Researchers Database

oonuki yosiyuki

    SurgicalNeurology Research Associate
Contact: y.onukijichi.ac.jp
Last Updated :2021/12/04

Researcher Information

Degree

  • Ph.D.(Erasmus University Rotterdam)

J-Global ID

Research Interests

  • Gene therapy   Time perception   Learning   Memory   Sleep   

Research Areas

  • Humanities & social sciences / Cognitive sciences

Academic & Professional Experience

  • 2020 - Today  Jichi Medical UniversityDepartment of NeurosurgeryAssistant Professor

Published Papers

  • Yoshiyuki Onuki, Sayaka Ono, Takeshi Nakajima, Karin Kojima, Naoyuki Taga, Takahiro Ikeda, Mari Kuwajima, Yoshie Kurokawa, Mitsuhiro Kato, Kensuke Kawai, Hitoshi Osaka, Toshihiko Sato, Shin-Ichi Muramatsu, Takanori Yamagata
    Brain communications 3 (3) fcab078  2021 
    Aromatic l-amino acid decarboxylase (AADC) is an essential dopamine-synthesizing enzyme. In children with AADC deficiency, the gene delivery of AADC into the putamen, which functionally interacts with cortical regions, was found to improve motor function and ameliorate dystonia. However, how the restoration of dopamine in the putamen in association with cortico-putaminal networks leads to therapeutic effects remains unclear. Here, we examined neuroimaging data of eight patients with AADC deficiency (five males and three females, age range 4-19 years) who received the AADC gene therapy of the bilateral putamen in an open-label phase 1/2 study. Using high-resolution positron emission tomography with a specific AADC tracer, 6-[18F]fluoro-l-m-tyrosine (FMT), we showed that FMT uptake increased in the broad area of the putamen over the years. Then, with the structural connectivity-based parcellation of the putaminal area, we found that motor improvement is associated with dopaminergic restoration of the putaminal area that belongs to the prefrontal cortico-putaminal network. The prefrontal area dominantly belongs to the frontoparietal control network, which contributes to cognitive-motor control function, including motor initiation and planning. The results suggest that putaminal dopamine promotes the development of an immature motor control system, particularly in the human prefrontal cortex that is primarily affected by AADC deficiency.
  • Miyata S, Tominaga K, Sakashita E, Urabe M, Onuki Y, Gomi A, Yamaguchi T, Mieno M, Mizukami H, Kume A, Ozawa K, Watanabe E, Kawai K, Endo H
    Scientific reports 9 (1) 9787 - 9787 2019/07 [Refereed][Not invited]
     
    Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II-IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.
  • Kojima K, Nakajima T, Taga N, Miyauchi A, Kato M, Matsumoto A, Ikeda T, Nakamura K, Kubota T, Mizukami H, Ono S, Onuki Y, Sato T, Osaka H, Muramatsu SI, Yamagata T
    Brain : a journal of neurology 142 (2) 322 - 333 0006-8950 2019/01 [Refereed][Not invited]
  • Cathrin B. Canto, Yoshiyuki Onuki, Bastiaan Bruinsma, Ysbrand D. van der Werf, Chris I. De Zeeuw
    TRENDS IN NEUROSCIENCES 40 (5) 309 - 323 0166-2236 2017/05 [Refereed][Not invited]
     
    We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology, cerebro-cerebellar interactions during sleep, or the contributions of sleep to cerebellum-dependent memory consolidation. Likewise, we do not understand why cerebellar malfunction can lead to changes in the sleep-wake cycle and sleep disorders. In this review, we evaluate how sleep and cerebellar processing may influence one another and highlight which scientific routes and technical approaches could be taken to uncover the mechanisms underlying these interactions.
  • Robin Broersen, Yoshiyuki Onuki, Abdel R. Abdelgabar, Cullen B. Owens, Samuel Picard, Jessica Willems, Henk-Jan Boele, Valeria Gazzola, Ysbrand D. Van der Werf, Chris I. De Zeeuw
    PLOS ONE 11 (8) e0162042  1932-6203 2016/08 [Refereed][Not invited]
     
    Many daily life activities demand precise integration of spatial and temporal information of sensory inputs followed by appropriate motor actions. This type of integration is carried out in part by the cerebellum, which has been postulated to play a central role in learning and timing of movements. Cerebellar damage due to atrophy or lesions may compromise forward-model processing, in which both spatial and temporal cues are used to achieve prediction for future motor states. In the present study we sought to further investigate the cerebellar contribution to predictive and reactive motor timing, as well as to learning of sequential order and temporal intervals in these tasks. We tested patients with spinocerebellar ataxia type 6 (SCA6) and healthy controls for two related motor tasks; one requiring spatio-temporal prediction of dynamic visual stimuli and another one requiring reactive timing only. We found that healthy controls established spatio-temporal prediction in their responses with high temporal precision, which was absent in the cerebellar patients. SCA6 patients showed lower predictive motor timing, coinciding with a reduced number of correct responses during the 'anticipatory' period on the task. Moreover, on the task utilizing reactive motor timing functions, control participants showed both sequence order and temporal interval learning, whereas patients only showed sequence order learning. These results suggest that SCA6 affects predictive motor timing and temporal interval learning. Our results support and highlight cerebellar contribution to timing and argue for cerebellar engagement during spatio-temporal prediction of upcoming events.
  • Ilse M. Verweij, Yoshiyuki Onuki, Eus J. W. Van Someren, Ysbrand D. Van der Werf
    BEHAVIORAL NEUROSCIENCE 130 (3) 298 - 304 0735-7044 2016/06 [Refereed][Not invited]
     
    Growing evidence suggests that sleep is important for procedural learning, but few studies have investigated the effect of sleep on the temporal aspects of motor skill learning. We assessed the effect of a 90-min day-time nap on learning a motor timing task, using 2 adaptations of a serial interception sequence learning (SISL) task. Forty-two right-handed participants performed the task before and after a 90-min period of sleep or wake. Electroencephalography (EEG) was recorded throughout. The motor task consisted of a sequential spatial pattern and was performed according to 2 different timing conditions, that is, either following a sequential or a random temporal pattern. The increase in accuracy was compared between groups using a mixed linear regression model. Within the sleep group, performance improvement was modeled based on sleep characteristics, including spindle-and slow-wave density. The sleep group, but not the wake group, showed improvement in the random temporal, but especially and significantly more strongly in the sequential temporal condition. None of the sleep characteristics predicted improvement on either general of the timing conditions. In conclusion, a daytime nap improves performance on a timing task. We show that performance on the task with a sequential timing sequence benefits more from sleep than motor timing. More important, the temporal sequence did not benefit initial learning, because differences arose only after an offline period and specifically when this period contained sleep. Sleep appears to aid in the extraction of regularities for optimal subsequent performance.
  • Yoshiyuki Onuki, Eus J. W. Van Someren, Chris I. De Zeeuw, Ysbrand D. Van der Werf
    CEREBRAL CORTEX 25 (2) 313 - 321 1047-3211 2015/02 [Refereed][Not invited]
     
    The hippocampus and cerebellum play a role in the process of temporal memory formation. The interaction between these brain regions during the prediction of motor executions nevertheless remains unclear. Using fMRI, we show here that the hippocampus and cerebellum are co-activated during a timing-dependent task that requires accurate prediction timing of finger movements following preceding visual cues, but not during 2 control tasks: a reaction task requiring identical coordination of individual and combined fingers without predicting the motor timing, or an imagery task. In addition, functional connectivity analyses reveal that the hippocampus showed increased functional connectivity with the bilateral hemispheres of the cerebellum. These results suggest that hippocampal-cerebellar interplay occurs during spatio-temporal prediction of movements on the basis of visuomotor integration.

MISC

  • 大谷 啓介, 川合 謙介, 五味 玲, 佐藤 信, 内山 拓, 大貫 良幸, 石下 洋平, 日本てんかん学会てんかん専門医療施設(センター)検討委員会  てんかん研究  37-  (3)  766  -778  2020/01  [Not refereed][Not invited]
     
    【はじめに】日本の地方におけるてんかん診療に関する報告はなく、その実態は不明である。われわれは、地方におけるてんかん診療の現状を明らかにすべく調査研究を行った。【方法】自治医科大学卒業生は出身都道府県で一定期間の地域医療従事が義務付けられており、都市部以外の地域でプライマリケア医としててんかん診療にあたることが多いため、今回の調査対象とした。アンケートの内容は、診断や治療などに加え、社会福祉や運転免許、後方病院との連携、都道府県てんかんセンターの周知度など、幅広く設定し、Webアンケート形式で行った。【結果】診療内容に関しては、ガイドラインが広く浸透している一方、検査内容や使用できる薬剤に制限があるなどの問題点が明らかになった。てんかんセンターの認知度はいまだ低く、医療連携について多くの課題が存在することが明らかになった。【結語】本調査では、自治医科大学卒業医師に対するWebアンケートを通して、地方におけるてんかん診療の現状や、地域医療を行っているてんかん非専門医の感じている問題点などが明らかになった。(著者抄録)
  • 宮田 五月, 難波 克成, 檜垣 鮎帆, 大貫 良幸, 山口 崇, 川合 謙介  脳神経外科と漢方 = Journal of neurosurgery and kampo medicine : 日本脳神経外科漢方医学会機関誌  5-  48  -52  2019/10  [Not refereed][Not invited]
     
    69歳、女性。進行する動眼神経麻痺で発症した脳底動脈・上小脳動脈分岐部動脈瘤に対してBioactive coilを用いて脳動脈瘤コイル塞栓術を施行した。術後、脳動脈瘤周囲に浮腫性変化を認めたため、ステロイド治療を開始した。しかし治療効果を認めず、脳浮腫の増悪、水頭症も合併した。五苓散を追加投与することで、脳浮腫および水頭症は改善した。ステロイド難治例に対する治療の選択肢の一つとなる可能性がある。(著者抄録)
  • ミニブタ皮質脳波測定による軟膜下皮質多切術の安全性の検討
    石下 洋平, 庭山 雅嗣, 齋藤 敏之, 大貫 良幸, 内山 拓, 横田 英典, 渡辺 英寿, 川合 謙介  てんかん研究  37-  (2)  532  -532  2019/09  [Not refereed][Not invited]
  • 救急医療情報を活用したてんかんに起因する交通事故の後向き観察研究
    伴 知晃, 手塚 正幸, 大貫 良幸, 内山 拓, 大谷 啓介, 石下 洋平, 米川 力, 中嶋 剛, 川合 謙介  日本交通科学学会誌  19-  (Suppl.)  91  -91  2019/06  [Not refereed][Not invited]
  • Isolated hand palsyを呈した脳梗塞 機能的MRIによる機能局在解析の検討
    古谷 浩平, 小澤 忠嗣, 大貫 良幸, 金 蓮姫, 横瀬 美里, 鈴木 雅之, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 松浦 徹, 川合 謙介, 藤本 茂  臨床神経学  58-  (Suppl.)  S279  -S279  2018/12  [Not refereed][Not invited]
  • 大貫 良幸, Abramson Charles I  心理学史・心理学論  6-  33  -43  2004/12  [Not refereed][Not invited]

Research Grants & Projects

  • 大脳皮質-海馬ネットワークへの侵襲的計測・介入による時間見積機能の神経基盤の解明
    日本学術振興会:科学研究費助成事業 若手研究
    Date (from‐to) : 2021/04 -2024/03 
    Author : 大貫 良幸
  • Multi-scale investigation of cerebral anatomo-functional changes induced by long-term electrical stimulation and surgical intervention
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 川合 謙介, 石下 洋平, 島崎 久仁子, 手塚 正幸, 中嶋 剛, 國井 尚人, 佐藤 信, 高橋 宏知, 大谷 啓介, 大貫 良幸
  • 実臨床における海馬の時間予想機構の解明
    文部科学省:科学研究費補助金 若手研究
    Date (from‐to) : 2019/04 -2021/03 
    Author : 大貫良幸
  • 睡眠中の心的イメージに対する情動の作用機序の解明
    文部科学省:特別研究員奨励費
    Date (from‐to) : 2018/04 -2021/03 
    Author : 大貫良幸


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