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The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders. This article is protected by copyright. All rights reserved.

Aim Anodal transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) is known as one of the useful applications for improving depressive symptoms or cognitive performance. Antidepressive effects by anodal tDCS over the left DLPFC are expected, but the neural mechanisms of these effects are still unclear. Further, in depression, reduced performance and left prefrontal hypofunction during verbal fluency task (VFT) are generally known. However, few studies have examined the effect of tDCS on the language-related cerebral network. We aimed to investigate whether anodal tDCS at the left DLPFC affects cognitive performance and the neural basis of verbal fluency. Methods Nineteen healthy volunteers participated in this study. The effects of tDCS on cognitive behavior and cerebral function were evaluated by 1) performance and accuracy of implicit/explicit motor learning task (serial reaction time task: SRTT/sequential finger-tapping task: SFTT), and 2) cerebral activation while the subjects were performing VFT by using a functional MRI protocol of a randomized sham-controlled, within-subjects cross-over design. Results Reaction times of implicit motor learning task were significantly faster by tDCS in comparison with sham. Further, language-related left prefrontal-parahippocampal-parietal activation was significantly less by tDCS compared with sham. Significant correlation was observed between shortened response time in SRTT and decreased cerebral activation during VFT by tDCS. Conclusion Anodal tDCS over the left DLPFC could improve cognitive behavior of implicit motor learning by improving brain function of the frontoparietal-parahippocampal region related to motor learning, as well as language-related regions. This article is protected by copyright. All rights reserved.

Exercise and sports are increasingly being implemented in the management of schizophrenia. The process of action perception is as important as that of motor execution for learning and acquiring new skills. Recent studies have suggested that body-selective extrastriate body area (EBA) in the posterior temporal-occipital cortex is involved not only in static visual perception of body parts but also in the planning, imagination, and execution of actions. However, functional abnormality of the EBA in schizophrenia has yet to be investigated. Using functional magnetic resonance imaging (fMRI) with a task designed to activate the EBA by sports-related actions, we aimed to elucidate functional abnormality of the EBA during observation of sports-related actions in patients with schizophrenia. Twelve schizophrenia patients and 12 age-sex-matched control participants participated in the study. Using sports-related motions as visual stimuli, we examined brain activations during observation of context-congruent actions relative to context-incongruent actions by fMRI. Compared with controls, the patients with schizophrenia demonstrated diminished activation in the EBA during observation of sports-related context-congruent actions. Furthermore, the EBA activation in patients was negatively correlated with the severity of negative and general psychopathology symptoms measured by the Positive and Negative Syndrome Scale. Dysfunction of the EBA might reflect a difficulty in representing dynamic aspects of human actions and possibly lead to impairments of simulation, learning, and execution of actions in schizophrenia.

Aim: Neuroimaging studies on biological motion have established the view that the posterior superior temporal sulcus (pSTS) is involved in detecting intention of others. Those studies have consistently reported other regions such as body-selective extrastriate body area (EBA) and motion-sensitive middle temporal, in close proximity to pSTS. Whether EBA responds only to static body parts or has a more extended role as part of a system for inferring intention of others has remained an elusive issue. The aim of the present study was to investigate the role of EBA in processing goal-directed actions. Methods: Twelve healthy volunteers participated in the present study. Using sports-related motions as visual stimuli, brain activations were examined during observation of goal-directed actions and non-goal-directed actions on functional magnetic resonance imaging. Results: Compared to non-goal-directed actions, goal-directed actions produced greater activations in EBA along with the mirror neuron system. Conclusions: EBA might contribute to understanding others' actions by representing the dynamic aspects of human motions.

Background Neuroimaging studies have demonstrated either reduced left-lateralized activation or reversed language dominance in schizophrenia. These findings of left hemispheric dysfunction could be attributed to language processing tasks, which activate mainly left hemispheric function. Recent functional magnetic resonance imaging studies reported right-lateralized temporal activation by human voice perception, but few studies have investigated activation by human voice in schizophrenia. We aimed to clarify the cerebral function of language processing in schizophrenia patients by considering cerebral activation of human voice perception. Methods Fourteen right-handed schizophrenia patients and 14 right-handed controls with matched handedness, sex, and education level were scanned by functional magnetic resonance imaging while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). Results Under the SEN-SND and SEN-rSEN contrasts including language processing, patients showed less activation of the left hemisphere than controls in the language-related fronto-tempo-parietal region, hippocampus, thalamus and cingulate gyrus. Under the rSEN-SND contrast including human voice perception, patients showed less activation than controls in the right-lateralized temporal cortices and bilateral posterior cingulate. Conclusions Our results indicate that schizophrenia patients have impairment of broader bilateral cortical-subcortical regions related to both the semantic network in the left hemisphere and the voice-specific network in the right hemisphere.

Recent neuroimaging studies have demonstrated abnormal central emotional processing in psychiatric disorders. The dopamine (DA) systems and serotonin (5-HT) systems are the main target of psychopharmacotherapy. DA D2 receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) are widely used in psychiatric practice. Investigating the effects of these drugs on emotional processing should lead to a better understanding of the pathophysiology and pharmacotherapy of neuropsychiatric disorders. We aimed to examine effects of dopaminergic and serotonergic manipulation on neural responses to unpleasant pictures in healthy volunteers using pharmacological fMRI. Thirteen healthy male subjects participated in a single-blind, randomized, placebo-controlled design study. Each subject participated in three fMRI sessions. In each session, participants were orally administered either 25 mg of sultopride or 50 mg of fluvoxamine or placebo prior to scanning, and neural responses to unpleasant and neutral pictures were recorded. Despite no significant differences being found in the subjective ratings of affective pictures across three sessions, compared to placebo, acute treatments of DA D2 receptor antagonists and SSRIs commonly attenuated the amygdala activity, although both treatments had slightly different modulatory effects on other components of the neural circuit of emotional processing. This study has shown that even acute treatment of drugs that manipulate neurotransmitter systems could affect brain activation associated with emotional processing in human brain. At the same time, our findings suggest that pharmacological fMRI could be a powerful tool for investigating the neurophysiological properties of drugs targeting neuropsychiatric disorders.

Objective Contactin-associated protein-like2 (CNTNAP2) is one of the risk markers in the pathogenesis of language impairment and thought disturbance, such as autism spectrum disorders and schizophrenia. Although recent neuroimaging studies have demonstrated that CNTNAP2 polymorphisms affect left-hemispheric function of language processing, no study has investigated the influence of these polymorphisms on right-hemispheric function involved in human voice perception, and handedness. We investigated whether CNTNAP2 polymorphisms (rs7794745 and rs2710102) affect voice-specific brain function and handedness. Method One hundred and eight healthy Japanese volunteers (74 right-handed and 34 non-right-handed) had their brain function examined while they were passively listening to reverse sentences (rSEN), identifiable non-vocal sounds (SND), and sentences (SEN). The study protocol was approved by Ethics Committee. After complete explanation of the study, written informed consent was obtained from all subjects. Data analysis of fMRI was performed with statistical parametric mapping software SPM8. Genomic DNA samples were extracted from peripheral blood using standard procedures. Since these SNPs are known as biological high-risk markers for ASD, epilepsy, mental retardation, schizophrenia, and cognitive impairment, we investigated the genotype of brain function in these 2 SNPs: (rs7794745 and rs2710102) in CNTNAP2. The genotyping of all subjects was determined in comparison with control DNA confirmed by sequencing in the SNP pattern. Genotype of rs7794745 is A/A, A/T, and T/T; that of rs2710102 is G/G, G/A, A/A. The genotypes were classified into A/A and A/T in rs7794745, and G/G and A carriers (G/A and A/A) in rs2710102, respectively. Results In full factorial design analysis, rs7794745 (A/A or A/T) A— rs2710102 (G/G or A carrier (A/G and A/A)) A— voice-specific response (rSEN or SND), the main effect of rs7794745 (A/A or A/T) was significantly revealed at the right middle frontal gyrus (MTG) and bilateral superior temporal gyrus (STG). This result suggests that rs7794745 genotype impacts on voice-specific brain function. Furthermore, interaction effect was significantly observed among MTG-STG activations by human voice perception, rs7794745 (A/A or A/T), and handedness. Conclusion CNTNAP2 polymorphisms could be one of the remarkable biomarkers verifying genetic influence in voice-specific brain function and handedness in psychiatric disorders.

Background/Aims Mazindol is known as one of the anorexiants for morbid obesity. According to previous study, the pharmacological property is similar to amphetamine, and this drug has an augmenting role of dopamine and serotonin by the inhibition of presynapse transporter. However, the neural basis of how mazindol acts on affective processing has been unclear. We investigated the cerebral response to nonverbal affective vocalisation to clarify the effect of mazindol by functional magnetic resonance imaging (fMRI). Methods 20 healthy subjects (11 males, 9 females: mean age: 28.2 years, SD=6.4) participated in this study. The study protocol was approved by the ethics committee of Nippon Medical School, and all subjects provided their informed consent. This experiment was performed by randomised controlled trial. Each subject underwent two fMRI experiments, taking either a placebo or 0.5 mg of mazindol 2 hours before the scan. For each subject, the two experiments were separated by at least 2 weeks. Event-related fMRI experiments were performed in this study. The subjects listened to 3 types of emotional sounds: happy, sad, and neutral sounds. Each subject judged whether the emotional valence was positive, negative, or neutral. Data analysis was performed by statistical parametric mapping (SPM8). Results As for fMRI accuracy, two-way repeated ANOVA (3 emotions×2 medications (placebo/mazindol)) showed no significant difference both in main effect of emotion (F (2, 76)=1.22, p>0.05), and in main effect of medication (placebo/mazindol: F (1, 38)=2.01, p>0.05). The fMRI experiment according to two-way repeated ANOVA showed significant difference both in main effect of emotion (F (2, 76)=60.7, p In cerebral response, two-way repeated ANOVA showed significant difference in main effect of emotion at the bilateral superior temporal gyrus, and left prefrontal gyrus (p Conclusion According to these results, cerebral function in vocal affective processing was changed by the action of madindol, especially in the area associated with dopaminergic neuron including medial frontal cortex and anterior cingulate.

International audience; The Montreal Affective Voices (MAVs) consist of a database of non-verbal affect bursts portrayed by Canadian actors, and high recognitions accuracies were observed in Canadian listeners. Whether listeners from other cultures would be as accurate is unclear. We tested for cross-cultural differences in perception of the MAVs: Japanese listeners were asked to rate the MAVs on several affective dimensions and ratings were compared to those obtained by Canadian listeners. Significant Group × Emotion interactions were observed for ratings of Intensity, Valence, and Arousal. Whereas Intensity and Valence ratings did not differ across cultural groups for sad and happy vocalizations, they were significantly less intense and less negative in Japanese listeners for angry, disgusted, and fearful vocal-izations. Similarly, pleased vocalizations were rated as less intense and less positive by Japanese listeners.These results demonstrate important cross-cultural differences in affec-tive perception not just of non-verbal vocalizations expressing positive affect (Sauter et al., 2010), but also of vocalizations expressing basic negative emotions.

Impaired self-monitoring and abnormalities of cognitive bias have been implicated as cognitive mechanisms of hallucination; regions fundamental to these processes including inferior frontal gyrus (IFG) and superior temporal gyrus (STG) are abnormally activated in individuals that hallucinate. A recent study showed activation in IFG-STG to be modulated by auditory attractiveness, but no study has investigated whether these IFG-STG activations are impaired in schizophrenia. We aimed to clarify the cerebral function underlying the perception of auditory attractiveness in schizophrenia patients. Cerebral activation was examined in 18 schizophrenia patients and 18 controls when performing Favorability Judgment Task (FJT) and Gender Differentiation Task (GDT) for pairs of greetings using event-related functional MRI. A full-factorial analysis revealed that the main effect of task was associated with activation of left IFG and STG. The main effect of Group revealed less activation of left STG in schizophrenia compared with controls, whereas significantly greater activation in schizophrenia than in controls was revealed at the left middle frontal gyrus (MFG), right temporo-parietal junction (TPJ), right occipital lobe, and right amygdala (p

We have developed a new educational/clinical ontology named the "Haghighi-Koeda Mood Disorder Ontology", which involves both medical and psychological approaches for mood disorders in order to promote the exchange of information between psychiatrists and psychologists. Data was gathered from more than 5000 articles published in journals and websites specialized in life science. We evaluated and selected articles which were related to 4 main categories of mood disorders. Using Protege 3.4 beta, information related to mood disorders was classified by class/subclass tree in an ontological structure. Then we developed a web-based interface system on the internet enabling the implementation of the ontology. In addition, we have designed an online scale for automated diagnosis of mood disorder. For evaluating experiments, we compare this ontology with "Decisionbase" of which content deals with mood disorders. Evaluation was in accordance with our selected criteria via the AHP (Analysis of Hierarchical Processing) method. The results demonstrated the noteworthy superiority of our ontology. We believe that combining knowledge of medical science with that in psychological fields is a key to improving the quality of diagnosis and promoting appropriate treaTMent in all psychiatric disorders.

Comprehending conversation in a crowd requires appropriate orienting and sustainment of auditory attention to and discrimination of the target speaker. While a multitude of cognitive functions such as voice perception and language processing work in concert to subserve this ability, it is still unclear which cognitive components critically determine successful discrimination of speech sounds under constantly changing auditory conditions. To investigate this, we present a functional magnetic resonance imaging (fMRI) study of changes in cerebral activities associated with varying challenge levels of speech discrimination. Subjects participated in a diotic listening paradigm that presented them with two news stories read simultaneously but independently by a target speaker and a distracting speaker of incongruent or congruent sex. We found that the voice of distracter of congruent rather than incongruent sex made the listening more challenging, resulting in enhanced activities mainly in the left temporal and frontal gyri. Further, the activities at the left inferior, left anterior superior and right superior loci in the temporal gyrus were shown to be significantly correlated with accuracy of the discrimination performance. The present results suggest that the subregions of bilateral temporal gyri play a key role in the successful discrimination of speech under constantly changing auditory conditions as encountered in daily life.

Neuroimaging studies have demonstrated that the brain regions implicated in moral cognition. However, those studies have focused exclusively on violation of social norms and negative moral emotions, and very little effort has been expended on the investigation of positive reactions to moral excellence. It remains unclear whether the brain regions implicated in moral cognition have specific roles in processing moral violation or, more generally, process human morality per se. Using functional magnetic resonance imaging, brain activations during evaluation of moral beauty and depravity were investigated. Praiseworthiness for moral beauty was associated with activation in the orbitofrontal cortex, whereas blameworthiness for moral depravity was related to the posterior superior temporal sulcus. Humans might have developed different neurocognitive systems for evaluating blameworthiness and praiseworthiness. The central process of moral beauty evaluation might be related to that of aesthetic evaluation. Our finding might contribute to a better understanding of human morality.

We aimed to investigate the neural correlates associated with judgments of a positive self-conscious emotion, pride, and elucidate the difference between pride and a basic positive emotion, joy, at the neural basis level using functional magnetic resonance imaging. Study of the neural basis associated with pride might contribute to a better understanding of the pride-related behaviors observed in neuropsychiatric disorders. Sixteen healthy volunteers were studied. The participants read sentences expressing joy or pride contents during the scans. Pride conditions activated the right posterior superior temporal sulcus and left temporal pole, the regions implicated in the neural substrate of social cognition or theory of mind. However, against our prediction, we did not find brain activation in the medial prefrontal cortex, a region responsible for inferring others' intention or self-reflection. Joy condition produced activations in the ventral striatum and insula/operculum, the key nodes of processing of hedonic or appetitive stimuli. Our results support the idea that pride is a self-conscious emotion, requiring the ability to detect the intention of others. At the same time, judgment of pride might require less self-reflection compared with those of negative self-conscious emotions such as guilt or embarrassment.

Summary Objectives : In our previous functional magnetic resonance imaging (fMRI) study, we determined that there was distinct left hemispheric dominance for lexical- semantic processing without the influence of human voice perception in right-handed healthy subjects. However, the degree of right-handedness in the right-handed subjects ranged from 52 to 100 according to the Edinburgh Handedness Inventory (EHI) score. In the present study, we aimed to clarify the correlation between the degree of right-handedness and language dominance in the fronto-temporo-parietal cortices by examining cerebral activation for lexical-semantic processing. Methods : Twenty-seven normal right-handed healthy subjects were scanned by fMRI while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). Fronto-temporo-parietal activation was observed in the left hemisphere under the SEN - rSEN contrast, which included lexical- semantic processing without the influence of human voice perception. Laterality Indexwas calculated as LI = (L - R)/(L + R) X 100, L: left, R: right. Results : Laterality Index in the fronto-temporo-parietal cortices did not correlate with the degree of right-handedness in EHI score. Conclusions : The present study indicated that the degree of right-handedness from 52 to 100 in EHI score had no effect on the degree of left hemispheric dominance for lexical-semantic processing in right-handed healthy subjects.

Jealousy-related behaviors such as intimate partner violence and morbid jealousy are more common in males. Principal questionnaire studies suggest that men and women have different modules to process cues of sexual and emotional infidelity. We aimed to elucidate the neural response to sentences depicting sexual and emotional infidelity in men and women using functional magnetic resonance imaging. Although there was no sex difference in the self-rating score of jealousy for sexual and emotional infidelity, men and women showed different brain activation patterns in response to the two types of infidelity. During jealous conditions, men demonstrated greater activation than women in the brain regions involved in sexual/aggressive behaviors such as the amygdala and hypothalamus. In contrast, women demonstrated greater activation in the posterior superior temporal sulcus. Our fMRI results are in favor of the notion that men and women have different neuropsychological modules to process sexual and emotional infidelity. Our findings might contribute to a better understanding of the neural basis of the jealousy-related behaviors predominantly observed in males.

We aimed to investigate the neural substrates associated with evaluative process of moral emotions. Using functional magnetic resonance imaging (fMRI), we examined the similarities and differences between evaluative process of guilt and that of embarrassment at the neural basis level. Study of the neural basis of judgments of moral emotions might contribute to a better understanding of the amoral behavior observed in neurological and psychiatric disorders. Nineteen healthy volunteers were studied. The participants read sentences carrying neutral, guilty, or embarrassing contents during the scans. Both guilt and embarrassment conditions commonly activated the medial prefrontal cortex (MPFC), left posterior superior temporal sulcus (STS), and visual cortex. Compared to guilt condition, embarrassment condition produced greater activation in the right temporal cortex (anterior), bilateral hippocampus, and visual cortex. Most of these regions have been implicated in the neural substrate of social cognition or Theory of Mind (ToM). Our results support the idea that both are self-conscious emotions, which are social emotions requiring the ability to represent the mental states of others. At the same time, our functional fMRI data are in favor of the notion that evaluative process of embarrassment might be a more complex process than that of guilt.

Although emotional dysfunction is considered a fundamental symptom of schizophrenia, studies investigating the neural basis of emotional dysfunction in schizophrenia are few. Using functional magnetic resonance imaging (fMRI) and a task viewing affective pictures, we aimed to examine automatic emotional response and to elucidate the neural basis of impaired emotional processing in schizophrenia. Fifteen healthy volunteers and 15 schizophrenics were studied. During the scans, the subjects were instructed to indicate how each of the presented pictures made them feel. Whole brain activities in response to the affective pictures were measured by fMRI. Controls recruited the neural circuit including amygdaloid–hippocampal region, prefrontal cortex, thalamus, basal ganglia, cerebellum, midbrain, and visual cortex while viewing unpleasant pictures. Despite an equal behavioral result to controls, the patients showed less activation in the components of the circuit (right amygdala, bilateral hippocampal region, medial prefrontal cortex (MPFC), basal ganglia, thalamus, cerebellum, midbrain, and visual cortex). This study demonstrated functional abnormalities in the neural circuit of emotional processing in schizophrenia. In particular, decreased activation in the right amygdala and MPFC appears to be an important finding related to dysfunctional emotional behavior in schizophrenia.

Objective Post-concussion syndrome after traffic accident is often clinically associated with prolonged cognitive impairment due to brain lesions, but sometimes a symptom like amnesia may occur without structural abnormality in neuroimaging. The question is whether cognitive impairment may be caused by subtle lesions that cannot be detected with conventional structural MRI or CT. We report a case in which measurement of cognitive function with functional Magnetic Resonance Imaging (fMRI) was useful to assess the organic origin of an amnesic disorder after concussion. Method A 48 year old female suffered from prolonged memory disturbance after concussion. Her brain structural CT and MRI (T1 and T2) appeared normal. Her consciousness level was alert. Insomnia, physical anxiety, and depressive symptom were not observed. In order to investigate cerebral function with regards to memory processing, we carried out an fMRI study to test working memory (WM) for emotional voice stimuli from the Montreal Affective Voices. Furthermore, the neurobehavioral cognitive status was tested with a battery of neuropsychological tests (Cognistat). Results Brain structural CT and MRI were normal, however, the patient9s cerebral activation was significantly reduced in the bilateral hippocampi and left inferior frontal gyrus compared to 14 healthy control subjects in the WM vs Rest contrast. Furthermore, amnesic deficits were observed in Cognistat. Conclusion These results demonstrate that fMRI along with neuropsychological assessment is a useful tool to unravel organic origin of an amnesic disorder even if structural brain imaging appears normal.

Objective Although language and culture are different in each area in the world, how does culture affect the recognition of nonverbal emotional vocalisations? A previous study on non-verbal emotional vocalisations has shown a cross-cultural effect in Western and African participants. However, nobody has ever investigated the cross-cultural differences between Japanese and Caucasian participants in their emotional response to non-verbal vocal sounds. In the present study, we aimed to investigate cross-cultural effect between Caucasian subjects and Japanese subjects when the subjects listen to nonverbal affect bursts. Method 30 Japanese subjects (15 males) participated in this study. The data of Japanese subjects were compared with data from 30 Canadian subjects (15 males). Subjects listened to the Montreal Affective Voices (MAVs), which consist of a database of nonverbal affect bursts portrayed by Canadian actors. Each voice was evaluated using three criteria: perceived emotional intensity in each of the eight emotions (Anger, Disgust, Fear, Pain, Sadness, Surprise, Happiness, and Pleasure), perceived valence, and perceived arousal. To investigate cross-cultural differences between Japanese and Canadian participants, mixed 2×8 ANOVAs with Group (Japanese, Canadian) and Emotion (eight emotions) as factors were calculated on ratings of Intensity, Valence, and Arousal. Results Significant Group × Emotion interactions were observed for ratings of intensity, valence and arousal (intensity: F(5.5, 313.5) = 9.137, p Conclusion This study demonstrates important cross-cultural differences in the perception of non-verbal affect bursts and extends recent observations by showing that these cross-cultural differences are also found for negative emotions.