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ABSTRACT: Whispered speech is often used in direct person-to-person communication as a means to confidentiality. Compared with normally vocalized speech, whispered speech is predominantly unvoiced, i.e., produced without vocal fold vibration, and has no clear fundamental frequency. By using near-infrared spectroscopy (NIRS), we assessed cortical hemodynamic response patterns to normally vocalized and whispered speech in adult listeners (n = 13). Stimuli consisted of 20-s strings of Japanese word associations spoken by a female voice. Average oxygenated hemoglobin values (oxy-Hb) were obtained over two regions of interest (ROIs). Results showed that oxy-Hb values during the perception of normally vocalized speech were highest over the left temporal ROI, but not significantly different from values measured over other ROIs. Oxy-Hb values during whispered speech were highest over the right temporal ROI and significantly higher (p < 0.05) than those obtained over the left temporal ROI. No significant differences, however, were found in oxy-Hb comparisons between normally vocalized and whispered speech, although the right temporal ROI comparison bordered on significance, with whisper inducing the higher value. Together, the results seem to suggest that whispered speech is a potent catalyst of cortical hemodynamic activity, especially over the right temporal cortex, in spite of its relatively modest sound level as compared to normal speech.
The Journal of the Acoustical Society of America 05/2013; 133(5):3606. · 1.55 Impact Factor
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Mitsuru Kikuchi,
Yuko Yoshimura,
Kiyomi Shitamichi,
Sanae Ueno,
Hirotoshi Hiraishi,
Toshio Munesue,
Tetsu Hirosawa,
Yasuki Ono,
Tsunehisa Tsubokawa,
Yoshihiro Inoue,
Manabu Oi,
Yo Niida,
Gerard B Remijn,
Tsutomu Takahashi,
Michio Suzuki,
Haruhiro Higashida, Yoshio Minabe
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ABSTRACT: Socio-communicative impairments are salient features of autism spectrum disorder (ASD) from a young age. The anterior prefrontal cortex (aPFC), or Brodmann area 10, is a key processing area for social function, and atypical development of this area is thought to play a role in the social deficits in ASD. It is important to understand these brain functions in developing children with ASD. However, these brain functions have not yet been well described under conscious conditions in young children with ASD. In the present study, we focused on the brain hemodynamic functional connectivity between the right and the left aPFC in children with ASD and typically developing (TD) children and investigated whether there was a correlation between this connectivity and social ability. Brain hemodynamic fluctuations were measured non-invasively by near-infrared spectroscopy (NIRS) in 3- to 7-year-old children with ASD (n = 15) and gender- and age-matched TD children (n = 15). The functional connectivity between the right and the left aPFC was assessed by measuring the coherence for low-frequency spontaneous fluctuations (0.01 - 0.10 Hz) during a narrated picture-card show. Coherence analysis demonstrated that children with ASD had a significantly higher inter-hemispheric connectivity with 0.02-Hz fluctuations, whereas a power analysis did not demonstrate significant differences between the two groups in terms of low frequency fluctuations (0.01 - 0.10 Hz). This aberrant higher connectivity in children with ASD was positively correlated with the severity of social deficit, as scored with the Autism Diagnostic Observation Schedule. This is the first study to demonstrate aberrant brain functional connectivity between the right and the left aPFC under conscious conditions in young children with ASD.
PLoS ONE 01/2013; 8(2):e56087. · 4.09 Impact Factor
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Mitsuru Kikuchi,
Yuko Yoshimura,
Kiyomi Shitamichi,
Sanae Ueno,
Tetsu Hirosawa,
Toshio Munesue,
Yasuki Ono,
Tsunehisa Tsubokawa,
Yasuhiro Haruta,
Manabu Oi,
Yo Niida,
Gerard B Remijn,
Tsutomu Takahashi,
Michio Suzuki,
Haruhiro Higashida, Yoshio Minabe
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ABSTRACT: A subset of individuals with autism spectrum disorder (ASD) performs more proficiently on certain visual tasks than may be predicted by their general cognitive performances. However, in younger children with ASD (aged 5 to 7), preserved ability in these tasks and the neurophysiological correlates of their ability are not well documented. In the present study, we used a custom child-sized magnetoencephalography system and demonstrated that preserved ability in the visual reasoning task was associated with rightward lateralisation of the neurophysiological connectivity between the parietal and temporal regions in children with ASD. In addition, we demonstrated that higher reading/decoding ability was also associated with the same lateralisation in children with ASD. These neurophysiological correlates of visual tasks are considerably different from those that are observed in typically developing children. These findings indicate that children with ASD have inherently different neural pathways that contribute to their relatively preserved ability in visual tasks.
Scientific Reports 01/2013; 3:1139.
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ABSTRACT: OBJECTIVE In schizophrenia, alterations within the prefrontal cortical GABA system appear to be most prominent in neurons that contain parvalbumin or somatostatin but not calretinin. The transcription factors Lhx6 and Sox6 play critical roles in the specification, migration, and maturation of parvalbumin and somatostatin neurons, but not calretinin neurons, and continue to be strongly expressed in this cell type-specific manner in the prefrontal cortex of adult humans. The authors investigated whether Lhx6 and/or Sox6 mRNA levels are deficient in schizophrenia, which may contribute to cell type-specific disturbances in cortical parvalbumin and somatostatin neurons. METHOD The authors used quantitative PCR and in situ hybridization with film and grain counting analyses to quantify mRNA levels in postmortem samples of prefrontal cortex area 9 of 42 schizophrenia subjects and 42 comparison subjects who had no psychiatric diagnoses in life, as well as antipsychotic-exposed monkeys. RESULTS In schizophrenia subjects, the authors observed lower mRNA levels for Lhx6, parvalbumin, somatostatin, and glutamate decarboxylase (GAD67; the principal enzyme in GABA synthesis), but not Sox6 or calretinin. Cluster analysis revealed that a subset of schizophrenia subjects consistently showed the most severe deficits in the affected transcripts. Grain counting analyses revealed that some neurons that normally express Lhx6 were not detectable in schizophrenia subjects. Finally, lower Lhx6 mRNA levels were not attributable to psychotropic medications or illness chronicity. CONCLUSIONS These data suggest that in a subset of individuals with schizophrenia, Lhx6 deficits may contribute to a failure of some cortical parvalbumin and somatostatin neurons to successfully migrate or develop a detectable GABA-ergic phenotype.
American Journal of Psychiatry 09/2012; · 12.54 Impact Factor
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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
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ABSTRACT: 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, 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 500 ms 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.
Neuroscience Letters 03/2012; 515(2):141-6. · 2.11 Impact Factor
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ABSTRACT: 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 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.
Neurochemistry International 02/2012; · 2.86 Impact Factor
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Yuko Yoshimura,
Mitsuru Kikuchi,
Kiyomi Shitamichi,
Sanae Ueno,
Gerard B Remijn,
Yasuhiro Haruta,
Manabu Oi,
Toshio Munesue,
Tsunehisa Tsubokawa,
Haruhiro Higashida, Yoshio Minabe
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ABSTRACT: Language 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.
European Journal of Neuroscience 02/2012; 35(4):644-50. · 3.63 Impact Factor
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ABSTRACT: The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV) or somatostatin (SST). Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+) channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K(+) channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35)S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.
PLoS ONE 01/2012; 7(8):e43904. · 4.09 Impact Factor
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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
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ABSTRACT: 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 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.
Scientific Reports 01/2012; 2:384.
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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
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ABSTRACT: 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 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.
Journal of Neuroscience 10/2011; 31(42):14984-8. · 7.11 Impact Factor
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Mitsuru Kikuchi,
Tetsu Hirosawa,
Masamichi Yokokura,
Shunsuke Yagi,
Norio Mori,
Etsuji Yoshikawa,
Yujiro Yoshihara,
Genichi Sugihara,
Kiyokazu Takebayashi,
Yasuhide Iwata,
Katsuaki Suzuki,
Kazuhiko Nakamura,
Takatoshi Ueki, Yoshio Minabe,
Yasuomi Ouchi
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ABSTRACT: Brain β-amyloid (Aβ) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral Aβ deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and Aβ deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [(18)F]FDG, Aβ deposits with [(11)C]PIB, and regional cerebral blood flow during control and working memory tasks by H(2)(15)O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of Aβ deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable Aβ deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people.
Journal of Neuroscience 08/2011; 31(31):11193-9. · 7.11 Impact Factor
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ABSTRACT: Schizophrenia has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical circuitry. Alterations in gamma band oscillations have attracted a great deal of interest as they appear to represent a pathophysiological process of cortical dysfunction in schizophrenia. Gamma band oscillations reflect local cortical activities, and the synchronization of these activities among spatially distributed cortical areas has been suggested to play a central role in the formation of networks. To assess global coordination across spatially distributed brain regions, Omega complexity (OC) in multichannel EEG was proposed. Using OC, we investigated global coordination of resting-state EEG activities in both gamma (30-50 Hz) and below-gamma (1.5-30 Hz) bands in drug-naïve patients with schizophrenia and investigated the effects of neuroleptic treatment. We found that gamma band OC was significantly higher in drug-naïve patients with schizophrenia compared to control subjects and that a right frontal electrode (F3) contributed significantly to the higher OC. After neuroleptic treatment, reductions in the contribution of frontal electrodes to global OC in both bands correlated with the improvement of schizophrenia symptomatology. The present study suggests that frontal brain processes in schizophrenia were less coordinated with activity in the remaining brain. In addition, beneficial effects of neuroleptic treatment were accompanied by improvement of brain coordination predominantly due to changes in frontal regions. Our study provides new evidence of improper intrinsic brain integration in schizophrenia by investigating the resting-state gamma band activity.
Biological Psychiatry 06/2011; 130(1-3):187-94. · 8.28 Impact Factor
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ABSTRACT: 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 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.
Brain research 02/2011; 1383:242-51. · 2.46 Impact Factor
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ABSTRACT: Adult neurogenesis in the mammalian brain is well-known to occur in the subgranular zone of the hippocampus. As the hippocampus is related to learning, memory, and emotions, adult hippocampal neurogenesis possibly contributes to these functions. Adult neurogenesis is modulated by polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids that are essential for normal brain development, maintenance, and function. They are reported to improve spatial learning and memory in rodents and cognitive functions in humans. However, detailed mechanisms of PUFA effects still remain obscure. PUFA are functionally linked with chaperons called fatty acid-binding proteins (FABP). FABP uptake and transport PUFA to different intracellular organelles. Intriguingly, PUFA were determined as ligands for G protein-coupled receptor 40 (GPR40), a cell membrane receptor abundantly expressed in the brain and the pancreas of primates. While the role of GPR40 in pancreatic β-cells is associated with insulin secretion, its role in the brain is not yet clarified presumably because of its absence in the rodent brain. The purpose of this review is to discuss the role of PUFA in adult neurogenesis, considering the role of GPR40 and FABP in the hippocampal neurogenic niche. Here, the authors would like to introduce a PUFA-GPR40 signaling pathway that is specific for the primate brain.
Journal of Pharmacological Sciences 01/2011; 116(2):163-72. · 2.08 Impact Factor
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ABSTRACT: 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 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.
Biological & Pharmaceutical Bulletin 01/2011; 34(9):1369-72. · 1.66 Impact Factor
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ABSTRACT: 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 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.
PLoS ONE 01/2011; 6(7):e22912. · 4.09 Impact Factor
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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
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[hide abstract]
ABSTRACT: 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 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.
Neuroreport 12/2010; 21(17):1106-10. · 1.66 Impact Factor
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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
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ABSTRACT: 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 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.
Neuroscience Research 06/2010; 67(2):181-91. · 2.25 Impact Factor
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Haruhiro Higashida,
Olga A. Lopatina,
T. Yoshihara,
Yu A. Pichugina,
Andrei A. Soumarokov,
Toshio Munesue, Yoshio Minabe,
Mitsuru Kikuchi,
Yasuki Ono,
N. Korshunova,
Alla B. Salmina
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ABSTRACT: Oxytocin in the hypothalamus is the biological basis of social recognition, trust, love and bonding. Previously, we showed that CD38, a proliferation marker in leukaemia cells, plays an important role in the hypothalamus in the process of oxytocin release in adult mice. Disruption of Cd38 (Cd38 (-/-)) elicited impairment of maternal behaviour and male social recognition in adult mice, similar to the behaviour observed in Oxt and oxytocin receptor (Oxtr) gene knockout (Oxt (-/-) and Oxtr (-/-), respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalisation calls was lower in Cd38 (-/-) than Cd38( +/+) pups. However, these behavioural changes were much milder than those observed in Oxt (-/-) and Oxtr (-/-) mice, indicating less impairment of social behaviour in Cd38 (-/-) pups. These phenotypes appeared to be caused by the high plasma oxytocin levels during development from the neonatal period 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 plasma oxytocin differentiation. Breastfeeding was an important exogenous source of plasma oxytocin regulation before weaning as a result of the presence of oxytocin in milk and the dam's mammary glands. The dissimilarity between Cd38 (-/-) infant behaviour and those of Oxt (-/-) or Oxtr (-/-) mice can be explained partly by this exogenous source of oxytocin. These results suggest that secretion of oxytocin into the brain in a CD38-dependent manner may play an important role in the development of social behaviour.
Journal of Neuroendocrinology 02/2010; · 3.14 Impact Factor
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ABSTRACT: 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 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-naïve 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/min; 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.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2009; 33(8):1474-8. · 3.25 Impact Factor
