掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）   共著区分：共著  

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）   共著区分：共著  

掲載種別：研究論文（学術雑誌）  

Various positron emission tomography (PET) probes have been developed to assess in vivo activities in humans of drug transporters, which aid in the prediction of pharmacokinetic properties of drugs and the impact of drug-drug interactions. We developed a new PET probe, sodium (3R, 5R)-3, 5-dihydroxy-7-((1S, 2S, 6S, 8S)-6-hydroxy-2-methyl-8- ((1-[11C]-(E)-2-methyl-but-2-enoyl) oxy) -1, 2, 6, 7, 8, 8a-hexahydronaphthalen-1-yl) heptanoate ([11C]DPV), and demonstrated its usefulness for the quantitative investigation of Oatps (gene symbol SLCO) and Mrp2 (gene symbol ABCC2) in rats. To further analyze the species differences and verify the pharmacokinetic parameters in humans, serial PET scanning of the abdominal region with [11C]DPV was performed in six healthy volunteers with and without an OATP1Bs and MRP2 inhibitor, rifampicin (600 mg, oral), in a crossover fashion. After intravenous injection, [11C]DPV rapidly distributed to the liver and kidney followed by secretion into the bile and urine. Rifampicin significantly reduced the liver distribution of [11C]DPV 3-fold, resulting in a 7.5-fold reduced amount of excretion into the bile and the delayed elimination of [11C]DPV from the blood circulation. The hepatic uptake clearance (CLuptake, liver) and canalicular efflux clearance (CLint, bile) of [11C]DPV (544 ± 204 and 10.2 ± 3.5 µl/min per gram liver, respectively) in humans were lower than the previously reported corresponding parameters in rats (1800 and 298 µl/min per gram liver, respectively) (Shingaki et al., 2013). Furthermore, rifampicin treatment significantly reduced CLuptake, liver and CLint, bile by 58% and 44%, respectively. These results suggest that PET imaging with [11C]DPV is an effective tool for quantitatively characterizing the OATP1Bs and MRP2 functions in the human hepatobiliary transport system.

DOI： 10.1124/dmd.118.080408

PubMed

掲載種別：研究論文（学術雑誌）  

Some components of the neural circuits underlying innate odor-evoked responses have recently been elucidated. Odor information detected by the olfactory receptors is transmitted from the olfactory bulb to the cortical amygdala, where physiological and emotional states such as attraction or avoidance are controlled. Thus, activation of specific olfactory receptors can elicit changes in physiological and/or psychological state. Here, we examined on the odorant Hex-Hex Mix, which has been reported to induce anti-fatigue effects. Fatigue is a prevalent condition that is often related to overwork and psychological stress. Various anti-fatigue treatments have been developed, including supplements and odorants. However, the mechanisms underlying the anti-fatigue effects of these substances are currently unclear. In the present study, we analyzed the involvement of the olfactory system in the mechanisms underlying this effect. We identified the human olfactory receptors activated by Hex-Hex Mix, and evaluated whether activation of these olfactory receptors by a newly developed odorant elicited a similar anti-fatigue effect to Hex-Hex Mix. We assessed anti-fatigue effects with behavioral tests, and 17 healthy males performed the 2-back test as a fatigue-inducing task with or without exposure to the new odorant. Immediately before and after the task, participants performed a cognitive task to evaluate their level of mental fatigue. We found that the difference value of the correct response rate on the cognitive task in the evaluation session was significantly different between in the odorant condition and in the without-odorant condition during the fatigue-inducing session suggesting that the new odorant may improve performance in the fatigue-inducing condition. The results indicated that the new odorant activates the same olfactory receptors as Hex-Hex Mix, which has been reported to induce anti-fatigue effects. Our findings suggest that the olfactory receptors in the olfactory system may be involved in the attenuation of fatigue.

DOI： 10.1371/journal.pone.0195263

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）  

The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development.

DOI： 10.1016/j.dmpk.2017.09.003

PubMed

掲載種別：研究論文（学術雑誌）   共著区分：共著  

掲載種別：研究論文（学術雑誌）  

Stress is a risk factor for the onset of mental disorders. Although stress response varies across individuals, the mechanism of individual differences remains unclear. Here, we investigated the neural basis of individual differences in response to mental stress using magnetoencephalography (MEG). Twenty healthy male volunteers completed the Temperament and Character Inventory (TCI). The experiment included two types of tasks: a non-stress-inducing task and a stress-inducing task. During these tasks, participants passively viewed non-stress-inducing images and stress-inducing images, respectively, and MEG was recorded. Before and after each task, MEG and electrocardiography were recorded and subjective ratings were obtained. We grouped participants according to Novelty seeking (NS) - tendency to be exploratory, and Harm avoidance (HA) - tendency to be cautious. Participants with high NS and low HA (n = 10) assessed by TCI had a different neural response to stress than those with low NS and high HA (n = 10). Event-related desynchronization (ERD) in the beta frequency band was observed only in participants with high NS and low HA in the brain region extending from Brodmann's area 31 (including the posterior cingulate cortex and precuneus) from 200 to 350 ms after the onset of picture presentation in the stress-inducing task. Individual variation in personality traits (NS and HA) was associated with the neural response to mental stress. These findings increase our understanding of the psychological and neural basis of individual differences in the stress response, and will contribute to development of the psychotherapeutic approaches to stress-related disorders.

DOI： 10.1007/s11682-015-9479-0

掲載種別：研究論文（学術雑誌）   共著区分：共著  

掲載種別：研究論文（学術雑誌）  

Background: Changes of resting brain activities after visual food stimulation might affect the feeling of pleasure in eating food in daily life and spontaneous appetitive motives. We used magnetoencephalography (MEG) to identify brain areas related to the activity changes.
Methods: Fifteen healthy, right-handed males [age, 25.4 +/- 5.5 years; body mass index, 22.5 +/- 2.7 kg/m(2) (mean +/- SD)] were enrolled. They were asked to watch food or mosaic pictures for 5 min and to close their eyes for 3 min before and after the picture presentation without thinking of anything. Resting brain activities were recorded during two eye-closed sessions. The feeling of pleasure in eating food in daily life and appetitive motives in the study setting were assessed by visual analogue scale (VAS) scores.
Results: The.-band power of resting oscillatory brain activities was decreased after the food picture presentation in the right insula [Brodmann's area (BA) 13], the left orbitofrontal cortex (OFC) (BA11), and the left frontal pole (BA10). Significant reductions of the a-band power were observed in the dorsolateral prefrontal cortex (DLPFC) (BA46). Particularly, the feeling of pleasure in eating food was positively correlated with the power decrease in the insula and negatively with that in the DLPFC. The changes in appetitive motives were associated with the power decrease in the frontal pole.
Conclusions: These findings suggest automatic brain mechanics whereby changes of the resting brain activity might be associated with positive feeling in dietary life and have an impact on the irresistible appetitive motives through emotional and cognitive brain functions.

DOI： 10.1186/s12993-016-0110-3

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）   共著区分：共著  

掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0095763

掲載種別：研究論文（学術雑誌）  

Background: Sleep plays an important role in health promotion, and increased skin temperature is thought to promote rapid sleep onset. The objective of this study was to investigate whether the use of a shower bathing device with a water pillar design would increase skin temperature during the bathing and sleep periods and have a sleepinducing effect. Material/Methods: In this crossover experiment, 10 healthy male volunteers were randomized into three groups of different types of shower bathing: normal bathing, normal shower bathing, and water pillar shower bathing. After a 10-minute bathing period, a 20-minute period during which they dried off and put on sleep wear, and a 40-minute rest period, participants moved to a bed and lay in a supine position with their eyes closed for 60 minutes. Results: The participants in the water pillar shower bathing group reported being able to fall asleep more easily than the normal shower bathing group. Sleep onset latency was shorter in the water pillar shower bathing group than in the other two groups. Skin temperatures were higher in the water pillar shower bathing group than in the normal shower bathing group throughout the bathing and sleep periods, but no significant differences were seen in rectal temperatures between these two groups during most of the sleep period. Conclusions: These results indicate that water pillar shower bathing increases skin temperature and thereby promotes more rapid sleep onset.

DOI： 10.12659/MST.900800

掲載種別：研究論文（学術雑誌）  

Fatigue is defined as a condition or phenomenon of decreased ability and efficiency of mental and/or physical activities, caused by excessive mental or physical activities, diseases, or syndromes. It is often accompanied by a peculiar sense of discomfort, a desire to rest, and reduced motivation, referred to as fatigue sensation. Acute fatigue is a normal condition or phenomenon that disappears after a period of rest; in contrast, chronic fatigue, lasting at least 6 months, does not disappear after ordinary rest. Chronic fatigue impairs activities and contributes to various medical conditions, such as cardiovascular disease, epileptic seizures, and death. In addition, many people complain of chronic fatigue. For example, in Japan, more than one third of the general adult population complains of chronic fatigue. It would thus be of great value to clarify the mechanisms underlying chronic fatigue and to develop efficient treatment methods to overcome it. Here, we review data primarily from behavioral, electrophysiological, and neuroimaging experiments related to neural dysfunction as well as autonomic nervous system, sleep, and circadian rhythm disorders in fatigue. These data provide new perspectives on the mechanisms underlying chronic fatigue and on overcoming it.

DOI： 10.1007/s12576-015-0399-y

掲載種別：研究論文（学術雑誌）  

Background: Fatigue, defined as difficulty initiating or sustaining voluntary activities, can be classified as physical or mental. In this study, we use magnetoencephalography (MEG) to quantify the effect of physical fatigue on neural activity under the condition of simulated physical load.
Methods: Thirteen healthy right-handed male volunteers participated in this study. The experiment consisted of one fatigue-inducing physical task session performed between two MEG sessions. During the 10-min physical task session, participants performed maximum-effort handgrips with the left hand lasting 1 s every 4 s; during MEG sessions, 3-min recordings were made during the eyes-closed state. MEG data were analyzed using narrow-band adaptive spatial filtering methods.
Results: Alpha-frequency band (8-13 Hz) power in the left postcentral gyrus, precentral gyrus, and middle frontal gyrus (Brodmann's areas 1, 2, 3, 4, 6, and 46) were decreased after performing the physical fatigue-inducing task.
Conclusions: These results show that performing the physical fatigue-inducing task caused activation of the left sensorimotor and prefrontal areas, manifested as decreased alpha-frequency band power in these brain areas. Our results increase understanding of the neural mechanisms of physical fatigue.

DOI： 10.1186/s12993-015-0079-3

掲載種別：研究論文（学術雑誌）  

Paget's disease of bone (PDB) is a chronic disorder characterized by localized bone regions with excessive bone turnover. Although oral risedronate (17.5 mg daily for 8 weeks) was recently approved in Japan, its efficacy is not well understood. We retrospectively examined the efficacy of oral risedronate in PDB patients in a clinical setting. Eleven patients whose serum alkaline phosphatase (ALP) level exceeded the upper limit of the normal range were treated. Patients whose ALP levels normalized and remained so for 12 months after therapy initiation were defined as responders. Treatment was repeated if bone pain recurred or if serum ALP levels increased at least 25% above the nadir. Six patients (55%) were responsive to the therapy. A higher prevalence of skull lesions, higher serum calcium levels at treatment initiation and antecedent treatments of bisphosphonates were predictors of resistance against the therapy. Fresh frozen serum samples obtained from some treatment sessions were evaluated for metabolic bone markers such as bone-specific ALP (BAP), type I procollagen N-terminal pro-peptide (PINP), N-treminal crosslinking telopeptide of type I collagen and C-treminal crosslinking telopeptide of type I collagen (CTX). A significant reduction of P1NP preceded that of serum ALP levels in the responders, which was followed by a similar occurrence for BAP and osteocalcin (BGP) levels. A temporary decrease in CTX levels was noted. No significant changes in markers (including ALP level) were observed in non-responder and repeat-treatment groups. P1NP levels may be more useful than ALP levels in assessing treatment efficacy. Repeat treatment effectiveness for the repeat-treatment group was limited.

DOI： 10.1007/s00774-014-0623-5

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）  

Using [C-11]raclopride, a dopamine D-2/D-3 receptor antagonist, we undertook a positron emission tomography (PET) study to investigate the involvement of the dopaminergic neurotransmitter system when subjects viewed the pictures of partners to whom they were romantically attached. Ten subjects viewed pictures of their romantic partners and, as a control, of friends of the same sex for whom they had neutral feelings during the PET study. We administered [C-11]raclopride to subjects using a timing for injecting the antagonist which had been determined in previous studies to be optimal for detecting increases in the amount of dopamine released by stimulation. The results demonstrated statistically significant activation of the dopaminergic system in two regions, the medial orbitofrontal cortex (mOFC) and medial prefrontal cortex, the former of which has been strongly implicated in a variety of rewarding experiences, including that of beauty and love. A positive correlation was obtained in mOFC between excitement levels and dopaminergic activation only in the love but not in the control condition.

DOI： 10.3389/fnhum.2015.00191

掲載種別：研究論文（学術雑誌）  

There have been several studies which have tried to clarify the neural mechanisms of fatigue sensation; however fatigue sensation has multiple aspects. We hypothesized that past experience related to fatigue sensation is an important factor which contributes to future formation of fatigue sensation through the transfer to memories that are located within specific brain structures. Therefore, we aimed to investigate the neural mechanisms of fatigue sensation related to memory. In the present study, we investigated the neural activity caused by re-experiencing the fatigue sensation that had been experienced during a fatigue-inducing session. Thirteen healthy volunteers participated in fatigue and non-fatigue experiments in a crossover fashion. In the fatigue experiment, they performed a 2-back test session for 40 min to induce fatigue sensation, a rest session for 15 min to recover from fatigue, and a magnetoencephalography (MEG) session in which they were asked to re-experience the state of their body with fatigue that they had experienced in the 2-back test session. In the non-fatigue experiment, the participants performed a free session for 15 min, a rest session for 15 min, and an MEG session in which they were asked to re-experience the state of their body without fatigue that they had experienced in the free session. Spatial filtering analyses of oscillatory brain activity showed that the delta band power in the left Brodmann's area (BA) 39, alpha band power in the right pulvinar nucleus and the left BA 40, and beta band power in the left BA 40 were lower when they re-experienced the fatigue sensation than when they re-experienced the fatigue-free sensation, indicating that these brain regions are related to re-experiencing the fatigue sensation. Our findings may help clarify the neural mechanisms underlying fatigue sensation.

DOI： 10.1371/journal.pone.0122455

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）  

Adequate rest is essential to avoid fatigue and disruption of homeostasis. However, the neural mechanisms underlying the decision to rest are not well understood. In the present study, we aimed to clarify the neural mechanisms of this decision-making process using magnetoencephalography. Fifteen healthy volunteers participated in decision and control experiments performed in a cross-over fashion. In the decision experiment, participants performed 1,200 reverse Stroop test trials and were intermittently asked to decide whether they wanted to take a rest or continue. In the control experiments, participants performed 1,200 reverse Stroop test trials and were instructed to press a response button intermittently without making any decision. Changes in oscillatory brain activity were assessed using a narrow-band adaptive spatial filtering method. The levels of decrease in theta (4-8 Hz) band power in left Brodmann's area (BA) 31, alpha (8-13 Hz) band power in left BA 10 and BA 9, and beta (13-25 Hz) band power in right BA 46 and left BA 10 were greater in trials when the participant opted to rest (rest trials) than those in control trials. The decrease in theta band power in BA 31 in the rest trials was positively correlated with the subjective level of fatigue after the decision experiment. These results demonstrated that the dorsolateral prefrontal cortex, frontal pole, and posterior cingulate cortex play a role in the decision to rest in the presence of fatigue. These findings may help clarify the neural mechanisms underlying fatigue and fatigue-related problems.

DOI： 10.1371/journal.pone.0109740

掲載種別：研究論文（学術雑誌）  

Fatigue is defined as a decline in the ability and efficiency of mental and/or physical activities that is caused by excessive mental and/or physical activities. Fatigue can be classified as physical or mental. Mental fatigue manifests as potentially impaired cognitive function and is one of the most significant causes of accidents in modern society. Recently, it has been shown that the neural mechanisms of mental fatigue related to cognitive task performance are more complex than previously thought and that mental fatigue is not caused only by impaired activity in task-related brain regions. There is accumulating evidence supporting the existence of mental facilitation and inhibition systems. These systems are involved in the neural mechanisms of mental fatigue, modulating the activity of task-related brain regions to regulate cognitive task performance. In this review, we propose a new conceptual model: the dual regulation system of mental fatigue. This model contributes to our understanding of the neural mechanisms of mental fatigue and the regulatory mechanisms of cognitive task performance in the presence of mental fatigue.

DOI： 10.1515/revneuro-2014-0028

掲載種別：研究論文（学術雑誌）  

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. C-11-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (C-11-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used C-11-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. Methods: Nine CFS/ME patients and 10 healthy controls underwent C-11-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, nondisplaceable binding potential (BPND) values were determined using linear graphical analysis with the cerebellum as a reference region. Results: The BPND values of C-11-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BPND values of C-11-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BPND values in the cingulate cortex and thalamus positively correlated with pain score, and the BPND value in the hippocampus positively correlated with depression score. Conclusion: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

DOI： 10.2967/jnumed.113.131045

掲載種別：研究論文（学術雑誌）  

'Hara-Hachibu' in Japanese means a subjective sense by which we stop eating just before the motivation to eat is completely lost, a similar concept to caloric restriction (CR). Insular cortex is a critical platform which integrates sensory information into decision-making processes in eating behavior. We compared the responses of insular cortex, as assessed by magnetoencephalography (MEG), immediately after presentation of food images in the Fasting condition with those in the 'Hara-Hachibu' condition. Eleven healthy, right-handed males [age, 27.2 +/- 9.6 years; body mass index, 22.6 +/- 2.1 kg/m(2) (mean +/- SD)] were enrolled in a randomized, two-crossover experiment (Fasting and 'Hara-Hachibu' conditions). Before the MEG recordings in the 'Hara-Hachibu' condition, the participants consumed rice balls as much as they judged themselves to have consumed shortly before reaching satiety. During the MEG recordings, they viewed food pictures projected on a screen. The intensities of MEG responses to viewing food pictures were significantly lower in the 'Hara-Hachibu' condition than those in the Fasting condition (P<0.05). The intensities of the MEG responses to the visual food stimuli in the 'Hara-Hachibu' condition was positively associated with the factor-3 (food tasted) (r=0.693, P=0.018) and aggregated scores (r=0.659, P=0.027) of the Power of Food Scale, a self-report measure of hedonic hunger. These findings may help to elucidate the neural basis of variability of appetite phenotypes under the condition of CR among individuals, and to develop possible strategies for the maintenance of adequate CR in daily life. (C) 2014 The Authors. Published by Elsevier B.V.

DOI： 10.1016/j.brainres.2014.04.021

掲載種別：研究論文（学術雑誌）  

Mental fatigue can be defined as a psychobiological state caused by prolonged periods of demanding cognitive activity and manifests as a reduced efficiency in cognitive performance. Mental fatigue is one of the most significant causes of accidents in modem society. Therefore, understanding the neural mechanisms of mental fatigue is important. However, the neural mechanisms of mental fatigue are not fully understood. In this study, we investigated the neural activity that results from mental fatigue caused by a continuous attention load. We used magnetoencephalography (MEG) to evaluate the neural activities during the attention task. Ten healthy male volunteers participated in this study. They performed a continuous attention task lasting 10 min. Subjective ratings of mental fatigue, mental stress, boredom, and sleepiness were performed just after the task trial. MEG data were analyzed using narrow-band adaptive spatial filtering methods. An increase in the beta-frequency band (13-25 Hz) power in the right inferior and middle frontal gyri (Brodmann's areas 44 and 9 respectively) was caused by the mental fatigue. The increase in the beta-frequency band power in the right middle frontal gyrus was negatively associated with the self-reported level of mental stress and was positively associated with those of boredom and sleepiness. These results demonstrate that performing a continuous mental fatigue-inducing task causes changes in the activation of the prefrontal cortex, and manifests as an increased beta-frequency power in this brain area as well as sleepiness. Our results contribute to greater understanding of the neural mechanisms of mental fatigue. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2014.03.009

掲載種別：研究論文（学術雑誌）  

Chronic cognitive fatigue is characterized by a sensation of long-lasting fatigue that impairs cognitive functions. Facilitation and inhibition systems in the central nervous system play primary roles in determining the output to the peripheral system, that is, performance. Sensory input from the peripheral system to the central nervous system activates the inhibition system to limit performance, whereas motivational input activates the facilitation system to enhance performance. The dysfunction of the facilitation system and central sensitization and classical conditioning of the inhibition system play important roles in the pathophysiology of chronic cognitive fatigue. Because the dorsolateral prefrontal cortex receives input from both the facilitation and inhibition systems to determine performance, metabolic, functional, and structural impairments of the dorsolateral prefrontal cortex induced by repetitive and prolonged overwork, stress, and stress responses contribute to the impaired functioning and cognitive performance that occur in people with chronic cognitive fatigue. This hypothesis of the regulatory mechanism of performance provides a new perspective on the neural mechanisms underlying chronic cognitive fatigue. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.mehy.2014.02.013

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）  

It is important to clarify the neural mechanisms underlying fatigue sensation. There have been several studies which identified brain regions in which the level of the neural activities was correlated with the subjective level of fatigue. However, the neural activity evoked when we evaluate our level of fatigue may not be related to the subjective level of fatigue. Thus, we tried to identify the neural activities caused by the evaluation of the level of fatigue, which may not be related to the subjective level of fatigue. We used magnetoencephalography (MEG) to measure neural activity in 10 healthy participants enrolled in our study. During MEG recordings, participants were asked to evaluate the level of physical fatigue in their right hand in time with execution cues (evaluation session) or to direct attention to their right hand in time with execution cues (control session). Equivalent current dipole (ECD) analysis was performed to localize the neural activity limited to the evaluation session. In the evaluation session, ECDs with mean latencies of approximately 380 ms were observed in nine of 10 participants. These were localized in the posterior cingulate cortex (PCC), while in the control session, the ECDs in the same brain region were observed in only two of 10 participants. The proportion of participants in whom ECDs were observed in the PCC in the evaluation session was significantly higher than that in the control session (McNemar test). In addition, the intensities of the ECDs were positively associated with the extent to which the participants successfully evaluated the fatigue in their right hand in the evaluation session. These data suggest that the PCC is involved in the neural substrates associated with self-evaluation of physical fatigue. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2013.12.049

掲載種別：研究論文（学術雑誌）  

We sought to clarify the neural effect of mental fatigue on physical fatigue using magnetoencephalography (MEG) and classical conditioning techniques. Eleven right-handed volunteers participated in this study. On the first day, participants performed fatigue-inducing maximum handgrip trials for 10 min; metronome sounds were started 5 min after the beginning of the trials. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause physical fatigue. On the next day, MEG recordings during the imagery of maximum grips of the right hand guided by the metronome sounds were performed for 10 min just before (control session) and after (mental fatigue session) a 30-min fatigue-inducing mental task session. In the right anterior cingulate cortex (Brodmann's area 23), the alpha-band event-related synchronization of the mental fatigue session relative to the control session within the time window of 500-600 ms after the onset of handgrip cue sounds was identified. We demonstrated that mental fatigue suppresses activities in the right anterior cingulate cortex during physical fatigue. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2013.10.018

掲載種別：研究論文（学術雑誌）  

Currently, little is known about the brain function that allows individuals to suppress eating behavior. The present study used magnetoencephalography (MEG) to examine changes in neural activity over time that were related to suppression of motivation to eat in 11 healthy males. The MEG experiment consisted of four motivation sessions and four suppression sessions in an alternating and counterbalanced order. During MEG recordings, participants viewed a set of food pictures and mosaic pictures projected onto a screen, and were then asked to rate their motivation to eat and the suppression of the motivation to eat during the recordings. The present study demonstrated a higher beta-band (13-25 Hz) event-related synchronization (ERS) level during the suppression sessions relative to the motivation sessions in the left supplementary motor area (SMA) 200-300 ms after the start of food picture presentation. Similar differences were also observed in theta-band (4-8 Hz) event-related desynchronization (ERD) in the left dorsolateral prefrontal cortex (DLPFC) after 500-600 ms. Negative relationships were observed between these levels of MEG responses and the number of food items for which the participants reported the motivation to eat during the MEG recordings. These findings indicate that the left DLPFC and SMA, particularly the DLPFC, play prominent roles in the suppression of motivation to eat. This may help to clarify the temporal aspects of the neural basis of self-control of appetitive motivation as well as aid development of self-control strategies such as cognitive behavioral therapy for patients with disordered appetite. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2013.11.005

掲載種別：研究論文（学術雑誌）  

Fatigue is a common complaint among young adults. We investigated whether eating behaviors are associated with fatigue in this population. The participants consisted of 117 healthy students attending Osaka City University. They completed questionnaires assessing fatigue and eating behaviors. To identify the factors associated with the prevalence of fatigue, multivariate logistic regression analysis adjusted for gender was performed. The Emotional Eating subscale score of the Japanese version of Three-Factor Eating Questionnaire Revised 21-item and stress response in food intake (large decrease vs. no change) were positively associated with the prevalence of fatigue assessed by the Japanese version of the Chalder Fatigue Scale. The finding suggests that emotional eating and decrease in amount of food intake under mental stress were associated with fatigue in healthy young adults. Our findings may help to clarify the mechanisms underlying fatigue-eating coupling as well as the etiology of diseases related to abnormal eating behavior.

DOI： 10.1080/08964289.2013.833082

掲載種別：研究論文（学術雑誌）  

Fatigue is defined as a condition or phenomenon of declined ability and efficiency of mental and/or physical activities, caused by excessive mental or physical activities, diseases, or syndromes. Acute fatigue is a normal condition that disappears after a period of rest; in contrast, chronic fatigue does not disappear after an ordinary rest. Chronic fatigue impairs daily activities and contributes to various medical conditions and death. In addition, many people complain of chronic fatigue. It would thus be of great value to clarify the mechanisms underlying chronic fatigue and to develop efficient treatment methods to overcome it. Here, we review data primarily from behavioral, neurophysiological, and neuroimaging experiments related to the neural mechanisms underlying chronic fatigue. We propose that repetitive and prolonged overwork and/or stress cause neural damage of a facilitation system, as well as central sensitization and classical conditioning of an inhibition system. We also propose a new treatment strategy for chronic fatigue on the basis of its underlying neural mechanisms.

DOI： 10.1515/revneuro-2013-0035

掲載種別：研究論文（学術雑誌）  

Central inhibition plays an important role in physical performance during physical fatigue. We tried to clarify the neural mechanism of central inhibition during physical fatigue using the magnetoencephalography (MEG) and a classical conditioning technique. Twelve right-handed volunteers participated in this study. Participants underwent MEG recording during the imagery of maximum gips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. The next day, MEG recording during the imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of the fatigue sensation in the right hand and sympathetic nerve activity on the second day were significantly higher than those on the first day. In the right dorsolateral prefrontal cortex (Brodmann's area 46), the alpha-band event-related desynchronization (ERD) of the second MEG session relative to the first session with the time window of 200 to 300 ms after the onset of handgrip cue sounds was identified. The ERD level in this brain region was positively associated with the change in subjective level of right hand fatigue after the conditioning session and was negatively associated with that of the sympathetic nerve activity. We demonstrated that the right dorsolateral prefrontal cortex is involved in the neural substrates of central inhibition during physical fatigue. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2013.08.054

掲載種別：研究論文（学術雑誌）  

In daily communication, we can usually still hear the spoken words as if they had not been masked and can comprehend the speech when spoken words are masked by background noise. This phenomenon is known as phonemic restoration. Since little is known about the neural mechanisms underlying phonemic restoration for speech comprehension, we aimed to identify the neural mechanisms using magnetoencephalography (MEG). Twelve healthy male volunteers with normal hearing participated in the study. Participants were requested to carefully listen to and understand recorded spoken Japanese stories, which were either played forward (forward condition) or in reverse (reverse condition), with their eyes closed. Several syllables of spoken words were replaced by 300-ms white-noise stimuli with an inter-stimulus interval of 1.6-20.3 s. We compared MEG responses to white-noise stimuli during the forward condition with those during the reverse condition using time-frequency analyses. Increased 3-5 Hz band power in the forward condition compared with the reverse condition was continuously observed in the left inferior frontal gyrus [Brodmann's areas (BAs) 45, 46, and 47] and decreased 18-22 Hz band powers caused by white-noise stimuli were seen in the left transverse temporal gyrus (BA 42) and superior temporal gyrus (BA 22). These results suggest that the left inferior frontal gyrus and left transverse and superior temporal gyri are involved in phonemic restoration for speech comprehension. Our findings may help clarify the neural mechanisms of phonemic restoration as well as develop innovative treatment methods for individuals suffering from impaired speech comprehension, particularly in noisy environments. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2013.09.010

掲載種別：研究論文（学術雑誌）  

An enhanced facilitation system caused by motivational input plays an important role in supporting performance during physical fatigue. We tried to clarify the neural mechanisms of the facilitation system during physical fatigue using magnetoencephalography (MEG) and a classical conditioning technique. Twelve right-handed volunteers participated in this study. Participants underwent MEG recording during the imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The metronome sounds were used as conditioned stimuli and maximum handgrip trials as unconditioned stimuli. The next day, they were randomly assigned to two groups in a single-blinded, two-crossover fashion to undergo two types of MEG recordings, that is, for the control and motivation sessions, during the imagery of maximum grips of the right hand guided by metronome sounds for 10 min. The alpha-band event-related desynchronizations (ERDs) of the motivation session relative to the control session within the time windows of 500 to 700 and 800 to 900 ms after the onset of handgrip cue sounds were identified in the sensorimotor areas. In addition, the alpha-band ERD within the time window of 400 to 500 ms was identified in the right dorsolateral prefrontal cortex (Brodmann's area 46). The ERD level in the right dorsolateral prefrontal cortex was positively associated with that in the sensorimotor areas within the time window of 500 to 700 ms. These results suggest that the right dorsolateral prefrontal cortex is involved in the neural substrates of the facilitation system and activates the sensorimotor areas during physical fatigue.

DOI： 10.1371/journal.pone.0080731

掲載種別：研究論文（学術雑誌）  

Mental fatigue, manifest as a reduced efficiency for mental work load, is prevalent in modern society. It is important to understand the neural mechanisms of mental fatigue and to develop appropriate methods for evaluating mental fatigue. In this study we quantified the effect of a long-duration mental fatigue-inducing task on neural activity. We used magnetoencephalography (MEG) to examine the time course change of neural activity over the long duration of the task trials. Nine healthy male volunteers participated in this study. They performed two mental fatigue-inducing tasks on separate days. The order of task presentation was randomized in a single-blinded, crossover fashion. Each task consisted of 25-min mental fatigue-inducing 0- or 2-back task session for three times. Subjective rating of mental fatigue sensation and electrocardiogram, and resting state MEG measurements were performed just before and after each task session. MEG data were analyzed using narrow-band adaptive spatial filtering methods. Alpha band (8-13 Hz) power in the visual cortex decreased after performing the mental fatigue-inducing tasks, and the decrease of alpha power was greater when they performed 2-back task trials. The decrease in alpha power was positively associated with the self-reported level of mental fatigue sensation and sympathetic nerve activity level. These results demonstrate that performing the prolonged mental fatigue-inducing task causes overactivation of the visual cortex, manifest as decreased alpha power in this brain region. Our results increase understanding of the neural mechanisms of mental fatigue and can be used to develop new quantitative methods to assess mental fatigue. © 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2013.07.022

PubMed

掲載種別：研究論文（学術雑誌）  

Background: Material/Methods: Results: Conclusions: We aimed to determine the brain areas related to food motivation and to examine individual variability using magnetoencephalography (MEG) during a fasted state. Correlation analysis was performed between MEG responses and the subscale and aggregated scores of the Power of Food Scale (PFS) and body mass index (BMI). Eight healthy, right-handed males [age, 29.0±10.4 years
BMI, 22.7±2.4 kg/m2 (mean ±SD)] were enrolled. The MEG experiment consisted of 2 food sessions and 2 control sessions in an alternating and counterbalanced order. During the MEG recordings, participants viewed a set of food pictures (food session) or mosaic pictures (control session) projected on a screen. When participants viewed pictures of food items, we were able to estimate equivalent current dipoles (ECDs) in the insular cortex in all participants peaked approximately 300 ms after the onset of each picture presentation. When they viewed mosaic pictures, 1 of 8 participants exhibited corresponding ECDs. Of note, significant correlations were observed between the intensities of the MEG responses and the subscale scores of Factor 1 (food available) (r=0.846, P=0.008) and those of Factor 2 (food present) (r=0.875, P=0.004), the aggregated scores of PFS (r=0.820, P=0.013), and BMI (r=0.898, P=0.002). PERSONONLY We demonstrated the involvement of the immediate neural responses of the insular cortex in individual differences in appetitive motivation. The signal intensities of the insular cortex were associated with self-awareness of appetitive motive. © Med Sci Monit, 2013.

DOI： 10.12659/MSM.889234

PubMed

掲載種別：研究論文（学術雑誌）  

Background: Fatigue is a common symptom in modern society. There has been a recent resurgence of interest in traditional remedies for fatigue. Chicken essence, which is rich in anserine and carnosine, has been widely taken in Asian countries as a traditional remedy with various aims, including attenuation of physical and mental fatigue. However, the evidence for its efficacy specifically for mental fatigue remains unclear. We examined the effect of essence of chicken on mental fatigue in humans, using our established fatigue-inducing task and evaluation methods.
Material/Methods: In this placebo-controlled crossover study, 20 healthy male volunteers were randomized to receive daily oral administration of essence of chicken or placebo drink provided by Cerebos Pacific Ltd. via Suntory holdings Ltd. for 4 weeks. The participants performed 2-back test trials as a fatigue-inducing mental task and then had a rest session. Just before and after each session, they completed cognitive task trials focusing on selective attention to evaluate the level of mental fatigue.
Results: After essence of chicken intake for 1 and 4 weeks, the reaction times on the cognitive task trials after the rest session were significantly shorter than those at baseline, and significant changes were not observed with placebo intake. The reaction times before and after the fatigue-inducing session were not altered by either essence of chicken or placebo intake.
Conclusions: We showed that daily intake of essence of chicken could be effective for the recovery from mental fatigue and is a promising candidate for use as an anti-fatigue food.

DOI： 10.12659/MSM.883971

掲載種別：研究論文（学術雑誌）  

Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG). Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs) in the posterior cingulated cortex (PCC), with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.

DOI： 10.1371/journal.pone.0070949

掲載種別：研究論文（学術雑誌）  

Background: It has been proposed that an inappropriately conditioned fatigue sensation could be one cause of chronic fatigue. Although classical conditioning of the fatigue sensation has been reported in rats, there have been no reports in humans. Our aim was to examine whether classical conditioning of the mental fatigue sensation can take place in humans and to clarify the neural mechanisms of fatigue sensation using magnetoencephalography (MEG).
Methods: Ten and 9 healthy volunteers participated in a conditioning and a control experiment, respectively. In the conditioning experiment, we used metronome sounds as conditioned stimuli and two-back task trials as unconditioned stimuli to cause fatigue sensation. Participants underwent MEG measurement while listening to the metronome sounds for 6 min. Thereafter, fatigue-inducing mental task trials (two-back task trials), which are demanding working-memory task trials, were performed for 60 min; metronome sounds were started 30 min after the start of the task trials (conditioning session). The next day, neural activities while listening to the metronome for 6 min were measured. Levels of fatigue sensation were also assessed using a visual analogue scale. In the control experiment, participants listened to the metronome on the first and second days, but they did not perform conditioning session. MEG was not recorded in the control experiment.
Results: The level of fatigue sensation caused by listening to the metronome on the second day was significantly higher relative to that on the first day only when participants performed the conditioning session on the first day. Equivalent current dipoles (ECDs) in the insular cortex, with mean latencies of approximately 190 ms, were observed in six of eight participants after the conditioning session, although ECDs were not identified in any participant before the conditioning session.
Conclusions: We demonstrated that the metronome sounds can cause mental fatigue sensation as a result of repeated pairings of the sounds with mental fatigue and that the insular cortex is involved in the neural substrates of this phenomenon.

DOI： 10.1186/1744-9081-9-24

掲載種別：研究論文（学術雑誌）  

Context: Exposure to a natural environment has been reported to be associated with positive effects on mental well-being. However, no report has examined the effects of a house designed with an open space connected to nature on recovery from fatigue. Objective: The purpose of this study was to examine the effects of such an open space on recovery from mental fatigue. Design: Placebo-controlled, crossover design. Setting: Participants were randomized into open (connected to nature) and closed (not connected to nature) conditions. Participants: Sixteen healthy female volunteers were enrolled. Intervention: After a 30-minute fatigue-inducing mental task, participants moved to an open or closed recovery room for 30 minutes. Main Outcome Measures: As fatigue-evaluating mental tasks, participants performed advanced trail making tests for 20 minutes. They were asked to rate their levels of fatigue, relaxation, comfort, and healing on a visual analogue scale from 0 (minimum) to 100 (maximum) to evaluate their subjective mental. They also underwent accelerated plethysmography. Results: After the recovery session, lower total error counts of a cognitive test, greater levels of subjective relaxation, comfort, and healing, and lower levels of waveform index-1 assessed via accelerated plethysmography were observed in participants exposed to the open condition compared with the closed condition. These results provide evidence that the use of a house designed with an open space connected to nature during the recovery session improved cognitive function and subjective mental states. Hence, open space was effective for helping recovery from mental fatigue. © 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.explore.2012.12.006

PubMed

掲載種別：研究論文（学術雑誌）  

Fatigue is a common symptom in modern society. To clarify the mechanisms underlying fatigue, we examined task performances and subjective scale scores associated with two different types of mental fatigue. The study group consisted of 20 healthy participants, who performed 0-back or 2-back test trials for 30 min as a fatigue-inducing task session. Just before and after the session, they completed advanced trail making test (ATMT) for 30 min and completed subjective scales to measure fatigue, sleepiness, and other factors. After the 0-back or 2-back task session, impairment of task performance was significant as assessed by increased error count in ATMT. In contrast, although task performance as assessed by mean reaction time during the 2-back task trials did not change over time, longer reaction time was observed over time during the 0-back task trials. After the 0-back task session, subjective levels of fatigue and sleepiness were increased
while after the 2-back task session, although subjective level of fatigue was increased, that of sleepiness was not altered. Two different types of mental fatigue produce different styles of task performance. We present a new conceptual hypothesis regarding the mechanism underlying the association between mental fatigue and task performance. © 2012 Elsevier GmbH.

DOI： 10.1016/j.npbr.2012.07.002

掲載種別：研究論文（学術雑誌）  

Background: Fatigue has a multi-factorial nature. We examined the effects of two types of mental fatigue on spontaneous oscillatory brain activity using magnetoencephalography (MEG).
Methods: Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of a 30-min fatigue-inducing 0- or 2-back test session and two evaluation sessions performed just before and after the fatigue-inducing mental task session.
Results: After the 0-back test, decreased alpha power was indicated in the right angular gyrus and increased levels in the left middle and superior temporal gyrus, left postcentral gyrus, right superior frontal gyrus, left inferior frontal gyrus, and right medial frontal gyrus. After the 2-back test, decreased alpha power was indicated in the right middle and superior frontal gyrus and increased levels in the left inferior parietal and superior parietal lobules, right parahippocampal gyrus, right uncus, left postcentral gyrus, left middle frontal gyrus, and right inferior frontal gyrus. For beta power, increased power following the 0-back test was indicated in the left middle temporal gyrus, left superior frontal gyrus, left cingulate gyrus, and left precentral gyrus. After the 2-back test, decreased power was suggested in the left superior frontal gyrus and increased levels in the left middle temporal gyrus and left inferior parietal lobule. Some of these brain regions might be associated with task performance during the fatigue-inducing trials.
Conclusions: Two types of mental fatigue may produce different alterations of the spontaneous oscillatory MEG activities. Our findings would provide new perspectives on the neural mechanisms underlying mental fatigue.

DOI： 10.1186/1744-9081-9-2

掲載種別：研究論文（学術雑誌）  

Chronic fatigue syndrome (CFS) is characterized by a profound, disabling, and unexplained sensation of fatigue lasting an unexplained severe fatigue which lasts for at least 6 months with a combination of various symptoms, and it impairs patients' ability to live their days normally. Patients with CFS complain of neuropsychological symptoms, including cognitive impairment (thinking difficulties, decreased alertness, and impaired memory and concentration), chronic widespread pain (muscle pain, pain in multiple joints, headaches, and sore throat), and depressive symptoms. In addition, many studies have shown abnormalities in the central nervous system (CNS) in patients with CFS. These findings suggest that the CNS is primarily involved in the pathophysiology of CFS. Here, we review data primarily from behavioral, electrophysiological, and neuroimaging experiments related to neural dysfunction in CFS. Dysfunction of a facilitation system and central sensitization and classical conditioning of an inhibition system in the CNS seem to play pivotal roles in the pathophysiology of CFS. We also propose a treatment strategy for CFS on the basis of these suggested underlying neural mechanisms. © 2013 - IOS Press.

DOI： 10.3233/NIB-130065

掲載種別：研究論文（学術雑誌）  

Background: A depressive state is a common symptom in the elderly and often accompanies cognitive impairment. The coexistence of depressive symptoms and cognitive impairment is a serious problem, as it increases adverse outcomes for health, functional status, and mortality. It would thus be of great value to clarify the cognitive dysfunction associated with depressive symptoms. We aimed to identify the cognitive dysfunction, in particular, impairment of the response inhibition component of executive function, associated with depressive symptoms in elderly females using the Simple Color Reaction Test and Modified Stroop Color-Word Test.
Material/Methods: The study group consisted of 35 elderly women. They performed cognitive function task trials for 9 min. Univariate logistic regression analyses were performed to identify factors associated with the prevalence of the depressive state.
Results: Longer reaction time and lower correction rate of response inhibition trials were related to the prevalence of the depressive symptoms.
Conclusions: Impaired function of response inhibition may be a specific feature of the depressive state. Our findings may help clarify the neural mechanisms underlying the depressive state of elderly females.

DOI： 10.12659/MSM.883596

掲載種別：研究論文（学術雑誌）  

Background: Fatigue can be classified as mental and physical depending on its cause, and each type of fatigue has a multi-factorial nature. We examined the effect of mental fatigue on the central nervous system using electroencephalography (EEG) in eighteen healthy male volunteers.
Methods: After enrollment, subjects were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of four 30-min fatigue-inducing 0- or 2-back test sessions and two evaluation sessions performed just before and after the fatigue-inducing sessions. During the evaluation session, the participants were assessed using EEG. Eleven electrodes were attached to the head skin, from positions F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, and O2.
Results: In the 2-back test, the beta power density on the Pz electrode and the alpha power densities on the P3 and O2 electrodes were decreased, and the theta power density on the Cz electrode was increased after the fatigue-inducing mental task sessions. In the 0-back test, no electrodes were altered after the fatigue-inducing sessions.
Conclusions: Different types of mental fatigue produced different kinds of alterations of the spontaneous EEG variables. Our findings provide new perspectives on the neural mechanisms underlying mental fatigue.

DOI： 10.1186/1744-9081-8-48

掲載種別：研究論文（学術雑誌）  

Fatigue is a common complaint in modem society. As photosensitivity is associated with fatigue, this study aimed to clarify the relationship between neural response to visual stimuli and fatigue using a 160-channel whole-head-type magnetoencephalographic system. Twelve healthy male volunteers were enrolled. Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform acute fatigue-inducing mental task sessions, i.e., 0-back or 2-back test for 30 min. Visual evoked magnetic field (VEF) intensities were evaluated by standardized low-resolution brain electromagnetic tomography modified for a quantifiable method. VEF consisted of two phases, and although acute fatigue did not alter the VEF intensities and the intensities before the acute fatigue-inducing mental task sessions were not correlated with the Chalder's Fatigue Scale scores in either of the two phases, the intensities after the 0-back test trials for 30 min in Phase 1 and those after the 2-back test trials in Phase 2 were significantly correlated with the fatigue scale scores. The daily level of fatigue was related to VEF intensity after the acute mental fatigue loads. Our findings provide new perspectives to evaluate our daily level of fatigue as well as to clarify the neural mechanisms underlying it. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2012.03.056

掲載種別：研究論文（学術雑誌）  

The neural substrates of the fatigue sensation have not been totally identified. Several lines of evidence demonstrate that seeing emotional changes in others activates brain regions involved in experiencing similar emotions. We hypothesized that there exists a mirror system regarding the fatigue sensation and that brain regions associated with the fatigue sensation may be activated by viewing other individuals expressing fatigue. In this study, we attempted to identify the neural substrates activated by viewing other fatigued individuals using magnetoencephalography (MEG). Twelve healthy participants were enrolled in our study after providing written informed consent. During MEG recordings, they viewed a set of pictures projected on a screen. The pictures, which were presented in a randomized order, were of a person with a fatigued or neutral facial expression. When participants viewed pictures of people with fatigued expressions, we were able to estimate equivalent current dipoles (ECDs) in the posterior cingulate cortex (PCC) in 9 of 12 participants approximately 300 ms after the onset of each picture presentation. When they viewed pictures of people with neutral expressions, we were not able to estimate corresponding ECDs for any participant. The PCC is the brain region activated by viewing others expressing fatigue, suggesting existence of the shared neural substrates of felt and observed fatigue. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2012.03.031

掲載種別：研究論文（学術雑誌）  

The purpose of this study was to establish a method for imaging the process of gastrointestinal (GI) absorption and subsequent biodistribution in the human body after oral drug administration, using positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG). First, we developed a method to deliver the radiotracer safely into the stomach using soft gelatin capsules to avoid any significant exposure to the pharyngoesophageal region. Second, we performed pharmacokinetic (PK) analyses on time radioactivity profiles in GI tissues and blood to calculate the gastric emptying and intestinal elimination rate constants and to estimate the fluid volume in the lumen of the small intestine from PET image analysis.This is the first study involving oral administration of a PET probe in humans, and the results demonstrate the high potential of PET technology to investigate the GI absorption and PK profiles of drugs in humans.

DOI： 10.1038/clpt.2011.267

掲載種別：研究論文（学術雑誌）  

Background: Considering the high prevalence of dementia, it would be of great value to develop effective tools to improve cognitive function. We examined the effects of a human-type communication robot on cognitive function in elderly women living alone. Material/Methods: In this study, 34 healthy elderly female volunteers living alone were randomized to living with either a communication robot or a control robot at home for 8 weeks. The shape, voice, and motion features of the communication robot resemble those of a 3-year-old boy, while the control robot was not designed to talk or nod. Before living with the robot and 4 and 8 weeks after living with the robot, experiments were conducted to evaluate a variety of cognitive functions as well as saliva cortisol, sleep, and subjective fatigue, motivation, and healing. Results: The Mini-Mental State Examination score, judgement, and verbal memory function were improved after living with the communication robot
those functions were not altered with the control robot. In addition, the saliva cortisol level was decreased, nocturnal sleeping hours tended to increase, and difficulty in maintaining sleep tended to decrease with the communication robot, although alterations were not shown with the control. The proportions of the participants in whom effects on attenuation of fatigue, enhancement of motivation, and healing could be recognized were higher in the communication robot group relative to the control group. Conclusions: This study demonstrates that living with a human-type communication robot may be effective for improving cognitive functions in elderly women living alone.

DOI： 10.12659/MSM.883350

PubMed

掲載種別：研究論文（学術雑誌）  

Objective: Fatigue decreases efficiency in performing daily tasks, and this is a common symptom in modern society. It would thus be of great value to clarify the mechanism underlying fatigue and to develop efficient methods to evaluate fatigue. We examined cognitive function associated with two types of mental fatigue.
Methods: Twenty healthy volunteers were randomised to perform rest or fatigue-inducing mental task session (0-back or 2-back test session) for 30 min in a 3-way crossover design. Just before and after each session, participants completed cognitive task trials to evaluate simple and conflict-controlling selective attention (response inhibition).
Results: Changes in the reaction time of simple selective attention task after the 2-back test session were longer and changes after the 0-back test session had a trend toward being longer than those after the rest session. In addition, changes in the percent error for Stroop effect after the 2-back test session were significantly higher than those after the rest session, although those after the 0-back test session were not.
Conclusions: Different types of mental fatigue produced different styles of deteriorated cognitive performances. Impaired selective attention may be a specific feature of mental fatigue, and a higher mental load may introduce a greater level of impaired conflict control or response inhibition.

掲載種別：研究論文（学術雑誌）  

N-terminal propeptide of type I procollagen (PINP) is a marker of newly formed type I collagen. However, its role in hypophosphatemic rickets/osteomalacia has not yet been established. Metabolic bone markers were examined in patients with oncogenic osteomalacia (OOM) and X-linked hypophosphatemic rickets (XLH), and in healthy controls. OOM and XLH patients were found to have hypophosphatemia secondary to elevated levels of serum fibroblast growth factor 23 (FGF-23). OOM patients had reduced levels of 1,25-dihydroxy vitamin D (1,25D) compared with XLH patients and healthy controls, despite attenuation of the reduction in these levels in the XLH patients secondary to active vitamin D supplementation. In contrast to patients with XLH, OOM patients showed a significant increase in serum PINP, which is suggestive of accelerated bone matrix formation. Bone alkaline phosphatase (BAP) and the BAP/PINP ratio were also increased in OOM but not in XLH patients, suggesting the presence of a disturbance in bone mineralization in OOM. Long-term supplementation of active form vitamin D and inorganic phosphate (IP) may have attenuated the defect in bone mineralization in the XLH patients, resulting in the normalization of PINP, BAP, and the BAP/PINP ratio. The present results suggest that, as with BAP, PINP is an appropriate metabolic bone marker in the assessment of hypophosphatemic rickets/osteomalacia.

DOI： 10.1007/s12020-011-9512-z

掲載種別：研究論文（学術雑誌）  

Serum calcium is one of major regulators of PTH amino-terminal (N-terminal) truncation and secretion of full-length (1-84)PTH from parathyroid glands. However, the effect of active vitamin D-3 on PTH truncations remains controversial. To determine whether active vitamin D-3 accelerates the truncation of PTH, the vitamin D-3 analogue alfacalcidol was administered to patients with pseudohypoparathyroidism type Ib (PHP Ib). Both the (1-84)PTH molecule and N-terminally truncated fragments such as (7-84)PTH can be measured by commercially available two-site total PTH (T-PTH) assays. The development of whole PTH (W-PTH) assays specific for full-length (1-84)PTH. has enabled us to distinguish between N-terminally truncated PTH and full-length (1-84)PTH. W-PTH/T-PTH ratios were calculated and used as an index of PTH N-terminal truncations. Both serum W-PTH and T-PTH levels were elevated in untreated PHP Ib patients. The administration of alfacalcidol reduced both the w-pm and T-PTH levels; however, the W-PT1/T-PTH ratios were stable. Serum calcium levels were significantly and negatively correlated with both the W-PTH and T-PTH levels, but not with the W-PTH/T-PTH ratios. Thus, the administration of an active vitamin D-3 analogue did not seem to have a major effect on the rate of PTH N-terminal truncation, even though it did reduce the secretion of both full-length and truncated PTH. Possibly, active vitamin D-3 attenuates the effect of elevated calcium on PTH N-terminal truncation in PHP Ib patients.

DOI： 10.1507/endocrj.K10E-012

掲載種別：研究論文（学術雑誌）  

Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.

DOI： 10.1007/s00223-010-9369-9

掲載種別：研究論文（学術雑誌）  

We have used functional magnetic resonance imaging to study the neural correlates of motivation, concentrating on the motivation to learn and gain monetary rewards. We compared the activation in the brain obtained during reported high states of motivation for learning, with the ones observed when the motivation was based on monetary reward. Our results show that motivation to learn correlates with bilateral activity in the putamen, and that the higher the reported motivation, as derived from a questionnaire that each subject filled prior to scanning, the greater the change in the BOLD signals within the putamen. Monetary motivation also activated the putamen bilaterally, though the intensity of activity was not related to the monetary reward. We conclude that the putamen is critical for motivation in different domains and the extent of activity of the putamen may be pivotal to the motivation that drives academic achievement and thus academic successes. (c) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.neuroimage.2008.04.253

掲載種別：研究論文（学術雑誌）  

Motivation is an important psychological concept in academic learning. Subjects performed jigsaw puzzle and square puzzle sessions (as difficulty variant task) and 80%, 50%, and 20% completion sessions (as completion variant task). After square puzzle or 20% completion sessions, subjective motivation decreased. Although baseline scores on an academic motivation scale were negatively correlated with changes in subjective motivation for the square puzzle session, a positive correlation was observed for the 20% completion session. These suggest that while continual completion of facile task trials may support the motivation of college students with lower academic motivation, attempting difficult task trials may sustain that of those with higher academic motivation.

DOI： 10.1080/00207450701242982

掲載種別：記事・総説・解説・論説等（学術雑誌）  

掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.1016/j.neures.2011.07.1172

掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.1016/j.neures.2011.07.711

掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.1016/j.neures.2011.07.862

掲載種別：記事・総説・解説・論説等（学術雑誌）  

掲載種別：記事・総説・解説・論説等（学術雑誌）  

掲載種別：記事・総説・解説・論説等（学術雑誌）   共著区分：単著  

会議種別：口頭発表（一般）  

会議種別：口頭発表（一般）  

会議種別：口頭発表（一般）