Hit Reaction Time Research Articles

Cerebrovascular Reactivity and Cognitive Function in Hypertensive and Non‐Hypertensive Adults

Hypertension and its vascular consequences contribute to cognitive dysfunction. Accelerated cerebrovascular aging in hypertension may impair cognitive function by impairing cerebrovascular reactivity. Cerebrovascular reactivity in hypertension is often assessed by manipulating CO2, which may not directly reflect reactivity occurring from changes in metabolic supply and neuronal demand during a cognitive task (i.e. neurovascular coupling). The purpose of this study was to compare macro‐ and microvascular hemodynamics at rest and during cognitive activity (Stroop task) in 30 middle‐aged, medicated hypertensive (HTN) and 30 age‐, sex‐, and body mass index (BMI)‐matched non‐HTN adults (56±6 yrs, BMI 28.2±2.9 kg/m2; 32 men). Brachial mean pressure (MP) was measured from an oscillometric cuff. Macrovascular measures included common carotid artery (CCA) mean blood flow from ultrasound and middle cerebral artery (MCA) mean blood velocity from transcranial Doppler. Conductance was calculated as blood flow and mean velocity relative to MP for CCA and MCA, respectively. Microvascular measures included prefrontal cortex (PFC) oxy‐(O2Hb) and deoxyhemoglobin (HHb), and tissue saturation index (TSI) via near‐infrared spectroscopy. Data were analyzed using a 2×2 repeated measures ANOVA but are expressed as change from baseline. Accuracy and hit reaction times were computed to assess cognitive performance. Stroop accuracy (Non‐HTN 95±4%, HTN 95±3%) and reaction time (Non‐HTN 960±142 ms, HTN 998±148 ms) were similar between groups (p>0.05). CCA and MCA conductance were not altered during Stroop (p>0.05). PFC HHb decreased similarly in both groups (p<0.05), while TSI response during Stroop tended to differ (p=0.09) between groups. A significant interaction revealed HTN increased O2Hb during Stroop, while O2Hb was unaltered in Non‐HTN. Differences in O2Hb responses remained when expressed relative to MP. Changes in PFC TSI were positively associated with Stroop accuracy in HTN (r=0.41, p<0.05) but not Non‐HTN (r=0.16, p>0.05). Our data indicate that HTN and Non‐HTN have similar pressure‐mediated macrovascular hyperemia to cognitive activity resulting in a maintenance of macrovascular conductance. HTN exhibit greater increases in O2Hb to achieve similar cognitive performance compared to Non‐HTN, perhaps suggestive of early cerebral aging in HTN. The augmented O2Hb response may contribute to overall tissue oxygenation (TSI) which is associated with preserved cognitive performance in HTN.Support or Funding InformationSupported by an AHA Pre‐Doctoral Fellowship and Foundation Research Grant from ACSMThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Association between Lifelong Greenspace Exposure and 3-Dimensional Brain Magnetic Resonance Imaging in Barcelona Schoolchildren

Background:Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure.Objective:We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school.Methods:We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across buffers around all residential addresses since birth to estimate each participant’s lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory (d′ from computerized n-back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores.Results:Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness.Conclusion:Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876

Impact of commuting exposure to traffic-related air pollution on cognitive development in children walking to school

A few studies have found associations between the exposure to traffic-related air pollution at school and/or home and cognitive development. The impact on cognitive development of the exposure to air pollutants during commuting has not been explored. We aimed to assess the role of the exposure to traffic-related air pollutants during walking commute to school on cognitive development of children. We performed a longitudinal study of children (n = 1,234, aged 7–10 y) from 39 schools in Barcelona (Catalonia, Spain) who commuted by foot to school. Children were tested four times during a 12-month follow-up to characterize their developmental trajectories of working memory (d’ of the three-back numbers test) and inattentiveness (hit reaction time standard error of the Attention Network Test). Average particulate matter ≤2.5 μm (PM2.5), Black Carbon (BC) and NO2 concentrations were estimated using Land Use Regression for the shortest walking route to school. Differences in cognitive growth were evaluated by linear mixed effects models with age-by-pollutant interaction terms. Exposure to PM2.5 and BC from the commutes by foot was associated with a reduction in the growth of working memory (an interquartile range increase in PM2.5 and BC concentrations decreased the annual growth of working memory by 5.4 (95% CI [-10.2, -0.6]) and 4.6 (95% CI [-9.0, -0.1]) points, respectively). The findings for NO2 were not conclusive and none of the pollutants were associated with inattentiveness. Efforts should be made to implement pedestrian school pathways through low traffic streets in order to increase security and minimize children's exposure to air pollutants.

Prenatal and postnatal polybrominated diphenyl ether (PBDE) exposure and measures of inattention and impulsivity in children

Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16±3weeks of gestation and during childhood at 1, 2, 3, 5, and 8years. We assessed children's attention and impulse control using the Conners' Continuous Performance Test-Second Edition (CPT-II) at 8years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3years: β=4.0 [95% CI: −2.4, 10.5]; at 5years: β=4.6 [95% CI: −2.8, 12.0]; at 8years: β=4.1 [95% CI: −3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: β=15.0 milliseconds (ms) [95% CI: −15.8, 45.8]; 5years: β=20.6ms [95% CI: −20.8, 61.9]; 8years: β=28.6ms [95% CI: −12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d′), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research.

Prenatal and postnatal exposure to NO2 and child attentional function at 4–5 years of age

BackgroundPrenatal and postnatal exposure to air pollution has been linked to cognitive impairment in children, but very few studies have assessed its association with attentional function. ObjectivesTo evaluate the association between prenatal and postnatal exposure to nitrogen dioxide (NO2) and attentional function in children at 4–5years of age. MethodsWe used data from four regions of the Spanish INMA—Environment and Childhood—Project, a population-based birth cohort. Using land-use regression models (LUR), we estimated prenatal and postnatal NO2 levels in all of these regions at the participants' residential addresses. We assessed attentional function using the Kiddie-Conners Continuous Performance Test (K-CPT). We combined the region-specific adjusted effect estimates using random-effects meta-analysis. ResultsWe included 1298 children with complete data. Prenatal exposure to NO2 was associated with an impaired standard error of the hit reaction time (HRT(SE)) (increase of 1.12ms [95% CI; 0.22 a 2.02] per 10μg/m3 increase in prenatal NO2) and increased omission errors (6% [95% CI; 1.01 to 1.11] per 10μg/m3 increase in prenatal NO2). Postnatal exposure to NO2 resulted in a similar but borderline significant increase of omission errors (5% [95% CI; =0.99 to 1.11] per 10μg/m3 increase in postnatal NO2). These associations did not vary markedly between regions, and were mainly observed in girls. Commission errors and lower detectability were associated with prenatal and postnatal exposure to NO2 only in some regions. ConclusionsThis study indicates that higher exposure to ambient NO2, mainly during pregnancy and to a lesser extent postnatally, is associated with impaired attentional function in children at 4–5years of age.

A Longitudinal Study on Attention Development in Primary School Children with and without Teacher-Reported Symptoms of ADHD.

Background: Prospective longitudinal studies are essential in characterizing cognitive trajectories, yet few of them have been reported on the development of attention processes in children. We aimed to explore attention development in normal children and children with attention deficit and hyperactivity disorder (ADHD) symptoms in a repeated measures design using the attention network test (ANT).Methods: The population sample included 2,835 children (49.6% girls) aged 7–11 years from 39 schools in Barcelona (Catalonia, Spain) who performed the ANT four times from January 2012 to March 2013. According to teacher ratings, 10.5% of the children presented ADHD symptoms. We performed multilevel mixed-effects linear regression models, adjusting for school and individual, to test the effects of age-related growth on the ANT networks: alerting, orienting and executive attention, and three measurements related to attentiveness: median of hit reaction time (HRT), hit reaction time standard error (HRT-SE) and variability.Results: We observed age-related growth in all the outcomes, except orienting. The curves were steeper at the younger groups, although for alertness the improvement was further at the oldest ages. Gender and ADHD symptoms interacted with age in executive attention, HRT and variability. Girls performed better in executive attention at young ages although boys reached females at around 10 years of age. For HRT, males showed faster HRT. However, girls had a more pronounced improvement and reached the levels of boys at age 11. Children with ADHD symptoms had significant differences in executive attention, HRT and variability compared to children without ADHD symptoms.Conclusions: We detected an ongoing development of some aspects of attention in primary school children, differentiating patterns by gender and ADHD symptoms. Our findings support the ANT for assessing attention processes in children in large epidemiological studies.

Effect of exposure to polycyclic aromatic hydrocarbons on basal ganglia and attention-deficit hyperactivity disorder symptoms in primary school children

BackgroundPolycyclic aromatic hydrocarbons (PAHs) have been proposed as environmental risk factors for attention deficit hyperactivity disorder (ADHD). The effects of these pollutants on brain structures potentially involved in the pathophysiology of ADHD are unknown. ObjectiveThe aim of this study was to investigate the effects of PAHs on basal ganglia volumes and ADHD symptoms in school children. MethodsWe conducted an imaging study in 242 children aged 8–12years, recruited through a set of representative schools of the city of Barcelona, Spain. Indoor and outdoor PAHs and benzo[a]pyrene (BPA) levels were assessed in the school environment, one year before the MRI assessment. Whole-brain volumes and basal ganglia volumes (caudate nucleus, globus pallidus, putamen) were derived from structural MRI scans using automated tissue segmentation. ADHD symptoms (ADHD/DSM-IV Scales, American Psychiatric Association 2002) were reported by teachers, and inattentiveness was evaluated with standard error of hit reaction time in the attention network computer-based test. ResultsTotal PAHs and BPA were associated with caudate nucleus volume (CNV) (i.e., an interquartile range increase in BPA outdoor level (67pg/m3) and indoor level (76pg/m3) was significantly linked to a decrease in CNV (mm3) (β=−150.6, 95% CI [−259.1, −42.1], p=0.007, and β=−122.4, 95% CI [−232.9, −11.8], p=0.030 respectively) independently of intracranial volume, age, sex, maternal education and socioeconomic vulnerability index at home). ADHD symptoms and inattentiveness increased in children with higher exposure to BPA, but these associations were not statistically significant. ConclusionsExposure to PAHs, and in particular to BPA, is associated with subclinical changes on the caudate nucleus, even below the legislated annual target levels established in the European Union. The behavioral consequences of this induced brain change were not identified in this study, but given the caudate nucleus involvement in many crucial cognitive and behavior processes, this volume reduction is concerning for the children's neurodevelopment.

Association Between Sluggish Cognitive Tempo Symptoms and Attentional Network and Working Memory in Primary Schoolchildren

Background: Few consistent data are available in relation to the cognitive and neuropsychological processes involved in sluggish cognitive tempo (SCT) symptoms. The objective of this study was to determine the association of working memory and attentional networks with SCT symptoms in primary schoolchildren. Methods: The participants were schoolchildren aged 7 to 10 years (n = 183) from primary schools in Catalonia (Spain). All the participants completed a working memory task (n-back) and an attentional network task (ANT). Their parents completed an SCT-Child Behavior Checklist self-report and a questionnaire concerning sociodemographic variables. Teachers of the participants provided information on ADHD symptoms and learning determinants. Results: SCT symptoms were correlated with lower scores in both the n-back and ANT. In multivariate regression analysis, SCT symptoms were associated with slower hit reaction times from the ANT. Conclusions: Our results suggest that SCT symptoms are associated with a neuropsychological profile that is different from the classical ADHD profile and characterized by slower reaction times.

Dissociative symptoms are associated with neurocognitive dysfunction in patients with MDD

IntroductionIt is widely reported that persons with major depressive disorder (MDD) show impaired performance on cognitive functioning, including frontotemporally mediated cognitive functions. The presence of cognitive dysfunction among patients with dissociative symptoms in trauma-related disorders may contribute to poorer treatment outcomes. Patients with major depressive disorder (MDD) frequently report dissociative symptoms. Here we investigate association of dissociative symptoms and neurocognitive dysfunction in patients with depression. We predicted that higher levels of dissociative symptoms among persons with MDD would be associated with lower scores on objective measures of frontotemporally mediated neurocognitive functions.MethodsPatients who met DSM-V diagnostic criteria for a primary diagnosis of recurrent MDD were recruited. The Hamilton Rating Scale for Depression (HAM-D) was administered to assess the severity of depressive symptoms. To assess dissociative symptoms participants completed the Multiscale Dissociation Inventory (MDI). Two groups of patients were selected and matched. One group consisted of 13 patients having MDD and dissociative symptoms and second group consisted of 12 patients having MDD only. To measure frontotemporally mediated cognitive functioning following tests were administered: Color Trails Test; Wisconsin Card Sorting Test; Conners’ Continuous Performance Test (CPT). To examine group differences on clinical and neuropsychological scores, two-tailed independent samples t-tests was performed.ResultsGroup comparisons of performance on neuropsychological tests showed that participants with depression and dissociative symptoms performed worse on Color Trails Test Part 2 completion time, a measure of mental flexibility and processing speed. MDI depersonalization scores were correlated with measures of processing speed, mental flexibility and sustained attention. Specifically, Color Trails Test Part 2 scores were negatively correlated with depersonalization symptoms, where lower scores indicate slower completion time. Depersonalization symptoms on the MDI were also related to the CPT Hit Reaction Time Interstimulus Interval Change (a measure of vigilance), such that higher levels of depersonalization were related to better performance in a less active environment.ConclusionsOur results suggest that dissociation is related to specific subtle impairments in neurocognitive functioning. Dissociative symptoms should ideally be assessed before treatment, as they may influence MDD treatment response. The findings point towards the need to further examine the impact of dissociation on functioning in patients with depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. NCT02178995. This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints.

Evidence-Based Assessment of ADHD in Youth Using a Receiver Operating Characteristic Approach

Guidelines exist for the assessment of attention deficit/hyperactivity disorder (ADHD), but they are often unclear as to how a clinician should consider multiple informants, methods, and co-occurring symptoms to reach an overall diagnostic probability for an individual patient. The current study used receiver operating characteristic analyses and evidence-based medicine methods to evaluate the Achenbach System of Empirically Based Assessment measures and the Conners’ Continuous Performance Test for ADHD diagnosis in youth. Children (n = 379) and their parent(s) presented at an outpatient clinic for a psychoeducational assessment. Analyses examined the diagnostic efficiency and utility of study measures for predicting a best-estimate ADHD diagnosis. The Child Behavior Checklist Attention Problems construct, Teacher Report Form Attention Problems construct, and Hit Reaction Time Standard Error showed adequate diagnostic efficiency and unique contributions to the prediction of ADHD, Combined Type diagnosis. None of these measures showed good diagnostic efficiency or utility for the prediction of ADHD, Predominantly Inattentive Type. Child anxiety did not moderate the relations between predictors and ADHD diagnosis. Both the Child Behavior Checklist and Teacher Report Form Attention Problems constructs can discriminate youth with ADHD, Combined Type from other clinic-referred youth. Although Hit Reaction Time Standard Error also showed diagnostic utility, the decision to include a computerized measure should consider time and expense and be utilized in cases where diagnostic probability is unclear. Finally, anxiety may be associated with elevated attention problems, but it does not appear that anxiety affects diagnostic cutoffs for ADHD.

Elevations on select Conners’ CPT-II scales indicate noncredible responding in adults with traumatic brain injury

ABSTRACTElevations on certain Conners’ CPT-II scales are known to be associated with invalid responding. However, scales and cutoffs vary across studies. In addition, the methodology behind developing performance validity tests (PVTs) has been challenged for mistaking true impairment for noncredible presentation. Using ability-based tests as a PVT makes clinicians especially vulnerable to this criticism. The present study examined the ability of CPT-II to dissociate effort from impairment in 47 adults clinically referred for neuropsychological assessment. CPT-II scales previously identified as PVTs (Omissions, Commissions, Hit Reaction Time SE, Variability, and Perseverations) produced classification accuracies hovering around .50 sensitivity at .90 specificity. The subsample that failed these PVTs performed within normal range on other tests of working memory, processing speed, visual attention, and executive function. Results suggest that the select CPT-II based PVTs are sensitive to invalid responding, and are associated with depression and anxiety, but are unrelated to cognitive functioning.

A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children.

BackgroundAttention function filters and selects behaviorally relevant information. This capacity is impaired in some psychiatric disorders and has been proposed as an endophenotype for Attention-Deficit/Hyperactivity Disorder; however, its genetic basis remains largely unknown. This study aimed to identify single nucleotide polymorphism (SNPs) associated with attention function.Materials and MethodsThe discovery sample included 1655 children (7–12 years) and the replication sample included 546 children (5–8 years). Five attention outcomes were assessed using the computerized Attentional Network Test (ANT): alerting, orienting, executive attention, Hit Reaction time (HRT) and the standard error of HRT (HRTSE). A Genome-wide Association Study was conducted for each outcome. Gene set enrichment analyses were performed to detect biological pathways associated with attention outcomes. Additional neuroimaging analyses were conducted to test neural effects of detected SNPs of interest.ResultsThirteen loci showed suggestive evidence of association with attention function (P<10−5) in the discovery sample. One of them, the rs4321351 located in the PID1 gene, was nominally significant in the replication sample although it did not survive multiple testing correction. Neuroimaging analysis revealed a significant association between this SNP and brain structure and function involving the frontal-basal ganglia circuits. The mTOR signaling and Alzheimer disease-amyloid secretase pathways were significantly enriched for alerting, orienting and HRT respectively (FDR<5%).ConclusionThese results suggest for the first time the involvement of the PID1 gene, mTOR signaling and Alzheimer disease-amyloid secretase pathways, in attention function during childhood. These genes and pathways have been proposed to play a role in neuronal plasticity, memory and neurodegenerative disease.

Not All Differences between Patients with Schizophrenia and Healthy Subjects Are Pathological: Performance on the Conners' Continuous Performance Test.

This study analyzed attentional performance in patients with schizophrenia during a continuous performance task requiring a high response rate. The Conners' Continuous Performance Test-II (CPT-II) was administered to 64 patients with schizophrenia and 64 healthy comparison subjects. A cross-sectional design was used in order to allow analysis of the means between patients and healthy subjects. Differences in performance were assessed for significance using ANCOVA. Percentiles were also analyzed in order to determine whether a participant showed normal or pathological performance. Pearson's correlation was used to detect possible relationships between attentional performance and psychopathology. Of the 12 CPT-II measures, response style and slowing of reaction time (RT) between targets increased to similar extents between patients and healthy comparison subjects. Patients performed significantly less well than non-patient group on all other measures. Nevertheless, patient's performance on four of these measures remained within the normal range, and patient's performance on the remaining measures qualified as pathological only in the case of variability in hit RT. No significant correlations between attention performance and symptoms were found. These results suggest that although patients may show lower attentional functioning than non-patients on tasks requiring a high response rate, their attentional performance remains within the normal range on most dimensions.

Effects of yohimbine and drug cues on impulsivity and attention in cocaine-dependent men and women and sex-matched controls

BackgroundDeficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women. MethodsIn a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors’ Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure session ResultsHealthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0–1.3), χ21=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4–0.8), χ21=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6–14.7), χ21=30.1, p<0.001]. Cocaine-dependent women exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354±13 vs. Male 415±14; t89=2.6, p=0.012]. ConclusionsThese data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals.

Prenatal particulate air pollution and neurodevelopment in urban children: Examining sensitive windows and sex-specific associations

BackgroundBrain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex. ObjectivesWe implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter≤2.5μm (PM2.5) and children's neurodevelopment. MethodsWe assessed 267 full-term urban children's prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners' CPT-II), and memory (general memory [GM] index and its components — verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined. ResultsMothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31–38weeks with lower IQ, at 20–26weeks gestation with increased OEs, at 32–36weeks with slower HRT, and at 22–40weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18–26weeks with reduced VIM, at 12–20weeks with reduced GM). ConclusionsIncreased PM2.5 exposure in specific prenatal windows may be associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups.

New suggestive genetic loci and biological pathways for attention function in adult attention-deficit/hyperactivity disorder.

Attention deficit is one of the core symptoms of the attention-deficit/hyperactivity disorder (ADHD). However, the specific genetic variants that may be associated with attention function in adult ADHD remain largely unknown. The present study aimed to identifying SNPs associated with attention function in adult ADHD and tested whether these associations were enriched for specific biological pathways. Commissions, hit-reaction time (HRT), the standard error of HRT (HRTSE), and intraindividual coefficient variability (ICV) of the Conners Continuous Performance Test (CPT-II) were assessed in 479 unmedicated adult ADHD individuals. A Genome-Wide Association Study (GWAS) was conducted for each outcome and, subsequently, gene set enrichment analyses were performed. Although no SNPs reached genome-wide significance (P < 5E-08), 27 loci showed suggestive evidence of association with the CPT outcomes (P < E-05). The most relevant associated SNP was located in the SORCS2 gene (P = 3.65E-07), previously associated with bipolar disorder (BP), Alzheimer disease (AD), and brain structure in elderly individuals. We detected other genes suggested to be involved in synaptic plasticity, cognitive function, neurological and neuropsychiatric disorders, and smoking behavior such as NUAK1, FGF20, NETO1, BTBD9, DLG2, TOP3B, and CHRNB4. Also, several of the pathways nominally associated with the CPT outcomes are relevant for ADHD such as the ubiquitin proteasome, neurodegenerative disorders, axon guidance, and AD amyloid secretase pathways. To our knowledge, this is the first GWAS and pathway analysis of attention function in patients with persistent ADHD. Overall, our findings reinforce the conceptualization of attention function as a potential endophenotype for studying the molecular basis of adult ADHD. © 2015 Wiley Periodicals, Inc.

Association between traffic-related air pollution in schools and cognitive development in primary school children: a prospective cohort study.

BackgroundAir pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development.Methods and FindingsWe conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10–700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home.Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%–8.8%] versus 11.5% [95% CI 8.9%–12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%–23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation.ConclusionsChildren attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.

Parallel rarebits: A novel, large‐scale visual field screening method

BackgroundRarebit perimetry () is a computer‐based perimetric testing program with sensitivity and specificity for detection of visual field defects comparable to traditional automated perimetry. To make large‐scale screening more efficient, we developed a parallel rarebit perimetric method to screen groups of subjects simultaneously. We then used this method to report the mean hit rate (MHR) among subjects aged 13 to 19 years.MethodsRarebit perimetry was installed on computers in an existing school computer laboratory. All subjects provided medical and demographic information and underwent a basic visual examination. Testing instructions were provided to groups of up to 35 subjects and rarebit perimetry was subsequently administered. Two or three test supervisors answered questions and ensured that subjects were well aligned with their test screens. Mean hit rate, reaction times, error rates and testing time were calculated, and time estimates for rarebit, frequency doubling perimetry and Humphrey 24‐2 Swedish Interactive Thresholding Algorithm (SITA) fast test were compared.ResultsA total of 364 rarebit perimetric tests were conducted on 182 subjects. Of these, 154 subjects met our inclusion criteria for the reference range (three testing errors or less and visual acuity 6/9 or better). The average mean hit rate was 94.3 ± 4.63 per cent. Screening of 500 subjects using this parallel rarebit perimetric method would require approximately nine hours, which is far less than an estimated 77 hours required for frequency doubling perimetry ‐20 screening tests or an estimated 127 hours required for Humphrey 24‐2 SITA fast tests.ConclusionUsing our methods, rarebit perimetry can be administered in parallel to groups of subjects. The mean hit rate was comparable to that reported in previously published studies. This parallel technique may improve the efficiency of large‐scale visual field screenings.

The n-back test and the attentional network task as measures of child neuropsychological development in epidemiological studies.

Computerized neuropsychological tests offered several advantages for large epidemiological studies to assess child neuropsychological development. We aimed to evaluate the psychometric properties and criterion validity of 2 computerized tests (n-back and attentional network task [ANT]) used to assess the working memory and attention function, respectively. As part of the BREATHE (BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn) project, we evaluated the neuropsychological development of 2,904 children between 7 to 9 years of age. The main outcomes of the n-back test were d' scores and hit reaction time (RT) (HRT). The outcomes measured for ANT were incorrect responses, omissions, alerting, orienting, and conflict. We also collected data of child's sex, age, school achievement, ADHD symptomatology, behavioral problems, and maternal education. We observed that the d' scores and HRT showed acceptable internal consistency, reasonable factorial structure, as well as good criterion validity and statistical dependencies. Regarding the ANT, incorrect responses, omissions, and conflict score had acceptable criterion validity although the internal consistency of the ANT was low. We strongly recommend the use of these tests in environmental epidemiological studies as valid, objective, and easy-to-apply measures of child neuropsychological development.