Previous studies have revealed that physical activity can affect brain function and cognitive decline. Additionally, we confirmed that brain activation in the (PFC) during a cognitive task was correlated with cognitive function. Based on these findings, we hypothesized that brain activation also affects cognitive function, which increases due to stimulation from physical activity. The purpose of this study was to verify causal relationships between physical activity, PFC activation, and cognitive function using the statistical method of path analyses in a multi-model approach.Forty-six healthy volunteers (10 males, mean age: 76.1, standard deviation: 6.8) participated in this study. Informed consent was obtained from all participants prior to enrollment. This study was approved by the Ethics Committee of Seirei Christopher University (approval No. 10067). We assessed physical activity via participants’self-reports, determined PFC activation during a dual task using near-infrared spectroscopy, and measured cognitive function with the Trail-Making Test Part B. To determine the causal relationship between physical activity, PFC activation, and cognitive function, path analyses were conducted using AMOS 16 structural equation modeling. The structural equation model was a good fit (root mean square error of approximation = 0.001). Several significant direct paths were identified: (1) from physical activity to PFC activation (b = 0.37), and (2) from PFC activation to cognitive function (b = 0.32). This study statistically revealed the causal relationships between physical activity, PFC activation, and cognitive function. Path analyses indicated that physical activity affected cognitive function via PFC activation.

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It is very interesting to determine whether disturbance of mastication following occlusal dysfunction has an effect on mental stress. Therefore, an experimental occlusal interference was attached, and the effect on dopamine release from the rat was examined.
The extracellular fluid dopamine volume of the was measured by the brain microdialysis method.
1. Though experimental occlusal interference during nonfunctional periods was intraoral, it. was found that the metabolism of the dopamine did not change.
2. Experimental occlusal interference during functional periods, that is, feeding periods with cubed food under occlusal interference increased the dopamine volume. It was clarified that experimental occlusal interference strongly impacts the affect of the rat by changing the metabolism of dopamine in the .
3. Cubed food and powdered food increased the dopamine volume in the same way. It was found that there was no difference in transition of the increase in the dopamine volume from the difference in the texture of the food.
Experimental occlusal interference related to feeding behavior affected dopamine metabolism in the rat , and it was clarified that a strong stress reaction was induced by experimental occlusal interference.

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In a complex and changing environment, the validity of rules or goals might change in terms of their associated reward and cost, and we often face the necessity to make a strategic decision to adaptively shift between these behavioral rules or goals.　Such a decision entails assessment of the value (cost and benefit) of current and alternative rules or reward resources for the individual, and also for the group, in socially advanced species.　Cognitive abilities such as flexibility in adapting to a changing environment and adaptive foraging to seek a better environment might depend on such cognitive functions that enable a thorough assessment of the value of different options and a proper and timely decision to choose the most appropriate goal.　A distributed neural network involving prefrontal and medial frontal cortices regulates the use of cognitive resources to optimize exploitation of current reward resources, while minimizing the associated cost.　This is referred to as executive control of goal directed behavior.　Recent studies suggest that dorsolateral prefrontal, orbitofrontal and anterior cingulate cortices are involved in optimizing the exploitation of the current reward sources however, the most rostral part of the

(frontopolar cortex) plays a crucial role in adjusting the tendency for exploitation, versus exploration of other alternative resources, by assessing the value of alternative tasks/goals and re-distribution of our cognitive resources.　Maintaining a proper balance between exploitation and exploration tendencies might be a fundamental cognitive ability necessary for foraging behavior and cognitive flexibility in adapting to environmental demands.

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Objective: Footbaths are employed in nursing practice in East Asian countries. Assessing the effects of footbaths based on the findings of multiple physiological responses is relevant to ensuring evidence-based nursing practice. This study aimed to investigate the effects of thermal stimulation by a footbath on

activity and autonomic nervous function. Methods: This study was a randomized controlled crossover trial conducted on healthy participants from a college student population. Each participant underwent a footbath in warm water and a control condition for 10 min on two different days. The order of the two treatments was randomized. The oxygenated hemoglobin concentration in the , laterality scores of the oxygenated hemoglobin concentration changes, and autonomic responses were evaluated. Results: A total of 17 healthy participants were recruited. A footbath in warm water significantly reduced both the and sympathetic nerve activities 7 min after the start of the footbath compared with the control condition. Moreover, a footbath in warm water tended to activate the left rather than the right . Conclusions: The changes in the activity and autonomic nervous function were associated with the relaxing effect of the thermal stimulation by the footbath. Furthermore, this effect was highest at 7 min after the start of the footbath. This study has the potential to contribute to the evidence-based use of footbaths. Trial Registration: UMIN-CTR Clinical Trial: UMIN000033735

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ADHD is one of the most prevalent childhood psychiatric disorders. Although ADHD is not caused by a single cause, many studies suggest that ADHD can be explained as prefrontal dysfunctions. Since the participates in working memory, attentional control, inhibition of inappropriate behavior, and regulation of emotion and motivation, the fact that many children exhibiting ADHD show disinhibition of behavioral responses and difficulty in sustained attention suggests strong contribution of the to ADHD. Studies also suggest that ADHD is related to deficits of dopamine-related functions, because methylphenidate, which is a dopamine transporter inhibitor, is the most effective drug for the treatment of ADHD and because genetic studies suggest the relations between ADHD and dopamine functions. The is the cortical area where the most strong dopamine innervation is observed. In addition, local injection of dopamine-related drugs to the produces modulation of task-related activity and behavioral deficits in cognitive task performances. Thus, the dysfunction of dopamine-related modulation in the could be possible candidates of biological causes of ADHD. To prove this notion, it is now necessary to make a primate model of ADHD by artificially disturbing dopamine functions in the clonically and examine its behavior and neural activities. [Jpn J Physiol 55 Suppl:S56 (2005)]

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The patterns of the multisynaptic inputs from the prefrontal areas to the primary motor cortex (MI) were studied by means of retrograde transsynaptic transport of rabies virus. Previous studies revealed that transsynaptic labeling of 1st-, 2nd-, and 3rd-order neurons with the virus occurs at 2, 3, and 4 days postinjection periods. In the present study, the virus was injected into the hindlimb, proximal forelimb, or distal forelimb representation of the MI of macaque monkeys, and, 4 days after the injection, the distribution of labeled neurons was examined in the . After the viral injection into the hindlimb representation, prefrontal labeling was observed mainly in the medial that is located on the medial wall of the hemisphere. After the injection into the proximal forelimb representation, a large number of neurons were labeled in the dorsolateral , mainly in its dorsal sector. After the injection into the distal forelimb representation, very dense labeling was observed in the ventral sector of the dorsolateral . The present results suggest that there may be a somatotopic organization in the . Functional implications for this organization will be discussed in terms of intracortical inputs to the prefrontal areas. [Jpn J Physiol 55 Suppl:S185 (2005)]

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Chronic pain often has an unknown cause, and many patients with chronic pain learn to accept that their pain is incurable and pharmacologic treatments are only temporarily effective. Complementary and integrative health approaches for pain are thus in high demand. One such approach is soft touch, e.g., adhesion of pyramidal thorn patches in a pain region. The effects of patch adhesion on pain relief have been confirmed in patients with various types of pain. A recent study using near-infrared spectroscopy revealed that the dorsolateral

(DLPFC), especially the left side, is likely to be inactivated in patients experiencing pain relief during patch treatment. Mindfulness meditation is another well-known complementary and integrative approach for achieving pain relief. The relation between pain relief due to mindfulness meditation and changes in brain regions, including the DLPFC, has long been examined. In the present review article, we survey the literature describing the effects of the above-mentioned complementary and integrative treatments on pain relief, and outline the important brain regions, including the DLPFC, that are involved in analgesia. We hope that the present article will provide clues to researchers who hope to advance neurosensory treatments for pain relief without medication.

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In order to determine if disturbances in mastication resulting from occlusal dysfunction affect mental stress, I created experimental occlusal interferences in rats and monitored dopamine release in their .Extracellular fluid dopamine volume in the was measured by the brain microdialysis method.When the animals with occlusal interferences were fed cubed food, there was an increase in dopamine volume in the .Experimental occlusal interference affected dopamine metabolism in the rat when the animals were fed, clearly inducing a strong stress reaction.

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Brain stem lesions and stimulation effects upon prefrontal electrical activity in relation to limbic evoked potentials and after-discharges were studied in 20 squirrel monkeys. The studies were performed under phencyclidine hydrochloride (Sernylan) anesthesia.
After-discharges elicited from the amygdala and hippocampus propagated to the following the lesion in the field H of Forel, whereas the septal stimulation elicited a self-sustained prefrontal after-discharge and a limbic after-discharge. Evoked potentials in the with the stimulation of the septum, amygdala, and hippocampus were attenuated by the conditioning stimuli in the field H of Forel.
It was concluded that the lesion in the field H of Forel increased the excitability of to limbic stimulation and after-discharges.

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The has been shown to be involved in the regulation of emotions. It has been also reported that the related to the positive mood in mothers viewing pictures of their newborn infants. This study sought to determine the influence of sex and parental status on the prefrontal activity elicited by discrimination tasks of infant facial expressions. We measured NIRS activity of the in adults (male group, non-parent female group and mother group) when they see pictures on screen to judge a) the kind of pictures, b) the sex of adults, c) the emotion of adult facial expressions, d) the sex of infants, e) the emotion of infant facial expressions. This study was approved by the ethics committee of Nagasaki University. When subjects judge the emotion of infant, the concentration of delta oxygenated hemoglobin (oxyHb) was significantly increased in the right only in mother group compared with male and non-parent female groups (One way ANOVA followed by bonferoni / Dunn post hoc test; p<0.05). However, the left activity was not increased in any groups. No significant differences were found among the groups in the other discrimination tasks. These results suggest that the right frontal cortex is involved in maternal attachment behaviors. [J Physiol Sci. 2007;57 Suppl:S168]

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Cerebral hemodynamics plays an important role in cognitive performance, and as such, age-related cognitive dysfunction and cerebral hypoperfusion increase the risk of dementia. However, age-related changes in cerebral oxygenation and cognitive function remain unclear. The aim of this study was to investigate age-related declines in cerebral oxygenation and executive function cross-sectionally. Ninety-eight healthy Japanese adults (age range: 23-79 years; 40 males, 58 females) participated in the present study using local advertisements. The participants were divided into 4 age groups: young (20-39 years; M15/F7), 50s (50-59 years; M10/F12), 60s (60-69 years; M9/F31), and 70s (70-79 years; M6/F8). We measured oxygenated hemoglobin (oxy-Hb) signal change in the

during the Stroop task, and calculated Stroop interference time in cross-sectional design. This test is widely used to measure the ability to properly control attention and behavior in executing tasks, and to evaluate executive functions mainly associated with the . Oxy-Hb signal changes in the left in the 60s and 70s groups were significantly lower than those in the young group (both P < 0.05). Additionally, Stroop interference time was significantly longer in the 60s and 70s groups than in the young group (both P < 0.05). Furthermore, differences in oxy-Hb signal change between the left and right were evident only in the young group. These results suggest that the age-related decrease in executive function is associated with decrease in the cerebral oxygenation hemodynamics in the left .

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Medial (MPFC) activation has been observed in studies of many types related to emotion regulation, self and familiar other-knowledge, mentalizing, morality, reward, and uncertainty. Furthermore, the anterior cingulate cortex (ACC) and the lateral (LPFC), which have reciprocal connections with MPFC, are considered necessary for cognitive regulation. Based on these findings, Nakao, Takezawa, and Miyatani (2006) proposed an integrative explanation for MPFC function: MPFC has a function of representing a benchmark that reduces conflict among many possible answers by biasing either choice of behavior. In this article, we review studies related to MPFC function and the benchmark hypothesis with recent new findings. Additionally, we discuss emotion regulation, which was not described in Nakao et al. (2006), in relation to the benchmark hypothesis.

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  Previous studies have shown that acute systemic administration of ethanol induced striatal ascorbic acid (AA) release in mice and rats. Undercutting the completely eliminated ethanol-induced AA release in rat striatum. In the present study, in vivo brain dialysis coupled with high performance liquid chromatography (HPLC)-electrochemical detection was used to evaluate the effect of ethanol on the release of AA in the , compared to that in the striatum of freely moving mice. The results showed that ethanol (4.0 g/kg i.p.) similarly induced AA release in the and striatum of freely moving mice.

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ADHD is one of the most prevalent childhood psychiatric disorders and could be explained as a prefrontal dysfunction. Studies suggest that ADHD is related to deficits of dopamine-related functions, because methylphenidate, which is a dopamine transporter inhibitor, is the most effective medication for the treatment of ADHD. The is the cortical area where the most strong dopamine innervation is observed. Local acute injection of dopamine-related drugs to the produces modulation of task-related activity and behavioral deficits in cognitive task performances. Thus, the dysfunction of dopamine-related modulation in the could be a possible candidate of biological causes of ADHD. To prove this idea, in the future we are going to inject 6-OHDA into infant monkeys' to disturb dopamine functions chronically and compare its behavior with normal monkeys.

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トルエンはシンナーの主要な成分で，吸入により酩酊感を得ることができる．近年まで，トルエンの神経薬理学的影響に焦点をあてている実験データは極めて少ない．この研究では，トルエンによる中枢神経系への作用を調べた．自由行動下のラットで，トルエン吸入曝露の間の大脳皮質内側前頭前野（mPFC）と側坐核（NAcc）におけるノルアドレナリンとドパミンの濃度変化をin vivoマイクロダイアリシスを用いて研究した．7,000ppmのトルエンの吸入は，mPFCとNAccで細胞外ノルアドレナリンとドパミン濃度を増加させた．NAccにおいて，ノルアドレナリンとドパミンは，それぞれの基準値に対して210％と178％まで増加した．mPFCにおいて，ノルアドレナリンとドパミンはそれぞれ，306％と183％まで増加した．両方の部位で，ノルアドレナリンの増加は，ドパミンの増加より大きかった．1,000ppmと3,000ppmのトルエンの吸入では，細胞外ノルアドレナリンとドパミンの濃度に有意な影響をあたえなかった．トルエン吸入は，薬物依存に特に重要な役割を果たす中脳辺縁系ドパミン神経に関与することが明らかになった．これらの結果はまた，吸入によるトルエンへの曝露がノルアドレナリン作動性神経の興奮性を高めることも示唆する．

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Cyclosporine is widely used in immunosuppressive therapy for organ transplantation and autoimmune disease. However, cyclosporine administration causes neuropsychological side effects such as depression, anxiety, confusion, and tremor in some patients. We have previously shown that cyclosporine induces anxiety-related behaviour and decreases social behaviour in mice, and that clozapine partially restored social behaviour in cyclosporine-injected mice. The has been shown to control anxiety-related and social behaviour. In the present study, we examined effects of cyclosporine and clozapine upon release of dopamine and serotonin within the . Microdialysis probes were inserted in the of urethane anaesthetized mice, and contents of dopamine and serotonin in the perfusates were measured by HPLC with electrochemical detection. Release of dopamine and serotonin was reduced in the cyclosporine-treated mice. In the mice that received both cyclosporine and clozapine, dopamine release was not reduced. All these data are consistent with the hypothesis that cyclosporine disturbs social behaviour as a result of reduced dopamine release in the . [J Physiol Sci. 2007;57 Suppl:S135]

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Whereas brain studies of symbol manipulations, including thinking and tool-use, have been extensively performed in human with brain-imaging techniques, neuronal data for this issue have been limited. However, recent studies with monkeys have provided some interesting data that allow us to hypothesize neuronal mechanisms of symbol manipulations. For example, neuronal groups of the code and retain behavioral meaning/abstract information for guiding goal-directed motor acts. These neurons appear to play a role in manipulating and retaining of symbolic information. Further, the is well known as a center of working memory, which contains “executive” associated with manipulation of information and control of brain systems. Based on these and other findings, we can hypothesize that the has a neuronal system for “executive symbol manipulation”. The executive is a central neuronal system of goal-directed symbol manipulations for controlling other brain systems, and this system would first evolve for tool-use and eventually develop for language and other symbol manipulations. Since the executive symbol manipulation is a possible neuronal system of the and can be examined with non-human primates, this hypothesis would be useful for leading neuronal studies of brain mechanisms of symbol manipulations.

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Experimental studies to understand prefrontal functions started after Jacobsen (1936) first reported that bilateral prefrontal lesions produced a permanent deficit of delayed-response performance in monkeys. However, neurophysiological experiments to understand neural mechanisms of prefrontal functions began in the early 1970s using awake behaving monkeys first by Kubota's group in Japan and Fuster's group in USA. These groups reported many important and basic findings, including the finding of delay-period activity and its characteristics. Although spatial tasks, such as a delayed-response task or a delayed alternation task, were initially used to examine neural mechanisms of prefrontal functions, non-spatial tasks, such as a delayed matching-to-sample task, were also used for these experiments in the 1980s and the importance of delay-period activity was gradually recognized as a key activity to understand prefrontal functions. In the late 1980s, Goldman-Rakic proposed "working memory" as a key concept to combine findings of behavioral and neurophysiological experiments using animals with findings of clinical studies using human frontal patients and to interpret all these findings using one common concept. Her proposal was supported by a series of neurophysiological and behavioral studies conducted by her group. The term working memory became a key word in prefrontal studies in the 1990s, especially in non-invasive brain imaging studies. Although working memory may not be an appropriate concept to interpret functions of whole , working memory is a useful concept to understand functions of the lateral . Only a small number of groups in the world started neurophysiological studies in the primate in the 1970s. Studies of prefrontal functions have now become one of the major fields in neuroscience. The is the most important cortical area to understand the human mind. Although a huge volume of new findings regarding prefrontal functions have been accumulated since the 1970s, the is still a not-well-understood cortical area. We need further experiments to solve the secrets of prefrontal functions.

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Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the prototype for a potential new generation of glutamate-based antidepressants that rapidly relieve symptoms of depression within hours of treatment. Studies in rodents have demonstrated that neuroplasticity in the medial

(mPFC) is critical for the antidepressant actions of ketamine. However, effector circuits downstream of the mPFC underlying the rapid antidepressant responses remain unknown. To address this issue, we used optogenetic and chemogenetic circuit mapping in rodent models for studying depression, demonstrating the role of the basolateral amygdala (BLA) and bed nucleus of stria terminalis (BNST) as downstream targets of the mPFC mediating distinct behavioral effects of ketamine. By inhibiting isolated mPFC projections in the period immediately following ketamine administration, we found that mPFC-mediated activation of BLA principal neurons, and subsequent projections to the ventral hippocampus, mediate a subset of ketamine&apos;s persistent antidepressant-like effects on passive coping behavior but not on anxiety-like and reward-seeking behaviors. In contrast, mPFC projections to the BNST are necessary and sufficient to produce persistent antidepressant-like effects on anxiety-like and reward-seeking behaviors but not on passive coping behavior. Therefore, our data support a model where distinct downstream circuits of the mPFC contribute to producing separate antidepressant-like behavioral responses.

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