研究者業績

武田 湖太郎

タケダ コタロウ  (Kotaro Takeda)

基本情報

所属
藤田医科大学 保健衛生学部 リハビリテーション学科 臨床療法科学 准教授
学位
博士

連絡先
ktakedafujita-hu.ac.jp
研究者番号
50618733
ORCID ID
 https://orcid.org/0000-0002-0446-4043
J-GLOBAL ID
200901034389316890
Researcher ID
F-8948-2019
researchmap会員ID
5000092948

外部リンク

論文

 96
  • Yohei Hasebe, Shigefumi Yokota, Isato Fukushi, Kotaro Takeda, Masashi Yoshizawa, Hiroshi Onimaru, Yosuke Kono, Shuei Sugama, Makoto Uchiyama, Keiichi Koizumi, Jouji Horiuchi, Yoshihiko Kakinuma, Mieczyslaw Pokorski, Takako Toda, Masahiko Izumizaki, Yasuo Mori, Kanji Sugita, Yasumasa Okada
    Scientific Reports 14 22984 2024年10月3日  査読有り
    Abstract The reflexive excitation of the sympathetic nervous system in response to psychological stress leads to elevated blood pressure, a condition that persists even after the stress has been alleviated. This sustained increase in blood pressure, which may contribute to the pathophysiology of hypertension, could be linked to neural plasticity in sympathetic nervous activity. Given the critical role of astrocytes in various forms of neural plasticity, we investigated their involvement in maintaining elevated blood pressure during the post-stress phase. Specifically, we examined the effects of arundic acid, an astrocytic inhibitor, on blood pressure and heart rate responses to air-jet stress. First, we confirmed that the inhibitory effect of arundic acid is specific to astrocytes. Using c-Fos immunohistology, we then observed that psychological stress activates neurons in cardiovascular brain regions, and that this stress-induced neuronal activation was suppressed by arundic acid pre-treatment in rats. By evaluating astrocytic process thickness, we also confirmed that astrocytes in the cardiovascular brain regions were activated by stress, and this activation was blocked by arundic acid pre-treatment. Next, we conducted blood pressure measurements on unanesthetized, unrestrained rats. Air-jet stress elevated blood pressure, which remained high for a significant period during the post-stress phase. However, pre-treatment with arundic acid, which inhibited astrocytic activation, suppressed stress-induced blood pressure elevation both during and after stress. In contrast, arundic acid had no significant impact on heart rate. These findings suggest that both neurons and astrocytes play integral roles in stress-induced blood pressure elevation and its persistence after stress, offering new insights into the pathophysiological mechanisms underlying hypertension.
  • Shin Kitamura, Kotaro Takeda, Shintaro Uehara, Taiki Yoshida, Hirofumi Ota, Shigeo Tanabe, Kazuya Takeda, Soichiro Koyama, Hiroaki Sakurai, Yoshikiyo Kanada
    Frontiers in Medicine 11 1239916 2024年3月13日  査読有り責任著者
    Introduction Qualitative information in the form of written reflection reports is vital for evaluating students’ progress in education. As a pilot study, we used text mining, which analyzes qualitative information with quantitative features, to investigate how rehabilitation students’ goals change during their first year at university. Methods We recruited 109 first-year students (66 physical therapy and 43 occupational therapy students) enrolled in a university rehabilitation course. These students completed an open-ended questionnaire about their learning goals at the time of admission and at 6 and 12 months after admission to the university. Text mining was used to objectively interpret the descriptive text data from all three-time points to extract frequently occurring nouns at once. Then, hierarchical cluster analysis was performed to generate clusters. The number of students who mentioned at least one noun in each cluster was counted and the percentages of students in each cluster were compared for the three periods using Cochran’s Q test. Results The 31 nouns that appeared 10 or more times in the 427 sentences were classified into three clusters: “Socializing,” “Practical Training,” and “Classroom Learning.” The percentage of students in all three clusters showed significant differences across the time periods (p < 0.001 for “Socializing”; p < 0.01 for “Practical Training” and “Classroom Learning”). Conclusion These findings suggest that the students’ learning goals changed during their first year of education. This objective analytical method will enable researchers to examine transitional trends in students’ reflections and capture their psychological changes, making it a useful tool in educational research.
  • Hiroshi Onimaru, Isato Fukushi, Keiko Ikeda, Itaru Yazawa, Kotaro Takeda, Yasumasa Okada, Masahiko Izumizaki
    Neuroscience 528 89-101 2023年9月15日  査読有り
  • Isato Fukushi, Keiko Ikeda, Kotaro Takeda, Masashi Yoshizawa, Yosuke Kono, Yohei Hasebe, Mieczyslaw Pokorski, Yasumasa Okada
    Frontiers in Neural Circuits 17 1006424 2023年3月22日  査読有り
    Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic respiratory pathologies, which may be conducive to a sudden unexpected death in epilepsy (SUDEP). Recent studies provide evidence that brain microglia are involved with both respiratory and ictal processes. Here, we investigated the hypothesis that microglia could interact with hypoxia-induced seizures. To this end, we recorded electroencephalogram (EEG) and acute ventilatory responses to hypoxia (5% O2 in N2) in conscious, spontaneously breathing adult mice. We compared control vehicle pre-treated animals with those pre-treated with minocycline, an inhibitory modulator of microglial activation. First, we histologically confirmed that hypoxia activates microglia and that pre-treatment with minocycline blocks hypoxia-induced microglial activation. Then, we analyzed the effects of minocycline pre-treatment on ventilatory responses to hypoxia by plethysmography. Minocycline alone failed to affect respiratory variables in room air or the initial respiratory augmentation in hypoxia. The comparative results showed that hypoxia caused seizures, which were accompanied by the late phase ventilatory suppression in all but one minocycline pre-treated mouse. Compared to the vehicle pre-treated, the minocycline pre-treated mice showed a delayed occurrence of seizures. Further, minocycline pre-treated mice tended to resist post-ictal respiratory arrest. These results suggest that microglia are conducive to seizure activity in severe hypoxia. Thus, inhibition of microglial activation may help suppress or prevent hypoxia-induced ictal episodes.
  • Atsumi Takeo, Hideto Okazaki, Kotaro Takeda, Yuki Nakagawa, Shigeru Sonoda
    Technology and Health Care 31(2) 517-525 2023年3月15日  査読有り
    BACKGROUND: The number of wheelchair users is increasing as the population ages. However, there is still lack of tools to objectively assess posture during wheelchair propulsion. OBJECTIVE: The purpose of this study was to develop a system to measure trunk and pelvis ROM (range of motion) while driving a wheelchair and to assess the reproducibility of the measured posture changes and cyclic fluctuations during propulsion. METHODS: Motion recorders were attached to the sternum and pelvis of fifteen healthy adults, and a pressure sensor was attached to the right heel. Subjects drove a standard wheelchair using their right leg and trunk and pelvis ROM was measured in two separate sessions. To detect the trend of postural changes during propulsion, a trend curve was computed from the measured ROM using a low-pass filter and then subtracted from the measured ROM waveforms. The resulting curves were normalized and averaged, and the maximum, minimum, and amplitude of the cyclic variation during propulsion were assessed for reproducibility. RESULTS: Intraclass correlation coefficients of the maximum, minimum, and amplitude ranged from 0.65 to 0.84. CONCLUSIONS: The proposed method can estimate the posture change and the periodic fluctuation during wheelchair propulsion with high reproducibility.
  • Isato Fukushi, Shigefumi Yokota, Kotaro Takeda, Jiro Terada, Akira Umeda, Masashi Yoshizawa, Yosuke Kono, Yohei Hasebe, Hiroshi Onimaru, Mieczyslaw Pokorski, Yasumasa Okada
    Brain Research 1795 148061 2022年11月15日  査読有り
  • Masashi Yoshizawa, Isato Fukushi, Kotaro Takeda, Yosuke Kono, Yohei Hasebe, Keiichi Koizumi, Keiko Ikeda, Mieczyslaw Pokorski, Takako Toda, Yasumasa Okada
    Journal of Physiological Sciences 72(1) 26 2022年10月13日  査読有り
    Abstract Microglia modulate cardiorespiratory activities during chronic hypoxia. It has not been clarified whether microglia are involved in the cardiorespiratory responses to acute hypoxia. Here we investigated this issue by comparing cardiorespiratory responses to two levels of acute hypoxia (13% O2 for 4 min and 7% O2 for 5 min) in conscious unrestrained rats before and after systemic injection of minocycline (MINO), an inhibitor of microglia activation. MINO increased blood pressure but not lung ventilation in the control normoxic condition. Acute hypoxia stimulated cardiorespiratory responses in MINO-untreated rats. MINO failed to significantly affect the magnitude of hypoxia-induced blood pressure elevation. In contrast, MINO tended to suppress the ventilatory responses to hypoxia. We conclude that microglia differentially affect cardiorespiratory regulation depending on the level of blood oxygenation. Microglia suppressively contribute to blood pressure regulation in normoxia but help maintain ventilatory augmentation in hypoxia, which underscores the dichotomy of central regulatory pathways for both systems.
  • Hidetada Matsuoka, Mieczyslaw Pokorski, Kotaro Takeda, Yasumasa Okada, Keita Harada, Masumi Inoue
    Journal of University of Occupational and Environmental Health (J UOEH) 44(3) 249-255 2022年9月1日  査読有り
  • 長岡佑馬, 北俣康介, 矢代大祐, 弓場井一裕, 駒田諭, 武田湖太郎
    電気学会論文誌D(産業応用部門誌) 142(3) 232-240 2022年3月1日  査読有り最終著者
  • Itaru Yazawa, Shuntaro Okazaki, Shigefumi Yokota, Kotaro Takeda, Isato Fukushi, Masashi Yoshizawa, Hiroshi Onimaru, Yasumasa Okada
    Neuroscience Letters 771 136421 2022年2月6日  査読有り
    Astrocytes are thought to play a crucial role in providing structure to the spinal cord and maintaining efficient synaptic function and metabolism because their fine processes envelop the synapses of neurons and form many neuronal networks within the central nervous system (CNS). To investigate whether putative astrocytes and putative neurons distributed on the ventral horn play a role in the modulation of lumbar locomotor central pattern generator (CPG) networks, we used extracellular recording and optical imaging techniques and recorded the neural output from the left L5 ventral root and the calcium activity of putative astrocytes and neurons in the L5 ventral horn at the same time when activating an isolated L1-L5 spinal cord preparation from rats aged 0-2 days. Optical measurements detected cells that showed a fluorescence intensity change under all experimental conditions, namely, (1) 5-HT + NMDA, (2) TTX, and (3) TTX + Low K+. These cells were semiautomatically identified using an in-house MATLAB-based program, as putative astrocytes and neurons according to the cell classification, i.e., increased or decreased fluorescence intensity change (ΔF/F0), and subjective judgment based on their soma size. Coherence and its phase were calculated according to the calcium activity of the putative astrocytes and putative neurons, and neural output was calculated during fictive locomotion with in-house MATLAB-based programs. We found that the number of putative astrocytes activated by applying low K+ tends not to differ from that activated by applying the protease-activated receptor 1 (PAR1) selective agonist TFLLR-NH2 (TFLLR). Moreover, the calcium activity of several putative astrocytes and neurons synchronized with locomotor-like activity at a frequency range below 0.5 Hz and the time lag between peaks of cellular calcium activity and locomotor-like activity ranged from -1000 to + 1000 ms. These findings presumably indicates that these putative astrocytes and neurons in the left L5 ventral horn require -1000 to + 1000 ms to communicate with lumbar CPG networks and maintain efficient synaptic function and metabolism in activated lumbar CPG networks. This finding suggests the possibility that putative astrocytic and neuronal cells in the L5 ventral horn contribute to generating the rhythms and patterns of locomotor-like activity by activated CPG networks in the first to fifth lumbar spinal cord.
  • Daisuke Ishii, Kiyoshige Ishibashi, Kotaro Takeda, Hiroshi Yuine, Satoshi Yamamoto, Yuki Kaku, Arito Yozu, Yutaka Kohno
    Frontiers in Human Neuroscience 15 761186 2021年11月1日  査読有り
    Neural plasticity compensates for the loss of motor function after stroke. However, whether neural plasticity occurs in the somatosensory pathways after stroke is unknown. We investigated the left–right somatosensory interaction in two hemorrhagic patients using a paired somatosensory evoked potentials (p-SEPs) recorded at CP3 and CP4, which was defined as an amplitude difference between the SEPs of paired median nerve stimulations to both sides and that of single stimulation to the affected side. Patient 1 (61-year-old, left thalamic hemorrhage) has a moderate motor impairment, severe sensory deficit, and complained of pain in the affected right upper limb. Patient 2 (72-year-old, right thalamic hemorrhage) had slight motor and sensory impairments with no complaints of pain. Single SEPs (s-SEPs) were obtained by stimulation of the right and left median nerves, respectively. For paired stimulations, 1 ms after the first stimulation to the non-affected side, followed by a second stimulation to the affected side. In patient 1, a s-SEP with stimulation to the non-affected side and a p-SEP were observed in CP4. However, a s-SEP was not observed in either hemisphere with stimulation to the affected side. On the other hand, in patient 2, a s-SEP in CP3 with stimulation to the non-affected side and in CP4 with stimulation to the affected side were observed; however, a p-SEP was not observed. In addition, to investigate the mechanism by which ipsilateral median nerve stimulation enhances contralateral p-SEP in patient 1, we compared the SEP averaged over the first 250 epochs with the SEP averaged over the second 250 epochs (total number of epochs recorded: 500). The results showed that in the patient 1, when the bilateral median nerve was stimulated continuously, the habituation did not occur and the response was larger than that of the s-SEP with unilateral median nerve stimulation. In the current case report, the damage to the thalamus may cause neuroplasticity in terms of the left–right interaction (e.g., left and right S1). The somatosensory input from the affected side may interfere with the habituation of the contralateral somatosensory system and conversely increase the response.
  • Kotaro Takeda, Toru Yamada, Akihiro Ishikawa, Yoshihiro Inoue, Yohei Otaka, Rieko Osu
    Journal of Rehabilitation Neurosciences 21(1) 17-22 2021年10月29日  招待有り筆頭著者
    Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging method for recording cerebral hemodynamics. Tolerance of motion is considered an advantage of fNIRS when compared with other imaging techniques. However, fNIRS signals are often contaminated by scalp blood flow (SBF) signals due to motion of the subject. In the present study, we recorded changes in the concentrations of oxygenated and deoxygenated hemoglobin by multidistance source-detector probes during whole body tilting with the head and trunk fixed, and demonstrated that the change in body direction against gravity causes SBF signal contamination. Non-negligible parallel changes in oxygenated and deoxygenated hemoglobin during trunk tilt were observed in long-distance channels (conventional 30 mm), as well as those in short-distance channels (15 mm) reflecting SBF changes. Because the tilt angle-dependent changes in the long channels were correlated highly with those in the short channels, the fluctuation caused by the trunk tilt could be considered SBF signal contamination. The contamination was successfully removed by a multidistance method and by a hemodynamic modality separation method.
  • Isato Fukushi, Kotaro Takeda, Mieczyslaw Pokorski, Yosuke Kono, Masashi Yoshizawa, Yohei Hasebe, Akito Nakao, Yasuo Mori, Hiroshi Onimaru, Yasumasa Okada
    Frontiers in Physiology 12 757731 2021年10月8日  査読有り
    Acute hypoxia increases ventilation. After cessation of hypoxia loading, ventilation decreases but remains above the pre-exposure baseline level for a time. However, the mechanism of this post-hypoxic persistent respiratory augmentation (PHRA), which is a short-term potentiation of breathing, has not been elucidated. We aimed to test the hypothesis that astrocytes are involved in PHRA. To this end, we investigated hypoxic ventilatory responses by whole-body plethysmography in unanesthetized adult mice. The animals breathed room air, hypoxic gas mixture (7% O2, 93% N2) for 2min, and again room air for 10min before and after i.p. administration of low (100mg/kg) and high (300mg/kg) doses of arundic acid (AA), an astrocyte inhibitor. AA suppressed PHRA, with the high dose decreasing ventilation below the pre-hypoxic level. Further, we investigated the role of the astrocytic TRPA1 channel, a putative ventilatory hypoxia sensor, in PHRA using astrocyte-specific Trpa1 knockout (asTrpa1−/−) and floxed Trpa1 (Trpa1f/f) mice. In both Trpa1f/f and asTrpa1−/− mice, PHRA was noticeable, indicating that the astrocyte TRPA1 channel was not directly involved in PHRA. Taken together, these results indicate that astrocytes mediate the PHRA by mechanisms other than TRPA1 channels that are engaged in hypoxia sensing.
  • Rikitaro Sako, Satoshi Yamamoto, Kotaro Takeda, Masahiro Wakatabi, Minoru Daira, Tetsuichi Hondera, Takayuki Oota, Ami Fujii, Yoshitaka Okamoto, Satoshi Sugiyama, Yoshifumi Ozasa
    Interdisciplinary Neurosurgery 25 101126-101126 2021年9月  査読有り責任著者
    We report a patient with bilateral medial medullary infarctions, which is a rare type of ischemic stroke. A 64-year-old Japanese man demonstrated bilateral hemiplegia, sensory dysfunction, ataxia, and dysphagia. The left-dominant but bilateral medial medulla lesions indicated hyperintensity on the T2-weighted image at 1.5 months after the onset. On the time-of-flight magnetic resonance angiography (TOF-MRA) performed at the onset, the right vertebral artery was partially narrowed and the left vertebral artery was not confirmed. Basi-parallel anatomical scanning-magnetic resonance imaging (BPAS-MRI) revealed that both sides of the vertebral arteries had a uniform diameter, which means there was no arterial hypoplasia nor arterial dissection. These results suggest that atherosclerosis in the bilateral vertebral artery caused occlusion of the perforator artery, resulting in the bilateral medial medullary infarctions. The combined use of TOF-MRA and BPAS-MRI could help improve the accuracy of diagnosis and be helpful for post-stroke management.
  • Akira Umeda, Masahiro Ishizaka, Akane Ikeda, Kazuya Miyagawa, Atsumi Mochida, Hiroshi Takeda, Kotaro Takeda, Isato Fukushi, Yasumasa Okada, David Gozal
    Sensors - Basel 21(16) 5636 2021年8月21日  査読有り
    In the field of respiratory clinical practice, the importance of measuring carbon dioxide (CO2) concentrations cannot be overemphasized. Within the body, assessment of the arterial partial pressure of CO2 (PaCO2) has been the gold standard for many decades. Non-invasive assessments are usually predicated on the measurement of CO2 concentrations in the air, usually using an infrared analyzer, and these data are clearly important regarding climate changes as well as regulations of air quality in buildings to ascertain adequate ventilation. Measurements of CO2 production with oxygen consumption yield important indices such as the respiratory quotient and estimates of energy expenditure, which may be used for further investigation in the various fields of metabolism, obesity, sleep disorders, and lifestyle-related issues. Measures of PaCO2 are nowadays performed using the Severinghaus electrode in arterial blood or in arterialized capillary blood, while the same electrode system has been modified to enable relatively accurate non-invasive monitoring of the transcutaneous partial pressure of CO2 (PtcCO2). PtcCO2 monitoring during sleep can be helpful for evaluating sleep apnea syndrome, particularly in children. End-tidal PCO2 is inferior to PtcCO2 as far as accuracy, but it provides breath-by-breath estimates of respiratory gas exchange, while PtcCO2 reflects temporal trends in alveolar ventilation. The frequency of monitoring end-tidal PCO2 has markedly increased in light of its multiple applications (e.g., verify endotracheal intubation, anesthesia or mechanical ventilation, exercise testing, respiratory patterning during sleep, etc.).
  • Daisuke Ishii, Kiyoshige Ishibashi, Hiroshi Yuine, Kotaro Takeda, Satoshi Yamamoto, Yuki Kaku, Arito Yozu, Yutaka Kohno
    Frontiers in Systems Neuroscience 15 698758 2021年8月17日  査読有り
    Hyper-adaptability, the ability to adapt to changes in the internal environment caused by neurological disorders, is necessary to recover from various disabilities, such as motor paralysis and sensory impairment. In the recovery from motor paralysis, the pre-existing neural pathway of the ipsilateral descending pathway, which is normally suppressed and preserved in the course of development, is activated to contribute to the motor control of the paretic limb. Conversely, in sensory pathways, it remains unclear whether there are compensatory pathways which are beneficial for the recovery of sensory impairment due to damaged unilateral somatosensory pathways, such as thalamic hemorrhage. Here, we investigated the interaction between the left and right somatosensory pathways in healthy humans using paired median nerve somatosensory evoked potentials (SEPs). Paired median nerve SEPs were recorded at CP3 and CP4 with a reference of Fz in the International 10–20 System. The paired median nerve stimulation with different interstimulus intervals (ISIs; 1, 2, 3, 5, 10, 20, 40, 60, and 100 ms) was performed to test the influence of the first stimulus (to the right median nerve) on the P14, P14/N20, and N20/P25 components induced by the second stimulus (left side). Results showed that the first stimulation had no effect on SEP amplitudes (P14, P14/N20, and N20/P25) evoked by the second stimulation in all ISI conditions, suggesting that there might not be a neural connectivity formed by a small number of synapses in the left–right interaction of the somatosensory pathway. Additionally, the somatosensory pathway may be less diverse in healthy participants.
  • Naoto Endo, Daisuke Ishii, Kiyoshige Ishibashi, Satoshi Yamamoto, Kotaro Takeda, Yutaka Kohno
    Journal of Back and Musculoskeletal Rehabilitation 34(4) 631-637 2021年7月13日  査読有り
    BACKGROUND: Rotator cuff muscles are structurally and functionally different from other upper-limb muscles because they are responsible for glenohumeral joint stability. Neuromuscular electrical stimulation (NMES) induces excitability changes (increase or decrease) of the corticospinal tract (CST) in the peripheral muscles, such as those of the finger. However, it remains unclear whether similar results are obtained when targeting the infraspinatus muscle, which has properties that differ from other muscles, in healthy subjects. OBJECTIVE: We investigated the immediate effects of NMES on the corticospinal excitability of the infraspinatus muscle, a rotator cuff muscle, in healthy subjects. METHODS: Thirteen healthy right-handed men (mean age: 26.77 ± 2.08 years) participated in this study. The motor evoked potentials (MEPs) and the maximum compound muscle action potential (Mmax) were recorded before NMES to the right infraspinatus and within 15 minutes after the end of the NMES. RESULTS: NMES on the infraspinatus muscle significantly increased its MEP amplitude (Pre: 0.45 mV [0.33–0.48]; Post: 0.54 mV [0.46–0.60] (median [lower quartile to higher quartile]); p= 0.005) but had no effect on Mmax (Pre: 2.95 mV [2.59–4.71]; Post: 3.35 mV [2.76–4.72]; p= 0.753). CONCLUSIONS: NMES application to the infraspinatus muscle increases CST excitability without producing immediate changes in the neuromuscular junction or muscle hypertrophy.
  • Yoshimitsu Hashizume, Shoko Kaichida, Kotaro Takeda, Jun Nishii
    ICIC Express Letters, Part B: Applications 12(12) 595-601 2021年7月  査読有り
    The variability of the minimum toe clearance (MTC) has been considered as a risk parameter for stumbling and falling, especially in elderly people. This study evaluates the hypothesis that MTC variability increases with age because the inter-joint synergy – suppressing the variability of the toe position relative to the hip position – deteriorates. We recorded the leg joint trajectories of six young and six old subjects during level walking, and the strength of joint synergies at the instant of MTC was evaluated based on uncontrolled manifold analysis. The results indicated that the variance of toe height from the ground was larger in the older group, although the joint synergies observed in both age groups exhibited no statistical difference. This fact suggested that the increase in the variability of the MTC might not result from the functional decline of inter-joint synergy but from the instability of the hip height.
  • Hiroshi Onimaru, Itaru Yazawa, Kotaro Takeda, Isato Fukushi, Yasumasa Okada
    Frontiers in Physiology 12 645904 2021年3月25日  査読有り
    It is supposed that the nucleus of the solitary tract (NTS) in the dorsal medulla includes gas sensor cells responsive to hypercapnia or hypoxia in the central nervous system. In the present study, we analyzed cellular responses to hypercapnia and hypoxia in the NTS region of newborn rat <italic>in vitro</italic> preparation. The brainstem and spinal cord were isolated from newborn rat (P0-P4) and were transversely cut at the level of the rostral area postrema. To detect cellular responses, calcium indicator Oregon Green was pressure-injected into the NTS just beneath the cut surface of either the caudal or rostral block of the medulla, and the preparation was superfused with artificial cerebrospinal fluid (25–26°C). We examined cellular responses initially to hypercapnic stimulation (to 8% CO2 from 2% CO2) and then to hypoxic stimulation (to 0% O2 from 95% O2 at 5% CO2). We tested these responses in standard solution and in two different synapse blockade solutions: (1) cocktail blockers solution including bicuculline, strychnine, NBQX and MK-801 or (2) TTX solution. At the end of the experiments, the superfusate potassium concentration was lowered to 0.2 from 3 mM to classify recorded cells into neurons and astrocytes. Excitation of cells was detected as changes of fluorescence intensity with a confocal calcium imaging system. In the synaptic blockade solutions (cocktail or TTX solution), 7.6 and 8% of the NTS cells responded to hypercapnic and hypoxic stimulation, respectively, and approximately 2% of them responded to both stimulations. Some of these cells responded to low K+, and they were classified into astrocytes comprising 43% hypercapnia-sensitive cells, 56% hypoxia-sensitive cells and 54% of both stimulation-sensitive cells. Of note, 49% of the putative astrocytes identified by low K+ stimulation were sensitive to hypercapnia, hypoxia or both. In the presence of a glia preferential blocker, 5 mM fluoroacetate (plus 0.5 μM TTX), the percentage of hypoxia-sensitive cells was significantly reduced compared to those of all other conditions. This is the first study to reveal that the NTS includes hypercapnia and hypoxia dual-sensitive cells. These results suggest that astrocytes in the NTS region could act as a central gas sensor.
  • Izumi Nagashima, Kotaro Takeda, Yusuke Harada, Hideki Mochizuki, Nobuaki Shimoda
    Frontiers in Human Neuroscience 15 615584 2021年3月10日  査読有り責任著者
    Mental imagery of movement is a potentially valuable rehabilitation task, but its therapeutic efficacy may depend on the specific cognitive strategy employed. Individuals use two main strategies to perform the hand mental rotation task (HMRT), which involves determining whether a visual image depicts a left or right hand. One is the motor imagery (MI) strategy, which involves mentally simulating one’s own hand movements. In this case, task performance as measured by response time (RT) is subject to a medial–lateral effect wherein the RT is reduced when the fingertips are directed medially, presumably as the actual motion would be easier. The other strategy is to employ visual imagery (VI), which involves mentally rotating the picture and is not subject to this medial–lateral effect. The rehabilitative benefits of the HMRT are thought to depend on the MI strategy (mental practice), so it is essential to examine the effects of individual factors such as age, image perspective (e.g., palm or back of the hand), and innate ability (as indicated by baseline RT) on the strategy adopted. When presented with pictures of the palm, all subjects in the current study used the MI strategy, regardless of age and ability. In contrast, when subjects were presented with pictures of the back of the hand, the VI strategy predominated among the young age group regardless of performance, while the strategy used by middle-age and elderly groups depended on performance ability. In the middle-age and elderly groups, the VI approach predominated in those with high performance skill, whereas the MI strategy predominated among those with low performance skill. Thus, higher-skill middle-aged and elderly individuals may not necessarily form a motion image during the HMRT, potentially limiting rehabilitation efficacy.
  • Akira Umeda, Kazuya Miyagawa, Atsumi Mochida, Hiroshi Takeda, Kotaro Takeda, Yasumasa Okada, David Gozal
    Frontiers in Physiology 11 583735 2020年10月22日  査読有り
    Obstructive sleep apnea (OSA) patients are at risk for increased blood pressure and carotid intima-media thickness (IMT), with pulmonary hypertension and right-sided heart failure potentially developing as well. Chronic intermittent hypoxia (IH) has been used as an OSA model in animals, but its effects on vascular beds have not been evaluated using objective unbiased tools. Previously published and current experimental data in mice exposed to IH were evaluated for IMT in aorta and pulmonary artery (PA) after IH with or without normoxic recovery using software for meta-analysis, Review Manager 5. Because IMT data reports on PA were extremely scarce, atherosclerotic area percentage from lumen data was also evaluated. IH significantly increased IMT parameters in both aorta and PA as illustrated by Forest plots (P < 0.01), which also confirmed that IMT values after normoxic recovery were within the normal range in both vascular beds. One-sided scarce lower areas in Funnel Plots were seen for both aorta and PA indicating the likelihood of significant publication bias. Forest and Funnel plots, which provide unbiased assessments of published and current data, suggest that IH exposures may induce IMT thickening that may be reversed by normoxic recovery in both aorta and PA. In light of the potential likelihood of publication bias, future studies are needed to confirm or refute the findings. In conclusion, OSA may induce IMT thickening (e.g., aorta and/or PA), but the treatment (e.g., nasal continuous positive airway pressure) will likely lead to improvements in such findings.
  • Makoto Uchiyama, Akito Nakao, Yuki Kurita, Isato Fukushi, Kotaro Takeda, Tomohiro Numata, Ha Nam Tran, Seishiro Sawamura, Maximilian Ebert, Tatsuki Kurokawa, Reiko Sakaguchi, Alexander J. Stokes, Nobuaki Takahashi, Yasumasa Okada, Yasuo Mori
    Current Biology 30(17) 3378-3396 2020年9月  査読有り
    Hypoxia sensors are essential for regulating local oxygen (O2) homeostasis within the body. This is especially pertinent within the CNS, which is particularly vulnerable to O2 deprivation due to high energetic demand. Here, we reveal hypoxia-monitoring function exerted by astrocytes through an O2-regulated protein trafficking mechanism within the CNS. Strikingly, cultured mouse astrocytes isolated from the parafacial respiratory group (pFRG) and retrotrapezoid nucleus (RTN) region are capable of rapidly responding to moderate hypoxia via the sensor cation channel transient receptor potential (TRP) A1 but, unlike multimodal sensory neurons, are inert to hyperoxia and other TRPA1 activators (carbon dioxide, electrophiles, and oxidants) in normoxia. Mechanistically, O2 suppresses TRPA1 channel activity by protein internalization via O2-dependent proline hydroxylation and subsequent ubiquitination by an E3 ubiquitin ligase, NEDD4-1 (neural precursor cell-expressed developmentally down-regulated protein 4). Hypoxia inhibits this process and instantly accumulates TRPA1 proteins at the plasma membrane, inducing TRPA1-mediated Ca2+ influx that triggers ATP release from pFRG/RTN astrocytes, potentiating respiratory center activity. Furthermore, astrocyte-specific Trpa1 disruption in a mouse brainstem-spinal cord preparation impedes the amplitude augmentation of the central autonomic respiratory output during hypoxia. Thus, reversible coupling of the TRPA1 channels with O2-dependent protein translocation allows astrocytes to act as acute hypoxia sensors in the medullary respiratory center.
  • Makoto Watanabe, Kotaro Takeda, Shinichiro Maeshima, Takaji Suzuki, Shigeru Sonoda
    Journal of Stroke and Cerebrovascular Diseases 29(9) 105063-105063 2020年9月  査読有り
    Background and objective After cerebral hemorrhage, cognitive functions and activities of daily living (ADL) are affected by various factors, including hematoma volume and patient age. In the present study, we investigated the effect of age and hematoma volume on cognitive functions and on ADL. Methods The sample comprised 274 patients (183 men and 91 women; mean age 58.2 ± 12.5 years) with putaminal hemorrhage who were hospitalized in a convalescent rehabilitation ward. Hematoma volume was estimated from computed tomography imaging at stroke onset. Cognitive functions were evaluated using Raven's Colored Progressive Matrices test (RCPM) and the Mini-Mental State Examination (MMSE) at hospital admission, while ADL score was assessed at discharge using the Functional Independence Measure motor subscale (FIM-M). In the present study, we classified the patients into six groups according to whether they were non-elderly or elderly (cutoff age, 60 years) and whether their hematoma was small, medium, or large (cutoff volumes, 20 and 40 mL, respectively). Subsequently, the scores on the RCPM, MMSE, and FIM-M were compared among the groups. Results In both age groups, patients with a larger hematoma volume had lower RCPM and MMSE scores. Patients <60 years old exhibited different trends in their RCPM and MMSE scores, such that the RCPM score showed a step-wise decrease according to hematoma volume, while a difference in the MMSE score was only observed at the 20 mL boundary. Most of the younger patients (<60 years of age) attained high FIM-M scores at discharge, as long as their hematoma volume was either medium or small (<40 mL). This age group had higher RCPM scores on admission, which may have contributed to their higher FIM-M scores on discharge. Conclusions In the present study, we demonstrated that advancing age increases the effect of hematoma volume on RCPM and MMSE scores and identified differences in the effects observed on these two scores. Thus, it may be important to use the RCPM alongside the MMSE for patient assessment.
  • Yosuke Kono, Shigefumi Yokota, Isato Fukushi, Yosuke Arima, Hiroshi Onimaru, Shuntaro Okazaki, Kotaro Takeda, Itaru Yazawa, Masashi Yoshizawa, Yohei Hasebe, Keiichi Koizumi, Mieczyslaw Pokorski, Takako Toda, Kanji Sugita, Yasumasa Okada
    Scientific Reports 10(1) 13325 2020年8月  査読有り
    Psychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifier of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.
  • Isato Fukushi, Kotaro Takeda, Makoto Uchiyama, Yuki Kurita, Mieczyslaw Pokorski, Shigefumi Yokota, Shuntaro Okazaki, Jouji Horiuchi, Yasuo Mori, Yasumasa Okada
    Journal of Comparative Neurology 528(8) 1257-1264 2020年6月  査読有り
    Seizures are induced when subjects are exposed to severe hypoxia. It is followed by ventilatory fall-off and eventual respiratory arrest, which may underlie the pathophysiology of death in patients with epilepsy and severe respiratory disorders. However, the mechanisms of hypoxia-induced seizures have not been fully understood. Because astrocytes are involved in various neurological disorders, we aimed to investigate whether astrocytes are operational in seizure generation and respiratory arrest in a severe hypoxic condition. We examined the effects of astrocytic activation blockade on responses of EEG and ventilation to severe hypoxia. Adult mice were divided into two groups; in one group (n = 24) only vehicle was injected, and in the other group (n = 24) arundic acid, an inhibitory modulator of astrocytic activation, was administered before initiation of recording. After recording EEG and ventilation by whole body plethysmography in room air, the gas in the recording chamber was switched to 5% oxygen (nitrogen balanced) until a seizure and ventilatory depression occurred, followed by prompt switch back to room air. Severe hypoxia initially increased ventilation, followed by a seizure and ventilatory suppression in all mice examined. Fourteen mice without arundic acid showed respiratory arrest during loading of hypoxia. However, 22 mice pretreated with arundic acid did not suffer from respiratory arrest. Time from the onset of hypoxia to the occurrence of seizures was significantly longer in the group with arundic acid than that in the group without arundic acid. We suggest that blockade of astrocytic activation delays the occurrence of seizures and prevents respiratory arrest.
  • Hitoshi Ohnishi, Kotaro Takeda, Makoto Watanabe, Shinichiro Maeshima, Shigeru Sonoda
    Journal of Stroke and Cerebrovascular Diseases 29(6) 104812-104812 2020年6月  査読有り責任著者
    Purpose: Computed tomography (CT) is used for initial assessment of patients with suspected stroke. Motor outcome prediction using the initial CT image is important for clinical rehabilitation. However, there is inconsistency in the results reported by the few publications on hematoma volume and motor outcomes in patients with putaminal hemorrhage. To clarify the direction of hematoma and relationship between the hematoma volume and motor outcomes in patients with putaminal hemorrhage using an initial CT image, we evaluated the volume of direction of hematoma in 170 patients in the subacute phase after putaminal hemorrhage using CT at stroke onset. Methods: The patients were divided into 5 groups according to the direction of the hematoma. For each group, Spearman's correlation coefficients were calculated to investigate the relationship between hematoma volume and motor outcomes. Motor outcomes were assessed using the motor items of Stroke Impairment Assessment Set, which are impairment indexes for the distal and proximal functions of the upper and lower extremities after stroke. Results: Hematoma volume was significantly correlated with all the motor items in the group whose hematoma extended to the posterior limb of the internal capsule alone (Bonferroni corrected P <.05). On the other hand, significant correlations between hematoma volume and motor outcomes could not be found in almost all the other groups. Conclusions: Motor outcome after putaminal hemorrhage can be predicted by evaluating the progression of hematoma to the corticospinal tract and its volume using CT images at stroke onset.
  • Noriko Numata, Yoshiyuki Hirano, Chihiro Sutoh, Daisuke Matsuzawa, Kotaro Takeda, Rikukage Setsu, Eiji Shimizu, Michiko Nakazato
    Eating and Weight Disorders 25(1) 59-67 2020年2月  査読有り
    PURPOSE: This study sought to identify the prefrontal cortex hemodynamic response that is dependent on cognitive performance in patients with bulimic disorders (BD), and investigate its association with personality characteristics. METHODS: Nineteen female patients with BD and 23 healthy women were recruited. Their personality characteristics related to eating disorders were examined using a self-reporting questionnaire, namely the eating disorder inventory-2 (EDI-2). Cerebral blood flow response in the prefrontal cortex during the digit span backward task (DSBT) was measured using near-infrared spectroscopy (NIRS). Change in oxygenated hemoglobin concentration (ΔoxyHb), obtained using NIRS, were used as an index of brain activity. Further, the relationship between prefrontal cortical activity and personality characteristics was investigated in patients with BD. RESULTS: The cognitive performance of patients with BD was significantly lower in the DSBT compared with healthy subjects. There was no difference between the groups in ΔoxyHb during the task. Task scores of patients with BD correlated with asceticism and perfectionism. Moreover, the asceticism score was negatively correlated with ΔoxyHb of the bilateral prefrontal cortex in patients with BD. CONCLUSION: The results suggest that cognitive performance and brain activity induced during DSBT might be affected by asceticism in BD patients. LEVEL OF EVIDENCE: III, case-control study.
  • Akira Umeda, Kazuya Miyagawa, Atsumi Mochida, Hiroshi Takeda, Kotaro Takeda, Yasumasa Okada, David Gozal
    Respiratory Physiology & Neurobiology 273 103332 2020年2月  査読有り
    BACKGROUND AND OBJECTIVE: Body weight of patients with obstructive sleep apnea after initiation of nasal continuous positive airway pressure appears to increase. We hypothesized that intermittent hypoxia (IH) will decrease energy expenditure (EE), and that normoxic recovery will lead to body weight gains. METHODS: C57BL/6 J male mice were exposed to either 12 h/day of mild IH (alternating FIO2-10-11% and 21%; 640 s cycle), or severe IH (FIO2-6-7%-21%; 180 s cycle) or sham IH daily for 4 or 8 weeks. After exposures, EE was evaluated while mice were kept under normoxia for 5 weeks and organ histology was evaluated. RESULTS: EE was not decreased by IH. However, visceral white adipocyte size after normoxic recovery was significantly increased in severe IH in an intensity-dependent manner. CONCLUSION: Our hypothesis that IH would decrease EE was not corroborated. However, IH and normoxic recovery seem to promote severity-dependent enlargement of visceral adipocytes, likely reflecting altered energy preservation mechanisms induced by IH.
  • Hiroyuki Miyasaka, Kotaro Takeda, Hitoshi Ohnishi, Abbas Orand, Shigeru Sonoda
    Applied Sciences - Basel 9(18) 3925 2019年9月  査読有り責任著者
    Sensory disorder is a factor preventing recovery from motor paralysis after stroke. Although several robot-assisted exercises for the hemiplegic upper limb of stroke patients have been proposed, few studies have examined improvement in function in stroke patients with sensory disorder using robot-assisted training. In this study, the efficacies of robot training for the hemiplegic upper limb of three stroke patients with complete sensory loss were compared with those of 19 patients without complete sensory loss. Robot training to assist reach motion was performed in 10 sessions over a 2-week period for 5 days per week at 1 h per day. Before and after the training, the total Fugl-Meyer Assessment score excluding coordination and tendon reflex (FMA-total) and the FMA shoulder and elbow score excluding tendon reflex (FMA-S/E) were evaluated. Reach and path errors (RE and PE) during the reach motion were also evaluated by the arm-training robot. In most cases, both the FMA-total and the FMA-S/E scores improved. Cases with complete sensory loss showed worse RE and PE scores. Our results suggest that motor paralysis is improved by robot training. However, improvement may be varied according to the presence or absence of somatic sensory feedback.
  • Izumi Nagashima, Kotaro Takeda, Nobuaki Shimoda, Yusuke Harada, Hideki Mochizuki
    Frontiers in Human Neuroscience 13 252 2019年7月19日  査読有り責任著者
    A hand mental rotation task (HMRT) is a task wherein a person judges whether an image of a rotated hand is of the right or left hand. Two performance strategies are expected to come into play when performing these tasks: a visual imagery (VI) strategy, in which an image is mentally rotated, and a motor imagery (MI) strategy, in which the movement of a person’s own hand is simulated. Although elderly people generally take some time to perform these tasks, ability differs greatly between individuals. The present study hypothesizes that there is a relationship between differences in task performance strategy and performance ability, and it compares performance strategy among elderly people divided into groups with a short mental rotation time and a long mental rotation time. In response to images of the palm, both groups displayed a medial-lateral effect in which responses were faster for images where the third finger was rotated toward the midline of the body than images rotated in the opposite direction, and we inferred that an MI strategy was primarily employed. Meanwhile, in response to images of the back of the hand, a medial-lateral effect was also observed in the group with a long mental rotation time and not in the group with the shortest mental rotation time (VI strategy). These results suggest that different strategies for performing HMRT task are used by elderly people with a short mental rotation time and those with a long mental rotation time.
  • Hideki Mochizuki, Kotaro Takeda, Yutaka Sato, Izumi Nagashima, Yusuke Harada, Nobuaki Shimoda
    PloS One 14(7) e0220414 2019年7月  査読有り責任著者
    This study explored gender differences in correct response rates and response times on a task involving left or right arrow selection and another involving the transformation of mental rotation of the hand. We recruited 15 healthy, right-handed men (age 24.5 ± 6.4) and 15 healthy, right-handed women (age 21.3 ± 4.9). For the tasks, we used pictures of left and right arrows and 32 hand pictures (left and right, palm and back) placed in cons (each at 45° from 0° to 315°). Hand and arrow pictures alternated and were shown at random. Participants decided as quickly as possible whether each picture was left or right. To compare the time taken for the transformation of mental rotation of the hand, we subtracted the average arrow response time from that for the left and right hand pictures for each participant. Correct response rates did not differ significantly between men and women or left and right for either arrow or hand pictures. Regardless of gender, the response time was longer for the left arrow picture than right arrow picture. The response time for the hand picture was longest for both men and women for pictures at rotation angles that were most difficult to align with participants' hands. While there was no difference between men's responses for left and right hand pictures, the responses of women were longer for left than right hand pictures and also than those of men. These findings suggest that both men and women mainly perform the hand mental rotation task with implicit motor imagery. On the other hand, the gender difference in performance might be explained by the difference in balance with other strategies, such as visual imagery, and by cognitive, neurophysiological, and morphological differences.
  • Daisuke Ishii, Kotaro Takeda, Satoshi Yamamoto, Akira Noguchi, Kiyoshige Ishibashi, Kenya Tanamachi, Arito Yozu, Yutaka Kohno
    Frontiers in Behavioral Neuroscience 13 1 2019年1月  査読有り責任著者
    The integration of multiple sensory modalities allows us to adapt to the environment of the outside world. It is widely known that visual stimuli interfere with the processing of auditory information, which is involved in the ability to pay attention. Additionally, visuospatial attention has the characteristic of laterality. It is unclear whether this laterality of visuospatial attention affects the processing of auditory stimuli. The sensorimotor gating system is a neurological process, which filters out unnecessary stimuli from environmental stimuli in the brain. Prepulse inhibition (PPI) is an operational measure of the sensorimotor gating system, which a weaker prestimulus (prepulse), such as a visual stimulus, inhibits the startle reflex elicited by a subsequent robust startling stimulus (pulse) such as a tone. Therefore, we investigated whether the visual stimulus from the left or right visual space affects the sensorimotor gating system in a "rest" task (low attentional condition) and a "selective attention" task (high attentional condition). In the selective attention task, we found that the target prepulse presented in the left and bilateral visual fields suppressed the startle reflex more than that presented in the right visual field. By contrast, there was no laterality of PPI in the no-target prepulse condition, and there was no laterality of PPI in the rest task. These results suggest that the laterality of visuospatial attention affects the sensorimotor gating system depending on the attentional condition. Moreover, the process of visual information processing may differ between the left and right brain.
  • Shiho Mizuno, Kotaro Takeda, Shinichiro Maeshima, Shigeru Sonoda
    Topics in Stroke Rehabilitation 25(6) 438-444 2018年9月  査読有り
    Objective To assess quantitatively the efficacy of oral baclofen for spasticity poststroke. Methods The participants were 29 persons poststroke with increased resistance to passive ankle dorsiflexion and ankle clonus on clinical assessment. Baclofen was administered at 20 mg/day for 1 week. The ankle joint was passively dorsiflexed at either 5°/s (slow stretch) or 90°/s (fast stretch) by a custom-built device. The ankle joint angle and resistive torque were measured during the ramp-and-hold stretch, with gastrocnemius electromyogram. The main outcome measures were the numbers of ankle clonus during hold, and the torques at 10° of ankle dorsiflexion in slow stretch (T-slow) and fast stretch (T-fast). Moreover, the velocity-dependent torque (ΔT = T-fast - T-slow) was compared between before and after oral baclofen. Results The numbers of ankle clonus, T-slow, T-fast, and ΔT for all participants did not exhibit significant differences between before and after baclofen administration. However, reduction in the number of ankle clonus of five or more was accompanied with a reduction in ΔT (4.0 ± 1.8 Nm) in three participants (the responders). Conclusion Although the responder rate was low, some participants responded to oral baclofen. Thus, a short-term trial of oral baclofen, and quantitative and electrophysiological assessments of muscle tone and ankle clonus are recommended.
  • Izumi Nagashima, Kotaro Takeda, Yutaka Sato, Hideki Mochizuki, Yusuke Harada, Nobuaki Shimoda
    Journal of Ergonomic Technology 17 60-67 2017年12月  査読有り
    Purpose: The hand mental rotation task (HMRT), in which participants judge whether a picture of a hand is of the left or right hand, is thought to induce a participant’s motor imagery. This application of this task in rehabilitation has begun. However, the task performance strategy used on presentation with a picture of the back of the hand and the palm in elderly individuals has not been sufficiently elucidated. In this study, we examined the performance strategy of the HMRT in response to pictures of the back of the hand and the palm among elderly individuals. Participants and methods: A total of 75 right-handed individuals aged 65 years or older (38 men and 37 women, 74.9 ± 5.8 years old) were included in this study. From the position in which the middle finger was located at 0 degrees vertically, the pictures of the left/right hand and the back of the hand/the palm were turned in increments of 60 degrees in presentation, and the response time (RT) and correctness of responses were recorded. The RT to the left and right arrows was also measured, and the ΔRT was derived by subtracting the RT to the arrows from the RT to the hand pictures. A repeated measures ANOVA was conducted on the ΔRT with three factors: whether the hand was left or right, whether the back of the hand or the palm of the hand was pictured, and the presented angle. Conclusions: We suggest that the motor imagery strategy was combined with the visual imagery strategy when pictures of the back of the hand were presented and that the motor imagery strategy was used when pictures of the palm were presented. These results indicate that frequent use of pictures of the palm may be effective when the HMRT is used for rehabilitation of elderly individuals.
  • Shiho Mizuno, Shigeru Sonoda, Kotaro Takeda, Shinichiro Maeshima
    Topics in Stroke Rehabilitation 24(8) 567-572 2017年12月  査読有り
    Background Individuals exhibiting hemiplegia and increased ankle plantar flexors muscle tone following stroke are frequently prescribed an ankle-foot orthosis (AFO) to regain functional ambulation. The effect of muscle tone on ankle kinetics when walking with an AFO remains unknown. Objectives To investigate the effect of plantar flexion (PF) muscle tone on ankle plantar flexion torque during walking with an ankle-foot orthosis Methods The study included 80 participants with first-ever stroke whose manual muscle testing (MMT) of ankle DF 0-4, and 10 healthy subjects. Participants were instructed to walk on a treadmill, at a comfortable speed, wearing an instrumented AFO. Minimum PF torque during the last half of swing was extracted as an outcome measure. Resistive PF torques during passive slow and fast stretches were measured with a custom-built device, with torques at 10° DF (T10°-slow and T10°-fast) extracted as defining parameters for stiffness and muscle tone, respectively. Results Correlations between both T10°-slow and T10°-fast variables with minimum PF torque were fair among ankle DF MMT 0-3 groups (r = 0.71 -0.74, p < 0.01), with no correlation observed among the MMT 4 group and healthy subjects. Conclusions Effects of muscle tone on ankle kinetics during swing phase, with an AFO, were observed in persons with severe ankle DF paresis. Quantitative evaluation of ankle kinetics during gait with an AFO in addition to evaluation of muscle tone at rest is contributory to objective assessment of a muscle tone, not subjective rating scale at rest, or visual inspection of walking.
  • Toshinari Kazuta, Kotaro Takeda, Rieko Osu, Satoshi Tanaka, Ayako Oishi, Kunitsugu Kondo, Meigen Liu
    American Journal of Physical Medicine & Rehabilitation 96(8) 565-571 2017年8月  査読有り筆頭著者
    OBJECTIVE: The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. DESIGN: Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. RESULTS: The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P < 0.01). There was a significant difference (P < 0.01) between the anodal and sham conditions in the number of correctly recalled words within the first five words (primacy region) over the second to fifth trial trials, but not in the middle (next five words) or recency (last five words) regions. CONCLUSIONS: Anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients.
  • Kotaro Takeda, Genichi Tanino, Hiroyuki Miyasaka
    Medical Devices: Evidence and Research 10 207-213 2017年8月  査読有り招待有り筆頭著者責任著者
    Neuromuscular electrical stimulation (NMES), specifically functional electrical stimulation (FES) that compensates for voluntary motion, and therapeutic electrical stimulation (TES) aimed at muscle strengthening and recovery from paralysis are widely used in stroke rehabilitation. The electrical stimulation of muscle contraction should be synchronized with intended motion to restore paralysis. Therefore, NMES devices, which monitor electromyogram (EMG) or electroencephalogram (EEG) changes with motor intention and use them as a trigger, have been developed. Devices that modify the current intensity of NMES, based on EMG or EEG, have also been proposed. Given the diversity in devices and stimulation methods of NMES, the aim of the current review was to introduce some commercial FES and TES devices and application methods, which depend on the condition of the patient with stroke, including the degree of paralysis.
  • Abbas Orand, Hiroyuki Miyasaka, Kotaro Takeda, Genichi Tanino, Takeshi Chihara, Hidehiko Beppu, Shigeru Sonoda
    Biocybernetics and Biomedical Engineering 37(1) 114-123 2017年1月  査読有り
    The consistency of torque measurements during repetitive moving arm movements and also during passive wrist movements at two angular velocities of slow (similar to 6 degrees/s) and moderate (similar to 120 degrees/s) was investigated. The designed and developed device was applied to 3 cases, to a spring, to 8 able-bodied subjects and to 2 hemiplegic patients. While the mean of the intra-class correlation coefficient of subjects were 0.65 and 0.75 for slow and moderate angular velocities, those of the hemiplegic patients and the spring respectively ranged between excellent values of 0.93-1 and 0.91-1. The Pearson's product-moment correlation coefficients of the 3 cases for the 2 slow and moderate angular velocities ranged between 0.80 and 1. We could verify that the device can be used in our future researches and it can (1) reliably rotate a moving arm horizontally with angular velocities between 3 and 350 degrees/s constantly in a range of motion between -60 and 60 degrees and (2) simultaneously capture the data of angular displacement, torque, and two electromyogram activities. For the standardization of our future studies with the device, we could verify the stability of the last two repeated passive wrist movements in case of patients. The results of the study with the able-bodied subjects are also important as a reference for our studies with the hemiplegic. (C) 2017 The Authors. Published by Elsevier B.V. on behalf of Nalecz Institute of Biocybemetics and Biomedical Engineering of the Polish Academy of Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Genichi Tanino, Yutaka Tomita, Abbas Orand, Kotaro Takeda, Ken Tomida, Hiroyuki Miyasaka, Kensuke Ohno, Sayaka Okamoto, Shigeru Sonoda
    Technology and Disability 28(4) 139-144 2017年1月  査読有り
    BACKGROUND: Electrical stimulation is shown to be effective for the amelioration of paralysis. The stimulation pattern can have a direct relation to injected charge in the stimulated area resulting in a wider area stimulation and consequently better recovery. OBJECTIVE: In this study, we investigated the effect of two electrical stimulation waveforms, rectangular and exponentially climbing. Three parameters of current, voltage, and knee extension torque of the 2 waveforms were recorded and used for the comparison of the two waveforms. METHODS: Fifteen male and 15 female able-bodied subjects (age: 25.0 ± 3.2) were recruited. Electrical stimulation was applied to right quadriceps muscles. At the maximum tolerable intensity, the 3 parameters were recorded for each of the 2 waveforms. Using the recorded knee extension torques, the adjusted maximum electrically induced contraction to voluntary torques in percent (%MEIC) of the two waveforms were calculated. Together with the other two parameters, current and voltage, the 2 waveforms were compared. RESULTS: The %MEIC and maximum voltage were significantly higher with the exponentially climbing waveform than with the rectangular waveform (%MEIC: p < 0.05, max voltage: p < 0.01). The maximum current did not differ significantly between conditions. CONCLUSION: These results indicate that an exponentially climbing waveform may induce stronger torque than a rectangular waveform and might thus be useful when applying NMES in clinical situations.
  • Abbas Orand, Genichi Tanino, Hiroyuki Miyasaka, Kotaro Takeda, Shigeru Sonoda
    International Journal of Electrical and Computer Engineering 6(6) 2682-2688 2016年12月  査読有り
    In this paper, a programmable, multi-pattern, wide frequency and duty cycle range electrical stimulator is presented. Using a programmable micro-controller, two waves of carrier and modulating sources are produced. By modulating the two sources, 3 bi-phasic charge-balanced rectangular, triangular and sinusoidal stimulating patterns are produced. The frequency range of the carrier is fixed at 2.5 kHz and the carrier source frequency can be adjusted between 1 and 500 Hz. The duty cycle of both sources can be adjusted between 10% and 90%.
  • Minoru Shibui, Hideki Mochizuki, Kotaro Takeda, Yutaka Sato, Izumi Nagashima, Yusuke Harada, Nobuaki Shimoda
    Journal of Ergonomic Technology 16(1) 24-30 2016年12月  査読有り
    Purpose: We compared the response times for each presented angle in a hand mental rotation task (HMRT) in patients with schizophrenia in order to investigate performance strategies adopted when patients were required to determine whether a presented picture showed a left or right hand. Patients and Methods: Twenty-three right-handed patients with schizophrenia (15 male and 8 female, mean age 39.5 ± 11.6 years) performed the HMRT. A total of 96 pictures randomly featuring left or right hands, either palm or back of hand, rotated in six different angles (at a 60° intervals) were presented to participants. Participants were instructed to determine the left or right for each picture as fast and as accurately as possible by pressing the left or right key. Conclusion: Response times were longer for the angles that were difficult for participants to simulate. These results indicate that participants utilize a motor imagery strategy to perform HMRTs.
  • Jiro Terada, Isato Fukushi, Kotaro Takeda, Yohei Hasebe, Mieczyslaw Pokorski, Koichiro Tatsumi, Yasumasa Okada
    Respiratory Research 17(1) 148 2016年11月14日  査読有り
    BACKGROUND: Modafinil is a wake-promoting drug and has been widely used for daytime sleepiness in patients with narcolepsy and other sleep disorders. A recent case series reported that daily oral modafinil alleviated hypercapnic respiratory failure in patients with COPD. However, the precise action of modafinil on respiration such as hypercapnic and/or hypoxic ventilatory responses remains unclear. The aim of this study is to clarify the effect of modafinil on the ventilatory control. METHODS: We investigated the hypothesis that modafinil enhances resting ventilation as well as the stimulatory ventilatory responses to hypercapnia and hypoxia. We addressed the issue by examining minute ventilation, respiratory rate and volume components using plethysmography, combined with a concurrent EEG monitoring of the level of wakefulness before and after administration of modafinil in two doses of 100 mg/kg and 200 mg/kg in unanesthetized mice. In addition, we monitored the effect of the lower dose of modafinil on mice locomotor activity in a freely moving condition by video-recording. RESULTS: Wakefulness, locomotor activity and variability of the breathing pattern in tidal volume were promoted by both doses of modafinil. Neither dose of modafinil increased the absolute values of resting ventilation or promoted the ventilatory responses to hypercapnia and hypoxia. Rather, higher dose of modafinil slightly suppressed respiratory rate in room air condition. CONCLUSIONS: Modafinil is conducive to the state of wakefulness but does not augment resting ventilation or the hyperventilatory responses to chemical stimuli in unanesthetized rodents.
  • Hiroyuki Miyasaka, Abbas Orand, Hitoshi Ohnishi, Genichi Tanino, Kotaro Takeda, Shigeru Sonoda
    Medical Engineering & Physics 38(11) 1172-1175 2016年11月  査読有り責任著者
    We investigated whether untriggered neuromuscular electrical stimulation (NMES) can increase the effectiveness of shoulder and elbow robotic training in patients with hemiparesis. Thirty subacute stroke patients were randomly equally allocated to robot only (RO) and robot and electrical stimulation (RE) groups. During training, shoulder and elbow movements were trained by operating the robotic arm with the paretic arm, and the robotic device helped to move the arm. In the RE group, the anterior deltoid and triceps brachii muscles were electrically stimulated at sub-motor threshold intensity. Training was performed (approximately 1h/day, 5 days/week for 2 weeks) in addition to regular rehabilitation. Active range of motion (ROM) values of shoulder flexion and abduction, and Fugl-Meyer assessment (FMA) scores were measured before and after training. Active shoulder ROM was significantly better after than before training in the RE group; however, no such improvement was noted in the RO group. FMA scores were significantly better in both groups, and there was no significant difference between the groups. Untriggered NMES might increase the effectiveness of shoulder and elbow robotic training in patients with hemiparesis. Additionally, NMES at a sub-motor threshold during robotic training might facilitate activation of paretic muscles, resulting in paralysis improvement.
  • Takanori Sato, Isao Nambu, Kotaro Takeda, Takatsugu Aihara, Okito Yamashita, Yuko Isogaya, Yoshihiro Inoue, Yohei Otaka, Yasuhiro Wada, Mitsuo Kawato, Masa-Aki Sato, Rieko Osu
    NeuroImage 141 120-132 2016年11月1日  査読有り
    Functional near-infrared spectroscopy (fNIRS) is used to measure cerebral activity because it is simple and portable. However, scalp-hemodynamics often contaminates fNIRS signals, leading to detection of cortical activity in regions that are actually inactive. Methods for removing these artifacts using standard source-detector distance channels (Long-channel) tend to over-estimate the artifacts, while methods using additional short source-detector distance channels (Short-channel) require numerous probes to cover broad cortical areas, which leads to a high cost and prolonged experimental time. Here, we propose a new method that effectively combines the existing techniques, preserving the accuracy of estimating cerebral activity and avoiding the disadvantages inherent when applying the techniques individually. Our new method accomplishes this by estimating a global scalp-hemodynamic component from a small number of Short-channels, and removing its influence from the Long-channels using a general linear model (GLM). To demonstrate the feasibility of this method, we collected fNIRS and functional magnetic resonance imaging (fMRI) measurements during a motor task. First, we measured changes in oxygenated hemoglobin concentration (∆Oxy-Hb) from 18 Short-channels placed over motor-related areas, and confirmed that the majority of scalp-hemodynamics was globally consistent and could be estimated from as few as four Short-channels using principal component analysis. We then measured ∆Oxy-Hb from 4 Short- and 43 Long-channels. The GLM identified cerebral activity comparable to that measured separately by fMRI, even when scalp-hemodynamics exhibited substantial task-related modulation. These results suggest that combining measurements from four Short-channels with a GLM provides robust estimation of cerebral activity at a low cost.
  • Yusuke Harada, Hideki Mochizuki, Kotaro Takeda, Izumi Nagashima, Yutaka Sato, Motonaru Uchihara, Nobuaki Shimoda
    Journal of Ergonomic Technology 16(1) 15-23 2016年11月  査読有り
    Purpose: We compared the accuracy and response times for a hand mental rotation task (HMRT) in patients with hemiplegic stroke in order to investigate performance strategies adopted when patients were required to determine whether a presented picture showed a left or right hand. Patients and Methods: Twenty-eight patients with hemiplegic stroke performed the HMRT (14 patients with left-hemisphere brain damage: 59.5 ± 15.8 years; 14 patients with right-hemisphere brain damage: 65.6 ± 14.9 years). Hand pictures featuring various combinations of three factors (left or right hand, palm or back of hand, and six angular orientations were randomly presented. The third finger pointing upward was defined as an angle of 0°, and clockwise rotation occurred in increments of 60°. Participants were instructed to use their non-paralyzed hand to press the button in the determined direction (e.g., in the case of a left hand picture, the left button was pressed) as quickly and as accurately as possible. Results: The accuracy in the HMRT was lowest for angles of 180°, and an increasing trend in accuracy was observed as the picture was rotated clockwise or counterclockwise towards 0°. The ΔRT was also longest for angles of 180° and tended to decrease as 0° was approached. Moreover, when compared with RTs for pictures of hand angles that were easier to replicate, those for pictures of hand angles that were difficult to replicate were longer. Conclusion: These results indicate that patients with hemiplegic stroke utilize a mental transformation strategy to perform HMRTs, and that this strategy involves simulation of one’s own hand movements (motor imagery strategy).
  • Mieczyslaw Pokorski, Kotaro Takeda, Yasumasa Okada
    Advances in Experimental Medicine and Biology 952 1-8 2016年8月  査読有り
    This review tackles the unresolved issue of the existence of oxygen sensor in the body. The sensor that would respond to changes in tissue oxygen content, possibly along the hypoxia-normoxia-hyperoxia spectrum, rather than to a given level of oxygen, and would translate the response into lung ventilation changes, the major adaptive process. Studies on oxygen sensing, for decades, concentrated around the hypoxic ventilatory response generated mostly by carotid body chemoreceptor cells. Despite gaining a substantial insight into the cellular transduction pathways in carotid chemoreceptors, the exact molecular mechanisms of the chemoreflex have never been conclusively verified. The article briefly sums up the older studies and presents novel theories on oxygen, notably, hypoxia sensing. These theories have to do with the role of transient receptor potential cation TRPA1 channels and brain astrocytes in hypoxia sensing. Although both play a substantial role in shaping the ventilatory response to hypoxia, neither can yet be considered the ultimate sensor of hypoxia. The enigma of oxygen sensing in tissue still remains to be resolved.
  • Isato Fukushi, Kotaro Takeda, Shigefumi Yokota, Yohei Hasebe, Yutaka Sato, Mieczyslaw Pokorski, Jouji Horiuchi, Yasumasa Okada
    Respiratory Physiology & Neurobiology 226 24-29 2016年6月  査読有り
    Mild hypoxia increases ventilation, but severe hypoxia depresses it. The mechanism of hypoxic ventilatory depression, in particular, the functional role of the cerebrum, is not fully understood. Recent progress in glial physiology has provided evidence that astrocytes play active roles in information processing in various brain functions. We investigated the hypothesis that astrocytic activation is necessary to maintain the cerebral function and ventilation in hypoxia, by examining the responses of EEG and ventilation to severe hypoxia before and after administration of a modulator of astrocytic function, arundic acid, in unanesthetized mice. Ventilatory parameters were measured by whole body plethysmography. When hypoxic ventilatory depression occurred, gamma frequency band of EEG was suppressed. Arundic acid further suppressed ventilation, and the EEG power was suppressed in a dose-dependent manner. Arundic acid also suppressed hypoxia-induced c-Fos expression in the hypothalamus. We conclude that severe hypoxia suppresses the cerebral function which could reduce the stimulus to the brainstem resulting in ventilatory depression. Astrocytic activation in hypoxia may counteract both cerebral and ventilatory suppression.
  • Kotaro Takeda, Mieczyslaw Pokorski, Yasumasa Okada
    Advances in Experimental Medicine and Biology 921 45-50 2016年5月  査読有り筆頭著者
    Dimethyl sulfoxide (DMSO) is commonly used as a solvent for hydrophobic substances, but the compound's innate bioactivity is an area of limited understanding. In this investigation we seek to determine the analgesic potential of DMSO. We addressed the issue by assessing the perception of thermal pain stimulus, using a 55 °C hotplate design, in conscious mice. The latency of withdrawal behaviors over a range of incremental accumulative intraperitoneal DMSO doses (0.5-15.5 g/kg) in the same mouse was taken as a measure of thermal endurance. The findings were that the latency, on average, amounted to 15-30 s and it differed inappreciably between the sequential DMSO conditions. Nor was it different from the pre-DMSO control conditions. Thus, DMSO did not influence the cutaneous thermal pain perception. The findings do not lend support to those literature reports that point to the plausible antinociceptive potential of DMSO as one of a plethora of its innate bioactivities. However, the findings concern the mouse's footpad nociceptors which have specific morphology and stimulus transduction pathways, which cannot exclude DMSO's antinociceptive influence on other types of pain or in other types of skin. Complex and as yet unresolved neural mechanisms of perception of cutaneous noxious heat stimulus should be further explored with alternative experimental designs.
  • Shiho Mizuno, Shigeru Sonoda, Kotaro Takeda, Shinichiro Maeshima
    Journal of Stroke and Cerebrovascular Diseases 25(4) 946-53 2016年4月  査読有り
    BACKGROUND: Quantification of increased muscle tone for patients with spasticity has been performed to date using various devices to replace the manual scales, such as the modified Ashworth scale or the Tardieu scale. We developed a device that could measure resistive plantar flexion (PF) torque of the ankle during passive dorsiflexion (DF) as an indicator of muscle tone of ankle plantar flexors. METHODS: The primary objective was to explore the test-retest intrarater reliability of a custom-built device. Participants were 11 healthy subjects (7 men, 4 women; mean age 47.0 years) and 22 patients with poststroke hemiplegia (11 hemorrhagic, 11 ischemic; 14 men, 8 women; mean age 57.2 years). The device was affixed to the ankle. Subjects were seated with knees either flexed or extended. The ankle was passively dorsiflexed from 20° of PF to more than 10° of DF at 5°/second (slow stretch) or 90°/second (fast stretch). Angle and torque were measured twice during the stretches. The intraclass correlation coefficients (ICCs) of torque at 10° of DF (T10) in the 4 conditions-slow and fast stretches with knee flexed or extended-were calculated. RESULTS: The T10 ICCs of the 4 conditions were .95-.99 in both groups. The healthy subjects showed significantly higher T10 of knee extension than of knee flexion during slow and fast stretches. The patients showed increased velocity-dependent torque during fast stretches. CONCLUSIONS: Excellent reliability was observed. The device is suitable for measuring resistive PF torque during passive stretch in a flexed knee condition.
  • Satoshi Shibata, Daisuke Yashiro, Kazuhiro Yubai, Satoshi Komada, Kotaro Takeda
    Proc IEEJ Intl Workshop SAMCON 1-6 2016年3月  査読有り最終著者

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    Acta Pshychol; Adv Biomed Eng; Appl Sci (Basel); Brain Lang; Brain Res; Cereb Cortex; Cogn Neurodyn; Comput Biol Med; Front Med; Front Neurosci; IEEE Access; Laterality; J Cent Nerv Syst Dis; J Ergon Technol; J Exerc Sci Fit; J Neuroeng Rehabil; J Rehabil Neurosci; Jpn J Compr Rehabil Sci; Med Eng Phys; Medicina (Kaunas); Neurosci Lett; Neurosci Res; Neuroreport; Physiother Theory Pract; Spat Cogn Comput; Tohoku J Exp Med; 医学と生物学; 日本転倒予防学会誌; 日本ロボット学会誌; 脳科学とリハビリテーション; バイオメカニズム学会誌

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  • 筋電・トルクの計測系と干渉しない簡便でワイヤレスな関節角度計 *本研究ニーズに関する産学共同研究の問い合わせは藤田医科大学産学連携推進センター(fuji-san@fujita-hu.ac.jp)まで