Masahiro Matsunaga

Aichi Medical University, Okazaki, Aichi, Japan

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Publications (33)99.32 Total impact

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    ABSTRACT: Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude positive emotions when they experienced positive events and had a higher subjective happiness level.
    PLoS ONE 01/2014; 9(4):e93771. · 3.53 Impact Factor
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    ABSTRACT: We investigated whether vagal tone, as assessed by heart rate variability (HRV), moderates the neural correlates of immune and physiological responses to acute stress. Participants with low and high baseline HRV underwent a reversal learning task as an acute stressor. Natural killer cells, norepinephrine, and adrenocorticotropic hormone in peripheral blood changed with acute stress in the high HRV group only. Activity in the prefrontal cortex and striatum correlated with the immune and physiological indices in the high HRV group. High vagal tone may reflect more flexible top-down brain regulation of immune and physiological activity.
    Journal of neuroimmunology 05/2013; · 2.84 Impact Factor
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    ABSTRACT: The somatic marker hypothesis asserts that decision-making can be guided by feedback of bodily states to the brain. In line with this hypothesis, the present study tested whether sympathetic activity shows an association with a tonic dimension of decision-making, exploratory tendency represented by entropy in information theory, and further examined the neural mechanisms of the association. Twenty participants performed a stochastic reversal learning task that required decision-making in an unstable and uncertain situation. Regional cerebral blood flow was evaluated using (15)O-water positron emission tomography (PET), and cardiovascular indices and concentrations of catecholamine in peripheral blood were also measured, during the task. In reversal learning, increased epinephrine during the task positively correlated with larger entropy, indicating a greater tendency for exploration in decision-making. The increase of epinephrine also correlated with brain activity revealed by PET in the somatosensory cortices, anterior insula, dorsal anterior cingulate cortex, and dorsal pons. This result is consistent with previously reported brain matrixes of representation of bodily states and interoception. In addition, activity of the anterior insula specifically affected entropy, suggesting possible mediation of this brain region between peripheral sympathetic arousal and exploration in decision-making. These findings shed a new light about a role of bodily states in decision-making and underlying neural mechanisms.
    Neuroscience 04/2013; · 3.12 Impact Factor
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    ABSTRACT: OBJECTIVES: This study aimed to examine one of biological correlates, pro-inflammatory cytokine, in rejection of unfair financial offers in the Ultimatum Game (UG), where the division of a sum of money is proposed and the player can accept or reject this offer. METHODS: Nineteen participants played 20 trials of the UG as responders, and they were proposed unfair offers in a half of the trials. Baseline levels of several pro-inflammatory and anti-inflammatory cytokines, subjective happiness, and depression of them were measured. RESULTS: Participants with higher levels of the pro-inflammatory cytokine, interleukin (IL)-6 rejected fewer unfair offers. This effect of IL-6 levels on decision-making was independent from other pro-inflammatory cytokines, anti-inflammatory cytokines, subjective happiness, and depression. CONCLUSIONS: These results suggested that chronic higher levels of IL-6 might affect functions of neural regions related to decision making, and thus can modulate rejection of unfair offers.
    Neuro endocrinology letters 02/2013; 34(4):47-51. · 0.93 Impact Factor
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    ABSTRACT: The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.
    PLoS ONE 01/2013; 8(8):e72523. · 3.53 Impact Factor
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    ABSTRACT: The reputation of others influences partner selection in human cooperative behaviors through verbal reputation representation. Although the way in which humans represent the verbal reputations of others is a pivotal issue for social neuroscience, the neural correlates underlying the representation of verbal reputations of others are unclear. Humans primarily depend on self-evaluation when assessing reputation of self. Likewise, humans might primarily depend on self-evaluation of others when representing their reputation. As interaction promotes the formation of more nuanced, individualized impressions of an interaction partner, humans tend to form self-evaluations of persons with whom they are intimate in their daily life. Thus, we hypothesized that the representation of reputation of others is modulated by intimacy due to one's own evaluation formation of that person. To test this hypothesis, we conducted a functional magnetic resonance imaging experiment with 11 pairs of romantic partners while they viewed an evaluation of a target person (self, partner [intimate other], or stranger [non-intimate other]), made by other evaluators. When compared with strangers, viewing evaluations of self and partner activated overlapping regions in the medial prefrontal cortex. Verbal reputation of self-specific activation was found in the precuneus, which represents self-related processing. The data suggest that midline structures represent reputation of self. In addition, intimacy-modulated activation in the medial prefrontal cortex suggests that the verbal reputation of intimate others is represented similarly to reputation of self. These results suggest that the reputation representation in the medial prefrontal cortex is engaged by verbal reputation of self and intimate others stemming from both own and other evaluators' judgments.
    PLoS ONE 01/2013; 8(9):e74958. · 3.53 Impact Factor
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    ABSTRACT: Mindfulness is currently attracting a great deal of attention as a psychotherapy technique. It is defined as bringing one's complete attention to the experiences occurring in the present moment in a nonjudgmental or accepting way. The Five Facet Mindfulness Questionnaire (FFMQ) was developed to assess individual differences in mindfulness states. The FFMQ is composed of five facets representing elements of mindfulness: non-reactivity to inner experience, non-judging, acting with awareness, describing, and observing. In the present study, we applied voxel-based morphometry to investigate the relationship between the brain structure and each facet as measured by the FFMQ. The results showed a positive association between the describing facet of mindfulness on the FFMQ and gray matter volume in the right anterior insula and the right amygdala. In conclusion, mindfulness was related with development in parts of the somatic marker circuit of the brain.
    PLoS ONE 01/2012; 7(9):e46377. · 3.53 Impact Factor
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    ABSTRACT: The idea that perceived happiness may be associated with health and well-being is a recent topic of focus. However, the neurobiological mechanisms underlying the positive effects of happiness on psychological and physiological wellness remain obscure. In this study, we attempted to clarify the association between systemic inflammation and happiness. We recruited 160 healthy volunteers for experiment 1 and compared peripheral inflammatory markers, namely the concentrations of pro-inflammatory cytokines in the serum, between perceived high-happiness and low-happiness groups. Subsequently, we recruited 7 romantic couples for experiment 2 and investigated changes in peripheral pro-inflammatory cytokine levels after the evocation of happiness, which was induced by warm physical contact with the partner. We found that circulating levels of interferon-γ (IFN-γ), which can affect brain functions and induce depressive symptoms, were lower in the high-happiness group than in the low-happiness group. A negative correlation between the levels of perceived happiness and IFN-γ concentrations was also observed. Furthermore, we also found that experimentally induced happiness could reduce peripheral IFN-γ levels. These results revealed an association between the perception of happiness and systemic inflammation. Increased happiness may suppress the peripheral circulation of pro-inflammatory cytokines.
    Neuro endocrinology letters 08/2011; 32(4):458-63. · 0.93 Impact Factor
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    ABSTRACT: Animal studies have revealed that chronic stress shifts cognitive strategies from the flexible goal-directed action to the simple and rigid habit action. In addition, stress-induced atrophy in the prefrontal cortex and dorsomedial striatum which are involved in the goal-directed action and hypertrophy of the dorsolateral striatum which is critical for the habit action were parallel with the effects of chronic stress on behaviors. The present study tested whether these previous findings in animal studies are compatible in humans by analyzing effects of chronic stress on neural and cardiovascular responses, which are likely important for performing appropriate actions. Twenty healthy men exposed to low or high chronic job stress performed a stochastic reversal learning task, which required cognitive flexibility and the goal-directed action. Regional cerebral blood flow was evaluated during the task using (15)O-water positron emission tomography, and cardiovascular parameters such as blood pressure and heart rate were also measured. During the reversal learning task, whereas participants with low chronic job stress exhibited activity in the anterior caudate, as well as orbitofrontal cortex, ventrolateral prefrontal cortex, insula, and midbrain, which might be related to the goal-directed action, participants with high chronic job stress exhibited no activity in such brain regions. Furthermore, participants with high chronic job stress exhibited less reactivity in diastolic blood pressure, which might be mediated by anterior cingulate cortical activity. These findings, in line with previous studies, suggested that chronic job stress correlates with less activity in brain regions related to the goal-directed action, and insensitive physiological responses in humans.
    Neuroscience 07/2011; 193:193-204. · 3.12 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
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    ABSTRACT: The "Proust phenomenon" occurs when a certain smell evokes a specific memory. Recent studies have demonstrated that odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli because of the direct neural communication between the olfactory system and the amygdala. The amygdala is known to regulate various physiological activities including the endocrine and immune systems; therefore, odor-evoked autobiographic memory may trigger various psychological and physiological responses; however, the responses elicited by this memory remains obscure. In this study, we aimed to investigate the psychological and physiological responses accompanying odor-evoked autobiographic memory. Methods: We recruited healthy male and female volunteers and investigated changes in their mood states and autonomic nervous, endocrine, and immune activities when autobiographic memory was evoked in the participants by asking them to smell an odor(s) that was nostalgic to them. The autobiographic memories associated with positive emotion resulted in increased positive mood states, such as comfort and happiness, and decreased negative mood states, such as anxiety. Furthermore, heart rate was decreased, skin-conductance level was increased, and peripheral interleukin-2 level was decreased after smelling the nostalgic odor. These psychological and physiological responses were significantly correlated. The present study suggests that odor-evoked autobiographic memory along with a positive feeling induce various physiological responses, including the autonomic nervous and immune activities. To the best of our knowledge, the present study is the first to observe an interaction between odor-evoked autobiographic memories and immune function.
    Neuro endocrinology letters 01/2011; 32(6):774-80. · 0.93 Impact Factor
  • Neuroscience Research - NEUROSCI RES. 01/2011; 71.
  • Hiroki Murakami, Masahiro Matsunaga, Hideki Ohira
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    ABSTRACT: The effects of anticipated threat situations and the valence of the stimuli on the deceleration of the phasic heart rate (HR) were investigated in a single experiment using an S1-S2 paradigm. There were certain S1 cues that were always expected to be followed by neutral pictures (S2 stimuli), and uncertain S1 cues that had a 50% probability of being followed by neutral or unpleasant pictures (S2 stimuli). Greater phasic HR deceleration was observed for S2 stimuli following uncertain S1 cues than for S2 stimuli following certain S1 cues, regardless of the valence of the S2 stimuli. This result suggests that an anticipated threat situation in which participants anticipate facing potentially unpleasant stimuli leads to the allocation of more attentional resources. Additionally, correlation analyses revealed that highly anxious individuals tended to show greater HR deceleration in response to unpleasant stimuli, possibly reflecting maladaptive attentional bias for threat stimuli.
    International journal of psychophysiology: official journal of the International Organization of Psychophysiology 04/2010; 77(1):21-5. · 3.05 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
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    ABSTRACT: Limbic system activation that occurs when a person experiences several emotions is primarily represented by the amygdala output that influences autonomic brainstem nuclei that control autonomic nervous function, thus modulating the endocrine and immune systems. Amygdala activity is modulated by the serotonin transporter gene-linked polymorphic region (5HTTLPR); however, whether variations in 5HTTLPR influence central nervous and immune activities in response to positive stimuli remains unclear. Here, we found that seeing a favorite person induced significantly higher amygdala activity in individuals with the 5HTTLPR SS genotype than in others. This activity was positively correlated with changes in the NK cell proportion among peripheral lymphocytes. Thus, 5HTTLPR influences attraction and the associated interactions between the central nervous and immune systems in affectively positive situations.
    Neuroscience Letters 11/2009; 468(3):211-5. · 2.03 Impact Factor
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    ABSTRACT: A short (S) variant, compared to a long (L) variant, of the promoter region of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been related to emotional hyper-reactivity. We tested whether the 5HTTLPR could modulate acute stress responses in the brain and, the cardiovascular and neuroendocrine systems. Ten Japanese male participants carrying double copies of the S alleles and 10 Japanese males carrying S and L alleles conducted a mental arithmetic task, and their regional cerebral blood flow by (15)O positron emission tomography and cardiovascular and neuroendocrine parameters were measured. During the acute stress task, the participants with the SS alleles showed stronger reactivity in blood pressure and secretion of epinephrine, compared to the participants with the SL and LL alleles. Furthermore, the SS carriers showed greater activation in stress-related brain regions such as the hypothalamus, cerebellum, midbrain, and pulvinar compared to the SL and LL carriers during the acute stress task. The present findings indicated that the S allele of the 5HTTLPR is associated with greater brain and physiological reactivity to acute stress in Japanese men.
    Stress (Amsterdam, Netherlands) 09/2009; 12(6):533-43. · 3.21 Impact Factor
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    ABSTRACT: Warm physical contact may positively influence our health and well-being; however, it has not been investigated yet whether serum proteins are influenced by warm physical contact in healthy couples. In this study, we focused on psychological and physiological effects of warm partner contact in healthy couples. When participants freely kissed and hugged their romantic partners, they were asked to subjectively evaluate their present emotions. Furthermore, changes of serum proteins were determined by using ProteinChip surface enhanced laser desorption/ionization-time-of-flight-mass spectrometry (SELDI-TOF-MS). We characterized these proteins by using biochemical techniques combined with gel filtration high performance liquid chromatography (HPLC), reverse-phase HPLC, and sequencing analyses. Romantic couples became happier and less irritated after kissing and hugging. Accompanying these psychological changes, SELDI-TOF-MS indicated that the intensities of 66-k Da, 11.7-k Da, and 5.9-k Da serum proteins were increased. These proteins were identified as serum albumin and beta2-microglobulin, and probably fibrinogen fragment. The feeling of happiness positively correlated and the feeling of irritation negatively correlated with intensities of serum albumin and beta2-microglobulin. These results suggest that psychological stress may be reduced and we may feel happiness when we kiss and hug a romantic partner. Furthermore, these results also suggest that warm partner contact influences peripheral circulating proteins, more importantly, may promote health and well-being.
    Neuro endocrinology letters 07/2009; 30(2):227-36. · 0.93 Impact Factor
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    ABSTRACT: Acute stress elicits redistribution of lymphocyte subsets, especially natural killer (NK) cells, probably for preparatory defense against potential invasion of antigens in fight-flight situations. We previously reported that regulation of lymphocyte redistribution is based on the evaluation of the controllability of a stressor (Kimura, K., Ohira, H., Isowa, T., Matsunaga, M., Murashima, S. 2007. Regulation of lymphocytes redistribution via autonomic nervous activity during stochastic learning. Brain Behav. Immun. 21, 921-934; Ohira, H., Isowa, T., Nomura, M., Ichikawa, N., Kimura, K., Miyakoshi, M., Iidaka, T., Fukuyama, S., Nakajima, T., Yamada, J. 2008. Imaging brain and immune association accompanying cognitive appraisal of an acute stressor. Neuroimage 39, 500-514). Specifially, lymphocyte redistribution is somewhat attenuated when a stressor is uncontrollable, probably to save biological energy in a situation where appropriate coping is unclear. We infer that this phenomenon might reflect top-down regulation over peripheral immune function by higher-ordered brain regions. To investigate the neural basis of such a phenomenon, we simultaneously recorded regional cerebral blood flow using (15)O-water positron emission tomography and cardiovascular (blood pressure and heart rate), neuroendocrine (epinephrine, norepinephrine, and adrenocorticotropic hormone), and immune (proportions of NK cells and helper T cells in blood) indices in 16 male subjects who performed a stochastic learning task with manipulation of controllability (controllable vs. uncontrollable). Consistent with previous studies, the proportion of peripheral NK cells was attenuated in an uncontrollable stress condition. The dorsolateral prefrontal and orbitofrontal cortices were activated in the uncontrollable situation but not in the controllable condition, and additionally, these prefrontal brain regions significantly correlated with the degree of redistribution of NK cells in the uncontrollable condition. The results of the study suggest these brain regions are involved in both evaluation of the controllability of a stressor and regulation of immune function.
    NeuroImage 06/2009; 47(3):897-907. · 6.25 Impact Factor
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    ABSTRACT: It has been demonstrated that concentrations of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are elevated by acute stress. Although several studies confirmed robust changes in IL-6, how acute stress affects other cytokines was less clear. Therefore, the present study simultaneously examined the effects of acute stress on several pro-inflammatory cytokines. Sixteen male participants were given the Trier Social Stress Test (TSST). Blood samples were collected at baseline, immediately after, and 30, 60, and 90min after the TSST. IL-1beta significantly increased immediately after the TSST and returned to the baseline level after 30min. Additionally, this elevation of IL-1beta was correlated with the perceived intensity of stress. These results showed that the concentration of IL-1beta is rapidly regulated, and that elevation of the IL-1beta level could possibly be attributed to transient mobilization of monocytes caused by sympathetic nervous activation. Moreover, a transient increase of IL-1beta might be conveyed to the brain and play a role in forming negative emotional states.
    Biological psychology 06/2009; 82(1):25-32. · 4.36 Impact Factor
  • Hiroki Murakami, Hideki Ohira, Masahiro Matsunaga, Kenta Kimura
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    ABSTRACT: The present study aimed to investigate the dissociable effects of two forms of self-focus on emotional and autonomic responses. One form is suppression, which includes the suppression of heart rate and self-evaluation of performance. The other is observation, which includes attention to one's own heart rate with no suppression and no evaluation. 26 undergraduate and graduate students from the Nagoya University campus (13 men, 13 women), ages 18 to 24 years (M = 20.7, SD = 1.6) were recruited. Participants were provided with their own heart rate as feedback for 5 min., during which participants conducted a self-focus manipulation. Several days after the experimental session for one condition, the same participants conducted another experimental session for the other condition. Instruction to suppress enhanced physiological arousal and subsequent negative emotions; however, instruction to observe did not increase physiological arousal or negative emotions.
    Perceptual and Motor Skills 05/2009; 108(2):531-9. · 0.49 Impact Factor

Publication Stats

145 Citations
99.32 Total Impact Points


  • 2013
    • Aichi Medical University
      • Department of Health and Psychosocial Medicine
      Okazaki, Aichi, Japan
  • 2012
    • National Center of Neurology and Psychiatry
      Кодаиры, Tōkyō, Japan
  • 2011–2012
    • The Graduate University for Advanced Studies
      • • Division of Cerebral Integration
      • • Department of Cerebral Research
      Миура, Kanagawa, Japan
  • 2009–2010
    • Fujita Health University
      • • School of Medicine
      • • Department of Neurology
      Nagoya, Aichi, Japan
  • 2008–2010
    • Nagoya University
      • Graduate School of Environmental Studies
      Nagoya-shi, Aichi-ken, Japan