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

<p>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.</p>

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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

<p>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.</p>

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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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