Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model.

Fibromyalgia (FM) is an intractable disease with a chief complaint of chronic widespread pain. Amitriptyline (AMI) and duloxetine (DLX), which are antidepressant drugs, have been reported to ameliorate pain in patients with FM and pain-related behaviors in several rodent models of FM. However, the mechanisms of action of AMI and DLX are not yet fully understood. Here, we examined the effects of these drugs on the responsiveness of superficial dorsal horn (SDH) neurons in the spinal cord, using a rat FM model developed by injecting a biogenic amine depleter (reserpine). Extracellular recordings of SDH neurons in vivo demonstrated that bath application of AMI and DLX at concentrations of 0.1-1.0 mM on the dorsal surface of the spinal cord markedly suppressed spontaneous discharge and von Frey filament-evoked mechanical firing in SDH neurons. The suppression induced by the drugs was noted in a concentration-dependent manner and the suppressive effects resolved after washing the spinal cord surface. These results show that SDH neurons are the site of action for AMI and DLX in a rat reserpine-induced FM model. Spinal mechanisms may underlie the therapeutic effects of these drugs in patients with FM.

Regional activity and effective connectivity within the frontoparietal network during precision walking with visual cueing: an fNIRS study.

Precision walking (PW) incorporates precise step adjustments into regular walking patterns to navigate challenging surroundings. However, the brain processes involved in PW control, which encompass cortical regions and interregional interactions, are not fully understood. This study aimed to investigate the changes in regional activity and effective connectivity within the frontoparietal network associated with PW. Functional near-infrared spectroscopy data were recorded from adult subjects during treadmill walking tasks, including normal walking (NOR) and PW with visual cues, wherein the intercue distance was either fixed (FIX) or randomly varied (VAR) across steps. The superior parietal lobule (SPL), dorsal premotor area (PMd), supplementary motor area (SMA), and dorsolateral prefrontal cortex (dlPFC) were specifically targeted. The results revealed higher activities in SMA and left PMd, as well as left-to-right SPL connectivity, in VAR than in FIX. Activities in SMA and right dlPFC, along with dlPFC-to-SPL connectivity, were higher in VAR than in NOR. Overall, these findings provide insights into the roles of different brain regions and connectivity patterns within the frontoparietal network in facilitating gait control during PW, providing a useful baseline for further investigations into brain networks involved in locomotion.

Characteristics of auditory steady-state responses to different click frequencies in awake intact macaques.

BACKGROUND: Auditory steady-state responses (ASSRs) are periodic evoked responses to constant periodic auditory stimuli, such as click trains, and are suggested to be associated with higher cognitive functions in humans. Since ASSRs are disturbed in human psychiatric disorders, recording ASSRs from awake intact macaques would be beneficial to translational research as well as an understanding of human brain function and its pathology. However, ASSR has not been reported in awake macaques. RESULTS: Electroencephalograms (EEGs) were recorded from awake intact macaques, while click trains at 20-83.3 Hz were binaurally presented. EEGs were quantified based on event-related spectral perturbation (ERSP) and inter-trial coherence (ITC), and ASSRs were significantly demonstrated in terms of ERSP and ITC in awake intact macaques. A comparison of ASSRs among different click train frequencies indicated that ASSRs were maximal at 83.3 Hz. Furthermore, analyses of laterality indices of ASSRs showed that no laterality dominance of ASSRs was observed. CONCLUSIONS: The present results demonstrated ASSRs, comparable to those in humans, in awake intact macaques. However, there were some differences in ASSRs between macaques and humans: macaques showed maximal ASSR responses to click frequencies higher than 40 Hz that has been reported to elicit maximal responses in humans, and showed no dominant laterality of ASSRs under the electrode montage in this study compared with humans with right hemisphere dominance. The future ASSR studies using awake intact macaques should be aware of these differences, and possible factors, to which these differences were ascribed, are discussed.

Configural Cues Associated with Reward Elicit Theta Oscillations of Rat Retrosplenial Cortical Neurons Phase-Locked to LFP Theta Cycles.

Previous behavioral studies implicated the retrosplenial cortex (RSC) in stimulus-stimulus associations, and also in the retrieval of remote associative memory based on EEG theta oscillations. However, neural mechanisms involved in the retrieval of stored information of such associations and memory in the RSC remain unclear. To investigate the neural mechanisms underlying these processes, RSC neurons and local field potentials (LFPs) were simultaneously recorded from well-trained rats performing a cue-reward association task. In the task, simultaneous presentation of two multimodal conditioned stimuli (configural CSs) predicted a reward outcome opposite to that associated with the individual presentation of each elemental CS. Here, we show neurophysiological evidence that the RSC is involved in stimulus-stimulus association where configural CSs are discriminated from each elementary CS that is a constituent of the configural CSs, and that memory retrieval of rewarding CSs is associated with theta oscillation of RSC neurons during CS presentation, which is phase-locked to LFP theta cycles. The results suggest that cue (elementary and configural CSs)-reinforcement associations are stored in the RSC neural circuits, and are retrieved in synchronization with LFP theta rhythm.

A Parkinson's disease patient displaying increased neuromelanin-sensitive areas in the substantia nigra after rehabilitation with tDCS: a case report.

Previous studies have reported that transcranial direct current stimulation (tDCS) of the frontal polar area (FPA) ameliorated motor disability in patients with Parkinson's disease (PD). Here we report changes in neuromelanin (NM) imaging of dopaminergic neurons before and after rehabilitation combined with anodal tDCS over the FPA for 2 weeks in a PD patient. After the intervention, the patient showed clinically meaningful improvements while the NM-sensitive area in the SN increased by 18.8%. This case study is the first report of NM imaging of the SN in a PD patient who received tDCS.Abbreviations FPA: front polar area; PD: Parkinson's disease; NM: neuromelanin; DCI: DOPA decarboxylase inhibitor; STEF: simple test for evaluating hand function; TUG: timed up and go test; TMT: trail-making test; SN: substantia nigra; NM-MRI: neuromelanin magnetic resonance imaging; MCID: the minimal clinically important difference; SNpc: substantia nigra pars compacta; VTA: ventral tegmental area; LC: locus coeruleus; PFC: prefrontal cortex; M1: primary motor cortex; MDS: Movement Disorder Society; MIBG: 123I-metaiodobenzylguanidine; SBR: specific binding ratio; SPECT: single-photon emission computed tomography; DAT: dopamine transporter; NIBS: noninvasive brain stimulation; tDCS: transcranial direct current stimulation; MAOB: monoamine oxidase B; DCI: decarboxylase inhibitor; repetitive transcranial magnetic stimulation: rTMS; diffusion tensor imaging: DTI; arterial spin labeling: ASL.

Rat Retrosplenial Cortical Involvement in Wayfinding Using Visual and Locomotor Cues.

The retrosplenial cortex (RSC) has been implicated in wayfinding using different sensory cues. However, the neural mechanisms of how the RSC constructs spatial representations to code an appropriate route under different sensory cues are unknown. In this study, rat RSC neurons were recorded while rats ran on a treadmill affixed to a motion stage that was displaced along a figure-8-shaped track. The activity of some RSC neurons increased during specific directional displacements, while the activity of other neurons correlated with the running speed on the treadmill regardless of the displacement directions. Elimination of visual cues by turning off the room lights and/or locomotor cues by turning off the treadmill decreased the activity of both groups of neurons. The ensemble activity of the former group of neurons discriminated displacements along the common central path of different routes in the track, even when visual or locomotor cues were eliminated where different spatial representations must be created based on different sensory cues. The present results provide neurophysiological evidence of an RSC involvement in wayfinding under different spatial representations with different sensory cues.

High molecular weight amyloid ß1-42 oligomers induce neurotoxicity via plasma membrane damage.

Amyloid ß-protein (Aß) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high MW (HMW) aggregates such as protofibrils, and ultimately fibrils. These Aß species can generally form amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed to reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates amyloid oligomers in AD neuropathology, but the precise mechanisms are uncertain. We examined the mechanisms of neuronal dysfunction from HMW-Aß1-42 exposure by measuring membrane integrity, reactive oxygen species (ROS) generation, membrane lipid peroxidation, membrane fluidity, intracellular calcium regulation, passive membrane electrophysiological properties, and long-term potentiation (LTP). HMW-Aß1-42 disturbed membrane integrity by inducing ROS generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and impaired LTP. The damaging effects of HMW-Aß1-42 were significantly greater than those of LMW-Aß1-42. Therapeutic reduction of HMW-Aß1-42 may prevent AD progression by ameliorating direct neuronal membrane damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, T., Imamura, K., Inoue, H., Nakamura, S., Inoue, T., Kimura, A., Yano, S., Nishijo, H., Kiuchi, Y., Teplow, D. B., Ono, K. High molecular weight amyloid ß1-42 oligomers induce neurotoxicity via plasma membrane damage.

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.

Similarity in Neuronal Firing Regimes across Mammalian Species.

UNLABELLED: The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT: By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities.

Ingestion of dried-bonito broth (dashi) facilitates PV-parvalbumin-immunoreactive neurons in the brain, and affects emotional behaviors in mice.

OBJECTIVES: Emerging evidence suggests that traditional diets and nutrition have a significant impact on brain development, and could contribute to the promotion of mental health and prevention of psychiatric disorders in children and adolescents. Moreover, deficits in parvalbumin (PV)-immunoreactive and/or GABAergic neurons are closely associated with various psychiatric disorders in children and adolescents. To investigate the possible neural mechanisms of diet involvement in mental health, we analyzed the effects of dried-bonito dashi (Japanese fish broth) (DBD) on PV-immunoreactive neurons and emotional behaviors in young mice. METHODS: Male mice after weaning were fed DBD for 60 days, and tested with a resident-intruder test for aggressiveness and a forced swimming test for depression-like symptoms. After the behavioral testing, PV-immunoreactive neurons in the brain were immunohistochemically analyzed. RESULTS: The results indicated that DBD intake decreased aggressiveness and depression-like symptoms, and increased the densities of PV-immunoreactive neurons in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and superior colliculus. These behavioral changes were correlated with the densities of PV-immunoreactive neurons in the mPFC, amygdala, and hippocampus. However, subdiaphragmatic vagotomy did not affect the effects of DBD on emotional behaviors, although it nonspecifically decreased the densities of PV-immunoreactive neurons. DISCUSSION: The results suggest that DBD might modulate emotional behaviors by promoting PV-immunoreactive and/or GABAergic neuronal activity through parallel routes. The present results highlight a new mechanism for diet involvement in brain functions, and suggest that DBD might have therapeutic potential for the promotion of mental health.

Effects of high fat diet and perinatal dioxin exposure on development of body size and expression of platelet-derived growth factor receptor ß in the rat brain.

Environmental exposure to dioxins, consumption of a high fat diet, and platelet-derived growth factor receptor ß signaling in the brain affect feeding behavior, which is an important determinant of body growth. In the present study, we investigated the effects of prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fact diet after weaning on body growth and expression of platelet-derived growth factor receptor ß in the brain in rat pups. Subjects from the control and dioxin exposure groups were assigned to 1 of 3 different diet groups: standard diet, high fat diet in the juvenile period, or high fat diet in adulthood. Body weight gain rate in the juvenile high fat diet group and the length gain rate in the adult high fat diet group were greater than the corresponding values in the standard diet group only in male offspring, although the effects of dioxin exposure on growth were not significant. Consumption of a high fat diet decreased platelet-derived growth factor receptor ß levels in the amygdala and hippocampus in both sexes compared to control groups, while 2,3,7,8-tetrachlorodibenzo-p-dioxin decreased platelet-derived growth factor receptor platelet-derived growth factor receptor ß levels in the amygdala and striatum only in females receiving an high fat diet. Furthermore, platelet-derived growth factor receptor ß levels in the hippocampus and platelet-derived growth factor receptor ß striatum were inversely correlated with increases in body length, while changes in platelet-derived growth factor receptor ß in the amygdala and nucleus accumbens were significantly correlated to body weight gain or body mass index. In conclusion, these findings suggest that these 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fat diet-induced changes in body growth and feeding behaviors might be partially mediated by changes in brain platelet-derived growth factor receptor ß levels.

Effects of Perinatal Dioxin Exposure on Development of Children during the First 3 Years of Life.

OBJECTIVE: To investigate the longitudinal effects of perinatal exposure to dioxin on neurodevelopment and physical growth of a birth cohort during the first 3 years of life. STUDY DESIGN: A total of 217 mother-infant pairs living in a dioxin-contaminated area in Vietnam were followed up. Perinatal dioxin exposure of infants was estimated by the measurement of dioxin levels in breast milk of nursing mothers. Neurodevelopment of infants and children, including cognitive, language, and motor development, was determined at 4 months, 1 year, and 3 years of age. Physical growth, including weight, height, and head and abdominal circumferences, was measured at birth, 1 and 4 months, and 1 and 3 years of age. Multivariate mixed models were applied for analyzing repeated measures. RESULTS: In boys, composite motor and gross motor scores were decreased with increasing exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TetraCDD). The high toxic equivalent of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs-TEQ) group showed a significant decrease in expressive communication score. In girls, there was no decreased score in any neurodevelopment aspects in high-exposure groups. All body size measures in boys were decreased in the high-exposure groups of 2,3,7,8-TetraCDD and PCDDs/PCDFs-TEQ. In girls, high 2,3,7,8-TetraCDD and PCDDs/PCDFs-TEQ exposure was associated with increased head and abdominal circumferences. CONCLUSIONS: Perinatal dioxin exposure affects physical growth and neurodevelopment of infants and children in the first 3 years of life in a sex-specific manner.

Comparative anatomy of the arm muscles of the Japanese monkey (Macaca fuscata) with some comments on locomotor mechanics and behavior.

BACKGROUND: The anatomical literature on the genus Macaca has focused mainly on the rhesus monkey. However, some aspects in the positional behaviors of the Japanese monkey may be different from those in rhesus monkey, suggesting that the anatomical details of these species are divergent. METHODS: Four thoracic limbs of Macaca fuscata adults were dissected. RESULTS: The arm muscles in Japanese macaques are more similar to rhesus monkeys and Papio; these characteristics are closer to those of bearded capuchins than apes, indicating more proximity of this genus to New World primates. CONCLUSIONS: The anatomical features observed favor quadrupedal locomotor behaviors on the ground and in arboreal environments. Japanese monkeys, rhesus monkeys, and bearded capuchins, which share more primitive characteristics in their arm muscles, present features that favor both arboreal and quadrupedal locomotor behaviors, whereas apes, mainly Pan and Gorilla, which spend more time on the ground, present more quadrupedal specializations.

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.

The Development of Vibration System for Applying Magnetic Resonance Elastography (MRE) to the Supraspinatus Muscle.

Palpation is a standard clinical tool to diagnose abnormal stiffness changes in soft tissues. However, it is difficult to palpate the supraspinatus muscle because it locates under the trapezius muscle. The magnetic resonance elastography (MRE) uses harmonic mechanical excitation to quantitatively measure the stiffness (shear modulus) of both the superficial and deep tissues. The purpose of this study was to build a vibration system for applying the MRE to the supraspinatus muscle. In this study, a power amplifier and a pneumatic pressure generator were used to supply vibrations to a vibration pad. Six healthy volunteers underwent MRE. We investigated the effects of position (the head of the humerus and the trapezius muscle) of the vibration pad on the patterns of wave propagation (wave image). When the vibration pad was placed in the trapezius muscle, the wave images represented clear wave propagation. On the other hand, when the vibration pad was placed in the head of the humerus, the wave images represented unclear wave propagation. This result might be caused by wave interferences resulting from the vibrations from bones and an intramuscular tendon of the supraspinatus muscle. The mean shear modulus also was 8.12 ± 1.83 (mean ± SD) kPa, when the vibration pad was placed in the trapezius muscle. Our results demonstrated that the vibration pad should be placed in the trapezius muscle in the MRE of the supraspinatus muscle.

Phenolic compounds prevent the oligomerization of α-synuclein and reduce synaptic toxicity.

Lewy bodies, mainly composed of α-synuclein (αS), are pathological hallmarks of Parkinson's disease and dementia with Lewy bodies. Epidemiological studies showed that green tea consumption or habitual intake of phenolic compounds reduced Parkinson's disease risk. We previously reported that phenolic compounds inhibited αS fibrillation and destabilized preformed αS fibrils. Cumulative evidence suggests that low-order αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds (myricetin (Myr), curcumin, rosmarinic acid (RA), nordihydroguaiaretic acid, and ferulic acid) on αS oligomerization. Using methods such as photo-induced cross-linking of unmodified proteins, circular dichroism spectroscopy, the electron microscope, and the atomic force microscope, we showed that Myr and RA inhibited αS oligomerization and secondary structure conversion. The nuclear magnetic resonance analysis revealed that Myr directly bound to the N-terminal region of αS, whereas direct binding of RA to monomeric αS was not detected. Electrophysiological assays for long-term potentiation in mouse hippocampal slices revealed that Myr and RA ameliorated αS synaptic toxicity by inhibition of αS oligomerization. These results suggest that Myr and RA prevent the αS aggregation process, reducing the neurotoxicity of αS oligomers. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds on α-synuclein (αS) oligomerization. Phenolic compounds, especially Myricetin (Myr) and Rosmarinic acid (RA), inhibited αS oligomerization and secondary structure conversion. Myr and RA ameliorated αS synaptic toxicity on the experiment of long-term potentiation. Our results suggest that Myr and RA prevent αS aggregation process and reduce the neurotoxicity of αS oligomers. Phenolic compounds are good candidates of disease modifying drugs for α-synucleinopathies.

Dioxins and Nonortho PCBs in Breast Milk of Vietnamese Mothers Living in the Largest Hot Spot of Dioxin Contamination.

Bien Hoa Air Base is the largest dioxin contamination hot spot in Vietnam. In 2012, we recruited 216 mothers who were living in 10 communities around Bien Hoa Air Base and had delivered newborns at a prefecture hospital, and we investigated recent exposure levels of dioxins and nonortho PCBs in their breast milk. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) was present at 2.6 pg/g lipid in primiparae and 2.2 pg/g lipid in multiparae. Among multiparae and total subjects, significant high prevalence of 2,3,7,8-tetraCDD≥5 pg/g lipid and 2,3,7,8-tetraCDD contribution≥40% were observed in mothers living in the five communities closest to Bien Hoa Air Base. The TEQ for nonortho PCBs was 1.6 pg-TEQ/g lipid for primiparae, and this was even lower than that in the unsprayed area. The length of residency was a strong factor to increase dioxins, including 2,3,7,8-tetraCDD. Residency in the five communities with the highest exposure was a specific risk factor for increased 2,3,7,8-tetraCDD in breast milk. Food intake might contribute partly to the increased levels of dioxin congeners other than 2,3,7,8-tetraCDD in breast milk. These results suggest that Bien Hoa Air Base has led to elevated 2,3,7,8-tetraCDD levels in breast milk of mothers in nearby areas even in the recent years.

Selective Medial Prefrontal Cortex Responses During Live Mutual Gaze Interactions in Human Infants: An fNIRS Study.

To investigate the role of the prefrontal cortex (PFC) in processing multimodal communicative ostensive signals in infants, we measured cerebral hemodynamic responses by using near-infrared spectroscopy (NIRS) during the social interactive play "peek-a-boo", in which both visual (direct gaze) and auditory (infant-directed speech) stimuli were presented. The infants (mean age, around 7 months) sat on their mother's lap, equipped with an NIRS head cap, and looked at a partner's face during "peek-a-boo". An eye-tracking system simultaneously monitored the infants' visual fixation patterns. The results indicate that, when the partner presented a direct gaze, rather than an averted gaze, toward an infant during social play, the infant fixated on the partner's eye region for a longer duration. Furthermore, hemodynamic activity increased more prominently dorsomedial prefrontal cortex (mPFC) in response to social play with a partner's direct gaze compared to an averted gaze. In contrast, hemodynamic activity increased in the right dorsolateral prefrontal cortex (R-lPFC) regardless of a partner's eye gaze direction. These results indicate that a partner's direct gaze shifts an infant's attention to the partner's eyes for interactive communication, and specifically activates the mPFC. The differences in hemodynamic responses between the mPFC and R-lPFC suggest functional differentiation within the PFC, and a specific role of the mPFC in the perception of face-to-face communication, especially in mutual gaze, which is essential for social interaction.

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.