Standard Behavioral Tests Research Articles

Persistent Behavioral Deficits in Rats after Parasagittal Fluid Percussion Injury.

Although traumatic brain injury (TBI) is now considered a chronic disease, few studies have investigated the long-term behavioral deficits elicited by a well-established rodent model of injury. Here we evaluate behavioral measures, commonly used in TBI research, to determine which tests are useful for studying long-term effects of brain injury in rats. Male Sprague-Dawley rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid-percussion injury (FPI), sham injury, or maintenance as naïve cohorts. Rats underwent neuroscore, beam-balance, and beam-walk tests for 3 days after injury. Subsequently, in separate groups at 3, 6, or 12 months, they were re-tested on the same tasks followed by a working memory version of the Morris water maze. On post-injury days (PIDs) 1-3, significant effects of injury on neuroscore, beam-balance, and beam-walk were observed. Differences in the beam-walk task were not detectable at any of the later time-points. However, deficits persisted in beam-balance out to 3 months and neuroscore out to 6 months. Working memory deficits persisted out to 12 months, at which time a reference memory deficit was also evident. These data suggest that balance and motor coordination recovered more quickly than neurological deficits. Furthermore, while deficits in working memory remained stable over the 12-month period, the late onset of the reference memory deficit points to the progressive nature of the injury, or an age/TBI interaction. In conclusion, standard behavioral tests are useful measures of persistent behavioral deficits after parasagittal FPI and provide evidence that TBI is a chronic condition that can change over time and worsen with age.

Similar recent selection criteria associated with different behavioural effects in two dog breeds

Selection during the last decades has split some established dog breeds into morphologically and behaviourally divergent types. These breed splits are interesting models for behaviour genetics since selection has often been for few and well-defined behavioural traits. The aim of this study was to explore behavioural differences between selection lines in golden and Labrador retriever, in both of which a split between a common type (pet and conformation) and a field type (hunting) has occurred. We hypothesized that the behavioural profiles of the types would be similar in both breeds. Pedigree data and results from a standardized behavioural test from 902 goldens (698 common and 204 field) and 1672 Labradors (1023 and 649) were analysed. Principal component analysis revealed six behavioural components: curiosity, play interest, chase proneness, social curiosity, social greeting and threat display. Breed and type affected all components, but interestingly there was an interaction between breed and type for most components. For example, in Labradors the common type had higher curiosity than the field type (F1,1668 = 18.359; P < 0.001), while the opposite was found in goldens (F1,897 = 65.201; P < 0.001). Heritability estimates showed considerable genetic contributions to the behavioural variations in both breeds, but different heritabilities between the types within breeds was also found, suggesting different selection pressures. In conclusion, in spite of similar genetic origin and similar recent selection criteria, types behave differently in the breeds. This suggests that the genetic architecture related to behaviour differs between the breeds.

Abstract # 1779 Select behavioral and physiological changes persist in novel cancer survivor model

Even after successful cancer treatment, survivors report distinct physical and mental health problems, which reduce quality of life. Little is known about the mechanisms underlying the enduring neurobehavioral consequences of a former cancer experience. The objective of this project was to develop a tumor-resected “survivor” mouse model by which to investigate these persistent effects. We hypothesized that mouse mammary tumors induce neuroinflammation, increase affective-like behaviors, and cognitive function, all of which are attenuated by tumor resection. Murine cancer cells (67NR) were injected into mammary fat pads of 9-week old, group-housed anesthetized female Balb/c mice. Non-tumor controls underwent sham surgery. Body mass and tumor size were recorded biweekly. These tumors are non-metastatic and after 2 weeks (tumors ∼ 0.75 cm3), tumors in some mice were surgically resected (“survivor” group) with clean margins (no recurrence). Two weeks after these treatments (sham, tumor, tumor resection), all mice were tested using a battery of standardized behavioral tests. To assess immune activation, inflammatory gene expression was quantified in various brain regions, as well as circulating inflammatory markers and immune cells. Preliminary results indicate that tumor resection attenuated IL-1beta expression in the hippocampus and specific peripheral immune measures. However, circulating immune cell trafficking and behavior did not return to levels of tumor-free control mice, suggesting that the influence of tumors endures. These immune changes may mediate prolonged behavioral comorbidities.

Оценка отдаленных результатов комбинированного применения тиоктовой кислоты с метотрексатом на модели ревматоидного артрита

Представлены результаты изучения длительной комбинированной терапии метотрексатом (1 мг/кг, внутрибрюшинно, 1 раз в неделю, 3 мес) и тиоктовой кислотой (11 мг/кг, внутрижелудочно, ежедневно, 1 мес) животных с моделированным адъювантным артритом в сравнении с монотерапией тиоктовой кислотой и метотрексатом. Критерием эффективности терапии служили выживаемость крыс, данные плетизмометрических показателей лапок, лабораторных показателей периферической крови, рентгенологического исследования суставов. Оценку функционального состояния ЦНС крыс проводили на 45 день эксперимента с использованием поведенческих тестов «открытое поле» и «приподнятый крестообразный лабиринт». Комбинированное применение препаратов нормализует эмоциональное реагирование у животных в условиях модели ситуативной тревожности. Показано, что комбинированное применение тиоктовой кислоты с метотрексатом повышает эффективность терапии адъювантного артрита, значительнее подавляя вторичное аутоиммунное воспаление, нормализуя показатели периферической крови и увеличивая выживаемость животных по сравнению с 3-месячной монотерапией метотрексатом.

EPV 18. Localized changes of oscillatory activity in delirium: Evidence for biomarkers of cognitive dysfunction from a large retrospective case-control quantitative EEG study

Objective Delirium is a common disorder that is associated with increased morbidity. The clinically heterogeneous phenotype and lack of objective disease markers are major causes of misdiagnosis leading to variable and potentially detrimental treatment decisions. A better understanding of pathophysiological mechanisms underlying this disorder are necessary to facilitate diagnosis and guide therapy. Methods We searched the EEG database of a German university hospital between years 2004 and 2014 for recordings of patients diagnosed with delirium (DSM-V criteria) and age-matched controls (n = 129 and 414, respectively). Standardized total and frequency band specific power spectra of continuous EEG data were compared between conditions (i.e. control vs. delirium) by analysis of variance and topographically by source statistics. Results As well-established, spectral variability was decreased in the delta and theta band in the delirium group. Faster frequencies exhibited increased variability. The occipital peak frequency was slowed from 10 Hz in the control group to 1 Hz in the delirium group. CONDITION x FREQUENCY exhibited a significant interaction (F = 845, p Fig. 1 ). Conclusions This is the first study to provide evidence for topographically specific changes in oscillatory activity in delirium. These results contribute to our understanding of pathomechanisms underlying behavioral disturbances and provide the intriguing perspective to serve as diagnostic and therapeutic biomarkers. Yet, current evidence requires confirmation by prospective studies including standardized diagnostic criteria and behavioral tests.

Chemogenetic Activation of Melanopsin Retinal Ganglion Cells Induces Signatures of Arousal and/or Anxiety in Mice

SummaryFunctional imaging and psychometric assessments indicate that bright light can enhance mood, attention, and cognitive performance in humans. Indirect evidence links these events to light detection by intrinsically photosensitive melanopsin-expressing retinal ganglion cells (mRGCs) [1, 2, 3, 4, 5, 6, 7, 8, 9]. However, there is currently no direct demonstration that mRGCs can have such an immediate effect on mood or behavioral state in any species. We addressed this deficit by using chemogenetics to selectively activate mRGCs, simulating the excitatory effects of bright light on this cell type in dark-housed mice. This specific manipulation evoked circadian phase resetting and pupil constriction (known consequences of mRGC activation). It also induced c-Fos (a marker of neuronal activation) in multiple nuclei in the hypothalamus (paraventricular, dorsomedial, and lateral hypothalamus), thalamus (paraventricular and centromedian thalamus), and limbic system (amygdala and nucleus accumbens). These regions influence numerous aspects of autonomic and neuroendocrine activity and are typically active during periods of wakefulness or arousal. By contrast, c-Fos was absent from the ventrolateral preoptic area (active during sleep). In standard behavioral tests (open field and elevated plus maze), mRGC activation induced behaviors commonly interpreted as anxiety like or as signs of increased alertness. Similar changes in behavior could be induced by bright light in wild-type and rodless and coneless mice, but not melanopsin knockout mice. These data demonstrate that mRGCs drive a light-dependent switch in behavioral motivation toward a more alert, risk-averse state. They also highlight the ability of this small fraction of retinal ganglion cells to realign activity in brain regions defining widespread aspects of physiology and behavior.

SU‐C‐204‐02: Behavioral and Pathologic Differences in Mice Exposed to Proton Minibeam Arrays Versus Proton Broad Beams

Purpose:Minibeam therapy using protons or light‐ions offers a theoretical reduction of biologic damage to tissues upstream of a tumor compared to broad‐beam therapy while providing equal tumor control. The purpose of this study was to investigate behavioral and pathologic differences in mice after exposure of healthy brain to proton minibeam arrays versus proton broad beams.Methods:Twenty‐four C57BL/6J juvenile mice were divided into 5 study arms: sham irradiation (NoRT), broad‐beam 10 Gy (BB10), minibeam 10Gy (MB10), broad‐beam 30 Gy (BB30), and minibeam 30 Gy (MB30), approximate integral entrance doses. Circular beams of 100 MeV protons with 7‐mm diameter were delivered laterally through the brain, either as broad beams or as planar minibeam arrays having 300‐micron beam width and 1‐mm spacing on center. Mice were followed for 8 months using standard behavioral tests. Pathologic studies were carried out at 8 months after irradiation.Results:Peak entrance doses were 10.0, 23.8, 30.0, and 71.3 Gy for mice in BB10, MB10, BB30, and MB30, respectively. Despite the high single‐fraction doses, no animals showed signs of radiation sickness or neurophysical impairment over the 8‐month study duration. The Morris water maze alternate‐starting‐position trial showed significant evidence of better spatial learning for mice in MB10 versus BB10 (p=0.026), but other behavioral tests showed no significant differences. Glial fibrillary acidic protein stains showed gliosis in arms BB10, BB30, and MB30 but not in NoRT or MB10. A secondary finding was categorically higher epilation in broad‐beam arms compared with their minibeam dose counterparts.Conclusion:Our findings indicate trends that, despite the higher peak doses, proton minibeam therapy can reduce radiation side effects in shallow tissue and brain compared to proton broadbeam therapy. As the behavioral findings were mixed, confirmation studies are needed with larger numbers of animals.AAPM Research Seed Funding Grant

Quantification of visual function assessment using remote eye tracking in children: validity and applicability

Measurements of visual and oculomotor functions are essential for providing tailored support to visually impaired children. In young or intellectually disabled children these measurements can be difficult or even impossible to perform. Recordings of orienting gaze in response to specific visual information, made with eye tracking, may offer a solution. The aim of this study was to observe and quantify eye tracking (ET)-based gaze responses to provide information about visual and oculomotor functioning, and to compare this information with standard visual function assessments (VFA). One hundred and twenty-six visually impaired children from 1-14years underwent a VFA. Next they underwent a remote ET test. Four aspects of oculomotor control (nystagmus, fixation, saccades, pursuit) and three visual functions (visual field, contrast, colour) were selected to compare both methods. Performance was assessed (1) during VFA using standard behavioural observation and test scores and (2) after ET by observing and scoring the eye movement recordings. Validity, in terms of agreement between results, was measured by correlation analyses. From the orienting gaze responses, quantitative parameters (gain, fixation duration and directional saccades) were calculated to characterize visual performance. Good agreement between the two test methods was found for observational assessment of oculomotor control and visual functions (correlations ranging from rs =0.39 to rs =0.69). The quantitative parameters of visual performance showed distinct results between children with and without specific functional impairments, both in children aged 1-6 and 7-14years. Eye tracking-based gaze recordings are a promising tool to assess oculomotor and visual performance in a communication-free manner. Calculating quantitative parameters from specific gaze responses could assist in the characterization of functional visual performance in children, independent of age. Gaze responses are a useful addition to standard VFA in clinical practice.

Genotype by environment interactions for behavioral reactivity in sheep.

In sheep, social reactivity and reactivity to humans are relevant behavioral responses that are used to investigate the behavioral adaptation of farm animals to various rearing conditions. Such traits were previously reported as heritable and associated with several QTLs. However, few behavior-related genotype by environment (G × E) interactions have been reported to date. The experiment was performed on 2,989 male and female lambs issued from 30 sires. Every sire had progeny reared under both intensive and extensive conditions. After weaning, all lambs were individually exposed to two standardized behavioral tests. A broad range of behaviors including vocalizations, locomotion, localization, vigilance, and flight distance were assessed. Two complementary statistic approaches, with and without assumptions on the biological significance of behaviors, were performed to investigate social reactivity and reactivity to humans. G × E interactions were investigated based on the genetic correlations estimated for each factor or trait between farming conditions; those significantly different from 1 indicating a G × E. Environmental effects showed that social reactivity and reactivity to humans were higher in intensively reared lambs. The heritability of factors or traits used to measure social reactivity and reactivity to humans was similar in both rearing conditions. Estimated heritabilities were high for vocalizations in response to social isolation, moderate for locomotion and vigilance in response to social isolation, and low for both flight distance to an approaching human and proximity to a motionless human. No significant G × E interaction was found for vocalizations. G × E interactions were found for locomotion, vigilance and flight distance. Genetic correlations between both environments were low to moderate for vigilance, locomotion and flight distance. Vocalization in response to social isolation with or without human presence was identified as a robust trait and could be used to improve sheep sociability, independently of the environment. A G × E interaction was observed for behavioral reactivity to humans. Although moderate, the genetic correlation for this trait between intensive and extensive conditions could be used to select sires in the same environment by taking into account the G × E and to produce in different environments progenies that are less reactive to humans.

P.4.015 Hippocampal overexpression of interleukin-1ß induces neurogenesis-associated cognitive deficits in adult male rats

A new spontaneous mouse mutation named fierce (frc) is deleted for the nuclear receptor Nr2e1 gene (also known as Tlx, mouse homolog of Drosophila tailless). The fierce mutation is genetically and phenotypically similar to Nr2e1 targeted mutations previously studied on segregating genetic backgrounds. However, we have characterized the fierce brain, eye, and behavioural phenotypes on three defined genetic backgrounds (C57BL/6J, 129P3/JEms, and B6129F1). The data revealed many novel and background-dependent phenotypic characteristics. Whereas abnormalities in brain development, hypoplasia of cerebrum and olfactory lobes, were consistent on all three backgrounds, our novel finding of enlarged ventricles in 100% and overt hydrocephalus in up to 30% of fierce mice were unique to the C57BL/6J background. Developmental eye abnormalities were also background-dependent with B6129F1-frc mice having less severe thinning of optic layers and less affected electroretinogram responses. Impaired regression of hyaloid vessels was observed in all backgrounds. Furthermore, retinal vessels were deficient in size and number in 129P3/JEms-frc and B6129F1-frc mice but almost entirely absent in C57BL/6J-frc mice. We present the first standardized behavioural tests conducted on Nr2e1 mutant mice and show that C57BL/6J-frc and B6129F1-frc mice have deficits in sensorimotor assays and are hyperaggressive in both sexes and backgrounds. However, C57BL/6J-frc mice were significantly more aggressive than B6129F1-frc mice. Overall, this extensive characterization of the fierce mutation is essential to its application for the study of behavioural, and brain and eye developmental disorders. In addition, the background-dependent differences revealed will enable the identification of important genetic modifiers.

Chloral hydrate sedation for auditory brainstem response (ABR) testing in children: Safety and effectiveness

IntroductionThe auditory brainstem response (ABR) test is used to identify hearing loss and measure hearing thresholds of infants and children who cannot be tested using standard behavioral hearing testing methods. In order for the ABR to yield useful data, a child must be asleep throughout the duration of the test. In many centers, this is achieved through the use of a general anesthetic, with its inherent risks and costs. Since 2004, ABRs have been routinely conducted at BC Children's Hospital in an ambulatory care setting under oral chloral hydrate sedation, with monitoring by a specialist nurse. The aim of this retrospective study was to assess the effectiveness and safety of nurse-led sedation with chloral hydrate for ABR testing at our tertiary pediatric center. MethodsMedical and audiology records were reviewed for children aged 6 months to 17 years who underwent ABR testing from 2004 to 2012. We reviewed the dosage of drug used, condition of the child after chloral hydrate administration, adverse effects, audiological results, patients’ vital signs, and the effectiveness of the sedative in keeping the child asleep throughout the duration of the test. Frequency distributions were derived for adverse outcomes. Results725 ABR records encompassing 635 children (multiple ABR tests in some children) were reviewed. The average dose of chloral hydrate used was 52mg/kg. The majority of sedated ABR's (80.8%) were completed without any incident. Significant events [apnea and/or bradycardia], minor complications [vomiting, hypoxemia, prolonged sedation, and/or tachypnea] and restlessness were noted in 3.4%, 6.2%, and 5.0% of the cases, respectively. The majority of these issues resolved without medical intervention, such as the need to provide supplementary oxygen. In 95.9% of ABRs, chloral hydrate was successful in sedating the child adequately to answer the audiological question. ConclusionsThis forms the largest study to date on oral sedation for ABR testing. Based on our results, the use of chloral hydrate in the presence of a sedation nurse was a safe and reliable method of performing ABR in infants and children. This may be of significant value to centres worldwide exploring alternatives to general anesthesia for ABR testing.

Motor Performance is Impaired Following Vestibular Stimulation in Ageing Mice.

Balance and maintaining postural equilibrium are important during stationary and dynamic movements to prevent falls, particularly in older adults. While our sense of balance is influenced by vestibular, proprioceptive, and visual information, this study focuses primarily on the vestibular component and its age-related effects on balance. C57Bl/6J mice of ages 1, 5–6, 8–9 and 27–28 months were tested using a combination of standard (such as grip strength and rotarod) and newly-developed behavioral tests (including balance beam and walking trajectory tests with a vestibular stimulus). In the current study, we confirm a decline in fore-limb grip strength and gross motor coordination as age increases. We also show that a vestibular stimulus of low frequency (2–3 Hz) and duration can lead to age-dependent changes in balance beam performance, which was evident by increases in latency to begin walking on the beam as well as the number of times hind-feet slip (FS) from the beam. Furthermore, aged mice (27–28 months) that received continuous access to a running wheel for 4 weeks did not improve when retested. Mice of ages 1, 10, 13 and 27–28 months were also tested for changes in walking trajectory as a result of the vestibular stimulus. While no linear relationship was observed between the changes in trajectory and age, 1-month-old mice were considerably less affected than mice of ages 10, 13 and 27–28 months. Conclusion: this study confirms there are age-related declines in grip strength and gross motor coordination. We also demonstrate age-dependent changes to finer motor abilities as a result of a low frequency and duration vestibular stimulus. These changes showed that while the ability to perform the balance beam task remained intact across all ages tested, behavioral changes in task performance were observed.

Experimental nerve transfer model in the rat forelimb.

SummaryBackgroundNerve transfers are a powerful tool in extremity reconstruction, but the neurophysiological effects have not been adequately investigated. As 81 % of nerve injuries and most nerve transfers occur in the upper extremity with its own neurophysiological properties, the standard rat hindlimb model may not be optimal in this paradigm. Here we present an experimental rat forelimb model to investigate nerve transfers.MethodsIn ten male Sprague-Dawley rats, the ulnar nerve was transferred to the motor branch of long head of the biceps. Sham surgery was performed in five animals (exposure/closure). After 12 weeks of regeneration, muscle force and Bertelli test were performed and evaluated.ResultsThe nerve transfer successfully reinnervated the long head of the biceps in all animals, as indicated by muscle force and behavioral outcome. No aberrant reinnervation occurred from the original motor source. Muscle force was 2,68 N ± 0.35 for the nerve transfer group and 2,85 N ± 0.39 for the sham group, which was not statically different (p = 0.436). The procedure led to minor functional deficits due to the loss of ulnar nerve function; this, however, could not be quantified with any of the presented measures.ConclusionThe above-described rat model demonstrated a constant anatomy, suitable for nerve transfers that are accessible to standard neuromuscular analyses and behavioral testing. This model allows the study of both neurophysiologic properties and cognitive motor function after nerve transfers in the upper extremity.

Individual differences in foraging decisions: information-gathering strategies or flexibility?

Information on where to find food patches, their quality, and food variance can have implications for fitness and survival when a current food patch fails. Individuals have been found to vary in their response to changes in food availability, and this has been related to several personality traits in animals such as exploration behavior that measures activity in a novel environment. We examined if personality-related variation in reactions to food availability change could be explained by information-gathering strategies (IGSs), where individuals vary in investing in sampling known patches as a trade-off to seeking new patches. We also examined if these relationships can be explained by an alternative hypothesis where individuals are expected to express variation in behavioral flexibility (BF). The BF hypothesis predicted that individuals rely more on either internal/prior or external/current information. In addition to a standardized exploration behavior test, we designed a new 5-day-long experiment where individual reactions to changes in food availability were measured using wild great tits (Parus major). We found that slow exploring individuals sampled empty food patches more than fast exploring individuals, supporting the IGS hypothesis. We found no evidence for personality-related differences in feeder choice in response to changes in food availability, nor personality-related differences in flexibility in behavioral responses.

The correlation between alopecia and temperament in rhesus macaques (Macaca mulatta) at four primate facilities.

Alopecia is a ubiquitous, multifaceted problem at facilities caring for captive rhesus macaques. There is a wide range of potential etiologies for the hair loss, including compromised immune function, dermatological pathologies, and environmental factors. However, few studies have examined whether various temperamental traits affect vulnerability to develop alopecia. We examined the correlation between alopecia and temperament in 101 (51M) indoor-housed rhesus macaques at four national primate centers. We utilized a cage side version of the Human Intruder test (HIT) to assess response to four conditions: no human present (Alone), human intruder standing next to the cage without making eye contact (Profile), intruder making direct eye contact (Stare) and intruder with back turned (Back). Behavior from all videos was quantified at one facility. We used generalized linear modeling to examine the relationship between behavior on the HIT and alopecia, controlling for facility, age, and sex. There was a significant negative correlation between alopecia and various behaviors associated with an inhibited or anxious temperament, including self-directed behavior (β = -0.15, P < 0.001) and freeze in the Profile period (β = -0.0092, P < 0.001), and defensive behaviors (β = -0.0094, P < 0.001) and time spent in the back of the cage in the Stare period (β = -0.0023, P = 0.015). Individuals with an inhibited or anxious temperament had less alopecia than others. Further, there were facility differences with respect to several variables on the HIT, including defensive behavior in Stare and freeze in Profile. These results suggest that temperament can influence the development of alopecia in rhesus macaques. Our results also highlight the degree to which facility differences can affect outcomes on standardized behavioral tests. Am. J. Primatol. 79:e22504, 2017. © 2015 Wiley Periodicals, Inc.

Behavior of laboratory beagles: Assessment in a standardized behavior test using novel stimuli and situations

Abstract Laboratory dogs should be sociable with humans and react in a relaxed way when confronted with new stimuli and situations. This is of particular advantage when dogs are used in animal experiments and for the handling of dogs and animal welfare, in general. We determined the reactions of laboratory dogs to different stimuli and manipulations and evaluated the dogs' behaviors to these in the context of housing condition, sex, age, and origin of the dogs. Ninety purpose bred, 1- to 10-year-old laboratory beagles of both sexes from 4 research facilities were subjected to: a new, standardized behavioral test including unfamiliar situations, varied and novel manipulations not routinely involved in physical examination as performed by an unfamiliar person, and novel optical and acoustic stimuli. An earlier article reported on these dogs' responses to approaches and physical examination by known and unknown people (Doring et al., 2014). Here, we concentrate on the effects of environmental stimuli and atypical manipulations. Videotape-based assessment and scoring of the dogs' behavior showed distinct patterns of reactions. Most dogs reacted with interest toward the unfamiliar test person and readily established contact. Many dogs reacted with uncertainty to the unfamiliar object and sound. Signals that may indicate conflict or distress (muzzle licking, paw lifting, and panting) were observed in some of the dogs in all facilities and in all parts of the test. Lowest body language scores indicated by anxious and/or submissive postures were observed when the dogs' muzzles were held shut or when the dogs were covered with a thin cloth. Characteristic housing conditions of the different facilities significantly affected several endpoints. Male dogs were significantly less fearful than females in several parameters and older and facility-bred dogs were significantly less fearful. Housing conditions, sex, age, and origin of the dogs markedly affected their behavior.

N1 and P2 to words and wordlike stimuli in late elementary school children and adults.

In an investigation of the development of fine-tuning for word processing across the late elementary school years as indexed by the posterior N1 and P2 components of the ERP waveform, third, fourth, and fifth graders and a comparison group of adults viewed words, pseudowords, nonpronounceable letter strings, and false font strings in a semantic categorization task. In adults, N1 was larger to and P2 was later to words as compared to pseudowords, a finely tuned effect of lexicality reflecting specialization for word processing. In contrast, in each group of children, N1 was larger to letter strings than false font strings and P2 was larger to false font strings than letter strings, reflecting coarse encoding for orthography. In regression analyses, scores on standardized behavioral test measures of orthographic knowledge, decoding skill, and fluency predicted N1 amplitude; these effects were not significant with age included as a separate predictor. None of the behavioral scores, in models including or not including age, predicted P2 amplitude. In direct comparisons between groups, there were multiple differences between the child and adult groups for both N1 and P2 amplitude effects, and only a single significant difference between two child groups. Overall, the findings suggest a lengthy developmental time course for the fine-tuning of early word processing as indexed by N1 and P2.

Genetic evaluation of traits in a standardized behavioral test for potential guide dog puppies using crossbreed models

Abstract Two thousand one hundred twenty-seven potential guide dog puppies of 2 breeds and their crosses underwent a standardized applied-stimulus behavioral test at 6 weeks of age. The responses of the puppies were scored on a 7-point scale according to either responsiveness (reaction to human assessor) or confidence (reaction to environmental stimuli) on stimuli comprising: following when called, retrieve, gentle restraint, noise, stroking, a toy squirrel, encouragement to go through a tunnel, and encouragement to go over a ramp. It has been shown previously that some of these stimuli showed association with success in guide dog training. The results of each component of the test were analyzed using restricted maximum likelihood univariate animal models, and 8 of the 11 estimated heritabilities were significantly different from zero. Most of the crossbreeding parameter estimates were not detectably larger than zero, likely reflecting the small size of the dataset and the relatively close relationship between the 2 pure breeds. These results suggest that the behavioral test results (and the estimated breeding values produced from them) could be useful in identifying which puppies to use as breeding stock.

Effects of a Clown–Nurse Educational Intervention on the Reduction of Postoperative Anxiety and Pain Among Preschool Children and Their Accompanying Parents in South Korea

This study examined the effects of a clown-nurse educational intervention on children undergoing day surgery for strabismus. This was a quasi-experimental study, using a nonequivalent control group, non-synchronized design. Fifty preschool children and their parents were invited to participate. The children in the intervention group (n=23) received clown therapy and subsequently reported significantly lower states of physiological anxiety, which was evidenced by systolic blood pressure, standardized behavioral anxiety tests, and post-surgery pain, than the control group (n=27). In addition, the parents in the experimental group showed a low state of physiological anxiety, evidenced by systolic blood pressure, pulse rates, standardized behavioral anxiety tests, and state-trait anxiety. The use of preoperative clown intervention may alleviate postoperative problems, not only for children, but also for their parents.

Neurotoxicity may be an overlooked consequence of benzo[a]pyrene exposure that is relevant to human health risk assessment.

Benzo[a]pyrene (BaP) is a well-studied environmental compound that requires metabolic activation to have a carcinogenic effect. The neurotoxicity of BaP has received considerably less attention than its carcinogenicity. Environmental exposure to BaP correlates with impaired learning and memory in adults, and poor neurodevelopment in children. We carried out a comprehensive literature review to examine the neurotoxicity of BaP. The data were used to identify potential point of departure (POD) values for cancer and neurotoxicity endpoints using benchmark dose (BMD) modelling to compare the utility of both endpoints in the risk assessment of BaP. The POD for neurotoxicity in rodents, based on a standard behavioural test (Morris water maze), was 0.025 mg BaP/kg-bw-day compared to 0.54 mg BaP/kg-bw-day for rodent forestomach carcinogenicity, suggesting that neurotoxic endpoints are more sensitive than cancer endpoints for health risks associated with BaP exposure. Using the limited number of published studies on this topic, we propose a preliminary mode of action (MOA) to explain BaP-induced neurotoxicity in rodents. The MOA includes: (1) BaP binding to the aryl hydrocarbon receptor (AHR); (2) AHR-dependent modulation of the transcription of N-methyl-d-aspartate glutamate receptor (NMDAR) subunits; (3) NMDAR-mediated loss of neuronal activity and decreased long-term potentiation; and (4) compromised learning and memory. More data are needed to explore the proposed neurotoxic MOA. In addition, we consider alternative MOAs, including the hypothesis that BaP-mediated DNA damage may lead to either carcinogenicity or neurotoxicity, depending on the tissue. Our proposed MOA is intended to serve as a basis for hypothesis testing in future studies. We emphasise that further studies are needed to validate the proposed MOA, to evaluate its human relevance, and to explore other potential mechanisms of BaP neurotoxicity.