Toshio Munesue

Publications of Toshio Munesue

• Spatiotemporal frequency characteristics of cerebral oscillations during the perception of fundamental frequency contour changes in one-syllable intonation.

  Authors: Sanae Ueno, Eiichi Okumura, Gerard B Remijn, Yuko Yoshimura, Mitsuru Kikuchi, Kiyomi Shitamichi, Kikuko Nagao, Masayuki Mochiduki, Yasuhiro Haruta, Norio Hayashi, Toshio Munesue, Tsunehisa Tsubokawa, Manabu Oi, Hideo Nakatani, Haruhiro Higashida, Yoshio Minabe

  Neuroscience letters. 03/2012;

  Accurate perception of fundamental frequency (F0) contour changes in the human voice is important for understanding a speaker's intonation, and consequently also his/her attitude. In this study, weAccurate perception of fundamental frequency (F0) contour changes in the human voice is important for understanding a speaker's intonation, and consequently also his/her attitude. In this study, we investigated the neural processes involved in the perception of F0 contour changes in the Japanese one-syllable interjection "ne" in 21 native-Japanese listeners. A passive oddball paradigm was applied in which "ne" with a high falling F0 contour, used when urging a reaction from the listener, was randomly presented as a rare deviant among a frequent "ne" syllable with a flat F0 contour (i.e., meaningless intonation). We applied an adaptive spatial filtering method to the neuromagnetic time course recorded by whole-head magnetoencephalography (MEG) and estimated the spatiotemporal frequency dynamics of event-related cerebral oscillatory changes in the oddball paradigm. Our results demonstrated a significant elevation of beta band event-related desynchronization (ERD) in the right temporal and frontal areas, in time windows from 100 to 300 and from 300 to 500ms after the onset of deviant stimuli (high falling F0 contour). This is the first study to reveal detailed spatiotemporal frequency characteristics of cerebral oscillations during the perception of intonational (not lexical) F0 contour changes in the human voice. The results further confirmed that the right hemisphere is associated with perception of intonational F0 contour information in the human voice, especially in early time windows.

• Social memory, amnesia, and autism: Brain oxytocin secretion is regulated by NAD(+) metabolites and single nucleotide polymorphisms of CD38.

  Authors: Haruhiro Higashida, Shigeru Yokoyama, Jian-Jun Huang, Li Liu, Wen-Jie Ma, Shirin Akther, Chiharu Higashida, Mitsuru Kikuchi, Yoshio Minabe, Toshio Munesue

  Neurochemistry international. 02/2012;

  Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which isPreviously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C>A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C>T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD and in family members of three pedigrees with variable levels of ASD or ASD traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while two showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials.

• Language performance and auditory evoked fields in 2- to 5-year-old children.

  Authors: Yuko Yoshimura, Mitsuru Kikuchi, Kiyomi Shitamichi, Sanae Ueno, Gerard B Remijn, Yasuhiro Haruta, Manabu Oi, Toshio Munesue, Tsunehisa Tsubokawa, Haruhiro Higashida, Yoshio Minabe

  The European journal of neuroscience. 02/2012; 35(4):644-50.

  Language development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performedLanguage development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech-evoked responses during rapid-rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2- to 5-year-old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children.

• Oxytocin attenuates feelings of hostility depending on emotional context and individuals' characteristics.

  Authors: Tetsu Hirosawa, Mitsuru Kikuchi, Haruhiro Higashida, Eiichi Okumura, Sanae Ueno, Kiyomi Shitamichi, Yuko Yoshimura, Toshio Munesue, Tsunehisa Tsubokawa, Yasuhiro Haruta, Hideo Nakatani, Takanori Hashimoto, Yoshio Minabe

  Scientific reports. 01/2012; 2:384.

  In humans, oxytocin (OT) enhances prosocial behaviour. However, it is still unclear how the prosocial effects of OT are modulated by emotional features and/or individuals' characteristics. In aIn humans, oxytocin (OT) enhances prosocial behaviour. However, it is still unclear how the prosocial effects of OT are modulated by emotional features and/or individuals' characteristics. In a placebo-controlled design, we tested 20 healthy male volunteers to investigate these behavioural and neurophysiological modulations using magnetoencephalography. As an index of the individuals' characteristics, we used the empathy quotient (EQ), the autism spectrum quotient (AQ), and the systemising quotient (SQ). Only during the perception of another person's angry face was a higher SQ a significant predictor of OT-induced prosocial change, both in the behavioural and neurophysiological indicators. In addition, a lower EQ was only a significant predictor of OT-induced prosocial changes in the neurophysiological indicators during the perception of angry faces. Both on the behavioural and the neurophysiological level, the effects of OT were specific for anger and correlated with a higher SQ.

• CD38 and its role in oxytocin secretion and social behavior.

  Authors: Haruhiro Higashida, Shigeru Yokoyama, Mitsuru Kikuchi, Toshio Munesue

  Hormones and behavior. 12/2011;

  Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release,Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release, an essential component of social cognition. Herein we describe data detailing the molecular mechanism of CD38-dependent OXT secretion in CD38 knockout mice. We also review studies that used OXT, OXT receptor (OXTR), or CD38 knockout mice. Additionally, we compare the behavioral impairments that occur in these knockout mice in relation to the OXT system and CD38. This review also examines autism spectrum disorder (ASD), which is characterized by social and communication impairments, in relation to defects in the OXT system. Two single nucleotide polymorphisms (SNPs) in the human CD38 gene are possible risk factors for ASD via inhibition of OXT function. Further analysis of CD38 in relation to the OXT system may provide a better understanding of the neuroendocrinological roles of OXT and CD38 in the hypothalamus and of the pathophysiology of ASD.

• Lateralized theta wave connectivity and language performance in 2- to 5-year-old children.

  Authors: Mitsuru Kikuchi, Kiyomi Shitamichi, Yuko Yoshimura, Sanae Ueno, Gerard B Remijn, Tetsu Hirosawa, Toshio Munesue, Tsunehisa Tsubokawa, Yasuhiro Haruta, Manabu Oi, Haruhiro Higashida, Yoshio Minabe

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 10/2011; 31(42):14984-8.

  Recent neuroimaging studies support the view that a left-lateralized brain network is crucial for language development in children. However, no previous studies have demonstrated a clear link betweenRecent neuroimaging studies support the view that a left-lateralized brain network is crucial for language development in children. However, no previous studies have demonstrated a clear link between lateralized brain functional network and language performance in preschool children. Magnetoencephalography (MEG) is a noninvasive brain imaging technique and is a practical neuroimaging method for use in young children. MEG produces a reference-free signal, and is therefore an ideal tool to compute coherence between two distant cortical rhythms. In the present study, using a custom child-sized MEG system, we investigated brain networks while 78 right-handed preschool human children (32-64 months; 96% were 3-4 years old) listened to stories with moving images. The results indicated that left dominance of parietotemporal coherence in theta band activity (6-8 Hz) was specifically correlated with higher performance of language-related tasks, whereas this laterality was not correlated with nonverbal cognitive performance, chronological age, or head circumference. Power analyses did not reveal any specific frequencies that contributed to higher language performance. Our results suggest that it is not the left dominance in theta oscillation per se, but the left-dominant phase-locked connectivity via theta oscillation that contributes to the development of language ability in young children.

• Emotional responses associated with self-face processing in individuals with autism spectrum disorders: An fMRI study.

  Authors: Tomoyo Morita, Hirotaka Kosaka, Daisuke N Saito, Makoto Ishitobi, Toshio Munesue, Shoji Itakura, Masao Omori, Hidehiko Okazawa, Yuji Wada, Norihiro Sadato

  Social neuroscience. 09/2011;

  Individuals with autism spectrum disorders (ASD) show impaired emotional responses to self-face processing, but the underlying neural bases are unclear. Using functional magnetic resonance imaging,Individuals with autism spectrum disorders (ASD) show impaired emotional responses to self-face processing, but the underlying neural bases are unclear. Using functional magnetic resonance imaging, we investigated brain activity when 15 individuals with high-functioning ASD and 15 controls rated the photogenicity of self-face images and photographs of others' faces. Controls showed a strong correlation between photogenicity ratings and extent of embarrassment evoked by self-face images; this correlation was weaker among ASD individuals, indicating a decoupling between the cognitive evaluation of self-face images and emotional responses. Individuals with ASD demonstrated relatively low self-related activity in the posterior cingulate cortex (PCC), which was related to specific autistic traits. There were significant group differences in the modulation of activity by embarrassment ratings in the right insular (IC) and lateral orbitofrontal cortices. Task-related activity in the right IC was lower in the ASD group. The reduced activity in the right IC for self-face images was associated with weak coupling between cognitive evaluation and emotional responses to self-face images. The PCC is responsible for self-referential processing, and the IC plays a role in emotional experience. Dysfunction in these areas could contribute to the lack of self-conscious behaviors in response to self-reflection in ASD individuals.

• A Missense Mutation in CD38 Associated with Autism Spectrum Disorder in Three Pedigrees

  Authors: Haruhiro Higashida, Toshio Munesue, Shigeru Yokoyama, Minako Hashii, Keita Koizumi, Akihiro Matsushima

  08/2011;

  ISBN: 978-953-307-493-1

• 'Time slip' phenomenon in adolescents and adults with autism spectrum disorders: case series.

  Authors: Shinnichi Tochimoto, Koichi Kurata, Toshio Munesue

  Psychiatry and clinical neurosciences. 06/2011; 65(4):381-3.

  In recent years, it has been noticed that adolescent and adult patients with autism spectrum disorder (ASD) sometimes visit psychiatric medical institutions. In some cases, these patients commit anIn recent years, it has been noticed that adolescent and adult patients with autism spectrum disorder (ASD) sometimes visit psychiatric medical institutions. In some cases, these patients commit an act of violence and are dealt with by psychiatric emergency and forensic psychiatric services. In this report, we present two cases with ASD who visited a psychiatric emergency service because of the 'time slip' phenomenon, and discuss the clinical significance of this phenomenon.

• Hemodynamic responses to visual stimuli in cortex of adults and 3- to 4-year-old children.

  Authors: Gerard B Remijn, Mitsuru Kikuchi, Yuko Yoshimura, Kiyomi Shitamichi, Sanae Ueno, Kikuko Nagao, Toshio Munesue, Haruyuki Kojima, Yoshio Minabe

  Brain research. 02/2011; 1383:242-51.

  In this study we used near-infrared spectroscopy (NIRS) to measure relative changes in cortical hemodynamics from 19 adult and 19 preschool children (aged 3-4 years old), while they watched epochs ofIn this study we used near-infrared spectroscopy (NIRS) to measure relative changes in cortical hemodynamics from 19 adult and 19 preschool children (aged 3-4 years old), while they watched epochs of static and motion pictures extracted from TV programs. The spatio-temporal characteristics of oxygenated and deoxygenated hemoglobin volumes (oxy- and deoxy-Hb) of both subject groups were described and compared where appropriate for five regions of interest (ROIs). These were striate, left and right middle temporal, and left and right temporo-parietal areas. Over these areas, deoxy-Hb volumes did not differ between both groups. Preschool data showed significant increases in oxy-Hb over striate, middle temporal and temporo-parietal areas in response to visual motion stimuli. Static stimuli caused a significant oxy-Hb increase over striate and left middle temporal areas. Surprisingly, changes in adult oxy-Hb were not profound and did not show a significant oxy-Hb increase in striate and middle temporal areas in response to the motion stimuli, warranting further research. In spite of oxy-Hb volume differences, oxy-Hb recovery to baseline followed a similar pattern in both groups in response to both static and motion stimuli. Together, the results suggest that near-infrared spectroscopy is a viable method to investigate cortical development of preschool children by monitoring their hemodynamic response patterns.

• EEG microstate analysis in drug-naive patients with panic disorder.

  Authors: Mitsuru Kikuchi, Thomas Koenig, Toshio Munesue, Akira Hanaoka, Werner Strik, Thomas Dierks, Yoshifumi Koshino, Yoshio Minabe

  PloS one. 01/2011; 6(7):e22912.

  Patients with panic disorder (PD) have a bias to respond to normal stimuli in a fearful way. This may be due to the preactivation of fear-associated networks prior to stimulus perception. Based onPatients with panic disorder (PD) have a bias to respond to normal stimuli in a fearful way. This may be due to the preactivation of fear-associated networks prior to stimulus perception. Based on EEG, we investigated the difference between patients with PD and normal controls in resting state activity using features of transiently stable brain states (microstates). EEGs from 18 drug-naive patients and 18 healthy controls were analyzed. Microstate analysis showed that one class of microstates (with a right-anterior to left-posterior orientation of the mapped field) displayed longer durations and covered more of the total time in the patients than controls. Another microstate class (with a symmetric, anterior-posterior orientation) was observed less frequently in the patients compared to controls. The observation that selected microstate classes differ between patients with PD and controls suggests that specific brain functions are altered already during resting condition. The altered resting state may be the starting point of the observed dysfunctional processing of phobic stimuli.

• CD38 gene knockout juvenile mice: a model of oxytocin signal defects in autism.

  Authors: Haruhiro Higashida, Shigeru Yokoyama, Toshio Munesue, Mitsuru Kikuchi, Yoshio Minabe, Olga Lopatina

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1369-72.

  Oxytocin (OXT) in the hypothalamus is the biological basis of social recognition, trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an important role in the hypothalamus in theOxytocin (OXT) in the hypothalamus is the biological basis of social recognition, trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an important role in the hypothalamus in the process of OXT release in adult mice. Disruption of Cd38 (Cd38(-/-)) produced impairment of maternal behavior and male social recognition in mice, similar to the behavior observed in Oxt and OXT receptor (Oxtr) gene knockout (Oxt(-/-) and Oxtr(-/-), respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalization (USV) calls was lower in Cd38(-/-) than Cd38(+/+) pups. These phenotypes seemed to be caused by the high plasma OXT levels during development from neonates to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of differentiating plasma OXT. Contribution by breastfeeding was an important exogenous source for regulating plasma OXT before weaning by the presence of OXT in milk and the dam's mammary glands. The dissimilarity of Cd38(-/-) infant behaviour to Oxt(-/-) or Oxtr(-/-) mice can be explained partly by this exogenous source of OXT. These results suggest that secretion of OXT into the brain in a CD38-dependent manner may play an important role in the development of social behavior, and mice with OXT signalling deficiency, including Cd38(-/-), Oxt(-/-) and Oxtr(-/-) mice are good animal models for developmental disorders, such as autism.

• Neurovascular coupling in the human somatosensory cortex: a single trial study.

  Authors: Mitsuru Kikuchi, Kiyomi Shitamichi, Sanae Ueno, Yuko Yoshimura, Gerard B Remijn, Kikuko Nagao, Toshio Munesue, Koichi Iiyama, Tsunehisa Tsubokawa, Yasuhiro Haruta, Yoshihiro Inoue, Katsumi Watanabe, Takanori Hashimoto, Haruhiro Higashida, Yoshio Minabe

  Neuroreport. 12/2010; 21(17):1106-10.

  Oscillations in the higher frequency range are closely related to regional brain hemodynamic changes. Here we investigated this neurovascular coupling in humans in response to electrical stimulationOscillations in the higher frequency range are closely related to regional brain hemodynamic changes. Here we investigated this neurovascular coupling in humans in response to electrical stimulation of the right median nerve. In a single-trial study, we simultaneously recorded hemodynamic fluctuations in the somatosensory cortex by near infrared spectroscopy and brain neuronal oscillations by whole-head magnetoencephalography (MEG). The results from six volunteers showed that neural fluctuations at β or γ-band power were correlated with hemodynamic fluctuation during stimulus conditions. These correlations were prominent with a time delay of 5-7 s. This study provides new direct evidence that hemodynamic onset lags specific neural oscillations in the order of seconds in human awake conditions using noninvasive methods.

• Two genetic variants of CD38 in subjects with autism spectrum disorder and controls.

  Authors: Toshio Munesue, Shigeru Yokoyama, Kazuhiko Nakamura, Ayyappan Anitha, Kazuo Yamada, Kenshi Hayashi, Tomoya Asaka, Hong-Xiang Liu, Duo Jin, Keita Koizumi [......] Minako Hashii, Sarwat Amina, Fabio Malavasi, Eric J Huang, Jiasheng Zhang, Nobuaki Shimizu, Takeo Yoshikawa, Akihiro Matsushima, Yoshio Minabe, Haruhiro Higashida

  Neuroscience research. 06/2010; 67(2):181-91.

  The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play aThe neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.

• Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders.

  Authors: Hirotaka Kosaka, Masao Omori, Toshio Munesue, Makoto Ishitobi, Yukiko Matsumura, Tetsuya Takahashi, Kousuke Narita, Tetsuhito Murata, Daisuke N Saito, Hitoshi Uchiyama, Tomoyo Morita, Mitsuru Kikuchi, Kimiko Mizukami, Hidehiko Okazawa, Norihiro Sadato, Yuji Wada

  NeuroImage. 05/2010; 50(4):1357-63.

  Enlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with PDD haveEnlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with PDD have abnormally enlarged brain volumes. However, little is known about brain volume abnormalities in young adults with PDD. We explored gray matter (GM) volume in young adults with PDD. T1-weighted volumetric images were acquired with a 3-T magnetic resonance scanner from 32 males with high-functioning PDD (23.8+/-4.2 years; Full Scale Intelligence Quotient [FSIQ]=101.6+/-15.6) and 40 age-matched normal male control subjects (22.5+/-4.3 years; FSIQ=109.7+/-7.9). Regional GM volumes were compared between the two groups using voxel-based morphometry (VBM) with the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). Compared with the control group, the high-functioning PDD group showed significantly less GM in the right insula, the right inferior frontal gyrus, and the right inferior parietal lobule. A conservative threshold confirmed considerably smaller volumes in the right insula and inferior frontal gyrus. In these areas, negative correlations were found between Autism Spectrum Quotient scores and GM volume, although no significant correlations were found between each subject's FSIQ and GM volume. No regions showed greater GM volumes in the high-functioning PDD group. The insular cortex, which works as a relay area for multiple neurocognitive systems, may be one of the key regions underlying the complex clinical features of PDD. These smaller GM volumes in high-functioning PDD subjects may reflect the clinical features of PDD itself, rather than FSIQ.

• Heart rate variability in drug-naïve patients with panic disorder and major depressive disorder.

  Authors: Mitsuru Kikuchi, Akira Hanaoka, Tomokazu Kidani, Gerard Bastiaan Remijn, Yoshio Minabe, Toshio Munesue, Yoshifumi Koshino

  Progress in neuro-psychopharmacology & biological psychiatry. 09/2009;

  Power spectral analysis of electrocardiogram (ECG) R-R intervals is useful for the detection of autonomic dysfunction in various clinical disorders. Although both panic disorder (PD) and majorPower spectral analysis of electrocardiogram (ECG) R-R intervals is useful for the detection of autonomic dysfunction in various clinical disorders. Although both panic disorder (PD) and major depressive disorder (MDD) are known to have effects on the cardiac autonomic nervous system, no previous study has tested this among drug-naïve (i.e. no history of treatment) patients with MDD and PD in the same study. The purpose of this study was to compare cardiac autonomic functions among drug-naive patients with MDD and PD and those of healthy controls. Subjects were 17 drug-naïve PD patients, 15 drug-naïve MDD patients and 15 normal controls. ECGs were recorded under both supine resting and supine deep-breathing conditions (10-12 breaths/minute; 0.17-0.20 Hz). We measured the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. As expected, deep breathing induced an increase in HF power and a decrease in the LF/HF ratio in healthy controls. Compared to these controls, however, the MDD group had a lower response to regular deep breathing in LF power and in LF/HF ratio. PD patients showed intermediate results between normal controls and MDD patients. The results indicate that the reactivity to deep breathing revealed diminished cardiac autonomic reactivity in drug-naïve MDD patients.

• CD38 is critical for social behaviour by regulating oxytocin secretion.

  Authors: Duo Jin, Hong-Xiang Liu, Hirokazu Hirai, Takashi Torashima, Taku Nagai, Olga Lopatina, Natalia A Shnayder, Kiyofumi Yamada, Mami Noda, Toshihiro Seike [......] Naoya Noguchi, Ichiro Kato, Hiroshi Okamoto, Akihiro Matsushima, Alla Salmina, Toshio Munesue, Nobuaki Shimizu, Sumiko Mochida, Masahide Asano, Haruhiro Higashida

  Nature. 04/2007; 446(7131):41-5.

  CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show thatCD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.

• [Developmental expressive writing disorder]

  Authors: Toshio Munesue

  Ryōikibetsu shōkōgun shirīzu. 02/2003;

• [Mixed disorder of scholastic skills]

  Authors: Toshio Munesue

  Ryōikibetsu shōkōgun shirīzu. 02/2003;

• Excessive water drinking behavior in autism

  Authors: Katsuyuki Terai, Toshio Munesue, Michio Hiratani

  Brain and Development.

  The aim of this study was to determine the incidence of polydipsia in 49 autistic children, and also the influence of psychotropic drugs and residential factors on water drinking behavior, asThe aim of this study was to determine the incidence of polydipsia in 49 autistic children, and also the influence of psychotropic drugs and residential factors on water drinking behavior, as compared with in 89 mentally retarded children, in schools for mentally handicapped children in Fukui prefecture. Questionnaires were used to detect polydipsia and to assess the severity of the water drinking behavior in the autistic children and mentally retarded children. The incidence of polydipsia in the autistic children tended to be higher (P=0.074) than that in the retarded children. The severity of water drinking behavior was significantly higher in autism (P=0.022) than in mental retardation. The majority of the autistic children with polydipsia had been taking no psychotropic drugs. The incidence of polydipsia showed no significant difference between two residential situations, i.e. `not at home' and `at home'. The present study suggests that polydipsia or excessive water drinking behavior occurs more often in autism than in mental retardation, possibly due to some intrinsic factor in autism itself.