Hidehiko Takahashi

Publications (82)423.57 Total impact

• Article: Global Association Between Cortical Thinning and White Matter Integrity Reduction in Schizophrenia.

  Akihiko Sasamoto, Jun Miyata, Manabu Kubota, Kazuyuki Hirao, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Masaaki Hazama, Genichi Sugihara, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: Previous neuroimaging studies have revealed that both gray matter (GM) and white matter (WM) are altered in several morphological aspects in schizophrenia patients. Although several studies reported associations between GM and WM alterations in restricted regions, the existence of a global association between GM and WM pathologies is unknown. Considering the wide distribution of GM morphological changes and the profound genetic background of WM abnormalities, it would be natural to postulate a global association between pathologies of GM and WM in schizophrenia. In this investigation, we studied 35 schizophrenia patients and 35 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging (DTI) and investigated the association between GM thickness and WM fractional anisotropy (FA) as a proxy of pathology in each tissue. To investigate cortical thickness, surface-based analysis was used. The mean cortical thickness for the whole brain was computed for each hemisphere, and group comparisons were performed. For DTI data, mean FA for the whole brain was calculated, and group comparisons were performed. Subsequently, the correlation between mean cortical thickness and mean FA was investigated. Results showed that the mean cortical thickness was significantly thinner, and the mean FA was significantly lower in schizophrenia patients. Only in the patient group the mean cortical thickness and mean FA showed significant positive correlations in both hemispheres. This correlation remained significant even after controlling for demographic and clinical variables. Thus, our results indicate that the GM and WM pathologies of schizophrenia are intertwined at the global level.
  Schizophrenia Bulletin 03/2013; · 8.80 Impact Factor
• Article: Superiority illusion arises from resting-state brain networks modulated by dopamine.

  Makiko Yamada, Lucina Q Uddin, Hidehiko Takahashi, Yasuyuki Kimura, Keisuke Takahata, Ririko Kousa, Yoko Ikoma, Yoko Eguchi, Harumasa Takano, Hiroshi Ito, Makoto Higuchi, Tetsuya Suhara
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  ABSTRACT: The majority of individuals evaluate themselves as superior to average. This is a cognitive bias known as the "superiority illusion." This illusion helps us to have hope for the future and is deep-rooted in the process of human evolution. In this study, we examined the default states of neural and molecular systems that generate this illusion, using resting-state functional MRI and PET. Resting-state functional connectivity between the frontal cortex and striatum regulated by inhibitory dopaminergic neurotransmission determines individual levels of the superiority illusion. Our findings help elucidate how this key aspect of the human mind is biologically determined, and identify potential molecular and neural targets for treatment for depressive realism.
  Proceedings of the National Academy of Sciences 02/2013; · 9.68 Impact Factor
• Article: Acute NK1 receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers.

  Kanako Saji, Yumiko Ikeda, Woochan Kim, Yoshitoshi Shingai, Amane Tateno, Hidehiko Takahashi, Yoshiro Okubo, Haruhisa Fukayama, Hidenori Suzuki
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  ABSTRACT: The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK1) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK1 receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK1 receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK1 receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK1 receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.
  The International Journal of Neuropsychopharmacology 02/2013; · 4.58 Impact Factor
• Article: Regional gray matter reduction correlates with subjective quality of life in schizophrenia.

  Shiho Ubukata, Jun Miyata, Miho Yoshizumi, Teruhisa Uwatoko, Kazuyuki Hirao, Hironobu Fujiwara, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Manabu Kubota, Akihiko Sasamoto, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: Subjective quality of life (QOL) has been recognized as an important consideration in schizophrenia. Several symptoms and neurocognitive functions were shown to be correlated with subjective QOL; however its determinants are not well understood. In this study, we investigated the association between brain structural abnormalities and subjective QOL in patients with schizophrenia. Forty-five schizophrenia patients and 48 age, sex, and education-matched healthy participants underwent magnetic resonance imaging (MRI), and the Schizophrenia Quality of Life Scale (SQLS) was used to rate subjective QOL. We performed voxel-based morphometry (VBM) to investigate regional brain alterations. Relative to normal controls, schizophrenia patients exhibited gray matter reductions mainly in the frontal and temporal regions. Worse psychosocial subscale of SQLS was associated with gray matter (GM) reduction in the right dorsolateral prefrontal cortex (DLPFC), and worse motivation/energy subscale was associated with gray matter reduction in the left superior frontal sulcus, left parahippocampal gyrus, and the left inferior temporal gyrus. The correlation between DLPFC GM volume and psychosocial subscale of SQLS disappeared after controlling for severity of psychopathology, while the other correlations remained significant when controlled by demographic and clinical variables. Combining imaging techniques with psychosocial methods would help to elucidate those factors that are associated with QOL.
  Journal of psychiatric research 02/2013; · 3.72 Impact Factor
• Article: Effects of chewing on cognitive processing speed.

  Yoshiyuki Hirano, Takayuki Obata, Hidehiko Takahashi, Atsumichi Tachibana, Daigo Kuroiwa, Toru Takahashi, Hiroo Ikehira, Minoru Onozuka
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  ABSTRACT: In recent years, chewing has been discussed as producing effects of maintaining and sustaining cognitive performance. We have reported that chewing may improve or recover the process of working memory; however, the mechanisms underlying these phenomena are still to be elucidated. We investigated the effect of chewing on aspects of attention and cognitive processing speed, testing the hypothesis that this effect induces higher cognitive performance. Seventeen healthy adults (20-34years old) were studied during attention task with blood oxygenation level-dependent functional (fMRI) at 3.0 T MRI. The attentional network test (ANT) within a single task fMRI containing two cue conditions (no cue and center cue) and two target conditions (congruent and incongruent) was conducted to examine the efficiency of alerting and executive control. Participants were instructed to press a button with the right or left thumb according to the direction of a centrally presented arrow. Each participant underwent two back-to-back ANT sessions with or without chewing gum, odorless and tasteless to remove any effect other than chewing. Behavioral results showed that mean reaction time was significantly decreased during chewing condition, regardless of speed-accuracy trade-off, although there were no significant changes in behavioral effects (both alerting and conflict effects). On the other hand, fMRI analysis revealed higher activations in the anterior cingulate cortex and left frontal gyrus for the executive network and motor-related regions for both attentional networks during chewing condition. These results suggested that chewing induced an increase in the arousal level and alertness in addition to an effect on motor control and, as a consequence, these effects could lead to improvements in cognitive performance.
  Brain and Cognition 01/2013; · 3.17 Impact Factor
• Article: Influence of contact with schizophrenia on implicit attitudes towards schizophrenia patients held by clinical residents.

  Ataru Omori, Amane Tateno, Takashi Ideno, Hidehiko Takahashi, Yoshitaka Kawashima, Kazuhisa Takemura, Yoshiro Okubo
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  ABSTRACT: BACKGROUND: Patients with schizophrenia and their families have suffered greatly from stigmatizing effects. Although many efforts have been made to eradicate both prejudice and stigma, they still prevail even among medical professionals, and little is known about how contact with schizophrenia patients affects their attitudes towards schizophrenia. METHODS: We assessed the impact of the renaming of the Japanese term for schizophrenia on clinical residents and also evaluated the influence of contact with schizophrenia patients on attitudes toward schizophrenia by comparing the attitudes toward schizophrenia before and after a one-month clinical training period in psychiatry. Fifty-one clinical residents participated. Their attitudes toward schizophrenia were assessed twice, before and one month after clinical training in psychiatry using the Implicit Association Test (IAT) as well as Link's devaluation-discrimination scale. RESULTS: The old term for schizophrenia, "Seishin-Bunretsu-Byo", was more congruent with criminal than the new term for schizophrenia, "Togo-Shitcho-Sho", before clinical training. However, quite opposite to our expectation, after clinical training the new term had become even more congruent with criminal than the old term. There was no significant correlation between Link's scale and IAT effect. CONCLUSIONS: Renaming the Japanese term for schizophrenia still reduced the negative images of schizophrenia among clinical residents. However, contact with schizophrenia patients unexpectedly changed clinical residents' attitudes towards schizophrenia negatively. Our results might contribute to an understanding of the formation of negative attitudes about schizophrenia and assist in developing appropriate clinical training in psychiatry that could reduce prejudice and stigma concerning schizophrenia.
  BMC Psychiatry 11/2012; 12(1):205. · 2.55 Impact Factor
• Article: Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [11C]DASB and (S,S)-[18F]FMeNER-D2.

  Tsuyoshi Nogami, Harumasa Takano, Ryosuke Arakawa, Tetsuya Ichimiya, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Takeshi Sasaki, Keisuke Takahata, Masayuki Suzuki, Tomohisa Nagashima, Takaaki Mori, Hitoshi Shimada, Hajime Fukuda, Mizuho Sekine, Amane Tateno, Hidehiko Takahashi, Hiroshi Ito, Yoshiro Okubo, Tetsuya Suhara
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  ABSTRACT: Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported >80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [11C]DASB and (S,S)-[18F]FMeNER-D2, in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED50 was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupancies were observed in a dose-dependent manner. Both 5-HTT and NET occupancies were about 40% by milnacipran at 100 mg, the dose most commonly administered to MDD patients.
  The International Journal of Neuropsychopharmacology 10/2012; · 4.58 Impact Factor
• Article: Alexithymia and reduced white matter integrity in schizophrenia: A diffusion tensor imaging study on impaired emotional self-awareness.

  Manabu Kubota, Jun Miyata, Akihiko Sasamoto, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: Alexithymia is characterized by deficits in emotional self-awareness. A number of previous studies have revealed impaired emotional self-awareness in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, its relationship with alexithymia remains unclear. The present study investigated associations between alexithymia and white matter integrity, to seek the neural basis of impaired emotional self-awareness in schizophrenia. Forty-four patients with schizophrenia and 44 age-, gender- and predicted IQ level-matched healthy controls underwent diffusion-weighted imaging. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20). We applied tract-based spatial statistics to investigate the correlation between the TAS-20 total score and white matter fractional anisotropy (FA). TAS-20 scores were significantly higher in patients than in controls. In the patient group only, FA was negatively correlated with the TAS-20 total score in the corpus callosum, mostly the left part of the superior and inferior longitudinal fasciculi, the inferior occipito-frontal fasciculus, the anterior and posterior thalamic radiation, and the precuneus white matter. These results suggest that schizophrenia is associated with alexithymia, and that reduced white matter integrity within these regions constitutes an important pathology underlying impaired self-emotional awareness in schizophrenia.
  Biological Psychiatry 09/2012; 141(2-3):137-43. · 8.28 Impact Factor
• Article: Thalamocortical Disconnection in the Orbitofrontal Region Associated With Cortical Thinning in Schizophrenia.

  Manabu Kubota, Jun Miyata, Akihiko Sasamoto, Genichi Sugihara, Hidefumi Yoshida, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: CONTEXT Dysfunction of the thalamocortical pathway has been proposed as a putative underlying pathology of schizophrenia. Although the mechanisms involved remain unclear, postmortem studies suggest the involvement of altered neural projections from the thalamus to layers within the prefrontal cortex. OBJECTIVES To investigate thalamocortical connectivity in schizophrenia and to examine its possible association with cortical thinning in vivo. DESIGN Case-control cross-sectional study. SETTING Department of Psychiatry at Kyoto University Hospital, Japan. PATIENTS AND OTHER PARTICIPANTS A total of 37 patients with schizophrenia and 36 age-, sex-, and education-matched healthy controls recruited from the local community underwent diffusion-weighted imaging and T1-weighted 3-dimensional magnetic resonance imaging. MAIN OUTCOME MEASURES Probabilistic tractography was performed to investigate thalamocortical pathways. Group differences in mean fractional anisotropy (FA) values were examined in the entire thalamocortical pathway, the thalamolateral prefrontal pathway, the thalamomedial prefrontal pathway, and the thalamo-orbitofrontal pathway. Surface-based analysis was performed to investigate cortical thickness, and the correlation between FA values and cortical thickness was examined. RESULTS The patient group exhibited reduced FA values within the right thalamo-orbitofrontal pathway (P < .05 for the 8 group comparisons of FA, Bonferroni correction). In the patient group only, the mean FA value for this pathway was positively correlated with thickness of the right frontal polar and lateral orbitofrontal cortices (P < .05, clusterwise correction). CONCLUSIONS These results suggest that, in schizophrenia, regional thalamocortical white matter pathology is specifically associated with cortical pathology in regions where fibers connect.
  Archives of general psychiatry 09/2012; · 12.26 Impact Factor
• Article: Monoamines and assessment of risks.

  Hidehiko Takahashi
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  ABSTRACT: Over the past decade, neuroeconomics studies utilizing neurophysiology methods (fMRI or EEG) have flourished, revealing the neural basis of 'boundedly rational' or 'irrational' decision-making that violates normative theory. The next question is how modulatory neurotransmission is involved in these central processes. Here I focused on recent efforts to understand how central monoamine transmission is related to nonlinear probability weighting and loss aversion, central features of prospect theory, which is a leading alternative to normative theory for decision-making under risk. Circumstantial evidence suggests that dopamine tone might be related to distortion of subjective reward probability and noradrenaline and serotonin tone might influence aversive emotional reaction to potential loss.
  Current opinion in neurobiology 06/2012; · 7.21 Impact Factor
• Article: Quantification of dopamine transporter in human brain using PET with 18F-FE-PE2I.

  Takeshi Sasaki, Hiroshi Ito, Yasuyuki Kimura, Ryosuke Arakawa, Harumasa Takano, Chie Seki, Fumitoshi Kodaka, Saori Fujie, Keisuke Takahata, Tsuyoshi Nogami, Masayuki Suzuki, Hironobu Fujiwara, Hidehiko Takahashi, Ryuji Nakao, Toshimitsu Fukumura, Andrea Varrone, Christer Halldin, Toru Nishikawa, Tetsuya Suhara
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  ABSTRACT: (18)F-(E)-N-(3-iodoprop-2E-enyl)-2β-carbofluoroethoxy-3β-(4-methylphenyl)nortropane ((18)F-FE-PE2I) is a new PET radioligand with a high affinity and selectivity for the dopamine transporter (DAT). In nonhuman primates, (18)F-FE-PE2I showed faster kinetics and less production of radiometabolites that could potentially permeate the blood-brain barrier than did (11)C-PE2I. The aims of this study were to examine the quantification of DAT using (18)F-FE-PE2I and to assess the effect of radiometabolites of (18)F-FE-PE2I on the quantification in healthy humans. A 90-min dynamic PET scan was obtained for 10 healthy men after intravenous injection of (18)F-FE-PE2I. Kinetic compartment model analysis with a metabolite-corrected arterial input function was performed. The effect of radiometabolites on the quantification was evaluated by time-stability analyses. The simplified reference tissue model (SRTM) method with the cerebellum as a reference region was evaluated as a noninvasive method of quantification. After the injection of (18)F-FE-PE2I, the whole-brain radioactivity showed a high peak (∼3-5 standardized uptake value) and fast washout. The radioactive uptake of (18)F-FE-PE2I in the brain was according to the relative density of the DAT (striatum > midbrain > thalamus). The cerebellum showed the lowest uptake. Tissue time-activity curves were well described by the 2-tissue-compartment model (TCM), as compared with the 1-TCM, for all subjects in all regions. Time stability analysis showed stable estimation of total distribution volume with 60-min or longer scan durations, indicating the small effect of radiometabolites. Binding potentials in the striatum and midbrain were well estimated by the SRTM method, with modest intersubject variability. Although the SRTM method yielded a slight underestimation and overestimation in regions with high and low DAT densities, respectively, binding potentials by the SRTM method were well correlated to the estimates by the indirect kinetic method with 2-TCM. (18)F-FE-PE2I is a promising PET radioligand for quantifying DAT. The binding potentials could be reliably estimated in both the striatum and midbrain using both the indirect kinetic and SRTM methods with a scan duration of 60 min. Although radiometabolites of (18)F-FE-PE2I in plasma possibly introduced some effects on the radioactivity in the brain, the effects on estimated binding potential were likely to be small.
  Journal of Nuclear Medicine 06/2012; 53(7):1065-73. · 6.38 Impact Factor
• Article: Honesty mediates the relationship between serotonin and reaction to unfairness.

  Hidehiko Takahashi, Harumasa Takano, Colin F Camerer, Takashi Ideno, Shigetaka Okubo, Hiroshi Matsui, Yuki Tamari, Kazuhisa Takemura, Ryosuke Arakawa, Fumitoshi Kodaka, Makiko Yamada, Yoko Eguchi, Toshiya Murai, Yoshiro Okubo, Motoichiro Kato, Hiroshi Ito, Tetsuya Suhara
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  ABSTRACT: How does one deal with unfair behaviors? This subject has long been investigated by various disciplines including philosophy, psychology, economics, and biology. However, our reactions to unfairness differ from one individual to another. Experimental economics studies using the ultimatum game (UG), in which players must decide whether to accept or reject fair or unfair offers, have also shown that there are substantial individual differences in reaction to unfairness. However, little is known about psychological as well as neurobiological mechanisms of this observation. We combined a molecular imaging technique, an economics game, and a personality inventory to elucidate the neurobiological mechanism of heterogeneous reactions to unfairness. Contrary to the common belief that aggressive personalities (impulsivity or hostility) are related to the high rejection rate of unfair offers in UG, we found that individuals with apparently peaceful personalities (straightforwardness and trust) rejected more often and were engaged in personally costly forms of retaliation. Furthermore, individuals with a low level of serotonin transporters in the dorsal raphe nucleus (DRN) are honest and trustful, and thus cannot tolerate unfairness, being candid in expressing their frustrations. In other words, higher central serotonin transmission might allow us to behave adroitly and opportunistically, being good at playing games while pursuing self-interest. We provide unique neurobiological evidence to account for individual differences of reaction to unfairness.
  Proceedings of the National Academy of Sciences 02/2012; 109(11):4281-4. · 9.68 Impact Factor
• Source

  Available from: PubMed Central

  Article: Functional significance of central D1 receptors in cognition: beyond working memory.

  Hidehiko Takahashi, Makiko Yamada, Tetsuya Suhara
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  ABSTRACT: The role of dopamine D1 receptors in prefrontal cortex function, including working memory, is well acknowledged. However, relatively little is known about their role in other cognitive or emotional functions. We measured both D1 and D2 receptors in the brain using positron emission tomography in healthy subjects, with the aim of elucidating how regional D1 and D2 receptors are differentially involved in cognitive and emotional functions beyond working memory. We found an inverted U-shaped relation between prefrontal D1 receptor availability and Wisconsin Card Sorting Test performance, indicating that too little or too much D1 receptor stimulation impairs working memory or set shifting. In addition, variability of D1 receptor availability in the amygdala and striatum was related to individual differences in emotional responses and decision-making processes, respectively. These observations suggest that the variability of available D1 receptors might be associated with individual differences in brain functions that require phasic dopamine release. An interdisciplinary approach combining molecular imaging of dopamine neurotransmission with cognitive neuroscience and clinical psychiatry will provide new perspectives for understanding the neurobiology of neuropsychiatric disorders such as schizophrenia, addiction and Parkinson's disease, as well as novel therapeutics for cognitive impairments observed in them.
  Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 01/2012; 32(7):1248-58. · 5.46 Impact Factor
• Source

  Available from: Motoichiro Kato

  Article: Neural circuits in the brain that are activated when mitigating criminal sentences.

  Makiko Yamada, Colin F Camerer, Saori Fujie, Motoichiro Kato, Tetsuya Matsuda, Harumasa Takano, Hiroshi Ito, Tetsuya Suhara, Hidehiko Takahashi
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  ABSTRACT: In sentencing guilty defendants, jurors and judges weigh 'mitigating circumstances', which create sympathy for a defendant. Here we use functional magnetic resonance imaging to measure neural activity in ordinary citizens who are potential jurors, as they decide on mitigation of punishment for murder. We found that sympathy activated regions associated with mentalising and moral conflict (dorsomedial prefrontal cortex, precuneus and temporo-parietal junction). Sentencing also activated precuneus and anterior cingulate cortex, suggesting that mitigation is based on negative affective responses to murder, sympathy for mitigating circumstances and cognitive control to choose numerical punishments. Individual differences on the inclination to mitigate, the sentence reduction per unit of judged sympathy, correlated with activity in the right middle insula, an area known to represent interoception of visceral states. These results could help the legal system understand how potential jurors actually decide, and contribute to growing knowledge about whether emotion and cognition are integrated sensibly in difficult judgments.
  Nature Communications 01/2012; 3:759. · 7.40 Impact Factor
• Article: It's Not My Fault: Postdictive Modulation of Intentional Binding by Monetary Gains and Losses.

  Keisuke Takahata, Hidehiko Takahashi, Takaki Maeda, Satoshi Umeda, Tetsuya Suhara, Masaru Mimura, Motoichiro Kato
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  ABSTRACT: Sense of agency refers to the feeling that one's voluntary actions caused external events. Past studies have shown that compression of the subjective temporal interval between actions and external events, called intentional binding, is closely linked to the experience of agency. Current theories postulate that the experience of agency is constructed via predictive and postdictive pathways. One remaining problem is the source of human causality bias; people often make misjudgments on the causality of voluntary actions and external events depending on their rewarding or punishing outcomes. Although human causality bias implies that sense of agency can be modified by post-action information, convincing empirical findings for this issue are lacking. Here, we hypothesized that sense of agency would be modified by affective valences of action outcomes. To examine this issue, we investigated how rewarding and punishing outcomes following voluntary action modulate behavioral measures of agency using intentional binding paradigm and classical conditioning procedures. In the acquisition phase, auditory stimuli were paired with positive, neutral or negative monetary outcomes. Tone-reward associations were evaluated using reaction times and preference ratings. In the experimental session, participants performed a variant of intentional binding task, where participants made timing judgments for onsets of actions and sensory outcomes while playing simple slot games. Our results showed that temporal binding was modified by affective valences of action outcomes. Specifically, intentional binding was attenuated when negative outcome occurred, consistent with self-serving bias. Our study not only provides evidence for postdictive modification of agency, but also proposes a possible mechanism of human causality bias.
  PLoS ONE 01/2012; 7(12):e53421. · 4.09 Impact Factor
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  Available from: PubMed Central

  Article: Effect of cooperation level of group on punishment for non-cooperators: a functional magnetic resonance imaging study.

  Fumitoshi Kodaka, Hidehiko Takahashi, Makiko Yamada, Harumasa Takano, Kazuhiko Nakayama, Hiroshi Ito, Tetsuya Suhara
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  ABSTRACT: Sometimes we punish non-cooperators in our society. Such behavior could be derived from aversive emotion for inequity (inequity aversion) to make non-cooperators cooperative. Thus, punishing behavior derived from inequity is believed to be important for maintaining our society. Meanwhile, our daily experiences suggest that the degree of cooperation by the members of society (cooperation level of the group) could change the punishing behavior for non-cooperators even if the inequity were equal. Such effect of the cooperation level of the group cannot be explained by simple inequity aversion. Although punishment-related brain regions have been reported in previous functional magnetic resonance imaging (fMRI) study, little is known about such regions affected by the cooperation level of the group. In the present fMRI study, we investigated the effect of the cooperation level of the group on the punishing behavior for non-cooperators and its related brain activations by a paradigm in which the degree of the cooperative state varied from low to high. Punishment-related activations were observed in brain regions such as the anterior insula, dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). The quantity of punishment in a high cooperation context was greater than in a low cooperation context, and activation in the right DLPFC and ACC in a high cooperation context showed greater activity than in a low cooperation context. This indicates that the cooperation level of the group, as well as aversive emotion for inequity, is the important factor of punishing behavior.
  PLoS ONE 01/2012; 7(7):e41338. · 4.09 Impact Factor
• Article: Effects of Dopamine D(2) Receptor Partial Agonist Antipsychotic Aripiprazole on Dopamine Synthesis in Human Brain Measured by PET with L-[β-(11)C]DOPA.

  Hiroshi Ito, Harumasa Takano, Ryosuke Arakawa, Hidehiko Takahashi, Fumitoshi Kodaka, Keisuke Takahata, Tsuyoshi Nogami, Masayuki Suzuki, Tetsuya Suhara
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  ABSTRACT: Dopamine D(2) receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2) receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11)C]raclopride and L-[β-(11)C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2) receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2) receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.
  PLoS ONE 01/2012; 7(9):e46488. · 4.09 Impact Factor
• Article: Abnormal asymmetry of white matter integrity in schizophrenia revealed by voxelwise diffusion tensor imaging.

  Jun Miyata, Akihiko Sasamoto, Katja Koelkebeck, Kazuyuki Hirao, Keita Ueda, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Manabu Kubota, Hidenao Fukuyama, Nobukatsu Sawamoto, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right-handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract-based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 × (left - right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward-shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex.
  Human Brain Mapping 10/2011; 33(7):1741-9. · 5.88 Impact Factor
• Article: Transcultural differences in brain activation patterns during theory of mind (ToM) task performance in Japanese and Caucasian participants.

  Katja Koelkebeck, Kazuyuki Hirao, Ryousaku Kawada, Jun Miyata, Teruyasu Saze, Shiho Ubukata, Shoji Itakura, Yasuhiro Kanakogi, Patricia Ohrmann, Jochen Bauer, Anya Pedersen, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: Theory of mind (ToM) functioning develops during certain phases of childhood. Factors such as language development and educational style seem to influence its development. Some studies that have focused on transcultural aspects of ToM development have found differences between Asian and Western cultures. To date, however, little is known about transcultural differences in neural activation patterns as they relate to ToM functioning. EXPERIMENTAL METHODS: The aim of our study was to observe ToM functioning and differences in brain activation patterns, as assessed by functional magnetic resonance imaging (fMRI). This study included a sample of 18 healthy Japanese and 15 healthy Caucasian subjects living in Japan. We presented a ToM task depicting geometrical shapes moving in social patterns. We also administered questionnaires to examine empathy abilities and cultural background factors. Behavioral data showed no significant group differences in the subjects' post-scan descriptions of the movies. The imaging results displayed stronger activation in the medial prefrontal cortex (MPFC) in the Caucasian sample during the presentation of ToM videos. Furthermore, the task-associated activation of the MPFC was positively correlated with autistic and alexithymic features in the Japanese sample. In summary, our results showed evidence of culturally dependent sociobehavioral trait patterns, which suggests that they have an impact on brain activation patterns during information processing involving ToM.
  Social neuroscience 09/2011; 6(5-6):615-26. · 3.17 Impact Factor
• Article: Social impairment in schizophrenia revealed by Autism-Spectrum Quotient correlated with gray matter reduction.

  Akihiko Sasamoto, Jun Miyata, Kazuyuki Hirao, Hironobu Fujiwara, Ryosaku Kawada, Shinsuke Fujimoto, Yusuke Tanaka, Manabu Kubota, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi, Toshiya Murai
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  ABSTRACT: One of the difficulties facing schizophrenia patients is a failure to construct appropriate relationships with others in social situations. This impairment of social cognition is also found in autism-spectrum disorder (ASD). Considering such commonality between the two disorders, in this study we adopted the Autism-Spectrum Quotient (AQ) score to assess autistic traits, and explored the association between such traits and gray matter (GM) alterations of the brain in schizophrenia. Twenty schizophrenia patients and 25 healthy controls underwent structural magnetic resonance imaging (MRI), and AQ was assessed, comprising five subscales measuring different facets of autistic traits. Voxel-based morphometry (VBM) was applied to investigate the correlation between these AQ scores and regional GM alterations. Schizophrenia patients showed significantly higher scores in total AQ, and in four of the five subscales, compared to healthy controls. The total AQ score in schizophrenia showed significant negative correlation with GM volume reduction in the cortical area surrounding the left superior temporal sulcus (STS), which is considered to be important in social perception. Our findings suggest a possible neuroanatomical basis of autistic tendencies in schizophrenia.
  Social neuroscience 09/2011; 6(5-6):548-58. · 3.17 Impact Factor