Elucidation of the pathophysiological mechanism of the cases who have no effect on ADHD medication using fNIRS

• Project/Area Number: 15K19627
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Jichi Medical University
• Principal Investigator: Nagashima Masako 自治医科大学, 医学部, 講師 (70438662)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 機能的近赤外線分光法 / 注意欠如・多動障害 / 自閉症スペクトラム / 塩酸メチルフェニデート徐放剤 / 抑制機能課題 / fNIRS / ADHD

Outline of Final Research Achievements

We examined the neural substrate of the effects of methylphenidate (MPH) on inhibition control in medication-naive ADHD and ADHD with ASD children using fNIRS in a randomized, double-blind, placebo-controlled, crossover design. We investigated cortical activation in the right inferior or middle frontal gyrus (IFG/MFG). In the ADHD without ASD group, unmedicated children exhibited no activation in right IFG/MFG, but MPH medication led to increased right IFG/MFG activation. In the ADHD with ASD group, right IFG/MFG activation was observed before taking MPH, but MPH medication resulted in decreased right IFG/MFG activation. Behavioral assessment showed a significant improvement in both groups one month after oral administration of MPH. In cases where MPH was effective, these results suggest that ADHD with ASD is not simply a mixture of ADHD and ASD pure disorders, but rather that it has its own distinct neuropathology. We will examine cases in which MPH is ineffective as a next step.

Research Products

• [Journal Article] Methylphenidate Elicited Distinct NeuropharmacologicalActivation Patterns Between Medication Naive AttentionDeficit Hyperactivity Disorder Children With and WithoutComorbid Autism Spectrum Disorder: A Functional Near Infrared Spectroscopy Study (2018)
  • Author(s): Tatsuya Tokuda,Takahiro Ikeda,Yukifumi Monden , Sakae G Mizushima, Hideo Shimoizumi,Takeshi Inoue,Masako Nagashima, Keiichi Shimamura, Akari Arakawa,Megumi Kobayashi, MasamiK Yamaguchi, Chie Kuroiwa,Yuta Ujiie, Haruka Dan, Yasushi Kyutoku, Takamichi Taniguchi,TakanoriYamagata, So Kanazawa, Ryouichi Sakuta, Ippeita Dan
  • Journal Title: Neuropsychlatry Volume: 8 Pages: 739-744
  • Peer Reviewed / Open Access
• [Journal Article] Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS. (2015)
  • Author(s): Monden Y, Dan I, Nagashima M, Dan H, Uga M, Ikeda T, Tsuzuki D, Kyutoku Y, Gunji Y, Hirano D, Taniguchi T, Shimoizumi H, Watanabe E, Yamagata T.
  • Journal Title: NeuroImage Clinical Volume: 9 Pages: 1-12
  • DOI: 10.1016/j.nicl.2015.06.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] fNIRS-based assessment of individual classification of ADHD children by right prefrontal hemodynamic responses during an inhibition task (2017)
  • Author(s): Masako Nagashima, Yukifumi Monden, Ippeita Dan, Takahiro Ikeda, Minako Uga, Hideo Shimoizumi, Takanori Yamagata
  • Organizer: 国際小児神経学会
  • Int'l Joint Research
• [Presentation] fNIRS-based assessment of individual classification of ADHD children during an inhibition task (2016)
  • Author(s): Masako Nagashima, Yukifumi Monden, Ippeita Dan, Takahiro Ikeda, Minako Uga, Hideo Shimoizumi, Takanori Yamagata
  • Organizer: 小児神経学会総会
  • Place of Presentation: 京王プラザ (東京都 新宿）
  • Year and Date: 2016-06-03
• [Presentation] fNIRS-based assessment during an inhibition task to classify ADHD children at the individual level (2016)
  • Author(s): Masako Nagashima,Yukifumi Monden, Ippeita Dan, Atsushi Maki, Hiroki Sato, Takahiro Ikeda, Minako Uga, Hideo Shimoizumi, Takanori Yamagata
  • Organizer: 国際ADHD学会
  • Place of Presentation: The Singapore Expo Convention and Exhibition Center (シンガポール）
  • Year and Date: 2016-05-25
  • Int'l Joint Research
• [Presentation] fNIRSを用いた塩酸メチルフェニデート治療薬内服後の脳機能変化の検討 (2016)
  • Author(s): 長嶋雅子, 門田行史, 檀一平太, 宇賀美奈子, 徳田竜也, 池田尚広, 山岸佑也,下泉秀夫, 山形崇倫
  • Organizer: 日本ADHD学会
  • Place of Presentation: 筑波大学東京キャンパス（東京）
  • Year and Date: 2016-02-20
• [Presentation] Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS (2015)
  • Author(s): Masako Nagashima,Yukifumi Monden, Ippeita Dan, Atsushi Maki, Takanori Yamagata
  • Organizer: 自治医科大学シンポジウム
  • Place of Presentation: 自治医科大学（栃木）
  • Year and Date: 2015-09-04
• [Presentation] fNIRS-based neuropharmacological assessment of methylphenidate and atomoxetine on inhibition and attention network in pediatric attention deficit/hyperactivity disorder (2015)
  • Author(s): Masako Nagashima, Yukifumi Monden, Ippeita Dan, Haruka Dan, Tsutomu Mizutani, Hideo Shimoizumi, Eiju Watanabe, Takanori Yamagata
  • Organizer: OMICS Group conferences World congress on Pharmacology
  • Place of Presentation: ブリスベン
  • Year and Date: 2015-07-20
• [Presentation] 内服歴のないADHD児の塩酸メチルフェニデート徐放剤内服前後の脳機能変化 (2015)
  • Author(s): 長嶋雅子、門田行史、檀一平太、池田尚広、下泉秀夫、 渡辺英寿、山形崇倫
  • Organizer: 日本薬物脳波学会
  • Place of Presentation: コガノイ ベイ ホテル（和歌山）
  • Year and Date: 2015-06-26
• [Presentation] fNIRS-based assessment of MPH effect in drug-naïve ADHD: a double-blind, placebo-controlled study (2015)
  • Author(s): Masako Nagashima, Yukifumi Monden, Ippeita Dan, Tsutomu Mizutani,Takahiro Ikeda,Hideo Shimoizumi, Eiju Watanabe, Takanori Yamagata
  • Organizer: 小児神経学会総会
  • Place of Presentation: 帝国ホテル（大阪）
  • Year and Date: 2015-05-28
• [Book] High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications (2018)
  • Author(s): Yukifumi Monden, Masako Nagashima, Haruka Dan, Takahiro Ikeda, Yasushi Kyutoku, Takanori Yamagata and Ippeita Dan
  • Total Pages: 18
  • Publisher: Ahmet Mesrur Halefo
• [Remarks] 門田研究室
  • URL: http://ped-brain-lab.xii.jp/wp/