ramesh Babu, Thangavelu

2014-01-01

The effect of indoor environment may have an influence on the performance, productivity health and well-being of office workers. Environmental factors such as indoor temperature and illumination have been investigated at three levels. A neurobehavioral test (NBT) has been proposed for the evaluation of office workersc performance. A field lab to emulate an office has been created. In controlled condition of environmental factors, the neurobehavioral test was conducted. The response time and the number of errors in each test have been recorded. A randomized block factorial design was used to analyze the responses of office worker's performance. The results revealed that the independent and interaction effect of temperature and illumination have significant effect on the office workers' performance. The effect of indoor room temperature has more influences than the effect of illumination. The effect of indoor temperature has 38.56% of contribution on the performance. The optimum levels of indoor temperature at 21°C and illumination at 1000 lux have improved the work performance and health of office workers. The indoor room temperature and illumination are more influence on the performance of the office workers. It may be concluded that the impact of indoor room temperature (38.56%) is more on the office worker's performance than the effect of illumination (19.91%). Further, it may be concluded that the optimum level of indoor room temperature (21°C) and illumination (1000lux) have improved the work performance, health and productivity of office workers.

Chronic Exposure to Uranium from Gestation: Effects on Behavior and Neurogenesis in Adulthood

PubMed Central

Dinocourt, Céline; Culeux, Cécile; Legrand, Marie; Elie, Christelle; Lestaevel, Philippe

2017-01-01

Uranium exposure leads to cerebral dysfunction involving for instance biochemical, neurochemical and neurobehavioral effects. Most studies have focused on mechanisms in uranium-exposed adult animals. However, recent data on developing animals have shown that the developing brain is also sensitive to uranium. Models of uranium exposure during brain development highlight the need to improve our understanding of the effects of uranium. In a model in which uranium exposure began from the first day of gestation, we studied the neurobehavioral consequences as well as the progression of hippocampal neurogenesis in animals from dams exposed to uranium. Our results show that 2-month-old rats exposed to uranium from gestational day 1 displayed deficits in special memory and a prominent depressive-like phenotype. Cell proliferation was not disturbed in these animals, as shown by 5-bromo-2′deoxyuridine (BrdU)/neuronal specific nuclear protein (NeuN) immunostaining in the dentate gyrus. However, in some animals, the pyramidal cell layer was dispersed in the CA3 region. From our previous results with the same model, the hypothesis of alterations of neurogenesis at prior stages of development is worth considering, but is probably not the only one. Therefore, further investigations are needed to correlate cerebral dysfunction and its underlying mechanistic pathways. PMID:28513543

Khat Use and Neurobehavioral Functions: Suggestions for Future Studies

PubMed Central

Hoffman, Richard; al’Absi, Mustafa

2010-01-01

Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures. PMID:20553832

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure

PubMed Central

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-01-01

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N = 33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 µg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL × sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. PMID:25936521

Chronic Exposure to Uranium from Gestation: Effects on Behavior and Neurogenesis in Adulthood.

PubMed

Dinocourt, Céline; Culeux, Cécile; Legrand, Marie; Elie, Christelle; Lestaevel, Philippe

2017-05-17

Uranium exposure leads to cerebral dysfunction involving for instance biochemical, neurochemical and neurobehavioral effects. Most studies have focused on mechanisms in uranium-exposed adult animals. However, recent data on developing animals have shown that the developing brain is also sensitive to uranium. Models of uranium exposure during brain development highlight the need to improve our understanding of the effects of uranium. In a model in which uranium exposure began from the first day of gestation, we studied the neurobehavioral consequences as well as the progression of hippocampal neurogenesis in animals from dams exposed to uranium. Our results show that 2-month-old rats exposed to uranium from gestational day 1 displayed deficits in special memory and a prominent depressive-like phenotype. Cell proliferation was not disturbed in these animals, as shown by 5-bromo-2'deoxyuridine (BrdU)/neuronal specific nuclear protein (NeuN) immunostaining in the dentate gyrus. However, in some animals, the pyramidal cell layer was dispersed in the CA3 region. From our previous results with the same model, the hypothesis of alterations of neurogenesis at prior stages of development is worth considering, but is probably not the only one. Therefore, further investigations are needed to correlate cerebral dysfunction and its underlying mechanistic pathways.

The Relationship between Prenatal and Postnatal Exposure to Polychlorinated Biphenyls (PCBs) and Cognitive, Neuropsychological, and Behavioral Deficits: A Critical Appraisal

ERIC Educational Resources Information Center

Cicchetti, Domenic V.; Kaufman, Alan S.; Sparrow, Sara S.

2004-01-01

Our purpose in this report is to evaluate scientifically that body of literature relating the effects of prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) upon neurobehavioral, health-related, and cognitive deficits in neonates, developing infants, children, and adults. The data derive from seven cohorts: six cohorts of mothers…

Visual Perception and Visual-Motor Integration in Very Preterm and/or Very Low Birth Weight Children: A Meta-Analysis

ERIC Educational Resources Information Center

Geldof, C. J. A.; van Wassenaer, A. G.; de Kieviet, J. F.; Kok, J. H.; Oosterlaan, J.

2012-01-01

A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual…

Adolescents and Alcohol: Acute Sensitivities, Enhanced Intake, and Later Consequences*

PubMed Central

Spear, Linda Patia

2014-01-01

Adolescence is an evolutionarily conserved developmental period characterized by notable maturational changes in brain along with various age-related behavioral characteristics, including the propensity to initiate alcohol and other drug use and consume more alcohol per occasion than adults. After a brief review of adolescent neurobehavioral function from an evolutionary perspective, the paper will turn to assessment of adolescent alcohol sensitivity and consequences, with a focus on work from our laboratory. After summarizing evidence showing that adolescents differ considerably from adults in their sensitivity to various effects of alcohol, potential contributors to these age-typical sensitivities will be discussed, and the degree to which these findings are generalizable to other drugs and to human adolescents will be considered. Recent studies are then reviewed to illustrate that repeated alcohol exposure during adolescence induces behavioral, cognitive, and neural alterations that are highly specific, replicable, persistent and dependent on the timing of the exposure. Research in this area is in its early stages, however, and more work will be necessary to characterize the extent of these neurobehavioral alterations and further determine the degree to which observed effects are specific to alcohol exposure during adolescence. PMID:24291291

Cadmium neurotoxicity to a freshwater planarian.

PubMed

Wu, Jui-Pin; Lee, Hui-Ling; Li, Mei-Hui

2014-11-01

Although freshwater planarians are evolutionarily primitive, they are some of the simplest bilateral animals possessing integrated neural networks similar to those in vertebrates. We attempted to develop planarian Dugesia japonica as a model for investigating the neurotoxicity of environmental pollutants such as cadmium (Cd). This study was therefore designed to study the effects of Cd on the locomotor activity, neurobehavior, and neurological enzymes of D. japonica. After planarians were exposed to Cd at high concentrations, altered neurobehavior was observed that exhibited concentration-dependent patterns. Morphological alterations in Cd-treated planarians included irregular shape, body elongation, screw-like hyperkinesia, and bridge-like position. To study the direct effects of Cd on neurological enzymes, tissue homogenates of planarians were incubated in vitro with Cd before their activity was measured. Results showed that acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), and monoamine oxidase A (MAO-A) activities were inhibited in a concentration-dependent manner. MAO-B activity was significantly induced by Cd at low concentrations and inhibited at high concentrations. Changes in the in vivo activity of AChE and ATPase were also found after planarians were treated with Cd at a sublethal concentration (5.56 μM). These observations indicate that neurotransmission systems in planarians are disturbed after Cd exposure.

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open-field activity in Sprague-Dawley rats.

PubMed

Sprowles, Jenna L N; Hufgard, Jillian R; Gutierrez, Arnold; Bailey, Rebecca A; Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

2017-10-01

Most antidepressants inhibit monoamine reuptake. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) act on the 5-HT transporter (SERT) whereas norepinephrine-dopamine reuptake inhibitors (NDRIs) act on the norepinephrine and dopamine transporters. Epidemiological reports link SSRI use during pregnancy to an increased prevalence of autism spectrum disorder (ASD). We previously showed that perinatal exposure to the SSRI citalopram (CIT) results in rodent offspring that exhibit a number of behaviors consistent with an ASD-like phenotype. The present study examined the effect of perinatal exposure to CIT (at a lower dose), another SSRI, fluoxetine (FLX), and an NDRI, bupropion (BUP). Gravid Sprague-Dawley rats were subcutaneously injected twice per day (6h apart) with 5mg/kg CIT, 5mg/kg FLX, 15mg/kg BUP, or saline (SAL) from embryonic day (E) 6-21, and directly to the pups from postnatal day (P) 1-20. As adults, one male/female from each litter was given one of a series of tests. Both SSRI-exposed groups showed spatial learning deficits in Morris and radial water mazes, increased marble burying, increased acoustic startle, hypoactivity, and attenuated activity to the stimulating effect of the NMDA-R antagonist MK-801. The BUP-exposed group showed a reduction in elevated zero-maze quadrant entries and increased stimulated open-field activity following (+)-amphetamine challenge. These results reinforce concern about the use of antidepressants during pregnancy and highlight how the two classes of drugs produce different constellations of effects with more effects associated with the SSRIs. Further investigation into how antidepressants alter brain development leading to enduring adverse neurobehavioral effects is warranted. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

The neurobehavior ontology: an ontology for annotation and integration of behavior and behavioral phenotypes.

PubMed

Gkoutos, Georgios V; Schofield, Paul N; Hoehndorf, Robert

2012-01-01

In recent years, considerable advances have been made toward our understanding of the genetic architecture of behavior and the physical, mental, and environmental influences that underpin behavioral processes. The provision of a method for recording behavior-related phenomena is necessary to enable integrative and comparative analyses of data and knowledge about behavior. The neurobehavior ontology facilitates the systematic representation of behavior and behavioral phenotypes, thereby improving the unification and integration behavioral data in neuroscience research. Copyright © 2012 Elsevier Inc. All rights reserved.

Commentary to Krishna et al. (2014): brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water.

PubMed

Kumasaka, Mayuko Y; Yajima, Ichiro; Ohgami, Nobutaka; Naito, Hisao; Omata, Yasuhiro; Kato, Masashi

2014-05-01

Krishna et al. (Arch Toxicol 88(1):47-64, 2014) recently published the results of a study in which adult C57BL/6 mice were subchronically exposed to 400,000 μg/L manganese (Mn) using manganese chloride via drinking water for 8 weeks and examined the neurotoxic effects. After 5 weeks of Mn exposure, significant deposition of Mn in all of the brain regions examined by magnetic resonance imaging was detected. After 6 weeks of Mn exposure, neurobehavioral deficits in an open field test, a grip strength test, and a forced swim test were observed. Eight weeks of Mn exposure increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, but did not alter the levels of striatal dopamine, its metabolites and serotonin. Krishna et al. also reported significant increases in mRNA levels of GFAP (an astrocyte activation marker), HO-1 (an oxidative stress marker) and NOS2 (a nitrosative stress marker), and in protein expression level of GFAP in the substantia nigra pars reticulata after 8 weeks of Mn exposure. These results suggest that 400,000 μg/L Mn exposure via drinking water in mice induces neurobehavioral deficits, serotonergic imbalance, and glial activation accompanied by an increase in brain Mn deposition. The report by Krishna et al. is interesting because the studies on the neurobehavioral effect of Mn exposure by drinking water in mice are very limited. However, Mn concentrations previously reported in well drinking water (Agusa et al. in Vietnam Environ Pollut 139(1):95-106, 2006; Buschmann et al. in Environ Int 34(6):756-764, 2008; Hafeman et al. in Environ Health Perspect 115(7):1107-1112, 2007; Wasserman et al. in Bangladesh Environ Health Perspect 114(1):124-129, 2006) were lower than 400,000 μg/L.

Effects of high fat diet and bamboo extract supplement on anxiety- and depression-like neurobehaviors in mice

PubMed Central

Del Rosario, Adeline; McDermott, Mindy M.; Panee, Jun

2015-01-01

High fat diet is a major causative factor of overweight and obesity, which are associated with increased risk of neuropsychiatric diseases, such as anxiety and depression. In this study, we investigated the protective effects of bamboo extract (BEX) on anxiety- and depression-like neurobehaviors in mice treated with a high fat diet. Male mice with CD-1 genetic background were treated for 2 months with either a standard or a high fat diet (10% or 45% calories from fat, respectively), with or without BEX supplement (11 g dry mass per 17 MJ). The anxiety levels of the mice were evaluated using open field and hole-board tests, and depression was measured using force swimming test. The anxiety responses of the animals were found significantly increased after high fat diet treatment, and this elevation was effectively abolished by BEX supplement. High fat diet seemed to have an anti-depressive effect in the mice at the tested time point, but the effect of BEX supplement on the depression level of the animals was not conclusive. High fat diet significantly decreased total glutathione content in the blood while BEX supplement increased glutathione oxidation. In summary, this study showed that decreased total glutathione concentration in the blood co-occurred with high fat treatment, high anxiety level and low depression level in the mice; and when supplemented in a high fat diet, BEX had anxiolytic effect in the mice. PMID:22313665

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

PubMed

Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

2018-01-01

HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.

Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates.

PubMed

Eluvathingal, Thomas J; Behen, Michael E; Chugani, Harry T; Janisse, James; Bernardi, Bruno; Chakraborty, Pulak; Juhasz, Csaba; Muzik, Otto; Chugani, Diane C

2006-10-01

We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha-[(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning, controlling for the number and location of cortical tubers, revealed that the cerebellar lesion group had higher overall autistic symptomatology. Within-group analyses of the cerebellar lesion group revealed that children with right-sided cerebellar lesions had higher social isolation and communicative and developmental disturbance compared with children with left-sided cerebellar lesions. The side of the cerebellar lesion was not related to adaptive behavior functioning. These findings provide additional empiric support for a role of the cerebellum in autistic symptomatology. Further investigation of the potential role of the right cerebellum in autism, particularly with regard to the dentatothalamofrontal circuit, is warranted.

Environmental Investigation Report for Fort Douglas. Volume 1 - text

DTIC Science & Technology

1994-03-01

o o CM O ~^ -O t^ O CM K3 V V ^ "C3 o M CM CO NT- NT— N* NT— o o co co o o o o o -* O CM ^t CO C\\J CM CD CD in... vitamin D, which is responsible for maintenance of calcium homeostasis in the body; neurobehavioral effects and growth retardation in prenatally-exposed

Assessment of neurotoxic effects and brain region distribution in rat offspring prenatally co-exposed to low doses of BDE-99 and methylmercury.

PubMed

Zhao, Wenchang; Cheng, Jinping; Gu, Jinmin; Liu, Yuanyuan; Fujimura, Masatake; Wang, Wenhua

2014-10-01

Exposure to polybrominated diphenyl ether (PDBE) and methylmercury (MeHg) can occur simultaneously as both contaminants are found in the same food sources, especially fish, seafood, marine mammals and milk. The aim of this study was to assess the effects of exposure to low levels of MeHg (2.0 μg mL(-1) in drinking water) and BDE-99 (0.2 mg kg(-1) d(-1)) from gestational day 6 to postnatal day (PND) 21, alone and in combination, on neurobehavioral development and redox responses in offspring. The present study demonstrated an interaction due to co-exposure with low doses of MeHg and BDE-99 enhanced developmental neurotoxic effects. These effects were manifested as the delayed appearance of negative geotaxis reflexes, impaired motor coordination, and induction of oxidative stress in the cerebellum. In particular, the cerebellum may be a sensitive target for combined MeHg and BDE-99 toxicity. The neurotoxicity of low dose MeHg was exacerbated by the presence of low dose of BDE-99. It is concluded that prenatal co-exposure to MeHg and BDE-99 causes oxidative stress in the cerebellum of offspring by altering the activity of different antioxidant enzymes and producing free radicals. Hg retention was not affected by co-exposure to BDE-99. However, MeHg co-exposure seemed to increase BDE-99 concentrations in selected brain regions in pups compared to pups exposed to BDE-99 only. These results showed that the adverse effects following prenatal co-exposure to MeHg and BDE-99 were associated with tissue concentrations very close to the current human body burden of this persistent bioaccumulative compound. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats

PubMed Central

Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.

2010-01-01

This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concentrations of 0 (control), 0.15, 1.5, 75, 750, and 2250 ppm daily from gestation day 0 through lactation day 21. F1 offspring were evaluated using the following tests: detailed clinical observations (postnatal days [PNDs] 4, 11, 21, 35, 45, and 60), auditory startle (PNDs 20 and 60), motor activity (PNDs 13, 17, 21, and 61), learning and memory using the Biel water maze (PNDs 22 and 62), and brain and nervous system neuropathology and brain morphometry (PNDs 21 and 72). For F1 offspring, there were no treatment-related neurobehavioral effects, nor was there evidence of neuropathology or effects on brain morphometry. Based on maternal and offspring body weight reductions, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was 75 ppm (5.85 and 13.1 mg/kg/day during gestation and lactation, respectively), with no treatment-related effects at lower doses or nonmonotonic dose responses observed for any parameter. There was no evidence that BPA is a developmental neurotoxicant in rats, and the NOAEL for developmental neurotoxicity was 2250 ppm, the highest dose tested (164 and 410 mg/kg/day during gestation and lactation, respectively). PMID:20164145

Pre- and Postnatal Exposure to Low Dose Glufosinate Ammonium Induces Autism-Like Phenotypes in Mice

PubMed Central

Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

2014-01-01

Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 – two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods. PMID:25477793

Assessing biological effects of fluoxetine in developing zebrafish embryos using gas chromatography-mass spectrometry based metabolomics.

PubMed

Mishra, Priti; Gong, Zhiyuan; Kelly, Barry C

2017-12-01

Continuous low-dose exposure of pharmaceutically active compounds (PhACs) in aquatic ecosystems is a concern worldwide. In this study, we utilized a gas chromatography mass spectrometry (GC-MS) based metabolomics approach to assess endogenous metabolite changes in developing zebrafish embryos exposed to different concentrations of the widely used antidepressant, fluoxetine. Embryos were exposed from 2 h post fertilization (hpf) until 96 hpf. Using the Fiehn GC-MS library, a total of 31 metabolites were positively identified in embryos. Statistical analyses revealed significant dysregulation of 11 metabolites in fluoxetine exposed embryos. Metabolite classes that were significantly altered included, amino acids, monosaccharides, glycerophosphates, fatty acids, carboxylic acid derivatives and sugars. Concentrations of amino acids, maltose, d-malic acid, 3-phosphoglycerate and d-glucose were significantly reduced in exposed embryos. Conversely, concentrations of citric acid were in some cases significantly elevated in exposed embryos. Metabolic pathway analysis revealed perturbation of five main pathways, including (i) alanine, aspartate and glutamate metabolism, (ii) phenylalanine, tyrosine and tryptophan biosynthesis, (iii) phenylalanine metabolism. (iv) tyrosine metabolism and (v) starch and sucrose metabolism. The results indicate fluoxetine exposure causes perturbation of energy and amino acid metabolism, which may adversely impact embryogenesis due to depletion of energy reserves during this period. Also, the observed alterations in aspartic acid, phenylalanine and tyrosine in fluoxetine exposed embryos suggests potential disruption of normal neurobehavioral and liver function. The results further demonstrate that GC-MS based metabolomics is an effective approach for assessing toxicodynamics and threshold effect levels of environmental pollutants in aquatic organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

NASA Technical Reports Server (NTRS)

Dijk, D. J.; Neri, D. F.; Wyatt, J. K.; Ronda, J. M.; Riel, E.; Ritz-De Cecco, A.; Hughes, R. J.; Elliott, A. R.; Prisk, G. K.; West, J. B.;

21st century neurobehavioral theories of decision making in addiction: Review and evaluation.

PubMed

Bickel, Warren K; Mellis, Alexandra M; Snider, Sarah E; Athamneh, Liqa N; Stein, Jeffrey S; Pope, Derek A

2018-01-01

This review critically examines neurobehavioral theoretical developments in decision making in addiction in the 21st century. We specifically compare each theory reviewed to seven benchmarks of theoretical robustness, based on their ability to address: why some commodities are addictive; developmental trends in addiction; addiction-related anhedonia; self-defeating patterns of behavior in addiction; why addiction co-occurs with other unhealthy behaviors; and, finally, means for the repair of addiction. We have included only self-contained theories or hypotheses which have been developed or extended in the 21st century to address decision making in addiction. We thus review seven distinct theories of decision making in addiction: learning theories, incentive-sensitization theory, dopamine imbalance and systems models, opponent process theory, strength models of self-control failure, the competing neurobehavioral decision systems theory, and the triadic systems theory of addiction. Finally, we have directly compared the performance of each of these theories based on the aforementioned benchmarks, and highlighted key points at which several theories have coalesced. Copyright © 2017 Elsevier Inc. All rights reserved.

Celebrating the 125th anniversary of the American Psychological Association: A quarter century of neuropsychology.

PubMed

Brown, Gregory G; Anderson, Vicki; Bigler, Erin D; Chan, Agnes S; Fama, Rosemary; Grabowski, Thomas J; Zakzanis, Konstantine K

2017-11-01

The American Psychological Association (APA) celebrated its 125th anniversary in 2017. As part of this celebration, the APA journal Neuropsychology has published in its November 2017 issue 11 papers describing some of the advances in the field of neuropsychology over the past 25 years. The papers address three broad topics: assessment and intervention, brain imaging, and theory and methods. The papers describe the rise of new assessment and intervention technologies, the impact of evidence for neuroplasticity on neurorehabilitation. Examples of the use of mathematical models of cognition to investigate latent neurobehavioral processes, the development of the field of neuropsychology in select international countries, the increasing sophistication of brain imaging methods, the recent evidence for localizationist and connectionist accounts of neurobehavioral functioning, the advances in neurobehavioral genomics, and descriptions of newly developed statistical models of longitudinal change. Together the papers convey evidence of the vibrant growth in the field of neuropsychology over the quarter century since APA's 100th anniversary in 1992. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Association of aryl hydrocarbon receptor gene polymorphism with the neurobehavioral function and autonomic nervous system function changes induced by benzo[a]pyrene exposure in coke oven workers.

PubMed

Zhang, Hongmei; Nie, Jisheng; Li, Xin; Niu, Qiao

2013-03-01

To analyze the association of aryl hydrocarbon receptor (AhR) gene polymorphism and the neurotoxicity induced by benzo[a]pyrene (B[a]P) in coke oven workers. Subjects, 214 coke oven workers and 81 controls, were detected for neurobehavioral function and autonomic nervous system (ANS) function. Airborne B[a]P concentration, urinary 1-hydroxypyrene level, and AhR gene polymorphisms were determined and analyzed for their association with B[a]P neurotoxicity. Neurobehavioral function and ANS function were significantly decreased and dependent on B[a]P dose. The AhR GG, GA, and AA genotypes in G1661A fitted the Hardy-Weinberg equation, whereas C1549T and G1708A gene mutants were not detected. Indices indicating neurotoxicity showed no significant difference among individuals with AA, GG, or GA genotype except for the confusion-bewilderment (P > 0.05). The AhR gene polymorphism is not thought to correlate with B[a]P neurotoxicity among coke oven workers.

Neonatal abstinence syndrome: Neurobehavior at 6 weeks of age in infants with or without pharmacological treatment for withdrawal.

PubMed

Heller, Nicole A; Logan, Beth A; Morrison, Deborah G; Paul, Jonathan A; Brown, Mark S; Hayes, Marie J

2017-07-01

Use and abuse of prescription opioids and concomitant increase in Neonatal Abstinence Syndrome (NAS), a condition that may lead to protracted pharmacological treatment in more than 60% of infants, has tripled since 2000. This study assessed neurobehavioral development using the NICU Network Neurobehavioral Scale in 6-week old infants with prenatal methadone exposure who did (NAS+; n = 23) or did not (NAS-; n = 16) require pharmacological treatment for NAS severity determined by Finnegan Scale. An unexposed, demographically similar group of infants matched for age served as comparison (COMP; n = 21). NAS+, but not NAS- group, had significantly lower scores on the regulation (p < .01) and quality of movement (p < .01) summary scales than the COMP group. The NAS+ and NAS- groups had higher scores on the stress-abstinence scale than the COMP group (p < .05). NAS diagnosis (NAS +) was associated with poorer regulation and quality of movement at 6 weeks of age compared to infants without prenatal methadone exposure from the same demographic. © 2017 Wiley Periodicals, Inc.

S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice.

PubMed

Ornoy, Asher; Weinstein-Fudim, Liza; Tfilin, Matanel; Ergaz, Zivanit; Yanai, Joseph; Szyf, Moshe; Turgeman, Gadi

2018-01-16

A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight. From day 50, we carried out neurobehavioral tests and assessment of the antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT activity, lipid peroxidation and the expression of antioxidant genes. Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that were more prominent in males. Changes in the activity of SOD and CAT increased lipid peroxidation and changes in the expression of antioxidant genes were observed in the prefrontal cortex of VPA treated mice, more prominent in females, while ASD like behavior was more prominent in males. There were no changes in the redox potential of the liver. The co-administration of VPA and SAM alleviated most ASD like neurobehavioral symptoms and normalized the redox potential in the prefrontal cortex. Early postnatal VPA administration induces ASD like behavior that is more severe in males, while the redox status changes are more severe in females; SAM corrects both. VPA-induced ASD seems to result from epigenetic changes, while the redox status changes may be secondary. Copyright © 2018. Published by Elsevier Inc.

Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy.

PubMed

Eckman, Elizabeth A; Pacheco-Quinto, Javier; Herdt, Aimee R; Halperin, John J

2018-01-11

Lyme encephalopathy, characterized by non-specific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to CNS infection. Identical symptoms occur in innumerable other inflammatory states and may reflect the effect of systemic immune mediators on the CNS. Multiplex immunoassays were used to characterize the inflammatory profile in serum and CSF from Lyme and non-Lyme patients with a range of symptoms to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. CSF CXCL13 was elevated dramatically in confirmed neuroborreliosis (n=8) and to a lesser extent in possible neuroborreliosis (n=11) and other neuroinflammatory conditions (n=44). Patients with Lyme (n=63) or non-Lyme (n=8) encephalopathy had normal CSF findings, but had elevated serum levels of IL-7, TSLP, IL-17A, IL-17F, and MIP-1α/CCL3. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody (ITAb) production. However, CXCL13 does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory ITAb, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The Differential Effects of Regular Shift Work and Obstructive Sleep Apnea on Sleepiness, Mood and Neurocognitive Function.

PubMed

Cori, Jennifer M; Jackson, Melinda L; Barnes, Maree; Westlake, Justine; Emerson, Paul; Lee, Jacen; Galante, Rosa; Hayley, Amie; Wilsmore, Nicholas; Kennedy, Gerard A; Howard, Mark

2018-06-15

To assess whether poor sleep quality experienced by regular shift workers and individuals with obstructive sleep apnea (OSA) affects neurobehavioral function similarly, or whether the different etiologies have distinct patterns of impairment. Thirty-seven shift workers (> 24 hours after their last shift), 36 untreated patients with OSA, and 39 healthy controls underwent assessment of sleepiness (Epworth Sleepiness Scale [ESS]), mood (Beck Depression Index, State Trait Anxiety Inventory [STAI], Profile of Mood States), vigilance (Psychomotor Vigilance Task [PVT], Oxford Sleep Resistance Test [OSLER], driving simulation), neurocognitive function (Logical Memory, Trails Making Task, Digit Span Task, Victoria Stroop Test) and polysomnography. Sleepiness (ESS score; median, interquartile range) did not differ between the OSA (10.5, 6.3-14) and shift work (7, 5-11.5) groups, but both had significantly elevated scores relative to the control group (5, 3-6). State anxiety (STAI-S) was the only mood variable that differed significantly between the OSA (35, 29-43) and shift work (30, 24-33.5) groups, however both demonstrated several mood deficits relative to the control group. The shift work and control groups performed similarly on neurobehavioral tasks (simulated driving, PVT, OSLER and neurocognitive tests), whereas the OSA group performed worse. On the PVT, lapses were significantly greater for the OSA group (3, 2-6) than both the shift work (2, 0-3.5) and control (1, 0-4) groups. Shift workers and patients with OSA had similar sleepiness and mood deficits relative to healthy individuals. However, only the patients with OSA showed deficits on vigilance and neurocognitive function relative to healthy individuals. These findings suggest that distinct causes of sleep disturbance likely result in different patterns of neurobehavioral dysfunction. © 2018 American Academy of Sleep Medicine.

Division III Collision Sports Are Not Associated with Neurobehavioral Quality of Life

PubMed Central

Taylor, Alex M.; Berkner, Paul; Sandstrom, Noah J.; Peluso, Mark W.; Kurtz, Matthew M.; Pascual-Leone, Alvaro; Mannix, Rebekah

2016-01-01

Abstract We sought to determine whether the exposure to the sub-concussive blows that occur during division III collegiate collision sports affect later life neurobehavioral quality-of-life measures. We conducted a cross-sectional study of alumni from four division III colleges, targeting those between the ages of 40–70 years, using several well-validated quality-of-life measures for executive function, general concerns, anxiety, depression, emotional and behavior dyscontrol, fatigue, positive affect, sleep disturbance, and negative consequences of alcohol use. We used multivariable linear regression to assess for associations between collision sport participation and quality-of-life measures while adjusting for covariates including age, gender, race, annual income, highest educational degree, college grades, exercise frequency, and common medical conditions. We obtained data from 3702 alumni, more than half of whom (2132) had participated in collegiate sports, 23% in collision sports, 23% in non-contact sports. Respondents with a history of concussion had worse self-reported health on several measures. When subjects with a history of concussion were removed from the analyses in order to assess for any potential effect of sub-concussive blows alone, negative consequences of alcohol use remained higher among collision sport athletes (β-coefficient 1.957, 95% CI 0.827-3.086). There were, however, no other significant associations between exposure to collision sports during college and any other quality-of-life measures. Our results suggest that, in the absence of a history of concussions, participation in collision sports at the Division III collegiate level is not a risk factor for worse long-term neurobehavioral outcomes, despite exposure to repeated sub-concussive blows. PMID:26193380

Paradoxical Neurobehavioral Rescue by Memories of Early-Life Abuse: The Safety Signal Value of Odors Learned during Abusive Attachment

PubMed Central

Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M

2015-01-01

Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood—in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70–90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation. PMID:25284320

Paradoxical neurobehavioral rescue by memories of early-life abuse: the safety signal value of odors learned during abusive attachment.

PubMed

Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M

2015-03-01

Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood-in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70-90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation.

A Neurobehavioral Phenotype of Blast Traumatic Brain Injury and Psychological Stress in Male and Female Rats

DTIC Science & Technology

2012-02-03

from lasting effects ( Martin et al., 2008). TBI, one of the signature wounds of the Global War on Terrorism, is one type of injury with long- term...are closed head injuries and 68% result from exposure to blast (Hoge et al., 2008; Martin , Lu, Helmick, French, & Warden, 2008; Wojcik et al., 2010...Returning Warriors also are affected by these disorders and the associations between TBI and ASD and the lasting effects of PTSD is unclear ( Martin et

Prosocial effects of nicotine and ethanol in adolescent rats through partially dissociable neurobehavioral mechanisms

PubMed Central

Trezza, Viviana; Baarendse, Petra J.J.; Vanderschuren, Louk J.M.J.

2009-01-01

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at doses that reduced anxiety. The effects of nicotine on social play were blocked by the opioid receptor antagonist naloxone, the CB1 cannabinoid receptor antagonist SR141716A, and the dopamine receptor antagonist alpha-flupenthixol. The effects of ethanol were blocked by SR141716A and alpha-flupenthixol, but not by naloxone. Combined administration of subeffective doses of nicotine and ethanol only modestly enhanced social play. These results show that the facilitatory effects of nicotine and ethanol on social play are behaviorally specific and mediated through neurotransmitter systems involved in positive emotions and motivation, through partially dissociable mechanisms. Furthermore, the stimulating effects of nicotine and ethanol on social play behavior are independent of their anxiolytic-like properties. PMID:19657330

Prosocial effects of nicotine and ethanol in adolescent rats through partially dissociable neurobehavioral mechanisms.

PubMed

Trezza, Viviana; Baarendse, Petra J J; Vanderschuren, Louk J M J

2009-11-01

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at doses that reduced anxiety. The effects of nicotine on social play were blocked by the opioid receptor antagonist naloxone, the CB(1) cannabinoid receptor antagonist SR141716A, and the dopamine receptor antagonist alpha-flupenthixol. The effects of ethanol were blocked by SR141716A and alpha-flupenthixol, but not by naloxone. Combined administration of subeffective doses of nicotine and ethanol only modestly enhanced social play. These results show that the facilitatory effects of nicotine and ethanol on social play are behaviorally specific and mediated through neurotransmitter systems involved in positive emotions and motivation, through partially dissociable mechanisms. Furthermore, the stimulating effects of nicotine and ethanol on social play behavior are independent of their anxiolytic-like properties.

The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

NASA Technical Reports Server (NTRS)

Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

2003-01-01

OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological "cost" which accumulates over time.

Does Farming Have an Effect on Health Status? A Comparison Study in West Greece

PubMed Central

Demos, Konstantinos; Sazakli, Eleni; Jelastopulu, Eleni; Charokopos, Nikolaos; Ellul, John; Leotsinidis, Michalis

2013-01-01

Investigating the health status of agricultural workers is a challenging goal. Contradictory outcomes concerning farmers’ health are reported in the literature. In this cross-sectional study, certain clinical and neurobehavioral health outcomes were compared between farmers and non-farmers living in the same rural area. Farmers (328) and non-farmers (347), matched per age and sex, were selected randomly in an agricultural area in West Greece. Both groups underwent haematological and biochemical examinations and were administered two neurobehavioral tests, namely the Mini-Mental State Examination (MMSE) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Sociodemographic, personal medical, nutritional and lifestyle data were recorded. According to personal statements, farmers suffered from hypertension, cardiovascular, orthopaedic and ENT problems in higher frequency. Haematocrit, haemoglobin and serum cholinesterase’s activity were found to be lower among farmers. Lower prevalence of hypertension and better performances on MMSE and MADRS tests were recorded in young farmers in relation to young non-farmers, while these findings were reversed in older ages. Odds Ratios were calculated through multivariate logistic regression models. Factors affecting these impairments remain to be clarified. PMID:23442558

Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis.

PubMed

Ray, A; Gulati, K; Rai, N

2017-01-01

Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness. © 2017 Elsevier Inc. All rights reserved.

Managing neurobehavioral capability when social expediency trumps biological imperatives

PubMed Central

Spaeth, Andrea M.; Goel, Namni; Dinges, David F.

2013-01-01

Sleep, which is evolutionarily conserved across species, is a biological imperative that cannot be ignored or replaced. However, the percentage of habitually sleep-restricted adults has increased in recent decades. Extended work hours and commutes, shift work schedules, and television viewing are particularly potent social factors that influence sleep duration. Chronic partial sleep restriction, a product of these social expediencies, leads to the accumulation of sleep debt over time and consequently increases sleep propensity, decreases alertness, and impairs critical aspects of cognitive functioning. Significant interindividual variability in the neurobehavioral responses to sleep restriction exists—this variability is stable and phenotypic—suggesting a genetic basis. Identifying vulnerability to sleep loss is essential as many adults cannot accurately judge their level of impairment in response to sleep restriction. Indeed, the consequences of impaired performance and the lack of insight due to sleep loss can be catastrophic. In order to cope with the effects of social expediencies on biological imperatives, identification of biological (including genetic) and behavioral markers of sleep loss vulnerability as well as development of technological approaches for fatigue management are critical. PMID:22877676

Does farming have an effect on health status? A comparison study in west Greece.

PubMed

Demos, Konstantinos; Sazakli, Eleni; Jelastopulu, Eleni; Charokopos, Nikolaos; Ellul, John; Leotsinidis, Michalis

2013-02-26

Investigating the health status of agricultural workers is a challenging goal. Contradictory outcomes concerning farmers' health are reported in the literature. In this cross-sectional study, certain clinical and neurobehavioral health outcomes were compared between farmers and non-farmers living in the same rural area. Farmers (328) and non-farmers (347), matched per age and sex, were selected randomly in an agricultural area in West Greece. Both groups underwent haematological and biochemical examinations and were administered two neurobehavioral tests, namely the Mini-Mental State Examination (MMSE) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Sociodemographic, personal medical, nutritional and lifestyle data were recorded. According to personal statements, farmers suffered from hypertension, cardiovascular, orthopaedic and ENT problems in higher frequency. Haematocrit, haemoglobin and serum cholinesterase's activity were found to be lower among farmers. Lower prevalence of hypertension and better performances on MMSE and MADRS tests were recorded in young farmers in relation to young non-farmers, while these findings were reversed in older ages. Odds Ratios were calculated through multivariate logistic regression models. Factors affecting these impairments remain to be clarified.

Reliability of concentrations of organophosphate pesticide metabolites in serial urine specimens from pregnancy in the Generation R study

PubMed Central

Spaan, Suzanne; Pronk, Anjoeka; Koch, Holger M.; Jusko, Todd A.; Jaddoe, Vincent W.V.; Shaw, Pamela A.; Tiemeier, Henning M.; Hofman, Albert; Pierik, Frank H.; Longnecker, Matthew P.

2014-01-01

The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the present study, urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined in 120 pregnant women participating in the Generation R Study in Rotterdam. Intra-class correlation coefficients (ICCs) across serial urine specimens taken at <18, 18–25, and >25 weeks of pregnancy were determined to assess reliability. Geometric mean total DAP metabolite concentrations were 229 (GSD 2.2), 240 (GSD 2.1), and 224 (GSD 2.2) nmol/g creatinine across the three periods of gestation. Metabolite concentrations from the serial urine specimens in general correlated moderately. The ICCs for the six DAP metabolites ranged from 0.14 to 0.38 (0.30 for total DAPs), indicating weak to moderate reliability. Although the DAP metabolite levels observed in this study are slightly higher and slightly more correlated than in previous studies, the low to moderate reliability indicates a high degree of within-person variability, which presents challenges for designing well-powered epidemiologic studies. PMID:25515376

Resilience: A psychobiological construct for psychiatric disorders.

PubMed

Shrivastava, Amresh; Desousa, Avinash

2016-01-01

Understanding of psychopathology of mental disorder is evolving, particularly with availability of newer insight from the field of genetics, epigenetics, social, and environmental pathology. It is now becoming clear how biological factors are contributing to development of an illness in the face of a number of psychosocial factors. Resilience is a psychobiological factor which determines individual's response to adverse life events. Resilience is a human capacity to adapt swiftly and successfully to stressful/traumatic events and manage to revert to a positive state. It is fundamental for growth of positive psychology which deals with satisfaction, adaptability, contentment, and optimism in people's life. Of late, there has been a paradigm shift in the understanding of resilience in context of stress risk vulnerability dimension. It is a neurobiological construct with significant neurobehavioral and emotional features which plays important role in deconstructing mechanism of biopsychosocial model of mental disorders. Resilience is a protective factor against development of mental disorder and a risk factor for a number of clinical conditions, e.g. suicide. Available information from scientific studies points out that resilience is modifiable factor which opens up avenues for a number of newer psychosocial as well as biological therapies. Early identification of vulnerable candidates and effectiveness of resilience-based intervention may offer more clarity in possibility of prevention. Future research may be crucial for preventive psychiatry. In this study, we aim to examine whether resilience is a psychopathological construct for mental disorder.

Toxicologic evaluation of DHA-rich algal oil: Genotoxicity, acute and subchronic toxicity in rats.

PubMed

Schmitt, D; Tran, N; Peach, J; Bauter, M; Marone, P

2012-10-01

DHA-rich algal oil ONC-T18, tested in a battery of in vitro and in vivo genotoxicity tests, did not show mutagenic or genotoxic potential. The acute oral LD50 in rats has been estimated to be greater than 5000 mg/kg of body weight. In a 90-day subchronic dietary study, administration of DHA-rich algal oil at concentrations of 0, 10,000, 25,000, and 50,000 ppm in the diet for 13 weeks did not produce any significant toxicologic manifestations. The algal oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral endpoints, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, or necropsy findings. The no observed adverse effect level (NOAEL) was the highest level fed of 50,000 ppm which is equivalent to 3,305 and 3,679 mg/kg bw/day, for male and female rats, respectively. The studies were conducted as part of an investigation to examine the safety of DHA-rich algal oil. The results confirm that it possesses a toxicity profile similar to other currently marketed algal oils and support the safety of DHA-rich algal oil for its proposed use in food. Copyright © 2012 Elsevier Ltd. All rights reserved.

Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure.

PubMed

Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

2015-07-02

Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N=33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 μg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL×sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neuroprotective effect of Feronia limonia on ischemia reperfusion induced brain injury in rats

PubMed Central

Rakhunde, Purushottam B.; Saher, Sana; Ali, Syed Ayaz

2014-01-01

Objectives: Brain stroke is a leading cause of death without effective treatment. Feronia limonia have potent antioxidant activity and can be proved as neuroprotective against ischemia-reperfusion induced brain injury. Materials and Methods: We studied the effect of methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) and Vitamin E as reference standard drug on 30 min induced ischemia, followed by reperfusion by testing the neurobehavioral tests such as neurodeficit score, rota rod test, hanging wire test, beam walk test and elevated plus maze. The biochemical parameters, which were measured in animals brain were catalase, superoxide dismutase (SOD), malondialdehyde and nitric oxide in control and treated rats. Results: The methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) treated groups showed a statistically significant improvement in the neurobehavioral parameters such as motor performance (neurological status, significant increase in grasping ability, forelimb strength improvement in balance and co-ordination). The biochemical parameters in the brains of rats showed a significant reduction in the total nitrite (P < 0.01) and lipid peroxidation (P < 0.01), also a significant enhanced activity of enzymatic antioxidants such as catalase (P < 0.01) and SOD (P < 0.05). Conclusion: These observations suggest the neuroprotective and antioxidant activity of F. limonia and Vitamin E on ischemia reperfusion induced brain injury and may require further evaluation. PMID:25538333

Neuroprotective effect of Feronia limonia on ischemia reperfusion induced brain injury in rats.

PubMed

Rakhunde, Purushottam B; Saher, Sana; Ali, Syed Ayaz

2014-01-01

Brain stroke is a leading cause of death without effective treatment. Feronia limonia have potent antioxidant activity and can be proved as neuroprotective against ischemia-reperfusion induced brain injury. We studied the effect of methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) and Vitamin E as reference standard drug on 30 min induced ischemia, followed by reperfusion by testing the neurobehavioral tests such as neurodeficit score, rota rod test, hanging wire test, beam walk test and elevated plus maze. The biochemical parameters, which were measured in animals brain were catalase, superoxide dismutase (SOD), malondialdehyde and nitric oxide in control and treated rats. The methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) treated groups showed a statistically significant improvement in the neurobehavioral parameters such as motor performance (neurological status, significant increase in grasping ability, forelimb strength improvement in balance and co-ordination). The biochemical parameters in the brains of rats showed a significant reduction in the total nitrite (P < 0.01) and lipid peroxidation (P < 0.01), also a significant enhanced activity of enzymatic antioxidants such as catalase (P < 0.01) and SOD (P < 0.05). These observations suggest the neuroprotective and antioxidant activity of F. limonia and Vitamin E on ischemia reperfusion induced brain injury and may require further evaluation.

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

PubMed Central

2010-01-01

Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

PubMed

Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

2010-10-19

Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.

A critical appraisal of atomoxetine in the management of ADHD

PubMed Central

Childress, Ann C

2016-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder beginning in childhood and often continuing into adulthood. A wealth of data shows that ADHD symptoms respond well to pharmacological treatment. Stimulant medications, including amphetamine and methylphenidate, are most commonly used to treat ADHD. However, with the approval of atomoxetine (Strattera®, [ATX]) by the US Food and Drug Administration in late 2002, an effective non-stimulant option became available. The US Food and Drug Administration approved ATX for the treatment of ADHD in children, adolescents, and adults. Although the effect size of ATX is generally lower than that of stimulants, the American Academy of Child and Adolescent Psychiatry Practice Parameter for the treatment of ADHD lists ATX as a first-line treatment option. ATX is widely prescribed and accounted for 6% of the prescriptions of ADHD visits in the US in 2010. Numerous trials have found that ATX improves quality of life and emotional lability in addition to core ADHD symptoms. Although some improvement may be seen in a patient as early as one week after the initiation of treatment, ATX generally takes longer to have a full effect. The median time to response using 25% improvement in ADHD symptoms in pooled trials was 3.7 weeks. Data from these trials indicate that the probability of symptom improvement may continue to increase up to 52 weeks after treatment is initiated. ATX has been shown to be safe and effective in combination with stimulants. It has also been studied systematically in subjects with ADHD and comorbid oppositional defiant disorder, anxiety, depression, and substance use disorders. The mechanism of action of ATX, its efficacy, and adverse events reported in trials is reviewed. PMID:26730199

A cost-effectiveness analysis of lisdexamfetamine dimesylate in the treatment of adults with attention-deficit/hyperactivity disorder in the UK.

PubMed

Zimovetz, Evelina A; Joseph, Alain; Ayyagari, Rajeev; Mauskopf, Josephine A

2018-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults. Estimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX). A 1-year decision-analytic model was developed. Health outcomes included response, non-response and inability to tolerate. Efficacy data were obtained from a mixed-treatment comparison (MTC). Response was a score of 1 or 2 on the Clinical Global Impression-Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utilities were identified via a systematic literature review. Health care resource use estimates were obtained via a survey of clinicians. Daily drug costs were estimated from mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses (PSAs) were performed. LDX dominated MPH-ER and ATX; reducing mean per-patient annual cost by £5 and £200, and increasing mean quality-adjusted life years (QALYs) by 0.005 and 0.009, respectively. In the PSA, the probability of cost-effectiveness for LDX vs. MPH-ER and ATX at a threshold of £20,000 per QALY was 61% and 80%, respectively. From the perspective of the UK NHS, LDX is likely to provide a cost-effective treatment for adults with ADHD. This conclusion may be drawn with more certainty in comparison with ATX than with MPH-ER.

Fetal Iron Deficiency and Genotype Influence Emotionality in Infant Rhesus Monkeys123

PubMed Central

Golub, Mari S; Hogrefe, Casey E

2015-01-01

Background: Anemia during the third trimester of fetal development affects one-third of the pregnancies in the United States and has been associated with postnatal behavioral outcomes. This study examines how fetal iron deficiency (ID) interacts with the fetal monoamine oxidase A (MAOA) genotype. MAOA metabolizes monoamine neurotransmitters. MAOA polymorphisms in humans affect temperament and modify the influence of early adverse environments on later behavior. Objective: The aim of the study was to advance translation of developmental ID research in animal models by taking into account genetic factors that influence outcomes in human populations. Methods: Male infant rhesus monkeys 3–4 mo old born to mothers fed an ID (10 ppm iron) diet were compared with controls (100 ppm iron). Infant monkeys with high- or low-transcription rate MAOA polymorphisms were equally distributed between diet groups. Behavioral responses to a series of structured experiences were recorded during a 25-h separation of the infants from their mothers. Results: Infant monkeys with low-transcription MAOA polymorphisms more clearly demonstrated the following ID effects suggested in earlier studies: a 4% smaller head circumference, a 39% lower cortisol response to social separation, a 129% longer engagement with novel visual stimuli, and 33% lesser withdrawal in response to a human intruder. The high MAOA genotype ID monkeys demonstrated other ID effects: less withdrawal and emotionality after social separation and lower “fearful” ratings. Conclusion: MAOA × ID interactions support the role of monoamine neurotransmitters in prenatal ID effects in rhesus monkeys and the potential involvement of common human polymorphisms in determining the pattern of neurobehavioral effects produced by inadequate prenatal nutrition. PMID:25733484

Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)--a controlled multicenter study of a non-pharmacological treatment approach.

PubMed

Holtmann, Martin; Pniewski, Benjamin; Wachtlin, Daniel; Wörz, Sonja; Strehl, Ute

2014-08-13

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and has often a chronic course persisting into adulthood. However, up to 30% of children treated with stimulants either fail to show an improvement or suffer adverse side effects, including decreased appetite, insomnia and irritability and there is no evidence of long term efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback is an effective additional or alternative treatment for children with ADHD, leading to e.g. significant and stable improvement in behavior, attention and IQ. Significant treatment effects of neurofeedback have also been verified in meta-analyses. Most of the trials, however, have been criticized for methodological difficulties, particularly lacking appropriate control conditions and number of patients included. This randomized study examines the efficacy of slow cortical potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by comparing two active treatment modalities. A total of 144 patients with ADHD, older than six and younger than ten years, in some cases with additional pharmacological treatment, are included in this trial. In five trial centres patients are treated either with SCP-feedback or electromyographic (EMG) -feedback in 25 sessions within 3 months. A comprehensive test battery is conducted before and after treatment and at follow-up 6 month later, to assess core symptoms of ADHD, general psychopathology, attentional performance, comorbid symptoms, intelligence, quality of life and cortical arousal. The efficacy of SCP-feedback training for children with ADHD is evaluated in this randomized controlled study. In addition to behavior ratings and psychometric tests neurophysiological parameters serve as dependent variables. Further, the choice of EMG-biofeedback as an active control condition is debated. Current Controlled Trials ISRCTN76187185. Registered 5 February 2009.

Neurobehavioral effects of exposure to traffic-related air pollution and transportation noise in primary schoolchildren.

PubMed

van Kempen, Elise; Fischer, Paul; Janssen, Nicole; Houthuijs, Danny; van Kamp, Irene; Stansfeld, Stephen; Cassee, Flemming

2012-05-01

Children living close to roads are exposed to both traffic noise and traffic-related air pollution. There are indications that both exposures affect cognitive functioning. So far, the effects of both exposures have only been investigated separately. To investigate the relationship between air pollution and transportation noise on the cognitive performance of primary schoolchildren in both the home and school setting. Data acquired within RANCH from 553 children (aged 9-11 years) from 24 primary schools were analysed using multilevel modelling with adjustment for a range of socio-economic and life-style factors. Exposure to NO(2) (which is in urban areas an indicator for traffic-related air pollution) at school was statistically significantly associated with a decrease in the memory span length measured during DMST (χ(2)=6.8, df=1, p=0.01). This remained after additional adjustment for transportation noise. Statistically significant associations were observed between road and air traffic noise exposure at school and the number of errors made during the 'arrow' (χ(2)=7.5, df=1, p=0.006) and 'switch' (χ(2)=4.8, df=1, p=0.028) conditions of the SAT. This remained after adjustment for NO(2). No effects of air pollution exposure or transportation noise exposure at home were observed. Combined exposure of air pollution and road traffic noise had a significant effect on the reaction times measured during the SRTT and the 'block' and the 'arrow' conditions of the SAT. Our results provide some support that prolonged exposure to traffic-related air pollution as well as to noise adversely affects cognitive functioning. Copyright © 2012 Elsevier Inc. All rights reserved.

Validation and Application of Pharmacokinetic Models for Interspecies Extrapolations in Toxicity Risk Assessments of Volatile Organics

DTIC Science & Technology

1988-08-30

Ai _.. ;:: -- I. OVERALL OBJECTIVE AND STATEMENT OF WORK The overall objective of the proposed project is to investigate the scientific basis...development and inter-species correlations with toxicity. A second series of tissue disposition experiments will be conducted to determine what ...elimination of halocarbons is hepatic metabolism. If metabolism plays a significant role in the disposition and subsequent neurobehavioral effects of

Effects of Nano-MnO2 on Dopaminergic Neurons and the Spatial Learning Capability of Rats

PubMed Central

Li, Tao; Shi, Tingting; Li, Xiaobo; Zeng, Shuilin; Yin, Lihong; Pu, Yuepu

2014-01-01

This study aimed to observe the effect of intracerebrally injected nano-MnO2 on neurobehavior and the functions of dopaminergic neurons and astrocytes. Nano-MnO2, 6-OHDA, and saline (control) were injected in the substantia nigra and the ventral tegmental area of Sprague-Dawley rat brains. The neurobehavior of rats was evaluated by Morris water maze test. Tyrosine hydroxylase (TH), inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) expressions in rat brain were detected by immunohistochemistry. Results showed that the escape latencies of nano-MnO2 treated rat increased significantly compared with control. The number of TH-positive cells decreased, GFAP- and iNOS-positive cells increased significantly in the lesion side of the rat brains compared with the contralateral area in nano-MnO2 group. The same tendencies were observed in nano-MnO2-injected rat brains compared with control. However, in the the positive control, 6-OHDA group, escape latencies increased, TH-positive cell number decreased significantly compared with nano-MnO2 group. The alteration of spatial learning abilities of rats induced by nano-MnO2 may be associated with dopaminergic neuronal dysfunction and astrocyte activation. PMID:25101772

Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis

PubMed Central

da Silveira, Cinthia Cristina Sousa de Menezes; Fernandes, Luanna Melo Pereira; Silva, Mallone Lopes; Luz, Diandra Araújo; Gomes, Antônio Rafael Quadros; Machado, Christiane Schineider; de Lira, Tatiana Onofre; Ferreira, Antonio Gilberto

2016-01-01

Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP) rich in triterpenoids, primarily lupeol and β-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control), EEYP (1, 3, 10, and 30 mg/kg), or diazepam, fluoxetine, and caffeine (positive controls) 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product. PMID:27822336

Neurobehavioral Functioning and Survival Following Lung Transplantation

PubMed Central

Blumenthal, James A.; Carney, Robert M.; Freedland, Kenneth E.; O’Hayer, C. Virginia F.; Trulock, Elbert P.; Martinu, Tereza; Schwartz, Todd A.; Hoffman, Benson M.; Koch, Gary G.; Davis, R. Duane; Palmer, Scott M.

2014-01-01

Background: Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. Methods: The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. Results: One hundred eleven patients died over a mean follow-up of 10.8 years (SD = 0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR] = 1.09, P = .012) and memory performance (HR = 1.11, P = .030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored > 13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR = 1.85 [95% CI, 1.04, 3.28], P = .036). Conclusions: Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation. Trial registry: ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov PMID:24233282

Age- and gender-dependent impairments of neurobehaviors in mice whose mothers were exposed to lipopolysaccharide during pregnancy.

PubMed

Wang, Hua; Meng, Xiu-Hong; Ning, Huan; Zhao, Xian-Feng; Wang, Qun; Liu, Ping; Zhang, Heng; Zhang, Cheng; Chen, Gui-Hai; Xu, De-Xiang

2010-02-01

Lipopolysaccharide (LPS)-induced intrauterine infection has been associated with neurodevelopmental injury in rodents. The purpose of the present study was to analyze the dynamic changes of neurobehaviors in mice whose mothers were exposed to LPS during pregnancy. The pregnant mice were intraperitoneally (i.p.) injected with LPS (8 microg/kg) daily from gestational day (gd) 8 to gd 15. A battery of neurobehavioral tasks was performed in mice at postnatal day (PND) 70, 200, 400 and 600. Results showed that the spatial learning and memory ability, determined by radial six-arm water maze (RAWM), were obviously impaired in two hundred-day-old female mice and four hundred-day-old male mice whose mothers were exposed to LPS during pregnancy. Open field test showed that the number of squares crossed and peripheral time, a marker of anxiety and exploration activity, were markedly increased in two hundred-day-old female mice following prenatal LPS exposure. In addition, prenatal LPS exposure significantly shortened the latency to the first grid crossing in six hundred-day-old female offspring. Moreover, sensorimotor impairment in the beam walking was observed in two hundred-day-old female mice whose mothers were exposed to LPS during pregnancy. Species-typical behavior examination showed that prenatal LPS exposure markedly increased weight burrowed in seventy-day-old male offspring and six hundred-day-old female offspring. Correspondingly, prenatal LPS exposure significantly reduced weight hoarded in two hundred-day-old female offspring. Taken together, these results suggest that prenatal LPS exposure induces neurobehavioral impairments at adulthood in an age- and gender-dependent manner. 2009 Elsevier Ireland Ltd. All rights reserved.

Environmental pollutants and disease in American children: estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities.

PubMed Central

Landrigan, Philip J; Schechter, Clyde B; Lipton, Jeffrey M; Fahs, Marianne C; Schwartz, Joel

2002-01-01

In this study, we aimed to estimate the contribution of environmental pollutants to the incidence, prevalence, mortality, and costs of pediatric disease in American children. We examined four categories of illness: lead poisoning, asthma, cancer, and neurobehavioral disorders. To estimate the proportion of each attributable to toxins in the environment, we used an environmentally attributable fraction (EAF) model. EAFs for lead poisoning, asthma, and cancer were developed by panels of experts through a Delphi process, whereas that for neurobehavioral disorders was based on data from the National Academy of Sciences. We define environmental pollutants as toxic chemicals of human origin in air, food, water, and communities. To develop estimates of costs, we relied on data from the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, National Center for Health Statistics, the Bureau of Labor Statistics, the Health Care Financing Agency, and the Practice Management Information Corporation. EAFs were judged to be 100% for lead poisoning, 30% for asthma (range, 10-35%), 5% for cancer (range, 2-10%), and 10% for neurobehavioral disorders (range, 5-20%). Total annual costs are estimated to be $54.9 billion (range $48.8-64.8 billion): $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders. This sum amounts to 2.8 percent of total U.S. health care costs. This estimate is likely low because it considers only four categories of illness, incorporates conservative assumptions, ignores costs of pain and suffering, and does not include late complications for which etiologic associations are poorly quantified. The costs of pediatric environmental disease are high, in contrast with the limited resources directed to research, tracking, and prevention. PMID:12117650

Controlled human exposure to methyl tertiary butyl ether in gasoline: symptoms, psychophysiologic and neurobehavioral responses of self-reported sensitive persons.

PubMed Central

Fiedler, N; Kelly-McNeil, K; Mohr, S; Lehrer, P; Opiekun, R E; Lee, C; Wainman, T; Hamer, R; Weisel, C; Edelberg, R; Lioy, P J

2000-01-01

The 1990 Clean Air Act mandated oxygenation of gasoline in regions where carbon monoxide standards were not met. To achieve this standard, methyl tertiary butyl ether (MTBE) was increased to 15% by volume during winter months in many locations. Subsequent to the increase of MTBE in gasoline, commuters reported increases in symptoms such as headache, nausea, and eye, nose, and throat irritation. The present study compared 12 individuals selected based on self-report of symptoms (self-reported sensitives; SRSs) associated with MTBE to 19 controls without self-reported sensitivities. In a double-blind, repeated measures, controlled exposure, subjects were exposed for 15 min to clean air, gasoline, gasoline with 11% MTBE, and gasoline with 15% MTBE. Symptoms, odor ratings, neurobehavioral performance on a task of driving simulation, and psychophysiologic responses (heart and respiration rate, end-tidal CO(2), finger pulse volume, electromyograph, finger temperature) were measured before, during, and immediately after exposure. Relative to controls, SRSs reported significantly more total symptoms when exposed to gasoline with 15% MTBE than when exposed to gasoline with 11% MTBE or to clean air. However, these differences in symptoms were not accompanied by significant differences in neurobehavioral performance or psychophysiologic responses. No significant differences in symptoms or neurobehavioral or psychophysiologic responses were observed when exposure to gasoline with 11% MTBE was compared to clean air or to gasoline. Thus, the present study, although showing increased total symptoms among SRSs when exposed to gasoline with 15% MTBE, did not support a dose-response relationship for MTBE exposure nor the symptom specificity associated with MTBE in epidemiologic studies. Images Figure 1 Figure 2 PMID:10964796

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine.

PubMed

Ramakrishnan, Sridhar; Wesensten, Nancy J; Kamimori, Gary H; Moon, James E; Balkin, Thomas J; Reifman, Jaques

2016-10-01

Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. © 2016 Associated Professional Sleep Societies, LLC.

Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

PubMed

Nishiwaki, Y; Maekawa, K; Ogawa, Y; Asukai, N; Minami, M; Omae, K

2001-11-01

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed.

Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

PubMed Central

Nishiwaki, Y; Maekawa, K; Ogawa, Y; Asukai, N; Minami, M; Omae, K

2001-01-01

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed. PMID:11713003

Comparative neurobehavioral study of a polybrominated biphenyl-exposed population in Michigan and a nonexposed group in Wisconsin.

PubMed Central

Valciukas, J A; Lilis, R; Wolff, M S; Anderson, H A

1978-01-01

An analysis of findings regarding the prevalence and time course of symptoms and the results of neurobehavioral testing among Michigan and Wisconsin dairy farmers, is reported. Reviewed are: (1) differences in the prevalence of neurological symptoms at the time of examination; (2) differences in the incidence and time course of symptoms for the period 1972--1976; (3) differences among populations and subgroups (sex and age) regarding performance test scores; (4) correlations between performance test scores and neurological symptoms; and (5) correlations between serum PBB levels as indicators of exposure and performance tests and neurological symptoms. PMID:209977

MYSTERIES OF THE HUMAN FETUS REVEALED

PubMed Central

SANDMAN, CURT A

2015-01-01

The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Lacey's, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk.. PMID:26303720

Oxidative stress and neurobehavioral problems in pediatric acute lymphoblastic leukemia patients undergoing chemotherapy.

PubMed

Stenzel, Stephanie L; Krull, Kevin R; Hockenberry, Marilyn; Jain, Neelam; Kaemingk, Kris; Miketova, Petra; Moore, Ida M

2010-03-01

Neurobehavioral problems after chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) have been a recent focus of investigation. This study extended previous research that suggested oxidative stress as a potential mechanism for chemotherapy-induced central nervous system injury by examining early markers of oxidative stress in relation to subsequent neurobehavioral problems. Oxidized and unoxidized components of phosphatidylcholine (PC) were measured in the cerebrospinal fluid of 87 children with ALL at diagnosis, induction, and consolidation. Behavioral assessments were conducted postconsolidation and at the end of chemotherapy. Results revealed a significant association between physiologic reactivity (high vs. low PC changes from diagnosis) and behavioral outcomes (high vs. low pathology). Elevated oxidized PC fraction change was predictive of increased problems with aggression at the end of therapy as well as postconsolidation adaptability. Furthermore, symptoms of hyperactivity systematically changed over time in relation to both unoxidized PC and oxidized PC fraction reactivity. These findings suggest that symptoms of behavioral problems occur early in the course of chemotherapy and that increases in the cerebrospinal fluid PC markers of oxidative stress during induction and consolidation may help to predict certain future behavioral problems.

Biological, developmental, and neurobehavioral factors relevant to adolescent driving risks.

PubMed

Dahl, Ronald E

2008-09-01

This article reviews emerging knowledge about key aspects of neurobehavioral development, with an emphasis on the development of self-regulation over behavior and emotions and its relevance to driving risks among youth. It begins with a brief overview of recent advances in understanding adolescent brain maturation and presents a heuristic model focusing on brain-behavior-social-context interactions during adolescent development. The article considers the relatively slow neurobehavioral maturation of cognitive control and emphasizes the importance of affective influences on decision making. It points to several questions about programs and policies that may help to protect high-risk youth during this important maturational period. The heuristic model is then used to examine a specific neuroregulatory system during adolescence--the regulation of sleep and arousal. This focus on sleep illustrates key points about brain-behavior-social-context interactions by looking at both biological and social influences on sleep in teens. Moreover, sleep has direct relevance to understanding a specific dimension of driving risk in youth. Sleep deprivation is rampant among adolescents, and the consequences of insufficient sleep (sleepiness, lapses in attention, susceptibility to aggression, and negative synergy with alcohol) appear to contribute significantly to driving risks in teens.

The efficacy of a restart break for recycling with optimal performance depends critically on circadian timing.

PubMed

Van Dongen, Hans P A; Belenky, Gregory; Vila, Bryan J

2011-07-01

Under simulated shift-work conditions, we investigated the efficacy of a restart break for maintaining neurobehavioral functioning across consecutive duty cycles, as a function of the circadian timing of the duty periods. As part of a 14-day experiment, subjects underwent two cycles of five simulated daytime or nighttime duty days, separated by a 34-hour restart break. Cognitive functioning and high-fidelity driving simulator performance were tested 4 times per day during the two duty cycles. Lapses on a psychomotor vigilance test (PVT) served as the primary outcome variable. Selected sleep periods were recorded polysomnographically. The experiment was conducted under standardized, controlled laboratory conditions with continuous monitoring. Twenty-seven healthy adults (13 men, 14 women; aged 22-39 years) participated in the study. Subjects were randomly assigned to a nighttime duty (experimental) condition or a daytime duty (control) condition. The efficacy of the 34-hour restart break for maintaining neurobehavioral functioning from the pre-restart duty cycle to the post-restart duty cycle was compared between these two conditions. Relative to the daytime duty condition, the nighttime duty condition was associated with reduced amounts of sleep, whereas sleep latencies were shortened and slow-wave sleep appeared to be conserved. Neurobehavioral performance measures ranging from lapses of attention on the PVT to calculated fuel consumption on the driving simulators remained optimal across time of day in the daytime duty schedule, but degraded across time of night in the nighttime duty schedule. The 34-hour restart break was efficacious for maintaining PVT performance and other objective neurobehavioral functioning profiles from one duty cycle to the next in the daytime duty condition, but not in the nighttime duty condition. Subjective sleepiness did not reliably track objective neurobehavioral deficits. The 34-hour restart break was adequate for maintaining performance in the case of optimal circadian placement of sleep and duty periods (control condition) but was inadequate (and perhaps even detrimental) for maintaining performance in a simulated nighttime duty schedule (experimental condition). Current US transportation hours-of-service regulations mandate time off duty but do not consider the circadian aspects of shift scheduling. Reinforcing a recent trend of applying sleep science to inform policymaking for duty and rest times, our findings indicate that restart provisions in hours-of-service regulations could be improved by taking the circadian timing of the duty schedules into account.

Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial.

PubMed

Porsteinsson, Anton P; Drye, Lea T; Pollock, Bruce G; Devanand, D P; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L; Mintzer, Jacobo E; Munro, Cynthia A; Pelton, Gregory; Rabins, Peter V; Rosenberg, Paul B; Schneider, Lon S; Shade, David M; Weintraub, Daniel; Yesavage, Jerome; Lyketsos, Constantine G

2014-02-19

Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory. The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability. The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013. Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram (n = 94) or placebo (n = 92) for 9 weeks. Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based on response and tolerability. Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI), ability to complete activities of daily living (ADLs), caregiver distress, cognitive safety (based on scores from the 30-point Mini Mental State Examination [MMSE]), and adverse events. Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was -0.93 (95% CI, -1.80 to -0.06), P = .04. Results from the mADCS-CGIC showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26% of placebo recipients, with estimated treatment effect (odds ratio [OR] of being at or better than a given CGIC category) of 2.13 (95% CI, 1.23-3.69), P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (-1.05 points; 95% CI, -1.97 to -0.13; P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1; P = .01) were seen in the citalopram group. Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day. clinicaltrials.gov Identifier: NCT00898807.