Neurobehavioral Research Articles

Effects of urinary of organophosphate metabolites on nerve conduction and neurobehavioral performance among farmers in northern Thailand.

Farmers are regarded as a high-risk population for pesticide exposure because of the frequency of their occupational exposure to organophosphate (OP) pesticides. The purposes of this study were 1) to compare urinary OP metabolites, nerve conduction, and neurobehavioral (NB) performance between farmers and a control group, as well as between baseline measurement and after spraying OP pesticides; 2) to investigate the factors associated with increased urinary OP metabolites after spraying OP pesticides; and 3) to investigate the effects of OP metabolites on changes in nerve conduction and NB performance after spraying OP pesticides. This study was conducted with a sample size of 71 farmers and a control group of 26. The findings showed that after spraying OP pesticides total dialkylphosphate (DAP) levels were significantly higher than baseline levels. Multiple linear regression showed that increased urinary OP metabolites among farmers after spraying pesticides were negatively associated with wearing a mask when spraying OP pesticides and positively associated with the number of years of farm work and type of sprayer equipment. The results also showed a positive association between the increased urinary total diethylphosphate (DEP) levels and the decreased amplitude of motor nerve conduction. Furthermore, a positive correlation was observed between increased urinary total DEP and decreased right amplitude of sympathetic skin response (SSR). An increase in urinary total DMP was positively associated with a decrease in raw score and a standard score of visual-motor integration (VMI). Our findings provide evidence that exposure to OP pesticides can cause a deficit in nerve conduction and NB performance in farmers. These findings may contribute to the early detection of neurological disease and inform strategies to prevent damage to the peripheral and central nervous systems.

The reliability of neurobehavioral tests in a thai adult population.

The purpose of this study was to investigate the test-retest reliability of NB tests in a Thai adult population and examine the impact of demographic data on NB tests. The aspects of the tests chosen were memory, attention, hand-eye coordination, motor speed, and dexterity. The three NB tests used were digit span, Purdue Pegboard, and visual-motor integration. All three were administered to a population of 30 Thai adults. The outcomes of all Pearson's correlation coefficient tests (r) were positive and greater than 0.60, and subtest-retest reliability correlation coefficients ranged from 0.63 (p<0.001) to 0.81 (p<0.001). Interestingly, the outcomes of all of these tests were not affected by demographic data, with the exception of the Purdue Pegboard test, in which performance on the preferred hand and both hands assessment was weakly associated with age (β=-0.09, p<0.001 and β=-0.08, p<0.05, respectively). NB tests have adequate reliability and are useful for the evaluation of clinical memory, attention, hand-eye coordination, motor speed, and dexterity in Thai adults. These tests were not affected by demographic data. However, further studies to measure the validity of the digit span, Purdue Pegboard, and visual-motor integration tests are needed.

Reliability of a computer-based neurobehavioral assessment test battery for Bangladeshi adolescent children

In developing countries, there is a need for low-cost neurobehavioral (NB) test batteries for vulnerable populations, particularly for children exposed to environmental neurotoxicants. The objective of the current study was to assess the feasibility and test-retest reliability of the Behavioral Assessment and Research System (BARS) in children from a rural community in Bangladesh. Fifty healthy adolescents living in the Health Effects of Arsenic Longitudinal Study (HEALS) area in Araihazar, Bangladesh completed all six tests from the BARS in two test sessions scheduled two weeks apart. The BARS tests evaluated NB functions such as motor coordination, attention, memory, and information processing speed. The reliability assessment, evaluated by test-retest correlations demonstrated moderate to strong correlations (i.e., correlation coefficients ranged from 0.43 to 0.85), which were statistically significant (p < 0.05). Paired t-tests for comparing the test and retest outcomes indicated significant improvement in NB performance, highlighting learning and practice effects. NB performance improved with increasing age in most cases. Adolescent boys performed better than the girls in Finger Tapping, Digit Span, and Simple Reaction Time, whereas the girls performed better in Continuous Performance and Symbol Digit tests. The reliability scores (Pearson’s correlations 0.43−0.85) were consistent with other children studies in different cultural settings. The effects of age and sex on NB tests were also consistent with findings reported in other countries. Overall, the findings of the study support the feasibility of using this computer-based test system to assess vulnerability of brain health due to environmental exposures among rural Bangladeshi children.

Changes in Biomarkers and Neurodevelopmental Outcomes Among Male Adolescent Pesticide Applicators and Non-Applicators

Background. Although organophosphorus pesticides are increasingly restricted for use in the United States, many of these pesticides are still being used in low- and middle-income countries. This may lead to adolescents being environmentally and occupationally exposed to pesticides. While most human and animal research has focused on exposures during the perinatal period, and a few studies have focused on exposure during childhood, there is a paucity of data examining exposures during adolescence, a critical period of brain organization.Methods. Male adolescent pesticide applicators and non-applicators in Egypt (N=249) were recruited to characterize changes in biomarkers and neurobehavioral (NB) outcomes across application seasons. Test sessions included the collection of biological samples and NB testing.Results. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) metabolite levels, a chlorpyrifos-specific metabolite, increased in both applicators and non-applicators during the application season and recovered after application ended. Biomarkers of effect, e.g., butyrylcholinesterase (BChE) activity, showed a pattern of inhibition and recovery associated with chlorpyrifos (CPF) application that is repeated across years. TCPy levels, were inversely associated with BChE activity. Importantly, adolescents show BChE inhibition at much lower levels of TCPy (28.9 µg/g creatinine) than adults (&gt;110µg/g creatinine). Neurobehavioral deficits among male applicators increased during the application season and persisted after application ceased. These sustained deficits were present in the absence of red blood cell AChE inhibition. An exposure response gradient between symptoms of attention and hyperactivity/impulsivity and TCPy levels was identified.Discussion. These findings demonstrate that occupational exposure among male adolescents were predictive of sustained cognitive problems, while also demonstrating that youth living in agricultural communities in the Nile Delta are receiving significant environmental exposures. Due to the large number of adolescents living and working in rural communities worldwide, there remains a critical need to investigate the vulnerability of adolescents, who may be both occupationally and environmentally exposed to pesticides.

Thyroid hormones and neurobehavioral functions among adolescents chronically exposed to groundwater with geogenic arsenic in Bangladesh

Groundwater, the major source of drinking water in Bengal Delta Plain, is contaminated with geogenic arsenic (As) enrichment affecting millions of people. Children exposed to tubewell water containing As may be associated with thyroid dysfunction, which in turn may impact neurodevelopmental outcomes. However, data to support such relationship is sparse. The purpose of this study was to examine if chronic water As (WAs) from Holocene alluvial aquifers in this region was associated with serum thyroid hormone (TH) and if TH biomarkers were related to neurobehavioral (NB) performance in a group of adolescents. A sample of 32 healthy adolescents were randomly drawn from a child cohort in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh. Half of these participants were consistently exposed to low WAs (<10 μg/L) and the remaining half had high WAs exposure (≥10 μg/L) since birth. Measurements included serum total triiodothyronine (tT3), free thyroxine (fT4), thyrotropin (TSH) and thyroperoxidase antibodies (TPOAb); concurrent WAs and urinary arsenic (UAs); and adolescents' NB performance. WAs and UAs were positively and significantly correlated with TPOAb but were not correlated with TSH, tT3 and fT4. After accounting for covariates, both WAs and UAs demonstrated positive but non-significant relationships with TSH and TPOAb and negative but non-significant relationships with tT3 and fT4. TPOAb was significantly associated with reduced NB performance indicated by positive associations with latencies in simple reaction time (b = 82.58; p < 0.001) and symbol digit (b = 276.85; p = 0.005) tests. TSH was significantly and negatively associated with match-to-sample correct count (b = −0.95; p = 0.05). Overall, we did not observe significant associations between arsenic exposure and TH biomarkers although the relationships were in the expected directions. We observed TH biomarkers to be related to reduced NB performance as hypothesized. Our study indicated a possible mechanism of As-induced neurotoxicity, which requires further investigations for confirmatory findings.

Role of caregiver-reported outcomes in identification of children with prenatal alcohol exposure during the first year of life.

IntroductionEarlier identification of children with prenatal alcohol exposure (PAE) remains a challenge. The objective of this study was to identify neurobehavioral (NB) outcomes associated with PAE in infants.MethodsThis manuscript evaluates NB outcomes at 6.33±1.12 months of age in 93 infants (39 PAE and 54 No-PAE) recruited prospectively into the ENRICH cohort. PAE was assessed by prospective repeated TLFB interviews and a panel of ethanol biomarkers. NB outcomes were evaluated by the Bayley Scales of Infant Development (BSID-III), Parenting Stress Index (PSI), Infant Behavior Questionnaire (IBQ-R), and Infant Sensory Profile (ISP).ResultsMean maternal age at enrollment was 28.18 ±5.75, and 64.52 % were Hispanic/Latina. Across three TLFB calendars, absolute alcohol per day in the PAE group was 0.44±0.72, corresponding to low-moderate alcohol consumption. While no association was observed between PAE and BSID-III (p’s>0.05), PAE was associated with higher scores on the PSI difficult child scale (β̂ =13.9; p=0.015), total stress (β̂ =13.9; p=0.010), and IBQ negative affect (β̂ =8.60; p=0.008) measures after adjustment for covariates.ConclusionsCaregiver-reported assessments may provide a currently unrecognized opportunity to identify behavioral deficits, point to early interventions, and should be included in clinical assessments of infants at-risk for FASD.

Rasch Analysis and Functional Measurement in Post-Hospital Brain Injury Rehabilitation

Rasch analysis is a statistical technique used in determining statistical properties of functional measures for use in research and treatment. The technique was used in the current study to determine the reliability and validity of the Mayo Portland Adaptability Inventory-Version 4 (MPAI-4) for use with three different acquired brain injury samples. Subjects were 777 adults (each group comprised of 259 individuals) with acquired brain injury treated in one of three rehabilitation program types: Neurorehabilitation (NR), Neurobehavioral (NB), or Supported Living (SL). The MPAI-4 was administered to each participant upon admission to program. Rasch analysis was conducted to assess item fit, reliability, and separation statistics for MPAI-4 assessments conducted within each program. Item difficulty values were examined to determine if the MPAI-4 differentiated among groups based on deficit profiles. The results revealed that for each group, fit statistics fell with appropriate levels (0.5 – 1.5) for at least 24 of 29 items. Rasch person reliability statistics were 0.89 for NR and NB, and 0.90 for SL. Item reliability was 0.99 for each of the groups. Item difficulty values accurately differentiated the three groups based on their specific deficit profiles expected. Specifically, NR participants’ greatest deficits demonstrated by the MPAI-4 were within cognitive and physical functions. For the NB participants, the greater deficits demonstrated were within the behavioral and adjustment items. Supported Living participants had the most limitation within the instrumental activities of daily living items. As in prior research findings, the current Rasch analysis supported the use of the MPAI-4 within this heterogeneous, acquired brain injury population. This unique statistical approach translates to treatment priorities that may assist clinicians with identifying treatment goals specific to unique treatment group characteristics (e.g., NR, NB, and SL).

The impact of repeated organophosphorus pesticide exposure on biomarkers and neurobehavioral outcomes among adolescent pesticide applicators

ABSTRACTEgyptian adolescents are hired as seasonal workers to apply pesticides to the cotton crop and may perform this occupation for several years. However, few studies examined the effects of repeated pesticide exposure on health outcomes The goal of this study was to determine the impact of repeated pesticide exposure on neurobehavioral (NB) performance and biomarkers of exposure (urinary metabolite) and effect (cholinesterase activity). Eighty-four adolescents from two field stations in Menoufia, Egypt, were examined four times: before and during pesticide application season in 2010 and again before and during application season in 2011. At each of the four time points, participants completed a questionnaire, performed an NB test battery, and were assessed for urinary levels of the chlorpyrifos metabolite TCPy (3,5,6-trichloro-2-pyridinol) and blood cholinesterase activity. Following the study cohort over two consecutive pesticide application seasons revealed that TCPy levels significantly increased following exposure, and returned to baseline levels following the end of the application season. Blood butyryl cholinesterase activity exhibited a similar pattern. Although NB outcomes displayed learning and practice effects over time, deficits in performance were significantly associated with increased TCPy levels with reduction in the number of NB measures showing improvement over time. Biomarkers of exposure and effect demonstrated changes associated with pesticide application and recovery after application ended. Deficits in NB performance were correlated with elevated pesticide exposure. Data demonstrated that repeated pesticide exposure may exert a long-term adverse impact on human health.

Post-Hospital Brain Injury Rehabilitation: Comparison of Neurobehavioral Intensity and Neurorehabilitation Outcomes

To: 1) determine outcome differences between Neurorehabilitation (NR) and Neurobehavioral (NB) clients following post-hospital brain injury rehabilitation; 2) determine effectiveness of programming to reduce symptoms of behavioral dyscontrol among NB individuals; 3) identify predictors of independent functioning for each group.

Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study

Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61years (SD=12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators.

Neurobehavioral and Quality of Life Changes Associated with Growth Hormone Insufficiency after Complicated Mild, Moderate, or Severe Traumatic Brain Injury

Adult-onset growth hormone deficiency (GHD) has been associated with reduced quality of life (QOL) and neurobehavioral (NB) deficits. This prospective study tested the hypothesis that traumatic brain injury (TBI) patients with GHD or GH insufficiency (GHI) would exhibit greater NB/QOL impairment than patients without GHD/GHI. Complicated mild, moderate, and severe adult TBI patients (GCS score 3-14) had pituitary function and NB/QOL testing performed 6-9 months postinjury. GH-secretory capacity was assessed with a GHRH-arginine stimulation test and GHD and GHI were defined as peak GH<6 or <or=12 ng/mL (5th and 10th percentiles of healthy control subjects, respectively). Of 44 patients (mean age, 32+/-18 years; median GCS, 7), one (2%) was GHD, seven (16%) were GHI, and 36 (82%) were GH-sufficient at 6-9 months post-injury. Mean peak GH was 8.2+/-2.1 ng/mL in the GHD/GHI group versus 45.7+/-29 ng/mL in the GHsufficient group. The two groups were well-matched in injury characteristics, except that one patient with GHD had central hypogonadism treated with testosterone prior to NB/QOL testing. At 6-9 months postinjury, patients with GHD/GHI had higher rates of at least one marker of depression (p<0.01), and reduced QOL (by SF-36 Health Survey) in the domains of limitations due to physical health (p=0.02), energy and fatigue (p=0.05), emotional well-being (p=0.02), pain (p=0.01), and general health (p=0.05). Chronic GHI develops in approximately 18% of patients with complicated mild, moderate, or severe TBI, and is associated with depression and diminished QOL. The impact of GH replacement therapy on NB function and QOL in these TBI patients is being tested in a randomized placebo-controlled trial.

FETAL COCAINE EXPOSURE AND NEONATAL OUTCOMES: BIOLOGIC AND SELF-REPORT MEASURES. ▴ 1664

In 276 infants (132 cocaine-exposed and 144 non-exposed) recruited into a longitudinal study of fetal cocaine exposure at birth, standardized clinical interviews, urine screens, and meconium assays were used to assess the relationship of cocaine and polydrug exposure to infant birth and neonatal neurobehavioral outcomes. Clinical interviews yielded maternal self-report of frequency and severity of cocaine, alcohol, marijuana and tobacco use while pregnant. Meconium assays measured cocaine and its metabolites; cocaine (COC), Benzoylecgonine (BEN), M-O-H Benzoylecgonine (MOH), and cocaethylene (COCETH); marijuana (THC), and tobacco (COT). In addition to measuring birth parameters, Gardner's Neurobehavioral (NB) Assessment was administered at 2 weeks(corrected ages). In regressions controlling for alcohol, marijuana, and tobacco use, and GA if warranted, maternal report of higher frequency of days of cocaine use predicted lower infant BW (p <.02), GA (p <.02), and birth length (p <.03), but not head circumference. Meconium measures Ng BEN and MOH were related to birth length (r's = -.17 and -.14, p's <.05). Higher levels of COCETH, the metabolite formed from the combination of cocaine and alcohol, were related to increased attentional abnormalities (r =.18, p<.01) and to more sensory asymmetry (r =.20, p <.01) on the NB assessment. Higher levels of BEN and MOH were related to poorer head control(r's =.19, and.21, p's <.02). These data support a dose-response effect of in utero cocaine exposure on birth outcomes and neurobehavioral functioning.(NIDA 07957).

Clinical estimates of treatment adequacy.

Adequacy of rapid, high-efficiency therapies (RHET) in patients with end-stage renal failure involves comparisons with hemodialysis, the primary reference standard. However, the latter's adequacy is also insecurely rendered in descriptive, subjective terms that often embrace outcomes beyond legitimate expectations of the dialysis process. Many measurable abnormalities in renal failure contribute little to patients' clinical illness and respond poorly to dialysis. It is therefore proposed that adequacy for all proposed clinical treatment modalities, including RHET, be based on objective, quantitative measures of what such treatments actually do: control volume and dialyzable solute composition of the body fluids, and suppress the uremic illness. Recognition of the dialysis-responsive--and also disabling--uremic illness as an encephalopathic, neurobehavioral (NB) disorder logically led to objective documentation of quantitative NB impairments that varied inversely with the amount of hemodialysis and improved following renal transplantation. Similar objective documentations of RHET are needed.

55 HEAD CIRCUMFERENCE AT BIRTH AS A PREDICTOR OF NEUO-BEHAVIORAL OUTCOME

Neurobehavioral (NB) outcome of low birth weight infants was studied in relation to head circumference (HC) at birth. Infants weighed ≤2250 gms. and/or were <than 37 weeks gestation (Dubowitz examination). Follow-up NB evaluation performed on 127 infants at the corrected chronologic age of 7 months consisted of a neurologic examination and administration of the Bayley Mental Scale (MDI). Ninety-one infants (71.7%) had appropriate HC for gestational age (AHA, <10th percentile, Lubchenko) and 35 (28.3%) had a small HC (SHA). MDI was <80 in 34.3% of SHA infants compared to only 16.3% of AHA infants (p<0.05). Severe neurologic deficit was found in 20% of SHA infants compared to only 5.5% of AHA infants (p<0.05). The incidences of MDI<80 and severe neurologic deficit in subgroups of AHA and SHA were not significantly affected by whether total body weight was appropriate or small for gestational age (AGA or SGA). Thus: Previously reported associations of fetal body growth retardation with poor NB outcome probably apply primarily in those infants with fetal head growth retardation (SHA). Evaluation of HC at birth in relation to gestational age adds an important dimension to the prediction of neurologic outcome.