Noriaki Yahata

The University of Tokyo, Edo, Tōkyō, Japan

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Publications (45)154.83 Total impact

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    ABSTRACT: Recent studies have suggested oxytocin's therapeutic effects on deficits in social communication and interaction in autism spectrum disorder through improvement of emotion recognition with direct emotional cues, such as facial expression and voice prosody. Although difficulty in understanding of others' social emotions and beliefs under conditions without direct emotional cues also plays an important role in autism spectrum disorder, no study has examined the potential effect of oxytocin on this difficulty. Here, we sequentially conducted both a case-control study and a clinical trial to investigate the potential effects of oxytocin on this difficulty at behavioural and neural levels measured using functional magnetic resonance imaging during a psychological task. This task was modified from the Sally-Anne Task, a well-known first-order false belief task. The task was optimized for investigation of the abilities to infer another person's social emotions and beliefs distinctively so as to test the hypothesis that oxytocin improves deficit in inferring others' social emotions rather than beliefs, under conditions without direct emotional cues. In the case-control study, 17 males with autism spectrum disorder showed significant behavioural deficits in inferring others' social emotions (P = 0.018) but not in inferring others' beliefs (P = 0.064) compared with 17 typically developing demographically-matched male participants. They also showed significantly less activity in the right anterior insula and posterior superior temporal sulcus during inferring others' social emotions, and in the dorsomedial prefrontal cortex during inferring others' beliefs compared with the typically developing participants (P < 0.001 and cluster size > 10 voxels). Then, to investigate potential effects of oxytocin on these behavioural and neural deficits, we conducted a double-blind placebo-controlled crossover within-subject trial for single-dose intranasal administration of 24 IU oxytocin in an independent group of 20 males with autism spectrum disorder. Behaviourally, oxytocin significantly increased the correct rate in inferring others' social emotions (P = 0.043, one-tail). At the neural level, the peptide significantly enhanced the originally-diminished brain activity in the right anterior insula during inferring others' social emotions (P = 0.004), but not in the dorsomedial prefrontal cortex during inferring others' beliefs (P = 0.858). The present findings suggest that oxytocin enhances the ability to understand others' social emotions that have also required second-order false belief rather than first-order false beliefs under conditions without direct emotional cues in autism spectrum disorder at both the behaviour and neural levels.
    Brain : a journal of neurology. 08/2014;
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    ABSTRACT: The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.Molecular Psychiatry advance online publication, 29 July 2014; doi:10.1038/mp.2014.74.
    Molecular psychiatry. 07/2014;
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    ABSTRACT: Disturbances in semantic and phonological aspects of language processing are indicated in patients with schizophrenia, and in high-risk individuals for schizophrenia. To uncover neural correlates of the disturbances, a previous functional magnetic resonance imaging (fMRI) study using a visual lexical decision task in block design reported less leftward lateralization in the inferior frontal cortices, in patients with schizophrenia and individuals with high genetic risk for psychosis compared with normal control subjects. However, to our knowledge, no previous study has investigated contrasts between word and non-word processing that allow dissociation between semantic and phonological processing using event-related design visual lexical decision fMRI tasks in subjects with ultra-high-risk for psychosis (UHR) and patients with schizophrenia. In the current study, 20 patients with schizophrenia, 11 UHR, and 20 demographically matched controls underwent lexical decision fMRI tasks. Compared with controls, both schizophrenia and UHR groups showed significantly decreased activity in response to non-words compared with words in the inferior frontal regions. Additionally, decreased leftward lateralization in the non-word compared with word activity contrast was found in subjects with UHR compared with controls, which was not evident in patients with schizophrenia. The present findings suggest neural correlates of difficulty in phonological aspects of language processing during non-word processing in contrast to word, which at least partially commonly underlies the pathophysiology of schizophrenia and UHR. Together with a previous study in genetic high-risk subjects, the current results also suggest that reduced functional lateralization in the language-related frontal cortex may be a vulnerability marker for schizophrenia. Furthermore, the current result may suggest that the genetic basis of psychosis is presumed to be related to the evolution of the language capacity characteristic of humans.
    Schizophrenia Research 05/2014; · 4.59 Impact Factor
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    ABSTRACT: IMPORTANCE Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. OBJECTIVE To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. DESIGN, SETTING, AND PARTICIPANTS At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. INTERVENTIONS Single-dose intranasal administration of oxytocin (24 IU) and placebo. MAIN OUTCOMES AND MEASURES Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. RESULTS Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01). CONCLUSIONS AND RELEVANCE These findings provide the first neurobiological evidence for oxytocin's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.
    JAMA Psychiatry 12/2013; · 12.01 Impact Factor
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    ABSTRACT: Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in (1)H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent (1)H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in (1)H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.
    Schizophrenia Bulletin 09/2013; · 8.80 Impact Factor
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    ABSTRACT: A shorter duration of untreated psychosis in patients with schizophrenia results in better symptomatic and functional outcomes. Therefore, identifying biological markers in the early stages of psychosis is an important step toward early detection and intervention. Mismatch negativity (MMN) and P3a are leading candidate biomarkers. MMN measures differ in their sensitivity to varying deviants. However, this has not been fully addressed in assessing the early stages of psychosis. In the current study, we examined MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. To our knowledge, this is the first study that examined both MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. Participants consisted of 20 patients with first episode schizophrenia (FES), 21 ultra-high risk (UHR) individuals, and 22 healthy controls (HC). We measured dMMN/dP3a and fMMN/fP3a ERP components by means of a 64 electrodes-cap for EEG recording, and we used two-tone auditory oddball paradigms with 2000 stimuli. The amplitude of dMMN was significantly reduced in FES and UHR compared to HC. The amplitude of fMMN showed no significant difference among the three groups. The amplitudes of dP3a and fP3a were significantly reduced in FES and UHR compared to HC. These findings suggest that dMMN may have higher sensitivity than fMMN whereas dP3a and fP3a may have similar sensitivity in the early stages of psychosis.
    Schizophrenia Research 09/2013; · 4.59 Impact Factor
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    ABSTRACT: Sub-clinical autistic-like traits (ALTs) are continuously distributed in the general population and genetically linked to autism. Although identifying the neurogenetic backgrounds of ALTs might enhance our ability to identify those of autism, they are largely unstudied. Here, we have examined the neuroanatomical basis of ALTs and their association with the oxytocin receptor gene (OXTR) rs2254298A, a known risk allele for autism in Asian populations which has also been implicated in limbic-paralimbic brain structures. First, we extracted a four-factor structure of ALTs, as measured using the Autism-Spectrum Quotient, including "Prosociality", "Communication", "Details/patterns" and "Imagination" in 135 neurotypical adults (79 men, 56 women) to reduce the genetic heterogeneity of ALTs. Then, in the same population, voxel-based morphometry revealed that lower "Prosociality", which indicates strong ALTs, was significantly correlated with smaller regional gray matter volume in the right insula in males. Males with lower "Prosociality" also had less interregional structural coupling between the right insula and the ventral anterior cingulate cortex. Furthermore, males with OXTR rs2254298A had significantly smaller gray matter volume in the right insula. These results show that decreased volume of the insula is a neuroanatomical correlate of ALTs and a potential intermediate phenotype linking ALTs with OXTR in male subjects.
    Social Cognitive and Affective Neuroscience 08/2013; · 5.04 Impact Factor
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    ABSTRACT: Near-infrared spectroscopy (NIRS) is commonly used for studying human brain function. However, several studies have shown that superficial hemodynamic changes such as skin blood flow can affect the prefrontal NIRS hemoglobin (Hb) signals. To examine the criterion-related validity of prefrontal NIRS-Hb signals, we focused on the functional signals during a working memory (WM) task and investigated their similarity with blood-oxygen-level-dependent (BOLD) signals simultaneously measured by functional magnetic resonance imaging (fMRI). We also measured the skin blood flow with a laser Doppler flowmeter (LDF) at the same time to examine the effect of superficial hemodynamic changes on the NIRS-Hb signals. Correlation analysis demonstrated that temporal changes in the prefrontal NIRS-Hb signals in the activation area were significantly correlated with the BOLD signals in the gray matter rather than those in the soft tissue or the LDF signals. While care must be taken when comparing the NIRS-Hb signal with the extracranial BOLD or LDF signals, these results suggest that the NIRS-Hb signal mainly reflects hemodynamic changes in the gray matter. Moreover, the amplitudes of the task-related responses of the NIRS-Hb signals were significantly correlated with the BOLD signals in the gray matter across participants, which means participants with a stronger NIRS-Hb response showed a stronger BOLD response. These results thus provide supportive evidence that NIRS can be used to measure hemodynamic signals originating from prefrontal cortex activation.
    NeuroImage 06/2013; · 6.25 Impact Factor
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    ABSTRACT: Consumption of methamphetamine disturbs dopaminergic transmission and sometimes provokes schizophrenia-like-psychosis, named methamphetamine-associated psychosis (MAP). While previous studies have repeatedly reported regional volume reductions in the frontal and temporal areas as neuroanatomical substrates for psychotic symptoms, no study has examined whether such neuroanatomical substrates exist or not in patients with MAP. Magnetic resonance images obtained from twenty patients with MAP and 20 demographically-matched healthy controls (HC) were processed for voxel-based morphometry (VBM) using Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra. An analysis of covariance model was adopted to identify volume differences between subjects with MAP and HC, treating intracranial volume as a confounding covariate. The VBM analyses showed significant gray matter volume reductions in the left perisylvian structures, such as the posterior inferior frontal gyrus and the anterior superior temporal gyrus, and the frontopolar cortices, including its dorsomedial, ventromedial, dorsolateral, and ventrolateral portions, and white matter volume reduction in the orbitofrontal area in the patients with MAP compared with the HC subjects. The smaller regional gray matter volume in the medial portion of the frontopolar cortex was significantly correlated with the severe positive symptoms in the individuals with MAP. The volume reductions in the left perisylvian structure suggest that patients with MAP have a similar pathophysiology to schizophrenia, whereas those in the frontopolar cortices and orbitofrontal area suggest an association with antisocial traits or vulnerability to substance dependence.
    Schizophrenia Research 05/2013; · 4.59 Impact Factor
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    ABSTRACT: Social judgments often require resolution of incongruity in communication contents. Although previous studies revealed that such conflict resolution recruits brain regions including the medial prefrontal cortex (mPFC) and posterior inferior frontal gyrus (pIFG), functional relationships and networks among these regions remain unclear. In this functional magnetic resonance imaging study, we investigated the functional dissociation and networks by measuring human brain activity during resolving incongruity between verbal and nonverbal emotional contents. First, we found that the conflict resolutions biased by the nonverbal contents activated the posterior dorsal mPFC (post-dmPFC), bilateral anterior insula, and right dorsal pIFG, whereas the resolutions biased by the verbal contents activated the bilateral ventral pIFG. In contrast, the anterior dmPFC (ant-dmPFC), bilateral superior temporal sulcus, and fusiform gyrus were commonly involved in both of the resolutions. Second, we found that the post-dmPFC and right ventral pIFG were hub regions in networks underlying the nonverbal- and verbal-content-biased resolutions, respectively. Finally, we revealed that these resolution-type-specific networks were bridged by the ant-dmPFC, which was recruited for the conflict resolutions earlier than the two hub regions. These findings suggest that, in social conflict resolutions, the ant-dmPFC selectively recruits one of the resolution-type-specific networks through its interaction with resolution-type-specific hub regions.
    Social Cognitive and Affective Neuroscience 04/2013; · 5.04 Impact Factor
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    ABSTRACT: Functional near-infrared spectroscopy (fNIRS) is a relatively new technique that can measure hemoglobin changes in brain tissues, and its use in psychiatry has been progressing rapidly. Although it has several disadvantages (e.g., relatively low spatial resolution and the possibility of shallow coverage in the depth of brain regions) compared with other functional neuroimaging techniques (e.g., functional magnetic resonance imaging and positron emission tomography), fNIRS may be a candidate instrument for clinical use in psychiatry, as it can measure brain activity in naturalistic position easily and non-invasively. fNIRS instruments are also small and work silently, and can be moved almost everywhere including schools and care units. Previous fNIRS studies have shown that patients with schizophrenia have impaired activity and characteristic waveform patterns in the prefrontal cortex during the letter version of the verbal fluency task, and part of these results have been approved as one of the Advanced Medical Technologies as an aid for the differential diagnosis of depressive symptoms by the Ministry of Health, Labor and Welfare of Japan in 2009, which was the first such approval in the field of psychiatry. Moreover, previous studies suggest that the activity in the frontopolar prefrontal cortex is associated with their functions in chronic schizophrenia and is its next candidate biomarker. Future studies aimed at exploring fNIRS differences in various clinical stages, longitudinal changes, drug effects, and variations during different task paradigms will be needed to develop more accurate biomarkers that can be used to aid differential diagnosis, the comprehension of the present condition, the prediction of outcome, and the decision regarding treatment options in schizophrenia. Future fNIRS researches will require standardized measurement procedures, probe settings, analytical methods and tools, manuscript description, and database systems in an fNIRS community.
    Frontiers in Psychiatry 01/2013; 4:145.
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    ABSTRACT: Previous research suggests that deficits in attention-emotion interaction are implicated in schizophrenia symptoms. Although disruption in auditory processing is crucial in the pathophysiology of schizophrenia, deficits in interaction between emotional processing of auditorily presented language stimuli and auditory attention have not yet been clarified. To address this issue, the current study used a dichotic listening task to examine 22 patients with schizophrenia and 24 age-, sex-, parental socioeconomic background-, handedness-, dexterous ear-, and intelligence quotient-matched healthy controls. The participants completed a word recognition task on the attended side in which a word with emotionally valenced content (negative/positive/neutral) was presented to one ear and a different neutral word was presented to the other ear. Participants selectively attended to either ear. In the control subjects, presentation of negative but not positive word stimuli provoked a significantly prolonged reaction time compared with presentation of neutral word stimuli. This interference effect for negative words existed whether or not subjects directed attention to the negative words. This interference effect was significantly smaller in the patients with schizophrenia than in the healthy controls. Furthermore, the smaller interference effect was significantly correlated with severe positive symptoms and delusional behavior in the patients with schizophrenia. The present findings suggest that aberrant interaction between semantic processing of negative emotional content and auditory attention plays a role in production of positive symptoms in schizophrenia. (224 words).
    PLoS ONE 01/2013; 8(12):e83201. · 3.53 Impact Factor
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    ABSTRACT: The differential diagnosis of autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.
    NeuroImage. Clinical. 01/2013; 4:53-63.
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    ABSTRACT: Longitudinal clinical investigations and biological measurements have determined not only progressive brain volumetric and functional changes especially around the onset of psychosis but also the abnormality of developmental pathways based on gene-environment interaction model. However, these studies have contributed little to clinical decisions on their diagnosis and therapeutic choices because of subtle differences between patients and healthy controls. A multi-modal approach may resolve this limitation and is favorable to explore the pathophysiology of psychosis. The integrative neuroimaging studies for schizophrenia targeting early intervention and prevention (IN-STEP) is a research project aimed at exploring the pathophysiological features of the onset of psychosis and investigating possible predictive biomarkers for the clinical treatment of psychosis. Since 2008, we have adopted blood sampling, neurocognitive batteries, neurophysiological assessment, structural imaging, and functional imaging longitudinally for help-seeking ultra-high-risk (UHR) individuals and patients with first-episode psychosis (FEP). Here, we intend to introduce the IN-STEP research study protocol and present preliminary clinical findings. Thirty-seven UHR individuals and 30 patients with FEP participated in this study. Six months later, there was no difference in objective and subjective scores between the groups, which suggests that young people having symptoms and functional deficits should be cared for regardless of their history of psychosis according to their clinical stages. The rate of transition to psychosis was 7.1%, 8.0%, and 35.3% (at 6, 12, and 24months, respectively). Through this research project, we expect to clarify the pathophysiological features around the onset of psychosis and improve the prognosis of psychosis through clinical application.
    Schizophrenia Research 12/2012; · 4.59 Impact Factor
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    ABSTRACT: Recent studies have suggested an important role for Broca's region and its right hemisphere counterpart in the pathophysiology of schizophrenia, owing to its roles in language and interpersonal information processing. Broca's region consists of the pars opercularis (PO) and the pars triangularis (PT). Neuroimaging studies have suggested that they have differential functional roles in healthy individuals and contribute differentially to the pathogenesis of schizophrenic symptoms. However, volume changes in these regions in subjects with ultra-high risk for psychosis (UHR) or first-episode schizophrenia (FES) have not been clarified. In the present 3 Tesla magnetic resonance imaging study, we separately measured the gray matter volumes of the PO and PT using a reliable manual-tracing volumetry in 80 participants (20 with UHR, 20 with FES, and 40 matched controls). The controls constituted two groups: the first group was matched for age, sex, parental socioeconomic background, and intelligence quotient to UHR (n=20); the second was matched for those to FES (n=20). Compared with matched controls, the volume of the bilateral PT, but not that of the PO, was significantly reduced in the subjects with UHR and FES. The reduced right PT volume, which showed the largest effect size among regions-of-interest in the both UHR and FES groups, correlated with the severity of the positive symptoms also in the both groups. These results suggest that localized gray matter volume reductions of the bilateral PT represent a vulnerability to schizophrenia in contrast to the PO volume, which was previously found to be reduced in patients with chronic schizophrenia. The right PT might preferentially contribute to the pathogenesis of psychotic symptoms.
    Schizophrenia Research 03/2012; 137(1-3):124-31. · 4.59 Impact Factor
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    ABSTRACT: Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.
    Translational psychiatry. 01/2012; 2:e178.
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    ABSTRACT: Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information.
    PLoS ONE 01/2012; 7(6):e39561. · 3.53 Impact Factor
  • Biological psychiatry 08/2011; · 8.93 Impact Factor
  • Japanese Journal of Ophthalmology 06/2011; 55(5):588-90. · 1.27 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the effects of acute paroxetine administration on brain activity related to motivation. Sixteen healthy subjects participated in a randomized, single-blind, no-drug/placebo-controlled, cross-over study. After administration of no drug, placebo or paroxetine (selective serotonin reuptake inhibitor; 20 mg), subjects underwent functional magnetic resonance imaging while performing a monetary incentive delay task. We analyzed the differences in brain activities of the reward anticipation/motor preparation period that are subject to motivational modulation. For this purpose, we subdivided the incentive trials on the basis of whether the reaction times (RT) were slower or faster than the subject's mean RT (slow RT and fast RT trials). No drug and placebo showed robust activation differences in the globus pallidus and putamen for the fast RT trials compared to the slow RT trials, whereas paroxetine showed none. Paroxetine showed significantly lower activations in the globus pallidus, insula, putamen and dorsolateral prefrontal cortex compared to no drug in the fast RT trials. Paroxetine single acute administration diminished brain activity induced by motivation in healthy subjects. This may partially explain the increased lack of motivation seen in patients with relatively mild symptoms after taking a dose of paroxetine for the first time.
    Psychiatry and Clinical Neurosciences 03/2011; 65(2):191-8. · 2.04 Impact Factor

Publication Stats

441 Citations
154.83 Total Impact Points

Institutions

  • 2010–2014
    • The University of Tokyo
      • • Department of Neuropsychiatry
      • • Department of Neuroscience
      Edo, Tōkyō, Japan
  • 2013
    • Daiwa House Central Research Laboratory
      Edo, Tōkyō, Japan
    • Tokyo Metropolitan Matsuzawa Hospital
      • Department of Psychiatry
      Edo, Tōkyō, Japan
  • 2004–2010
    • Nippon Medical School
      • • Department of Pharmacology
      • • Department of Neuropsychiatry
      Tokyo, Tokyo-to, Japan
    • Tokyo Medical and Dental University
      • Department of Psychiatry and Behavioral Science
      Edo, Tōkyō, Japan
  • 2005–2008
    • National Institute of Radiological Sciences
      • Molecular Imagining Center
      Chiba-shi, Chiba-ken, Japan