Published papers

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

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

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

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

Sense of agency refers to the feeling that one's voluntary actions caused external events. Past studies have shown that compression of the subjective temporal interval between actions and external events, called intentional binding, is closely linked to the experience of agency. Current theories postulate that the experience of agency is constructed via predictive and postdictive pathways. One remaining problem is the source of human causality bias; people often make misjudgments on the causality of voluntary actions and external events depending on their rewarding or punishing outcomes. Although human causality bias implies that sense of agency can be modified by post-action information, convincing empirical findings for this issue are lacking. Here, we hypothesized that sense of agency would be modified by affective valences of action outcomes. To examine this issue, we investigated how rewarding and punishing outcomes following voluntary action modulate behavioral measures of agency using intentional binding paradigm and classical conditioning procedures. In the acquisition phase, auditory stimuli were paired with positive, neutral or negative monetary outcomes. Tone-reward associations were evaluated using reaction times and preference ratings. In the experimental session, participants performed a variant of intentional binding task, where participants made timing judgments for onsets of actions and sensory outcomes while playing simple slot games. Our results showed that temporal binding was modified by affective valences of action outcomes. Specifically, intentional binding was attenuated when negative outcome occurred, consistent with self-serving bias. Our study not only provides evidence for postdictive modification of agency, but also proposes a possible mechanism of human causality bias. © 2012 Takahata et al.

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

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

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

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.

INTRODUCTION: 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.

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.

Interoception has been proposed as a factor that influences various psychological processes (Khalsa et al., 2018). Afferent signals from the cardiovascular system vary across cardiac cycle phases. Heartbeat-evoked potentials (HEP) and event-related potentials (ERP) were measured to examine whether interoceptive signals differed between cardiac cycle phases. Simultaneously, participants performed an auditory oddball task in which the timing of the presenting stimulus was synchronized with the heartbeat. Pure tones were presented at 10 ms (late diastole condition), 200 ms (systole condition), or 500 ms after the R wave (diastole condition). Greater HEP amplitudes were observed when the tone was presented during diastole than during systole or late diastole. ERP showed the same tendency: a greater amplitude was observed during diastole than systole or late diastole. These results suggest that the processing of interoception reflected by HEP and exteroception reflected by ERP share attentional resources when both stimuli coincide. When the tone was presented during systole, attention to the internal state decreased compared with when the tone was presented during diastole, and attention was distributed to both exteroception and interoception. Our study suggests that HEP may be considered an indication of a relative amount of resources to process the interoception.

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.

Facial skin blood flow (SkBF) has attracted attention as an autonomic indicator because it influences facial colour, which informs others of emotional states, and facial temperature related to social anxiety. Previous studies have examined the facial SkBF in people experiencing emotions; however, facial SkBF changes in the observers of emotions are poorly understood. Our study clarified facial SkBF changes related to observing others’ emotions by comparing the changes with other physiological indices. Thirty healthy participants (24 females; mean age: 22.17) observed six types of facial expressions (neutral, angry, and embarrassed expressions with and without facial blushing) and rated the emotional intensity of the other person. We measured their facial SkBF, finger SkBF, and cardiac RR interval as they made their observations. Facial SkBF generally decreased in relation to observing emotional faces (angry and embarrassed faces) and significantly decreased for angry expressions with blushing. None of the participants noticed blushing of facial stimuli. For the RR interval and finger SkBF, there was no variation depending on the observed facial expressions, although there was a general increase related to observation. These results indicated that facial SkBF is sensitive and reactive to emotional faces—especially angry faces with blushing— compared with other autonomic indices. The facial SkBF changes were not related to either RR interval changes or the intensity rating, suggesting that facial SkBF changes may be caused by vasoconstriction and have potential functions for our emotions. The decrease in facial SkBF may have a role in calming observers by preventing them from adopting the same emotional state as a person with intense anger. These findings clarify daily facial SkBF fluctuations and their relationship with our emotional processing in interpersonal situations.