研究者詳細 - 梅田　聡

論文 - 梅田　聡

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Effects of insular resection on interactions between cardiac interoception and emotion recognition

Terasawa Y., Motomura K., Natsume A., Iijima K., Chalise L., Sugiura J., Yamamoto H., Koyama K., Wakabayashi T., Umeda S.

Cortex （Cortex） 137 271 - 281 2021年04月

ISSN 00109452

The insular cortex is considered an important region for feeling emotions through interoception. Most studies that report the role of the insula in integrating interoception and emotion have used neuroimaging techniques such as functional magnetic resonance imaging (fMRI); however, there are limited neuropsychological studies. The effects of insular lesions on emotion and interoception have not been suitably investigated. In this study, we examined the role of the insular cortex in cardiac interoception and recognizing emotions from facial expressions by comparing them pre- and post-operatively in patients with glial tumors or brain metastases associated with the insular lobe. Although no significant difference in interoceptive accuracy was observed between the two phases, there were significant associations between the changes in interoceptive accuracy and sensitivity to expressions of anger and happiness. An increased error rate in the heartbeat counting task in the post-operation phase was associated with a decreased accuracy in recognizing anger and happiness. Since most patients had left insula lesions, generalizability of the findings to patients with right lesions is a future subject. To the best of our knowledge, this is the first study to examine the change in interoception and emotion after insular resection in humans. The study results indicate that removal of the insula affects the recognition of emotions such as anger and happiness through interoceptive processing.

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Alterations of Heartbeat Evoked Magnetic Fields Induced by Sounds of Disgust

Kato Y., Takei Y., Umeda S., Mimura M., Fukuda M.

Frontiers in Psychiatry （Frontiers in Psychiatry） 11 2020年07月

© Copyright © 2020 Kato, Takei, Umeda, Mimura and Fukuda. The majority of the models of emotional processing attribute subjective emotional feelings to physiological changes in the internal milieu, which are sensed by the interoceptive system. These physiological reactions evoked by emotional phenomena occur via the autonomic nervous system, and give rise to alterations in body-mind interactions that are characterized by heartbeat evoked magnetic fields (HEFs) involving brain regions associated with emotional perception. The current study used magnetoencephalography (MEG) to examine regional cortical activity and connectivity changes in HEFs provoked by the emotion of disgust. MEG results from 39 healthy subjects (22 female) revealed that passively listening to sounds of disgust elicited right insular cortical activity and enhancement of cortical connectivity between the right anterior ventral insular cortex and left ventromedial prefrontal cortex, demonstrated by phase lag indexes in the beta frequency range. Furthermore, inter-trial coherence significantly increased at 19 Hz and 23 Hz, and decreased at 14 Hz, which highlights the involvement of low beta oscillations in emotional processing. As these results were based on spontaneously triggered bioelectrical signals, more indigenous and induced signals were extracted with a block designed experiment. The insular cortices play an important role in emotional regulation and perception as the main cortical target for signals with interoceptive information, providing direct substrates of emotional feelings. The current results provide a novel insight into frequency properties of emotional processing, and suggest that emotional arousal evoked by listening to sounds of disgust partially impact the autonomic nervous system, altering HEFs via connectivity changes in the right anterior ventral insular cortex and left ventromedial prefrontal cortex.

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Neural and clinical changes of cognitive behavioural therapy versus talking control in patients with major depression: A study protocol for a randomised clinical trial

Katayama N., Nakagawa A., Abe T., Kurata C., Sasaki Y., Mitsuda D., Nakao S., Mizuno S., Ozawa M., Nakagawa Y., Ishikawa N., Umeda S., Terasawa Y., Tabuchi H., Kikuchi T., Mimura M.

BMJ Open （BMJ Open） 10 （ 2 ） 2020年02月

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. While major depression causes substantial distress and impairment for affected individuals and society, the effectiveness of cognitive behavioural therapy (CBT) in treating the condition has been established. However, the therapeutic mechanism underlying the efficacy of CBT remains unknown. This study aimed to describe a protocol for a randomised controlled trial that will measure the CBT-induced clinical and neural changes in patients with non-psychotic major depression. Methods and analysis The current study is a 16-week assessor-blinded, randomised, parallel-group trial with a 12-month follow-up as part of usual depression care at an outpatient clinic. Patients aged 20-69 years with major depressive disorder will be randomly assigned to receive either CBT in addition to their usual treatment or talking control in addition to their usual treatment for 16 weeks. The primary outcome is the functional changes in the brain areas that have been associated with future-oriented thinking at 16 weeks; secondary outcomes include changes in functional brain connectivity, severity and changes in the scores of objective and subjective clinical depression symptoms, proportion of responders and remitters and quality of life. The intention-to-treat analysis will be used. Ethics and dissemination All protocols and the informed consent form are compliant with the Ethics Guideline for Clinical Research (Japanese Ministry of Health, Labour and Welfare). Ethical Review Committees at the Keio University School of Medicine have approved the study protocol (version 3, 11 September 2017). We will disseminate research findings to scientific and general audiences through national and international conference presentations as well as lay summaries to the general public, including mental health consumer and publications in international peer-reviewed psychiatry and brain imaging journals. Trial registration number UMIN Clinical Trials Registry (UMIN000018155); Pre-results.

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Effects of Hop Bitter Acids, Bitter Components in Beer, on Cognition in Healthy Adults: A Randomized Controlled Trial

Fukuda T., Obara K., Saito J., Umeda S., Ano Y.

Journal of Agricultural and Food Chemistry （Journal of Agricultural and Food Chemistry） 68 （ 1 ） 206 - 212 2020年01月

ISSN 00218561

© 2019 American Chemical Society. The present study aimed to investigate the effects of matured hop bitter acids (MHBAs) on human cognition, mental fatigue, and mood state. In this randomized double-blind placebo-controlled study, 60 healthy adults (age 45-64 years) with self-awareness of cognitive decline were randomly divided into 2 groups and received either orally administered MHBAs (35 mg/day) or placebo for 12 weeks. Cognitive functions and mental states were assessed using neuropsychological tests or questionnaires at baseline and weeks 6 and 12 of the intervention. The change in verbal fluency score at week 6 compared with that at baseline was significantly higher in the MHBAs-treated group compared with that in the placebo group (P = 0.034), and Stroop test score at week 12 was significantly lower in the MHBAs-treated group compared with the placebo group (P = 0.019). Furthermore, subjective fatigue and anxiety at week 12 were significantly improved in the MHBAs-treated group (P = 0.008 and 0.043, respectively) compared with the placebo group. This is the first study to evaluate the effects of bitter ingredients in beer on cognition, subjective mood, and mental fatigue in a clinical trial. Our findings suggest that hop-derived bitter acids might be beneficial for cognition and mood state.

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Affective and temporal orientation of thoughts: Electrophysiological evidence

Ito Y., Shibata M., Tanaka Y., Terasawa Y., Umeda S.

Brain Research （Brain Research） 1719 148 - 156 2019年09月

ISSN 00068993

© 2019 Elsevier B.V. The factors that determine the content and valence of spontaneous thoughts have not yet been clarified. In this study, we focused on the effects of bodily states and depression and anxiety traits. Participants performed a past/future thinking task in which three-part sentences including temporal cues were presented in a sequential pattern, for example “in the near future/dreams/will come true”. We measured heartbeat-evoked potentials (HEPs)to assess affective processing, and event-related potentials (ERPs)to assess temporal processing of thoughts that emerged when the temporal cue words were presented. The HEPs predicted thought valence irrespective of personality traits. Larger N400 ERPs were observed in response to past-oriented than to future-oriented words in participants with higher levels of depression, whereas the opposite was the case in participants with higher social anxiety. Our data suggest that afferent signals modulate affective thought-orientations as triggers, and that individuals with depression and anxiety have sensitivity toward temporal information at the neural level.

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Anterior insular cortex stimulation and its effects on emotion recognition

Motomura K., Terasawa Y., Natsume A., Iijima K., Chalise L., Sugiura J., Yamamoto H., Koyama K., Wakabayashi T., Umeda S.

Brain Structure and Function （Brain Structure and Function） 224 （ 6 ） 2167 - 2181 2019年07月

ISSN 18632653

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. With the objective to investigate the role of the insula in recognizing emotion, we performed direct electrical stimulation over the anterior insular cortex during awake surgery while simultaneously delivering an emotional sensitivity task. We registered 18 consecutive patients with brain tumors associated with the insular lobe, who were undergoing tumor resection. An emotional sensitivity task was employed to measure the patients’ ability to recognize emotions from facial expressions before, during, and after awake surgery. Furthermore, we performed voxel-based lesion symptom mapping (VLSM) to identify the association between relevant brain lesions and emotion recognition. When we performed direct electrical stimulation over the anterior insular cortex during awake surgery, the results showed that the ability to recognize anger was significantly enhanced with the presence of anterior insular stimulation (p < 0.05). Comparing the performance in the emotional sensitivity task before and after surgery, the performance in the anger condition became worse (p < 0.01), but became better in the sadness condition after surgery (p < 0.01). In the case of anger recognition, lower scores in the correct response index were associated with lesions involving the left insula in the VLSM study. Direct electrical stimulation over the anterior insular cortex enhanced anger recognition in patients with insular tumors. In contrast, accuracy of anger recognition was significantly reduced, and sadness was improved, when the performance of emotional sensitivity was compared pre- and post-surgery. Our findings suggest that the insular cortex is involved in changes in emotion recognition, including anger and sadness recognition by modulating arousal level that is closely connected with interoception.

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Machiavellianism and early neural responses to others’ facial expressions caused by one's own decisions

Osumi T., Tsuji K., Shibata M., Umeda S.

Psychiatry Research （Psychiatry Research） 271 669 - 677 2019年01月

ISSN 0165-1781

© 2018 Elsevier B.V. The processing of social stimuli generated by one's own voluntary behavior is an element of social adaptation. It is known that self-generated stimuli induce attenuated sensory experiences compared with externally generated stimuli. The present study aimed to examine this self-specific attenuation effect on early stimulus processing in the case of others’ facial expressions during interpersonal interactions. In addition, this study explored the possibility that the self-specific attenuation effect on social cognition is modulated by antisocial personality traits such as Machiavellianism. We analyzed early components of the event-related brain potential in participants elicited by happy and sad facial expressions of others when the participant's decision was responsible for the others’ emotions and when the others’ facial expressions were independent of the participant's decision. Compared to the non-responsible condition, the responsible condition showed an attenuated amplitude of the N170 component in response to sad faces. Moreover, Machiavellianism explained individual differences in the self-specific attenuation effect depending on the affective valence of social signals. The present findings support the possibility that the self-specific attenuation effect extends to interpersonal interactions and imply that distorted cognition of others’ emotions caused by one's own behavior is associated with personality disorders that promote antisocial behaviors.

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Supplementation with whey peptide rich in β-lactolin improves cognitive performance in healthy older adults: A randomized, double-blind, placebo-controlled study

Kita M., Kobayashi K., Obara K., Koikeda T., Umeda S., Ano Y.

Frontiers in Neuroscience （Frontiers in Neuroscience） 13 （ APR ） 2019年

ISSN 16624548

Copyright © 2019 Kita, Kobayashi, Obara, Koikeda, Umeda and Ano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Epidemiological reports showed that consumptions of fermented dairy products are beneficial for cognitive decline in elderly. Our previous preclinical studies have demonstrated that intakes of whey peptide rich in the β-lactolin [β-lactopeptide of glycine-thereonine-tryptophan-tyrosine (GTWY)] improve memory and attention by regulating monoamine system, and clinical study using neuropsychological test suggested that consumptions with GTWY-rich whey peptide enhance cognitive performance associated with the frontal cortex activity. However, corresponding interventional studies in humans are limited. Objectives: to evaluate the effects of the whey peptide on cognitive functions in healthy older adults using a randomized, double-blinded, placebo-controlled trial design. 114 healthy subjects aged 50-75 were supplemented with the whey peptide or placebo for 12 weeks, and changes in cognitive function were assessed using neuropsychological tests at weeks 0, 6, and 12 of the intervention. Neuropsychological tests included assessments for memory functions (subtests from Wechsler memory scale-revised, standard verbal paired-associate learning test, and recognition memory test for faces), assessments for attention (cancelation and detection tests), and assessments for general cognitive functions (repeatable battery for assessments of neuropsychological status). Cerebral blood flow was also assessed using near-infrared spectroscopy (NIRS) after 6 weeks of intervention. This study was registered on the 19 November, 2017 in the database of the University Hospital Medical Information Network (UMIN) prior to enrollment of subjects (Registration No. UMIN000030461: https://www.umin.ac.jp/ctr/index-j.htm). In the whey peptide group, visual paired-associates I and visual cancelation tests were significantly improved compared with those in the placebo group at weeks 6 and 12 of the intervention, respectively. Visuospatial and constructional scores of the repeatable battery for assessments of neuropsychological status and standard verbal paired-associate learning tests (S-PA) also tended to be improved by the intervention at week 12. Daily intakes of GTWY-rich whey peptide show beneficial effects on cognitive performance, especially associative learning memory and control of attention, in healthy older adults and might prevent age-related cognitive declines.

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Frontopolar cortex activation associated with pessimistic future-thinking in adults with major depressive disorder

Katayama N., Nakagawa A., Umeda S., Terasawa Y., Kurata C., Tabuchi H., Kikuchi T., Mimura M.

NeuroImage: Clinical （NeuroImage: Clinical） 23 2019年

© 2019 The Author(s) Background: Pessimistic thinking about the future is one of the cardinal symptoms of major depressive disorder (MDD) and is an important domain of cognitive functioning associated with hopelessness. Neuroimaging studies have shown that the frontopolar cortex (Brodmann area [BA] 10) is involved in thinking about the future and demonstrated that patients with MDD have dysfunctions in BA10. However, the relationship between pessimistic thinking about the future and brain activity is unclear. Hence, we aimed to compare brain activity during future-thinking between patients with MDD and healthy individuals. Methods: We assessed 23 patients with current MDD and 23 healthy individuals. Participants were instructed to imagine the future or to recall the past using the future-thinking paradigm with four distinct temporal conditions (distant future, near future, distant past, and near past) during functional MRI. Resting-state functional MRI was also performed to explore the functional connectivity of BA10. Results: Compared with healthy individuals, patients with MDD had greater negative thinking about the distant future and exhibited increased activation in the medial BA10 when imagining the distant future, following small-volume correction focusing on the frontopolar a priori region of interest (family-wise error correction p < 0.05). Increased positive functional correlation between the right BA10 seed region and the posterior cingulate cortex was also observed. Conclusion: Patients with MDD who show greater pessimistic thinking about the distant future demonstrate increased activation in the frontopolar cortex. These findings are consistent with the hypothesis that frontopolar cortical dysfunction plays a key role in the hopelessness that manifests in patients with MDD.

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PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury

Takahata K., Kimura Y., Sahara N., Koga S., Shimada H., Ichise M., Saito F., Moriguchi S., Kitamura S., Kubota M., Umeda S., Niwa F., Mizushima J., Morimoto Y., Funayama M., Tabuchi H., Bieniek K.F., Kawamura K., Zhang M.R., Dickson D.W., Mimura M., Kato M., Suhara T., Higuchi M.

Brain （Brain） 142 （ 10 ） 3265 - 3279 2019年

ISSN 00068950

© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. Tau deposits is a core feature of neurodegenerative disorder following traumatic brain injury (TBI). Despite ample evidence from post-mortem studies demonstrating exposure to both mild-repetitive and severe TBIs are linked to tau depositions, associations of topology of tau lesions with late-onset psychiatric symptoms due to TBI have not been explored. To address this issue, we assessed tau deposits in long-term survivors of TBI by PET with 11C-PBB3, and evaluated those associations with late-life neuropsychiatric outcomes. PET data were acquired from 27 subjects in the chronic stage following mild-repetitive or severe TBI and 15 healthy control subjects. Among the TBI patients, 14 were diagnosed as having late-onset symptoms based on the criteria of traumatic encephalopathy syndrome. For quantification of tau burden in TBI brains, we calculated 11C-PBB3 binding capacity (cm3), which is a summed voxel value of binding potentials (BP*ND) multiplied by voxel volume. Main outcomes of the present study were differences in 11C-PBB3 binding capacity between groups, and the association of regional 11C-PBB3 binding capacity with neuropsychiatric symptoms. To confirm 11C-PBB3 binding to tau deposits in TBI brains, we conducted in vitro PBB3 fluorescence and phospho-tau antibody immunofluorescence labelling of brain sections of chronic traumatic encephalopathy obtained from the Brain Bank. Our results showed that patients with TBI had higher 11C-PBB3 binding capacities in the neocortical grey and white matter segments than healthy control subjects. Furthermore, TBI patients with traumatic encephalopathy syndrome showed higher 11C-PBB3 binding capacity in the white matter segment than those without traumatic encephalopathy syndrome, and regional assessments revealed that subgroup difference was also significant in the frontal white matter. 11C-PBB3 binding capacity in the white matter segment correlated with the severity of psychosis. In vitro assays demonstrated PBB3-positive tau inclusions at the depth of neocortical sulci, confirming 11C-PBB3 binding to tau lesions. In conclusion, increased 11C-PBB3 binding capacity is associated with late-onset neuropsychiatric symptoms following TBI, and a close correlation was found between psychosis and 11C-PBB3 binding capacity in the white matter.

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Spontaneous activation of event details in episodic future simulation

Ito Y., Terasawa Y., Umeda S., Kawaguchi J.

Frontiers in Psychology （Frontiers in Psychology） 10 （ MAR ） 2019年

© 2019 Ito, Terasawa, Umeda and Kawaguchi. Episodic future simulation is supported by both the retrieval and recombination of episodic details. It remains unclear, however, how individuals retrieve episodic details from memory to construct possible future scenarios; for this people must use details related to the planned future events appropriately. A potentially relevant cognitive process is the spontaneous activation of intention observed in prospective memory (i.e., the intention superiority effect). Previous studies on prospective memory have shown that the approximation of retrieval opportunities for future intentions activate related information, suggesting that the intention superiority effect is context-sensitive. We hypothesized that the same cognitive process underlies future simulation-that is, details related to future events should spontaneously become activated at the appropriate moment of future simulation to make that simulation plausible. In Experiment 1, participants took part in future experiments and formed intentions to perform particular actions for the next experiments. Subsequently, they imagined events that could occur up until they arrived at the experimental room on the day of the next experiment. During this exercise, they did not imagine engaging in the required experimental task. We measured the conceptual activation of intention-related information via a recognition task using intended action words as targets. The results showed the intention superiority effect-concepts related to participants' future intentions became active when envisioning future events approaching the next experiment. In Experiments 2 and 3, we ensured that the intention superiority effect in future simulation was context-sensitive by adding a control condition that required participants to imagine events other than the approaching future experiments. These results indicated that concepts related to the intended actions were spontaneously activated when imagined future events became both temporally and spatially close to the future simulation. Our finding suggests that spontaneous activation of details approaching the context of a future simulation helps in constructing plausible future scenarios.

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Dysconnectivity of the agency network in schizophrenia: A functional magnetic resonance imaging study

Koreki A., Maeda T., Okimura T., Terasawa Y., Kikuchi T., Umeda S., Nishikata S., Yagihashi T., Kasahara M., Nagai C., Moriyama Y., Den R., Watanabe T., Kikumoto H., Kato M., Mimura M.

Frontiers in Psychiatry （Frontiers in Psychiatry） 10 （ APR ） 2019年

Copyright © 2019 Koreki, Maeda, Okimura, Terasawa, Kikuchi, Umeda, Nishikata, Yagihashi, Kasahara, Nagai, Moriyama, Den, Watanabe, Kikumoto, Kato and Mimura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the “agency network” may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the “agency network.” Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

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Neurocognitive mechanisms of social anxiety and interoception

Terasawa Y., Umeda S.

Island of Reil (Insula) in the Human Brain: Anatomical, Functional, Clinical and Surgical Aspects （Island of Reil (Insula) in the Human Brain: Anatomical, Functional, Clinical and Surgical Aspects） 113 - 120 2018年07月

ISSN 9783319754673

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Effect of supplementation of a whey peptide rich in tryptophan-tyrosine-related peptides on cognitive performance in healthy adults

Kita Masahiro, Obara Kuniaki, Kondo Sumio, Umeda Satoshi, Ano Yasuhisa

Nutrients 10 （ 7 ） 2018年07月

ISSN 2072-6643

Background: Previous epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia. Enzymatic digestion of whey protein produces a whey peptide rich in tryptophan-tyrosine-related peptides which improve cognitive performance in mice. We evaluated the effects of whey peptides on cognitive functions in healthy adults in a randomized, double-blind, placebo-controlled design. Methods: 101 healthy adults (45 to 64 years), with a self-awareness of cognitive decline received either whey peptide or placebo supplements for 12 weeks. Changes in cognitive function were assessed using neuropsychological tests at 6 and 12 weeks after the start of supplementation. Results: Verbal fluency test (VFT) score changes tended to be higher in the whey peptide group compared with the placebo at 12 weeks. Subgroup analysis classified by the degree of subjective fatigue showed that changes in the VFT as well as the Stroop and subjective memory function tests between baseline and 6 weeks of intervention were significantly better in subjects with high-level fatigue from the whey peptide group as compared to the placebo group. Conclusions: Intake of whey peptide might improve cognitive function in healthy middle- and older-aged adults with high subjective fatigue levels. Further studies will elucidate the relationship among cognitive improvement, whey peptides, and psychological fatigue.

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Effect of supplementation of a whey peptide rich in tryptophan-tyrosine-related peptides on cognitive performance in healthy adults: A randomized, double-blind, placebo-controlled study

Kita M., Obara K., Kondo S., Umeda S., Ano Y.

Nutrients （Nutrients） 10 （ 7 ） 2018年07月

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Background: Previous epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia. Enzymatic digestion of whey protein produces a whey peptide rich in tryptophan-tyrosine-related peptides which improve cognitive performance in mice. We evaluated the effects of whey peptides on cognitive functions in healthy adults in a randomized, double-blind, placebo-controlled design. Methods: 101 healthy adults (45 to 64 years), with a self-awareness of cognitive decline received either whey peptide or placebo supplements for 12 weeks. Changes in cognitive function were assessed using neuropsychological tests at 6 and 12 weeks after the start of supplementation. Results: Verbal fluency test (VFT) score changes tended to be higher in the whey peptide group compared with the placebo at 12 weeks. Subgroup analysis classified by the degree of subjective fatigue showed that changes in the VFT as well as the Stroop and subjective memory function tests between baseline and 6 weeks of intervention were significantly better in subjects with high-level fatigue from the whey peptide group as compared to the placebo group. Conclusions: Intake of whey peptide might improve cognitive function in healthy middle- and older-aged adults with high subjective fatigue levels. Further studies will elucidate the relationship among cognitive improvement, whey peptides, and psychological fatigue.

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Functional Anatomy of Encoding/Retrieval Processing in the Medial Parietal Areas

Umeda S.

Brain and nerve = Shinkei kenkyu no shinpo （Brain and nerve = Shinkei kenkyu no shinpo） 70 （ 7 ） 763 - 769 2018年07月

ISSN 18816096

This article reviews memory functions in the medial parietal areas, which consist of the retrosplenial cortex, the posterior cingulate cortex, and the precuneus. These areas are involved in various cognitive functions including memory processing, spatial cognition, and self-related processing. Fundamental previous studies from the areas of neuropsychology, neuroimaging, psychiatry, and neurology, are covered to describe memory-related functions in the medial parietal areas. The focus is on the default mode network and the encoding/retrieval flip as key issues for understanding memory functions in the medial parietal areas.

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Interoception and Mental Health

Khalsa Sahib S., Adolphs Ralph, Cameron Oliver G., Critchley Hugo D., Davenport Paul W., Feinstein Justin S., Feusner Jamie D., Garfinkel Sarah N., Lane Richard D., Mehling Wolf E., Meuret Alicia E., Nemeroff Charles B., Oppenheimer Stephen, Petzschner Frederike H., Pollatos Olga, Rhudy Jamie L., Schramm Lawrence P., Simmons W. Kyle, Stein Murray B., Stephan Klaas E., Van den Bergh Omer, Van Diest Ilse, von Leupoldt Andreas, Paulus Martin P., Ainley Vivien, Al Zoubi Obada, Aupperle Robin, Avery Jason, Baxter Leslie, Benke Christoph, Berner Laura, Bodurka Jerzy, Breese Eric, Brown Tiffany, Burrows Kaiping, Cha Yoon Hee, Clausen Ashley, Cosgrove Kelly, Deville Danielle, Duncan Laramie, Duquette Patrice, Ekhtiari Hamed, Fine Thomas, Ford Bart, Garcia Cordero Indira, Gleghorn Diamond, Guereca Yvette, Harrison Neil A., Terasawa Yuuri, Umeda Satoshi

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 3 （ 6 ） 501 - 513 2018年06月

ISSN 2451-9022

Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.

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Interoception and Mental Health: A Roadmap

Khalsa S., Adolphs R., Cameron O., Critchley H., Davenport P., Feinstein J., Feusner J., Garfinkel S., Lane R., Mehling W., Meuret A., Nemeroff C., Oppenheimer S., Petzschner F., Pollatos O., Rhudy J., Schramm L., Simmons W., Stein M., Stephan K., Van den Bergh O., Van Diest I., von Leupoldt A., Paulus M., Ainley V., Al Zoubi O., Aupperle R., Avery J., Baxter L., Benke C., Berner L., Bodurka J., Breese E., Brown T., Burrows K., Cha Y., Clausen A., Cosgrove K., Deville D., Duncan L., Duquette P., Ekhtiari H., Fine T., Ford B., Garcia Cordero I., Gleghorn D., Guereca Y., Harrison N., Hassanpour M., Hechler T., Heller A., Hellman N., Herbert B., Jarrahi B., Kerr K., Kirlic N., Klabunde M., Kraynak T., Kriegsman M., Kroll J., Kuplicki R., Lapidus R., Le T., Hagen K., Mayeli A., Morris A., Naqvi N., Oldroyd K., Pané-Farré C., Phillips R., Poppa T., Potter W., Puhl M., Safron A., Sala M., Savitz J., Saxon H., Schoenhals W., Stanwell-Smith C., Teed A., Terasawa Y., Thompson K., Toups M., Umeda S., Upshaw V., Victor T., Wierenga C., Wohlrab C., Yeh H., Yoris A., Zeidan F., Zotev V., Zucker N.

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging （Biological Psychiatry: Cognitive Neuroscience and Neuroimaging） 3 （ 6 ） 501 - 513 2018年06月

ISSN 24519022

© 2017 Society of Biological Psychiatry Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.

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Retrospective time estimation following damage to the prefrontal cortex

Kurosaki Y., Terasawa Y., Ibata Y., Hashimoto R., Umeda S.

Journal of Neuropsychology （Journal of Neuropsychology） 14 （ 1 ） 135 - 153 2018年01月

ISSN 1748-6645

© 2018 The British Psychological Society Time estimation in patients with prefrontal cortex (PFC) damage is often inaccurate. The relationship between PFC and estimation of short time intervals has been examined. However, it remains unclear whether PFC damage affects estimation of longer time intervals. Here, we investigated the ability of patients and healthy subjects to verbally estimate a period of 30 min, using a method easily applied in clinical settings. In 99 patients with brain damage, we compared under and normal ranges of time in patients with PFC damage or damage to other brain areas with the chi-squared test. Subsequently, we conducted a discriminant analysis and a multiple linear regression analysis to identify specific brain areas affecting time estimation. We observed a significantly larger number of patients who overestimated 30 min in the group with bilateral PFC damage compared to patients with damage to other regions. Discriminant analysis revealed that damage of right lateral PFC and left medial PFC contributed to discrimination between the normal range and overestimation groups. Multiple linear regression analysis indicated that right lateral PFC damage strongly affected overestimation of a 30-min interval. Neuropsychological test results revealed lower general cognitive function scores and orientation scores in overestimation group. The length of estimated time and the score of delayed word recall were negatively correlated. We propose that these may require encoding, maintenance, and updating of memory and are indirectly related to contextual memory. We discuss hypotheses on contextual memory segmentation and reconstruction to clarify the mechanism of impaired time overestimation in PFC-damaged patients.

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Comparison of emotional processing assessed with fear conditioning by interpersonal conflicts in patients with depression and schizophrenia

Tani H., Tada M., Maeda T., Konishi M., Umeda S., Terasawa Y., Mimura M., Takahashi T., Uchida H.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 73 （ 3 ） 116 - 125 2018年01月

ISSN 1323-1316

© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology Aim: While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli. Methods: We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors’ faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants. Results: Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition. Conclusion: Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

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Sustained Attention Function Evaluation during Cooking Based on Egocentric Vision

Ooi Sho, Sano Mutsuo, Tabuchi Hajime, Saito Fumie, Umeda Satoshi

2017-January 107 - 113 2017年12月

The attention function has been classified into (i) sustained attention, (ii) selective attention, (iii) controlled attention, (iv) distributed attention, and (v) capacity for attention. Ordinarily, in order to evaluate the function of attention, the digital cancellation test (D-CAT) or trail making test (TMT) are employed. However, these evaluations are in the form of paper tests, and cannot effectively evaluate small changes in activities daily of living in real time. Accordingly, we focus on human behavior during the act of cooking, in which multitasking is common and many types of ordinary movements are performed. We previously proposed a method of evaluating distributive attention during cooking and showed its effectiveness. In this study, a method for evaluating sustained attention is proposed. Specifically, we acquire an egocentric video by an egocentric vision and estimate line-of-sight based on the visual attention model that is integrated from the three kind of models (category-specific attention, top-down attention, and bottom-up attention). After that, we define line-to-sight information from high saliency area on the visual attention model.

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The impact of interoception on memory

Terasawa Yuri, Umeda Satoshi

165 - 178 2017年12月

Using interoception as a keyword, this chapter has summarized how changes in the internal physical state are encoded and how the processing of interoceptive information affects the memory of episodes and events. Interoceptive information processing is discussed frequently in the context of emotion in psychology. On the other hand, research studies and literature that have examined its relation to episodic memory are rare. However, changes in the internal physical state exist at the foundation of various concepts that have examined its relationship with memory. To understand the relationship more precisely, we focused on the following issues in this chapter: emotional arousal and bodily responses; effects of bodily responses on memory encoding; judgment related to memories and bodily response; and insular cortex and memory consolidation. Throughout the chapter, we presented the possibility that change in the physical state itself plays a role in latently supporting the encoding and recollection process.

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Area 10, 38

Umeda Satoshi

Brain and nerve = Shinkei kenkyu no shinpo 69 （ 4 ） 355 - 365 2017年04月

ISSN 1881-6096

This paper reviews the structural specificities and functional roles in Brodmann areas 10 and 38. A number of studies have focused on both areas through various approaches including neuropsychology, neuroimaging, psychiatry, neurology, and neurosurgery. Both areas 10 and 38 may have a substantially very complex higher-order cognitive functions, which are quite hard to disentangle. Here, I picked up some fundamental perspectives for reviewing previous studies, to provide efficient research orientations for the elucidation of functions in both areas.

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Time course and localization of brain activity in humor comprehension

Shibata Midori, Terasawa Yuri, Osumi Takahiro, Masui Keita, Ito Yuichi, Sato Arisa, Umeda Satoshi

Brain Research 1657 215 - 222 2017年02月

ISSN 0006-8993

Although a number of studies have investigated the incongruity-detection and resolution process in humor comprehension, it is difficult to functionally and anatomically dissociate these processes. We used event-related potentials (ERP) and standardized low resolution brain electromagnetic tomography analysis (sLORETA) to examine the time course and localization of brain activity during incongruity detection and resolution. We used the same materials as in our previous fMRI study. Eighteen participants read funny and unfunny scenarios and judged whether the target sentence was funny or not. Results indicated that ERPs elicited by a funny punch line showed a P2 component followed by a P600 component over the centro-parietal electrode sites. Our sLORETA analysis of the P2 ERPs revealed a stronger activation for the funny vs. unfunny condition in the superior frontal gyrus (SFG) and medial prefrontal cortex (mPFC). For the P600 ERPs, the funny punch line elicited greater activation in the temporal-parietal regions. These results indicate that incongruity-detection processes activate the SFG and mPFC in the P2 time window, while incongruity-resolution processes generate activation at the temporal-parietal regions in the P600 time window. These results provide the evidence that verbal humor comprehension is processed in steps which start with the incongruity detection in the early P2 time window and followed by a P600 component reflecting incongruity resolution.

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Time course and localization of brain activity in humor comprehension: An ERP/sLORETA study

梅田聡

BRAIN RESEARCH 1657 215 - 222 2017年02月

研究論文（学術雑誌）, ISSN 0006-8993

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Prospective memory mediated by interoceptive accuracy

Umeda Satoshi, Tochizawa Saiko, Shibata Midori, Terasawa Yuri

Philosophical Transactions of the Royal Society B: Biological Sciences 371 （ 1708 ） 2016年11月

ISSN 0962-8436

Previous studies on prospective memory (PM), defined as memory for future intentions, suggest that psychological stress enhances successful PM retrieval. However, the mechanisms underlying this notion remain poorly understood. We hypothesized that PM retrieval is achieved through interaction with autonomic nervous activity, which is mediated by the individual accuracy of interoceptive awareness, as measured by the heartbeat detection task. In this study, the relationship between cardiac reactivity and retrieval of delayed intentions was evaluated using the event-based PM task. Participants were required to detect PM target letters while engaged in an ongoing 2-back working memory task. The results demonstrated that individuals with higher PM task performance had a greater increase in heart rate on PM target presentation. Also, higher interoceptive perceivers showed better PM task performance. This pattern was not observed for working memory task performance. These findings suggest that cardiac afferent signals enhance PM retrieval, which is mediated by individual levels of interoceptive accuracy. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

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Emotion disorders and abnormal perspiration

Umeda Satoshi

Brain and Nerve 68 （ 8 ） 893 - 901 2016年08月

ISSN 1881-6096

This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed.

Behavioral evidence of delayed prediction signals during agency attribution in patients with schizophrenia

Koreki Akihiro, Maeda Takaki, Fukushima Hirokata, Umeda Satoshi, Takahata Keisuke, Okimura Tsukasa, Funayama Michitaka, Iwashita Satoru, Mimura Masaru, Kato Motoichiro

Psychiatry Research 230 （ 1 ） 78 - 83 2015年11月

ISSN 0165-1781

Self-disturbance, a core feature of schizophrenia, recently has been explained from the standpoint of an abnormal sense of agency (SoA). Previous studies showed that aberrant SoA in schizophrenia arise from imprecise predictions about the sensory consequences of actions. However, the nature of the malfunctioning predictions remains unclear. We examined the temporally "delayed" nature of inadequate predictions. We studied 30 patients with schizophrenia and 30 healthy controls. Our original SoA task evaluates explicit experience of the temporal causal relationship between an intentional action and an effect on a computer screen under the presence of temporal biases. We introduced an adaptation with a "trial-by-trial" method that prolonged or shortened the temporal biases. We hypothesized that delayed prediction signals in schizophrenia could lead to a match in timing between predictions and actual outcomes, resulting in self-agency. The adjustment courses to changing temporal biases were evaluated. Patients with schizophrenia continued to feel self-agency even when the adjusted temporal bias was longer than 1000. ms. This result indicated that patient's prediction would be delayed in each trial. Our study empirically showed behavioral evidence for "delayed" prediction signals in a SoA paradigm for the first time.

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Behavioral evidence of delayed prediction signals during agency attribution in patients with schizophrenia

梅田聡

PSYCHIATRY RESEARCH 230 （ 1 ） 78 - 83 2015年11月

研究論文（学術雑誌）, ISSN 0165-1781

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Attenuated sensitivity to the emotions of others by insular lesion

梅田聡

FRONTIERS IN PSYCHOLOGY 6 78 - 83 2015年09月

研究論文（学術雑誌）, ISSN 1664-1078

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Fear conditioning induced by interpersonal conflicts in healthy individuals

Tada Mitsuhiro, Uchida Hiroyuki, Maeda Takaki, Konishi Mika, Umeda Satoshi, Terasawa Yuri, Nakajima Shinichiro, Mimura Masaru, Miyazaki Tomoyuki, Takahashi Takuya

PLoS ONE 10 （ 5 ） 2015年05月

Psychophysiological markers have been focused to investigate the psychopathology of psychiatric disorders and personality subtypes. In order to understand neurobiological mechanisms underlying these conditions, fear-conditioning model has been widely used. However, simple aversive stimuli are too simplistic to understand mechanisms because most patients with psychiatric disorders are affected by social stressors. The objective of this study was to test the feasibility of a newly-designed conditioning experiment using a stimulus to cause interpersonal conflicts and examine associations between personality traits and response to that stimulus. Twenty-nine healthy individuals underwent the fear conditioning and extinction experiments in response to three types of stimuli: a simple aversive sound, disgusting pictures, and pictures of an actors' face with unpleasant verbal messages that were designed to cause interpersonal conflicts. Conditioned response was quantified by the skin conductance response (SCR). Correlations between the SCR changes, and personality traits measured by the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised NEO Personality Inventory were explored. The interpersonal conflict stimulus resulted in successful conditioning, which was subsequently extinguished, in a similar manner as the other two stimuli. Moreover, a greater degree of conditioned response to the interpersonal conflict stimulus correlated with a higher ZANBPD total score. Fear conditioning and extinction can be successfully achieved, using interpersonal conflicts as a stimulus. Given that conditioned fear caused by the interpersonal conflicts is likely associated with borderline personality traits, this paradigm could contribute to further understanding of underlying mechanisms of interpersonal fear implicated in borderline personality disorder.

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Neurovisceral phenotypes in the expression of psychiatric symptoms

Eccles Jessica A., Owens Andrew P., Mathias Christopher J., Umeda Satoshi, Critchley Hugo D.

Frontiers in Neuroscience 9 （ JAN ） 2015年

ISSN 1662-4548

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety.

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Structural brain abnormalities in postural tachycardia syndrome

Umeda Satoshi, Harrison Neil Andrew, Gray Marcus A., Mathias Christopher J., Critchley Hugo D.

Frontiers in Neuroscience 9 （ JAN ） 2015年

ISSN 1662-4548

Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety and depression. Although the estimated prevalence of PoTS is approximately 5-10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited eleven patients with established PoTS and twenty-three age-matched normal controls. Group comparison of grey matter volume revealed diminished grey matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients.

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Neurovisceral phenotypes in the expression of psychiatric symptoms

Eccles Jessica A., Owens Andrew P., Mathias Christopher J., Umeda Satoshi, Critchley Hugo D.

Frontiers in Neuroscience 9 （ FEB ） 2015年

ISSN 1662-4548

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brain-body mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in "emotional" brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognized factors causing vasodilatation (as noted post-prandially, post-exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety.

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Structural brain abnormalities in postural tachycardia syndrome

Umeda Satoshi, Harrison Neil A., Gray Marcus A., Mathias Christopher J., Critchley Hugo D.

Frontiers in Neuroscience 9 （ MAR ） 2015年

ISSN 1662-4548

Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is approximately 5-10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited 11 patients with established PoTS and 23 age-matched normal controls. Group comparison of gray matter volume revealed diminished gray matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients.

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Integration of cognitive and affective networks in humor comprehension

Shibata Midori, Terasawa Yuri, Umeda Satoshi

Neuropsychologia 65 137 - 145 2014年12月

ISSN 0028-3932

Humor comprehension is a complex process that requires the detection and resolution of the incongruity, eliciting a positive feeling of mirth or reward. We conducted a functional magnetic resonance imaging (fMRI) study to identify the key factors involved in this complex process. To reduce the influence of other factors, we utilized a group of sentences that were nearly identical across conditions (i.e., the first two sentences and the punch line were identical, but the third sentence was different). We found that the punch line (target sentence) in the funny condition induced a perception of funniness and elicited greater activation in language and semantic neural networks, which have been implicated in comprehension processing (i.e., incongruity detection and resolution). We also found increased activation in the mesolimbic reward regions, which have been implicated in the experience of positive rewards in the funny condition. Psycho-physiological interaction analyses revealed that language and semantic regions, such as inferior frontal gyrus (IFG), middle temporal gyrus (MTG), superior temporal gyrus (STG), superior frontal gyrus (SFG), and inferior parietal lobule (IPL) are simultaneously activated during humor comprehension processing. These analyses also revealed that the right MTG, the left IPL, and IFG showed enhanced connectivity with the midbrain. Our findings suggest that these networks play a central role in incongruity detection and resolution, as well as in positive emotional response.

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Interoceptive sensitivity predicts sensitivity to the emotions of others

Terasawa Yuri, Moriguchi Yoshiya, Tochizawa Saiko, Umeda Satoshi

Cognition and Emotion 28 （ 8 ） 1435 - 1448 2014年11月

ISSN 0269-9931

Some theories of emotion emphasise a close relationship between interoception and subjective experiences of emotion. In this study, we used facial expressions to examine whether interoceptive sensibility modulated emotional experience in a social context. Interoceptive sensibility was measured using the heartbeat detection task. To estimate individual emotional sensitivity, we made morphed photos that ranged between a neutral and an emotional facial expression (i.e., anger, sadness, disgust and happy). Recognition rates of particular emotions from these photos were calculated and considered as emotional sensitivity thresholds. Our results indicate that participants with accurate interoceptive awareness are sensitive to the emotions of others, especially for expressions of sadness and happy. We also found that false responses to sad faces were closely related with an individual's degree of social anxiety. These results suggest that interoceptive awareness modulates the intensity of the subjective experience of emotion and affects individual traits related to emotion processing.

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Neural substrates for judgment of self-agency in ambiguous situations

Fukushima Hirokata, Goto Yurie, Maeda Takaki, Kato Motoichiro, Umeda Satoshi

PLoS ONE 8 （ 8 ） 2013年08月

The sense of agency is the attribution of oneself as the cause of one's own actions and their effects. Accurate agency judgments are essential for adaptive behaviors in dynamic environments, especially in conditions of uncertainty. However, it is unclear how agency judgments are made in ambiguous situations where self-agency and non-self-agency are both possible. Agency attribution is thus thought to require higher-order neurocognitive processes that integrate several possibilities. Furthermore, neural activity specific to self-attribution, as compared with non-self-attribution, may reflect higher-order critical operations that contribute to constructions of self-consciousness. Based on these assumptions, the present study focused on agency judgments under ambiguous conditions and examined the neural correlates of this operation with functional magnetic resonance imaging. Participants performed a simple but demanding agency-judgment task, which required them to report on whether they attributed their own action as the cause of a visual stimulus change. The temporal discrepancy between the participant's action and the visual events was adaptively set to be maximally ambiguous for each individual on a trial-by-trial basis. Comparison with results for a control condition revealed that the judgment of agency was associated with activity in lateral temporo-parietal areas, medial frontal areas, the dorsolateral prefrontal area, and frontal operculum/insula regions. However, most of these areas did not differentiate between self- and non-self-attribution. Instead, self-attribution was associated with activity in posterior midline areas, including the precuneus and posterior cingulate cortex. These results suggest that deliberate self-attribution of an external event is principally associated with activity in posterior midline structures, which is imperative for self-consciousness.

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Reasoning bias for the recall of one's own beliefs in a Smarties task for adults

Maehara Yukio, Umeda Satoshi

Japanese Psychological Research 55 （ 3 ） 292 - 301 2013年07月

ISSN 0021-5368

While many studies in the theory of mind (ToM) literature have investigated how we understand others' mental states, few have explored the mechanism by which we reflect on our own mental states. This study examined how adults reflect on their own and others' mental states within the same ToM task. To do so, we modified the Smarties task, one of the traditional ToM tasks for children. The results showed that adult participants were biased by outcome knowledge when recalling their false belief and that the participants who overestimated their false belief also overestimated the mental states of a naive other. These results were analogous to young children's failure in the Smarties task. Considering the current findings, we discuss possible cognitive processes that are common across children and adults when reflecting on their own mental states and the mental states of others. © Japanese Psychological Association 2013.

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How does interoceptive awareness interact with the subjective experience of emotion? An fMRI Study

Terasawa Yuri, Fukushima Hirokata, Umeda Satoshi

Human Brain Mapping 34 （ 3 ） 598 - 612 2013年03月

ISSN 1065-9471

Recent studies in cognitive neuroscience have suggested that the integration of information about the internal bodily state and the external environment is crucial for the experience of emotion. Extensive overlap between the neural mechanisms underlying the subjective emotion and those involved in interoception (perception of that which is arising from inside the body) has been identified. However, the mechanisms of interaction between the neural substrates of interoception and emotional experience remain unclear. We examined the common and distinct features of the neural activity underlying evaluation of emotional and bodily state using functional magnetic resonance imaging (fMRI). The right anterior insular cortex and ventromedial prefrontal cortex (VMPFC) were identified as commonly activated areas. As both of these areas are considered critical for interoceptive awareness, these results suggest that attending to the bodily state underlies awareness of one's emotional state. Uniquely activated areas involved in the evaluation of emotional state included the temporal pole, posterior and anterior cingulate cortex, medial frontal gyrus, and inferior frontal gyrus. Also the precuneus was functionally associated with activity of the right anterior insular cortex and VMPFC when evaluating emotional state. Our findings indicate that activation in these areas and the precuneus are functionally associated for accessing interoceptive information and underpinning subjective experience of the emotional state. Thus, awareness of one's own emotional state appears to involve the integration of interoceptive information with an interpretation of the current situation. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

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Anterior insular cortex mediates bodily sensibility and social anxiety

Terasawa Yuri, Shibata Midori, Moriguchi Yoshiya, Umeda Satoshi

Social Cognitive and Affective Neuroscience 8 （ 3 ） 259 - 266 2013年03月

ISSN 1749-5016

Studies in psychiatry and cognitive neuroscience have reported an important relationship between individual interoceptive accuracy and anxiety level. This indicates that greater attention to one's bodily state may contribute to the development of intense negative emotions and anxiety disorders. We hypothesized that reactivity in the anterior insular cortex underlies the intensity of interoceptive awareness and anxiety. To elucidate this triadic mechanism, we conducted functional magnetic resonance imaging (fMRI) and mediation analyses to examine the relationship between emotional disposition and activation in the anterior insular cortex while participants evaluated their own emotional and bodily states. Our results indicated that right anterior insular activation was positively correlated with individual levels of social anxiety and neuroticism and negatively correlated with agreeableness and extraversion. The results of the mediation analyses revealed that activity in the right anterior insula mediated the activity of neural correlates of interoceptive sensibility and social fear. Our findings suggest that attention to interoceptive sensation affects personality traits through how we feel emotion subjectively in various situations. © The Author (2012). Published by Oxford University Press.

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It's Not My Fault

Takahata Keisuke, Takahashi Hidehiko, Maeda Takaki, Umeda Satoshi, Suhara Tetsuya, Mimura Masaru, Kato Motoichiro

PLoS ONE 7 （ 12 ） 2012年12月

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. © 2012 Takahata et al.

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Enhanced repetition blindness with angry emotional faces

Yamaoka Kao, Umeda Satoshi

Psychologia 55 （ 3 ） 161 - 170 2012年

ISSN 0033-2852

Repetition blindness is defined as difficulty detecting repeated targets within an array of stimuli. However, it is unclear how emotion affects this phenomenon. In the present study, participants were exposed to happy and angry faces, and nonemotional stimuli shown in rapid serial visual presentation. They were required to identify the repeated targets, and the magnitude of repetition blindness was measured to indicate emotional effects. Analysis showed that, while there was no difference in accuracy between happy and angry faces on non-repeated trials, accuracy was significantly lower for angry faces on repeated trials inducing greater repetition blindness. This effect was stronger when the stimulus exposure rate was 150 msec, suggesting its early processes and strong capturing of attention. These results show that repetition blindness effect was stronger with angry faces, which is likely due to enhanced emotional alertness and increase in intensity of the processes inducing greater repetition blindness.

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Neural processing associated with comprehension of an indirect reply during a scenario reading task

Shibata Midori, Abe Jun ichi, Itoh Hiroaki, Shimada Koji, Umeda Satoshi

Neuropsychologia 49 （ 13 ） 3542 - 3550 2011年11月

ISSN 0028-3932

In daily communication, we often use indirect speech to convey our intention. However, little is known about the brain mechanisms that underlie the comprehension of indirect speech. In this study, we conducted a functional MRI experiment using a scenario reading task to compare the neural activity induced by an indirect reply (a type of indirect speech) and a literal sentence. Participants read a short scenario consisting of three sentences. The first two sentences explained the situation of the protagonists, whereas the third sentence had an indirect, literal, or unconnected meaning. The indirect reply condition primarily activated the bilateral fronto-temporal networks (Brodmann's Areas (BA) 47 and 21) and the dorso-medial prefrontal cortex (dmPFC). In the literal sentence condition, only the left fronto-temporal network (BA 45 and 21) and the dmPFC (posterior region) were activated. In addition, we found greater activation resulting from comprehension of an indirect reply than from literal sentence comprehension in the dmPFC, the left middle frontal area (BA 9), the bilateral inferior frontal area (BA 9/47), and the right middle temporal area (BA 21). Our findings indicate that the right and left fronto-temporal networks play a crucial role in detecting contextual violations, whereas the medial frontal cortex is important for generating inferences to make sense of remarks within a context. © 2011 Elsevier Ltd.

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Deficits in prospective memory following damage to the prefrontal cortex

Umeda Satoshi, Kurosaki Yoshiko, Terasawa Yuri, Kato Motoichiro, Miyahara Yasuyuki

Neuropsychologia 49 （ 8 ） 2178 - 2184 2011年07月

ISSN 0028-3932

Neuropsychological investigations of prospective memory (PM), representing memory of future intentions or plans, have evolved over the past two decades. The broadly accepted divisions involved in PM consist of a prospective memory component (PMC), a process for remembering to remember, and a retrospective memory component, a process for remembering the content of the intended action. Previous functional neuroimaing studies have provided some evidence that the rostral prefrontal cortex (BA10) is one of areas that is critical for prospective remembering. However, the question of whether damage to part of the prefrontal cortex affects attenuated performance for PMC remains unresolved. In this study, 74 participants with traumatic brain injury (TBI) including focal damage to frontal or temporal lobe areas were administered thirteen standard neuropsychological tests and the PM task. To identify influential areas contributing to PM performance, discriminant function analysis was conducted. The results indicated that the following three areas are highly contributory to PM performance: the right dorsolateral prefrontal cortex; the right ventromedial prefrontal cortex; and the left dorsomedial prefrontal cortex. Comparing differences in neuropsychological test scores showed that orientation scores were significantly higher in the greater PM performance group, suggesting that PMC represents an integrated memory function associated with awareness of current status. These data contribute to our understanding of the neural substrates and functional characteristics of the PMC. © 2011 Elsevier Ltd.

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Association between interoception and empathy

Fukushima Hirokata, Terasawa Yuri, Umeda Satoshi

International Journal of Psychophysiology 79 （ 2 ） 259 - 265 2011年02月

ISSN 0167-8760

Physiological bodily states play an important role in affective experiences. This study investigated whether the neural processing of internal body state (interoception) is associated with empathy, the understanding of the affective states of others. We used the 'heartbeat-evoked potential' (HEP), a surface electroencephalography (EEG) pattern, as a neural index of interoceptive processing. The HEP is contingent on the most prominent peak (R-wave) of the electrocardiogram (ECG) and is thought to reflect cortical processing of cardiac afferent input. Twenty-one healthy adults performed empathy and control tasks while EEG and ECG were recorded, where they made judgments based on either the affective or physical aspects of images of human eyes. HEP, ECG and heart rate in each task block were calculated and compared. Results showed that cardiac activity was not significantly different between tasks. In contrast, HEP showed a significant task difference, exhibited as an increased negativity during the empathy task over frontocentral sites at a latency of approximately 250-430. ms. Furthermore, a self-reported measure of empathy was associated with mean HEP amplitude during the period of task-related differentiation. These results suggest that afferent feedback from visceral activity may contribute to inferences about the affective state of others. © 2010 Elsevier B.V.

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Neural substrates of implicit cueing effect on prospective memory

Hashimoto Teruo, Umeda Satoshi, Kojima Shozo

NeuroImage 54 （ 1 ） 645 - 652 2011年01月

ISSN 1053-8119

Functional magnetic resonance imaging was used to examine the maintenance of intentions during an ongoing task involving implicit cues. Participants were required to detect target words while engaging in the ongoing task. Cues matched to the target category and cues matched to the action for targets were presented implicitly during the ongoing task. Implicit categorical target cues were found to enhance prospective memory performance, and implicit action cues accelerated responses more than irrelevant implicit cues in the prospective memory task. We found increased caudal anterior cingulate cortex (cACC) activity during the ongoing task with both implicit target and action cues, suggesting that alertness or preparatory attentional processes were strengthened by implicit cues. Implicit target cues elicited enhanced activity in the lateral anterior prefrontal cortex (Brodmann's area 10), which may be involved in dual processing of the ongoing task and the maintained intention. These results suggest that implicit cues may boost primitive attention toward an intended action and may be accessible to off-line maintenance. The facilitation of prospective target detection and the action execution by target cues were associated with increased supplementary motor area (SMA) activity. In contrast, we found enhanced premotor cortex (PMC) activation with action cue during the prospective memory task, suggesting that the PMC may be involved in stimulus-induced and rather automatic action. These results demonstrate the effectiveness of implicit cues for examining the maintenance of intention. Overall, we found that implicit target cues can facilitate prospective memory performance, and implicit action cues can accelerate responses. The above-mentioned neural underpinnings suggest that attentional and motor control processes are involved in the enhancement of prospective memory. © 2010 Elsevier Inc.

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Autonomic reactivity of hypothesis-testing in decision-making

Terasawa Yuri, Umeda Satoshi

Psychologia 53 （ 3 ） 195 - 206 2010年09月

ISSN 0033-2852

Given the results of studies using the Iowa Gambling Task (IGT), emotion-based sensitivity to an anticipated outcome of one's own behavior has been suggested to be a significant factor in making advantageous decisions. Hypotheses-testing in performing IGT is essential for learning correct rules and elicits autonomic reactivity. In this study, participants were asked to concentrate on hypothesis-testing to learn undisclosed rules in the task which framework was similar to the IGT, rather than maximizing monetary reward. The amplitudes of skin conductance responses (SCRs) prior to card selection and following feedback were attenuated as participants came to accurately comprehend the task rules. The attenuation of SCRs resulted from reduced motivation to continue the hypotheses-testing. Our findings provide some evidence that observed autonomic responses partially reflect emotional reactions associated with the hypothesis-testing.

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Acquired personality traits of autism following damage to the medial prefrontal cortex

Umeda Satoshi, Mimura Masaru, Kato Motoichiro

Social Neuroscience 5 （ 1 ） 19 - 29 2010年02月

ISSN 1747-0919

Recent neuroimaging studies on "theory of mind" have demonstrated that the medial prefrontal cortex (PFC) is involved when subjects are engaged in various kinds of mentalising tasks. Although a large number of neuroimaging studies have been published, a relatively small amount of neuropsychological evidence supports involvement of the medial PFC in theory of mind reasoning. We recruited two neurological cases with damage to the medial PFC and initially performed the standard neuropsychological assessments for intelligence, memory, and executive functions. To examine theory of mind performance in these two cases, four kinds of standard and advanced tests for theory of mind were used, including first- and second-order false belief tests, the strange stories test, and the faux pas recognition test. Both patients were also requested to complete the questionnaire for the autism-spectrum quotient. Neither case showed impairment on standard theory of mind tests and only mild impairments were seen on advanced theory of mind tests. This pattern of results is basically consistent with previous studies. The most interesting finding was that both cases showed personality changes after surgical operations, leading to characteristics of autism showing a lack of social interaction in everyday life. We discuss herein the possible roles of the medial PFC and emphasize the importance of using multiple approaches to understand the mechanisms of theory of mind and medial prefrontal functions. © 2009 Psychology Press.

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Simulator platform that enables social interaction simulation - SIGVerse

Inamura Tetsunari, Shibata Tomohiro, Sena Hideaki, Hashimoto Takashi, Kawai Nobuyuki, Miyashita Takahiro, Sakurai Yoshiki, Shimizu Masahiro, Otake Mihoko, Hosoda Koh, Umeda Satoshi, Inui Kentaro, Yoshikawa Yuichiro

212 - 217 2010年

Understanding mechanisms of intelligence of human beings and animals is one of the most important approaches to develop intelligent robot systems. Since the mechanisms of such real-life intelligent systems are so complex, physical interactions between agents and their environment and the social interactions between agents should be considered. Comprehension and knowledge in many peripheral fields such as cognitive science, developmental psychology, brain science, evolutionary biology, and robotics is also required. Discussions from an interdisciplinary aspect are very important for implementing this approach, but such collaborative research is time-consuming and labor-intensive, and it is difficult to obtain fruitful results from such research because the basis of experiments is very different in each research field. In the social science field, for example, several multi-agent simulation systems have been proposed for modeling factors such as social interactions and language evolution, whereas robotics researchers often use dynamics and sensor simulators. However, there is no integrated system that uses both physical simulations and social communication simulations. Therefore, we developed a simulator environment called SIGVerse that combines dynamics, perception, and communication simulations for synthetic approaches to research into the genesis of social intelligence. In this paper, we introduce SIGVerse, its example application and perspectives. ©2010 IEEE.

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Preserved priming but insensitivity to perceptual fluency on recognition judgments in Alzheimer's disease

Yano Madoka, Umeda Satoshi, Mimura Masaru

Psychogeriatrics 8 （ 4 ） 178 - 187 2008年

ISSN 1346-3500

Background: Previous research on Alzheimer's disease (AD) has not yielded a consensus regarding the preservation of automatic memory processes, although there is a consensus that conscious recollection processes are impaired in AD. Methods: In the present study, we examined perceptual specificity effects (PSEs) in word recognition judgments (explicit memory task; Experiment 1) and word fragment completion (implicit memory task; Experiment 2) performed by individuals with mild AD and elderly adults without dementia (controls). Results: In recognition judgments, control subjects, but not individuals with AD, demonstrated PSEs (Experiment 1). In contrast, neither group showed PSEs on word fragment completion and their priming magnitudes were comparable (Experiment 2). Conclusions: The findings suggest that perceptually automatic processes in explicit memory judgments and implicit memory processes are different and that the former are specifically impaired in AD. © 2008 The Author Journal compilation © 2008 The Japanese Psychogeriatric Society.

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Unilateral amygdala lesions hamper attentional orienting triggered by gaze direction

Akiyama Tomoko, Kato Motoichiro, Muramatsu Taro, Umeda Satoshi, Saito Fumie, Kashima Haruo

Cerebral Cortex 17 （ 11 ） 2593 - 2600 2007年11月

ISSN 1047-3211

The newly discovered deficit in a bilateral amygdala-damaged case, of not being able to allocate attention to the critical feature of a face (Adolphs R, Gosselin F, Buchanan TW, Tranel D, Schyns P, Damasio AR. 2005. A mechanism for impaired fear recognition after amygdala damage. Nature. 433:68 - 72.), has opened a new window into the function of the amygdala. This case implies that the amygdala might be essential in detecting potentially relevant social stimuli, and directing attention accordingly. In this study, we have sought to test this implication by investigating the behavioral performance of 5 unilateral amygdala-damaged subjects on spatial cueing tasks. The tasks employed central gaze and arrow direction as cues to trigger attentional orienting in peripheral target detection. Although age-matched normal controls demonstrated a significant congruency effect such that targets presented congruently to cue direction elicited faster detection, amygdala subjects demonstrated no such congruency effect for gaze cues in the face of a significant congruency effect for arrow cues. The results suggest that the social valence of a stimulus is critical for amygdala involvement in visual processing. The results also support the implicated role of the amygdala in detecting and analyzing relevant social stimuli, and orienting attention accordingly. © The Author 2007. Published by Oxford University Press. All rights reserved.

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Altered brain activation by a false recognition task in young abstinent patients with alcohol dependence

Akine Yoshihide, Kato Motoichiro, Muramatsu Taro, Umeda Satoshi, Mimura Masaru, Asai Yoshiyuki, Tanada Shuji, Obata Takayuki, Ikehira Hiroo, Kashima Haruo, Suhara Tetsuya

Alcoholism: Clinical and Experimental Research 31 （ 9 ） 1589 - 1597 2007年09月

ISSN 0145-6008

Background: Heavy alcohol intake induces both structural and functional changes in the central nervous system. Recent research developments converged on the idea that even in patients with alcohol dependence without apparent structural brain changes, some cognitive impairment exists, and associated functional change could be visualized by neuroimaging techniques. However, these data were from old (more than 50 years) patients using working memory and response inhibition tasks. Whether young abstinent patients show aberrant signs of brain activation is a matter of interest, specifically by the long-term memory retrieval task. Methods: Subjects were 9 young patients with alcohol dependence with long-term abstinent (8 males and 1 female) and age- and education-matched 9 healthy controls (7 males and 2 females). We used a modified false recognition task in a functional MRI study. Results: The young patients with alcohol dependence showed reduced activation in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), left pulvinar in the thalamus, and in the right ventral striatum, although behavioral performances and regional patterns of brain activation were similar between patients and controls. Conclusions: Long-term memory retrieval induced altered activations in prefrontal lobes, ACC, thalamus, and ventral striatum in young patients with alcohol dependence. These findings were correspondent to deficits of goal directed behavior, monitoring the erroneous responses, memory function, and drug-seeking behavior. Furthermore, these reduced activations can be considered as latent "lesions," suggesting subclinical pathology in alcoholic brains. © 2007 by the Research Society on Alcoholism.

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Dissociative contributions of medial temporal and frontal regions to prospective remembering

Umeda Satoshi, Nagumo Yumi, Kato Motoichiro

Reviews in the Neurosciences 17 （ 1-2 ） 267 - 278 2006年

ISSN 0334-1763

Prospective memory is memory of future intentions or plans in everyday life. Although some previous neuropsychological studies have stated that the prefrontal cortex and the medial temporal lobe are essential for successful prospective remembering, how the two regions contribute to prospective remembering remains unclear. We therefore used prospective memory training in the present study to investigate the neural mechanism of two components of prospective remembering: remembering to remember and remembering content. Two brain-damaged patients participated in this study: patient Y.O., who had lesions in the medial temporal lobe bilaterally, and patient T.K., who had a lesion in the basal forebrain and right medial frontal lobe. Both participants exhibited a severe antero-grade amnesic syndrome and had normal IQ scores. Before the prospective memory training the participants underwent several index memory tests to examine their general memory and prospective memory performance. The training consisted of requesting the participants to perform an original mini-day task, in which they were first asked to memorize five simple daily actions with their times for execution, and then to recall the content of the actions when shown a drawing of a clock showing the proper time for execution. A training session was carried out once a week for 3 months. After completing training, the participants were again requested to take the same index memory tests. The results of the training task showed that Y.O.'s memory performance had gradually improved across all sessions of training, but T.K.'s improvement was not as marked. A more detailed analysis revealed that Y.O.'s memory performance was better for recalling time than for recalling content, whereas T.K.'s memory performance was better for recalling content than for recalling time. Furthermore, the results of the final index memory tests showed that the only improvement in Y.O.'s prospective memory was in remembering to remember, and that the only improvement in T.K.'s prospective memory was in remembering content. These results provide strong evidence that these two remembering components of prospective memory have independent neural bases, with the basal forebrain and right medial frontal lobe being required for remembering to remember, and the medial temporal lobe being required for remembering content. The results also suggest that memory training is an effective, means of improving everyday memory. © Freund & Pettman.

Gaze but not arrows

Akiyama Tomoko, Kato Motoichiro, Muramatsu Taro, Saito Fumie, Umeda Satoshi, Kashima Haruo

Neuropsychologia 44 （ 10 ） 1804 - 1810 2006年

ISSN 0028-3932

Superior temporal sulcus (STS) activation has consistently been demonstrated in the normal brain when viewing eyes, and thus this area is implicated as a gaze processing region in humans. In a recent report, we have presented a case, M.J., with a well-circumscribed lesion to the right superior temporal gyrus (STG), who demonstrated impaired discrimination of gaze direction. In the aim to make distinct whether this impairment is unique to gaze, we have applied a spatial cueing paradigm established by Kingstone and colleagues. In our experiment, pictorial gaze and symmetrical arrows were centrally presented as non-predictive, spatial cues in detecting peripheral targets. Fifteen normal subjects and M.J. participated in the experiment. In concordance with previous reports, controls demonstrated a significant facilitation of reaction times in detecting targets cued by congruent gaze/arrows, compared with incongruent cues. In striking contrast, M.J. showed no such congruency advantage for gaze, in the face of a normal congruency advantage for arrows. We have demonstrated that a circumscribed lesion to the right STG impairs the ability to utilize biological directional information such as gaze, but leaves the non-biological counterpart (arrows) intact. This dissociation implies that indeed, the STS specializes in processing gaze. © 2006 Elsevier Ltd. All rights reserved.

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Functional network in the prefrontal cortex during episodic memory retrieval

Umeda Satoshi, Akine Yoshihide, Kato Motoichiro, Muramatsu Taro, Mimura Masaru, Kandatsu Susumu, Tanada Shuji, Obata Takayuki, Ikehira Hiroo, Suhara Tetsuya

NeuroImage 26 （ 3 ） 932 - 940 2005年07月

ISSN 1053-8119

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC. © 2005 Elsevier Inc. All rights reserved.

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虚記憶と前頭前野の機能について

梅田聡，加藤元一郎

臨床精神医学 32 1515-1520 2003年

研究論文（学術雑誌）, 共著

ミニデー課題を用いた展望記憶訓練: 側頭葉性健忘例と前脳基底部健忘例の比較について

南雲祐美，加藤元一郎，梅田聡，鹿島晴雄

認知リハビリテーション2003 123-130 2003年

研究論文（学術雑誌）, 共著

ミニデー課題を用いた展望記憶訓練の効果について

南雲祐美，加藤元一郎，梅田聡，吉村茂和，鹿島晴雄

認知リハビリテーション2002 90-94 2003年

研究論文（学術雑誌）, 共著

フォールスメモリ

梅田聡

臨床精神医学 31 1126-1128 2002年

研究論文（学術雑誌）, 単著, 査読有り

認知神経科学的アプローチによる近年の記憶研究の動向

梅田聡

精神神経学雑誌 104 115-118 2002年

研究論文（学術雑誌）, 単著, 査読有り

前頭葉損傷に伴う虚再認傾向の増加

梅田聡・小谷津孝明

基礎心理学研究 19 45-46 2001年09月

研究論文（学術雑誌）, 共著, 査読有り

False recognition in patients with ventromedial prefrontal lesions.

Umeda, S., Akine, Y., & Kato, M.

Brain and Cognition 47 362-365 2001年

研究論文（学術雑誌）, 共著, 査読有り

Directed forgetting effect in patients with frontal lobe damage.

Mimura, M., Komatsu, S., Kato, M., Umeda, S., Saito, F., & Kashima, H.

Brain and Cognition 47 343-346 2001年

研究論文（学術雑誌）, 共著, 査読有り

し忘れはなぜ起こるのか: 認知神経心理学から見た展望的記憶研究

梅田聡

認知リハビリテーション2001 1-10 2001年

研究論文（学術雑誌）, 単著, 査読有り

虚再認パラダイムを用いた前頭葉研究

梅田聡

神経心理学 17 170-174 2001年

研究論文（学術雑誌）, 単著, 査読有り

101. False recognition in patients with ventromedial prefrontal lesions

Umeda S., Akine Y., Kato M.

Brain and Cognition 47 （ 1-2 ） 362 - 365 2001年

ISSN 0278-2626

In the present study, we used the typical false recognition paradigm to test a hypothesis that the ventromedial prefrontal cortex (VMPFC) mediates event-category judgement and retrieving past similar events. Eight VMPFC patients and 10 normal subjects were first requested to learn 18 sets of 14 semantic associates. In the test phase, participants were asked to recognize paired words including true words, related lures, and unrelated lures. The VMPFC patients showed significantly higher false alarm rates than the normal subjects for lure words. A further analysis suggests that the VMPFC patients succeeded in judging the event category, yet they were more likely to fail to retrieve past similar events. © 2001 Academic Press.

95. Directed forgetting effect in patients with frontal lobe damage

Mimura M., Komatsu S., Kato M., Umeda S., Saito F., Kashima H.

Brain and Cognition 47 （ 1-2 ） 343 - 346 2001年

ISSN 0278-2626

To study the role of the frontal lobes in episodic remembering, directed forgetting effect of frontal patients was examined. Eight patients with frontal lobe damage, eight patients with temporoparietal lobe damage, and eight normal subjects were given a list of 24 nouns (12 remember-cued words and 12 forget-cued words). On the list method (Experiment 1), frontal patients were significantly impaired in recalling remember-cued items whereas they recalled inappropriate forget-cued items. Frontal patients showed much less directed forgetting effect than two control groups. On the item method (Experiment 2), performance of frontal patients was in between the other two groups. Patients with frontal lobe damage appeared to have impaired retrieval inhibition, and their retrieval process is interfered with by inappropriate stimuli which should be forgotten. © 2001 Academic Press.

コルサコフ症候群における展望的記憶

梅田聡，加藤元一郎，三村將，鹿島晴雄，小谷津孝明

神経心理学 16 193-199 2000年09月

研究論文（学術雑誌）, 共著, 査読有り

頭部外傷患者における展望的記憶

中村明義，宮原保之，梅田聡，藤井浩治，原晃一

神経外傷 22 53-57 1999年12月

研究論文（学術雑誌）, 共著, 査読有り

Prospective memory and its theoretical considerations

Umeda Satoshi, Koyazu Takaaki

Shinrigaku Kenkyu 69 （ 4 ） 317 - 333 1998年10月

ISSN 0021-5236

Prospective memory involves memory for future intentions in our everyday lives and it is one of the hot topics in current memory research. We reexamined what is prospective memory and discussed how intentions had been conceived of in the history of psychology. We emphasize the necessity of classifying a form of remembering intentions into the self-initiated existence-remembrance and its content-remembrance. Many studies on prospective memory in recent decades were reviewed with respect to the following perspectives: (1) how intentions are recollected, (2) what is remembering intentions based on, (3) how we attempt to avoid forgetting to do things, and (4) what is neuropsychological mechanism of remembering intentions. Requirements for experimental research on prospective memory are summarized and future directions are discussed.

展望的記憶研究の理論的考察

梅田聡，小谷津孝明

心理学研究 69 317-333 1998年

研究論文（学術雑誌）, 共著, 査読有り

計算システムとのインタラクション --- 楽しさを促進する要因に関する考察 ---

山本吉伸，松井孝雄，開一夫，梅田聡，安西祐一郎

認知科学 1 107-120 1994年

研究論文（学術雑誌）, 共著, 査読有り

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