Co-occurrence of phthalic acid esters (PAEs) and cyclic volatile methylsiloxanes (cVMSs) in fine particulate matter (PM0.5 and PM0.1) collected from an industrial area in Vietnam.

Distribution patterns of 10 phthalic acid diesters (PAEs) and four cyclic volatile methylsiloxanes (cVMSs) were investigated in fine particulate matter (PM0.1 and PM0.5) collected from Bac Ninh, an industrial province in Vietnam during September-October in 2021. Total concentrations of PAEs found in PM0.1 and PM0.5 were in the ranges of 1.76-372 (median: 34.0 ng/m3) and 2.23-895 ng/m3 (median: 15.4 ng/m3), respectively. Among PAEs, di-n-butyl phthalate (DBP) was the most abundant compound found in PM0.1, whereas, di-2-(ethyl)hexyl phthalate (DEHP) was measured at the highest concentration in PM0.5. Total concentrations of cVMSs measured in PM0.1 and PM0.5 were in the ranges of method quantification limit (MQL)-203 (median: 2.10 ng/m3) and MQL-537 ng/m3 (median: 0.389 ng/m3), respectively. Among cVMSs, decamethylcyclopentasiloxane (D5) was found at the highest concentration in both PM0.1 and PM0.5 fractions of particulate matter. The concentration ratios between PAEs and cVMSs in PM0.1/PM0.5 were greater than 1 (except di-n-octyl phthalate: DnOP), suggesting that these chemicals tend to sorb to PM0.1 more preferentially than PM0.5. Among sampling locations, high concentrations of PAEs and cVMSs were found at traffic intersections (Que Vo district) and a craft village (Tu Son city). Relatively stronger correlations existed between cVMSs pairs in PM0.1 and PM0.5 (correlation coefficient: 0.73-1) than those of PAEs (-0.83-0.90). The human exposure doses to PAEs and cVMSs through inhalation of particulate matter were estimated based on the measured concentrations in PM0.1 and PM0.5 fractions. The estimated exposure doses of PAEs and cVMSs for infants (7.1 ng/kg-bw/d and 2.5 ng/kg-bw/d) were higher than those for adults (2.6 ng/kg-bw/d and 0.9 ng/kg-bw/d).

Superior Neuronal Detection of Snakes and Conspecific Faces in the Macaque Medial Prefrontal Cortex.

Snakes and conspecific faces are quickly and efficiently detected in primates. Because the medial prefrontal cortex (mPFC) has been implicated in attentional allocation to biologically relevant stimuli, we hypothesized that it might also be highly responsive to snakes and conspecific faces. In this study, neuronal responses in the monkey mPFC were recorded, while monkeys discriminated 8 categories of visual stimuli. Here, we show that the monkey mPFC neuronal responses to snakes and conspecific faces were unique. First, the ratios of the neurons that responded strongly to snakes and monkey faces were greater than those of the neurons that responded strongly to the other stimuli. Second, mPFC neurons responded stronger and faster to snakes and monkey faces than the other categories of stimuli. Third, neuronal responses to snakes were unaffected by low-pass filtering of the images. Finally, activity patterns of responsive mPFC neurons discriminated snakes from the other stimuli in the second 50 ms period and monkey faces in the third period after stimulus onset. These response features indicate that the mPFC processes fast and coarse visual information of snakes and monkey faces, and support the hypothesis that snakes and social environments have shaped the primate visual system over evolutionary time.

Sex-specific effects of perinatal dioxin exposure on eating behavior in 3-year-old Vietnamese children.

BACKGROUND: We previously reported that perinatal dioxin exposure increased autistic traits in children living in dioxin-contaminated areas of Vietnam. In the present study, we investigated the impact of dioxin exposure on children's eating behavior, which is often altered in those with developmental disorders. METHODS: A total of 185 mother-and-child pairs previously enrolled in a birth cohort in dioxin-contaminated areas participated in this survey, conducted when the children reached 3 years of age. Perinatal dioxin exposure levels in the children were estimated using dioxin levels in maternal breast milk after birth. Mothers were interviewed using the Children's Eating Behaviour Questionnaire (CEBQ). A multiple linear regression model was used to analyze the association between dioxin exposure and CEBQ scores, after controlling for covariates such as location, parity, maternal age, maternal education, maternal body mass index, family income, children's gestational age at delivery, and children's age at the time of the survey. A general linear model was used to analyze the effects of sex and dioxin exposure on CEBQ scores. RESULTS: There was no significant association between most dioxin congeners or toxic equivalencies of polychlorinated dibenzo-p-dioxins/furans (TEQ-PCDDs/Fs) and CEBQ scores in boys, although significant associations between some eating behavior sub-scores and 1,2,3,4,6,7,8,9-octachlorodibenzofuran were observed. In girls, there was a significant inverse association between levels of TEQ-PCDFs and enjoyment of food scores and between levels of TEQ-PCDFs and TEQ-PCDDs/Fs and desire to drink scores. Two pentachlorodibenzofuran congeners and 1,2,3,6,7,8-hexachlorodibenzofuran were associated with a decreased enjoyment of food score, and seven PCDF congeners were associated with a decreased desire to drink score. The adjusted mean enjoyment of food score was significantly lower in children of both sexes exposed to high levels of TEQ-PCDFs. There was, however, a significant interaction between sex and TEQ-PCDF exposure in their effect on desire to drink scores, especially in girls. CONCLUSIONS: Perinatal exposure to dioxin can influence eating behavior in children and particularly in girls. A longer follow-up study would be required to assess whether emotional development that affects eating styles and behaviors is related to dioxin exposure.

Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes.

Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates' heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

Place-related neuronal activity in the monkey parahippocampal gyrus and hippocampal formation during virtual navigation.

Neuropsychological data in primates demonstrated a pivotal role of the hippocampal formation (HF) and parahippocampal gyrus (PH) in navigation and episodic memory. To investigate the role of HF and PH neurons in environmental scaling in primates, we recorded neuronal activities in the monkey HF and PH during virtual navigation (VN) and pointer translocation (PT) tasks. The monkeys had to navigate within three differently sized virtual spaces with the same spatial cues (VN task) or move a pointer on a screen (PT task) by manipulating a joystick to receive a reward. Of the 234 recorded neurons, 170 and 61 neurons displayed place-related activities in the VN and PT tasks, respectively. Significant differences were observed between the HF and PH neurons. The spatial similarity of place fields between the two different virtual spaces was lower in PH than in HF, while specificities of the neuronal responses to distal spatial cues were higher in PH than in HF. Spatial view information was predominately processed in posterior PH. The spatial scales (place field sizes) of the HF and PH neurons were reduced in the reduced virtual space, as shown in rodent place cells. These results suggest the complementary roles of HF (allocentric representation of landmarks) and PH (representation of the spatial layout of landmarks) in the recognition of a location during navigation.

Geranyl dihydrochalcones from Artocarpus altilis and their antiausteric activity.

Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100 % preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.

Neuronal responses to face-like stimuli in the monkey pulvinar.

The pulvinar nuclei appear to function as the subcortical visual pathway that bypasses the striate cortex, rapidly processing coarse facial information. We investigated responses from monkey pulvinar neurons during a delayed non-matching-to-sample task, in which monkeys were required to discriminate five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face-like patterns (three dark blobs on a bright oval), eye-like patterns and simple geometric patterns]. Of 401 neurons recorded, 165 neurons responded differentially to the visual stimuli. These visual responses were suppressed by scrambling the images. Although these neurons exhibited a broad response latency distribution, face-like patterns elicited responses with the shortest latencies (approximately 50 ms). Multidimensional scaling analysis indicated that the pulvinar neurons could specifically encode face-like patterns during the first 50-ms period after stimulus onset and classify the stimuli into one of the five different categories during the next 50-ms period. The amount of stimulus information conveyed by the pulvinar neurons and the number of stimulus-differentiating neurons were consistently higher during the second 50-ms period than during the first 50-ms period. These results suggest that responsiveness to face-like patterns during the first 50-ms period might be attributed to ascending inputs from the superior colliculus or the retina, while responsiveness to the five different stimulus categories during the second 50-ms period might be mediated by descending inputs from cortical regions. These findings provide neurophysiological evidence for pulvinar involvement in social cognition and, specifically, rapid coarse facial information processing.

Merosin-deficient congenital muscular dystrophy type 1a: detection of LAMA2 variants in Vietnamese patients.

Background: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A), also known as laminin-α2 chain-deficient congenital muscular dystrophy (LAMA2-MD), is an autosomal recessive disease caused by biallelic variants in the LAMA2 gene. In MDC1A, laminin- α2 chain expression is absent or significantly reduced, leading to some early-onset clinical symptoms including severe hypotonia, muscle weakness, skeletal deformity, non-ambulation, and respiratory insufficiency. Methods: Six patients from five unrelated Vietnamese families presenting with congenital muscular dystrophy were investigated. Targeted sequencing was performed in the five probands. Sanger sequencing was carried out in their families. Multiplex ligation-dependent probe amplification was performed in one family to examine an exon deletion. Results: Seven variants of the LAMA2 (NM_000426) gene were identified and classified as pathogenic/likely pathogenic variants using American College of Medical Genetics and Genomics criteria. Two of these variants were not reported in the literature, including c.7156-5_7157delinsT and c.8974_8975insTGAT. Sanger sequencing indicated their parents as carriers. The mothers of family 4 and family 5 were pregnant and a prenatal testing was performed. The results showed that the fetus of the family 4 only carries c.4717 + 5G>A in the heterozygous form, while the fetus of the family 5 carries compound heterozygous variants, including a deletion of exon 3 and c.4644C>A. Conclusion: Our findings not only identified the underlying genetic etiology for the patients, but also provided genetic counseling for the parents whenever they have an offspring.

Perinatal Dioxin Exposure and Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Children Living in a Dioxin Contamination Hotspot in Vietnam.

We examined children in Da Nang, a dioxin contamination hotspot in Vietnam, twice at 5 and 8 years of age, and investigated sex- and age-dependent differences in the effects of dioxin exposure on attention deficit hyperactivity disorder (ADHD) symptoms. We also studied autistic traits in children with ADHD symptoms. A total of 163 children participated in follow-up surveys at 5 and 8 years of age and were included in the present analysis. ADHD symptoms were assessed using an ADHD rating scale with inattention and hyperactivity-and-impulsivity (hyperactivity) subscales. Autistic behaviors were evaluated using the Autism Spectrum Rating Scale (ASRS). Perinatal dioxin exposure was indicated by dioxin levels in maternal breast milk. In boys, hyperactivity scores were significantly higher in the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) group only at 5 years of age. In girls, hyperactivity scores at 8 years of age were significantly higher in the high TCDD group, which was significantly associated with those at 5 years of age. In girls, ASRS unusual behavior scores were significantly higher with higher TCDD exposure and hyperactivity scores at 8 years of age. These results suggest that high perinatal TCDD exposure may increase ADHD likelihood and autistic traits, particularly in girls of 7-8 years of age.

Effect of Perinatal Dioxin Exposure Originating from Agent Orange on Gaze Behavior in 3-Year-Old Children Living in the Most Dioxin-Contaminated Areas in Vietnam.

We investigated the effect of perinatal dioxin exposure indicated by dioxins in breast milk on children's gaze behavior. We studied 142 children aged 3 years from the 2012 Bien Hoa birth cohort in a hotspot of dioxin contamination in Vietnam. Children's faces were viewed using the eye-tracking method. Associations between gaze behavior of faces and neurodevelopmental indices and head circumference were analyzed to determine whether poor gaze behavior indicates increased autistic traits in these children. The gaze fixation duration on facial areas when viewing 10 still images of children was calculated as the gaze behavior index. Autistic behavior was assessed using the Autism Spectrum Rating Scale, and language development was evaluated by the Bayley Scales of Infant and Toddler Development, Ver. 3. The face fixation duration (%) significantly decreased as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations increased in a dose−effect manner in girls, which suggested atypical gaze behavior for watching human faces. Furthermore, these girls with atypical gaze behavior showed lower social communication scores and smaller head sizes, suggesting increased autistic traits in girls. In conclusion, our findings show sex-specific effects (girls > boys) of perinatal TCDD exposure on gaze behavior in young children.

Effects of perinatal dioxin exposure on mirror neuron activity in 9-year-old children living in a hot spot of dioxin contamination in Vietnam.

BACKGROUND: For 8 years, we have followed up a birth cohort comprising 241 mother-and-infant pairs living around the Da Nang airbase, a hot spot of dioxin contamination in Vietnam, and have reported the impacts of perinatal dioxin exposure on the neurodevelopment of children at various ages. In the present study, 9 years after birth, we investigated the effects of perinatal dioxin exposure on mu and theta rhythms by analyzing EEG power during the execution and observation of hand movements, which indicate mirror neuron system activity. METHODS: One hundred fifty-five 9-year-old children (86 boys and 69 girls) from the Da Nang birth cohort participated in the EEG examination with free viewing of hand movements. The dioxin levels in their mothers' breast milk, measured 1 month after birth, were used as perinatal dioxin exposure markers. A log transform of the ratio of EEG power during execution or observation of the hand movements relative to the power during observation of a bouncing ball for theta and mu rhythms was used to evaluate mirror neuron activity. RESULTS: In both brain hemispheres, the log power ratio in the theta band was significantly higher (i.e., less reduction of power) during observation of hand movements in girls exposed to high levels of TCDD. In boys, however, dioxin congeners other than TCDD, including HxCDDs and several PCDF congeners, contributed to increased log power ratios in the theta band. Particularly for PCDF congeners, the log power ratios in the lowest group among 4 exposure groups were lowest and significantly increased (i.e., decreasing reduction of power) with increasing dose. CONCLUSION: Perinatal TCDD exposure may influence the mirror neuron system of the brain, which plays an important role for social-emotional behavior in children, particularly in girls living in a hot spot of dioxin contamination in Vietnam.

Dioxin exposure and sexual dimorphism of gaze behavior in prepubertal Vietnamese children living in Da Nang, a hot spot for dioxin contamination.

Previous studies have reported that dioxin exposure alters sexual dimorphism of play behavior in pre-pubertal children. We aimed to investigate the effects of perinatal dioxin exposure, indicated by dioxins in breast milk, on sexual dimorphism of gaze behavior after adjusting for salivary testosterone (T). Participants were pre-pubertal children in a hot spot for dioxin contamination originating from herbicide spraying in Vietnam. We used eye tracking to assess gaze behavior in 172 children (100 boys and 72 girls) aged 8-9 years. Two sets of 15 pairs of pictures, one oriented towards boys and one oriented towards girls, containing 5 pairs of toy photos (non-biological stimuli) and 10 pairs of human line drawings (biological stimuli) were shown to all children. The total fixation duration for each picture was extracted using Tobii studio software and a feminine index of gaze behavior was defined as the ratio of the summed fixation duration for the girl- vs boy-oriented versions of each stimuli. When viewing non-biological stimuli, feminine index scores significantly increased with TCDD (ß = 0.294) in girls only. For biological stimuli, however, feminine index scores significantly increased with TEQ-PCDD/Fs (ß = 0.269) in boys and with TCDD in girls (ß = 0.286). These associations were significant even after adjusting for salivary T levels, which were inversely associated with some dioxin congeners in girls. In addition, increased feminine index scores for biological stimuli were associated with lower cognitive scores for hand-movement and word-order tests in boys and for face-recognition tests in girls examined at 5 years of age. In conclusion, these results suggest that perinatal dioxin exposure may increase visual interest in girl-oriented objects through impairment of cognitive abilities in pre-pubertal Vietnamese children. PCDD congeners were associated with gaze behavior independently of T levels in boys, while this was only the case for TCDD levels in girls.

Dopamine D1 receptor modulates hippocampal representation plasticity to spatial novelty.

The human hippocampus is critical for learning and memory. In rodents, hippocampal pyramidal neurons fire in a location-specific manner, forming relational representations of environmental cues. The importance of glutamatergic systems in learning and in hippocampal neural synaptic plasticity has been shown. However, the role of dopaminergic systems in the response of hippocampal neural plasticity to novel and familiar spatial stimuli remains unclear. To clarify this important issue, we recorded hippocampal neurons from dopamine D(1) receptor knock-out (D1R-KO) mice and their wild-type (WT) littermates under the manipulation of distinct spatial cues in a familiar and a novel environment. Here we report that in WT mice, the majority of place cells quickly responded to the manipulations of distal and proximal cues in both familiar and novel environments. In contrast, the influence of distal cues on spatial firing in D1R-KO mice was abolished. In the D1R-KO mice, the influence of proximal cues was facilitated in a familiar environment, and in a novel environment most of the place cells were less likely to respond to changes of spatial cues. Our results demonstrate that hippocampal neurons in mice can rapidly and flexibly encode information about space from both distal and proximal cues to cipher a novel environment. This ability is necessary for many types of learning, and lacking D1R can radically alter this learning-related neural activity. We propose that D1R is crucially implicated in encoding spatial information in novel environments, and influences the plasticity of hippocampal representations, which is important in spatial learning and memory.

Brain cortical mapping by simultaneous recording of functional near infrared spectroscopy and electroencephalograms from the whole brain during right median nerve stimulation.

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5-15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity.

Adverse effects of maternal dioxin exposure on fetal brain development before birth assessed by neonatal electroencephalography (EEG) leading to poor neurodevelopment; a 2-year follow-up study.

We previously reported the adverse effects of perinatal dioxin exposure on child neurodevelopment around a former US military airbase in Vietnam. In the present study, we investigated the effects of maternal dioxin exposure on fetal brain development, which may predict neurodevelopmental outcomes in early childhood. A total of 55 newborns with mothers from dioxin-contaminated areas were recruited in the prefecture hospital in Bien Hoa, Vietnam. Dioxins in maternal breast milk collected 1 month after birth were used as a maternal exposure marker. Relative powers and coherence were computed from neonatal electroencephalogram (EEG) records during active sleep stages. Relationships between the EEG parameters and dioxin exposure markers were analyzed using linear regression and a general linear model after adjusting for gestational age, body length, and head circumference of infants at birth. Using data from 47 infants whose neurodevelopment was examined in a 2-year follow-up study, associations between EEG parameters and neurodevelopment were analyzed after adjusting for confounding factors. On the right frontal and parietal regions, relative delta powers were significantly decreased, and relative alpha and beta powers were significantly increased with increasing dioxin exposure. Increases in delta power and decreases in alpha power on the right frontal and parietal regions were associated with an increase in language scores at 2 years of age. Furthermore, intra- and inter-hemispheric coherence in theta and alpha bands were positively and inversely correlated with dioxin exposure, respectively, and increased intra-coherence in the right hemisphere was associated with lower language scores. These findings suggest that prenatal dioxin exposure affects neuronal activity and functional connectivity between brain regions, and may lead to poor language development.

Willughbeia cochinchinensis prevents scopolamine-induced deficits in memory, spatial learning, and object recognition in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Willughbeia cochinchinensis (WC) has been used in Vietnamese traditional medicine for the treatment of dementia as well as diarrhea, heartburn, and cutaneous abscess and as a diuretic. AIM: Alzheimer's disease (AD) is one of the most prevalent diseases in elderly individuals. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors have been widely used to treat patients with AD. In the present study, we investigated anti-AChE and anti-BChE activities of a natural product, WC, for its potential applications in therapies to prevent/treat dementia. MATERIALS AND METHODS: First, compounds extracted from WC were tested for their AChE and BChE inhibitory activities in vitro. Second, in vivo behavioral experiments were performed to investigate the effects of WC at doses of 100, 150, and 200mg/kg on scopolamine (1.5mg/kg)-induced memory and cognitive deficits in mice. The behavior of mice treated with and without WC and/or scopolamine was tested using the Y-maze, Morris water maze, and novel object recognition task. RESULTS: The results of the in vitro assay demonstrated anti-AChE and anti-BChE activities of the compounds extracted from WC. The results of behavioral experiments showed that the administration of WC prevented 1) scopolamine-induced decrease in spontaneous alternation (%) behavior in the Y-maze, 2) scopolamine-induced deficits in spatial learning and memory in the Morris water maze, and 3) scopolamine-induced deficits in novel object recognition. These results indicate that WC prevents cognitive and memory deficits induced by scopolamine injection. CONCLUSIONS: Our findings suggest that WC may represent a novel candidate for the treatment of memory and cognitive deficits in humans with dementia.

Impacts of Perinatal Dioxin Exposure on Motor Coordination and Higher Cognitive Development in Vietnamese Preschool Children: A Five-Year Follow-Up.

Dioxin concentrations remain elevated in the environment and in humans residing near former US Air Force bases in South Vietnam. Our previous epidemiological studies showed adverse effects of dioxin exposure on neurodevelopment for the first 3 years of life. Subsequently, we extended the follow-up period and investigated the influence of perinatal dioxin exposure on neurodevelopment, including motor coordination and higher cognitive ability, in preschool children. Presently, we investigated 176 children in a hot spot of dioxin contamination who were followed up from birth until 5 years old. Perinatal dioxin exposure levels were estimated by measuring dioxin levels in maternal breast milk. Dioxin toxicity was evaluated using two indices; toxic equivalent (TEQ)-polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs) and concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Coordinated movements, including manual dexterity, aiming and catching, and balance, were assessed using the Movement Assessment Battery for Children, Second Edition (Movement ABC-2). Cognitive ability was assessed using the nonverbal index (NVI) of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). In boys, total test and balance scores of Movement ABC-2 were significantly lower in the high TEQ- PCDDs/Fs group compared with the moderate and low exposure groups. NVI scores and the pattern reasoning subscale of the KABC-II indicating planning ability were also significantly lower in the high TCDD exposure group compared with the low exposure group of boys. However, in girls, no significant differences in Movement ABC-2 and KABC-II scores were found among the different TEQ-PCDDs/Fs and TCDD exposure groups. Furthermore, in high risk cases, five boys and one girl highly exposed to TEQ-PCDDs/Fs and TCDD had double the risk for difficulties in both neurodevelopmental skills. These results suggest differential impacts of TEQ-PCDDs/Fs and TCDD exposure on motor coordination and higher cognitive ability, respectively. Moreover, high TEQ-PCDDs/Fs exposure combined with high TCDD exposure may increase autistic traits combined with developmental coordination disorder.

Perinatal dioxin exposure and the neurodevelopment of Vietnamese toddlers at 1 year of age.

Dioxin concentrations remain elevated in both the environment and in humans residing near former US Air Force bases in South Vietnam. This may potentially have adverse health effects, particularly on infant neurodevelopment. We followed 214 infants whose mothers resided in a dioxin-contaminated area in Da Nang, Vietnam, from birth until 1 year of age. Perinatal exposure to dioxins was estimated from toxic equivalent (TEQ) levels of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (PCDDs/Fs-TEQ), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TetraCDD) concentrations in breast milk. In infants, daily dioxin intake (DDI) was used as an index of postnatal exposure through breastfeeding. Neurodevelopment of toddlers was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). No significant differences in neurodevelopmental scores were exhibited for cognitive, language or motor functions between four exposure groups of PCDDs/Fs-TEQ or 2,3,7,8-TetraCDD. However, social-emotional scores were decreased in the high PCDDs/Fs-TEQ group and the high 2,3,7,8-TetraCDD group compared with those with mild exposure, after adjusting for confounding factors. Cognitive scores in the mild, moderate, and high DDI groups were significantly higher than those in low DDI group, but there were no differences in cognitive scores among the three higher DDI groups. These results suggest that perinatal exposure to dioxins may affect social-emotional development of 1-year-old toddlers, without diminishing global neurodevelopmental function.

Hippocampal place cell responses to distal and proximal cue manipulations in dopamine D2 receptor-knockout mice.

The human hippocampus is critical for learning and memory. In rodents, hippocampal pyramidal neurons fire in a location-specific manner and form relational representations of environmental cues. The important roles of dopaminergic D1 receptors in learning and in hippocampal neural synaptic plasticity in novel environments have been previously shown. However, the roles of D2 receptors in hippocampal neural plasticity in response to novel and familiar spatial stimuli remain unclear. In order to clarify this issue, we recorded from hippocampal neurons in dopamine D2 receptor-knockout (D2R-KO) mice and their wild-type (WT) littermates during manipulations of distinct spatial cues in familiar and novel environments. Here, we report that D2R-KO mice showed substantial deficits in place-cell properties (number of place cells, intra-field firing rates, spatial tuning, and spatial coherence). Furthermore, although place cells in D2R-KO mice responded to manipulations of distal and proximal cues in both familiar and novel environments in a manner that was similar to place cells in WT mice, place fields were less stable in the D . The axes represent the differences between the peak and the valley of each waveform of EL2 and EL3.2R-KO mice in the familiar environment, but not in the novel environment. The present results suggested that D2 receptors in the hippocampus are important for place response stability. The place-cell properties of D2R-KO mice were similar to aged animals, suggesting that the alterations of place-cell properties in aged animals might be ascribed partly to alterations in the D2R in the HF of aged animals.

Monkey pulvinar neurons fire differentially to snake postures.

There is growing evidence from both behavioral and neurophysiological approaches that primates are able to rapidly discriminate visually between snakes and innocuous stimuli. Recent behavioral evidence suggests that primates are also able to discriminate the level of threat posed by snakes, by responding more intensely to a snake model poised to strike than to snake models in coiled or sinusoidal postures (Etting and Isbell 2014). In the present study, we examine the potential for an underlying neurological basis for this ability. Previous research indicated that the pulvinar is highly sensitive to snake images. We thus recorded pulvinar neurons in Japanese macaques (Macaca fuscata) while they viewed photos of snakes in striking and non-striking postures in a delayed non-matching to sample (DNMS) task. Of 821 neurons recorded, 78 visually responsive neurons were tested with the all snake images. We found that pulvinar neurons in the medial and dorsolateral pulvinar responded more strongly to snakes in threat displays poised to strike than snakes in non-threat-displaying postures with no significant difference in response latencies. A multidimensional scaling analysis of the 78 visually responsive neurons indicated that threat-displaying and non-threat-displaying snakes were separated into two different clusters in the first epoch of 50 ms after stimulus onset, suggesting bottom-up visual information processing. These results indicate that pulvinar neurons in primates discriminate between poised to strike from those in non-threat-displaying postures. This neuronal ability likely facilitates behavioral discrimination and has clear adaptive value. Our results are thus consistent with the Snake Detection Theory, which posits that snakes were instrumental in the evolution of primate visual systems.