Published papers

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC. © 2005 Elsevier Inc. All rights reserved.

Recent studies in cognitive neuroscience have suggested that the integration of information about the internal bodily state and the external environment is crucial for the experience of emotion. Extensive overlap between the neural mechanisms underlying the subjective emotion and those involved in interoception (perception of that which is arising from inside the body) has been identified. However, the mechanisms of interaction between the neural substrates of interoception and emotional experience remain unclear. We examined the common and distinct features of the neural activity underlying evaluation of emotional and bodily state using functional magnetic resonance imaging (fMRI). The right anterior insular cortex and ventromedial prefrontal cortex (VMPFC) were identified as commonly activated areas. As both of these areas are considered critical for interoceptive awareness, these results suggest that attending to the bodily state underlies awareness of one's emotional state. Uniquely activated areas involved in the evaluation of emotional state included the temporal pole, posterior and anterior cingulate cortex, medial frontal gyrus, and inferior frontal gyrus. Also the precuneus was functionally associated with activity of the right anterior insular cortex and VMPFC when evaluating emotional state. Our findings indicate that activation in these areas and the precuneus are functionally associated for accessing interoceptive information and underpinning subjective experience of the emotional state. Thus, awareness of one's own emotional state appears to involve the integration of interoceptive information with an interpretation of the current situation. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

Repetition blindness is defined as difficulty detecting repeated targets within an array of stimuli. However, it is unclear how emotion affects this phenomenon. In the present study, participants were exposed to happy and angry faces, and nonemotional stimuli shown in rapid serial visual presentation. They were required to identify the repeated targets, and the magnitude of repetition blindness was measured to indicate emotional effects. Analysis showed that, while there was no difference in accuracy between happy and angry faces on non-repeated trials, accuracy was significantly lower for angry faces on repeated trials inducing greater repetition blindness. This effect was stronger when the stimulus exposure rate was 150 msec, suggesting its early processes and strong capturing of attention. These results show that repetition blindness effect was stronger with angry faces, which is likely due to enhanced emotional alertness and increase in intensity of the processes inducing greater repetition blindness.

Superior temporal sulcus (STS) activation has consistently been demonstrated in the normal brain when viewing eyes, and thus this area is implicated as a gaze processing region in humans. In a recent report, we have presented a case, M.J., with a well-circumscribed lesion to the right superior temporal gyrus (STG), who demonstrated impaired discrimination of gaze direction. In the aim to make distinct whether this impairment is unique to gaze, we have applied a spatial cueing paradigm established by Kingstone and colleagues. In our experiment, pictorial gaze and symmetrical arrows were centrally presented as non-predictive, spatial cues in detecting peripheral targets. Fifteen normal subjects and M.J. participated in the experiment. In concordance with previous reports, controls demonstrated a significant facilitation of reaction times in detecting targets cued by congruent gaze/arrows, compared with incongruent cues. In striking contrast, M.J. showed no such congruency advantage for gaze, in the face of a normal congruency advantage for arrows. We have demonstrated that a circumscribed lesion to the right STG impairs the ability to utilize biological directional information such as gaze, but leaves the non-biological counterpart (arrows) intact. This dissociation implies that indeed, the STS specializes in processing gaze. © 2006 Elsevier Ltd. All rights reserved.

This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed.

Psychophysiological markers have been focused to investigate the psychopathology of psychiatric disorders and personality subtypes. In order to understand neurobiological mechanisms underlying these conditions, fear-conditioning model has been widely used. However, simple aversive stimuli are too simplistic to understand mechanisms because most patients with psychiatric disorders are affected by social stressors. The objective of this study was to test the feasibility of a newly-designed conditioning experiment using a stimulus to cause interpersonal conflicts and examine associations between personality traits and response to that stimulus. Twenty-nine healthy individuals underwent the fear conditioning and extinction experiments in response to three types of stimuli: a simple aversive sound, disgusting pictures, and pictures of an actors' face with unpleasant verbal messages that were designed to cause interpersonal conflicts. Conditioned response was quantified by the skin conductance response (SCR). Correlations between the SCR changes, and personality traits measured by the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised NEO Personality Inventory were explored. The interpersonal conflict stimulus resulted in successful conditioning, which was subsequently extinguished, in a similar manner as the other two stimuli. Moreover, a greater degree of conditioned response to the interpersonal conflict stimulus correlated with a higher ZANBPD total score. Fear conditioning and extinction can be successfully achieved, using interpersonal conflicts as a stimulus. Given that conditioned fear caused by the interpersonal conflicts is likely associated with borderline personality traits, this paradigm could contribute to further understanding of underlying mechanisms of interpersonal fear implicated in borderline personality disorder.

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.

This article reviews memory functions in the medial parietal areas, which consist of the retrosplenial cortex, the posterior cingulate cortex, and the precuneus. These areas are involved in various cognitive functions including memory processing, spatial cognition, and self-related processing. Fundamental previous studies from the areas of neuropsychology, neuroimaging, psychiatry, and neurology, are covered to describe memory-related functions in the medial parietal areas. The focus is on the default mode network and the encoding/retrieval flip as key issues for understanding memory functions in the medial parietal areas.

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.

Matured hop bitter acids (MHBA), produced by aging the hops used to make beer, activate the vagus nerve via bitter taste receptors and improve depression and cognitive function in mice. However, researchers have not investigated their effects on human autonomic nerves. This crossover study aimed to investigate the association between MHBA and the vagus nerve. We randomly assigned 34 participants (age: 30–64 years) into two sequences (n = 17 each). They performed cognitive tasks before and after a single supplementation with placebo or MHBA. We monitored the autonomic nerve activity using heart rate variability. Compared with placebo, MHBA supplementation significantly increased the high frequency (HF) and total power during cognitive tasks (322.2 ms2 [95 % confidence interval (CI), 28.0, 616.4]; p = 0.033 and 630.6 ms2 [95 % CI, 87.0, 1174.2]; p = 0.025, respectively). In summary, MHBA supplementation modulates the HF of parasympathetic nerve activity in healthy adults.