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Yasuyoshi Watanabe

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11 papers

1 author row

YNIMG Journal 2018 Journal Article

A voxel-based analysis of neurobiological mechanisms in placebo analgesia in rats

Ying Zeng
Di Hu
Wei Yang
Emi Hayashinaka
Yasuhiro Wada
Yasuyoshi Watanabe
Qunli Zeng
Yilong Cui

Placebo analgesia is the beneficial effect that follows despite a pharmacologically inert treatment. Modern neuroimaging studies in humans have delineated the hierarchical brain regions involved in placebo analgesia. However, because of the lack of proper approaches to perform molecular and cellular manipulations, the detailed molecular processes behind it have not been clarified. To address this issue, we developed an animal model of placebo analgesia in rats and analyzed the placebo analgesia related brain activity using small-animal neuroimaging method. We show here that gabapentin-based Pavlovian conditioning successfully induced placebo analgesia in neuropathic pain model rats and hierarchical brain regions are involved in placebo analgesia in rats, including the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), ventrolateral periaqueductal gray matter (vlPAG), etc. The functional couplings in placebo responders between the mPFC and vlPAG was interrupted by naloxone, an antagonist of μ opioid receptor. Moreover, both local chemical lesion and microinfusion of naloxone in the mPFC suppressed the placebo analgesia. These results suggest that the intrinsic μ opioid system in the mPFC causally contribute to placebo analgesia in rats, and the small-animal neuroimaging approach could provide important insights toward understanding the placebo effect in great detail.

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YNICL Journal 2016 Journal Article

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

Kei Mizuno
Junko Kawatani
Kanako Tajima
Akihiro T. Sasaki
Tetsuya Yoneda
Masanori Komi
Toshinori Hirai
Akemi Tomoda

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

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YNIMG Journal 2015 Journal Article

A voxel-based analysis of brain activity in high-order trigeminal pathway in the rat induced by cortical spreading depression

Yilong Cui
Hiroshi Toyoda
Takeo Sako
Kayo Onoe
Emi Hayashinaka
Yasuhiro Wada
Chihiro Yokoyama
Hirotaka Onoe

Cortical spreading depression (SD) is a self-propagating wave of depolarization that is thought to be an underling mechanism of migraine aura. Growing evidence demonstrates that cortical SD triggers neurogenic meningeal inflammation and contributes to migraine headaches via subsequent activation of trigeminal afferents. Although direct and indirect evidence shows that cortical SD activates the trigeminal ganglion (peripheral pathway) and the trigeminal nucleus caudalis (TNC, the first central site of the trigeminal nociceptive pathway), it is not yet known whether cortical SD activates the high-order trigeminal nociceptive pathway in the brain. To address this, we induced unilateral cortical SD in rats, and then examined brain activity using voxel-based statistical parametric mapping analysis of FDG-PET imaging. The results show that approximately 40h after the induction of unilateral cortical SD, regional brain activity significantly increased in several regions, including ipsilateral TNC, contralateral ventral posteromedial (VPM) and posterior thalamic nuclei (Po), the trigeminal barrel-field region of the primary somatosensory cortex (S1BF), and secondary somatosensory cortex (S2). These results suggest that cortical SD is a noxious stimulus that can activate the high-order trigeminal nociceptive pathway even after cortical SD has subsided, probably due to prolonged meningeal inflammation.

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YNICL Journal 2015 Journal Article

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

Kei Mizuno
Masaaki Tanaka
Hiroki C. Tanabe
Takako Joudoi
Junko Kawatani
Yoshihito Shigihara
Akemi Tomoda
Teruhisa Miike

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

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YNICL Journal 2013 Journal Article

Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder

Kei Mizuno
Tetsuya Yoneda
Masanori Komi
Toshinori Hirai
Yasuyoshi Watanabe
Akemi Tomoda

Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD.

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YNIMG Journal 2008 Journal Article

The neural basis of academic achievement motivation

Kei Mizuno
Masaaki Tanaka
Akira Ishii
Hiroki C. Tanabe
Hirotaka Onoe
Norihiro Sadato
Yasuyoshi Watanabe

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.

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YNIMG Journal 2004 Journal Article

Functional imaging of gustatory perception and imagery: “top-down” processing of gustatory signals

Masayuki Kobayashi
Masaki Takeda
Noriaki Hattori
Masaki Fukunaga
Tetsuya Sasabe
Noriko Inoue
Yasuo Nagai
Tohru Sawada

By recalling gustatory memories, it is possible to generate vivid gustatory perceptions in the absence of gustatory inputs. This gustatory image influences our gustatory processing. However, the mechanism of the “top-down” modulation of gustatory perception in the human is still unclear. Our findings propose a new perspective on the neural basis of gustatory processing. Although gustatory imagery and gustatory perception shared common parts of neural substrates, there was an asymmetrical topography of activation in the insula: the left insula was predominantly activated by gustatory imagery tasks. In addition, the middle and superior frontal gyri were not activated by gustatory perception but they participated in the generation of gustatory hallucinations. These regions in the frontal cortex may mediate the “top-down” control of retrieving gustatory information from the storage of long-term memories.

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YNIMG Journal 2003 Journal Article

Assessment of microPET performance in analyzing the rat brain under different types of anesthesia: comparison between quantitative data obtained with microPET and ex vivo autoradiography

Akira Matsumura
Shigekazu Mizokawa
Masaaki Tanaka
Yasuhiro Wada
Satoshi Nozaki
Fusao Nakamura
Susumu Shiomi
Hironobu Ochi

MicroPET (positron emission tomography) has been implemented for use in experiments with small animals. However, the quantification and optimal conditions for scanning are not established yet. The aim of this study was to compare the results obtained by microPET with those by ex vivo autoradiography of rat brain slices, based on the 2-[18F]fluoro-2-deoxy-d-glucose (FDG) method, and to establish the optimal conditions for scanning. As an example, we examined glucose metabolism in the rat brain under 6 types of anesthesia and in the conscious state. The scanning conditions for the rat brain were (1) use of a 4-mm-thick leaden jacket, (2) an energy window of 350–650 keV, and (3) a coincidence time window of 6 ns. Under these conditions, the quantitative ROI data from microPET showed a good correlation with the corresponding ROI data from FDG autoradiography in the animal study (r 2 = 0. 81). With our protocol, when anesthesia was started 40 min after the FDG injection, the glucose metabolism was almost the same as that in the conscious rat brain.

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YNIMG Journal 2002 Journal Article

Brain Regions Involved in Fatigue Sensation: Reduced Acetylcarnitine Uptake into the Brain

Hirohiko Kuratsune
Kouzi Yamaguti
Gudrun Lindh
Birgitta Evengård
Gisela Hagberg
Kiyoshi Matsumura
Masao Iwase
Hirotaka Onoe

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation. Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate. When we studied the cerebral uptake of acetylcarnitine by using [2-11C]acetyl-l-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann's area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum. These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

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YNIMG Journal 2002 Journal Article

Neural Substrates of Human Facial Expression of Pleasant Emotion Induced by Comic Films: A PET Study

Masao Iwase
Yasuomi Ouchi
Hiroyuki Okada
Chihiro Yokoyama
Shuji Nobezawa
Etsuji Yoshikawa
Hideo Tsukada
Masaki Takeda

Laughter or smile is one of the emotional expressions of pleasantness with characteristic contraction of the facial muscles, of which the neural substrate remains to be explored. This currently described study is the first to investigate the generation of human facial expression of pleasant emotion using positron emission tomography and H2 15O. Regional cerebral blood flow (rCBF) during laughter/smile induced by visual comics and the magnitude of laughter/smile indicated significant correlation in the bilateral supplementary motor area (SMA) and left putamen (P < 0. 05, corrected), but no correlation in the primary motor area (M1). In the voluntary facial movement, significant correlation between rCBF and the magnitude of EMG was found in the face area of bilateral M1 and the SMA (P < 0. 001, uncorrected). Laughter/smile, as opposed to voluntary movement, activated the visual association areas, left anterior temporal cortex, left uncus, and orbitofrontal and medial prefrontal cortices (P < 0. 05, corrected), whereas voluntary facial movement generated by mimicking a laughing/smiling face activated the face area of the left M1 and bilateral SMA, compared with laughter/smile (P < 0. 05, corrected). We demonstrated distinct neural substrates of emotional and volitional facial expression and defined cognitive and experiential processes of a pleasant emotion, laughter/smile.

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YNIMG Journal 2001 Journal Article

Cortical Networks Recruited for Time Perception: A Monkey Positron Emission Tomography (PET) Study

Hirotaka Onoe
Masashi Komori
Kayo Onoe
Hajime Takechi
Hideo Tsukada
Yasuyoshi Watanabe

The presence of an “internal clock” in the brain has been assumed to underlie the information processing related to time. This clock plays a critical role in time keeping and time perception, which are closely associated with integrated functions in the brain. To identify the brain areas recruited for time keeping and time perception, we performed positron emission tomography (PET) studies with rhesus monkeys to measure regional cerebral blood flow (rCBF) as an index of neural activity during time discrimination tasks of different durations ranging from 400 to 1500 ms. Changes in rCBF that covaried significantly with the durations of the target being perceived by subjects were found in the dorsolateral prefrontal cortex (DLPFC), the posterior part of the inferior parietal cortex, basal ganglia, and posterior cingulate cortex. Furthermore, a loss of neuronal function in the DLPFC caused by a local application of bicuculline resulted in the selective reduction of performance in time discrimination tasks. The results indicate that a neural network composed of the posterior inferior parietal cortex to the DLPFC plays a crucial role in the temporal monitoring process in time perception.

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