研究者詳細 - 梅田　聡

論文 - 梅田　聡

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総説安静時fMRIにおける動的機能結合の臨床応用

品川和志, 寺澤悠理, 梅田聡

BRAIN and NERVE （株式会社医学書院） 73 （ 11 ） 1267 - 1273 2021年11月

ISSN 18816096

The conventional analysis assumes a constant mental state during scanning and assesses the strength of functional connectivity as the average of the entire fMRI data. However, it is suggested that even at rest, functional connectivity may change with time, and the conventional analysis has not been able to fully evaluate its properties. To overcome this limitation, many studies propose an index called dynamic functional connectivity (dFC) or time-varying functional connectivity (TVFC) or the chronnectome. This article reviews the significance and methods of dFC, examples of its application in clinical studies, and its limitations. Finally, we discuss its potential for clinical application.

増大特集脳とからだ Ⅲ.中枢と末梢の相互作用主観的感情と内受容感覚の神経メカニズム

梅田聡

生体の科学（株式会社医学書院） 72 （ 5 ） 454 - 456 2021年10月

ISSN 03709531

増大特集脳とからだ Ⅲ.中枢と末梢の相互作用覚醒下手術による感情認識に関わる島皮質機能の解明-脳とこころの脳神経外科学・認知神経科学の融合型研究

本村和也, 寺澤悠理, 梅田聡

生体の科学（株式会社医学書院） 72 （ 5 ） 461 - 463 2021年10月

ISSN 03709531

Products With High Purchase Frequency Require Greater Inhibitory Control: An Event-Related Potential Study

Tsuji K., Shibata M., Terasawa Y., Umeda S.

Frontiers in Psychology 12 2021年09月

One’s past behavior influences their present behavior. The effects of such response history have often been tested using response inhibition tasks. Since previous studies have highlighted the effect of immediate action history formed directly before the subsequent response in a laboratory environment, we aimed to elucidate the longer-term effects of response history, using repetitive and habitual consumer behavior in daily life as the response history. We used event-related potentials recorded in a Go/No-go task to investigate brain activity related to inhibitory control, hypothesizing that stimuli with a high frequency of choice in everyday life would elicit stronger inhibition-related activity, that is, the No-go-N2 component. Participants were asked to evaluate the frequency of purchase and use of some products, such as food and drink or social networking services (SNS) in everyday situations. Images of each product were assigned as stimuli in the Go and No-go trials according to the frequency of choice. The results showed that frequently purchased No-go stimuli yielded a larger amplitude of the No-go-N2 component and a negative shift between 200 and 300ms after the presentation of No-go stimuli. The results suggest that frequently chosen products evoke stronger inhibition conflicts and require greater cognitive control to withhold a response. Our findings showed that repeated purchase behavior in daily life forms a response history and has a long-term influence on the inhibition of even simple approaching behaviors, such as button pressing.

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Effects of interoceptive accuracy in autonomic responses to external stimuli based on cardiac rhythm

Tanaka Y., Terasawa Y., Umeda S.

Plos One 16 （ 8 August ） 2021年08月

Interoceptive accuracy is an index of the ability to perceive an individual's internal bodily state, including heartbeat and respiration. Individual differences in interoceptive accuracy influence emotional recognition through autonomic nervous activity. However, the precise mechanism by which interoceptive accuracy affects autonomic reactivity remains unclear. Here, we investigated how cardiac reactivity induced by a non-affective external rhythm differed among individuals, using a heartbeat counting task. Because individuals with poor interoceptive accuracy cannot distinguish an external rhythm from their cardiac cycles, it has been hypothesized that the interoceptive effect on heart rate works differently in individuals with good interoceptive accuracy and those with poor interoceptive accuracy. Study participants observed a visual or auditory stimulus presented at a rhythm similar to the participants' resting heart rates. The stimulus rhythm was gradually changed from that of their resting heart rate, and we recorded electrocardiographs while participants were exposed to the stimuli. Individuals with good interoceptive accuracy exhibited a deceleration in heart rate when the rhythm of the auditory stimulus changed. In contrast, in the group with poor interoceptive accuracy, the heart rate decreased only when the stimulus became faster. They were unable to distinguish the rhythm of their own heartbeat from that of the external rhythm; therefore, we propose that such individuals recognize the stimuli at the pace of their heart rate. Individuals with good interoceptive accuracy were able to distinguish their heart rates from the external rhythm. A modality difference was not observed in this study, which suggests that both visual and auditory stimuli help mimic heart rate. These results may provide physiological evidence that autonomic reactivity influences the perception of the internal bodily state, and that interoception and the autonomic state interact to some degree.

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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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自己と他者に関する未来思考におけるポジティブバイアスの違い

伊藤友一, 田仲祐登, 辻幸樹, 品川和志, 柴田みどり, 寺澤悠理, 梅田聡

日本認知心理学会発表論文集（日本認知心理学会） 2020 （ 0 ） 41 - 41 2021年03月

人の思考には時間（過去/未来），感情（ネガティブ/ポジティブ），自己/他者など様々な方向性があり，特に未来に関する思考のポジティブバイアスが多くの先行研究で示されている。しかしながら，それらは個人的な未来の想像を主な対象としており，他者の未来の想像でも同様のバイアスが生じるのかは明らかでない。本研究では，「私（彼）は／将来／試験に…」のように文手がかりを，主語，時間，内容の順に呈示し，自己または他者の未来について思考するよう参加者に求めた。このとき思考の感情価は参加者が任意に決定した。ポジティブ思考数がネガティブ思考数より多いことを以てポジティブバイアスとし，その傾向が自己に関する思考と他者に関する思考との間で異なるかどうか検討した。その結果，他者の遠い未来を想像するときにより強いポジティブバイアスが生じており，自己-他者間で異なる感情処理がなされていることが示唆された。

Lewy小体病における自律神経障害と認知障害

朝比奈正人, 梅田聡

脳神経内科 95 749 - 755 2021年

CiNii Research

β-Lactolin Enhances Neural Activity, Indicated by Event-Related P300 Amplitude, in Healthy Adults: A Randomized Controlled Trial

Kanatome A., Ano Y., Shinagawa K., Ide Y., Shibata M., Umeda S.

Journal of Alzheimer S Disease 81 （ 2 ） 787 - 796 2021年

ISSN 13872877

Background: Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a Gly-Thr-Trp-Tyr lacto-tetrapeptide rich in fermented dairy products that improves memory retrieval, attention, and executive function in older adults with subjective cognitive decline and prevents the pathology of Alzheimer's disease in rodents. There has been no study on the effects of β-lactolin on neural activity in humans. Objective: We investigated the effects of β-lactolin on neural activity and cognitive function in healthy adults. Methods: In this randomized, double-blind, placebo-controlled study, 30 participants (45-64 years old) consumed β-lactolin or placebo for 6 weeks. Neural activity during auditory and language tasks was measured through 64-channel electroencephalography. Moreover, verbal fluency tests were performed at baseline and after 6 weeks. Results: The β-lactolin group had a significantly higher P300 amplitude at the Cp2 site (a part of the parietal lobe near the center of brain, p=0.011), and C4 site (the area between the frontal and parietal lobe, p=0.02) during the auditory tasks after 6 weeks than the placebo group. Thus, β-lactolin supplementation promoted neural activity in the parietal area, which increases concentration and attention during auditory cognitive tasks. Compared with the placebo group, the β-lactolin group also showed significant changes in the scores of verbal fluency test after 6 weeks (p=0.033). Conclusion: Our findings provide insight into the mechanisms underlying the effects of β-lactolin on attention in healthy adults.

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隠れマルコフモデルを用いた課題中の思考状態の推定

品川和志, 板垣翼, 梅田聡

日本心理学会大会発表論文集（公益社団法人日本心理学会） 85 （ 0 ） PI-044 - PI-044 2021年

マインドワンダリング（MW）研究では，課題中に提示されるプローブによってMWが捉えられる。そのため，実験中に提示されるプローブは，思考状態の正確な測定において重要である。これまでの手法では，課題集中あるいは課題無関連思考集中に二分するものが主流であった。しかし，思考状態は常にどちらかの思考に分類されるものではなく，複数の状態が共存することが考えられる。本研究では，Go/No-go課題を行っている最中に，思考状態の共存を認める思考プローブを提示し，検討を行った（N＝30）。結果として，複数の思考が共存しているという主観報告が得られた。一方で，主観報告が得られた背景にある状態を，隠れマルコフモデルを用いて推定すると，従来の手法同様，課題集中，MW，両者の中間という思考状態が推定された。さらに，MW状態である区間では他の状態と比較して，反応時間の分散の増加がみられた（F（2, 58）＝6.504, p＝.003）。従来のプローブ法と同様の状態が推定されたことから，従来の手法でもMWを十分捉えていると考えられるが，より正確にMWを捉えるためには，共存状態を考慮する必要があることが示唆された。

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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