Seisuke Fukuyama

Association of neural and physiological responses during voluntary emotion suppression.

Recent neuroimaging studies have shown that several prefrontal regions play critical roles in inhibiting activation of limbic regions during voluntary emotion regulation. The present study aimed to confirm prior findings and to extend them by identifying the frontal neural circuitry associated with regulation of peripheral physiological responses during voluntary emotion suppression. Ten healthy female subjects were presented with affectively positive, neutral, and negative pictures in each of an Attending and Suppression task. Regional cerebral blood-flow changes were measured using 15O-water positron emission tomography, and autonomic (heart rate: HR, skin conductance response: SCR) and endocrine (adrenocorticotropic hormone: ACTH) indices were measured during both tasks. The left amygdala and the right anterior temporal pole were activated during the Attending task, whereas activation was observed in the left lateral prefrontal cortex (LPFC), including the adjacent medial prefrontal cortex (MPFC), and medial orbitofrontal cortex (MOFC) during the Suppression task. In the Attending task, activation in the amygdala and MOFC positively correlated with magnitudes of the SCR and ACTH responses. Emotion suppression elicited enhancement of SCR and the strength of the effect positively correlated with activation in the MOFC. These results suggest that the MOFC plays a pivotal role in top-down regulation of peripheral physiological responses accompanying emotional experiences.

Associations among positive mood, brain, and cardiovascular activities in an affectively positive situation.

It is hypothesized that experiencing positive emotions such as pleasure leads to a perception of the body being in a positive state. This study demonstrated associations among positive mood, brain, and cardiovascular activities by simultaneously recording these activities when positive emotions were evoked in participants watching films revolving around a love story. Heart rate variability analysis revealed increased parasympathetic nervous activity while watching the film. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, superior temporal gyrus, inferior frontal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with subjective positive mood. Activities of brain regions considered to be related to interoceptive awareness, such as the insular cortex, anterior cingulate cortex, amygdala, and orbitofrontal cortex, were also temporally associated with the cardiovascular change. These results suggest that while an individual experiences positive emotions, activities of the central nervous system and cardiovascular system may be interrelated, and the brain may perceive the body to be in a positive state.

Imaging brain and immune association accompanying cognitive appraisal of an acute stressor.

Acute stress elicits multiple responses in autonomic, endocrine, and immune systems. Cognitive appraisal is believed to be one important modulator of such stress responses. To investigate brain substrates of crosstalks between the homeostasis-maintaining systems accompanying appraisal of stressor controllability, we simultaneously recorded regional cerebral blood flow (rCBF) using 15O-water positron emission tomography, cardiovascular indices (heart rate (HR) and blood pressure (BP)), neuroendocrine indices (concentrations of epinephrine, norepinephrine, and adrenocorticotropic hormone (ACTH) in blood), and immune indices (proportions of subsets of lymphocytes (NK cells, helper T cells, cytotoxic T cells, and B cells) in blood), in 11 male subjects who performed a mental arithmetic task with either high controllability (HC) and low controllability (LC). The LC task resulted in less sense of control in subjects than the HC task. Significant increases of rCBF in the medial and lateral orbitofrontal cortices (OFC), and in the medial and lateral prefrontal cortices (MPFC, LPFC) were observed by subtracting the HC task from the LC task. More importantly, significant positive correlations between rCBF and HR, BP, and NK cells were commonly found in the OFC and MPFC during the LC tasks, but not during the HC tasks. The present results showed for the first time that the prefrontal neural network including the OFC and MPFC might be one pivotal region for bi-directional functional association between the brain and peripheral autonomic and immune activities accompanying appraisal of an acute stressor.

Brain and autonomic association accompanying stochastic decision-making

To examine the functional association between brain and autonomic activities accompanying decision-making, we simultaneously recorded regional cerebral blood flow using (15)O-water positron emission tomography and event-related brain potentials (ERPs) time-locked to feedback of reward and punishment, as well as cardiovascular parameters, during a stochastic decision-making task. We manipulated the uncertainty of outcomes in the task; specifically, we compared a condition with high predictability of reward/punishment (contingent-reward condition) and a condition with low predictability of reward/punishment (random-reward condition). The anterior cingulate cortex (ACC) was commonly activated in both conditions. Compared with the contingent-reward condition, the orbitofrontal and right dorsolateral prefrontal cortices and dorsal striatum were activated in the random-reward condition, where subjects had to continue to seek contingency between stimuli and reward/punishment. Activation of these brain regions correlated with a positive component of ERPs locked to feedback signals (feedback-related positivity), which showed an association with behavioral decision-making in the contingent-reward condition. Furthermore, cardiovascular responses were attenuated in the random-reward condition, where continuous attention and contingency monitoring were needed, and such attenuation of cardiovascular responses was mediated by vagal activity that was governed by the rostral ACC. These findings suggest that the prefrontal-striatal network provides a neural basis for decision-making and modulation over the peripheral autonomic activity accompanying decision-making.

Regulation of natural killer cell redistribution by prefrontal cortex during stochastic learning.

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.

Chronic stress modulates neural and cardiovascular responses during reversal learning

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.

Brain activation by music in patients in a vegetative or minimally conscious state following diffuse brain injury

Abstract Objective: The aim of this study was to objectively evaluate the brain activity potential of patients with impaired consciousness in a chronic stage of diffuse brain injury (DBI) using functional MRI (fMRI) following music stimulation (MS). Methods: Two patients in a minimally conscious state (MCS) and five patients in a vegetative state (VS) due to severe DBI were enrolled along with 21 healthy adults. This study examined the brain regions activated by music and assessed topographical differences of the MS-activated brain among healthy adults and these patients. Results: MS was shown to activate the bilateral superior temporal gyri (STG) of both healthy adults and patients in an MCS. In four of five patients in a VS, however, no significant activation in STG could be induced by the same MS. The remaining patient in a VS displayed the same MS-induced brain activation in STG as healthy adults and patients in an MCS and this patient’s status also improved to an MCS 4 months after the study. Conclusions: The presence of STG activation by MS may predict a possible improvement of patients in a VS to MCS and fMRI employing MS may be a useful modality to objectively evaluate consciousness in these patients.

Diagnostic accuracy of [18F]-fluoro-l-dihydroxyphenylalanine positron emission tomography scan for persistent congenital hyperinsulinism in Japan

Objective  We aimed to elucidate the accuracy and limitations of [18F]‐fluoro‐l‐dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) for Japanese patients with congenital hyperinsulinism. Although [18F]DOPA PET is reported to be useful for precisely localizing the focal form of congenital hyperinsulinism, previous reports are mostly from European and North American centres.

Vagal nerve activity as a moderator of brain–immune relationships

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.

Polymorphism of the serotonin transporter gene modulates brain and physiological responses to acute stress in Japanese men

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 15O 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.