Increased Omission Errors Research Articles

Sharing traumatic experiences: earlier denial increases endorsement of misinformation from a co-witness

ABSTRACT People oftentimes experience traumatic events together with co-witnesses, who might remember incidents differently. Moreover, people experiencing such traumatic events may initially deny them but eventually come forward (e.g. to a co-witness). We examined how initial false denials affected participants’ endorsement of misinformation from a co-witness. Participants (N = 131) watched a trauma analogue video. Next, half were instructed to falsely deny seeing certain details in the video, whereas the other half responded honestly in an interview with the experimenter. After one week, participants discussed the video with a co-witness (confederate) who suggested misinformation. Finally, all participants’ memory for the interview and video were tested. Participants who initially denied were more likely to accept co-witness misinformation than honest participants. False denials were also related to increased omission errors regarding the interview, but not the video. Thus, even though false denials might increase endorsement of some misinformation, memory for core details might remain unaffected.

Context matters: task relevance shapes neural responses to emotional facial expressions

Recent research shows that emotional facial expressions impact behavioral responses only when their valence is relevant to the task. Under such conditions, threatening faces delay attentional disengagement, resulting in slower reaction times and increased omission errors compared to happy faces. To investigate the neural underpinnings of this phenomenon, we used functional magnetic resonance imaging to record the brain activity of 23 healthy participants while they completed two versions of the go/no-go task. In the emotion task (ET), participants responded to emotional expressions (fearful or happy faces) and refrained from responding to neutral faces. In the gender task (GT), the same images were displayed, but participants had to respond based on the posers’ gender. Our results confirmed previous behavioral findings and revealed a network of brain regions (including the angular gyrus, the ventral precuneus, the left posterior cingulate cortex, the right anterior superior frontal gyrus, and two face-responsive regions) displaying distinct activation patterns for the same facial emotional expressions in the ET compared to the GT. We propose that this network integrates internal representations of task rules with sensory characteristics of facial expressions to evaluate emotional stimuli and exert top-down control, guiding goal-directed actions according to the context.

Caregiver faces capture 6- to 10-year-old children's attention during an online visual search task.

Developing attention skills allow children to parse their complex world by orienting to a subset of especially salient or meaningful inputs. Infants and children are biased to orient to faces and have difficulty ignoring faces when they appear as distractors. Although these past findings suggest that faces are more salient than nonsocial stimuli, it is unclear whether specific types of faces capture attention to a greater extent than others. Caregiver faces are one of the most prevalent and socially motivating stimuli in infants' and children's environments, suggesting that they may be biased to orient to caregiver faces to a greater extent than faces in general. Forty-six 6- to 10-year-old children across the United States and Canada completed an online attention capture task in which participants searched for a target within arrays containing multiple distractors. During some trials, either a stranger or the child's caregiver's face appeared as one of the distractors. Children showed consistently poorer performance (i.e., increased omission errors, poorer accuracy, and slower response times) when the caregiver face appeared as a distractor, especially during trials in which the target was present and within larger search arrays. These increased performance costs indicate an enhanced orienting bias to caregiver faces, which may reflect increased motivational salience of these faces. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Noradrenaline and Movement Initiation Disorders in Parkinson's Disease: A Pharmacological Functional MRI Study with Clonidine.

Slowness of movement initiation is a cardinal motor feature of Parkinson’s disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson’s disease.

Social Robots for Evaluating Attention State in Older Adults.

Sustained attention is essential for older adults to maintain an active lifestyle, and the deficiency of this function is often associated with health-related risks such as falling and frailty. The present study examined whether the well-established age-effect on reducing mind-wandering, the drift to internal thoughts that are seen to be detrimental to attentional control, could be replicated by using a robotic experimenter for older adults who are not as familiar with online technologies. A total of 28 younger and 22 older adults performed a Sustained Attention to Response Task (SART) by answering thought probes regarding their attention states and providing confidence ratings for their own task performances. The indices from the modified SART suggested a well-documented conservative response strategy endorsed by older adults, which were represented by slower responses and increased omission errors. Moreover, the slower responses and increased omissions were found to be associated with less self-reported mind-wandering, thus showing consistency with their higher subjective ratings of attentional control. Overall, this study demonstrates the potential of constructing age-related cognitive profiles with attention evaluation instruction based on a social companion robot for older adults at home.

Cross-species evidence that nicotine widens the attentional window.

The ability to spread attention over items or locations is as important for everyday functioning as the ability to focus narrowly. Little is known about neuronal processes involved in broad monitoring, but indirect evidence suggests a role of nicotinic acetylcholine receptors (nAChRs). The present study tested whether the prototypical nAChR agonist nicotine enhances the ability of humans and rodents to maintain a broad attentional window. Fifty-three never-smokers wearing a nicotine (7mg/24h) or placebo patch performed an attention task requiring detection of stimuli presented randomly in one of four peripheral locations, with a central cue predicting the target location or indicating the need to spread attention over all locations. Nineteen rats performed the 5-choice serial reaction time task requiring detection of stimuli presented randomly in a horizontal array of five locations. Performance after nicotine (0.1 and 0.2mg/kg) or vehicle administration was analyzed as a function of target location eccentricity. In human subjects, nicotine caused greater reaction time reduction when all locations were monitored than when a single location was cued. In rats, nicotine attenuated the decline in stimulus detections and the increase in omission errors with greater target location eccentricity. The findings represent cross-species evidence that nAChR agonism facilitates the ability to spread attention broadly. This suggests that nAChR hypofunction may be central to broad monitoring deficits as seen, for example, in schizophrenia. The homology of findings between the rodent and the human paradigm contributes to validating a translational strategy for treatment development.

Economical Assessment of Working Memory and Response Inhibition in ADHD Using a Combined n-back/Nogo Paradigm: An ERP Study

The development of cognitive interventions in attention-deficit/hyperactivity disorder (ADHD) often requires the assessment of multiple cognitive functions. However, experimental settings consisting of various tasks are particularly strenuous for patients and can thus result in poor data quality. For the economical assessment of working memory and response inhibition, this study aims to validate a combined n-back/nogo paradigm by comparing it to single task versions and to demonstrate its applicability for ADHD research. Twenty-five healthy individuals and 34 ADHD patients between 9 and 16 years participated in this event-related potential (ERP) study. Healthy controls underwent single task versions of a 2-back working memory task and a go/nogo response inhibition task as well as the introduced combined 2-back/nogo task. This combined task demonstrated a comparable ERP structure for working memory and response inhibition aspects as single task versions. Behaviorally, higher working memory performance during the combined paradigm indicated lower task difficulty, while high correlations between combined and single task versions still indicated valid working memory measures. For response inhibition performance, different task versions resulted in similar outcomes. The application of the combined n-back/nogo paradigm in ADHD patients revealed the expected working memory and response inhibition deficits, increased omission errors, reaction times, and standard deviation of reaction time, as well as diminished n-back P3 and nogo P3 amplitudes. We conclude that the combined n-back/nogo task is an effective paradigm for the economical assessment of working memory and response inhibition deficits in ADHD on a behavioral and neurophysiological level.

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.

Age-dependent effects of repeated methamphetamine exposure on locomotor activity and attentional function in rats

Many adolescents use amphetamines which are the second most common abused illegal drugs. Methamphetamine (Meth), as a potent amphetamine affects attentional functions. However, the most significant factor for susceptibility to Meth is the age of exposure, most studies have examined the effects of Meth after early adolescence stage. The present experiment was aimed to investigate some possible short- and long-term effects of Meth at two distinct points of adolescence stage (early versus late) on 1) locomotor activity in adolescent rats and 2) attentional functions in their adulthood. Rats received Meth (5 mg/kg, i.p., for consecutive 10 days) during early adolescence (postnatal days (PND) 30–39) or late adolescence (PND 50–59). Locomotor activity was assessed after the first and tenth injections. Then, in adulthood, rats were trained and tested on the Five-choice serial reaction time task (5-CSRTT) to display possible attentional impairments. The first Meth administration in early exposed adolescent (EEA) group produced the highest level of activity, compared with the first exposure in late exposed adolescent (LEA) group and tenth administrations in both groups. In adulthood, LEA group significantly delayed learning the 5-CSRTT and exhibited attentional impairments, as demonstrated by significant reduced response accuracy and increased omission errors under pharmacological challenge, compared with control group. The susceptibility to Meth depends on the age of exposure and Meth administration during late adolescence stage may cause prolonged attentional deficits in adulthood.

Reduced Verification of Medication Alerts Increases Prescribing Errors.

Clinicians using clinical decision support (CDS) to prescribe medications have an obligation to ensure that prescriptions are safe. One option is to verify the safety of prescriptions if there is uncertainty, for example, by using drug references. Supervisory control experiments in aviation and process control have associated errors, with reduced verification arising from overreliance on decision support. However, it is unknown whether this relationship extends to clinical decision-making. Therefore, we examine whether there is a relationship between verification behaviors and prescribing errors, with and without CDS medication alerts, and whether task complexity mediates this. A total of 120 students in the final 2 years of a medical degree prescribed medicines for patient scenarios using a simulated electronic prescribing system. CDS (correct, incorrect, and no CDS) and task complexity (low and high) were varied. Outcomes were omission (missed prescribing errors) and commission errors (accepted false-positive alerts). Verification measures were access of drug references and view time percentage of task time. Failure to access references for medicines with prescribing errors increased omission errors with no CDS (high-complexity: χ 2(1) = 12.716; p < 0.001) and incorrect CDS (Fisher's exact; low-complexity: p = 0.002; high-complexity: p = 0.001). Failure to access references for false-positive alerts increased commission errors (low-complexity: χ 2(1) = 16.673, p < 0.001; high-complexity: χ 2(1) = 18.690, p < 0.001). Fewer participants accessed relevant references with incorrect CDS compared with no CDS (McNemar; low-complexity: p < 0.001; high-complexity: p < 0.001). Lower view time percentages increased omission (F(3, 361.914) = 4.498; p = 0.035) and commission errors (F(1, 346.223) = 2.712; p = 0.045). View time percentages were lower in CDS-assisted conditions compared with unassisted conditions (F(2, 335.743) = 10.443; p < 0.001). The presence of CDS reduced verification of prescription safety. When CDS was incorrect, reduced verification was associated with increased prescribing errors. CDS can be incorrect, and verification provides one mechanism to detect errors. System designers need to facilitate verification without increasing workload or eliminating the benefits of correct CDS.

The Multiple Object Test as a performance-based tool to assess the decline of ADL function in Parkinson's disease.

IntroductionAs cognitive-driven worsening of activities of the daily living (ADL) in Parkinson’s disease (PD) is the core feature of PD dementia (PDD), there is great need for sensitive quantitative assessment. Aim of our study was the evaluation of cognitive-driven worsening of ADL by the performance-based Multiple Object Test (MOT), offering an essential clinical advantage as it is quick and easy to apply in a clinical context even on severely impaired patients.Methods73 PD patients were assessed longitudinally over a period of 37 (6–49) months. According to their neuropsychological profile the sample was divided into two groups: PD patients with (n = 34, PD-CI) and without cognitive impairment (n = 39, PD-noCI). The MOT comprises five routine tasks (e.g. to make coffee) quick and easy to apply. Quantitative (total error number, processing time) and qualitative parameters (error type) were analyzed using non-parametric test statistic (e.g.Wilcoxon signed-rank test, binary logistic regression).ResultsMedian number of total errors (p = 0.001), processing time (p<0.001), perplexity (p = 0.035), and omission errors (p<0.001) increased significantly from baseline to follow-up in the total sample. Worsening of MOT performance was correlated to cognitive decline in the attention/ executive function and visuo-constructive domain. PD-CI showed an increase in omission errors (p = 0.027) compared to PD-noCI over time. This increase in omission errors between visits was further identified as a risk marker for PDD conversion.ConclusionThe MOT, especially frequency of omission errors, is a promising tool to rate PD patients objectively and might help to identify patients with a high risk for having mild cognitive impairment or dementia.

Reduced functional connectivity of fronto-parietal sustained attention networks in severe childhood abuse.

Childhood maltreatment is associated with attention deficits. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA, FKBP5) interaction on functional brain connectivity during sustained attention in medication/drug-free adolescents. Functional connectivity was compared, using generalised psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 21 age-and gender-matched adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed a parametrically modulated vigilance task requiring target detection with a progressively increasing load of sustained attention. Behaviourally, participants exposed to childhood abuse had increased omission errors compared to healthy controls. During the most challenging attention condition abused participants relative to controls exhibited reduced connectivity, with a left-hemispheric bias, in typical fronto-parietal attention networks, including dorsolateral, rostromedial and inferior prefrontal and inferior parietal regions. Abuse-related connectivity abnormalities were exacerbated in individuals homozygous for the risky C-allele of the single nucleotide polymorphism rs3800373 of the FK506 Binding Protein 5 (FKBP5) gene. Findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-parietal attention networks and that the FKBP5 genotype moderates neurobiological vulnerability to abuse. These findings represent a first step towards the delineation of abuse-related neurofunctional connectivity abnormalities, which hopefully will facilitate the development of specific treatment strategies for victims of childhood maltreatment.

Attention profiles in childhood absence epilepsy compared with attention-deficit/hyperactivity disorder

ObjectiveThis study aimed to compare the attention profiles of subjects with childhood absence epilepsy (CAE) to those of children with attention-deficit/hyperactivity disorder (ADHD) and controls. MethodWe retrospectively reviewed the medical records of 20 children (age 7.2 ± 1.6 years, 5 boys) in whom CAE was diagnosed at the Department of Pediatric Neurology of Asan Medical Center, Seoul, Korea. ADHD and control subjects were selected from children who visited the Department of Pediatric Psychiatry and were confirmed as having or not having ADHD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). The 20 children with CAE, 20 with ADHD and 20 controls completed the Advanced Test of Attention (ATA), which is a computerized continuous performance task. ResultsThe CAE subjects without ADHD showed increased Omission errors (p=.013) on the visual ATA and Response time (p=0.044) on the auditory ATA than the controls, although these differences did not remain significant after multiple comparison correction. The CAE subjects without ADHD had significantly decreased Response time variability on the visual ATA than the ADHD group (p<0.001). The CAE subjects with comorbid ADHD showed increased Commission errors (p=0.020) and Response time variability (p=0.016) on the visual ATA and increased Commission errors (p=0.022) on the auditory ATA than the CAE subjects without ADHD, although statistical significance disappeared after multiple comparison adjustments. ConclusionThese findings suggest that selective attention is impaired in children with CAE and comorbid ADHD contributes to further impairment of sustained attention and response inhibition.

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.

Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC. Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day). Compared with performance at baseline, THC negatively affected accuracy on spatial working memory trials while participants were maintained on placebo (p=0.012) but not guanfacine (p=0.497); compared with placebo, accuracy was significantly (p=0.003, Cohen's d=-0.640) improved while individuals were treated with guanfacine. Similarly, compared with baseline, THC increased omission errors on an attentional task while participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); compared with placebo, there were significantly (p=0.034, Cohen's d=0.838) fewer omissions while individuals were maintained on guanfacine. Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment. Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.

Automation bias in electronic prescribing

BackgroundClinical decision support (CDS) in e-prescribing can improve safety by alerting potential errors, but introduces new sources of risk. Automation bias (AB) occurs when users over-rely on CDS, reducing vigilance in information seeking and processing. Evidence of AB has been found in other clinical tasks, but has not yet been tested with e-prescribing. This study tests for the presence of AB in e-prescribing and the impact of task complexity and interruptions on AB.MethodsOne hundred and twenty students in the final two years of a medical degree prescribed medicines for nine clinical scenarios using a simulated e-prescribing system. Quality of CDS (correct, incorrect and no CDS) and task complexity (low, low + interruption and high) were varied between conditions. Omission errors (failure to detect prescribing errors) and commission errors (acceptance of false positive alerts) were measured.ResultsCompared to scenarios with no CDS, correct CDS reduced omission errors by 38.3% (p < .0001, n = 120), 46.6% (p < .0001, n = 70), and 39.2% (p < .0001, n = 120) for low, low + interrupt and high complexity scenarios respectively. Incorrect CDS increased omission errors by 33.3% (p < .0001, n = 120), 24.5% (p < .009, n = 82), and 26.7% (p < .0001, n = 120). Participants made commission errors, 65.8% (p < .0001, n = 120), 53.5% (p < .0001, n = 82), and 51.7% (p < .0001, n = 120). Task complexity and interruptions had no impact on AB.ConclusionsThis study found evidence of AB omission and commission errors in e-prescribing. Verification of CDS alerts is key to avoiding AB errors. However, interventions focused on this have had limited success to date. Clinicians should remain vigilant to the risks of CDS failures and verify CDS.

Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse.

Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.

Patterns of microstructural white matter abnormalities and their impact on cognitive dysfunction in the various phases of type I bipolar disorder

BackgroundIn recent years, diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in type I bipolar disorder (BD). However, WM alterations in the different phases of BD remain to be explored. The aims of this study is to investigate the WM alterations in the various phases of illness and their correlations with clinical and neurocognitive features. MethodsWe investigated the DTI-derived fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) in patients with type I BD (n=61) subdivided in manic (n=21), depressive (n=20) and euthymic phases (n=20) vs. healthy controls (n=42), using a tract-based spatial statistics (TBSS) approach. Then, we investigated whether the subgroups of patients in the various phases of illness present different patterns of WM abnormalities. Finally we studied the correlations between WM alterations and clinical-cognitive parameters. ResultsWe found a widespread alteration in WM microstructure (decrease in FA and increase in MD and RD) in BD when compared to controls. The various subgroups of BD showed different spatial patterns of WM alterations. A gradient of increasing WM abnormalities from the euthymic (low degree and localized WM alterations mainly in the midline structures) to the manic (more diffuse WM alterations affecting both midline and lateral structures) and, finally, to the depressive phase (high degree and widespread WM alterations), was found. Furthermore, the WM diffuse alterations correlated with cognitive deficits in BD, such as decreased fluency prompted by letter and decreased hits and increased omission errors at the continuous performance test. LimitationsPatients under treatment. ConclusionsThe WM alterations in type I BD showed different spatial patterns in the various phases of illness, mainly affecting the active phases, and correlated with some cognitive deficits. This suggests a complex trait- and state-dependent pathogenesis of WM abnormalities in BD.

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

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.

Effects of MDMA on olfactory memory and reversal learning in rats

The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions.