Published papers

Background: Pessimistic thinking about the future is one of the cardinal symptoms of major depression. Few studies have assessed changes in pessimistic thinking after undergoing cognitive behavioral therapy (CBT). A randomized clinical trial (RCT) was conducted with patients diagnosed with major depressive disorder (MDD) to determine whether receiving a course of CBT affects pessimistic future thinking using a future thinking task. Methods: Thirty-one patients with MDD were randomly assigned to either CBT (n = 16) or a talking control (TC) (n = 15) for a 16-week intervention. The main outcomes were the change in response time (RT) and the ratio of the responses for positive valence, measured by the future thinking task. Secondary outcomes included the GRID-Hamilton Depression Rating Scale, the Beck Depression Inventory-Second Edition (BDI-II), the Dysfunctional Attitude Scale (DAS), and the word fluency test (WFT). Results: Regarding the main outcomes, the CBT group showed reduced RT for the positive valence (within-group Cohen’s d = 0.7, p = 0.012) and negative valence (within-group Cohen’s d = 0.6, p = 0.03) in the distant future condition. The ratio of positive valence responses in both groups for all temporal conditions except for the distant past condition increased within group (distant future: CBT: Cohen’s d = 0.5, p = 0.04; TC: Cohen’s d = 0.8, p = 0.008; near future: CBT: Cohen’s d = 1.0, p < 0.001; TC: Cohen’s d = 1.1, p = 0.001; near past: CBT: Cohen’s d = 0.8, p = 0.005; TC: Cohen’s d = 1.0, p = 0.002). As for secondary outcomes, the CBT group showed greater improvement than the TC group regarding the need for social approval as measured by the DAS (p = 0.012). Conclusion: Patients with MDD who received CBT showed a reduced RT for the positive and negative valence in the distant future condition. RT in the future thinking task for depressed patients may be a potential objective measure for the CBT treatment process. Because the present RCT is positioned as a pilot RCT, a confirmatory trial with a larger number of patients is warranted to elucidate the CBT treatment process that influences future thinking. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021028, identifier UMIN000018155.

Interoception is sensation for the internal state of the body. Changes in the internal state of the body, such as the activity of internal organs and associated sensations and pain, are the instances of this sensation. It has been rapidly recognized over the past two decades and has come to attract attention as one of the elements underlying various mental functions. This paper outlines the definition of interoception, the systems of manifestation and dynamic regulation of interoception, the neural basis of interoception and methods of assessment.

The insular cortex is considered as a key region for the feeling emotion through interoception. Most studies reporting on the role of the insular cortex in the integration of interoception and emotion have used neuroimaging methods, but neuropsychological studies are limited. In the present study, we investigated the role of the insular cortex in emotion recognition in patients with tumors associated with the insular cortex by performing the heartbeat-counting and the facial expression recognition tasks before and after surgical resection. The results showed a significant association between changes in performance on the heartbeat-counting task before and after surgery and changes in sensitivity to angry and happy facial expressions. The results of this study indicate that resection of the insular region affects the recognition of emotions such as anger and happiness through interoception.

人の思考には時間(過去・未来)，感情(ポジティブ・ネガティブ），社会的(自己・他者)などの多様な方向性がある。先行研究は心拍誘発電位(HEP; heartbeat-evoked potential)を用いて，過去あるいは未来思考時の感情的方向が身体からの求心性信号を受けて規定されることを明らかにしている。しかし，感情的方向が思考生成のどの段階で決まるのかは明らかでない。本研究では，自己や他者の未来について思考する際の感情的方向性の生起時点を明らかにするため，脳波計測実験を行った。課題では，主語・時間・内容の3要素からなる文(例：私は／将来／試験に)を1要素ずつ呈示し，それに合わせて思考した上で，肯定あるいは否定的結末(例：自分が将来試験に受かるか否か)を自由に想像するよう参加者に求めた。結果，主語情報呈示時点のHEPで感情価による振幅の差が認められ，思考生成の最初期時点で身体からの求心性信号を受けて思考の感情的方向が規定されていることが明らかになった。

立位時の姿勢情報をフィードバックするトレーニングは，身体所有感の獲得を補助しメンタルヘルスを向上させる可能性がある．本研究では，モニタで提示された目標位置に足圧中心を移動・保持するトレーニングを行った．トレーニングが立位バランスに与える影響を調べるのに加え，ストレス負荷がかかる課題に対する身体的な反応が，トレーニングの有無によってどのように変化するかを比較した．

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。

Introduction: Although self-disturbances and emotional disturbances are common in schizophrenia, there is no integrated understanding to explain these symptoms. Interoception has a crucial role in the development of self and emotion, and interoceptive abnormality could lead to such symptoms. Methods: We compared interoceptive accuracy between controls and patients with schizophrenia. Forty-two patients and 30 healthy controls were recruited and their interoceptive accuracy was assessed using a heartbeat counting task. Participants were instructed to count the number of times they felt their own heartbeat during various measurement periods. Interoceptive accuracy was calculated based on the discrepancy between the number of reported and actual heartbeats during the measurement period. Participants also performed a time estimation task and were instructed to count the number of seconds there were during the same period. Time accuracy was calculated in a similar manner to that for the heartbeat. Participants also completed a questionnaire regarding interoception to assess their subjective experiences. Results: Interoceptive accuracy was significantly lower among patients with schizophrenia than in healthy controls (P =. 017), even after controlling for age, sex, time accuracy, anxiety, depression, educational level, and heart rate (HR). In addition, patients' positive and negative symptoms were significantly associated with their HR-adjusted interoceptive accuracy, especially hallucination. The discrepancy between HR-adjusted interoceptive accuracy and the score of the questionnaire was significantly associated with positive symptoms, especially delusion, but not negative symptoms. Discussion: These findings suggest that patients with schizophrenia have aberrant interoception. Aberrant interoception in schizophrenia could be a novel therapeutic target in future.

© 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.

© 2019 Ihara et al. Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and aIC associated with CNP and its related FAB.

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.

© 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.

© 2019 Electroconvulsive therapy (ECT) is the most effective antidepressant treatment. Biological predictors of clinical outcome to ECT are valuable. We aimed to examine multimodal magnetic resonance imaging (MRI) data that correlates to the efficacy of ECT. Structural and resting-state functional MRI data were acquired from 46 individuals (25 depressed individuals who received ECT, and 21 healthy controls). Whole-brain grey matter volume (GMV) and fractional amplitude of low frequency fluctuations (fALFF) were investigated to identify brain regions associated with post-ECT Hamilton Depression Rating Scale (HAM-D) total scores. GMV and fALFF values were compared with those in healthy controls using analysis of covariance (ANCOVA). Remission was defined by HAM-D ≤7. A multiple regression analysis revealed that pretreatment smaller GMV in the left thalamus was associated with worse response to ECT (i.e. higher post-ECT HAM-D). Pretreatment higher fALFF in the right anterior insula, and lower fALFF in the left thalamus and the cerebellum were associated with worse outcomes. The left thalamus was identified in both GMV and fALFF analyses. Nonremitters showed significantly smaller thalamic GMV compared to remitters and controls. We found that pretreatment thalamic volume and resting-state activity were associated with the efficacy of ECT. Our results highlight the importance of the thalamus as a possible biological predictor and its role in the underlying mechanisms of ECT action.

© 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.

© 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.

© 2019, The Author(s). Chronic pain (CP) is a global problem extensively associated with an unhealthy lifestyle. Time discounting (TD), a tendency to assign less value to future gains than to present gains, is an indicator of the unhealthy behaviors. While, recent neuroimaging studies implied overlapping neuro mechanisms underlying CP and TD, little is known about the specific relationship between CP and TD in behavior or neuroscience. As such, we investigated the association of TD with behavioral measures in CP and resting-state brain functional network in both CP patients and healthy subjects. Behaviorally, TD showed a significant correlation with meaningfulness in healthy subjects, whereas TD in patients only correlated with pain intensity. We identified a specific network including medial and dorsolateral prefrontal cortex (PFC) in default mode network (DMN) associated with TD in healthy subjects that showed significant indirect mediation effect of meaningfulness on TD. In contrast, TD in patients was correlated with functional connectivity between dorsolateral PFC (DLPFC) and temporal lobe that mediated the effect of pain intensity on TD in patients. These results imply that TD is modulated by pain intensity in CP patients, and the brain function associated to TD is shifted from a medial to lateral representation within the frontal regions.

© 2018 Association for Computing Machinery. Although mental illness is one of the most serious social problems, stress does not necessarily have a negative effect, on the contrary, an optimal amount of stress can result in individuals being able to perform better in tasks. While there have been several studies on estimating stress level from smartphone usage logs and several effective features were revealed as a result, there are few studies on estimating cognitive performance. Thus, in this paper, we explore several factors affecting the estimation of cognitive performance from smartphone logs. To conduct the analysis, we collected smartphone usage logs and Go/No-Go task data for 6 weeks from 39 participants in the wild. We found that the time to find intended app is related to cognitive performance. This result suggests that measuring the time to find intended app can be the effective feature of estimating cognitive performance from smartphone logs.