Published papers

Interoception is the perception of afferent information that arises from anywhere and everywhere within the body. Recently, interoceptive accuracy could be enhanced by cognitive training. Given that the anterior insula cortex (AIC) is a key node of interoception, we hypothesized that resting functional connectivity (RSFC) from AIC was involved in an effect of interoceptive training. To address this issue, we conducted a longitudinal intervention study using interoceptive training and obtained RSFC using fMRI before and after the intervention. A heartbeat perception task evaluated interoceptive accuracy. Twenty-two healthy volunteers (15 females, age 19.9 ± 2.0 years) participated. After the intervention, interoceptive accuracy was enhanced, and anxiety levels and somatic symptoms were reduced. Also, RSFC from AIC to the dorsolateral prefrontal cortex (DLPFC), superior marginal gyrus (SMG), anterior cingulate cortex (ACC), and brain stem, including nucleus tractus solitarius (NTS) were enhanced, and those from AIC to the visual cortex (VC) were decreased according to enhanced interoceptive accuracy. The neural circuit of AIC, ACC, and NTS is involved in the bottom-up process of interoception. The neural circuit of AIC, DLPFC, and SMG is involved in the top-down process of interoception, which was thought to represent the cognitive control of emotion. The findings provided a better understanding of neural underpinnings of the effect of interoceptive training on somatic symptoms and anxiety levels by enhancing both bottom-up and top-down processes of interoception, which has a potential contribution to the structure of psychotherapies based on the neural mechanism of psychosomatics.

Systemic inflammation affects psychological processes. Although the association between inflammation and psychophysiological state has been extensively investigated in patients with depression or inflammatory disease, how this relationship manifests in healthy individuals is not clearly known. Not all individuals exhibit distress in response to elevated inflammatory markers, suggesting the presence of psychological moderators. Elucidating the effect of elevated inflammatory markers on healthy adults would broaden the understanding of the relationship between inflammation and psychophysiological state. We investigated the moderating effect of individual factors, including emotion regulation, sleep quality, and interoceptive awareness, on the relationship between inflammatory markers and psychophysiological states in healthy adults. A total of 155 participants aged 30–59 years were assessed for inflammatory markers, individual factors, and subjective psychological and physical symptoms. Hierarchical regression and interaction models revealed that individuals with poor emotion regulation or low-quality sleep showed stronger associations between inflammatory markers and symptoms such as fatigue, somatic complaints, depression, and anxiety. Conversely, individuals with effective emotion regulation or high-quality sleep exhibited attenuated or even reversed associations, suggesting protective effects. Interoceptive awareness showed weaker and more context-dependent moderating effects. These results highlight the importance of psychological traits in modulating the effects of inflammation on mental and physical well-being in clinically healthy adults. Targeted interventions for enhancing emotion regulation and sleep quality may mitigate the psycho-physiological burden of inflammation and reduce the risk of future disease onset. The findings underscore the need for individualized psychoneuroimmunological models that incorporate trait-level moderators to explain variability in stress-related health outcomes.

© 2021, The Author(s). In modern society, many people have insomnia. Chronic insomnia has been noted as a risk factor for depression. However, there are few functional imaging studies of the brain on affective functions in chronic insomnia. This study aimed to investigate brain activities induced by emotional stimuli in chronic insomnia patients. Fifteen patients with primary insomnia and 30 age and gender matched healthy controls participated in this study. Both groups were presented images of fearful, happy, and neutral expressions consciously and non-consciously while undergoing MRI to compare the activity in regions of the brain responsible for emotions. Conscious presentation of the Happy-Neutral contrast showed significantly lower activation in the right orbitofrontal cortex of patients compared to healthy controls. The Happy-Neutral contrast presented in a non-conscious manner resulted in significantly lower activation of the ventral striatum, right insula, putamen, orbitofrontal cortex and ventral tegmental area in patients compared to healthy controls. Our findings revealed that responsiveness to positive emotional stimuli were decreased in insomniac patients. Specifically, brain networks associated with rewards and processing positive emotions showed decreased responsiveness to happy emotions especially for non-conscious image. The magnitude of activity in these areas also correlated with severity of insomnia, even after controlling for depression scale scores. These findings suggest that insomnia induces an affective functional disorder through an underlying mechanism of decreased sensitivity in the regions of the brain responsible for emotions and rewards to positive emotional stimuli.

Background: Despite the importance of Beck's theoretical cognitive model of psychopathology, the neural mechanisms underlying future thinking in cognitive behavioral therapy (CBT) remain elusive. Recent neuroimaging studies have shown that the function of the frontopolar cortex (Brodmann area 10 [BA10]) is associated with future thinking. We hypothesized that, compared with unstructured psychotherapy (talking control: TC), CBT may involve different neural responses in BA10 associated with future thinking. Methods: This randomized clinical trial included 38 adult patients with moderate-to-severe major depressive disorder who underwent up to 16 weeks of CBT or TC with a 6-month follow-up period. We evaluated changes in BA10 activation during distant future thinking using functional magnetic resonance imaging with a future-thinking task. We assessed frontal neurocognitive function and clinical symptoms at baseline and post-treatment. Depression severity and automatic thoughts were assessed at the 6-month follow-up. Results: We found decreased activation in the frontopolar cortex during distant future thinking after CBT (t = 3.00, df=15, p = 0.009) and no changes after TC. Further, the reduction in BA10 activity significantly correlated with changes in frontal cognitive function after the treatment (r = 0.48, p = 0.007), and in positive automatic thought after 6 months of treatments (r = 0.39; p = 0.03). Limitations: Relatively small sample size and homogenous clinical profile could limit the generalizability. Patients received pharmacotherapy including antidepressant. Conclusions: CBT appears to improve frontopolar cortex function during future thinking in a manner distinct from TC. Larger clinical trials are necessary to provide firm evidence whether BA10 activity may serve as a neuro-marker for monitoring successful depression treatment with CBT.

Cognitive behavioral therapy (CBT) and pharmacotherapy are primary treatments for major depressive disorder (MDD). However, their differential effects on the neural networks associated with rumination, or repetitive negative thinking, remain poorly understood. This study included 135 participants, whose rumination severity was measured using the rumination response scale (RRS) and whose resting brain activity was measured using functional magnetic resonance imaging (fMRI) at baseline and after 16 weeks. MDD patients received either standard CBT based on Beck’s manual (n = 28) or pharmacotherapy (n = 32). Using a hidden Markov model, we observed that MDD patients exhibited increased activity in the default mode network (DMN) and decreased occupancies in the sensorimotor and central executive networks (CEN). The DMN occurrence rate correlated positively with rumination severity. CBT, while not specifically designed to target rumination, reduced DMN occurrence rate and facilitated transitions toward a CEN-dominant brain state as part of broader therapeutic effects. Pharmacotherapy shifted DMN activity to the posterior region of the brain. These findings suggest that CBT and pharmacotherapy modulate brain network dynamics related to rumination through distinct therapeutic pathways.

Our thoughts are inherently dynamic and often wander far from our current situation (mind wandering, MW). Although previous research revealed that brain regions involved in arousal regulation modulate neural dynamics to facilitate the transition from MW to the awareness of its occurrence, the specific physiological states and afferent signals underlying this process remain unclear. In this study, we examined electroencephalography, electrocardiography, and respiration data before participants were aware of MW during a task in which they focused on external or internal stimuli (tones or their breath). We showed that the transition to awareness of MW was characterized by decreased alpha and beta activity and a suppression of the parietal later component of the heartbeat-evoked potential (HEP), a modulation pattern identified in this study as a marker of enhanced central processing based on its consistent appearance across internal attention conditions. Furthermore, when participants were instructed to focus on their breath, they were more likely to be in the exhalation phase during the transition to awareness of MW and in the inhalation phase when MW was reported. This respiratory pattern was accompanied by changes in cardiac activity and HEP amplitudes. Based on these findings, we propose that the transition from MW to the awareness of its occurrence is associated with diverse neural activity, including the enhanced processing of bodily signals that co-occurs with specific cardiac and respiratory dynamics.

A relationship between the awareness of mind-wandering (MW) and the disruption of MW because of external stimuli has previously been reported. Attention often fluctuates without external stimuli and such disruptions can spontaneously precede awareness of MW. To elucidate whether changes in attentional resources used by MW exist, we used event-related potentials (ERPs), focusing on the P300 (P3) ERP component as an index of attention to a task. Participants performed a simple task, in which they pressed a key in synchrony with continually presented tones. Moreover, they were asked to stop the response whenever they became aware of their MW. We analyzed the P3 induced by the tones before self-reports of MW using a state–space model that was used for analysis to detect changes over time. The results revealed that the mean amplitude of P3 increased significantly from the third to the second tone before the self-reports; no other clear increasing or decreasing tendencies were observed. We concluded that the attentional resources allocated to the main task returned, suggesting that such awareness requires a decrease in resources to task-unrelated thoughts. These findings highlight a transitional state related to awareness between the MW state and self-reports. Therefore, the state immediately before self-reports should not be defined as merely an MW state when using the self-caught method.

Interoception is the perception of the internal bodily state, including the autonomic nervous system. Recently, heartbeat evoked potentials (HEP) have been proposed as a measure of interoception. HEP is considered a brain potential with high temporal resolution reflecting afferent signals from the cardiovascular system without the need for subjective reporting. HEP relates to various cognitive responses such as attention, emotion, self-awareness, and symptoms of psychiatric disorders. In this review, we overview the studies of HEP, which is expected to be a useful index of mind-body interactions, and discuss the relationship between interoception and cognitive functions.

Interoception, the ability to perceive internal bodily signals, involves various mental processes. This study investigated moments when individuals experienced a change in their interoceptive state. Interoception affects the subjective feelings of emotions. However, whether changes in interoceptive processing occur when visceral changes are perceived as interoceptive sensations remains unclear. This study examined the psychophysiological markers of perceptual changes in the interoceptive state using heartbeat evoked potentials (HEP). Emotional photos were viewed by participants who were asked whether they experienced changes in their interoceptive state. The results showed that the HEP amplitude increased when participants had subjective awareness of changes in their interoceptive state. Notably, the HEP amplitude did not correlate with individual differences in interoceptive accuracy measured by the heartbeat counting task. When individuals perceive changes in their interoceptive state, this perception is reflected in the HEP amplitude. Multiple aspects of interoception are related to the emotional recognition and conscious attention to changing bodily states.

Aim: Schizophrenia (SZ) is characterized by abnormalities in self-representation, including an aberrant sense of agency (SoA). Experimentally observed abnormalities in force matching and intentional binding tasks suggest that the SoA in SZ is compromised at the implicit level. However, these task effects have been reported independently, leading to inconsistencies that complicate the understanding of SZ pathophysiology. Methods: Thirty-three patients with SZ and 37 nonclinical (healthy) controls (HCs) performed force matching and intentional binding tasks. The former task assessed sensory attenuation, while the latter evaluated an intentional binding effect, both measuring implicit levels of SoA. We previously observed that the cardiac phase (systole vs diastole) influences intentional binding. Therefore, we investigated the relationship between sensory attenuation and intentional binding, including this “cardiac effect,” which refers to the influence of cardiac interoceptive signals. Results: In SZ, significantly reduced sensory attenuation, a greater but nonsignificant intentional binding effect, and a significant opposite cardiac effect were observed compared with HCs. Sensory attenuation and intentional binding were significantly and positively correlated in the SZ group but not in the HC group. Across all participants, sensory attenuation correlated with the cardiac effect on intentional binding. This effect remained significant in the HC group but not in the SZ group. Conclusion: Group differences and task associations suggest shared mechanisms and pathophysiology in SZ, potentially involving impaired predictive processes and the failure of sensory attenuation. The cardiac effect may be explained by interoceptive sensory attenuation, and its failure could lead to a disturbed SoA in patients with SZ.

Background: Schizophrenia (SZ) is characterized by abnormalities in self-representation, including a disturbed sense of agency (SoA). The continuous processing of sensory information concerning the internal state of the body (interoception) is argued to be fundamental to neural representations of the self. We, therefore, tested if aberrant interoception underpins disturbances in SoA in SZ, focusing on cardiac interoceptive signaling. Methods: Forty-two SZ and 29 non-clinical participants (healthy controls; HC) performed an intentional binding task to measure SoA during concurrent heartbeat recording. The effect of cardiac interoceptive signals on SoA was measured by the difference in intentional binding effect during systole and diastole. This measure was standardized based on the overall intentional binding effect to control for non-cardiac factors, and then compared between SZ and HC. Results: Our study revealed a significant difference between SZ and HC groups, with opposite effects of cardiac systole on SoA. Specifically, cardiac systole disrupted SoA in SZ, contrasting with the enhanced SoA in HC. Across the SZ group, the extent to which SoA was disrupted by cardiac systole correlated significantly with a clinical proxy for symptom instability, namely the number of hospital admissions for hallucinations and delusions. Furthermore, the disruption was particularly observed in patients with severe hallucinations. Conclusions: This study revealed a disturbance in the impact of cardiac interoceptive signals on an implicit index of SoA in schizophrenia. This supports the notion that pathophysiological disruption of the central integration of interoceptive information increases vulnerability to disturbances in self-representation and the associated expression of schizophrenic symptoms.

This study investigates the short-term effects of biofeedback rehabilitation on postural balance performance, addressing a significant gap in existing research that has focused primarily on long-term outcomes. The present study aims to test the following hypothesis: Changes in the way sensory information is used through biofeedback training will lead to changes in postural balance performance in the short term. Experiments were conducted with five young, healthy individuals. Participants underwent biofeedback training sessions involving tasks such as maintaining the center of pressure of the feet within specific targets, and performed quiet standing tasks and standing tasks with both open and closed eyes before and after the training sessions.The results showed suggestive correlations between changes in sway during quiet standing and changes in sway with eyes open and closed before and after the training session, which differed between the training and control groups. This supports the hypothesis and suggests that biofeedback training may indirectly affect postural balance ability by altering the way sensory information is used and the existence of diverse strategies.Clinical Relevance - This leads to more effective biofeedback training designs based on reweighting in the use of sensory information

Purpose: This study examined the neural correlates in functional brain connectivity common to subjective and objective sleepiness. Because functional connectivity can be measured at rest and during tasks, it is well suited for exploring the commonalities between sleepiness during psychomotor vigilance task (PVT) and at rest with measurement of The Karolinska Sleepiness Scale (KSS). Serial resting and task-based fMRI measurements across various states of arousal may reveal a common neural substrate that does not vary with task demands. The neural basis shared by the PVT, an objective measure highly sensitive to sleep debt, and subjective reports of sleepiness may be robust markers for sleepiness and contribute to an improved understanding of the brain mechanisms underlying sleepiness. Participants and Methods: The participants were 16 healthy right-handed (self-reported) adult men who, after a 2-week home examination, participated in a 14-day/13-night experiment that included 9 days of extended sleep (12 h per night), followed by one night of total sleep deprivation (0 h), and recovery sleep. KSS and the PVT were used as subjective and objective measures of sleepiness, respectively. Functional connectivity in the brain during each condition were measured using fMRI. In particular, the association between the inverse of the reaction time to the PVT task and resting-state functional connectivity was analyzed using a general linear mixed model. Results: Functional connectivity in six pairs of regions commonly associated with the KSS and PVT were identified. These included the anterior cingulate cortex-posterior cingulate cortex (part of the default mode network) and thalamus-middle temporal cortex, indicating that connectivity in these brain regions were strongly associated with sleepiness. Conclusion: These results suggest a common neural substrate for subjective and objective sleepiness, which may be an important indicator of sleepiness. In addition, the functional connectivity between the thalamus and the middle temporal cortex may be a new network that deserves further attention in sleep research. The results of this study provide valuable insights into the effects of sleep deprivation and total sleep deprivation experienced in daily life on the brain and offer a new perspective on the expression of sleepiness in the brain.

In recent years, “interoception” has attracted attention as a cognitive science background for psychosomatic correlations. Interoception refers to the sensation of physiological states inside the body, such as breathing, heartbeat, and movement of the intestinal tract, and is considered a necessary function for maintaining homeostasis. In addition, interoceptive dysfunction has been observed in various stress-related disorders (e.g., PTSD, depression, anxiety disorders, psychosomatic disorders, and eating disorders).Interoceptive dysfunction has been widely studied in neuroscience and psychology. Interoceptive signals are believed to be concentrated in the insular cortex of the brain and projected to the amygdala, which is responsible for various emotional experiences. In addition, Damasio et al. showed that people with low interoceptive sensation are highly likely to engage in high-risk behaviors. These findings suggest that behavioral change is influenced by internal receptive sensations, which can be considered a factor that defines behavior. In our study, we observed a decrease in anxiety, a change in behavior, and a change in brain circuitry in the insular cortex when implementing a cognitive training task that directly strengthened the internal receptive sense.In this paper, we introduce the findings on abnormalities in interoceptive sensation as a model of psychosomatic correlations, and present the results of our intervention experiment that examined the relationship between interoceptive sensation and behavioral change.

We report a case with prosopagnosia for familiar faces due to a fresh cerebral infarction in the lateral region of the right occipital lobe in addition to an extensive old infarction of the left occipital lobe. The patient was a right-handed man in his 70s. Prosopagnosia and difficulties in recognizing facial expressions were observed, and attention function and processing speed were reduced in the present case. General cognitive function and visuospatial function remained normal except for facial cognition. Prosopagnosia was caused by the brain network dysfunction between the occipital face area, the fusiform face area and the anterior temporal lobe of the left and right hemispheres. Facial cognition, including age and gender judgments, was preserved. Diffusion tensor tractography suggested that this was due to the preservation of white matter fibres in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus of the right hemisphere. It is thought that cognitive rehabilitation to increase attention and processing speed is important for improving recognition of facial expressions.

Purpose: The thalamus, the region that forms the attentional network and transmits external sensory signals to the entire brain, is important for sleepiness. Herein, we examined the relationship between activity in the thalamus-seed brain network and subjective sleepiness. Materials and Methods: Fifteen healthy male participants underwent an experiment comprising a baseline evaluation and two successive interventions, a 9-day sleep extension followed by 1-night total sleep deprivation. Pre-and post-intervention tests included the Karolinska sleepiness scale and neuroimaging for arterial spin labeling and functional connectivity. We examined the association between subjective sleepiness and the functional magnetic resonance imaging indices. Results: The functional connectivity between the left or right thalamus and various brain regions displayed a significant negative association with subjective sleepiness, and the functional connectivity between the left and right thalamus displayed a significant positive association with subjective sleepiness. The graph theory analysis indicated that the number of positive functional connectivity related to the thalamus showed a strong negative association with subjective sleepiness, and conversely, the number of negative functional connectivity showed a positive association with subjective sleepiness. Arterial spin labeling analysis indicated that the blood flow in both the left and right thalami was significantly negatively associated with subjective sleepiness. Functional connectivity between the anterior cingulate cortex and salience network areas of the left insular cortex, and that between the anterior and posterior cingulate cortices showed a strong positive and negative association with subjective sleepiness, respectively. Conclusion: Subjective sleepiness and the thalamic-cortical network dynamics are strongly related, indicating the application of graph theory to study sleepiness and consciousness. These results also demonstrate that resting functional connectivity largely reflects the “state” of the subject, suggesting that the control of sleep and conscious states is essential when using functional magnetic resonance imaging indices as biomarkers.

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.

Research on mental health states involves paying increasing attention to changes in daily life. Researchers have attempted to understand such daily changes by relying on self-reporting through frequent assessment using devices (smartphones); however, they are mostly focused on a single aspect of mental health. Assessing the mental health of a person from various perspectives may help in the primary prevention of mental illness and the comprehensive measurement of mental health. In this study, we used users' smartphone logs to build a model to estimate whether the scores on three types of questionnaires related to quality of life and well-being would increase compared to the previous week (fluctuation model) and whether they would be higher compared to the average for that user (interval model). Sixteen participants completed three questionnaires once per week, and their smartphone logs were recorded over the same period. Based on the results, estimation models were built, and the F-score ranged from 0.739 to 0.818. We also analyzed the features that the estimation model emphasized. Information related to “physical activity,” such as acceleration and tilt of the smartphone, and “environment,” such as atmospheric pressure and illumination, were given more weight in the estimation than information related to “cyber activity,” such as usage of smartphone applications. In particular, in the Positive and Negative Affect Schedule (PANAS), 9 out of 10 top features in the fluctuation model and 7 out of 10 top features in the interval model were related to activities in the physical world, suggesting that short-term mood may be particularly heavily influenced by subjective activities in the human physical world.