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博士論文 脳梁を介したヒト運動機能調節の 経頭蓋磁気刺激法による
༤ኈㄽᩥ ⬻ᱱࢆࡋࡓࣄࢺ㐠ືᶵ⬟ㄪ⠇ࡢ ⤒㢌☢Ẽ่⃭ἲࡼࡿゎ᫂ ሐ ᾴ ⬻ᱱࢆࡋࡓࣄࢺ㐠ືᶵ⬟ㄪ⠇ࡢ ⤒㢌☢Ẽ่⃭ἲࡼࡿゎ᫂ ᮾிᏛᏛ㝔 ་Ꮫ⣔◊✲⛉ ⬻⚄⤒་Ꮫᑓᨷ ⚄⤒ෆ⛉Ꮫ ᣦᑟᩍဨ㸸㎷ ┬ḟ ᩍᤵ ⏦ㄳ⪅㸸ሐ ᾴ 1 ┠ ḟ ࠙せ᪨ࠚ ......................................................................................................................... 3 ࠙␎ㄒ୍ぴࠚ..................................................................................................................4 ࠙ᗎᩥࠚ ......................................................................................................................... 5 1. ⬻ᱱࡘ࠸࡚......................................................................................................... 5 2. ⤒㢌☢Ẽ่⃭ࡘ࠸࡚..................................................................................... 7 3. ᮏ◊✲ࡢᐇ㦂ᵓᡂ............................................................................................... 14 ࠙➨ 1 ❶ࠚ㍍ᗘㄆ▱ᶵ⬟㞀ᐖ࠾ࡅࡿ⬻༙⌫㐠ື㔝㛫ᢚไࡢῶᑡ ............... 18 㹙┠ⓗ㹛 ................................................................................................................... 19 㹙᪉ἲ㹛 ................................................................................................................... 21 㹙⤖ᯝ㹛 ................................................................................................................... 26 㹙⪃ᐹ㹛 ................................................................................................................... 31 ࠙➨ 2 ❶ࠚ⬻༙⌫㐠ື㔝㛫ᢚไឤぬධຊࡼࡿ㐠ື㔝ᢚไࡢ┦స⏝ࡑ ࡢ่⃭ᙉᗘ౫Ꮡᛶ ....................................................................................................... 36 㹙┠ⓗ㹛 ................................................................................................................... 37 㹙᪉ἲ㹛 ................................................................................................................... 39 㹙⤖ᯝ㹛 ................................................................................................................... 48 㹙⪃ᐹ㹛 ................................................................................................................... 58 ࠙➨ 3 ❶ࠚ୍ḟ㐠ື㔝༢┦ᛶ 4 㐃Ⓨ⤒㢌☢Ẽ่⃭㸦QPS㸧ࡼࡿᑐഃ୍ḟ 㐠ື㔝ࡢ㛗ᮇຠᯝㄏᑟ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢᙳ㡪 ............................... 63 㹙┠ⓗ㹛 ................................................................................................................... 64 㹙᪉ἲ㹛 ................................................................................................................... 68 㹙⤖ᯝ㹛 ................................................................................................................... 78 㹙⪃ᐹ㹛 ................................................................................................................... 88 ࠙⤖ㄽࠚ ....................................................................................................................... 95 ࠙ᘬ⏝ᩥ⊩ࠚ ............................................................................................................... 98 ࠙⌮㠃ࡢ㓄៖ࠚ ................................................................................................. 115 ࠙ㅰ㎡ࠚ ..................................................................................................................... 116 2 ࠙せ᪨ࠚ ࣄࢺ࠾ࡅࡿ⬻ᱱࢆࡋࡓ୧ഃ୍ḟ㐠ື㔝㸦M1㸧㛫ࡢᶵ⬟ㄪ⠇ὀ┠ࡋࠊ⤒㢌 ☢Ẽ่⃭ἲ㸦TMS㸧ࢆ⏝࠸࡚㠀くⓗศᯒࡋࡓࠋࡲࡎࠊ㍍ᗘㄆ▱ᶵ⬟㞀ᐖ ᝈ⪅࠾࠸࡚ࠊ୧ഃ M1 㛫ࡢᢚไᶵ⬟㸦IHI㸧ࡀ␗ᖖ࡛࠶ࡿࡇࢆ♧ࡋࡓࠋࡇࢀ ࡣឤぬධຊࡼࡿ M1 ᢚไ㸦SAI㸧ࡢ␗ᖖࡣ⊂❧ࡋࡓኚ࡛࠶ࡗࡓࠋḟࠊ ᖖே࡛ IHI SAI ࡣ┦ᢚไࡍࡿࡇࢆ᫂ࡽࡋࡓࠋࡉࡽࠊ TMS ࡼࡿ⬻ྍረᛶኚࡀᑐഃ༙⌫ࡶㄏᑟࡉࢀࡿࡇࢆ♧ࡋࠊࡇࢀࡣ⬻ᱱࢆࡋࡓ ᢚไ⣔࣭ಁ㏻⣔୧᪉ࡢㄪ⠇ᶵᵓࡢኚࢆకࡗ࡚࠸ࡓࠋ௨ୖࠊࣄࢺࡢ⬻ᱱࢆࡋ ࡓ M1 㛫ࡢ㐃⤡ࡀ㔜せ࡞⓶㉁㛫ㄪ⠇ࡢ୍ࡘ࡛࠶ࡾࠊ⚄⤒ྍረᛶᶵ⬟ࡶ㛵ࢃࡿࡇ ࢆ᫂ࡽࡋࡓࠋ 3 ࠙␎ㄒ୍ぴࠚ AD; Alzheimer’s disease ࣝࢶࣁ࣐࣮ AMT; active motor threshold ⦰㐠ື㜈್ CCS; contralateral conditioning stimulus ᑐഃ༙⌫ࡽࡢ᮲௳่⃭ CS; conditioning stimulus ᮲௳่⃭ CMCT; central motor conduction time ୰ᯡఏᑟ㛫 FDI; first dorsal interosseous muscle ➨୍⫼ഃ㦵㛫➽ ICF; intracortical facilitation ⓶㉁ෆಁ㏻ IHF; interhemispheric facilitation ⬻༙⌫㐠ື㔝㛫ಁ㏻ IHI; interhemispheric inhibition (transcallosal inhibition) ⬻༙⌫㐠ື㔝㛫ᢚไ ISI; interstimulus interval ่⃭㛫㛫㝸 LICI; long-interval intracortical inhibition 㛗₯⓶㉁ෆᢚไ LIHI; long-latency interhemisphric inhibition 㛗₯⬻༙⌫㐠ື㔝㛫ᢚไ LTD; long-term depression 㛗ᮇᢚᅽ LTP; long-term potentiation 㛗ᮇቑᙉ M1; primary motor cortex ୍ḟ㐠ື㔝 MCI; mild cognitive impairment ㍍ᗘㄆ▱ᶵ⬟㞀ᐖ MEP; motor evoked potential 㐠ືㄏⓎ㟁 MNS; median nerve stimulation ṇ୰⚄⤒่⃭ MSO; maximum stimulus output ᶵᲔࡢ᭱ฟຊ್ PAS; paired associative stimulation 㐃ྜᑐ่⃭ QPS; quadripulse TMS ༢┦ᛶ 4 㐃Ⓨ⤒㢌☢Ẽ่⃭ RMT; resting motor threshold Ᏻ㟼㐠ື㜈್ rTMS; repetitive TMS ⤒㢌☢Ẽ่⃭ SAI; short-latency afferent inhibition ឤぬධຊࡼࡿ୍ḟ㐠ື㔝ᢚไ SICF; short-interval intracortical facilitation ▷₯⓶㉁ෆಁ㏻ SICI; short-interval intracortical inhibition ▷₯⓶㉁ෆᢚไ SIHI; short-latency interhemispheric inhibition ▷₯⬻༙⌫㐠ື㔝㛫ᢚไ ST; sensory threshold ឤぬ㜈್ TBS; theta burst stimulation ࢩ࣮ࢱࣂ࣮ࢫࢺ่⃭ TMS; transcranial magnetic stimulation ⤒㢌☢Ẽ่⃭ TS; test stimulation ヨ㦂่⃭ 4 ࠙ᗎᩥࠚ 1. ⬻ᱱࡘ࠸࡚ ࣄࢺࡢ⬻⚄⤒⣔࠾࠸࡚⬻ᱱࡣᕥྑࡢ⬻༙⌫ࢆࡘ࡞ࡄ᭱ࡢ⥺⥔࡛࠶ࡾࠊ ከࡃࡢ⬻ᶵ⬟࠾࠸࡚㔜せ࡞ᙺࢆᯝࡓࡋ࡚࠸ࡿ⪃࠼ࡽࢀࡿ㸦ᅗ 1㸧[1]ࠋ⬻ᱱ ࢆᵓᡂࡍࡿ⥺⥔ࡢከࡃࡣᕥྑࡢ༙⌫ࡢ┦ྠࡍࡿ㒊ศࢆࡘ࡞ࡂࠊᕥྑ༙⌫㛫ࡢᶵ ⬟ㄪ⠇ᙺ❧ࡗ࡚࠸ࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋ⬻ᱱࢆ㏻ࡿ⚄⤒⥺⥔ࡣࠊ㒊ศࡀ ⬻⓶㉁ࡢ III ᒙᏑᅾࡍࡿ㗹య⣽⬊⏤᮶ࡋࠊከࡃࡢ⤊ᮎࡣ⯆ዧᛶࡢࢢࣝࢱ࣑ࣥ 㓟ࢆ⚄⤒ఏ㐩≀㉁ࡋࡓ asymmetric type ࡢࢩࢼࣉࢫࢆᙧᡂࡋ࡚࠸ࡿࠋື≀ᐇ㦂 ࡛ࡣࠊ⤊ᮎࡢࢩࢼࣉࢫࡣ NMDA ཷᐜయ㠀 NMDA ཷᐜయࡢ୧᪉ാࡁࠊ⬻ᱱ ࡢάືࡼࡾ༢ࢩࢼࣉࢫᛶࡢ⯆ዧᛶࢩࢼࣉࢫᚋ㟁ࢆㄏⓎࡍࡿࡇࡀከ࠸ࡀࠊ ୰ࡣ⤊ᮎࢩࢼࣉࢫ࿘ᅖࡢᢚไᛶᅾࢽ࣮ࣗࣟࣥࢆࡋ࡚ࢩࢼࣉࢫᛶᢚไ ᅗ 1 ࣄࢺࡢ⬻ᱱࡢᴫほ 㸦BodyParts3D, © 1998 ࣛࣇࢧ࢚ࣥࢫ⤫ྜࢹ࣮ࢱ࣮࣋ࢫࢭࣥࢱ࣮ licensed under CC ⾲♧ ⥅ᢎ 2.1 ᪥ᮏ㸧 5 ᛶࢩࢼࣉࢫᚋ㟁ࢆㄏⓎࡍࡿࡇࡀ࠶ࡿ▱ࡽࢀ࡚࠸ࡿ[2]ࠋ ᕥྑࡢ⬻༙⌫㛫ࡢ㐃⤡ࡣᶵ⬟ⓗ㔜せ࡛࠶ࡾࠊ⬻ᱱࡢ㞳᩿ೃ⩌࡛ࡣᕥᡭ ࡢኻ⾜ࢆጞࡵࡋࡓ㧗ḟᶵ⬟㞀ᐖࡀ⏕ࡌࡿࠋ ⬻ᱱࢆࡋࡓ୍ḟ㐠ື㔝㛫ࡢ㐃⤡ ᶵ⬟ࡣࠊᕥྑࡢ༠ㄪ㐠ື࡞㛵ࢃࡗ࡚࠸ࡿ⪃࠼ࡽࢀࡿࡀࠊ⮫ᗋ≧ࡋ࡚ ᤊ࠼ࡽࢀࡿࡇࡣᑡ࡞ࡃࠊ᳨ᰝἲࡶ࠶ࡲࡾ࡞࠸ࠋࡲࡓࠊ⚄⤒ᝈ࡛ࡣࠊከⓎᛶ ◳ࠊ⬻⾑⟶㞀ᐖࠊ⭘⒆࡞࡛⬻ᱱኚࡀぢࡽࢀࡿࠊ⬻ᱱ⳼ⷧࢆక ࠺②ᛶᑐ㯞⑷ࡸ➽ⴎ⦰ᛶഃ⣴◳ࠊࣝࢶࣁ࣐࣮㸦Alzheimer’s diseaseࠊ ௨ୗ AD㸧࡞ࡢ⚄⤒ኚᛶᝈ࡛ࡶ⬻ᱱࡢ␗ᖖࡀ▱ࡽࢀ࡚࠸ࡿࠋ ᮏ◊✲࡛ࡣࠊࣄࢺ࠾࠸࡚⬻ᱱࢆࡋࡓ㐠ືᶵ⬟ㄪ⠇ࡣ࠺࡞ࡗ࡚࠸ࡿࡢ ࠸࠺Ⅼ⯆ࢆᣢࡕࠊ≉୍ḟ㐠ື㔝㸦primary motor cortexࠊ௨ୗ M1㸧㛫ࡢ 㐃⤡ὀ┠ࡋࡓࠋ⬻ᱱࢆࡋࡓᢚไᶵ⬟࡞ࡢ㐠ືᶵ⬟ㄪ⠇ࡘ࠸࡚ࡣࠊື≀ ࢆࡣࡌࡵ[3]ࠊࣄࢺ࡛ࡶࡑࡢᶵ⬟ࡀ◊✲ࡉࢀ࡚࠸ࡿࡀ[4, 5]ࠊࡇࢀࡽࡀࣄࢺࡢ⬻࡛ ࡢࡼ࠺ാࡁࠊ୰ᯡ⚄⤒ᝈ࡛ࡢࡼ࠺࡞㞀ᐖࡀ⏕ࡌࡿࡘ࠸࡚ࡣࠊࣄࢺ ᑐࡍࡿධⓗ◊✲ࡢไ⣙ࡽᮍゎ᫂ࡢⅬࡀከ࠸ࠋࡑࡇ࡛ᮏ◊✲࡛ࡣࠊࣄࢺࡢ ⚄⤒⣽⬊ࢆ㠀くⓗ่⃭࡛ࡁࡿ⤒㢌☢Ẽ่⃭㸦transcranial magnetic stimulationࠊ௨ୗ TMS㸧ࡢᡭἲࢆ⏝࠸࡚ࠊ⬻ᱱࢆࡋࡓࣄࢺ㐠ືᶵ⬟ㄪ⠇ࡘ࠸ ࡚ゎ᫂ࡍࡿࡇࢆ┠ᣦࡋࡓࠋ 6 2. ⤒㢌☢Ẽ่⃭ࡘ࠸࡚ TMS ࡣࣄࢺ⬻⓶㉁ࡢ⚄⤒⣽⬊ࢆ㠀くⓗ่⃭ࡍࡿ᪉ἲ࡛࠶ࡿࠋᛴ㏿ኚ ࡍࡿ㟁ὶࢆࢥࣝෆὶࡍࡇࡼࡗ࡚ࠊㄏᑟ☢ሙࡢኚࢆࡋ࡚⬻ෆ 㟁ὶࢆច㉳ࡋࠊ⚄⤒⣽⬊ࢆ㟁Ẽⓗ่⃭ࡍࡿࡇࡀ࡛ࡁࡿ㸦ᅗ 2ࠊᅗ 3㸧[6] ࠋ 㢌⓶ୖࡽ┤᥋㧗ᅽ㟁Ẽ่⃭ࢆ࠾ࡇ࡞ࡗ࡚ࡶ⚄⤒⣽⬊ࢆ่⃭ࡍࡿࡇࡀ࡛ࡁࡿ ࡀࠊᙉ࠸③ࡳࢆక࠺ࡓࡵᛂ⏝ࡋࡃ࠸ࠋ୍᪉ࠊTMS ࡛ࡣ่⃭క࠺③ࡳࡀ ࢇ࡞ࡃࠊ⮫ᗋᛂ⏝ྥ࠸࡚࠸ࡿⅬࡀ≉ᚩ࡛࠶ࡾࠊࣄࢺ࠾ࡅࡿ⚄⤒άືࢆ ᐃࡍࡿ㔜せ࡞ᡭἲࡢ୍ࡘ࡞ࡗ࡚࠸ࡿࠋ Barker ࡣᡭࡢ M1 ࢆ TMS ่࡛⃭ࡋ࡚ᡭෆ➽ࡼࡾึࡵ࡚㐠ືㄏⓎ㟁㸦motor evoked potentialࠊ௨ୗ MEP㸧ࢆグ㘓ࡋࡓ[7]ࠋTMS ࡼࡾ MEP ࡀㄏⓎࡉࢀࡿᶵ ᗎࡣࠊࡋ࡚ M1 ෆࡢᅾࢽ࣮ࣗࣟࣥࡀ่⃭ࡉࢀࠊ⯆ዧᛶࢩࢼࣉࢫࢆࡋ࡚㛫 ᥋ⓗ㗹య⣽⬊ࡀ่⃭ࡉࢀࠊ⓶㉁⬨㧊㊰ࢆ㏻ࡗ࡚➽ࢆ⦰ࡍࡿࡶࡢ⪃࠼ࡽࢀ ᅗ 2 ⤒㢌☢Ẽ่⃭⨨ ᕥ㸸่⃭⨨ᮏయࠊྑ㸸8 ࡢᏐᆺࢥࣝ 7 ࡚࠸ࡿࠋࣄࢺ࡛◳⭷እ㟁ᴟࢆ⏝࠸࡚グ㘓ࡍࡿࠊTMS ᚋࡣࠊ㗹య⣽⬊ࡢ㍈⣴ ࢆ┤᥋่⃭ࡋࡓ⪃࠼ࡽࢀࡿ D-wave㸦direct wave㸧ࡼࡤࢀࡿୗ⾜㟁ࡼࡾࡶ 㐜࠸₯ࡢࠊ㛫᥋ⓗ㗹య⣽⬊ࡀ่⃭ࡉࢀ࡚ㄏⓎࡉࢀࡓ I-wave㸦indirect waves㸧 ࡀ⣙ 1.5 ms 㛫㝸࡛」ᩘグ㘓ࡉࢀࡿ[8]ࠋࡇࡢࡼ࠺ࠊ⓶㉁ෆ࡛ࢩࢼࣉࢫࢆࡋࡓ ᛂ࡛࠶ࡿࡓࡵࠊTMS ࡼࡾㄏⓎࡉࢀࡿ MEP ᖜࡣ M1 ෆࡢ⯆ዧᛶࡢኚࢆ㛫 ᥋ⓗᫎࡋࠊᢚไࡸಁ㏻ࡢᣦᶆ࡞ࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋ ᅗ 3 ⤒㢌☢Ẽ่⃭ࡼࡿ㐠ືㄏⓎ㟁グ㘓ࡢᶵᗎ 1 㢌እ࠾࠸ࡓ TMS ࢥࣝࠊᣢ⥆ࡢ▷࠸㟁ὶࡀὶࢀࡿࠋ 2 ㄏᑟ☢ሙࡀࢥࣝᆶ┤࡞᪉ྥ⏕ࡌࠊ㢌㦵ࢆ㏻ࡌ࡚㢌ෆ㐩ࡍࡿࠋ 3 ㄏᑟ☢ሙࡢᛴ⃭࡞㛫ኚࡼࡾࠊ⬻ෆ 㟁ὶࡀច㉳ࡉࢀࡿࠋ 4 ⚄⤒⣽⬊ࡀ่⃭ࡉࢀࠊ⓶㉁⬨㧊㊰ࢆ㏻ࡗ࡚➽㐠ືㄏⓎ㟁ࡀグ㘓ࡉࢀࡿࠋ 8 TMS ࢆ⏝࠸ࡓᐇ㦂࡛ࡣࠊ✀ࠎࡢ᮲௳่⃭ࢆ࠼ࡓ࠶ࡢ MEP ࡢᖜࡢኚࢆ ㄪࡿࡇ࡛ࠊ᮲௳่⃭ࡢ M1 ࡢᙳ㡪ࢆㄪࡿ conditioning-test paradigm ࡼ ࡤࢀࡿ᪉ἲࡀᗈࡃ⏝࠸ࡽࢀ࡚࠸ࡿࠋලయⓗࡣࠊM1 ࡢ༢Ⓨ TMS ࡼࡿヨ㦂 ่⃭㸦test stimulusࠊ௨ୗ TS㸧ࡼࡿ MEP ᖜࢆࠊM1 ࡢ༢Ⓨ TMS ຍ࠼࡚ ࠶ࡿ᮲௳่⃭㸦conditioning stimulusࠊ௨ୗ CS㸧ࢆຍ࠼ࡓࡢ MEP ᖜẚ㍑ࡋࠊ CS ࡛ࡢ MEP ᖜࡀ TS ࡛ࡢ MEP ᖜࡼࡾࡶࡁࡅࢀࡤࡑࡢ CS ࡣಁ㏻ᛶࡢຠ ᯝࠊᑠࡉࡅࢀࡤᢚไᛶࡢຠᯝࢆཬࡰࡋࡓุ᩿ࡍࡿ㸦ᅗ 4㸧ࠋࡇࢀࡲ࡛ࠊTS ྠࡌ M1 CS ࢆ࠼ࡿࡇ࡛ M1 ࡢ⓶㉁ෆ࡛ࡢಁ㏻ᛶ࣭ᢚไᛶࡢ⌧㇟[9, 10, 11, 12, 13]ࡀ࠶ࡿࡇࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋࡲࡓࠊᑠ⬻ࡸ๓㢌๓㔝࡞ M1 ௨እࡢ⬻㒊 M1 ࡢ⯆ዧᛶࡢㄪ⠇ᶵᵓࡸ[14, 15, 16, 17]ࠊឤぬධຊࡼࡿ M1 ᢚไ 㸦short-latency afferent inhibitionࠊ௨ୗ SAI㸧[18]ࡢᏑᅾࠊࡍ࡞ࢃࡕឤぬ㔝ࡀ M1 ཬࡰࡍᙳ㡪ࡶ᫂ࡽ࡞ࡗ࡚࠸ࡿ [19]ࠋࡑࡋ࡚ࠊࡇࡢᡭἲࢆ⏝࠸࡚ࠊ୧ഃ M1 㛫ࡢ⤖ྜࢆࡳࡿ᪉ἲࡶ㛤Ⓨࡉࢀ࡚࠸ࡿࠋࡲࡎࠊM1 㛫ࡢᢚไࢆࡳࡿࡶࡢࡋ࡚ࠊ 6㹼7 ms ௨ୖࡢ₯࡛ぢࡽࢀࡿ⬻༙⌫㐠ື㔝㛫ᢚไ㸦interhemispheric inhibitionࠊ ௨ୗ IHI㸧ࡀ࠶ࡾ[20]ࠊ㏫ M1 㛫ࡢಁ㏻ࢆࡳࡿࡶࡢࡋ࡚ࠊ4㹼5 ms ࡢ₯࡛ぢ ࡽࢀࡿ⬻༙⌫㐠ື㔝㛫ಁ㏻㸦interhemispheric facilitationࠊ௨ୗ IHF㸧ࡀ▱ࡽࢀ ࡚࠸ࡿ[21]ࠋࡇࡢ᪉ἲࢆ⏝࠸ࡿࡇࡼࡾࠊ୧ഃ㐠ື㔝㛫ࡢᢚไ࠾ࡼࡧಁ㏻ᛶࡢ ㄪ⠇ᶵ⬟ࡀẚ㍑ⓗ⡆༢ㄪࡿࡇࡀ࡛ࡁࡿࡓࡵࠊᮏ◊✲࡛ࡣࡇࢀࡽࡢ᪉ἲࢆ 9 ⏝࠸ࡓࠋࡇࡢ᪉ἲࡢⅬࡣࠊM1 ⓶㉁ෆࡢㄪ⠇ᶵ⬟ࡸࡢ⓶㉁ M1 ࡢ㐃⤡ࢆㄪ ࡿ᪉ἲ㢮ఝࡢ᪉ἲࢆ⏝࠸࡚࠸ࡿࡓࡵࠊࡇࢀࡽࡢ┦స⏝ࢆㄪࡿࡇࡀ ᐜ᫆࡞Ⅼ࡛࠶ࡿࠋ ᅗ 4 Conditioning-test paradigm TS ࡢࡁࡢ MEP㸦㯮⥺㸧ẚ㍑ࡋࠊ᮲௳่⃭ࢆ࠼ࡓሙྜ MEP ࡀࡁࡃ࡞ ࡗࡓሙྜ㸦㉥⥺㸧ࡣಁ㏻ᛶࠊMEP ࡀᑠࡉࡃ࡞ࡗࡓሙྜ㸦㟷⥺㸧ࡣᢚไᛶ࡛࠶ࡿࠋ 10 ࡇࡢ࠺ࡕࠊᅇ⏝࠸ࡓ IHI ࡣࠊᕥྑ༙⌫ࡢ M1 㛫ࡢ₯ࡀ 6ࠥ12 ms ⛬ᗘ ࡛ࡳࡽࢀࡿ⬻༙⌫㐠ື㔝㛫ᢚไᶵ⬟࡛࠶ࡿ㸦ᅗ ࠊᅗ 6㸧[22]ࠋTMS ࢆ⏝࠸ࡓ IHI ࡢ ᐃࡀ⬻ᱱࢆࡋࡓᶵ⬟࡛࠶ࡿ࠸࠺ࡇ㛵ࡋ࡚ࡣࠊIHI ࡀࠊ⓶㉁ࡢᢚ ไ⣔ࢆࡉ࡞࠸㟁Ẽ่⃭࡛ࡣᢚไࡉࢀ࡞࠸ࡇ[20]ࠊ⓶㉁ୗኚࡢᝈ⪅࡛ࡣᢚไ ຠᯝࡀಖࡓࢀࡿࡇ[23]ࠊ⬻ᱱḞᦆࡢᝈ⪅࡛ࡣᢚไຠᯝࡀᾘኻࡍࡿࡇ[24]ࠊ⬨ 㧊◳⭷እ㟁ᴟࡼࡿグ㘓ࡽᢚไࡀ M1 ࡢᅾࢽ࣮ࣗࣟࣥࢆࡋ࡚࠸ࡿ᥎ᐃ ࡉࢀࡿࡇ[25]ࡀሗ࿌ࡉࢀ࡚࠾ࡾࠊ㛫᥋ⓗ࡛ࡣ࠶ࡿࡶࡢࡢ TMS ࡼࡿ IHI ࡀ⬻ ᱱᶵ⬟ࢆᫎࡍࡿドᣐ࡛࠶ࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋࡲࡓࠊ⚄⤒ᝈ࠾࠸࡚ࠊTMS ࡼࡿ IHI ࡢᢚไຠᯝࡢ㞀ᐖࡀሗ࿌ࡉࢀ࡚࠾ࡾࠊṇᖖேࡸࣃ࣮࢟ࣥࢯࣥᝈ⪅࡛ ࡢ㙾ീ㐠ື[26, 27]ࠊࢪࢫࢺࢽ[28, 29]ࠊከⓎᛶ◳[30]࡞ࡀ࠶ࡆࡽࢀࡿࠋ 11 ᅗ 5 IHI ࡢ᪉ἲ㸦ᶍᘧᅗ㸧 ྑ M1 ࡼࡿᕥ M1 ᑐࡍࡿᢚไࢆࡳࡿሙྜࠊྑ M1 ᮲௳่⃭ࢆඛ⾜ࡉࡏࠊ ᕥ M1 ヨ㦂่⃭ࢆ࠼ࠊྑᡭෆ➽ࡼࡾ㐠ືㄏⓎ㟁ࢆ ᐃࡍࡿࠋ ᅗ 6 ᖖ⪅࠾ࡅࡿ IHI A. ௦⾲ⓗ࡞ MEP ἼᙧࠋM1 ༢Ⓨ่⃭ẚࠊpaired pulse stimulation ࡛ࡣ่⃭ 㛫㝸ࡀ 6ࠊ8ࠊ10 ms ࡢࡁ MEP ᖜࡀᑠࡉࡃ࡞ࡗ࡚࠸ࡿࠋ B. ᖖ⪅ 7 ྡࡢᖹᆒ್ࠋ่⃭㛫㝸 6ࠥ12 ms ࠾࠸࡚ IHI ࢆㄆࡵࡿࠋ 12 ࡲࡓࠊTMS ࡣ conditioning-test paradigm ࡢࡳ࡛ࡣ࡞ࡃࠊࡋ࡚࠼ࡿࡇ ࡼࡗ࡚㸦⤒㢌☢Ẽ่⃭ repetitive TMSࠊ௨ୗ rTMS㸧ࠊ⬻ྍረᛶࡢኚࢆㄏ ᑟࡍࡿࡇࡶ࡛ࡁࠊ㏆ᖺὀ┠ࡉࢀ࡚࠸ࡿࠋ⚄⤒ࡣࠊ⧞ࡾ㏉ࡋ่⃭ࢆཷࡅࡿࢩ ࢼࣉࢫࡢ㛗ᮇቑᙉ㸦long-term potentiationࠊ௨ୗ LTP㸧ࡸ㛗ᮇᢚᅽ㸦long-term depressionࠊ௨ୗ LTD㸧ࡀㄏᑟࡉࢀࡿࠋࡇࢀࡣࢩࢼࣉࢫྍረᛶࡤࢀࠊᏛ⩦ࡸ グ᠈ࡢᇶ┙࡞ࡗ࡚࠸ࡿ⏕⌮ᶵ⬟࡛࠶ࡿࠋ㐠ື㔝࠾࠸࡚ࡶࡇࡢ⚄⤒ྍረᛶኚ ࡀ㐠ືࡢㄪ⠇㛵ࢃࡗ࡚࠸ࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋࡇࡢྍረᛶኚࡣࠊrTMS ࢆ ࠼ࡓᚋ㛗㛫ᣢ⥆ࡍࡿ M1 ࡢ⯆ዧᛶኚࡼࡗ᳨࡚ฟࡍࡿࡇࡀ࡛ࡁࠊ✀ࠎ ࡢ่⃭ἲࡀ㛤Ⓨࡉࢀ࡚ࡁ࡚࠸ࡿࠋ㏆ᖺࠊࢃࢀࢃࢀࡶ༢┦ᛶ 4 㐃Ⓨ⤒㢌☢ Ẽ่⃭㸦quadripulse transcranial magnetic stimulationࠊ௨ୗ QPS㸧࠸࠺᪂ࡋ࠸᪉ ἲࢆ㛤Ⓨࡋ[31, 32]ࠊᚑ᮶ࡢ᪉ἲࡼࡾᙉຊ࡛ᣢ⥆㛫ࡢ㛗࠸ຠᯝࢆㄏⓎ࡛ࡁ࡚࠸ ࡿࠋࡇ࠺ࡋࡓ rTMS ࡢᡭἲࢆ⏝࠸ࡿࡇࡼࡾࠊࣄࢺࡢ㐠ື㔝ࡢྍረᛶኚࡀ ࡢ㡿ᇦࡢࡼ࠺ᙳ㡪ࡍࡿࡶㄪࡿࡇࡀ࡛ࡁࡿࠋࡲࡓࠊྍረᛶኚࢆ㉳ ࡇࡍࡇࡼࡾ⚄⤒ᝈࡢ⒪ࡶᛂ⏝ࡍࡿࡇࡀヨࡳࡽࢀ࡚࠸ࡿࠋ 13 3. ᮏ◊✲ࡢᐇ㦂ᵓᡂ ௨ୖࡢࡼ࠺ࠊࣄࢺࡢ⬻ᱱࢆࡋࡓ୧ഃ㐠ື㔝㛫ࡢᶵ⬟ㄪ⠇ࡣ㔜せ࡛࠶ࡾࠊ TMS ࡼࡿᡭἲࡣࡇࢀࢆゎ᫂ࡍࡿ࠶ࡓࡗ࡚᭷ຠ࡛࠶ࡿ⪃࠼ࡽࢀࡿࠋࡑࡇ࡛ࠊ ᮏ◊✲࡛ࡣࡇࡢⅬࡘ࠸࡚ࠊከゅⓗ᳨ウࡍࡿࡓࡵࠊ 1. ⚄⤒ኚᛶᝈ࠾ࡅࡿ㐠ື㔝㛫ᢚไᶵ⬟ࡢ␗ᖖࢆ TMS ࢆ⏝࠸᳨࡚ฟࡋࠊ デ᩿ࡸែᶵᗎࢆゎ᫂ࡍࡿ 2. 㐠ື㔝㛫ᢚไᶵ⬟ࡢ㐠ື㔝ᢚไᶵ⬟ࡢࣃ࣓࣮ࣛࢱ࣮ࡢ┦స⏝ ࡘ࠸᳨࡚ウࡋࠊࡑࡢᶵᗎࢆゎ᫂ࡍࡿ 3. 㐠ື㔝ࡢ㛗ᮇຠᯝㄏᑟࡢᑐഃࡢᙳ㡪⬻ᱱᶵ⬟ࡢ㛵ࢃࡾࢆㄪࡿ ࡇ࡛ࠊࣜࣁࣅࣜࢸ࣮ࢩࣙࣥ࡞ࡢᛂ⏝࠾ࡅࡿ⬻ᱱࡢᙺࢆゎ᫂ࡍࡿ ࡢ 3 Ⅼࢆ᫂ࡽࡍࡿࡇࢆ┠ⓗࡋࡓࠋ ࡲࡎᮏ◊✲ࡢ➨ 1 ❶ࡋ࡚ࠕ㍍ᗘㄆ▱ᶵ⬟㞀ᐖ࠾ࡅࡿ⬻༙⌫㐠ື㔝㛫ᢚ ไࡢῶᑡࠖ࠸࠺ࢸ࣮࣐࡛ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋ௦⾲ⓗ࡞⚄⤒ᝈࡢࡦࡘ࡛࠶ ࡿ AD ࡛ࡣࠊMRI ࡛ࡢᙧែᏛⓗ࡞␗ᖖ[33]ࡔࡅ࡛࡞ࡃࠊfMRI ࡛ࡢ connectivity ࡸ ⬻Ἴ࡛ࡢ coherence ࡞⬻ᱱ࡛ࡢᶵ⬟␗ᖖࡀ♧၀ࡉࢀ࡚࠾ࡾࠊ㍍ᗘㄆ▱ᶵ⬟㞀ᐖ 㸦mild cognitive impairmentࠊ௨ୗ MCI㸧࡛ࡶྠᵝ࡛࠶ࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋࡇࢀ ࡽࡢᝈ࠾࠸࡚ࠊ㐠ືᶵ⬟ࡀὀ┠ࡉࢀࡿࡇࡣ࠶ࡲࡾ࡞࠸ࡀࠊࡇࢀࡽࡢᝈ⪅ 14 ࠾࠸࡚㐠ືᶵ⬟㛵㐃ࡋࡓ functional MRI ࡛ࡢ␗ᖖࡢሗ࿌ࡶ࠶ࡾࠊ㧗ḟᶵ⬟ 㝈ᒁࡋ࡞࠸␗ᖖࡀ♧၀ࡉࢀ࡚࠸ࡿ[34]ࠋࡉࡽㄆ▱ᝈ⪅࡛ࡣࠊ୧ഃ M1 㛫ࡢ㐃 ⤡⥺⥔ࡀ࠶ࡿࡉࢀࡿ⬻ᱱᖿ㒊࠾࠸࡚ⴎ⦰ࡀࡳࡽࢀࡿࡢሗ࿌ࡶ࠶ࡾ[35]ࠊㄆ ▱ᶵ⬟㞀ᐖᝈ⪅࠾࠸࡚⬻ᱱࢆࡋࡓ㐠ືᶵ⬟ㄪ⠇ࢆ᳨ウࡍࡿࡇࡣࠊᝈᴫ ᛕࡸែᶵᗎࢆᗈࡃᤊ࠼ࡿୖ࡛㔜せ⪃࠼ࡽࢀࡓࠋࡑࡇ࡛ࠊᮏ◊✲࡛ࡣࡲࡎࠊ ⮫ᗋⓗࡣ㐠ືᶵ⬟␗ᖖࢆ♧ࡋ࡚࠸࡞࠸ MCI ᝈ⪅࠾࠸࡚ࠊTMS ࡼࡿ IHI ࡀ ␗ᖖ࡛࠶ࡿࢆ᳨ウࡋࠊ⬻ᱱᶵ⬟ࡘ࠸࡚ゎ᫂ࡍࡿࡇࢆ┠ⓗࡋࡓࠋࡲࡓࠊ ูࡢᢚไᶵ⬟࡛࠶ࡿ SAI ࡣ AD ࡛㞀ᐖࡉࢀ࡚࠸ࡿࡇࡀ▱ࡽࢀ࡚࠾ࡾࠊMCI ࠾࠸࡚ࡶ␗ᖖ࡛࠶ࡿࢆ᳨ウࡋࠊ㐠ື㔝ᑐࡍࡿ⓶㉁㛫ᢚไ⣔ࡘ࠸࡚ゎ᫂ࡍ ࡿࡇࡶ┠ⓗࡋࡓࠋ ḟ➨ 2 ❶ࡋ࡚ࠕ⬻༙⌫㐠ື㔝㛫ᢚไឤぬධຊࡼࡿ㐠ື㔝ᢚไࡢ┦ స⏝ࡑࡢ่⃭ᙉᗘ౫Ꮡᛶࠖ࠸࠺ࢸ࣮࣐࡛ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋSAI ࡣឤぬ㔝 㐠ື㔝ࡢ㐃㛵ࢆ♧ࡍࡶࡢ࡛࠶ࡾࠊࡇࢀࡲ࡛ࡢ⸆⌮Ꮫⓗ࡞᳨ウࡽࢥࣜࣥసື ᛶࡢᶵᗎࡀ⪃࠼ࡽࢀ࡚࠸ࡿ[36]ࠋࡇࢀࡲ࡛ TMS ࡛ゎ᫂ࡉࢀ࡚࠸ࡿᵝࠎ࡞ᢚไ ᛶ࣭ಁ㏻ᛶᅇ㊰ࡢ㛫ࡣࠊ┦స⏝ࡀࡳࡽࢀࡿࡶࡢࡀከᩘሗ࿌ࡉࢀ࡚࠸ࡿ[37]ࠋ ࠼ࡤࠊIHI ࡀᏑᅾࡍࡿ▷₯⓶㉁ෆᢚไ㸦short-interval intracortical inhibitionࠊ ௨ୗ SICI㸧ࡀῶᑡࡋࠊ㛗₯⓶㉁ෆᢚไ㸦long-interval intracortical inhibitionࠊ௨ 15 ୗ LICI㸧ࡀᏑᅾࡍࡿ IHI ࡀῶᑡࡍࡿࡇࡸ[38]ࠊSICI SAI ࡢ┦ᢚไ[39]ࠊ LICI SAI ࡢ┦ᢚไ[40]ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋࡇࡢࡼ࠺ࣄࢺࡢ⬻ෆࡣከࡃ ࡢ✀㢮ࡢᢚไᛶᅾࢽ࣮ࣗࣟࣥࡀᏑᅾࡋ[41]ࠊᢚไᶵ⬟㛫ࡢ┦స⏝ࡶ㔜せ࡞ᙺ ࢆᯝࡓࡋ࡚࠸ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋࡇࢀࡲ࡛ IHI SAI ࡢ┦స⏝ࡘ࠸ ࡚ࡣሗ࿌ࡀ࡞ࡗࡓࡓࡵࠊࡇࢀࡽࡢ┦స⏝ࡘ࠸࡚ࡼࡾヲ⣽ᢏ⾡ⓗ࡞᳨ウ ࢆ࠾ࡇ࡞࠺ᚲせࡀ࠶ࡿ⪃࠼ࠊࡇࡢᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋIHI SAI ࡣ୧⪅ࡶ 㒊ࡢ⓶㉁ࡽ M1 ⓶㉁ࡢㄪ⠇ᶵ⬟ࢆ᳨ฟࡍࡿຠᯝ࡛࠶ࡾࠊ୧⪅ࡢ┦స⏝ࢆ ᳨ウࡍࡿࡇ࡛⬻ෆ࠾ࡅࡿᢚไᶵ⬟ࡢㄪᩚᶵᵓࡘ࠸࡚ゎ᫂ࡍࡿࡇࢆ┠ⓗ ࡋࡓࠋ ᭱ᚋᮏ◊✲ࡢ➨ 3 ❶࡛ࡣࠊࠕ୍ḟ㐠ື㔝༢┦ᛶ 4 㐃Ⓨ⤒㢌☢Ẽ่⃭ 㸦QPS㸧ࡼࡿᑐഃ୍ḟ㐠ື㔝ࡢ㛗ᮇຠᯝㄏᑟ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢᙳ 㡪ࠖ࠸࠺ࢸ࣮࣐࡛ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋ ㏆ᖺࠊ⬻༞୰ᝈ⪅࠾࠸࡚ rTMS ࡞ࡼࡿ㠀くⓗ⬻่⃭ἲࡢࣜࣁࣅࣜࢸ࣮ ࢩࣙࣥࡢᛂ⏝ࡀὀ┠ࡉࢀ࡚࠸ࡿࠋ⬻᱾ሰ࡛ࡣ㞀ᐖഃࡽᖖഃࡢ IHI ࡀ␗ᖖ ࡛࠶ࡿࡓࡵ[42]ࠊᖖഃࡽ㞀ᐖഃࡢ⬻ࡢᢚไࡢࡳࡀ┦ᑐⓗᙉࡃ࡞ࡾࠊ㞀ᐖ ഃࡢᶵ⬟ᅇࢆ㜼ᐖࡋ࡚࠸ࡿࡢ࡛ࡣ࡞࠸࠸࠺༙⌫㛫ᑐ❧ࣔࢹࣝࡀᥦၐࡉࢀ ࡚࠸ࡿࠋࡇࡢࡇࡽࠊᖖഃ࡛ࡣ⬻άືࢆᢚไࡍࡿ᪉ྥࠊ㞀ᐖഃ࡛ࡣ⬻άື 16 ࢆάᛶࡍࡿ᪉ྥ rTMS ࢆ࠼ࡿ᪉ἲࡀࣜࣁࣅࣜࢸ࣮ࢩࣙࣥࡋ࡚⌧ᅾヨࡳ ࡽࢀ࡚࠸ࡿࡀࠊࡲࡔࡑࡢ᪉ἲࡀ☜❧ࡉࢀ࡚࠸ࡿࡣ࠸࠼࡞࠸[43]ࠋࡲࡓࠊᐇ㝿 ࡣࠊrTMS ࡞ࡢ㠀くⓗ⬻่⃭ἲ IHI ࡞ࡢ༙⌫㛫ㄪ⠇ࡢ㛵ಀࡘ࠸࡚ࡣࠊ ࡇࢀࡲ࡛࠶ࡲࡾ᳨ウࡉࢀ࡚࠾ࡽࡎࠊ⒪ࡢᛂ⏝ࡀ⪃࠼ࡽࢀ࡚࠸ࡿࡶࢃ ࡽࡎࠊࡑࡢ⌮ㄽⓗᇶ┙ࡣ༑ศ࡛࠶ࡿࠋ⚄⤒ྍረᛶኚࡢᑐഃࡢᙳ㡪ࡀࠊᚑ ᮶ࡢ୧ഃ M1 㛫ࡢᢚไࢆࡋࡓ⯆ዧࣂࣛࣥࢫࡢኚ࠸࠺௬ㄝࡢࡳ࡛ㄝ᫂ࡍࡿ ࡇࡶၥࡀṧࡿࠋࡑࡇ࡛ᮏ◊✲࡛ࡣࠊ⬻ྍረᛶㄏᑟ⬻༙⌫㐠ື㔝㛫ㄪ ⠇ࡢᙳ㡪࠸࠺Ⅼࡘ࠸࡚ࠊࡇࢀࡲ࡛ὀ┠ࡉࢀ࡚࠸ࡓᢚไᶵ⬟ࡔࡅ࡛࡞ ࡃࠊಁ㏻ᶵ⬟ࡶ↔Ⅼࢆ࠶࡚ࠊヲ⣽᳨ウࡋࡓࠋᐇ㝿ࡢᝈ⪅࠾࠸࡚ࡣࠊኚ 㒊ࡸ⛬ᗘࠊᶵ⬟㞀ᐖࡢ⛬ᗘ࡞ࡢಶேᕪࡀࡁ࠸ࡓࡵࠊࡲࡎࡣᖖே࠾࠸ ࡚◊✲ࢆ࠾ࡇ࡞࠸ࠊࡑࡢᚋࡢᝈ⪅ࡢᛂ⏝ࡢᇶ┙ࢆ┠ᣦࡍࡇࡋࡓࠋ 17 ࠙➨ 1 ❶ࠚ ㍍ᗘㄆ▱ᶵ⬟㞀ᐖ࠾ࡅࡿ⬻༙⌫㐠ື㔝㛫ᢚไࡢῶᑡ Tsutsumi R, et al. Reduced interhemispheric inhibition in mild cognitive impairment. Exp Brain Res 218: 21–26, 2012. [44] 18 㹙┠ⓗ㹛 MCI ࡣࠊṇᖖຍ㱋 AD ࢆࡣࡌࡵࡍࡿㄆ▱ࡢ㛫ࡢ⛣⾜≧ែ࡛࠶ࡿ⪃࠼ ࡽࢀ࡚࠸ࡿ[45, 46]ࠋ㏆ᖺࡢ voxel-based morphometry ࡸ diffusion tensor imaging ࡞ ࡢ᪂ࡋ࠸ MRI ᢏ⾡ࢆ⏝࠸ࡓ◊✲࡛ࠊMCI ࡸ AD ᝈ⪅࠾ࡅࡿ⬻ᱱࢆྵࡴⓑ㉁ ࡢኚࡀ♧ࡉࢀ࡚࠸ࡿ[33]ࠋ⌮Ꮫⓗ࡞◊✲࡛ࡶ AD ᝈ⪅࠾ࡅࡿ⬻ᱱࡢⴎ⦰ࡀ ࡳࡽࢀ࡚࠾ࡾࠊ༙⌫㛫ࡢ⤖ྜࡀ㉳ࡁࡿྍ⬟ᛶࡀ♧၀ࡉࢀ࡚࠸ࡿ[47]ࠋࡋࡋ ࡞ࡀࡽࠊMCI ࡸ AD ࠾ࡅࡿ⬻ᱱࡢⴎ⦰ࡀࠊࡢࡼ࠺࡞ᶵ⬟ⓗ࡞ኚࢆᘬࡁ㉳ ࡇࡍࡢࡣࡲࡔ࡛᫂࠶ࡿࠋᡃࠎࡣࠊࡇࢀࡽࡢᝈ࠾࠸࡚ࡣࠊ⓶㉁̾⓶㉁㛫ࡢ 㐃⤡ࡀ㞀ᐖࡉࢀ࡚࠸ࡿࡢ࡛ࡣ࡞࠸⪃࠼ࠊࡇࡢ◊✲࠾࠸࡚ MCI ᝈ⪅ࢆᑐ㇟ ࠊTMS ࢆ⏝࠸࡚⓶㉁̾⓶㉁㛫ࡢ㐃⤡ࢆホ౯ࡍࡿࡇࢆ┠ᣦࡋࡓࠋ TMS ࡣࠊ㠀くⓗࣄࢺࡢ⬻ࢆ่⃭࡛ࡁࡿ᪉ἲ࡛࠶ࡾࠊ⓶㉁ࡢ⯆ዧᛶࢆホ౯ ࡍࡿ᪉ἲࡋ࡚ AD ᝈ⪅ࡶᛂ⏝ࡉࢀ࡚࠸ࡿ[48, 49]ࠋ≉ࠊSAI [18]ࡣࠊAD ࡛ ῶᑡࡍࡿሗ࿌ࡉࢀ࡚࠸ࡿ[36]ࠋࡋࡋ࡞ࡀࡽࠊ୧ഃ M1 㛫ࡢ IHI ࡘ࠸࡚ࡣࡇ ࢀࡲ࡛ㄪࡽࢀ࡚࠸࡞࠸ࠋⓎ่⃭ࡼࡿ TMS ἲࢆ⏝࠸ࠊ୍ഃ༙⌫ࡢ TMS ࡼࡿ CS ࢆ 10 ms ⛬ᗘࡢ่⃭㛫㛫㝸㸦interstimulus intervalࠊ௨ୗ ISI㸧࡛ᑐഃ༙⌫ ࡢ TMS ๓࠼ࡿࠊMEP ࡀᢚไࡉࢀࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿ[20]ࠋࡇࡢᢚไࡣࠊ CS ഃࡢ M1 ࡽ⬻ᱱࢆࡋࡓಁ㏻ᛶ⥺⥔ࡼࡾάᛶࡉࢀࡓࠊTS ഃࡢ M1 ⓶㉁ ෆࡢᢚไ⣔ࡼࡾ⏕ࡌࡿ⪃࠼ࡽࢀ࡚࠸ࡿ[50]ࠋ 19 ࡇࡢ◊✲࡛ࡣࠊMCI ᝈ⪅࠾ࡅࡿ⬻ᱱᶵ⬟ࡘ࠸࡚ IHI ࢆᣦᶆࡋ࡚ホ౯ࡋ ࡓࠋࡲࡓࠊྠࡢホ౯᪉ἲࡋ࡚ࠊឤぬ㔝 M1 ࡢ⓶㉁Ѹ⓶㉁㛫㐃⤡ࢆ᥎ᐃ ࡍࡿࡶࡢࡋ࡚ SAI ࢆࠊM1 ࡢ⓶㉁ෆᶵ⬟ࢆ᥎ᐃࡍࡿࡶࡢࡋ࡚ SICIࠊ⓶㉁ෆಁ ㏻㸦intracortical facilitationࠊ௨ୗ ICF㸧ࡶྠ ᐃࡋࡓ[10]ࠋ 20 㹙᪉ἲ㹛 ᑐ㇟ 12 ྡࡢグ᠈㞀ᐖࢆక࠺ MCI ᝈ⪅ 16 ྡࡢᖖ㧗㱋⪅ࢆᑐ㇟ࡋࡓࠋᑐ㇟⪅ ࡣဨྑࡁ࡛࠶ࡗࡓࠋMCI ᝈ⪅ࡣᮾிᏛ་Ꮫ㒊㝃ᒓ㝔⚄⤒ෆ⛉ࠊ㜰ᕷ ❧Ꮫ་Ꮫ㒊㝃ᒓ㝔⚄⤒ෆ⛉ࡢཷデ⪅ࡽᢳฟࡋࡓࠋMCI ࡢデ᩿ࡣࠊ⚄⤒ෆ ⛉ᑓ㛛་ࡼࡗ࡚ࠊデ᩿ᇶ‽ἢࡗ࡚࠾ࡇ࡞ࢃࢀࡓ[45]ࠋᖹᆒᖺ㱋ࡣ MCI ᝈ⪅ 㸦ዪᛶ 7 ྡࠊ⏨ᛶ 5 ྡ㸧࡛ 72.3s9.3 ṓ㸦ᖹᆒsSDࠊ௨ୗྠᵝ㸧ࠊᖖ⪅㸦ዪᛶ 11 ྡࠊ⏨ᛶ 5 ྡ㸧࡛ 68.1s4.9 ṓ࡛࠶ࡗࡓࠋ࡚ࡢ MCI ᝈ⪅ࡣグ᠈㞀ᐖࢆッ࠼ ࡚࠾ࡾࠊ᳨ᰝࡢᖹᆒࡢ MMSE ࢫࢥ[51]ࡣ 25.3s2.4㸦21ࠥ29 ࡢ⠊ᅖ㸧࡛࠶ࡗ ࡓࠋᖹᆒࡢ⨯ᮇ㛫ࡣ 3.3s1.8 ᖺ㸦1ࠥ6 ᖺࡢ⠊ᅖ㸧࡛࠶ࡗࡓࠋ࡚ࡢᝈ⪅࡛ MRI ࡼࡿᾏ㤿ࡢⴎ⦰ࡀࡳࡽࢀࡓࡀࠊࡇࢀࡣᮏ◊✲ࡣ↓㛵ಀࡢᨺᑕ⥺⛉ᑓ㛛་ ࡼࡗ࡚デ᩿ࡉࢀࡓࠋࡢ⏬ീᡤぢࡋ࡚ࡣࠊ12 ྡࡢ MCI ᝈ⪅ࡢ࠺ࡕࠊ7 ྡࡣ PIB-PET ᳨ᰝࢆཷࡅ࡚࠾ࡾࠊဨࡀ␗ᖖ࡞࣑ࣟࢻ✚ࢆㄆࡵࡓ[52]ࠋࡲࡓࠊ ࡢ 5 ྡࡣ IMP-SPECT ᳨ᰝࢆཷࡅ࡚࠾ࡾࠊဨࡀഃ㢌㢌㡬ⴥ࠾ࡅࡿ⾑ὶపୗ ࢆㄆࡵࡓࠋࡇࢀࡽࡢ⤖ᯝࡽࠊNational Institute on Aging and Alzheimer’s Association workshop ࡢ recommendation ᚑ࠸[53]ࠊ࡚ࡢᝈ⪅ࡀ㧗ᗘ࡞࠸ࡋࡣ ୰➼ᗘࡢ MCI ࡛࠶ࡾࠊAD ⌮ࡀ⫼ᬒ࠶ࡿྍ⬟ᛶࡀ㧗࠸ุ᩿ࡋࡓࠋ12 ྡࡢ MCI ᝈ⪅ࡢ࠺ࡕ 5 ྡࡣࢻࢿ࣌ࢪࣝࢆᐃᮇⓗෆ᭹ࡋ࡚࠸ࡓࠋ 21 ࡚ࡢᑐ㇟⪅ࡶࡋࡃࡣࡑࡢㆤ⪅ࡀࡇࡢ◊✲ཧຍࡍࡿྠព᭩ࢆ᭩㠃࡛ᥦฟ ࡋࡓࠋᇶᮏⓗࡣࠊᮏேㆤ⪅ྠᖍࡢࡶྠព᭩ࢆྲྀᚓࡋࡓࡀࠊᮏேࡢุ ᩿⬟ຊࡀ༑ศ࡞ሙྜࡣࠊᐙ᪘➼ࡢㆤ⪅ࡼࡿᢎㅙࡋࡓࠋᮏ◊✲ࡣ࣊ࣝࢩ ࣥ࢟ᐉゝࡢ⌮ᣦ㔪ᇶ࡙ࡁࠊ୧Ꮫࡢ⌮ጤဨ࡛ᢎㄆࢆᚓ࡚࠾ࡇ࡞ࡗࡓࠋ グ㘓 ୧ഃࡢ➨୍⫼ഃ㦵㛫➽㸦first dorsal interosseous muscleࠊ௨ୗ FDI㸧ࡼࡾ┤ᚄ 9 mm ࡢ Ag/AgCl 㟁ᴟࢆ⏝࠸ࠊbelly-tendon ἲࡼࡾ⾲㠃➽㟁ᅗࢆグ㘓ࡋࡓࠋ⾲㠃➽㟁 ᅗࡢᛂࡣ 100ࠥ3000 Hz ࣇࣝࢱ࣮ࡉࢀࡓࣥࣉ㸦Biotop; GE Marquette Medical Systems Japan㸧ධຊࡉࢀࡓࠋࡑࡢᚋ 10 kHz ࡢࢧࣥࣉࣜࣥࢢ࿘Ἴᩘ࡚ ࢹࢪࢱࣝࡉࢀࠊࢥࣥࣆ࣮ࣗࢱ࣮ಖᏑࡋࠊᚋゎᯒࢆ࠾ࡇ࡞ࡗࡓ㸦TMS bistim tester; Medical Try System㸧ࠋ ⤒㢌☢Ẽ่⃭㸦TMS㸧 ᐇ㦂ࡢ㛫ࠊᑐ㇟⪅ࡣ᳔Ꮚᴦᗙࡾࠊ࢜ࢩࣟࢫࢥ࣮ࣉࣔࢽࢱ࣮࡛☜ㄆࡋ࡞ࡀ ࡽࠊFDI ࢆᏳ㟼≧ែಖࡘࡼ࠺ࡋࡓࠋTMS ࡢ่⃭ࡣࠊ☢Ẽ่⃭⨨ࡼࡾ༢┦ ᛶࡢ TMS ࣃࣝࢫࢆฟຊࡋࡓ㸦Magstim 200; Magstim Co.㸧ࠋྛヨ⾜㛫ࡢ㛫㝸ࡣ 8 s0.5 s タᐃࡋࡓࠋ࠶ࡽࡌࡵࠊᏳ㟼㐠ື㜈್㸦resting motor thresholdࠊ௨ୗ 22 RMT㸧ࠊ⦰㐠ື㜈್㸦active motor thresholdࠊ௨ୗ AMT㸧୰ᯡఏᑟ㛫㸦central motor conduction timeࠊ௨ୗ CMCT㸧ࢆࡑࢀࡒࢀ ᐃࡋࠊ⓶㉁⬨㧊㊰ࡢ␗ᖖࡀ࡞ ࠸ࡇࢆ☜ㄆࡋࡓࠋRMT ࡣᏳ㟼ࡋࡓ FDI ࠾࠸࡚ࠊ50ȣV ࡢᖜࡢ MEP ࡀ 10 ᅇ୰ 5 ᅇ௨ୖᚓࡽࢀࡿ᭱పࡢᶵᲔฟຊ್ࡋࠊᶵᲔࡢ᭱ฟຊ್㸦maximum stimulus outputࠊ௨ୗ MSO㸧ࡢྜ㸦%MSO㸧࡛♧ࡋࡓࠋAMT ࡣ FDI ࢆ㝶ព ⦰㸦᭱⦰ࡢ 5ࠥ10%㸧ࡋࡓࡁࠊ100ȣV ࡢᖜࡢ MEP ࡀ 10 ᅇ୰ 5 ᅇ௨ ୖᚓࡽࢀࡿ᭱పࡢᶵᲔฟຊ್ࡋࡓࠋCMCT ࡶᚑ᮶ࡢ᪉ἲ࡛ ᐃࡋࡓ[54]ࠋ ᐇ㦂 1㸸⬻༙⌫㐠ື㔝㛫ᢚไ IHI TS ࡣᕥ M1 ᑐࡋ࡚࠾ࡇ࡞࠸ࠊCS ࡣྑ M1 TS ࡼࡾ ISI 4ࠊ6ࠊ8ࠊ10ࠊ12 ms ࡑࢀࡒࢀඛ⾜ࡋ࡚࠾ࡇ࡞ࡗࡓࠋ୧᪉ࡢ่⃭ࡣ 8 ࡢᏐࢥࣝ㸦ྛࡢእᚄࡀ 9 cm㸧 ࢆ⏝࠸ࠊFDI ࡽ MEP ࢆㄏᑟࡍࡿࡢ᭱㐺࡞ሙᡤࢥࣝࢆ࠾࠸ࡓ㸦㢌㡬㒊ࡼ ࡾ⣙ 5 cm ഃ᪉㸧ࠋTS ࡢࢥࣝࡣ㢌⓶ୖࢥࣝࡀ᥋⥺᪉ྥ࡞ࡿࡼ࠺⨨ࡁࠊ ഐ▮≧⥺ࡽ 45rࡢゅᗘࢆࡘࡅࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀ๓ෆഃࡽᚋእഃὶ ࢀࡿࡼ࠺ࡋࡓࠋCS ࡢࢥࣝࡣ▮≧⥺᪉ྥ⨨ࡁࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀෆഃ ࡽእഃὶࢀࡿࡼ࠺ࡋࡓࠋTS CS ࡢ่⃭ᙉᗘࡣࠊᏳ㟼ࡢ FDI ࠾࠸࡚ࠊ ࡑࢀࡒࢀ༢Ⓨ่⃭ࢆࡋࡓ㝿ࡢ MEP ࡢ㡬Ⅼ㛫ᖜࡀᖹᆒ࡛ 0.5ࠥ1 mV ࡞ࡿࡼ࠺ タᐃࡋࡓࠋࡑࢀࡒࢀࡢ ISI ࡈ CS ࡢධࡗࡓ 8 ヨ⾜㸦5 ᮲௳8 ヨ⾜㸧ࠊ 23 TS ࡢࡳࡢ CS ࡞ࡋࡢ 16 ヨ⾜ࢆࣛࣥࢲ࣒࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 2㸸ឤぬධຊࡼࡿ㐠ື㔝ᢚไ SAI ࡇࡢᐇ㦂࡛ࡣࠊAD ࡛ῶᑡࡋ࡚࠸ࡿࡉࢀࡿ SAI [36] IHI ࢆẚ㍑ࡋࠊࡇࢀࡽ 2 ࡘࡢ⓶㉁ࡢᢚไᶵ⬟ࢆ࠶ࡽࢃࡍᣦᶆࡀ┦㛵㛵ಀ࠶ࡿ࠺ࢆㄪࡓࠋSAI ࡢ ᐃ᪉ἲࡋ࡚ࡣࠊTS ࡣᕥ M1 ࡢ TMS ࡋࠊCS ࡣᡭ㤳࠾ࡅࡿྑṇ୰⚄ ⤒่⃭ࡋࡓࠋṇ୰⚄⤒่⃭ࡣᣢ⥆㛫 0.2 ms ࡢ▴ᙧ㟁Ẽ่⃭㸦㝜ᴟࢆ㏆ഃ㸧 ࡋࠊTS ࡼࡾ 20 ms ඛ⾜ࡋ࡚࠼ࡓࠋCS ࡢ่⃭ᙉᗘࡣࠊẕᣦࡢ➽⦰ࡀࢃࡎ ࡳ࠼ࡿᙉᗘࡋࡓࠋCS ࡢධࡗࡓ 10 ヨ⾜ࠊTS ࡢࡳࡢ CS ࡞ࡋࡢ 20 ヨ⾜ࢆࣛ ࣥࢲ࣒࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 3㸸▷₯⓶㉁ෆᢚไ SICI ⓶㉁ෆಁ㏻ ICF ࡇࡢᐇ㦂࡛ࡣࠊM1 ⓶㉁ෆࡢ⯆ዧᛶࡀ␗ᖖ࠺ࢆ ᐃࡋࡓࠋMCI ᝈ⪅ 12 ྡ୰ 9 ྡࠊᑐ↷⩌ 16 ྡ୰ 13 ྡࡀࡇࡢ SICI ICF ࡢᐇ㦂ཧຍࡋࡓࠋCS TS ࡢ่⃭࣌ࡣࠊᕥ M1 ࠾࠸ࡓ୍ࡘࡢࢥࣝࡽ bistim module㸦Magstim Co.㸧 ࢆ⏝࠸࡚࠾ࡇ࡞ࡗࡓࠋCS ࡢ่⃭ᙉᗘࡣ AMT ࡢ 90%タᐃࡋࡓࠋSICI ࡛ࡣࠊCS ࡣ TS ࡢ ISI 2ࠊ3ࠊ4 ms ࡑࢀࡒࢀ๓࠼ࠊICF ࡛ࡣࠊCS ࡣ TS ࡢ ISI 8ࠊ10ࠊ15 ms ࡑࢀࡒࢀ๓࠼ࡓࠋࡑࢀࡒࢀࡢ ISI ࡈ CS ࡢධࡗࡓ 9 ヨ⾜㸦6 ᮲௳9 ヨ⾜㸧ࠊTS ࡢࡳࡢ CS ࡞ࡋࡢ 18 ヨ⾜ࢆࣛࣥࢲ࣒࠾ࡇ࡞ࡗࡓࠋ 24 ࢹ࣮ࢱゎᯒ ᖺ㱋ࠊ㌟㛗ࠊRMTࠊAMTࠊCMCTࠊྛᐇ㦂࠾ࡅࡿ TS ࡢ MEP ᖜࡘ࠸࡚ࠊ MCI ⩌ᑐ↷⩌࡛ࢫࢳ࣮ࣗࢹࣥࢺࡢ t ᳨ᐃࢆ⏝࠸࡚ẚ㍑ࡋࡓࠋMCI ⩌ࡢ୰࡛ࠊ ᖺ㱋ࠊMMSE ࢫࢥࠊ⨯ᮇ㛫ࡘ࠸࡚ࠊࢻࢿ࣌ࢪࣝෆ᭹⩌㠀ෆ᭹⩌࡛ࢫࢳ ࣮ࣗࢹࣥࢺࡢ t ᳨ᐃࢆ⏝࠸࡚ẚ㍑ࡋࡓࠋ3 ࡘࡢᐇ㦂ࡑࢀࡒࢀ࡛ࠊCS ୗࡢ MEP 㠀 CS ୗ㸦TS ࡢࡳ㸧ࡢ MEP ࡢᖹᆒ㡬Ⅼ㛫ᖜࡢẚࢆྛಶேࠊISI ࡈồࡵ ࡓࠋMCI ⩌ᑐ↷⩌࠾࠸࡚ࡇࡢ MEP ᖜẚࢆ ISI ࡈᖹᆒࡋ࡚ẚ㍑ࢆ࠾ࡇ ࡞ࡗࡓࠋ ᐇ㦂 1 ᐇ㦂 3㸸MCI ⩌ᑐ↷⩌ࡢ㛫࡛ࠊCS ࡢ MEP ᖜẚ࠼ࡿᙳ㡪ࢆẚ ㍑ࡍࡿࡓࡵࠊ2 せᅉࡼࡿ ᐃศᩓศᯒࢆᐇ⾜ࡋࡓࠋMCI ⩌ᑐ↷⩌ࢆ⩌㛫 ᅉᏊࠊISI ࢆ⩌ෆ㸦 ᐃ㸧ᅉᏊࡋࠊ⊂❧㸦ㄝ᫂㸧ኚᩘࡣ MEP ᖜẚࡋ ࡓࠋᚲせᛂࡌ࡚ Greenhouse-Geisser ࡼࡿ㠀⌫㠃ᛶࡢ⿵ṇࢆ࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 2㸸MCI ⩌ᑐ↷⩌ࡢ㛫࡛ SAI ࢆẚ㍑ࡍࡿࡓࡵࢫࢳ࣮ࣗࢹࣥࢺࡢ t ᳨ᐃࢆ ⏝࠸ࡓࠋMEP ᖜẚࡣࢻࢿ࣌ࢪࣝෆ᭹⩌㠀ෆ᭹⩌࡛ࡶྠᵝẚ㍑ࡋࡓࠋ IHI MMSE ࡶࡋࡃࡣ SAI ࡢ㛫ࡢ┦㛵ࡣ⥺ᙧᅇᖐศᯒࢆ⏝࠸࡚ゎᯒࡋࡓࠋࡇ ࡢゎᯒ࡛ࡣࠊIHI ࡢ್ࡣ ISI 10 ms ࡛ࡢ MEP ᖜẚࢆ௦⾲್ࡋࡓࠋ ⤫ィᏛⓗゎᯒࡣ PASW Statistics 18.0.0㸦IBM Corporation㸧ࢆ⏝࠸࡚࠾ࡇ࡞ࡗࡓࠋ p ್ < 0.05 ࢆ᭷ពุ᩿ࡋࡓࠋ 25 㹙⤖ᯝ㹛 ᖺ㱋ࠊ㌟㛗ࠊRMTࠊAMTࠊCMCTࠊྛᐇ㦂࠾ࡅࡿ TS ࡢ MEP ᖜࡢࡑࢀࡒ ࢀࡘ࠸࡚ࠊ2 ⩌㛫࡛᭷ពᕪࢆㄆࡵ࡞ࡗࡓ㸦⾲ 1㸧ࠋMCI ⩌ࡢ୰࡛ࡣࠊࢻࢿ࣌ ࢪࣝෆ᭹⩌㠀ෆ᭹⩌ࡢ㛫࡛ࠊᖺ㱋ࠊMMSE ࢫࢥࠊ⨯ᮇ㛫᭷ពᕪࢆㄆࡵ ࡞ࡗࡓ㸦⾲ 2㸧ࠋ ⾲ 1 2 ⩌㛫ࡢྛ✀ࣃ࣓࣮ࣛࢱ࣮ࡢẚ㍑ MCI ⩌㸦12 ྡ㸧 ᑐ↷⩌㸦16 ྡ㸧 p ᖺ㱋㸦ᖺ㸧 72.3 (9.3) 68.1 (4.9) 0.13 ㌟㛗㸦cm㸧 157.9 (6.4) 156.5 (7.6) 0.69 RMT㸦%MSO㸧 46.3 (12.5) 46.9 (7.7) 0.88 AMT㸦%MSO㸧 32.0 (7.9) 33.6 (6.6) 0.56 CMCT㸦ms㸧 6.7 (1.3) 6.8 (0.49) 0.89 MEP ᖜ ᐇ㦂 1 TS 0.87 (0.61) 0.75 (0.35) 0.52 㸦mV㸧 ᐇ㦂 1 CS 0.53 (0.27) 0.63 (0.38) 0.45 ᐇ㦂 2 TS 0.87 (0.41) 0.77 (0.36) 0.49 ᐇ㦂 3 TS 0.68 (0.35) 0.55 (0.39) 0.43 MCI ⩌ᑐ↷⩌࡛᭷ពᕪࡣㄆࡵ࡞ࡗࡓ㹙ᖹᆒ㸦SD㸧㹛ࠋRMT㸹Ᏻ㟼㐠ື㜈್ࠊ AMT㸹⦰㐠ື㜈್ࠊCMCT㸹୰ᯡఏᑟ㛫ࠊTS㸹ヨ㦂่⃭ࠊCS㸹᮲௳่⃭ࠋ ⾲ 2 MCI ᝈ⪅ࡢ⫼ᬒ ࢻࢿ࣌ࢪࣝ ࢻࢿ࣌ࢪࣝ ෆ᭹⩌㸦5 ྡ㸧 㠀ෆ᭹⩌㸦7 ྡ㸧 ᖺ㱋㸦ᖺ㸧 76.2 (3.7) 69.4 (11.3) 0.18 MMSE ࢫࢥ 25.0 (2.2) 25.4 (2.6) 0.78 ⨯ᮇ㛫㸦ᖺ㸧 4.2 (1.5) 2.6 (1.7) 0.12 p ࢻࢿ࣌ࢪࣝෆ᭹⩌㠀ෆ᭹⩌ࡢ㛫࡛᭷ពᕪࢆㄆࡵ࡞ࡗࡓ㹙ᖹᆒ㸦SD㸧㹛ࠋ 26 ᐇ㦂 1㸸IHI ᖹᆒࡢࢱ࣒ࢥ࣮ࢫ࡛ࡣࠊᑐ↷⩌ẚ㍑ࡋ࡚ MCI ⩌࡛ IHI ࡢῶᑡࢆㄆࡵࡓ[F (1,26) = 14.3, p = 0.001]ࠋISI ࡣ᭷ព࡞ຠᯝࢆㄆࡵࡓࡀ[F (4,104) = 3.8, p = 0.02]ࠊ⩌ ISI ࡢ㛫ࡢ┦స⏝᭷ព࡞ຠᯝࡣㄆࡵ࡞ࡗࡓ[F (4,104) = 1.4, p = 0.24]㸦ᅗ 7㸧ࠋMCI ⩌࠾࠸࡚ࠊࢻࢿ࣌ࢪࣝෆ᭹⩌㠀ෆ᭹⩌᭷ព࡞ᕪࡣㄆࡵ࡞ࡗࡓ[⩌ 㛫 F (1,10) = 0.005, p = 0.95; ISI F (4,40) = 0.5, p = 0.63; ⩌ISI F (4,40) = 1.1, p = 0.35]ࠋ ᅗ 7 IHI ࡢᖹᆒࢱ࣒ࢥ࣮ࢫࠋ MCI ᝈ⪅㸦㯮㸧࠾࠸࡚ᑐ↷⩌㸦ⓑ㸧ẚ㍑ࡋ࡚ IHI ࡀῶᑡࡋࡓࠋ࢚ࣛ ࣮ࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ 27 ᐇ㦂 2㸸SAI SAI ࡣࠊMCI ⩌(0.85s0.43)࠾࠸࡚ࠊᑐ↷⩌(0.50s0.25; P = 0.01)ẚ㍑ࡋ࡚ ᭷ពῶᑡࡋ࡚࠸ࡓ㸦ᅗ 8㸧ࠋMCI ⩌࠾࠸࡚ࠊࢻࢿ࣌ࢪࣝෆ᭹⩌(0.90s0.32) 㠀ෆ᭹⩌(0.82s0.52; p = 0.78)࡛ࡣ᭷ព࡞ᕪࡣㄆࡵ࡞ࡗࡓࠋ ᅗ 8 SAI ࡢ⤖ᯝࠋ ISI 20 ms ࠾ࡅࡿ MEP ᖜẚࡣࠊᑐ↷⩌ẚ࡚ MCI ⩌࡛᭷ពࡁࡗࡓࠋ ࢚࣮ࣛࣂ࣮ᶆ‽ㄗᕪࢆ♧ࡍࠋ 28 ᐇ㦂 3㸸SICI ICF MCI ⩌ᑐ↷⩌࠾࠸࡚ࠊSICI [⩌㛫 F (1,20) = 3.3, p = 0.08; ISI F (2,40) = 2.6, p = 0.09; ⩌ISI F (2,40) = 0.3, p = 0.72]ࡶ ICF [⩌㛫 F (1,20) = 0.2, p = 0.70; ISI F (2,40) = 2.4, p = 0.11; ⩌ISI F (2,40) = 0.8, p = 0.44]ࡶ᭷ពᕪࢆㄆࡵ࡞ࡗࡓ㸦ᅗ 9㸧ࠋ ᅗ 9 SICI ICF ࡢᖹᆒࢱ࣒ࢥ࣮ࢫࠋ MCI ⩌㸦㯮㸧ᑐ↷⩌㸦ⓑ㸧࠾࠸࡚᭷ពᕪࢆㄆࡵ࡞ࡗࡓࠋ࢚࣮ࣛࣂ࣮ ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ 29 MCI ᝈ⪅࠾࠸࡚ࠊIHI MMSE ࢫࢥ᭷ព࡞┦㛵ࡣぢࡽࢀ࡞ࡗࡓ(R2 = 0.002, p = 0.91, ᅗ 10A)ࠋIHI SAI ࡢ㛫ࡶࠊMCI ⩌(R2 = 0.15, p = 0.22)ࠊᑐ↷ ⩌(R2 = 0.09, p = 0.26)ࠊཧຍ⪅(R2 = 0.02, p = 0.48)ࡢ࠸ࡎࢀ࡛ࡶ᭷ព࡞┦㛵ࡣぢ ࡽࢀ࡞ࡗࡓ㸦ᅗ 10B㸧ࠋ ᅗ 10 ┦㛵㛵ಀࡢᩓᕸᅗ A. MCI ᝈ⪅ࡢ IHI MMSE ࢫࢥࡢ┦㛵࡛ࡣࠊ᭷ព࡞┦㛵ࡣㄆࡵ࡞ࡗࡓࠋ ࠊᑐ↷⩌㸦ⓑ㸧ࠊཧຍ⪅ࡢ࠸ࡎࢀ B. IHI SAI ࡢ┦㛵࡛ࡣࠊMCI ⩌㸦㯮㸧 ࡛ࡶ᭷ព࡞┦㛵ࡣㄆࡵ࡞ࡗࡓࠋ 30 㹙⪃ᐹ㹛 ᮏ◊✲࡛ࡣࠊࡲࡎ MCI ᝈ⪅࠾࠸࡚ IHI ࡀ᭷ពῶᑡࡋ࡚࠸ࡿࡇࢆ♧ࡋࡓࠋ ูࡢឤぬ㔝 M1 ࡢ㛫ࡢ⓶㉁Ѹ⓶㉁㛫⤖ྜࡢࣃ࣓࣮ࣛࢱ࣮ࢆ♧ࡍ SAI ࡶࡲࡓ MCI ᝈ⪅࠾࠸࡚ῶᑡࡋ࡚࠸ࡓࠋࡋࡋ࡞ࡀࡽࠊࡑࢀࡒࢀࡢῶᑡࡢ⛬ᗘࡣ┦㛵ࡋ࡞ ࡗࡓࠋ୍᪉ࠊM1 ෆࡢᢚไ࣭ಁ㏻ᶵ⬟ࢆ♧ࡍ SICI ICF ࡣ MCI ࡼࡾ㞀ᐖࡉ ࢀ࡚࠸࡞ࡗࡓࠋ MCI ᝈ⪅࠾ࡅࡿ IHI ࡢ␗ᖖ IHI ࡀ⬻ᱱࢆࡋࡓ⤒㊰ࡢᶵ⬟ࢆᫎࡋ࡚࠸ࡿࡓࡵࠊୖグࡢ⤖ᯝࡣ MCI ᝈ⪅ ࡛ M1 ࠾ࡅࡿ⬻༙⌫㐠ື㔝㛫ࡢ⓶㉁̾⓶㉁㛫⤖ྜࡢ㞀ᐖࢆ♧ࡋ࡚࠸ࡿ⪃࠼ ࡽࢀࡿࠋ ࡇࡢ㞀ᐖࢆᘬࡁ㉳ࡇࡋ࡚࠸ࡿ࣓࢝ࢽࢬ࣒ࡋ࡚ࠊ᭱ࡶ⪃࠼ࡽࢀࡿࡢࡣࠊ⬻ᱱ ⮬యࡀ MCI ࠾࠸࡚㞀ᐖࡉࢀ࡚࠾ࡾࠊIHI ࡢῶᑡࡣᑐഃ M1 ࡽࡢධຊࡢῶᑡ ࡼࡿ࠸࠺ࡶࡢ࡛࠶ࡿࠋከࡃࡢ MRI ࡢ◊✲࠾࠸࡚ࠊMCI ࡸ AD ᝈ⪅ࡢ⬻ᱱࡢ ᵓ㐀ኚࢆ♧ࡋ࡚࠸ࡿ[33, 55, 56]ࠋࡶ fMRI ࢆ⏝࠸ࡓ◊✲࡛ࠊグ᠈㞀ᐖࢆక ࠺ MCI ᝈ⪅࠾࠸୍࡚ḟ㐠ືឤぬ㔝㛫ࡢ⤖ྜࡀኚࡋ࡚࠸ࡿࡢሗ࿌ࡶ࠶ࡿ [57]ࠋࡇࢀࡽࡢሗ࿌ࡣ MCI ࠾࠸࡚⬻ᱱࡀ୍ḟⓗ㞀ᐖࡉࢀ࡚࠸ࡿ௬ㄝࢆᨭᣢ ࡍࡿࡶࡢ⪃࠼ࡽࢀࡓࠋ 31 ࡘ┠⪃࠼ࡽࢀࡿㄝ᫂ࡋ࡚ࡣࠊM1 ෆ࠾࠸࡚⬻ᱱ⥺⥔⤖ྜࡋ࡚࠸ࡿ ᅾࢽ࣮ࣗࣟࣥ㞀ᐖࡀ࠶ࡿ࠸࠺ࡶࡢ࡛࠶ࡿࠋࡇࢀࡽࡢᅾࢽ࣮ࣗࣟࣥࡣࠊ┤ ᥋ⓗ࠶ࡿ࠸ࡣࡢᅾࢽ࣮ࣗࣟࣥࡢᶵ⬟㞀ᐖࡼࡾḟⓗ㞀ᐖࡉࢀ࡚࠸ࡿ ྍ⬟ᛶࡀ࠶ࡿࠋ࠼ࡤࠊ2 ࡘࡢ CS ࢆ⏝࠸ࡓ TMS ࡢ◊✲࠾࠸࡚ࠊSICI 㛵㐃 ࡍࡿᅾࢽ࣮ࣗࣟࣥࡀࠊIHI 㛵㐃ࡍࡿᅾࢽ࣮ࣗࣟࣥᙳ㡪ࢆ࠼ࡓሗ࿌ࡀ࠶ ࡿ[58]ࠋᅇࡢᝈ⪅⩌࡛ࡶ SICI ࡣῶᑡࡍࡿഴྥࡀぢࡽࢀࡓࡀࠊ⤫ィᏛⓗ᭷ព ࡞ᕪ࡛ࡣ࡞ࡗࡓࠋࡇࢀࡽࡢ⤖ᯝࡽࠊ㍍ᗘࡢ SICI ␗ᖖࡢྍ⬟ᛶࡘ࠸࡚ ྰᐃࡍࡿࡇࡣࠊᑐ㇟⪅ࡢᩘࡀᑡ࡞ࡃ㍍ᗘࡢ␗ᖖࢆ᳨ฟ࡛ࡁ࡞ࡗࡓྍ⬟ᛶ ࡶ࠶ࡾࠊ࡛ࡁ࡞࠸࠸࠼ࡿࠋࡋࡋ࡞ࡀࡽࠊSICI ࡀᙉࡃ㞀ᐖࡉࢀ࡚࠸ࡓヂ࡛ࡣ ࡞ࡃࠊࡇࡢ␗ᖖࡢࡳ࡛ᅇࡳࡽࢀࡓ IHI ␗ᖖࢆㄝ࡛᫂ࡁࡿࡶࡢ࡛ࡣ࡞࠸⪃࠼ࡽ ࢀࡓࠋࡇࢀࡽࡢ㆟ㄽࡽࠊࡇࡢㄝ᫂ࡣ⤖ᯝࡢ୍㒊ࢆㄝ᫂ࡋ࠺ࡿྍ⬟ᛶࡣ࠶ࡿࡶ ࡢࡢࠊࡶࡗࡶࡽࡋ࠸ㄝ᫂ࡣ࡞ࡽ࡞࠸⪃࠼ࡽࢀࡓࠋ ୕ࡘ┠ࠊSAI ࡢῶᑡࡀ IHI ᙳ㡪ࢆཬࡰࡋࡓྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋࡋࡋ࡞ ࡀࡽࠊࡇࢀࡽ 2 ࡘࡢ␗ᖖࡢ⛬ᗘ᭷ព࡞┦㛵ࡀぢࡽࢀ࡞ࡗࡓࡇࡽࡣࠊࡇ ࡢྍ⬟ᛶࡣ⪃࠼ࡃ࠸ࠋᅇぢࡽࢀࡓ IHI ࡢῶᑡࡣ SAI ࡢῶᑡࡣ⊂❧⏕ࡌ ࡚࠸ࡿ⪃࠼ࡽࢀࡓࠋAD ᝈ⪅࡛ࢻࢿ࣌ࢪࣝࡀ SAI ࢆṇᖖࡉࡏࡓࡇࡽࠊSAI ࡣ⓶㉁ࡢࢥࣜࣥ⣔ᅇ㊰㛵㐃ࡍࡿࡶࡢ࡛࠶ࡿࡉࢀ࡚࠸ࡿ[36, 59, 60, 61]ࠋࡑࡢ ࡓࡵ IHI ࡢῶᑡࡣࢥࣜࣥ⣔ᅇ㊰ࡢ␗ᖖࡣ㛵㐃ࡀ࡞࠸ྍ⬟ᛶࡀ⪃࠼ࡽࢀࡓࠋᅇ 32 ࡢᝈ⪅࡛ࡣࠊIHI ࡶ SAI ࡶࢻࢿ࣌ࢪࣝෆ᭹ࡼࡿᙳ㡪ࡣཷࡅ࡞ࡗࡓࠋ IHI ࡢ⛬ᗘ MMSE ࢫࢥ┦㛵ࡣぢࡽࢀ࡞ࡗࡓࠋࡑࡢ⌮⏤ࡋ࡚ࡣࠊ MMSE ࢫࢥࡀ MCI ᝈ⪅࠾ࡅࡿࢃࡎ࡞ㄆ▱ᶵ⬟ࡢᕪࢆ᳨ฟ࡛ࡁ࡞ࡗࡓࡓ ࡵ⪃࠼ࡽࢀࡿࠋࡇࡢࡇࡽࠊ㏻ᖖࡢㄆ▱ᶵ⬟᳨ᰝ࡛ࡣ᳨ฟ࡛ࡁ࡞࠸ AD ⌮ࡢ᪩ᮇ᳨ฟ IHI ࡀᙺ❧ࡘྍ⬟ᛶࡀ♧၀ࡉࢀࡓࠋ TMS ࡼࡿࡢ⓶㉁⯆ዧᛶࡢホ౯ ᅇࡢ MCI ᝈ⪅࡛ࡣࠊSICI ICF ࡣ࠸ࡎࢀࡶṇᖖ࡛࠶ࡗࡓࠋࡇࢀࡲ࡛ࡢሗ࿌ ࡛ࡣࠊ᪩ᮇⓎ AD [62]ࡸ AD ㌿ࡋࡓ MCI [63]࡛ࡢ SICI ῶᑡࢆሗ࿌ࡋ࡚࠸ ࡿࡀࠊ㧗࠸ಶே㛫ࡢࡤࡽࡘࡁࡀぢࡽࢀ࡚࠸ࡓࠋICF ࡘ࠸࡚ࡣࡇࢀࡲ୍࡛ᐃࡋࡓ ぢゎࡀᚓࡽࢀ࡚࠸࡞࠸ࠋ௨๓ࡢሗ࿌࡛ࡣ SICI ࡸ ICF ࡣ AD ࡢ᪩ᮇデ᩿᭷⏝࡛ ࡣ࡞࠸⤖ㄽ࡙ࡅࡽࢀ࡚࠸ࡿ[63]ࠋᅇࡢ◊✲࡛ࡶ SICI ICF ࡣṇᖖ࡛࠶ࡗࡓ ࡀࠊSICI ࡘ࠸࡚ࡣ MCI ࡛ῶᑡࡋ࡚࠸ࡿഴྥ࠶ࡾࠊMCI ࡛ SICI ࡀ㍍ᗘῶᑡ ࡋ࡚࠸ࡿྍ⬟ᛶࡣྰᐃ࡛ࡁ࡞࠸⪃࠼ࡽࢀࡓࠋࡋࡋࠊMCI ࡸ AD ᪩ᮇ࠾࠸ ࡚⓶㉁ෆᅇ㊰࡛࠶ࡿ SICI ࡸ ICF ࡣỴᐃⓗ࡞ᙳ㡪ࡣཷࡅ࡚࠸࡞࠸⤖ㄽ࡙ࡅࡿࡇ ࡀ࡛ࡁࡓࠋ ୍᪉ SAI ࡣ AD ᝈ⪅࡛ῶᑡࡋ࡚࠸ࡿࡀࠊ௨๓ࡢㄽᩥ࠾࠸࡚ MCI ᝈ⪅࡛ SAI ࡀṇᖖ࡛࠶ࡿሗ࿌ࡉࢀ࡚࠸ࡿࡶࡢࡀ࠶ࡿ[64]ࠋࡇࡢ㐪࠸ࡣ MCI ࡢ⫼ᬒ⌮ࡢ 33 ከᵝࡉࡼࡿࡶࡢࡢྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋᅇࡢ◊✲࡛ࡣࠊ༙ศ௨ୖࡢ MCI ᝈ ⪅࠾࠸࡚ PIB-PET ᳨ᰝ࡛࣑ࣟࢻ✚ࢆ☜ㄆࡋ࡚࠾ࡾࠊᑗ᮶ AD ㌿ࡍ ࡿྜࡀ㧗࠸⪃࠼ࡽࢀࡿࠋࡑࡢࡓࡵࠊAD ⌮ࡀ⫼ᬒ࠶ࡿ MCI ᝈ⪅࡛ࡣࠊ ᪩ᮇ࡛࠶ࡗ࡚ࡶ SAI ࡀ␗ᖖ࡞ࡿࡢ࡛ࡣ࡞࠸⪃࠼ࡽࢀࡓࠋ ᮏ◊✲࠾࠸࡚ࠊ2 ࡘࡢタ࠾ࡅࡿ᳨ᰝࡀΰᅾࡋ࡚࠸ࡿࡇࡢᙳ㡪ࡘ࠸࡚ ࡣࠊࡲࡎࠊᶵᲔࡘ࠸࡚ࡣࠊ୍㒊ࡢ่⃭⨨ࡘ࠸࡚ࡣᮾிᏛࡽ㜰ᕷ❧ Ꮫᦙ㏦ࡋ࡚ྠ୍ࡢᶵᲔ࡛࠾ࡇ࡞ࡗࡓࡀࠊࡑࢀ௨እࡘ࠸࡚ࡣࠊタᐃࢆྠ୍ ࡋ࡚ᆒ୍ᛶࢆ☜ಖࡋࡓࠋࡲࡓࠊ่⃭ᙉᗘࡘ࠸࡚ࡣࠊᶵᲔࡢฟຊ್ࡢ⤯ᑐ್ ࡛ࡣ࡞ࡃࠊ⿕㦂⪅ࡈ➽㟁ᅗࡢᖜࢆᣦᶆࡋ࡚タᐃࡋ࡚࠸ࡿࡓࡵࠊᶵᲔࡢ 㐪࠸ࡢ⤖ᯝࡢᙳ㡪ࡣ↓ど࡛ࡁࡿࡶࡢ⪃࠼ࡽࢀࡓࠋࡉࡽࠊ᳨ᰝ⪅ࡣྠ୍ே ࡀ 2 タࡲࡓࡀࡗ࡚࠾ࡇ࡞ࡗࡓࡓࡵࠊࡑࢀࡼࡿࣂࢫࡣ㝖ࡋࡓࠋ⿕㦂 ⪅ࡢࣜࢡ࣮ࣝࢺࡘ࠸࡚ࡣࠊࡑࢀࡒࢀࡢ㝔࠾࠸࡚⚄⤒ෆ⛉ᑓ㛛་ࡢุ᩿࡛ እ᮶ࡽࣜࢡ࣮ࣝࢺࡋ࡚࠸ࡿࡓࡵࠊ㑅ᢥࣂࢫࡢྍ⬟ᛶࡣྰᐃ࡛ࡁ࡞࠸⪃ ࠼ࡽࢀࡓࠋ ࡲࡵ MCI ᝈ⪅࡛ࡣ⓶㉁̾⓶㉁㛫⤖ྜࡢᶵ⬟ࡀ⓶㉁ෆᶵ⬟ࡼࡾࡶᙉࡃ㞀ᐖࡉࢀ࡚࠸ 34 ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡓࠋࡘࡢ⓶㉁̾⓶㉁㛫⤖ྜᶵ⬟ࢆ࠶ࡽࢃࡍᣦᶆ࡛࠶ࡿ⪃ ࠼ࡽࢀࡿ SAI IHI ࡢ␗ᖖࢆ⤌ࡳྜࢃࡏࡿࡇ࡛ࠊAD ㌿ࡍࡿྍ⬟ᛶࡢ࠶ࡿ ᪩ᮇ MCI ᝈ⪅ࡢデ᩿᭷⏝࡛࠶ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡓࠋ௨ୖࡢ㆟ㄽࢆࡩࡲ࠼ࠊ MCI ᝈ⪅࡛ࡣ SAI ࡢᶵ⬟⊂❧ࡋ࡚ࠊ୧ഃ M1 ࢆࡘ࡞ࡄ⬻ᱱ㐃⤡ᶵ⬟ࡀ୍ḟⓗ 㞀ᐖࡉࢀ࡚࠸ࡿ⤖ㄽ࡙ࡅࡓࠋࡇࡢࡇࡽࠊ⬻ᱱࢆࡋࡓ୧ഃ M1 ࡢᢚไᶵ ᵓࡣ⚄⤒ኚᛶᝈ࠾ࡅࡿᶵ⬟ⓗ␗ᖖࡢ୍ࡘࡢᣦᶆ࡞ࡿࡇࡀ♧ࡉࢀࡓࠋ 35 ࠙➨ 2 ❶ࠚ ⬻༙⌫㐠ື㔝㛫ᢚไឤぬධຊࡼࡿ㐠ື㔝ᢚไࡢ┦స⏝ ࡑࡢ่⃭ᙉᗘ౫Ꮡᛶ Tsutsumi R, et al. Conditioning intensity dependent interaction between short-latency interhemispheric inhibition and short-latency afferent inhibition. J Neurophysiol 108: 1130–1137, 2012. [65] 36 㹙┠ⓗ㹛 ┠ⓗࢆᣢࡗࡓ㐠ືࢆ࠾ࡇ࡞࠺㝿ࠊM1 ࡣከࡃࡢධຊᅉᏊࡼࡾಟ㣭ࢆཷࡅ࡚ ࠸ࡿࠋ࠼ࡤࠊయᛶឤぬࠊどぬࠊ⫈ぬࠊᑠ⬻ࠊᇶᗏ᰾ධຊ࡞࡛࠶ࡿࠋࡇࢀࡽ ࡢධຊࡣ M1 ᑐࡋࠊ⊂❧࠶ࡿ࠸ࡣ┦ⓗస⏝ࡍࡿࠋࡇࡢ❶࡛ࡣᑐഃ M1 ࡽࡢධຊࠊឤぬ㔝ࡽࡢධຊࡢ㛵ಀὀ┠ࡋࡓࠋ ࡇࢀࡲ࡛ࡢሗ࿌࡛ࡣࠊM1 ᑐࡍࡿయᛶឤぬධຊࡣᑐഃ M1 ࡽࡢ⬻ᱱࢆࡋ ࡓධຊ㛵㐃ࡀ࠶ࡿࡇࡀ♧၀ࡉࢀ࡚࠸ࡿࠋ࠼ࡤࠊ▷㛫ࡢឤぬධຊࡢ႙ኻ ࡣ IHI ࢆῶᑡࡉࡏࡓࡾ[66]ࠊ∦㯞⑷ࡢ࠶ࡿ៏ᛶᮇࡢ⬻༞୰ᝈ⪅࡛ࡣࠊᖖഃࡢᡭ ࡢ⾲㠃㯞㓉ࡼࡾ㯞⑷ഃࡢᡭࡢ୍㐣ᛶࡢ㒊≉␗ᛶࢆకࡗࡓ㐠ືᶵ⬟ࡢᨵၿࢆ ㄆࡵࡓࡾࡍࡿ[67]࡞ࡢሗ࿌ࡀ࠶ࡿࠋࡇࢀࡽࡢ⤖ᯝࡣࠊM1 ᑐࡍࡿឤぬධຊ ⬻ᱱࡽࡢධຊࡢ㛵ಀࡢ㔜せᛶࢆ♧ࡋ࡚࠸ࡿࠋ TMS ࡼࡗ࡚ㄪࡽࢀࡿ IHI [20]ࡣࡘࡢ┦ࠊISI 10 ms ๓ᚋࡢ▷₯ IHI 㸦short-latency interhemispheric inhibitionࠊ௨ୗ SIHI㸧ࠊISI 40ࠥ50 ms ๓ᚋࡢ㛗 ₯ IHI㸦logn-latency interhemispheric inhibitionࠊ௨ୗ LIHI㸧ࡀ࠶ࡿࡇࡀ▱ࡽ ࢀ࡚࠸ࡿࠋࡇࡢࡘࡢ IHI ࡣูࡢ⚄⤒⣽⬊㞟ᅋࡼࡗ࡚㉳ࡁ࡚࠸ࡿ⪃࠼ࡽࢀ࡚ ࠸ࡿ[68, 69, 70]ࠋᡃࠎࡣࠊࡇࡢ◊✲࡛ࡣ SIHI ࢆ⏝࠸ࡓࡀࠊࡇࢀࡣ SIHI ࡀ▷㛫 ࡛స⏝ࡋࠊSAI ┤᥋ⓗ┦స⏝ࢆ㉳ࡇࡍ⪃࠼ࡓࡓࡵ࡛࠶ࡿࠋSAI ࡣᮎᲈࡢ యᛶឤぬ่⃭ࡼࡾ ISI 20 ms ๓ᚋ࡛ M1 ࢆᢚไࡍࡿࡶࡢ࡛࠶ࡿ[18]ࠋࡲࡓࠊIHI 37 SAI ௨እࡶ࠸ࡃࡘࡶ㒊ࡽࡢᢚไᛶࡢస⏝ࡀ▱ࡽࢀ࡚࠸ࡿࠋ ࡇࢀࡽᢚไᛶࡢ⚄⤒ᅇ㊰ྠኈࡢ┦స⏝ࡘ࠸࡚ࡣࠊࡇࢀࡲ࡛࠸ࡃࡘሗ࿌ ࡉࢀ࡚࠸ࡿࡶࡢࡢࠊ࠶ࡲࡾヲ⣽ࡣㄪࡽࢀ࡚࠸࡞࠸ࠋ࠼ࡤࠊSICI ࡣ SIHI ࡼࡾῶᑡࡋࠊSIHI ࡣ LICI ࡼࡾῶᑡࡍࡿ[38]ࠋ᭱㏆ࡢሗ࿌࡛ࡣࠊSICI SAI ࡢ ┦ᢚไ[39]ࡸ LICI SAI ࡢ┦ᢚไ[40]ࡶሗ࿌ࡉࢀ࡚࠸ࡿࠋ ࡇࢀࡽࡢ᪤ሗ࿌ࡽ᥎ᐃࡍࡿ SIHI SAI ࡢ㛫ࡶᢚไᛶࡢ┦స⏝ࡀ࠶ࡿ ࡢ࡛ࡣ࡞࠸ࡢ௬ㄝࡀ❧࡚ࡽࢀࡿࠋࡋࡋ࡞ࡀࡽࠊᢚไᛶຠᯝࡢ㛢ሰ࣭㣬 ࡞࡛ࡶྠࡌࡼ࠺࡞⤖ᯝࡀぢࡽࢀࡿྍ⬟ᛶࡀ࠶ࡿࠋࡑࡢࡓࡵࠊࡇࡢ◊✲࡛ࡣ SIHI SAI ࡢ┦స⏝ࡘ࠸࡚ࠊ่⃭ᙉᗘ౫Ꮡᛶࢆㄪࡿࡇࡋࠊභࡘࡢ␗࡞ࡿ ่⃭ᙉᗘࡢ⤌ࡳྜࢃࡏࢆ⏝࠸࡚ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋࡇࢀࡲ࡛ࡢሗ࿌࡛ࡣࠊIHI ᑐࡋ࡚ࡣ CS ᙉᗘࡼࡿᙳ㡪[70]ࠊSAI ᑐࡍࡿ CS ᙉᗘࡢᙳ㡪[71]ࠊSAI ᑐࡍ ࡿ TS CS ᙉᗘࡢᙳ㡪[72]ࡀ▱ࡽࢀ࡚࠸ࡿࠋࡑࡢࡓࡵࡇࡢ◊✲࠾࠸࡚ࡣࠊSIHI SAI ࡘ࠸࡚ࠊᙅ࠸ຠᯝ㣬ࡋࡓຠᯝࡢࡑࢀࡒࢀࡀᚓࡽࢀࡿ CS ᙉᗘࢆ⏝࠸ ࡚ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋ 38 㹙᪉ἲ㹛 ᑐ㇟ 11 ྡࡢྑࡁࡢᖖ⿕㦂⪅ྠពࢆᚓࡓࡢࡕᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋ⿕㦂⪅ࡣዪ ᛶ 2 ྡࠊ⏨ᛶ 9 ྡࠊᖹᆒᖺ㱋 37.5 ṓs7.8㸦SD㸧ࠊ29ࠥ49 ṓࡢ⠊ᅖ࡛࠶ࡗࡓࠋ࠸ ࡎࢀࡢ⿕㦂⪅ࡶ⚄⤒Ꮫⓗࠊ⢭⚄ⓗࠊࡑࡢࡢ་Ꮫⓗ࡞ၥ㢟ࡣ࡞ࡃࠊTMS ᑐࡍ ࡿ⚗ᚷࡶヱᙜࡋ࡞ࡗࡓࠋᮏ◊✲ࡣ࣊ࣝࢩࣥ࢟ᐉゝࡢ⌮ᣦ㔪ᇶ࡙ࡁࠊᮾ ிᏛ⌮ጤဨࡢᢎㄆࢆᚓ࡚࠾ࡇ࡞ࡗࡓࠋ グ㘓 ୧ഃ FDI ࡼࡾ┤ᚄ 9 mm ࡢ Ag/AgCl ⾲㠃㟁ᴟࢆ⏝࠸ࠊbelly-tendon ἲࡼࡾ MEP ࢆグ㘓ࡋࡓࠋ⾲㠃➽㟁ᅗࡢᛂࡣ 100ࠥ3000 Hz ࣇࣝࢱ࣮ࡉࢀࡓࣥࣉ 㸦Biotop; GE Marquette Medical Systems Japan㸧ධຊࡉࢀࡓࠋࡑࡢᚋ 10 kHz ࡢ ࢧࣥࣉࣜࣥࢢ࿘Ἴᩘ࡚ࢹࢪࢱࣝࡉࢀࠊࢥࣥࣆ࣮ࣗࢱ࣮ಖᏑࡋࠊᚋゎᯒ ࢆ࠾ࡇ࡞ࡗࡓ㸦TMS bistim tester; Medical Try System㸧ࠋ TMS ௨ୗࡢᐇ㦂ࡢ㛫ࠊ⿕㦂⪅ࡣ᳔Ꮚᴦᗙࡾࠊ࢜ࢩࣟࢫࢥ࣮ࣉࣔࢽࢱ࣮࡛☜ㄆ ࡋ࡞ࡀࡽࠊFDI ࢆᏳ㟼≧ែಖࡘࡼ࠺ࡋࡓࠋTMS ࡢ่⃭ࡣࠊ☢Ẽ่⃭⨨ࡼ ࡾ༢┦ᛶࡢ TMS ࣃࣝࢫࢆฟຊࡋࡓ㸦Magstim 200; Magstim Co.㸧ࠋྛヨ⾜㛫ࡢ㛫 39 㝸ࡣ 6s0.5 s タᐃࡋࡓࠋ࠶ࡽࡌࡵࠊᕥ༙⌫ࡢ RMT AMTࠊྑ༙⌫ࡢ RMT ࢆ ᐃࡋ࡚࠾࠸ࡓࠋRMT ࡣᏳ㟼ࡋࡓ FDI ࠾࠸࡚ࠊ50ȣV ࡢᖜࡢ MEP ࡀ 10 ᅇ୰ 5 ᅇ௨ୖᚓࡽࢀࡿ᭱పࡢᶵᲔฟຊ್ࡋࡓࠋAMT ࡣ FDI ࢆ㝶ព⦰㸦᭱ ⦰ࡢ 5ࠥ10%㸧ࡋࡓࡁࠊ100ȣV ࡢᖜࡢ MEP ࡀ 10 ᅇ୰ 5 ᅇ௨ୖᚓࡽ ࢀࡿ᭱పࡢᶵᲔฟຊ್ࡋࡓࠋ ᐇ㦂ࢹࢨࣥ ࡲࡎࠊSIHI㸦ᐇ㦂 1㸧 SAI㸦ᐇ㦂 2㸧ࡢࡑࢀࡒࢀࡘ࠸࡚ TS CS ᙉᗘࡼ ࡿᙳ㡪ࢆㄪࡓࠋࡑࡢᚋࠊ୧᪉ࡢ CS ࢆྠ࠼ࡿࡇ࡛ࠊSIHI SAI ࡢ┦ స⏝ࡘ࠸࡚ㄪࡓ㸦ᐇ㦂 3㸧 ࠋ␗࡞ࡿ่⃭ᙉᗘࡢ CS ࢆ࠼ࠊࡑࢀࡒࢀࡢ CS ࡢ࠼ࡓຠᯝࡘ࠸࡚ẚ㍑᳨ウࡋࡓ㸦ᅗ 11㸧ࠋ ᐇ㦂 1㸸SIHI 11 ྡࡢ⿕㦂⪅ࡀࡇࡢᐇ㦂ཧຍࡋࡓࠋTS ࡣᕥ M1ࠊCS ࡣᑐഃ༙⌫ࡽࡢ ᮲௳่⃭㸦contralateral conditioning stimulusࠊ௨ୗ CCS㸧ࡋ࡚ࠊྑ M1 TS ࡼ ࡾ 10 ms ඛ⾜ࡋ࡚࠼ࡓࠋ୧᪉ࡢ่⃭ࡣ 8 ࡢᏐࢥࣝ㸦ྛࡢእᚄࡀ 9 cm㸧 ࢆ⏝࠸ࠊFDI ࡽ MEP ࢆㄏᑟࡍࡿࡢ᭱㐺࡞ሙᡤࢥࣝࢆ⨨࠸ࡓ㸦㢌㡬㒊ࡼ ࡾ⣙ 5 cm ഃ᪉㸧ࠋTS ࡢࢥࣝࡣ㢌⓶ୖࢥࣝࡀ᥋⥺᪉ྥ࡞ࡿࡼ࠺⨨ࡁࠊ 40 ഐ▮≧⥺ࡽ 45rࡢゅᗘࢆࡘࡅࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀ๓ෆഃࡽᚋእഃὶ ࢀࡿࡼ࠺ࡋࡓࠋCS ࡢࢥࣝࡣ▮≧⥺᪉ྥ⨨ࡁࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀෆഃ ࡽእഃὶࢀࡿࡼ࠺ࡋࡓࠋTS ࡢ่⃭ᙉᗘࡣࠊᏳ㟼ࡢ FDI ࠾࠸࡚ࠊࡑࢀ ࡒࢀ༢Ⓨ่⃭ࢆࡋࡓ㝿ࡢ MEP ࡢ㡬Ⅼ㛫ᖜࡀ 0.6 mV㸦TS0.6mV㸧ࡶࡋࡃࡣ 0.3 ᅗ 11 ᐇ㦂ࢹࢨࣥྛᐇ㦂ࡢࣃ࣓࣮ࣛࢱ࣮᮲௳ࠋ TS ࡢ่⃭ᙉᗘࡣᕥ M1 ࠾ࡅࡿ TMS ࡛ㄏⓎࡉࢀࡿ MEP ࡢᖹᆒᖜ࡛࠶ࡽࢃࡉ ࢀ࡚࠸ࡿࠋ ᑐഃࡢ CS ࡢ่⃭ᙉᗘ㸦CCS㸧ࡣྑ M1 ࡢ RMT ࢆᇶ‽ࡋࡓಸ⋡ࠊྑṇ୰⚄ ⤒ࡢ่⃭ᙉᗘ㸦MNS㸧ࡣ่⃭ᑐࡍࡿឤぬ㜈್ ST ࢆᇶ‽ࡋࡓಸ⋡࡛࠶ࡽࢃ ࡉࢀ࡚࠸ࡿࠋ 41 mV㸦TS0.3mV㸧࡞ࡿࡼ࠺ࡋࡓࠋCS ࡢ่⃭ᙉᗘࡣࠊྑ M1 ࡢ RMT ࢆᇶ‽ ࡋ࡚ 1 ಸ㸦CCS1㸧ࠊ1.2 ಸ㸦CCS1.2㸧ࠊ1.4 ಸ㸦CCS1.4㸧ࠊ1.6 ಸ㸦CCS1.6㸧ࡢ 4 ✀㢮ࡋࡓࠋ ᐇ㦂 2㸸SAI 11 ྡ୰ 7 ྡࡀᐇ㦂 2 ཧຍࡋࡓࠋ⿕㦂⪅ࡣዪᛶ 1 ྡࠊ⏨ᛶ 6 ྡࠊᖹᆒᖺ㱋 37.3 ṓs7.3㸦SD㸧ࠊ29ࠥ46 ṓࡢ⠊ᅖ࡛࠶ࡗࡓࠋTS ࡣᕥ M1 ᑐࡍࡿ TMS ࡛࠶ࡾࠊ CS ࡣᡭ㤳࠾ࡅࡿྑṇ୰⚄⤒่⃭㸦median nerve stimulationࠊ௨ୗ MNS㸧࡛࠶ ࡗࡓࠋMNS ࡣᣢ⥆㛫 0.2 ms ࡢ▴ᙧ㟁Ẽ่⃭㸦㝜ᴟࢆ㏆ഃ㸧ࡋ TS ࡼࡾඛ ⾜ࡋ࡚࠼ࡓࠋCS TS ࡢ่⃭㛫㝸 ISI ࡣࠊ2 ms ้ࡳ࡛ᐃࡵࡓ SAI ࡢ್ࡀ᭱ ࡞ࡿ ISI ࢆಶேࡈタᐃࡋࡓࠋ᭱㐺࡞ ISI ࡣಶேࡼࡾ 18ࠥ22 ms ࡢ⠊ᅖ࡛ ࠶ࡾࠊᖹᆒࡣ 19.8 mss1.1㸦SD㸧࡛࠶ࡗࡓࠋMNS ᑐࡍࡿឤぬ㜈್㸦sensory thresholdࠊ௨ୗ ST㸧ࢆ๓ ᐃࡋࡓࠋTS ࡢ่⃭ᙉᗘࡣᐇ㦂 1 ྠᵝ TS0.6mV ࡶࡋࡃࡣ TS0.3mV ࡋࠊCS ࡢ่⃭ᙉᗘࡣࠊྑṇ୰⚄⤒ࡢ ST ࢆᇶ‽ࡋ࡚ 1.5 ಸ㸦MNS1.5㸧ࠊ3 ಸ㸦MNS3㸧ࠊ4.5 ಸ㸦MNS4.5㸧ࡢ 3 ✀㢮ࡋࡓࠋ 42 ᐇ㦂 3㸸SIHI SAI ࡢ㛫ࡢ┦స⏝ 11 ྡࡢ⿕㦂⪅ࡀࡇࡢᐇ㦂ཧຍࡋࡓࠋTS CS ࡣ࠸ࡎࢀࡶᐇ㦂 1 ᐇ㦂 2 ྠᵝタᐃࡋࡓࠋTS ࡢ่⃭ᙉᗘࡣࡍ࡚ TS0.6mV ࡋࡓࠋCS ࡢ่⃭ᙉᗘ ࡣ 6 ✀㢮ࡢ␗࡞ࡗࡓ่⃭ᙉᗘࡢ⤌ࡳྜࢃࡏࢆ⏝࠸ࡓࠋࡑࢀࡒࢀ CCS MNS ࡢ ⤌ࡳྜࢃࡏࡼࡾࠊCCS1+MNS1.5ࠊCCS1.2+MNS1.5ࠊCCS1.4+MNS1.5ࠊ CCS1+MNS3ࠊCCS1.2+MNS3ࠊCCS1.4+MNS3 ࡋࡓ㸦ᅗ 11㸧ࠋࡑࢀࡒࢀࡢ่⃭ ᮲௳ࡢ⤌ࡳྜࢃࡏࡘ࠸࡚ࠊ8 ࡘࡢ␗࡞ࡿ configuration ่࡛⃭ࢆ࠾ࡇ࡞ࡗࡓ㸦⾲ 3㸧ࠋConfiguration 3A-3D ࡛ࡣ TS0.6mV ࡛ࡢ SIHI SAI ࡢᙳ㡪ࢆㄪࡓࠋ Configuration 3E-3H ࡛ࡣࠊMEP ࡢᖜࢆᑠࡉࡃࡑࢁ࠼ࡿࡓࡵࠊTS ࡢ่⃭ᙉᗘࢆ ᙅࡵ่࡚⃭ࢆ࠾ࡇ࡞ࡗࡓࠋConfiguration 3E 3F ࡛ࡣࠊTS ࡢ่⃭ᙉᗘࢆ configuration 3C ࡛ MNS ࡢ᮲௳่⃭࡛ࡢ MEP ᖜྠࡌ࡞ࡿࡼ࠺ࡑࢁ࠼ࡓ 㸦0.6mVMNS㸧ࠋConfiguration 3G 3H ࡛ࡣࠊTS ࡢ่⃭ᙉᗘࢆ configuration 3B ࡛ CCS ࡢ᮲௳่⃭࡛ࡢ MEP ᖜྠࡌ࡞ࡿࡼ࠺ࡑࢁ࠼ࡓ㸦0.6mVCCS㸧ࠋ Configuration 3A-3Dࠊ3E 3Fࠊ3G 3Hࠊࡣ TS ࡢ่⃭ᙉᗘࡀ␗࡞ࡿࡓࡵࠊࡑࢀ ࡒࢀูࡢࢭࢵࢩࣙࣥࡋ࡚ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋ 43 ࢹ࣮ࢱゎᯒ ྛᐇ㦂࠾࠸࡚ࠊCS ࡢධࡗࡓ 15 ヨ⾜ࠊTS ࡢࡳࡢ CS ࡞ࡋࡢ 15 ヨ⾜ࢆࣛࣥ ࢲ࣒࠾ࡇ࡞ࡗࡓࠋCS ୗࡢ MEP 㠀 CS ୗ㸦TS ࡢࡳ㸧ࡢ MEP ࡢᖹᆒ㡬Ⅼ㛫 ᖜࡢẚ㸦MEP ᖜẚ㸧ࢆྛಶேࠊ᮲௳ࡈồࡵࡓࠋ ࡑࢀࡒࢀࡢᐇ㦂ࡀࠊTS ่⃭ᙉᗘࡼࡿ MEP ᖜࡢ㐪࠸ࡼࡾᙳ㡪ࡀ࡞ࡗ ࡓࡇࢆ☜ㄆࡍࡿࡓࡵࠊྛ᮲௳ࢆ⩌ෆᅉᏊࡋࡓ 1 せᅉࡼࡿ ᐃศᩓศ ᯒࢆ࠾ࡇ࡞ࡗࡓࠋ ⾲ 3 ᐇ㦂 3 ࡢࢹࢨࣥ Configuration TS㸦ᕥ M1㸧 3A 0.6 mV 3B 0.6 mV 3C 0.6 mV 3D 0.6 mV 3E 0.6 mVMNS 3F 0.6 mVMNS 3G 0.6 mVCCS 3H 0.6 mVCCS CCS㸦ྑ M1㸧 MNS㸦ྑṇ୰⚄⤒㸧 1/1.2/1.4 RMT 1.5/3 ST 1/1.2/1.4 RMT 1.5/3 ST 1/1.2/1.4 RMT 1.5/3 ST Configuration 3A-3D ࡛ࡣࠊTS0.6mV タᐃࡉࢀࠊSIHI SAI ࡢຠᯝࢆࡳࡓࠋ 3E/3F ࡛ࡣࠊ3C ࡢ MEP ࠶ࢃࡏ࡚ TS ࢆῶᙅࡉࡏࡓ TS0.6mVMNS ࢆ⏝࠸ࡓࠋ3G/3H ࡛ࡣࠊ3B ࡢ MEP ࠶ࢃࡏ࡚ TS ࢆῶᙅࡉࡏࡓ TS0.6mVCCS ࢆ⏝࠸ࡓࠋ 44 ᐇ㦂 1 ᐇ㦂 2 TS ᮲௳ CS ᮲௳ࢆ࠸ࡎࢀࡶ⩌ෆᅉᏊࡋࡓ 2 せᅉࡼࡿ ᐃศᩓศᯒ ࢆ࠾ࡇ࡞ࡗࡓࠋCS ࡢ่⃭ᙉᗘᑐࡍࡿ post hoc ศᯒࡣ࣎ࣥࣇ࢙࣮ࣟ⿵ṇࡼ ࡿከ㔜ẚ㍑࡛࠾ࡇ࡞ࡗࡓࠋᚲせᛂࡌ࡚㠀⌫㠃ᛶࡢ⿵ṇࡢࡓࡵ GreenhouseGeisser ⿵ṇࢆ࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 3 ࡲࡎࠊSAI ࡢ SIHI ᑐࡍࡿຠᯝࢆホ౯ࡍࡿࡓࡵࠊ ࠕSIHI without SAIࠖࠕSIHI with SAIࠖࢆẚ㍑ࡋࡓࠋࠕSIHI without SAIࠖࡣ㏻ᖖࡢ SIHI ྠᵝ࡛࠶ࡾࠊ configuration 3F (CCS) / configuration 3E (TS0.6mVMNS)ࡢ MEP ᖜẚ࡛ồࡵࡽࢀ ࡓࠋ ࠕSIHI with SAIࠖࡣ 2 ࡘࡢ CS ࡀ࠼࡚࠶ࡾ㸦CCS MNS㸧ࠊconfiguration 3D (CCS+MNS) / configuration 3C (MNS)ࡢ MEP ᖜẚ࡛ồࡵࡽࢀࡓࠋࡇࢀࡣ SAI ࡢ SIHI ᑐࡍࡿຠᯝࢆぢࡿ㝿ࡣ SIHI ࡢ್ࢆẚ㍑ࡍࡿᚲせࡀ࠶ࡿࡓࡵ࡛࠶ࡿࠋㄪ ᩚࡉࢀࡓ TS㸦configuration 3E㸧ࢆ⏝࠸ࡓ⌮⏤ࡋ࡚ࡣࠊศẕᙜࡓࡿ㒊ศࡢ MEP ᖜࢆྠࡌࡑࢁ࠼ࡿࡓࡵ࡛࠶ࡿࠋࡲࡎࠊㄪᩚࡉࢀࡓ༢Ⓨ MEP ࡢᖜ 㸦configuration 3C 3E㸧ࢆࡑࢀࡒࢀࡢ᮲௳࡛ paired t ᳨ᐃࢆ࠾ࡇ࡞ࡗࡓࠋࡑࡢ ᚋࠊ2 せᅉࡼࡿ ᐃศᩓศᯒࢆࠊࠕ6 ࡘࡢ่⃭᮲௳ࡢ⤌ࡳྜࢃࡏࠖࠕMNS ࡢ᭷↓㸦without SAI ࡲࡓࡣ with SAI㸧ࠖࢆ࠸ࡎࢀࡶ⩌ෆᅉᏊࡋ࡚࠾ࡇ࡞ࡗࡓࠋ 45 ྠࡌ่⃭᮲௳ࡢ⤌ࡳྜࢃࡏ࡛ SAI ࡢ᭷↓ࡢຠᯝࢆẚ㍑ࡍࡿࡓࡵࠊ࣎ࣥࣇ࢙࣮ࣟ ⿵ṇࡼࡿከ㔜ẚ㍑࡛ post hoc ศᯒࢆ࠾ࡇ࡞ࡗࡓࠋ ࡉࡽ㏫ࠊSIHI ࡢ SAI ᑐࡍࡿຠᯝࢆホ౯ࡍࡿࡓࡵࠊ ࠕSAI without SIHIࠖ ࠕSAI with SIHIࠖࢆẚ㍑ࡋࡓࠋࠕSAI without SIHIࠖࡣ㏻ᖖࡢ SAI ྠᵝ࡛࠶ࡾࠊ configuration 3H (MNS) / configuration 3G (TS0.6mVCCS)ࡢ MEP ᖜẚ࡛ồࡵࡽࢀ ࡓࠋࠕSAI with SIHIࠖࡣ 2 ࡘࡢ CS ࡀ࠼࡚࠶ࡾࠊconfiguration 3D (CCS+MNS) / configuration 3B (CCS)ࡢ MEP ᖜẚ࡛ồࡵࡽࢀࡓࠋࡇࢀࡣ SIHI ࡢ SAI ᑐࡍࡿ ຠᯝࢆぢࡿ㝿ࡣ SAI ࡢ್ࢆẚ㍑ࡍࡿᚲせࡀ࠶ࡿࡓࡵ࡛࠶ࡿࠋࡲࡎࠊㄪᩚࡉࢀ ࡓ༢Ⓨ MEP ࡢᖜ㸦configuration 3B 3G㸧ࢆࡑࢀࡒࢀࡢ᮲௳࡛ paired t ᳨ᐃࢆ ࠾ࡇ࡞ࡗࡓࠋࡑࡢᚋࠊ2 せᅉࡼࡿ ᐃศᩓศᯒࢆࠊࠕ6 ࡘࡢ่⃭᮲௳ࡢ⤌ ࡳྜࢃࡏࠖ ࠕCCS ࡢ᭷↓㸦without SIHI ࡲࡓࡣ with SIHI㸧ࠖࢆ࠸ࡎࢀࡶ⩌ෆᅉᏊ ࡋ࡚࠾ࡇ࡞ࡗࡓࠋྠࡌ่⃭᮲௳ࡢ⤌ࡳྜࢃࡏ࡛ SIHI ࡢ᭷↓ࡢຠᯝࢆẚ㍑ࡍࡿࡓ ࡵࠊ࣎ࣥࣇ࢙࣮ࣟ⿵ṇࡼࡿከ㔜ẚ㍑࡛ post hoc ศᯒࢆ࠾ࡇ࡞ࡗࡓࠋ ┦㛵ゎᯒ ┦స⏝ࡢᙉࡉ SIHI ࡶࡋࡃࡣ SAI ࡢ⛬ᗘࡢ┦㛵ࢆศᯒࡍࡿࡓࡵࠊ㔜ᅇᖐศ ᯒࢆ࠾ࡇ࡞ࡗࡓࠋ┦స⏝ࡢᙉࡉࡣ MEP ᖜẚࡢᕪࡋ࡚ィ⟬ࡋࡓࠋSAI ࡢ SIHI ᑐࡍࡿຠᯝࡣࠊΔSIHI = (3D/3C) – (3F/3E)ࡋ࡚ồࡵࠊSIHI ࡢ SAI ᑐࡍࡿຠ 46 ᯝࡣࠊΔSAI = (3D/3B) – (3H/3G)ࡋ࡚ồࡵࡓࠋ┠ⓗኚᩘࡣ ΔSIHI ࡶࡋࡃࡣ ΔSAI ࡛࠶ࡾࠊㄝ᫂ኚᩘࡣ SIHI ࡋ࡚ 3F/3EࠊSAI ࡋ࡚ 3H/3G ࢆタᐃࡋࡓࠋ ⤫ィᏛⓗゎᯒࡣ PASW Statistics 18.0.0㸦IBM㸧ࢆ⏝࠸ࡓࠋp ್ < 0.05 ࢆ᭷ព ุ᩿ࡋࡓࠋ 47 㹙⤖ᯝ㹛 ᕥ M1 ࡢ RMT ࡢᖹᆒࡣ 48.3s8.8%㸦SD㸧MSOࠊᕥ M1 ࡢ AMT ࡣ 32.6s6.6% MSOࠊྑ M1 ࡢ RMT ࡣ 55.4s10.1% MSO ࡛࠶ࡗࡓࠋ TS ࡼࡿ MEP ᖜࡣࠊ࠸ࡎࢀࡢᐇ㦂ࡢࡢ᮲௳࠾࠸࡚ࡶ᭷ព࡞ᕪࢆㄆࡵ ࡞ࡗࡓ㸦p > 0.56ࠊ⾲ 4㸧ࠋᐇ㦂 3 ࡛ࡣࠊ ㄪᩚࡉࢀࡓ TS ࡢ MEP ᖜࡣࠊ ࠕSIHI without SAI㸦3E ࡢ TS0.6mVMNS㸧ࠖࠕSIHI with SAI㸦3C ࡢ TS0.6mV+MNS㸧ࠖࡢ㛫㸦p > 0.60ࠊ⾲ 4㸧࡛ࡶࠊ ࠕSAI without SIHI㸦3G ࡢ TS0.6mVCCS㸧ࠖࠕSAI with SIHI㸦3B ࡢ TS0.6mV+CCS㸧ࠖࡢ㛫㸦p > 0.67ࠊ⾲ 4㸧࡛ࡶࠊ࡚ࡢ่⃭᮲௳ࡢ⤌ࡳྜࢃࡏ ࠾࠸࡚᭷ព࡞ᕪࢆㄆࡵ࡞ࡗࡓࠋᐇ㦂 1 ᐇ㦂 3 ࠾࠸࡚ࠊᑐഃ FDI ࡢ MEP ᖜࡣࠊCCS ࡢ่⃭ᙉᗘࢆୖࡆࡿᚑࡗ࡚ቑຍࡋࡓ㸦p < 0.01ࠊᅗ♧࡞ࡋ㸧ࠋ 48 ⾲ 4 ᮲௳ࡈࡢヨ㦂่⃭ࡢᖹᆒ MEP ᖜsᶆ‽ㄗᕪ㸦mV㸧 49 ᐇ㦂 1㸸SIHI ᑐࡍࡿ TS CS ࡢ่⃭ᙉᗘࡼࡿᙳ㡪 SIHI ᑐࡍࡿ TS CS ࡢ่⃭ᙉᗘࡼࡿᙳ㡪ࢆᅗ♧ࡋࡓ㸦ᅗ 12㸧ࠋCS ่⃭ ᙉᗘࡣ SIHI ࡢ⛬ᗘ᭷ព࡞ຠᯝࡀ࠶ࡗࡓ[F (3,30) = 26.3, p < 0.001, partial η2 = 0.73]ࠋTS ่⃭ᙉᗘࡼࡿຠᯝࡣഴྥࡀࡳࡽࢀࡿࡢࡳ࡛࠶ࡾ[F (1,10) = 3.9, p = 0.08, partial η2 = 0.28]ࠊTS CS ่⃭ᙉᗘᑐࡍࡿᅉᏊస⏝ࡣ᭷ព࡛࡞ ࡗࡓ[F (3,30) = 0.09, p = 0.96, partial η2 = 0.01]ࠋPost hoc ศᯒ࡛ࡣࠊCCS1 CCS1.2 ࡢ㛫㸦p = 0.006㸧ࠊCCS1.2 CCS1.4 ࡢ㛫㸦p = 0.02㸧᭷ពᕪࢆㄆࡵࡓࡀࠊCCS1.4 CCS1.6 ࡢ㛫ࡣ᭷ពᕪࢆㄆࡵ࡞ࡗࡓ㸦p = 1.00㸧ࠋTS ࡢ่⃭ᙉᗘࡣ TS0.6mV ࠾࠸࡚ 67.9s4.4% MSO㸦140.9% RMT ┦ᙜ㸧ࠊTS0.3mV ࠾࠸࡚ 61.8s4.6% MSO㸦127.2% RMT ┦ᙜ㸧࡛࠶ࡗࡓࠋ ᅗ 12 SIHI ᑐࡍࡿ TS CS ࡢ่⃭ᙉᗘࡼࡿᙳ㡪ࠋCS ่⃭ᙉᗘࡣ SIHI ᭷ព࡞ຠᯝࢆ♧ࡋࡓࡀࠊTS ่⃭ᙉᗘࡣ᭷ព࡞ຠᯝࡀぢࡽࢀ࡞ࡗࡓࠋ ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05, **p < 0.01 50 ᐇ㦂 2㸸SAI ᑐࡍࡿ TS CS ࡢ่⃭ᙉᗘࡼࡿᙳ㡪 SAI ᑐࡍࡿ TS CS ࡢ่⃭ᙉᗘࡼࡿᙳ㡪ࢆᅗ♧ࡋࡓ㸦ᅗ 13㸧ࠋCS ่⃭ ᙉᗘࡣ SAI ࡢ⛬ᗘ᭷ព࡞ຠᯝࡀ࠶ࡗࡓ[F (2,12) = 28.9, p < 0.001, partial η2 = 0.83]ࠋTS ่⃭ᙉᗘࡼࡿຠᯝ[F (1,6) = 0.03, p = 0.86, partial η2 = 0.01]ࠊTS CS ่⃭ᙉᗘᑐࡍࡿᅉᏊస⏝[F (2,12) = 0.11, p = 0.76, partial η2 = 0.02]ࡣ࠸ ࡎࢀࡶ᭷ព࡛࡞ࡗࡓࠋTS CS ᑐࡍࡿᅉᏊస⏝࠾࠸࡚ࡢࡳ Greenhouse-Geisser ⿵ṇࢆ㐺⏝ࡋࡓࠋPost hoc ศᯒ࡛ࡣࠊMNS1.5 MNS3 ࡢ㛫 ᭷ពᕪࢆㄆࡵࡓࡀ㸦p = 0.003㸧ࠊMNS3 MNS4.5 ࡢ㛫ࡣ᭷ពᕪࢆㄆࡵ࡞ࡗ ࡓ㸦p = 0.85㸧ࠋTS ࡢ่⃭ᙉᗘࡣ TS0.6mV ࠾࠸࡚ 67.3s4.7% MSO㸦139.2% RMT ┦ᙜ㸧ࠊTS0.3mV ࠾࠸࡚ 63.3s4.4% MSO㸦130.7% RMT ┦ᙜ㸧࡛࠶ࡗࡓࠋ ᅗ 13 SAI ᑐࡍࡿ TS CS ࡢ่⃭ᙉᗘࡼࡿᙳ㡪ࠋCS ่⃭ᙉᗘࡣ SAI ᭷ព࡞ຠᯝࢆ♧ࡋࡓࡀࠊTS ่⃭ᙉᗘࡣ᭷ព࡞ຠᯝࡀぢࡽࢀ࡞ࡗࡓࠋ ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ**p < 0.01 51 ᐇ㦂 3 SAI ࡢ SIHI ᑐࡍࡿຠᯝ ୍ேࡢ⿕㦂⪅ࡢ௦⾲ⓗ࡞Ἴᙧ㸦CCS1.4+MNS3 ࡢ᮲௳㸧ࢆᅗ 14 ♧ࡋࡓࠋ ᅗ 14 ᐇ㦂 3 ࡛ 1 ྡࡢ⿕㦂⪅ࡢྑ FDI ࡽᚓࡽࢀࡓ௦⾲ⓗ࡞ MEP Ἴᙧ 㸦CS1.4+MNS3㸧ࠋSAI ࡢ SIHI ᑐࡍࡿຠᯝࡀ♧ࡉࢀ࡚࠸ࡿࠋ A. TS ༢⊂࡛ 0.6 mV MEP㸦configuration 3A㸧ࠋB. TS0.6mV㸩MNS㸦3C㸧ࠋ C. TS0.6mV㸩CCS㸩MNS 㸦3D㸧ࠋD. B ྠࡌ MEP ࡞ࡿࡼ࠺ㄪᩚࡋࡓ TS 㸦3E㸧ࠋ E. D ࡢ TS0.6mVMNS㸩CCS㸦3F㸧ࠋ ࠕSIHI with SAI (C/B)ࠖࡀࠕSIHI without SAI (E/D)ࠖࡼࡾࡁࡃ࡞ࡗ࡚࠸ࡿࠋ ศẕࡢ B D ࡢ MEP ࡀ TS ࢆㄪᩚࡋࡓࡇࡼࡗ࡚ྠࡌ࡞ࡗ࡚࠸ࡿࠋ 52 ࠕSIHI with SAIࠖࡣᅗ 14 ࡢ C/B㸦㸻configuration 3D/3C㸧࡛࠶ࡾࠊ ࠕSIHI without SAI 㸦㏻ᖖࡢ SIHI㸧ࠖࡣᅗ 14 ࡢ E/D㸦㸻configuration 3F/3E㸧࡛࠶ࡾࠊᅗ 14 ࡢ B D ࡛ MEP ࡢࡁࡉࡀྠࡌ⛬ᗘ࡞ࡗ࡚࠸ࡿࠋྛ᮲௳࠾ࡅࡿᖹᆒࡢࢹ࣮ࢱࢆᅗ 15 ♧ࡋࡓࠋ SIHI ࡢ⛬ᗘᑐࡋࠊ่⃭⤌ࡳྜࢃࡏ᮲௳ࡀ᭷ព࡞ຠᯝࢆ♧ࡋ[F (5,50) = 10.5, p < 0.001, partial η2 = 0.51]ࠊSAI ࡣຠᯝࡢഴྥࢆㄆࡵࡓ[F (1,10) = 4.7, p = 0.055, partial η2 = 0.32]ࠋ่⃭⤌ࡳྜࢃࡏ᮲௳ SAI ࡼࡿᅉᏊస⏝ࡣ᭷ព࡛࠶ࡗ ࡓ[F (5,50) = 2.9, p = 0.023, partial η2 = 0.23]ࠋPost hoc ศᯒ࠾࠸࡚ SAI ࡣ SIHI ᑐࡋ 2 ࡘࡢ่⃭⤌ࡳྜࢃࡏ᮲௳㸦CCS1.2+MNS3 CCS1.4+MNS3㸧࡛᭷ព࡞ ຠᯝࢆ♧ࡋࡓ㸦⾲ 5㸧ࠋ SIHI ࡢ SAI ᑐࡍࡿຠᯝ ྛ᮲௳࠾ࡅࡿᖹᆒࡢࢹ࣮ࢱࢆᅗ 16 ♧ࡋࡓࠋSAI ࡢ⛬ᗘᑐࡋࠊ่⃭⤌ࡳ ྜࢃࡏ᮲௳ࡀ᭷ព࡞ຠᯝࢆ♧ࡋ[F (5,50) = 5.9, p = 0.01, partial η2 = 0.37]ࠊSIHI ࡣ ຠᯝࡢഴྥࢆㄆࡵࡓ[F (1,10) = 4.4, p = 0.063, partial η2 = 0.31]ࠋ่⃭⤌ࡳྜࢃࡏ᮲ ௳ SAI ࡼࡿᅉᏊస⏝ࡣ᭷ព࡛࡞ࡗࡓ[F (5,50) = 1.1, p = 0.39, partial η2 = 0.10]ࠋPost hoc ศᯒ࠾࠸࡚ SIHI ࡣ SAI ᑐࡋ 2 ࡘࡢ่⃭⤌ࡳྜࢃࡏ᮲௳ 㸦CCS1.2+MNS3 CCS1.4+MNS3㸧࡛᭷ព࡞ຠᯝࢆ♧ࡋࡓ㸦⾲ 5㸧ࠋ 53 ᅗ 15 SAI ࡢ SIHI ᑐࡍࡿຠᯝࠋయࡢゎᯒ࡛ࡣ SIHI ᑐࡋ࡚ SAI ࡣຠᯝࡀ ࠶ࡿഴྥࡀࡳࡽࢀࡓࠋPost hoc ゎᯒ࡛ࡣ CCS1.2+MNS3 CCS1.4+MNS3 ࡢ 2 ࡘࡢ᮲௳࠾࠸࡚᭷ព࡞ຠᯝࢆㄆࡵࡓࠋ ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05 54 ᅗ 16 SIHI ࡢ SAI ᑐࡍࡿຠᯝࠋయࡢゎᯒ࡛ࡣ SAI ᑐࡋ࡚ SIHI ࡣຠᯝ ࡀ࠶ࡿഴྥࡀࡳࡽࢀࡓࠋPost hoc ゎᯒ࡛ࡣ CCS1.2+MNS3 CCS1.4+MNS3 ࡢ 2 ࡘࡢ᮲௳࠾࠸࡚᭷ព࡞ຠᯝࢆㄆࡵࡓࠋ ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05 55 ┦㛵ゎᯒ SAI ࡢ SIHI ᑐࡍࡿຠᯝ࡛ࡣࠊ㔜ᅇᖐศᯒࡼࡿࣔࢹࣝ᭷ព࡞ຠᯝࢆㄆࡵ ࡓ[F (2,63) = 28.4, p < 0.001]ࠋᶆ‽೫ᅇᖐಀᩘࡣ SIHI ࡀ-0.68㸦p < 0.001㸧ࠊSAI ࡀ-0.04㸦p = 0.71㸧࡛࠶ࡗࡓࠋ┦㛵ಀᩘࡣ 0.69ࠊỴᐃಀᩘࡣ 0.46 ࡛࠶ࡗࡓࠋSIHI ࡢ SAI ᑐࡍࡿຠᯝ࡛ࡣࠊ㔜ᅇᖐศᯒࡼࡿࣔࢹࣝ᭷ព࡞ຠᯝࢆㄆࡵࡓ[F (2,63) = 12.9, p < 0.001]ࠋᶆ‽೫ᅇᖐಀᩘࡣ SIHI ࡀ-0.28㸦p = 0.01㸧ࠊSAI ࡀ-0.42 㸦p < 0.001㸧࡛࠶ࡗࡓࠋ┦㛵ಀᩘࡣ 0.54ࠊỴᐃಀᩘࡣ 0.29 ࡛࠶ࡗࡓࠋྛせ⣲ࡢ ᩓᕸᅗࡣᅗ 17 ♧ࡋࡓࠋ ⾲ 5 ᐇ㦂 3 ࠾ࡅࡿ⤫ィᏛⓗᩘ್ࡢࡲࡵ ᮲௳ MEP ᕪ F (1,10) p partial η2 SAI ࡢ SIHI ᑐࡍࡿຠᯝ CCS1 + MNS1.5 0.04 (0.08) 0.23 0.64 0.02 CCS1.2 + MNS1.5 0.08 (0.07) 1.66 0.23 0.14 CCS1.4 + MNS1.5 0.09 (0.07) 1.57 0.24 0.14 CCS1 + MNS3 0.03 (0.13) 0.04 0.84 0.004 CCS1.2 + MNS3 0.37 (0.15) 6.01 0.034* 0.38 CCS1.4 + MNS3 0.29 (0.10) 8.01 0.018* 0.45 SIHI ࡢ SAI ᑐࡍࡿຠᯝ CCS1 + MNS1.5 0.02 (0.09) 0.06 0.82 0.01 CCS1.2 + MNS1.5 0.07 (0.08) 0.98 0.35 0.09 CCS1.4 + MNS1.5 0.10 (0.13) 0.59 0.46 0.06 CCS1 + MNS3 0.08 (0.06) 1.68 0.22 0.14 CCS1.2 + MNS3 0.19 (0.08) 6.03 0.034* 0.38 CCS1.4 + MNS3 0.25 (0.11) 4.96 0.050* 0.33 MEP ᕪࡣᖹᆒ㸦ᶆ‽ㄗᕪ㸧㸦mV㸧࡛♧ࡍࠋ*p < 0.05 56 ᅗ 17 ┦స⏝ࡢᙉࡉ SIHI ࠶ࡿ࠸ࡣ SAI ࡢ⛬ᗘࡢ┦㛵ࠋ SIHI ࠶ࡿ࠸ࡣ SAI ࡀᙉ࠸ࠊ୧⪅㛫ࡢ┦స⏝ࡀᙉ࠸ഴྥࡀぢࡽࢀࡓࠋ㯮୕ ゅᙧࡣ SIHI ࢆ♧ࡋࠊᐇ⥺ࡀ⥺ᙧᅇᖐ┤⥺࡛࠶ࡿࠋⓑࡣ SAI ࢆ♧ࡋࠊ◚⥺ࡀ ⥺ᙧᅇᖐ┤⥺࡛࠶ࡿࠋ ᶓ㍈ࡣ SIHI ࠶ࡿ࠸ࡣ SAI ࡢ MEP ᖜẚࢆ♧ࡍࠋ⦪㍈ࡣ MEP ᖜẚࡢኚࢆ ♧ࡋࠊᕥᅗ࡛ࡣ ΔSIHI㸦 ࠕSIHI without SAIࠖࠕSIHI with SAIࠖࡢ㛫ࡢᕪ㸧 ࠊ ྑᅗ࡛ࡣ ΔSAI㸦ࠕSAI without SIHIࠖࠕSAI with SIHIࠖࡢ㛫ࡢᕪ㸧࡛࠶ࡿࠋ 57 㹙⪃ᐹ㹛 ࡇࡢ◊✲࡛ࡣࠊSIHI SAI ࡢ㛫ࡢ┦స⏝ࡘ࠸᳨࡚ウࢆ࠾ࡇ࡞ࡗࡓࠋࡇࢀ ࡽࡢ㛵ಀ࡛ࡣࠊ୍᪉ࡢᢚไࡼࡾ᪉ࡢᢚไࡀῶᑡࡍࡿࡇࡀ♧ࡉࢀࡓࡀࠊࡇ ࢀࡣ CS ࡢ่⃭ᙉᗘࡀ༑ศᙉࡃࠊ୧᪉ࡢᢚไࡀṇᖖぢࡽࢀࡿࡢࡳࡳࡽࢀࡓࠋ SIHI SAI ࡢ่⃭᮲௳౫Ꮡᛶ ᐇ㦂 1 ࠾࠸࡚ࠊSIHI ࡀస⏝ࡍࡿࡣࠊCS ࡀ㜈್௨ୖ࡛࡞ࡃ࡚ࡣ࡞ࡽࡎࠊࡼ ࡾᙉ࠸ CS ࡀ῝࠸ᢚไࡘ࡞ࡀࡗࡓࡀࠊCS ࡢ่⃭ᙉᗘࡣ 1.4 RMT ࡛㣬≧ែ 㐩ࡋࡓࠋࡼࡾᙉ࠸ CS ࡀࡁ࡞ SICI ࢆᘬࡁ㉳ࡇࡍࡇࡣ௨๓ࡢሗ࿌୍⮴ࡋ࡚ ࠸ࡓ[70]ࠋᙉ࠸ TS ࡼࡿࡁ࡞ MEP ࡢ᪉ࡀᢚไࡣὸ࠸ഴྥࡀࡳࡽࢀࡿࡀࠊࡇࡢ ᕪࡣ⤫ィᏛⓗࡣ᭷ព࡛ࡣ࡞ࡗࡓࠋࡇࢀࡽࡢ TS ࡼࡿᙳ㡪ࡶ௨๓ࡢሗ࿌ྠ ᵝࡢഴྥࡀぢࡽࢀࡓ[20, 38, 68]ࠋᐇ㦂 2 ࡛ࡣࠊࡼࡾᙉ࠸ CS ࡀ SAI ࡢࡼࡾ῝࠸ᢚ ไࡘ࡞ࡀࡗࡓࡀࠊCS ࡢ่⃭ᙉᗘࡣ 3 ST ࡛㣬≧ែ㐩ࡋࡓࠋࡇࡢ⤖ᯝࡣ௨๓ ࡢሗ࿌୍⮴ࡋ࡚࠸ࡓ[71, 72]ࠋᅇ⏝࠸ࡓ TS ࡢ่⃭ᙉᗘࡢ⠊ᅖෆ࡛ࡣ SAI ࡣᙳ㡪ࡣぢࡽࢀ࡞ࡗࡓࠋ SIHI SAI ࡢ┦స⏝ SIHI ࡢᏑᅾࡼࡾࠊSAI ࡢຠᯝࡣ CCS1.2+MNS3 CCS1.4+MNS3 ࡢ᮲௳࠾ 58 ࠸࡚ῶᙅࡋࡓࠋSAI ࡢᏑᅾࡼࡿ SIHI ᑐࡍࡿ㏫᪉ྥࡢῶᙅຠᯝࡶࡲࡓྠᵝࡢ ᮲௳࠾࠸࡚ࡳࡽࢀࡓࠋࡇࢀࡽ 2 ࡘࡢ CS ่⃭ᙉᗘࡣᢚไຠᯝࢆᘬࡁ㉳ࡇࡍࡢ ༑ศᙉ࠸่⃭ᙉᗘ࡛࠶ࡗࡓࠋࡢ่⃭ᙉᗘ࡛ࡣࠊ᭷ព࡞┦స⏝ࢆ㉳ࡇࡍࡢ ่⃭ࡀ༑ศ࡛࠶ࡗࡓ⪃࠼ࡽࢀࡓࠋ SIHI SAI ࡢ㛫ࡣ୧᪉ྥᛶࡢᢚไᛶࡢ┦స⏝ࡀㄆࡵࡽࢀࡓࠋࡇࡢ┦స ⏝ࡣ CS ࡀࡑࢀࡒࢀࡢᢚไࢆ༑ศច㉳࡛ࡁࡿ่⃭ᙉᗘ࡛ࡢࡳぢࡽࢀࡓࠋࡇࡢ┦ స⏝ࡘ࠸࡚᭱ࡶ⪃࠼ࡸࡍ࠸ㄝ᫂ࡣࠊSIHI SAI ࡢᅾࢽ࣮ࣗࣟࣥࡀ┤᥋ⓗ ࠾࠸ࢆᢚไࡍࡿ┦స⏝ࢆⓎࡋࡓ࠸࠺ࡶࡢ࡛࠶ࡿࠋྠࡌࡼ࠺࡞┤᥋ⓗ ࡞ᢚไᛶ┦స⏝ࡀ♧၀ࡉࢀࡓሗ࿌ࡣࡇࢀࡲ࡛ࡶ࠸ࡃࡘ࠶ࡾࠊSAI LICI [40]ࠊ SAI SICI [39]ࠊLIHI LICI [73]࡞ࡀ▱ࡽࢀ࡚࠸ࡿࠋᅇࡢ◊✲࡛ࡢ᪂ࡋ࠸ Ⅼࡋ࡚ࡣࠊSIHI SAI ࡢ┦స⏝ࡀ CS ࡢ่⃭ᙉᗘ౫Ꮡᛶ࡛࠶ࡿⅬ࡛࠶ࡿࠋ ࡇࢀࡣࠊ┦㛵ゎᯒ࠾࠸࡚ SIHI ࡢ⛬ᗘ SAI ࡢ SIHI ᑐࡍࡿຠᯝࡀ᭷ព┦ 㛵ࡋࡓⅬࡽࡶ࠸࠼ࡿࠋࡉࡽࠊSIHI ࡢ SAI ᑐࡍࡿຠᯝ SIHI ࡶࡋࡃࡣ SAI ࡢ⛬ᗘࡶ᭷ព࡞┦㛵ࡀࡳࡽࢀࡓࠋSAI ࡢ⛬ᗘ SAI ࡢ SIHI ᑐࡍࡿຠᯝࡣ ᭷ព࡞┦㛵ࡀࡳࡽࢀ࡞ࡗࡓࡀࠊࡇࢀࡣ SAI ࡢ᪉ࡀ SIHI ࡼࡾࡶ┦స⏝ࡀᙅ࠸ ࡓࡵ⪃࠼ࡽࢀࡓࠋࡇࡢࡇࡽࠊSIHI SAI ࡢ┦స⏝࠾ࡅࡿ SIHI ࡢඃ ᛶࡀ♧၀ࡉࢀࡓࠋ ูࡢㄝ᫂ࡢྍ⬟ᛶࡋ࡚ࡣࠊᢚไຠᯝࡢ㛢ሰࡶࡋࡃࡣ㣬ຠᯝࡀ⪃࠼ࡽࢀࡿࠋ 59 2 ࡘࡢᢚไᛶᅾࢽ࣮ࣗࣟࣥࡀ⓶㉁ෆࡢࡇࡢඹ㏻ࡢ⚄⤒⤖ྜࡋ࡚࠸ࡓሙ ྜࠊ୍᪉ࡢࢩࢫࢸ࣒ࡼࡾ⏕ᡂࡉࢀࡓᢚไࡀࡰ್᭱㐩ࡋ࡚࠸ࡿࠊࡢ ᢚไ⣔ࡢࢩࢫࢸ࣒ࡣࡑࢀࡉࡽᢚไࢆ㏣ຍࡍࡿࡇࡀ࡛ࡁ࡞࠸≧ែ࡞ࡿྍ ⬟ᛶࡀ࠶ࡿࠋ┦స⏝ࡀ CS ่⃭ᙉᗘࡢ༑ศᙉ࠸ࡁࡋ㉳ࡁ࡞ࡗࡓࡇࡣࠊ ࡇࡢㄝ᫂ࢆᨭᣢࡍࡿྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋࡢ่⃭⤌ࡳྜࢃࡏ᮲௳࡛┦స⏝ ࡀ㉳ࡁ࡞ࡗࡓࡢࡣࠊྜィࡢᢚไຠᯝ㔞ࡀ᭱㐩ࡋ࡚࠸࡞ࡗࡓࡓࡵ࡛࠶ࡿ ㄝ࡛᫂ࡁࡿࡶࡋࢀ࡞࠸ࠋࡇࡢ௬ㄝࢆࡶࡍࡿࠊCS ่⃭ᙉᗘࡀࡼࡾᙅ࠸ ሙྜࠊ࠼ࡤ CCS1.2+MNS3 ࡢሙྜࠊ┦స⏝ࡣࡼࡾᙉ࠸᮲௳ࠊ࠼ࡤ CCS1.4+MNS3 ࡼࡾࡶᙅ࠸ࡣࡎ࡛࠶ࡿࠋࡋࡋࠊᅇࡢ⤖ᯝࡽࡣࠊࡇࡢ 2 ࡘࡢ ่⃭⤌ࡳྜࢃࡏ᮲௳࡛ࡣ┦స⏝ࡣྠ⛬ᗘ࡛࠶ࡗࡓࠋࡇࡢࡇࡽࡣࠊSIHI SAI ࡢ┦స⏝ࡣࠊ㒊ศⓗࡣస⏝ࡋ࡚࠸ࡿࡶࡋࢀ࡞࠸ࡶࡢࡢࠊ㛢ሰࡶࡋࡃࡣ 㣬ຠᯝࡼࡗ࡚ㄝ᫂ࡍࡿࡇࡣ㞴ࡋ࠸ࡢ࡛ࡣ࡞࠸⪃࠼ࡽࢀࡓࠋ 2 ࡘࡢᢚไᛶᅇ㊰࡛࠶ࡿ SIHI SAI ࡀ࠾࠸ᢚไࡋ࠶࠺┦స⏝ࡢ⏕⌮Ꮫ ⓗ࡞ពࡋ࡚ࡣࠊM1 ࢆ㐣࡞ᢚไࡽಖㆤࡍࡿᙺࡀ࠶ࡿࡶࡋࢀ࡞࠸⪃ ࠼ࡽࢀࡓࠋSIHI SAI 㛵㐃ࡋ࡚ࠊSICI LICI ࠸࠺ 2 ࡘࡢᢚไᛶᅇ㊰ࢆࡋ ࡚ࠊࡇࢀࡲ࡛ㄪࡽࢀࡓ┦స⏝ࡶ࡚ᢚไᛶࡢຠᯝࢆ♧ࡋ࡚࠸ࡓࠋᅇࡢ⤖ ᯝ࠶ࢃࡏࠊSIHI ࡣ SICI ࢆῶᑡࡉࡏࠊSICI ࡣ SAI ࢆῶᑡࡉࡏࠊSAI ࡣ SIHI ࢆ ῶᑡࡉࡏࡓࠋࡲࡓࠊSAI ࡣ LICI ࢆῶᑡࡉࡏࠊLICI ࡣ SIHI ࢆῶᑡࡉࡏࠊSIHI ࡣ 60 SAI ࢆῶᑡࡉࡏࡓ[38, 39, 40]ࠋࡇࡢࡇࡣࠊ≉ᐃࡢ⚄⤒ᅇ㊰୍࡛᪉ྥᛶࡢ┦స ⏝ࡀ㉳ࡁࡿࡢ࡛ࡣ࡞ࡃࠊ㐣࡞ᢚไࢆ㜵ࡄඹ㏻ࡢᶵᵓ࡞ࡗ࡚࠸ࡿྍ⬟ᛶࡀ⪃ ࠼ࡽࢀࡓࠋᅇࡢ◊✲࠾࠸࡚┦ࡢᢚไᛶస⏝ࢆ♧ࡋࡓࡀࠊṧᛕ࡞ࡀࡽࡑࡢ ヲ⣽࡞ᶵᗎࡘ࠸࡚ࡣ᫂☜࡛ࡣ࡞࠸ࠋࡇࡢ┦స⏝ࡢᶵᗎ⏕⌮Ꮫⓗ࡞ពࡢ ゎ᫂ࡣࡉࡽ࡞ࡿ◊✲ࡀᚲせ࡛࠶ࡿ⪃࠼ࡽࢀࡓࠋ ᮏ◊✲ࡣ࠸ࡃࡘࡢ㝈⏺ࡀ࠶ࡿࠋࡦࡘࡣ LIHI ࡛࠶ࡿࠋLIHI ࡣ SIHI ࡣ ␗࡞ࡿ⚄⤒⣽⬊㞟ᅋࡼࡗ࡚㉳ࡁ࡚࠸ࡿ⪃࠼ࡽࢀ࡚࠸ࡿࠋSIHI LIHI ࡣ㛗₯ ࡢឤぬධຊࡼࡿ M1 ᢚไᑐࡋ࡚␗࡞ࡗࡓ┦స⏝ࢆ♧ࡍࡉࢀࡿ[68]ࠋࡇ ࡢࡇࡽࠊSIHI LIHI ࡀ SAI ᑐࡋ࡚␗࡞ࡗࡓ┦స⏝ࢆ♧ࡍྍ⬟ᛶࡶ⪃࠼ ࡽࢀࡿࠋLIHI SAI ࡢ㛫ࡢ┦స⏝ࢆࡉࡽ◊✲ࡍࡿࡇ࡛ࠊ⓶㉁ෆᅇ㊰ࡢࡉ ࡽ࡞ࡿゎ᫂ࡘ࡞ࡀࡿ⪃࠼ࡽࢀࡿࠋ ࡶ࠺୍ࡘࡢ㝈⏺ࡋ࡚ࡣࠊᕥྑ༙⌫㛫ࡢᕪ␗ࡀ࠶ࡆࡽࢀࡿࠋᅇࡢ◊✲࡛ࡣ ඃ㸦ᕥ㸧༙⌫ࢆᐇ㦂⏝࠸ࡓࠋIHI ࡘ࠸࡚୧ഃ༙⌫ࢆẚ㍑ࡍࡿሗ࿌ࡶぢࡽࢀ ࡚࠸ࡿࠋ࠸ࡃࡘࡢሗ࿌࡛ࡣࠊ⬻ᱱࢆࡋࡓඃ༙⌫ࡽ㠀ඃ༙⌫ࡢᢚไ ࡀᑐ᪉ྥࡼࡾࡶᙉࡗࡓࡉࢀࡿࡀ[74, 75]ࠊ༙⌫㛫࡛ᕪࡀ࡞ࡗࡓࡢሗ࿌ ࡶ࠶ࡿ[76, 77, 78]ࠋࡇࢀࡽࡢሗ࿌ࢆ⪃៖ࡍࡿࠊ༙⌫ࡢ㠀ᑐ⛠ᛶࡘ࠸࡚⌮ゎࡍ ࡿࡓࡵࠊᑗ᮶ⓗ㠀ඃ༙⌫࡛ࡢᐇ㦂ࡶ᳨ウࡍࡿᚲせࡀ࠶ࡿ⪃࠼ࡽࢀࡿࠋ 61 ௨ୖࡲࡵࡿࠊSIHI SAI ࡣ୧᪉ࡢ CS ᙉᗘࡀ༑ศ࡛࠶ࡿࡁࡢࡳ┦స ⏝ࢆᘬࡁ㉳ࡇࡋࠊ୍᪉ࡢᢚไࡀᏑᅾࡍࡿ᪉ࡢᢚไࡀῶᙅࡍࡿ࠸࠺ࡶࡢ࡛ ࠶ࡗࡓࠋSIHI SAI ࡢᅾࢽ࣮ࣗࣟࣥࡀ┤᥋ⓗ࠾࠸ࢆᢚไࡍࡿ┦స⏝ࢆ ่⃭ᙉᗘ౫ᏑᛶⓎࡋࡓࡇࡀゎ᫂ࡉࢀࡓࠋIHI SAI ࠸࠺✀㢮ࡢ⓶㉁㛫 ᢚไᶵᵓࡢ㛫ࠊ┦ࢆᢚไࡍࡿᶵ⬟ࡀ࠶ࡿࡇࡀึࡵ࡚♧ࡉࢀࡓࠋ 62 ࠙➨ 3 ❶ࠚ ୍ḟ㐠ື㔝༢┦ᛶ 4 㐃Ⓨ⤒㢌☢Ẽ่⃭㸦QPS㸧ࡼࡿ ᑐഃ୍ḟ㐠ື㔝ࡢ㛗ᮇຠᯝㄏᑟ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢᙳ㡪 Tsutsumi R, et al. Effects of the motor cortical quadripulse transcranial magnetic stimulation (QPS) on the contralateral motor cortex and interhemispheric interactions. J Neurophysiol 111: 26–35, 2014. [79] 63 㹙┠ⓗ㹛 ⬻ᱱࡣ୧ഃࡢ M1 ࢆ⤖ࡧࠊື≀ࡔࡅ࡛࡞ࡃ[80, 81]ࠊࣄࢺ࠾࠸࡚ࡶ[82, 83]୧ ᡭࢆࡗࡓ㐠ືไᚚ㔜せ࡞ᙺࢆᯝࡓࡋ࡚࠸ࡿࠋTMS ࢆ⏝࠸ࡿࡇ࡛⬻ᱱࢆ ࡋࡓ㐃⤡ࢆࣄࢺ࡛㠀くⓗㄪࡿࡇࡀ࡛ࡁࠊ୧ഃ M1 㛫ࡢ IHI IHF ࡢ୧ ᪉ࢆ TMS ࡢⓎ่⃭ἲࡼࡾ ᐃࡍࡿࡇࡀ࡛ࡁࡿ[20, 21, 76, 84, 23, 85, 86]ࠋ ࡲࡓࠊIHI ࡣᡭᣦ㐠ືࡢࢱࢫࢡࡼࡾኚࢃࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿ[87, 88]ࠋࡇࢀࡽ ࡢሗ࿌ࡽࠊ⬻ࡢྍረᛶኚࡶ࡞ࡗ࡚⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡀኚࡍࡿྍ ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋ ࣄࢺࡢ㐠ື㔝࠾ࡅࡿྍረᛶࢆㄪࡿࡓࡵࠊᵝࠎ࡞✀㢮ࡢ rTMS ࡀࡇࢀࡲ࡛ 㛤Ⓨࡉࢀ࡚ࡁ࡚࠸ࡿ[89, 90]ࠋ㏻ᖖࠊrTMS ࡣ M1 ᑐࡋ࡚࠾ࡇ࡞ࢃࢀࠊࡑࡢຠᯝ ࡢᣦᶆࡋ࡚ࡣࠊ่⃭ࡉࢀࡓ M1 ࡢ༢Ⓨ TMS ࡼࡿ MEP ᖜࢆ࠺ࡇࡀ ከ࠸ࠋrTMS ࡣ⓶㉁̾⓶㉁㛫⤖ྜࢆ⏝࠸่࡚⃭ࡋ࡚࠸࡞࠸㒊ࡢྍረᛶኚࢆㄏ ᑟࡍࡿࡇࡶ࡛ࡁࡿ⪃࠼ࡽࢀࡿࠋ่⃭ࡉࢀࡓ M1 ᑐഃ༙⌫ࡢ M1 ࡢྍረᛶኚ ࡘ࠸࡚ࡣࡇࢀࡲ࡛࠸ࡃࡘㄪࡽࢀ࡚࠸ࡿࡀࠊࡑࡢ⤖ᯝࡣ୍ᐃ࡛࡞࠸ࠋM1 ࡢ 1 Hz rTMS ᚋࡣ่⃭ഃࡣᢚᅽࡢຠᯝࢆㄏᑟࡍࡿࡉࢀࡿࡀࠊᑐഃ M1 ࡽࡢ MEP ᖜࡢኚࡘ࠸࡚ࠊቑࡋࡓࡍࡿሗ࿌ࡶῶᑡࡋࡓࡍࡿሗ࿌ࡶ ࠶ࡾࠊ่⃭ࣉࣟࢥ࣮ࣝࡢ㐪࠸࡞ࡀཎᅉࡋ࡚࠶ࡆࡽࢀ࡚࠸ࡿ[91, 92, 93, 94, 95, 96]ࠋࡢሗ࿌࡛ࡣ่⃭ഃቑᙉຠᯝࢆㄏᑟࡉࢀࡿࡉࢀࡿ 5 Hz M1 rTMS ᚋ 64 ᑐഃ MEP ᖜࡀቑࡋࡓࡀࠊ0.5 Hz M1 rTMS ᚋࡣኚࡀぢࡽࢀ࡞ࡗࡓ࠸ ࠺ࡶࡢࡶ࠶ࡿ[97]ࠋTheta burst stimulation㸦௨ୗ TBS㸧[98, 99]࠸࠺ᆒ୍࡞ࣜ ࢬ࣒ࡼࡿ rTMS ࢆ⏝࠸ࡓ◊✲࡛ࡶ⤖ᯝࡣ୍ᐃࡋ࡚࠾ࡽࡎࠊྠഃ M1 ࡣᢚᅽຠ ᯝࢆㄏᑟࡍࡿᣢ⥆ᛶ TBS ࡼࡾᑐഃ M1 ่⃭ࡢ MEP ᖜࡀቑ[100, 101]ࡶࡋ ࡃࡣῶᑡ[102]ࠊࡲࡓࠊྠഃ M1 ࡣቑᙉຠᯝࢆㄏᑟࡍࡿ㛫Ḟⓗ TBS ࡼࡾᑐഃ M1 ่⃭ࡼࡿ MEP ࡀῶᑡࡍࡿ[101, 103]࠸࠺ሗ࿌ࡀࡳࡽࢀࡿࠋ᭱㏆ࡢ paired associative stimulation㸦௨ୗ PAS㸧[104, 105]࠸࠺ឤぬධຊ M1 ่⃭ࢆ⤌ࡳྜ ࢃࡏࡓ rTMS ࡼࡿ◊✲࡛ࡣ่⃭ഃࡢቑᙉຠᯝㄏᑟࡢ⤖ᯝࠊᑐഃ M1 ࡛ࡢ MEP ቑࢆㄆࡵࡓ[106]ࠋࡇࡢࡼ࠺่⃭ഃࡢ rTMS ࡢຠᯝᑐഃ M1 ࡢኚࡣ୍ ᐃࡢ⤖ᯝࡀᚓࡽࢀ࡚࠸࡞࠸ࠋࡉࡽࠊࡇࢀࡽᑐഃࡢ MEP ኚ IHI ࡢኚࡢ㛵 ಀᛶࡘ࠸࡚ࡶ୍ᐃࡢ⤖ᯝࡀᚓࡽࢀ࡚࠸࡞࠸ࠋIHI ࡣ 1 Hz rTMS ࡛ῶᑡࡍࡿ࠸ ࠺ሗ࿌ࡀ࠶ࡿࡀࠊ2 ࡘࡢሗ࿌ࡢ㛫࡛ MEP ࡢኚࡘ࠸࡚ࡣ┦㐪ࡀࡳࡽࢀࡓ[92, 95]ࠋTBS ࡛ࡣ IHI ࡣኚࡋ࡞ࡗࡓ࠸࠺ሗ࿌[101]ࠊPAS ᚋࡣ IHI ࡀῶᑡࡋ ࡓ࠸࠺ሗ࿌[106]ࡶࡳࡽࢀࡓࠋ ᡃࠎࡣ᭱㏆᪂ࡋ࠸ rTMS ࡢ᪉ἲࡋ࡚ QPS ࢆሗ࿌ࡋࡓ[31, 32]ࠋQPS ࡣ่⃭ࡋ ࡓ M1 ᑐࡋࠊ୧᪉ྥᛶࡢྍረᛶࢆㄏᑟࡍࡿࡇࡀ࡛ࡁࡿࠋᅇࡢ◊✲࡛ᑐഃࡢ 㠀่⃭ഃ M1 ࡛ࡢ MEP ࡢ㛗ᮇຠᯝࢆࡳࡿࡓࡵ QPS ࢆ⏝࠸ࡓ⌮⏤ࡋ࡚ࡣ௨ୗ ࡢࡇࡀ࠶ࡆࡽࢀࡿࠋ㛗ᮇຠᯝࡢಶேෆኚືࡣ M1 ࡢ⓶㉁ෆᅇ㊰ࡼࡾᙳ㡪ࡉࢀ 65 ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿ[107]ࠋࡇࢀࡲ࡛ࡢሗ࿌࡛⏝࠸ࡽࢀ࡚࠸ࡿ rTMS ࡣࠊᚑ᮶ᆺ rTMSࠊPASࠊTBS ࡞ࡀ࠶ࡿࡀࠊ࠸ࡎࢀࡶ่⃭ࡉࢀࡓ M1 ࠾࠸࡚ࠊMEP ᖜ ࡢኚຍ࠼ࠊ⓶㉁ෆᢚไࡸಁ㏻ࡢኚࡶぢࡽࢀ࡚࠸ࡿࠋ่⃭ࡉࢀࡓ M1 ࠾ࡅ ࡿᢚไಁ㏻ࡢࣂࣛࣥࢫࡣࠊᑐഃࡢ㠀่⃭ഃ M1 」㞧࡞ᙳ㡪ࢆ࠼ࡿྍ⬟ᛶࡀ ࠶ࡿࠋ࡞ࡐ࡞ࡽࠊSICI ࡸ LICI ࡢᏑᅾࡼࡾ IHI ࢆῶᙅࡍࡿ[58]࡞㛵㐃ࡍࡿᙳ 㡪ࢆ࠼ࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵ࡛࠶ࡾࠊࡇࢀࡀಶேෆኚືࡢཎᅉ࡞ࡾ࠺ࡿࠋ୍ ᪉ࠊQPS ࡣ▷₯⓶㉁ෆಁ㏻㸦short-interval intracortical facilitationࠊ௨ୗ SICF㸧 MEP ࢆኚࡉࡏࡿ୍᪉ࠊSICI ࡸ LICI ᙳ㡪ࢆ࠼࡞࠸ࠋࡑࡢࡓࡵࠊQPS ࡼࡾᑐഃ M1 ⏕ࡌࡓኚࡣࠊࡢ᪉ἲ࡛ぢࡽࢀࡿࡇࡢࡼ࠺࡞㛵㐃ࡍࡿຠᯝࡢᙳ 㡪ࢆཷࡅ࡞࠸༢⣧࡞ࡶࡢ࡛࠶ࡿ⪃࠼ࡽࢀࡿࠋࡉࡽࡢ᪉ἲࠊ≉ TBS ࡣ ຠᯝࡢಶே㛫ኚືࡶࡁ࠸ࡇࡀ▱ࡽࢀ࡚࠸ࡿ[107]ࠋࡑࢀຍ࠼ࠊಶே㛫ኚື ࡘ࠸࡚࠸࠼ࡤࠊPAS ࡸ TBS ࡢຠᯝࡣ BDNF 㑇ఏᏊከᆺࡼࡿᙳ㡪ࢆཷࡅࡿ ࡉࢀࡿ[108]ࠋࡋࡋ࡞ࡀࡽ QPS ࡣ BDNF ࡼࡿಶே㛫ኚືࡀᑡ࡞࠸[109]ࠋࡑࡢ ࡓࡵࠊQPS ࢆ⏝࠸ࡿࡇ࡛ኚືᖜࢆᑠࡉࡃࡍࡿࡇ࡛ࡁࠊQPS ࡼࡿᑐഃ M1 ࡢຠᯝࢆ◊✲ࡋࡸࡍ࠸≧ែ࡞ࡿࠋࡇࢀࡀᮏ◊✲࡛ QPS ࢆ⏝࠸ࡓ⌮⏤࡛࠶ࡿࠋ ࢃࢀࢃࢀࡣࠊ⬻ᱱ⥺⥔࠾ࡅࡿఏ㐩ຠ⋡ࡢኚࡀᑐഃ M1 ᑐࡋ࡚⯆ዧᛶኚ ࢆᘬࡁ㉳ࡇࡍࡢ࡛ࡣ࡞࠸ࡢ௬ㄝࢆ⪃࠼ࠊ่⃭ࡋࡓ M1 ࡢྍረᛶኚࡀ㉳ࡁࡓ ࡋ࡚ࡶࠊ⬻ᱱᶵ⬟ࡀኚࡋ࡞࠸ሙྜࡣᑐഃ M1 ᑐࡋ࡚ຠᯝࢆཬࡰࡉ࡞࠸ࡢ 66 ࡛ࡣ࡞࠸⪃࠼ࡓࠋ ࡇࡢ◊✲࡛ࡣࠊM1 ᑐࡍࡿ QPS ࡀᑐഃ M1 ᑐࡋ࡚ྍረᛶࢆㄏᑟࡍࡿ࠺ ࢆㄪࠊྠ QPS ๓ᚋ࡛ࡢ⓶㉁ෆᅇ㊰ࡸ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࢆẚ㍑ࡋࡓࠋ 67 㹙᪉ἲ㹛 ᑐ㇟ 12 ྡࡢᖖ⿕㦂⪅ᑐࡋྠពࢆᚓࡓࡢࡕᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓࠋ⿕㦂⪅ࡣዪᛶ 2 ྡࠊ⏨ᛶ 10 ྡࠊᖹᆒᖺ㱋 38.4 ṓs7.1㸦SD㸧ࠊ30ࠥ49 ṓࡢ⠊ᅖ࡛࠶ࡗࡓࠋ࠸ࡎ ࢀࡢ⿕㦂⪅ࡶ⚄⤒Ꮫⓗࠊ⢭⚄ⓗࠊࡑࡢࡢ་Ꮫⓗ࡞ၥ㢟ࡣ࡞ࡃࠊTMS ᑐࡍࡿ ⚗ᚷࡶヱᙜࡋ࡞ࡗࡓ[110]ࠋ࡚ࡢ⿕㦂⪅ࡣྑࡁ࡛࠶ࡗࡓ[111]ࠋᮏ◊✲ࡢ ⿕㦂⪅ 12 ྡࡢ࠺ࡕࠊ10 ྡࡣ➨ 2 ❶ࡢ⿕㦂⪅ྠ୍࡛࠶ࡗࡓࡀࠊࡇࡢ 2 ࡘࡢ◊✲ ࡢ㛫ࡣ 6 ᭶௨ୖ✵࠸࡚࠾ࡾࠊ࠾࠸ࡢᐇ㦂ࡢᙳ㡪ࡣ࡞࠸⪃࠼ࡽࢀࡓࠋᮏ ◊✲ࡣ࣊ࣝࢩࣥ࢟ᐉゝࡢ⌮ᣦ㔪ᇶ࡙ࡁࠊᮾிᏛ⌮ጤဨࡢᢎㄆࢆᚓ࡚ ࠾ࡇ࡞ࡗࡓࠋ グ㘓 ୧ഃ FDI ࡼࡾ┤ᚄ 9 mm ࡢ Ag/AgCl ⾲㠃㟁ᴟࢆ⏝࠸ࠊbelly-tendon ἲࡼࡾ MEP ࢆグ㘓ࡋࡓࠋ⾲㠃➽㟁ᅗࡢᛂࡣ 100ࠥ3000 Hz ࣇࣝࢱ࣮ࡉࢀࡓࣥࣉ 㸦Biotop; GE Marquette Medical Systems Japan㸧ධຊࡉࢀࡓࠋࡑࡢᚋ 10 kHz ࡢ ࢧࣥࣉࣜࣥࢢ࿘Ἴᩘ࡚ࢹࢪࢱࣝࡉࢀࠊࢥࣥࣆ࣮ࣗࢱ࣮ಖᏑࡋࠊᚋゎᯒ ࢆ࠾ࡇ࡞ࡗࡓ㸦TMS Bistim Tester; Medical Try System㸧ࠋ ⓶㉁ࡢ⯆ዧᛶࡣ୧ഃ FDI ࡽࡢ MEP ࡢ㡬Ⅼ㛫ᖜ࡛ホ౯ࢆ࠾ࡇ࡞ࡗࡓࠋᐇ㦂 68 5 ࢆ㝖ࡃྛᐇ㦂ࡢ㛫ࠊᑐ㇟⪅ࡣ᳔Ꮚᴦᗙࡾࠊ࢜ࢩࣟࢫࢥ࣮ࣉࣔࢽࢱ࣮࡛☜ㄆ ࡋ࡞ࡀࡽࠊFDI ࢆᏳ㟼≧ែಖࡘࡼ࠺ࡋࡓࠋ⏝ព➽ࡢ㝶ព⦰ࡀΰධࡋࡓ ヨ⾜ࡣゎᯒࡽ㝖እࡋࡓࠋ TMS TMS ࡢ่⃭ࡣࠊᡭᣢࡕࡢ 8 ࡢᏐࢥࣝ㸦ྛࡢእᚄࡀ 9 cm; Magstim Co.㸧ࢆ ⏝࠸ࡓࠋ༢Ⓨࡢ༢┦ᛶ TMS ࣃࣝࢫࡣ☢Ẽ่⃭⨨㸦Magstim 200; Magstim Co.㸧 ࢆ⏝࠸࡚ฟຊࡋࡓࠋ୧ഃ FDI ࡽ MEP ࢆㄏᑟࡍࡿࡢ᭱㐺࡞ሙᡤ㸦FDI ࡢ࣍ࢵ ࢺࢫ࣏ࢵࢺ㸧ࡣᐇ㦂ࡢࡓࡧỴࡵࡓࠋ8 ࡢᏐࢥࣝࡣ㢌⓶ୖࢥࣝࡀ᥋⥺᪉ྥ ࡞ࡿࡼ࠺⨨ࡁࠊࣁࣥࢻࣝࡀᚋࢁᩳࡵ 45rࡢ᪉ྥ࡞ࡿ⨨⨨࠸ࡓࠋ1 cm ้ࡳ࡛๓ᚋᕥྑ᪉ྥືࡋ่࡚⃭ࡋࠊ᭱ࡶࡁ࡞ᛂࡀᚓࡽࢀࡿ᭱㐺࡞ሙᡤ ࢆỴࡵࡓࠋࡑࡢሙᡤ࡛࣌ࣥ㢌⓶ୖ༳ࢆࡘࡅࠊᐇ㦂ࢆ㏻ࡌ࡚ࢥࣝࢆྠࡌሙ ᡤ⨨ࡅࡿࡼ࠺ࡋࡓࠋ ࡑࢀࡒࢀࡢᐇ㦂ࡢ๓ࠊ୧ഃ FDI ࡢ RMT AMT ࢆ ᐃࡋࡓࠋRMT ࡣᏳ㟼 ࡋࡓ FDI ࠾࠸࡚ࠊ50ȣV ࡢᖜࡢ MEP ࡀ 10 ᅇ୰ 5 ᅇ௨ୖᚓࡽࢀࡿ᭱పࡢᶵ Ეฟຊ್ࡋࡓ[112]ࠋAMT ࡣ FDI ࢆ㝶ព⦰㸦᭱⦰ࡢ 5ࠥ10%㸧ࡋࡓࡁ ࠊ100ȣV ࡢᖜࡢ MEP ࡀ 10 ᅇ୰ 5 ᅇ௨ୖᚓࡽࢀࡿ᭱పࡢᶵᲔฟຊ್ࡋࡓࠋ ่⃭ᙉᗘࡣᶵᲔฟຊࡢ 1%༢࡛ኚ࠼್࡚ࢆỴࡵࡓࠋ 69 QPS ࡣࠊ≉ὀࡢ⤖ྜ⨨ࡘ࡞ࡀࢀࡓ 4 ࡘࡢ☢Ẽ่⃭⨨㸦Magstim 2002; Magstim Co.㸧ࡽ༢┦ᛶ TMS ࣃࣝࢫࢆฟຊࡋࡓ㸦ᅗ 18㸧ࠋࡇࡢ⨨ࡣ 4 ࡘࡢ่ ⃭⨨ࡽ㐃⥆ࡋࡓ 4 Ⓨࡢ༢┦ᛶ☢Ẽ่⃭ࢆ୍ࡘࡢࢥࣝࡽฟຊࡍࡿࡇࡀ ࡛ࡁࡿࠋQPS ࣉࣟࢺࢥ࣮ࣝࡣࠊ4 ࡘࡢ༢┦ᛶ TMS ࡀ ISI 5 ms㸦௨ୗ QPS-5㸧ࡸ ISI 50 ms㸦௨ୗ QPS-50㸧ࡈฟຊࡉࢀࠊࡇࡢ 4 㐃Ⓨࣂ࣮ࢫࢺࡀࣂ࣮ࢫࢺ㛫่ ⃭ 5 s㸦0.2 Hz㸧࡛ 30 ศ㛫⥆ࡃ࠸࠺ࡶࡢ࡛࠶ࡿ㸦ᅗ 19A㸧ࠋࡇࢀࡼࡾ㒊࡛ 360 ࣂ࣮ࢫࢺࠊィ 1440 Ⓨࡢ่⃭ࡀ࠼ࡽࢀࡿࠋࡇࡢᐇ㦂࡛ ISI 5 ms 50 ms ࡢ 2 ࡘࡢࣃ࣓࣮ࣛࢱ࣮ࢆ⏝࠸ࡓ⌮⏤ࡋ࡚ࡣࠊQPS-5 ࡀ่⃭ࡉࢀࡓ M1 ࡛ࡢ LTP ᵝ ຠᯝࡀ᭱ࡶぢࡽࢀࡿ่⃭᮲௳࡛࠶ࡿࡇࠊQPS-50 ࡀ่⃭ࡉࢀࡓ M1 ࡛ࡢ LTD ᵝ ຠᯝࡀ᭱ࡶぢࡽࢀࡿ่⃭᮲௳࡛࠶ࡿࡓࡵ࡛࠶ࡿ[32]ࠋ QPS ࡣᕥ M1 ᑐࡋ࡚࠾ࡇ࡞ࡗࡓࠋ8 ࡢᏐࢥࣝࡣ FDI ࡽ MEP ࢆㄏᑟࡍࡿ ᅗ 18 QPS ⏝ࡢ☢Ẽ่⃭⨨ 4 ྎࡢ☢Ẽ่⃭⨨ࡽࡢฟຊࡀ୍ࡘࡢࢥࣝࢆ㏻ࡋ࡚ฟຊࡉࢀࡿ 70 ࡢ᭱㐺࡞ሙᡤࠊ㢌⓶ୖࢥࣝࡀ᥋⥺᪉ྥ࡞ࡿࡼ࠺⨨ࡁࠊഐ▮≧⥺ ࡽ 45rࡢゅᗘࢆࡘࡅࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀ๓ෆഃࡽᚋእഃὶࢀࡿࡼ࠺ ࡋࡓࠋQPS ࡢ่⃭ᙉᗘࡣྑ FDI ࡢ AMT ࡢ 90%ࡋࡓࠋࡇࡢ่⃭ᙉᗘࢆ⏝࠸ࡓ ⌮⏤ࡋ࡚ࡣࠊྍረᛶࡢㄏᑟࡀ༑ศ࠾ࡇ࡞࠼ࡿ่⃭ᙉᗘ࡛࠶ࡿ☜ㄆࡉࢀ࡚ ࠸ࡿࡓࡵ࡛࠶ࡿ[31]ࠋ୧ഃ FDI ࡣ QPS ࡢ㛫ࠊᏳ㟼ಖࡓࢀࡓࠋ ᐇ㦂ࢹࢨࣥ ᅗ 19 QPS ࡢ่⃭ࣉࣟࢺࢥ࣮ࣝ㸦A㸧ᐇ㦂ࢹࢨࣥ㸦B㸧 A. 4 㐃Ⓨࡢ༢┦ᛶ TMS ࣃࣝࢫࡀ 5 s ࠾ࡁ 30 ศ⧞ࡾ㏉ࡉࢀࡿࠋࡑࢀࡒࢀࡢࣃ ࣝࢫෆࡢ ISI ࡣ 5 ms㸦QPS-5㸧 50 ms㸦QPS-50㸧タᐃࡋࡓࠋ B. QPS-5 ࡶࡋࡃࡣ QPS-50 ࡀᕥ M1 30 ศ㛫࠼ࡽࢀࡓࡀࠊࡑࡢ๓㸦pre㸧 QPS ⤊ᚋ 30 ศ㸦post㸧࡛ࡑࢀࡒࢀࡢࣃ࣓࣮ࣛࢱ࣮ࢆ ᐃࡋࡓࠋ 71 QPS ࡢᑐഃ M1 ᑐࡍࡿຠᯝࢆㄪࡿࡓࡵࠊᕥ M1 ᑐࡍࡿ QPS ࡢ๓㸦pre㸧 30 ศ㛫ࡢ QPS ⤊ᚋࡽ 30 ศᚋ㸦post㸧࠾࠸࡚ᵝࠎ࡞ࣃ࣓࣮ࣛࢱ࣮ࢆ ᐃࡋࡓ㸦ᅗ 19B㸧ࠋࡑࢀࡒࢀࡢࣃ࣓࣮ࣛࢱ࣮ࡢ ᐃࡣ 10㹼15 ศࢆせࡋࡓࠋࡑࡢ ࡓࡵࠊࣃ࣓࣮ࣛࢱ࣮ࡢ ᐃࢆ 5 ࡘࡢᐇ㦂ศࡋ࡚࠾ࡇ࡞࠺ࡇࡋࡓࠋྛᐇ 㦂ࡣྠࡌ⿕㦂⪅࠾࠸࡚ࡣ 1 㐌㛫௨ୖ࠶ࡅ࡚࠾ࡇ࡞ࡗࡓࠋᐇ㦂ࡢ㡰␒ࡣࣛࣥࢲ ࣒ࡋࠊ⿕㦂⪅㛫࡛බᖹࣂࣛࣥࢫࡀࢀࡿࡼ࠺ࡋࡓࠋ ᐇ㦂 1㸸୧ഃࡢ MEPࠊAMTࠊRMT ᑐࡍࡿ QPS ࡢᙳ㡪 ᐇ㦂 1 ࡛ࡣࠊMEP ࢆ୧ഃ FDI ࡽグ㘓ࡋࡓࠋ 12 ྡࡢ⿕㦂⪅ࡀཧຍࡋࡓࠋ MEP ࡣྑ M1 ࡶࡋࡃࡣᕥ M1 ࡢ FDI ࡢ࣍ࢵࢺࢫ࣏ࢵࢺ࡛ࡢ༢Ⓨ TMS ࡼࡾグ㘓 ࡋࡓࠋQPS ๓ࡢ pre ホ౯ࠊMEP ࡢᖜࡀ 0.5 mV ๓ᚋ࡞ࡿࡼ࠺ᕥྑࡑࢀ ࡒࢀࡢ่⃭ᙉᗘࢆタᐃࡋࠊྠࡌ่⃭ᙉᗘࢆ QPS ᚋࡢ post ホ౯ࡶ⏝࠸ࡓࠋ6 s0.5 s 㛫㝸࡛ 20 ヨ⾜ࡢ༢Ⓨ TMS ࢆࡑࢀࡒࢀࡢ༙⌫࡛࠾ࡇ࡞ࡗࡓࠋ୧ഃ࡛ RMT AMT ࡶࡑࢀࡒࢀࡢホ౯ ᐃࡋࡓࠋ ᐇ㦂 2㸸㠀่⃭ഃ M1 ࡢ MEP ࣜࢡ࣮ࣝࢺ࣮࢝ࣈᑐࡍࡿ QPS ࡢᙳ㡪 ᕥ FDI ᑐࡍࡿ MEP ࣜࢡ࣮ࣝࢺ࣮࢝ࣈ㸦่⃭ᙉᗘ㸫ᖜ᭤⥺㸧ࡢᐇ㦂 12 ྡ୰ 8 ྡࡀཧຍࡋࡓࠋᕥ FDI ᑐࡍࡿ࣍ࢵࢺࢫ࣏ࢵࢺ༢Ⓨ TMS ࢆ࠼ࡓࠋ6 72 s0.5 s 㛫㝸࡛ 100%, 110%, 120%, 130%, 140%, 150%, 160% RMT ࡢ่⃭ᙉᗘࡢ༢ Ⓨ TMS ࢆ 10 ヨ⾜ࡎࡘࣛࣥࢲ࣒࠼ࡓࠋ ᐇ㦂 3㸸㠀่⃭ഃ M1 ࡢ SICIࠊLICIࠊICFࠊSICF ᑐࡍࡿ QPS ࡢᙳ㡪 ᑐഃ M1 ࡢ⯆ዧᛶᢚไᛶᅇ㊰ࢆ TMS ࢆ⏝࠸ࡓⓎ᳨่⃭࡛ウࡋࡓࠋSICI ICF [10]ࠊLICI [9, 113]ࠊSICF [11, 13]ࢆ 12 ྡ୰ 9 ྡ࡛ㄪࡓࠋࡇࡢᐇ㦂࡛ࡣࠊTMS ࡣ QPS ᑐഃࡢྑ M1 ࠼ࠊMEP ࡣᕥ M1 ࡽグ㘓ࡋࡓࠋ SICI ࡣ ISI 3 ms ࠾࠸࡚ࠊCS ࡢ่⃭ᙉᗘࢆ 70%, 80%, 90% AMT ࡋࡓࠋICF ࡣ ISI 10 ms 15 ms ࠾࠸࡚ࠊCS ࡢ่⃭ᙉᗘࢆ 90% AMT ࡋࡓࠋLICI ࡣ ISI 100 ms ࠾࠸࡚ࠊCS ࡢ่⃭ᙉᗘࢆ 110% RMT ࡋࡓࠋTS ࡢ่⃭ᙉᗘࡣᏳ㟼ࡋࡓ ᕥ FDI ࡛ 0.5 mV ๓ᚋࡢ MEP ᖜࡀᚓࡽࢀࡿᙉࡉࡋࡓࠋ SICF ࡣ ISI 1.3, 1.5, 1.7 ms ࠾࠸࡚ᐇ㦂ࢆ࠾ࡇ࡞ࡗࡓ[11, 13, 114]ࠋ1 Ⓨ┠ࡢ่ ⃭㸦TS㸧ࡢ่⃭ᙉᗘࡣᏳ㟼ࡋࡓᕥ FDI ࡛ 0.5 mV ๓ᚋࡢ MEP ᖜࡀᚓࡽࢀࡿ ᙉࡉࠊ2 Ⓨ┠ࡢ่⃭㸦CS㸧ࡣ 90% AMT ࡋࡓࠋ AMT ࡣ QPS ᚋ᭷ពᕪࢆᣢࡗ࡚ኚࡋ࡞ࡗࡓࡓࡵࠊCS ࡢ่⃭ᙉᗘࡣྠࡌ ್ࢆ⏝࠸ࡓࠋ୍᪉ TS ࡢ่⃭ᙉᗘࡣ่⃭ᚋࡶ 0.5 mV ๓ᚋࡢ MEP ᖜࡀᚓࡽࢀ ࡿࡼ࠺ㄪᩚࢆ࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 4㸸IHI ᑐࡍࡿ QPS ࡢᙳ㡪 73 12 ྡࡢ⿕㦂⪅ࡀཧຍࡋࡓࠋᐇ㦂ࡣ᪤ሗ࿌ྠᵝⓎ่⃭ἲࢆ⏝࠸࡚࠾ࡇ ࡞ࡗࡓ[20, 115]ࠋTS ࡣᕥࡶࡋࡃࡣྑ M1 ࡛࠶ࡾࠊCS ࡣᑐഃࡢ M1 TS ࡼࡾ 10 ࡶࡋࡃࡣ 40 ms ඛ⾜ࡋ࡚࠼ࡓࠋ2 ࡘࡢ 8 ࡢᏐࢥࣝࢆ⏝࠸ࠊFDI ࡢ࣍ࢵࢺࢫ࣏ ࢵࢺୖ࠾࠸ࡓࠋ୧᪉ࡢࢥࣝࡣ㢌⓶ୖࢥࣝࡀ᥋⥺᪉ྥ࡞ࡿࡼ࠺࠾ࡁࠊ ഐ▮≧⥺ࡽ 45rࡢゅᗘࢆࡘࡅࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀ๓ෆഃࡽᚋእഃὶ ࢀࡿࡼ࠺ࡋࡓࠋTS CS ࡢ่⃭ᙉᗘࡣ QPS ࡢ๓ᚋࡶ 0.5 mV ๓ᚋࡢ MEP ᖜࡀᚓࡽࢀࡿᙉࡉタᐃࡋࡓࠋ ᐇ㦂 5㸸IHF ᑐࡍࡿ QPS ࡢᙳ㡪 12 ྡ୰ 8 ྡࡢ⿕㦂⪅ࡀཧຍࡋࡓࠋⰼᓥࡽࡣࣄࢺ㐠ື㔝࠾࠸࡚ࠊ₯ࡀ᪩࠸ IHF ࡀ࠶ࡾࠊ⬻ᱱࢆ㏻ࡿࡶࡢ࡛࠶ࡿሗ࿌ࡋࡓ[21]ࠋࡇࡢ₯ࡢ᪩࠸ಁ㏻ຠᯝࡣ I3 ᑐࡍࡿᛂࡋ࡚ほᐹࡉࢀࡓࡇࡽࠊI3 ࡢኚࢆほᐹࡍࡿࡓࡵࠊFDI ࢆ ㍍ᗘ㝶ព⦰ࡋࡓ≧ែ࡛࠾ࡇ࡞ࡗࡓࠋTS ࡣྑ M1ࠊCS ࡣᕥ M1 ࠊTS 4 ms ඛ⾜ࡋ࡚࠼ࡓࠋ2 ࡘࡢ 8 ࡢᏐࢥࣝࢆ⏝࠸ࠊFDI ࡢ࣍ࢵࢺࢫ࣏ࢵࢺୖ࠾࠸ࡓࠋ ྑ M1 ࠾࠸ࡓ TS ⏝ࡢࢥࣝࡣ㢌⓶ୖࢥࣝࡀ᥋⥺᪉ྥ࡞ࡿࡼ࠺⨨ࡁࠊ ࢥࣝࡢ୰ᚰ࡛㟁ὶࡀᚋ᪉ࡽ๓᪉ὶࢀࡿࡼ࠺ᚋࢁྥࡁ⨨࠸ࡓࠋᕥ M1 ࠾࠸ࡓ CS ⏝ࡢࢥࣝࡣ▮≧⥺᪉ྥ⨨ࡁࠊࢥࣝࡢ୰ᚰ࡛㟁ὶࡀෆഃࡽእ ഃὶࢀࡿࡼ࠺ࡋࡓࠋCS ࡢ่⃭ᙉᗘࡣྑ FDI ࡢ 120% AMT ࡋࡓࠋTS ࡢ่ 74 ⃭ᙉᗘࡣᕥ FDI ࡢᙅ⦰㸦᭱⦰ຊࡢ⣙ 10%㸧࠾࠸࡚ 0.3 mV ๓ᚋࡢ MEP ᖜࡀᚓࡽࢀࡿᙉࡉタᐃࡋࡓࠋ⦰ຊࡣᐇ㦂ࡢ㛫ࠊ࢜ࢩࣟࢫࢥ࣮ࣉࣔࢽࢱ࣮ ࡛☜ㄆࡋࡓࠋ ࢹ࣮ࢱゎᯒ ᐇ㦂 1 MEP ᖜࡢ⤯ᑐ್ࡘ࠸࡚ 2 せᅉࡼࡿ ᐃศᩓศᯒࢆ࠾ࡇ࡞ࡗࡓࠋࡑ ࢀࡒࢀࡢ➽࠾࠸࡚ QPS㸦QPS-5 QPS-50㸧 TIME㸦pre post㸧ࢆ⩌ෆᅉᏊ ࡋࡓࠋ㐠ື㜈್ࡘ࠸࡚ࡣࠊ%MSO ࢆࠊQPS㸦QPS-5 QPS-50㸧ࠊCONTRACTION 㸦RMT AMT㸧ࠊTIME㸦pre post㸧ࢆ⩌ෆᅉᏊࡋ࡚ࠊ3 せᅉࡼࡿ ᐃศᩓศᯒࢆ࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 2 QPS㸦QPS-5 QPS-50㸧ࠊTIME㸦pre post㸧ࠊINTENSITY㸦7 ᮲௳ࠊ100㹼160% RMT㸧ࢆ⩌ෆᅉᏊࡋ࡚ࠊ3 せᅉࡼࡿ ᐃศᩓศᯒࢆ࠾ࡇ࡞ࡗࡓࠋ ᐇ㦂 3㹼5 ྛᐇ㦂࠾࠸࡚ࠊCS ࡈࡑࢀࡒࢀ 10 ヨ⾜ࠊTS ࡢࡳࡢ CS ࡞ࡋࡢ 10 ヨ⾜ ࢆࣛࣥࢲ࣒࠼ࡓࠋCS ୗࡢ MEP 㠀 CS ୗ㸦TS ࡢࡳ㸧ࡢ MEP ࡢᖹᆒ㡬Ⅼ 㛫ᖜࡢẚࢆྛ᮲௳ࠊಶேࡈồࡵࡓࠋ 75 SICI ࡛ࡣ QPS㸦QPS-5 QPS-50㸧ࠊINTENSITY㸦70%ࠊ80%ࠊ90% AMT㸧ࠊTIME 㸦pre post㸧ࢆࠊICF ࡛ࡣ QPS㸦QPS-5 QPS-50㸧ࠊISI㸦10 ms 15 ms㸧ࠊTIME 㸦pre post㸧ࢆࠊSICF ࡛ࡣ QPS㸦QPS-5 QPS-50㸧ࠊISI㸦1.3 msࠊ1.5 msࠊ1.7 ms㸧ࠊTIME㸦pre post㸧ࢆࠊIHI ࡛ࡣᕥྑࡈ QPS㸦QPS-5 QPS-50㸧ࠊISI 㸦10 ms 40 ms㸧ࠊTIME㸦pre post㸧ࢆࠊࡑࢀࡒࢀ⩌ෆᅉᏊࡋ࡚ࠊ3 せᅉ ࡼࡿ ᐃศᩓศᯒࢆ࠾ࡇ࡞ࡗࡓࠋLICI IHF ࡛ࡣ QPS㸦QPS-5 QPS-50㸧 TIME㸦pre post㸧ࢆ⩌ෆᅉᏊࡋ࡚ࠊ2 せᅉࡼࡿ ᐃศᩓศᯒࢆᐇ⾜ ࡋࡓࠋᐇ㦂ࡀ᮲௳㛫ࡢヨ㦂่⃭ࡢ MEP ᖜࡢ㐪࠸ࡼࡗ࡚ᙳ㡪ࢆཷࡅ࡚࠸࡞࠸ ࡇࢆ☜ㄆࡍࡿࡓࡵࠊQPS-5 ࡢ๓ᚋࠊQPS-50 ࡢ๓ᚋࡑࢀࡒࢀ࡛㠀᮲௳่⃭ୗ 㸦ヨ㦂่⃭ࡢࡳ㸧ࡢ MEP ࢆᑐ㇟ paired t ᳨ᐃࢆ࠾ࡇ࡞ࡗࡓࠋ ┦㛵ゎᯒ MEP ᖜࡢኚ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢ㛫㛵㐃ࡀ࡞࠸࠺᳨ウࡍࡿ ࡓࡵ┦㛵ゎᯒࢆ࠾ࡇ࡞ࡗࡓࠋQPS-5 ࡢ᮲௳࠾࠸࡚ࠊΔMEPLtFDI㸦ᕥ FDI ࡢ QPS ᚋࡢ MEP ᖜ㸫QPS ๓ࡢ MEP ᖜ㸧ࢆ┠ⓗኚᩘࡋࠊΔMEPRtFDI㸦ྑ FDI ࡢ QPS ᚋࡢ MEP ᖜ㸫QPS ๓ࡢ MEP ᖜ㸧ࠊΔIHI㸦ᕥЍྑ M1 ࡢ 10 ms ࠾ࡅࡿ IHI ࡢ QPS ᚋࡢ MEP ᖜẚ㸫QPS ๓ࡢ MEP ᖜẚ㸧ࠊΔIHF㸦ᕥЍྑ M1 ࡢ IHF ࡢ QPS ᚋࡢ MEP ᖜẚ㸫QPS ๓ࡢ MEP ᖜẚ㸧ࡢ 3 ࡘࢆㄝ᫂ኚᩘࡋ࡚㔜ᅇ 76 ᖐศᯒࢆ࠾ࡇ࡞ࡗࡓࠋQPS-50 ࡘ࠸࡚ࡣ MEP ኚࡀ᭷ព࡛࡞ࡗࡓࡓࡵゎᯒ ࢆ࠾ࡇ࡞ࢃ࡞ࡗࡓࠋ ᚲせᛂࡌ࡚㠀⌫㠃ᛶࡢ⿵ṇࡢࡓࡵ Greenhouse-Geisser ⿵ṇࢆ࠾ࡇ࡞ࡗࡓࠋ⤫ ィᏛⓗゎᯒࡣ PASW Statistics 18.0.0㸦IBM㸧ࢆ⏝࠸ࡓࠋp ್ < 0.05 ࢆ᭷ពุ᩿ ࡋࡓࠋ 77 㹙⤖ᯝ㹛 ᐇ㦂 1㸸୧ഃࡢ MEPࠊAMTࠊRMT ᑐࡍࡿ QPS ࡢᙳ㡪 ᕥ M1 ᑐࡍࡿ QPS ᚋࠊ༢Ⓨ TMS ࡼࡿᕥ M1 ࡢ MEP㸦ྑ FDI ࡛グ㘓㸧ࡣ QPS-5 ᚋቑࡋࠊQPS-50 ᚋῶᑡࡋࡓ㸦ᅗ 20A㸧ࠋQPS ࡢຠᯝ[F (1,11) = 4.7, p = 0.053]ഴྥࡣㄆࡵࡓࡀࠊTIME ࡢຠᯝ[F (1,11) = 0.7, p = 0.43]ࡣㄆࡵ࡞ࡗ ࡓࠋQPSTIME ࡢస⏝[F (1,11) = 21.6, p < 0.001]ࢆ᭷ពㄆࡵࡓࠋ༢⣧ຠ ᯝ᳨ᐃ࡛ࡣࠊQPS-5 ࡢ TIME ࡼࡿኚ[F (1,11) = 8.4, p = 0.015]ࠊQPS-50 ࡢ TIME ࡼࡿኚ[F (1,11) = 11.7, p = 0.006]ࢆ࠸ࡎࢀࡶ᭷ពㄆࡵࡓࠋ ᅗ 20 MEP ᖜࡢኚ A. ᕥ M1 ࡢ༢Ⓨ TMS ᑐࡍࡿ MEP ᖜ㸦ྑ FDI グ㘓㸧ࡣ QPS-5 ᚋቑ ࡋࠊQPS-50 ᚋῶᑡࡋࡓࠋ B. ྑ M1 ࡢ༢Ⓨ TMS ᑐࡍࡿ MEP ᖜ㸦ᕥ FDI グ㘓㸧ࡣ QPS-5 ᚋቑ ࡋࡓࠋ⦪㍈ࡣ MEP ᖜ㸦mV㸧ࠊ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05 78 ᕥ M1 ᑐࡍࡿ QPS ᚋࠊ༢Ⓨ TMS ࡼࡿྑ M1 ࡢ MEP㸦ᕥ FDI ࡛グ㘓㸧ࡣ QPS-5 ᚋቑࡋࡓࡀࠊQPS-50 ᚋࡣ᭷ពࡣኚࡋ࡞ࡗࡓ㸦ᅗ 20B㸧ࠋQPS ࡢຠᯝ[F (1,11) = 0.3, p = 0.62]ࠊTIME ࡢຠᯝ[F (1,11) = 1.9, p = 0.19]ࠊQPS TIME ࡢస⏝[F (1,11) = 1.0, p = 0.34]ࡣ࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗࡓࠋ༢⣧ຠ ᯝ᳨ᐃ࡛ࡣࠊQPS-5 ࡢ TIME ࡼࡿኚ[F (1,11) = 8.9, p = 0.012]ࢆ᭷ពㄆࡵࡓ ࡀࠊQPS-50 ࡢ TIME ࡼࡿኚ[F (1,11) = 0.04, p = 0.84]ࡣㄆࡵ࡞ࡗࡓࠋ ୧༙⌫ࡢ RMT ࡶ AMT ࡶ QPS-5 ࡛ࡶ QPS-50 ࡛ࡶኚࡣぢࡽࢀ࡞ࡗࡓ㸦⾲ 6㸧ࠋᕥ M1 ࡛ࡣࠊCONTRACTION ࡢຠᯝ[F (1,11) = 63.6, p < 0.001]ࢆ᭷ពㄆ ࡵࡓࡀࠊQPS ࡢຠᯝ[F (1,11) = 0.001, p = 0.97]ࠊTIME ࡢຠᯝ[F (1,11) = 0.001, p = 0.97]ࠊQPSCONTRACTIONTIME ࡢస⏝[F (1,11) = 1.04, p = 0.33]ࡣ࠸ ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣࠊࡢ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋྑ M1 ࡛ࡣࠊCONTRACTION ࡢຠᯝ[F (1,11) = 102.5, p < 0.001]ࢆ᭷ពㄆࡵࡓࡀࠊQPS ࡢຠᯝ[F (1,11) = 1.54, p = 0.24]ࠊTIME ࡢ ຠᯝ[F (1,11) = 3.3, p = 0.094]ࠊQPSCONTRACTIONTIME ࡢస⏝[F (1,11) = 0.70, p = 0.42]ࡣ࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣࠊࡢ ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋ 79 ᐇ㦂 2㸸㠀่⃭ഃ M1 ࡢ MEP ࣜࢡ࣮ࣝࢺ࣮࢝ࣈᑐࡍࡿ QPS ࡢᙳ㡪 ࣜࢡ࣮ࣝࢺ࣓ࣥࢺ࣮࢝ࣈ࡛ࡣ QPS-5 ᚋ MEP ᖜࡢ᭷ព࡞ቑࢆㄆࡵࡓ㸦ᅗ 21A㸧ࡀࠊQPS-50 ᚋࡣኚࡣㄆࡵ࡞ࡗࡓ㸦ᅗ 21B㸧ࠋ INTENSITY ࡢຠᯝ[F (1,42) = 24.7, p < 0.001]ࢆ᭷ពㄆࡵࠊTIME ࡢຠᯝ [F (1,7) = 5.5, p = 0.052]ࡣഴྥࢆㄆࡵࡓࡀࠊQPS ࡢຠᯝ[F (1,7) = 1.0, p = 0.35] ࡣㄆࡵ࡞ࡗࡓࠋQPSTIMEINTENSITY ࡢస⏝[F (6,42) = 1.2, p = 0.32] ࡣ᭷ព࡛࡞ࡗࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣࠊQPS-5 ࠾࠸࡚ TIME ࡼࡿኚ ࢆ 130% RMT [F (1,7) = 9.5, p = 0.018]ࠊ150% RMT [F (1,7) = 7.6, p = 0.028]ࠊ 160% RMT [F (1,7) = 6.3, p = 0.040]࡛᭷ពㄆࡵࠊ120% RMT [F (1,7) = 4.5, p = 0.071]ࠊ140% RMT [F (1,7) = 4.3, p = 0.077]࡛ࡶຠᯝࡢഴྥࢆㄆࡵࡓࠋQPS-50 ࡛ ࡣࡢ่⃭ᙉᗘ࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋ ⾲ 6 QPS ๓ᚋࡢ⓶㉁ࡢ㐠ື㜈್㸦%MSO㸧 ᕥ M1 ྑ M1 QPS-5 ๓ QPS-5 ᚋ QPS-50 ๓ QPS-50 ᚋ RMT 47.2 (2.8) 46.1 (3.0) 46.7 (2.9) 47.5 (3.1) AMT 29.2 (1.6) 28.8 (1.8) 28.3 (1.9) 28.8 (1.9) RMT 49.9 (3.3) 51.8 (3.3) 48.9 (2.7) 49.8 (3.5) AMT 33.2 (1.8) 33.7 (1.7) 30.9 (1.5) 32.0 (2.1) RMT㸹Ᏻ㟼㐠ື㜈್ࠊAMT㸹⦰㐠ື㜈್ࢆᖹᆒ㸦ᶆ‽ㄗᕪ㸧࡛⾲♧ࠋ 80 ᅗ 21 MEP ᖜࡢࣜࢡ࣮ࣝࢺ࣓ࣥࢺ᭤⥺ A. ྑ M1 ࡢ༢Ⓨ TMS ᑐࡍࡿ MEP ᖜ㸦ᕥ FDI グ㘓㸧ࡣ QPS-5 ᚋቑ ࡋࡓࠋ B. QPS-50 ᚋࡣኚࡋ࡞ࡗࡓࠋᶓ㍈ࡣಶேࡢ RMT ࢆᇶ‽ࡋࡓ%⾲♧ࠊ⦪ ㍈ࡣ MEP ᖜ㸦mV㸧ࠊ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05ࠊ†p < 0.1 81 ᐇ㦂 3㸸㠀่⃭ഃ M1 ࡢ SICIࠊLICIࠊICFࠊSICF ᑐࡍࡿ QPS ࡢᙳ㡪 TS ࡼࡿ MEP ᖜࡣࡢ᮲௳࡛ࡶ TIME ࡼࡗ࡚ኚࡋ࡞ࡗࡓ㸦⾲ 7㸧ࠋ QPS-5 QPS-50 ࡢ࠸ࡎࢀࡢᚋ࡛ࡶ SICIࠊLICIࠊICFࠊSICF ᭷ព࡞ኚࡣㄆࡵ ࡞ࡗࡓ㸦ᅗ 22㸧ࠋ SICI ࡛ࡣࠊINTENSITY ࡢຠᯝ[F (2,16) = 10.7, p = 0.001]ࢆㄆࡵࠊ70% 90% AMT㸦p = 0.018㸧ࠊ80% 90% AMT㸦p = 0.012㸧ࡢ㛫ᕪࢆㄆࡵࡓࠋQPS ࡢຠ ᯝ[F (1,8) = 0.008, p = 0.93]ࠊTIME ࡢຠᯝ[F (1,8) = 0.02, p = 0.89]ࠊQPS INTENSITYTIME ࡢస⏝[F (2,16) = 0.04, p = 0.96]ࡢ࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ ࡗࡓࠋ ༢⣧㸫༢⣧ຠᯝ࡛ࡣࡢ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋ LICI ࡛ࡣࠊQPS ࡢຠᯝ[F (1,8) = 0.007, p = 0.93]ࠊTIME ࡢຠᯝ[F (1,8) = 0.004, p = 0.95]ࠊQPSTIME ࡢస⏝[F (1,8) = 0.001, p = 0.97]࠸ࡎࢀࡶ᭷ព࡛ ࡣ࡞ࡗࡓࠋ༢⣧ຠᯝ᳨ᐃ࡛ࡣࡢ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗ ࡓࠋ ⾲ 7 ྛᐇ㦂࡛ࡢヨ㦂่⃭ࡼࡿ MEP ᖜ㸦mV㸧 QPS-5 ๓ QPS-5 ᚋ p QPS-50 ๓ QPS-50 ᚋ p SICI/ICF/LICI 0.46 (0.07) 0.46 (0.11) 0.97 0.49 (0.07) 0.48 (0.08) 0.83 SICF 0.45 (0.10) 0.45 (0.09) 0.99 0.51 (0.08) 0.48 (0.08) 0.81 IHI㸦ྑЍᕥ㸧 0.57 (0.06) 0.70 (0.10) 0.34 0.63 (0.10) 0.68 (0.22) 0.56 IHI㸦ᕥЍྑ㸧 0.50 (0.06) 0.54 (0.06) 0.60 0.51 (0.03) 0.49 (0.07) 0.72 0.33 (0.01) 0.69 0.36 (0.08) 0.33 (0.05) 0.64 IHF 0.34 (0.03) ྛࣃ࣓࣮ࣛࢱ࣮ࢆᖹᆒ㸦ᶆ‽ㄗᕪ㸧࡛⾲♧ࠋ 82 ᅗ 22 ⓶㉁ෆᢚไ࣭ಁ㏻ࡢኚ A. ྑ M1 ࡢ SICI㸦70ࠊ80ࠊ90% AMT㸧ࡣኚࡋ࡞ࡗࡓࠋ B. ྑ M1 ࡢ LICI ࡣኚࡋ࡞ࡗࡓࠋ C. ྑ M1 ࡢ ICF㸦ISI 10 msࠊ15 ms㸧ࡣኚࡋ࡞ࡗࡓࠋ D. ྑ M1 ࡢ SICF㸦ISI 1.3 msࠊ1.5 msࠊ1.7 ms㸧ࡣኚࡋ࡞ࡗࡓࠋ ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ 83 ICF ࡛ࡣࠊQPS ࡢຠᯝ[F (1,8) = 0.06, p = 0.82]ࠊISI ࡢຠᯝ[F (1,8) = 1.8, p = 0.21]ࠊTIME ࡢຠᯝ[F (1,8) = 0.06, p = 0.82]ࠊQPSISITIME ࡢస⏝[F (1,8) = 0.62, p = 0.45]࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣࡢ ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋ SICF ࡛ࡣࠊQPS ࡢຠᯝ[F (1,8) = 0.05, p = 0.83]ࠊISI ࡢຠᯝ[F (2,16) = 0.39, p = 0.68]ࠊTIME ࡢຠᯝ[F (1,8) = 0.07, p = 0.80]ࠊQPSISITIME ࡢస⏝ [F (2,16) = 2.5, p = 0.11]࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣ ࡢ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋ ᐇ㦂 4㸸IHI ᑐࡍࡿ QPS ࡢᙳ㡪 ᕥ M1 ᑐࡍࡿ QPS ᚋࠊᕥЍྑ M1 ࡢ IHI㸦ISI 10 ms㸧ࡣ QPS-5 ᚋቑࡋࡓ ࡀࠊQPS-50 ᚋࡣኚࡏࡎࠊྑЍᕥ M1 ࡢ IHI ࡶኚࡋ࡞ࡗࡓ㸦ᅗ 23㸧ࠋ ᕥЍྑ M1 ࡢ IHI㸦ᕥ FDI グ㘓㸧࡛ࡣࠊQPS ࡢຠᯝ[F (1,11) = 1.6, p = 0.23]ࠊ ISI ࡢຠᯝ[F (1,11) = 0.02, p = 0.89]ࠊTIME ࡢຠᯝ[F (1,11) = 2.8, p = 0.13]ࠊ QPSISITIME ࡢస⏝[F (1,11) = 4.0, p = 0.07]ࡢ࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗ ࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣࠊQPS-5 ࡢ ISI 10 ms ࡢࡁࡢࡳ TIME ࡼࡿ᭷ ពᕪࢆㄆࡵࡓ[F (1,11) = 11.7, p = 0.006]ࠋ ྑЍᕥ M1 ࡢ IHI㸦ྑ FDI グ㘓㸧࡛ࡣࠊQPS ࡢຠᯝ[F (1,11) = 0.07, p = 0.79]ࠊ 84 ISI ࡢຠᯝ[F (1,11) = 1.38, p = 0.26]ࠊTIME ࡢຠᯝ[F (1,11) = 0.03, p = 0.87]ࠊ QPSISITIME ࡢస⏝[F (1,11) = 0.03, p = 0.86]ࡢ࠸ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗ ࡓࠋ༢⣧㸫༢⣧ຠᯝ᳨ᐃ࡛ࡣࡢ᮲௳࡛ࡶ TIME ࡼࡿኚࢆㄆࡵ࡞ࡗࡓࠋ ᅗ 23 IHI ࡢኚ A. ᕥЍྑ M1 ࡢ ISI 10 ms ࡛ࡢ IHI ࡣ QPS-5 ᚋቑࡋ QPS-50 ᚋ࡛ኚࡋ࡞ ࡗࡓࠋ B. ྑЍᕥ M1 ࡢ IHI ࡣኚ࡞ࡗࡓࠋ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05 85 ᐇ㦂 5㸸IHF ᑐࡍࡿ QPS ࡢᙳ㡪 ᕥ M1 ᑐࡍࡿ QPS ᚋࠊᕥЍྑ M1 ࡢ IHF ࡣ QPS-5 ᚋቑࡋࡓࡀࠊQPS-50 ᚋࡣኚࡋ࡞ࡗࡓ㸦ᅗ 24㸧ࠋQPS ࡢຠᯝ[F (1,7) = 0.63, p = 0.45]ࠊTIME ࡢ ຠᯝ[F (1,7) = 1.5, p = 0.26]ࠊQPSTIME ࡢస⏝[F (1,7) = 1.1, p = 0.33]ࡣ࠸ ࡎࢀࡶ᭷ព࡛ࡣ࡞ࡗࡓࠋ༢⣧ຠᯝ᳨ᐃ࡛ࡣࠊQPS-5 ᚋ IHF ᭷ព࡞ኚ ࢆㄆࡵࡓࡀ[F (1,7) = 7.7, p = 0.027]ࠊQPS-50 ᚋࡣኚࢆㄆࡵ࡞ࡗࡓ[F (1,7) < 0.001, p = 0.99]ࠋ ᅗ 24 IHF ࡢኚ ᕥЍྑ M1 ࡢ IHF ࡣ QPS-5 ᚋቑࡋࡓࡀ QPS-50 ᚋ࡛ࡣኚࡋ࡞ࡗࡓࠋ ࢚࣮ࣛࣂ࣮ࡣᶆ‽ㄗᕪࢆ♧ࡍࠋ*p < 0.05 86 ┦㛵ゎᯒ 㔜ᅇᖐศᯒࡼࡿࣔࢹࣝ᭷ព࡞ຠᯝࢆㄆࡵࡓ[F (3,8) = 5.79, p = 0.044]ࠋᶆ‽ ೫ᅇᖐಀᩘࡣ ΔMEPRtFDI ࡀ-0.27㸦t = -0.87, p = 0.43㸧ࠊΔIHI ࡀ-0.36㸦t = -1.47, p = 0.20㸧ࠊΔIHF ࡀ 0.89㸦t = 3.15, p = 0.025㸧࡛࠶ࡗࡓࠋΔMEPLtFDI ┦㛵ࡀぢࡽࢀ ࡓࡢࡣ ΔIHF ࡢࡳ࡛࠶ࡗࡓࠋ ┦㛵ಀᩘࡣ 0.88ࠊỴᐃಀᩘࡣ 0.78 ࡛࠶ࡗࡓࠋΔMEPLtFDI ΔIHF ࡢ㛫ࡢᩓᕸᅗࢆᅗ 25 ♧ࡋࡓࠋ ᅗ 25 MEP ᖜኚ IHF ኚࡢ┦㛵 QPS-5 ᚋࠊᕥЍྑ M1 ࡢ IHF ࡢኚࡀྑ M1 ࡢ༢Ⓨ TMS ᑐࡍࡿ MEP ᖜ㸦ᕥ FDI グ㘓㸧᭷ព┦㛵ࡋࡓࠋ ᶓ㍈ࡣ MEP ᖜࡢኚ㸦mV㸧ࠊ⦪㍈ࡣ IHF ࡢ MEP ᖜẚࡢኚࢆ♧ࡍࠋ 87 㹙⪃ᐹ㹛 ᮏ◊✲࡛ࡣࠊᑐഃ M1 ᑐࡍࡿ QPS ࡀ M1 ࡢྍረᛶࢆㄏᑟࡋࠊ⬻༙⌫㐠 ື㔝㛫ㄪ⠇ࡢኚࢆకࡗࡓࡇࢆ♧ࡋࡓࠋᕥ M1 ᑐࡍࡿ QPS-5 ࡣࠊ่⃭ࡋࡓ ᕥ M1 LTP ᵝࡢኚࢆࡶࡓࡽࡍࡀࠊ㠀่⃭ഃࡢྑ M1 ࡶ LTP ᵝኚࢆࡶࡓ ࡽࡋࡓࠋ୍᪉ࠊᕥ M1 ᑐࡍࡿ QPS-50 ࡣࠊ่⃭ࡋࡓᕥ M1 LTD ᵝࡢኚࢆࡶ ࡓࡽࡍࡀࠊ㠀่⃭ഃࡢྑ M1 ࡣ᭷ព࡞ኚࢆ㉳ࡇࡉ࡞ࡗࡓࠋ㠀่⃭ഃࡢྑ M1 ࡢ RMTࠊAMTࠊ⓶㉁ෆᢚไ㸦SICI LICI㸧ࠊ⓶㉁ෆಁ㏻㸦ICF SICF㸧ࡣ QPS-5 ࡢᚋ࡛ࡶ QPS-50 ࡢᚋ࡛ࡶኚࡋ࡞ࡗࡓࠋᕥЍྑ M1 ࡢ IHI ࡢᢚไࡢ⛬ ᗘ IHF ࡢಁ㏻ࡢ⛬ᗘࡣ࠸ࡎࢀࡶᕥ M1 ࡢ QPS-5 ᚋ᭷ពቑຍࡋࠊᕥ FDI ࡢ MEP ᖜࡢኚࡣ IHF ࡢኚ᭷ព࡞┦㛵ࡀぢࡽࢀࡓࠋࡇࢀࡣࠊM1 ࡢ rTMS ࡼࡾࠊIHI ࡔࡅ࡛࡞ࡃ IHF ࡀኚࡋࠊࡉࡽᑐഃࡢ MEP ᖜ᭷ព࡞┦㛵ࡀ ぢࡽࢀࡓࡢࡣ IHF ࡛࠶ࡗࡓࡇࢆ♧ࡋࡓ᭱ึࡢሗ࿌࡛࠶ࡿࠋࡉࡽࠊ୧ᡭࡢ MEP ᖜࡢኚࡀ┦㛵ࡋ࡞ࡗࡓࡇࡽࡣࠊ2 ࡘࡢ༙⌫ࡢྍረᛶኚࡀ⊂❧㉳ࡁ ࡚࠸ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡓࠋ rTMS ࡼࡿᑐഃ M1 ࡢኚ ࡇࢀࡲ࡛ࡢሗ࿌࡛ࡣࠊrTMS ่࡛⃭ഃ M1 LTP ᵝࡢኚࢆ㉳ࡇࡋࡓሙྜࠊᑐ ഃ M1 ࡛ࡣᵝࠎ࡞ᛂࡀぢࡽࢀࡓࠋ5 Hz rTMS PAS ࡣ㠀่⃭ഃ M1 ࡢ MEP ࢆ 88 ቑࡉࡏࡓ[97, 106]ࠋࡇࡢ୧ഃࡢ M1 ࡛ྠࡌ᪉ྥኚࡍࡿ⤖ᯝࡣᅇࡢ⤖ᯝ ୍⮴ࡍࡿࡶࡢࡀ࠶ࡿࠋ୍᪉ࠊ่⃭ഃ M1 LTP ᵝኚࢆᘬࡁ㉳ࡇࡍ iTBS ࡣࠊᑐ ഃ M1 ࡢ⯆ዧᛶࢆపୗࡉࡏࡓ[101, 103]ࠋrTMS ่࡛⃭ഃ M1 LTD ᵝࡢኚࢆ ㉳ࡇࡍሙྜ࡛ࡶྠᵝࠊᑐഃ M1 ࡢᛂࡣ୍ᐃ࡛ࡣ࡞ࡗࡓࠋ1 Hz rTMS ᚋࡣࠊ ᑐഃ M1 ࡘ࠸࡚⯆ዧᛶࡢቑࡶῶᑡࡶሗ࿌ࡉࢀ࡚࠸ࡿ[91, 92, 93, 94, 95, 96]ࠋ ่⃭ഃ M1 LTD ᵝኚࢆᘬࡁ㉳ࡇࡍ cTBS ࡶࠊᑐഃ M1 ࡘ࠸࡚ಁ㏻[98, 101] ࡶᢚไ[102]ࡶࡳࡽࢀࡓࠋࡇࢀࡽ rTMS ࡢ㐲㝸ຠᯝࡣࣉࣟࢺࢥ࣮ࣝࡢ㐪࠸ࡼࡗ ࡚㉳ࡁ࡚࠸ࡿࠋࡋࡋ࡞ࡀࡽࠊ᭱㏆ࡢ QPS ࢆ㝖࠸ࡓ rTMS ࡢᵝࠎ࡞ࣉࣟࢺࢥ࣮ ࣝࡢຠᯝࡢ㐪࠸ࢆぢࡓሗ࿌࡛ࡣࠊࡢ rTMS ࣉࣟࢺࢥ࣮ࣝᚋ࡛ࡶᑐഃ M1 ᭷ព ࡞ຠᯝࡣぢࡽࢀ࡞ࡗࡓࡉࢀࡓ[90]ࠋᮏ◊✲࡛ࡣࠊQPS-5 ࡀᑐഃ M1 ࡶྠ᪉ ྥᛶస⏝ࡍࡿ᭷ព࡞ຠᯝࢆㄏᑟࡋࡓࡇࢆ♧ࡋࡓࠋ ᑐഃ M1 ࡢኚ⬻༙⌫㐠ື㔝㛫ㄪ⠇ຠᯝ ᑐഃ M1 ࡢྍረᛶኚ IHI ࡸ IHF ࡞ࡢ⬻༙⌫㐠ື㔝㛫ࡢㄪ⠇ຠᯝࡢኚ ࡘ࠸࡚ࡣࠊࡇࢀࡲ࡛࠶ࡲࡾ᫂ࡽࡉࢀ࡚ࡇ࡞ࡗࡓࠋ㠀่⃭ഃ M1 LTP ᵝኚࢆ㉳ࡇࡋࡓ㝿ࡢ IHI ࡢኚࡣࠊࡇࢀࡲ࡛࠸ࡃࡘሗ࿌ࡉࢀ࡚࠸ࡿ[92, 95, 101, 106]ࠋTBS ࡣ IHI ኚࢆ⏕ࡌࡎ[101]ࠊ1 Hz rTMS PAS㸦25 ms㸧ࡣ MEP ቑ IHI ῶᑡࢆྠㄆࡵࡓ[92, 106]ࠋࡇࢀࡽࡢሗ࿌࡛ࡢඹ㏻ࡢゎ㔘ࡋ࡚ࡣࠊ 89 IHI ࡢῶᑡࡀ㠀่⃭ഃ M1 ࢆ⬺ᢚไࡉࡏࡓ࠸࠺ࡶࡢ࡛࠶ࡿࠋᮏ◊✲࡛ࡣࠊQPS-5 ࡀ㠀่⃭ഃ M1 ࡢ MEP ࢆቑࡉࡏࠊ่⃭ഃࡽ㠀่⃭ഃ M1 ࡢ IHI ࡶቑࡉ ࡏࡓࡇࢆ♧ࡋࡓࠋࡇࢀࡣࠊQPS-5 ࡼࡿᑐഃ M1 ࡢ LTP ᵝኚࡣࡇࢀࡲ࡛ ࡢࣉࣟࢺࢥ࣮࡛ࣝሗ࿌ࡉࢀ࡚࠸ࡿࡶࡢࡣ␗࡞ࡿᶵᗎ࡛⏕ࡌ࡚࠸ࡿྍ⬟ᛶࢆ ♧၀ࡋࡓࠋᮏ◊✲࡛ࡣࠊQPS ᚋࡢ IHF ࡢኚࡘ࠸࡚ึࡵ࡚ㄪࡓࡀࠊ่⃭ഃ ࡽ㠀่⃭ഃ M1 ࡢ IHF ࡶࡲࡓ QPS-5 ᚋቑࡋࡓࠋ ᅇࡢ◊✲࡛ࡣࠊQPS-5 ᚋࡢᑐഃ M1 ᑐࡍࡿ LTP ᵝኚࡀࠊᢚไᛶ࣭ಁ㏻ ᛶ୧᪉ࡢ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢኚࢆకࡗ࡚࠸ࡿࡇࡀ♧ࡉࢀࡓࠋࡉࡽࠊ IHF ࡢቑࡀ㠀่⃭ഃ M1 ࡛ࡢ LTP ᵝኚࡢ⛬ᗘ᭷ព┦㛵ࡋࡓ୍᪉ࠊIHI ࡢ ῶᑡࡣ┦㛵ࡀ࡞ࡗࡓࠋࡇࢀࡽ 3 ࡘࡢኚࡘ࠸࡚ࠊ௨ୗࡢࡼ࠺ㄝ࡛᫂ࡁ ࡿࡢ࡛ࡣ࡞࠸⪃࠼ࡓࠋ่⃭ഃ M1 ࡛ LTP ᵝኚࡀ㉳ࡁࡓ㝿ࠊ⬻ᱱࢆࡋࡓ ⯆ዧᛶࡢ⤖ྜᢚไᛶࡢ⤖ྜࡀ୧᪉ቑᙉࡉࢀࡿ㸦ᅗ 26㸧ࠋࢩࢼࣉࢫቑᙉࡣ⬻ᱱ⥺ ⥔࡛⏕ࡌࠊ㠀่⃭ഃ M1 ࡢ⯆ዧᛶࡶࡋࡃࡣᢚไᛶࡢᅾࢽ࣮ࣗࣟࣥᑐࡋྍረᛶ ኚࡀ⏕ࡌࡿࠋ⬻ᱱࢆࡋ࡚⯆ዧᛶస⏝ࡍࡿࢽ࣮ࣗࣟࣥࡣᑐഃࡢ㗹య⣽⬊ ▷࠸₯࡛స⏝ࡋࠊᢚไᛶస⏝ࡍࡿࢽ࣮ࣗࣟࣥࡣᅾࢽ࣮ࣗࣟࣥࢆࢆࡋ࡚ ࡼࡾ㛗࠸₯࡛ᑐഃࡢ㗹య⣽⬊స⏝ࡍࡿ⪃࠼ࡽࢀࡿࠋMEP ࢆ⏕ࡌࡉࡏࡿ TMS ࡣ₯ᅾⓗ࡞⯆ዧᛶᅾࢽ࣮ࣗࣟࣥస⏝ࡋࠊᢚไᛶᅾࢽ࣮࡛ࣗࣟࣥࡣ࡞ ࠸⪃࠼ࡽࢀࡿࡓࡵࠊLTP ᵝኚࡢᚋᑐഃ M1 ࡢ⯆ዧᛶࡀቑᙉࡋࡓ⪃࠼ࡽࢀ 90 ࡓࠋᅇぢࡽࢀࡓ 3 ࡘࡢኚࡘ࠸࡚ࠊࡢㄝ᫂ࡶ⪃࠼ࡽࢀࡿࠋࡋࡋ࡞ࡀࡽࠊ ࡇࢀࡽ 3 ࡘࡢᅉᯝ㛵ಀࢆ᥈ࡿࡇࡣᮏ◊✲ࡢ┠ⓗࡣࡋ࡚࠸࡞࠸ࠋ⫼ᬒ࠶ ࡿᶵᗎࡣ᫂ࡽ࡛ࡣ࡞࠸ࡶࡢࡢࠊQPS-5 ࡀࡢ rTMS ࡣ␗࡞ࡗ࡚ࡇࢀࡽࡢኚ ࢆᘬࡁ㉳ࡇࡋࡓࡇࡣ☜࡛࠶ࡿࠋ୍᪉ࠊQPS-50 ࡛ࡣ⬻ᱱᶵ⬟ࡢኚࡀぢࡽࢀ ࡎࠊᑐഃ M1 ࡛ࡢ MEP ኚࡶぢࡽࢀ࡞ࡗࡓࠋࡇࡢⅬࡘ࠸࡚ࡣᚋ㏙ࡍࡿࠋ ࡶ࠺୍ࡘὀ┠ࡍࡿⅬࡣࠊIHI ࠾࠸࡚ ISI 10 ms 40 ms ࡛ຠᯝࡀ␗࡞ࡗࡓⅬ ࡛࠶ࡿࠋSIHI㸦ISI 10 ms㸧ࡣቑᙉࡀぢࡽࢀࡓࡀࠊLIHI㸦IHI 40 ms㸧ࡣኚࡀぢࡽ ࢀ࡞ࡗࡓࠋࡇࡢ㞳ࡘ࠸࡚ࡣ Gilio ࡽࡢሗ࿌[92]୍⮴ࡋ࡚࠾ࡾࠊSIHI LIHI ࡀ␗࡞ࡿ࣓࢝ࢽࢬ࣒࡛⏕ࡌ࡚࠸ࡿ࠸࠺ㄝࢆᨭᣢࡍࡿࡶࡢ࡛࠶ࡿ[68]ࠋࡉࡽࠊ SIHI LIHI ࡣ GABAA GABAB ࠸ࡗࡓࠊ⚄⤒ఏ㐩≀㉁ࡢࢩࢫࢸ࣒ࡼࡿಟ ᅗ 26 M1 ࡢ QPS ࡀᑐഃ M1 ⬻༙⌫㐠ື㔝㛫ㄪ⠇ᙳ㡪ࡍࡿᶵᗎ㸦ᶍᘧᅗ㸧 ᕥ M1 ᑐࡍࡿ QPS ࡣᕥ M1 ࡢ㗹య⣽⬊ LTP ᵝኚࢆᘬࡁ㉳ࡇࡍࡔࡅ࡛࡞ࡃࠊ ᕥЍྑ M1 ࡢ⬻ᱱ⥺⥔ᑐࡋ࡚ࡶ LTP ᵝኚࢆᘬࡁ㉳ࡇࡍࠋྑ M1 ࠾࠸࡚ಁ ㏻ᛶࠊᢚไᛶࡢ୧᪉ࡢᅾࢽ࣮ࣗࣟࣥࡀቑᙉࡉࢀࡿࠋ*ࡣቑᙉࡉࢀࡓࢩࢼࣉࢫࡢ 㒊ࢆ♧ࡍࠋ 91 㣭ࡀ␗࡞ࡿሗ࿌ࡉࢀ࡚࠸ࡿ[116]ࠋ⚄⤒ఏ㐩ࢩࢫࢸ࣒ࡢ㐪࠸ࡀ SIHI LIHI ࡢ 㐪࠸ࢆㄝ࡛᫂ࡁࡿࡶࡢ࡛࠶ࡿࡶࡋࢀ࡞࠸⪃࠼ࡽࢀࡓࠋ LTP LTD ࡢ㐪࠸ ᮏ◊✲࡛ࡣࠊᑐഃ M1 ࡢຠᯝࡣ่⃭ഃ M1 LTP ᵝຠᯝࢆㄏᑟࡍࡿ QPS-5 ࡛ࡢࡳぢࡽࢀࠊ่⃭ഃ M1 LTD ᵝຠᯝࢆㄏᑟࡍࡿ QPS-50 ࡛ࡣぢࡽࢀ࡞ࡗࡓࠋ QPS-50 ࡀᑐഃ M1 LTD ᵝኚࢆㄏᑟࡍࡿࡇࡀ࡛ࡁ࡞ࡗࡓ⌮⏤ࡋ࡚ࠊ୍ ࡘࡢ༢⣧࡞ྍ⬟ᛶࡋ࡚ࡣࠊQPS-50 ࡢຠᯝࡀ QPS-5 ࡼࡾࡶᙅࡃࠊᑐഃ M1 ྍ ረᛶኚࢆ㉳ࡇࡍᙉຊ࡛ࡣ࡞ࡗࡓࡇࡀ⪃࠼ࡽࢀࡿࠋࡢྍ⬟ᛶࡋ࡚ ࡣࠊQPS-5 QPS-50 ࡀ⬻ᱱ⥺⥔㗹య㊰⥺⥔␗࡞ࡗ࡚స⏝ࡍࡿ࠸࠺ࡶࡢ࡛ ࠶ࡿࠋࡇࢀࡽ 2 ࡘࡢ⥺⥔ࡣ⏕⌮Ꮫⓗࡶ␗࡞ࡗࡓ≉ᚩࢆᣢࡗ࡚࠸ࡿࡇࡽ[117, 118, 119]ࠊrTMS ᑐࡍࡿᛂࡶ␗࡞ࡿࡇࡀ⪃࠼ࡽࢀࡿࠋࡲࡓ่⃭ࣉࣟࢺࢥ࣮ ࣝ౫Ꮡࡋࡓᙳ㡪ࡶ⪃࠼ࡽࢀࡿࠋ1 Hz rTMS ࡛ࡢሗ࿌࡛ࡣࠊ่⃭ᙉᗘࠊࢥࣝࡢ ྥࡁࠊࡢ᮲௳่⃭ࡢࣃ࣓࣮ࣛࢱ࣮ࡀ⤖ᯝᙳ㡪ࡍࡿ࠸ࢃࢀ࡚࠸ࡿ[91, 92, 93, 94, 95, 96]ࠋ⯆῝࠸ࡇࠊrTMS ࡢࣉࣟࢺࢥ࣮ࣝࡼࡽࡎࠊᑐഃ M1 ᑐࡋ࡚ ࡣಁ㏻ᛶࡢຠᯝࢆ♧ࡍሙྜࡀከࡃࠊᢚไᛶࡢຠᯝࢆ♧ࡍࡇࡣᑡ࡞࠸ࠋ ⮫ᗋᛂ⏝ 92 ⮫ᗋᛂ⏝ࡢほⅬࡽࡣࠊIHI ࡣ⬻༞୰ᝈ⪅࡛ὀ┠ࡉࢀ࡚࠸ࡿ[43]ࠋ⬻༞୰ᝈ⪅ ࡢ rTMS ࡢຠᯝࡘ࠸࡚ࡣࡇࢀࡲ࡛࠸ࡃࡘሗ࿌ࡉࢀ࡚࠸ࡿࠋᖖഃప㢖ᗘ 㸦ӌ1 Hz㸧่⃭ࢆ࠼ᑐഃᑐࡍࡿ IHI ࢆῶᙅࡋࡓࡾ[120, 121, 122]ࠊᝈഃ㧗 㢖ᗘ㸦㸼1 Hz㸧่⃭ࢆ࠼่⃭༙⌫ࡢ⯆ዧᛶࢆቑࡉࡏࡓࡾࡍࡿ[123]ࡇࡀ࠾ ࡇ࡞ࢃࢀ࡚࠸ࡿࠋࡇࢀࡽࡢ᪉ἲࡣ⬻༞୰ࡀ IHI ࡛␗ᖖ࡛࠶ࡿ࠸࠺ሗ࿌[42]ࡸࠊ rTMS ᚋ IHI ࡀῶᑡࡍࡿ࠸࠺ሗ࿌[122, 124]ࢆࡶࡋ࡚࠸ࡿࠋᡃࠎࡣࡇࡢ◊ ✲࡛ rTMS ᚋ IHI ࡔࡅ࡛࡞ࡃ IHF ࡶኚࡍࡿࡇࢆ♧ࡋࡓࠋࡑࡢᶵᗎࡘ࠸࡚ ࡣ᫂ࡽ࡛ࡣ࡞࠸ࡀࠊࡇࡢ⤖ᯝࡀࠊ∦㯞ᝈ⪅ࡢ㐠ືᶵ⬟ᅇᑐࡋ࡚ rTMS ࡼ ࡿ᪂ࡋ࠸ࣉ࣮ࣟࢳࡘ࡞ࡀࡿྍ⬟ᛶࡀ࠶ࡿࡢ࡛ࡣ࡞࠸⪃࠼ࡓࠋ ᮏ◊✲ࡢ㝈⏺ࡋ࡚ࡣࠊホ౯㛫ࡢၥ㢟ࡀᣲࡆࡽࢀࡿࠋᅇࡣ QPS ⤊ᚋ 30 ศᚋ࡛ࡢࡳ่⃭ᚋࡢホ౯ࢆ࠾ࡇ࡞ࡗࡓࠋࡇࡢࢱ࣑ࣥࢢࢆ㑅ࢇࡔ⌮⏤ࡋ࡚ࡣࠊ ่⃭ഃ M1 ࡛ࡇࡢ㛫᭱ࡶᙉ࠸ຠᯝࡀぢࡽࢀࡓࡓࡵ࡛࠶ࡿ[32]ࠋࡋࡋࠊࡢ ࢱ࣑ࣥࢢ࡛␗࡞ࡿຠᯝࡀぢࡽࢀࡿྍ⬟ᛶࡶྰᐃ࡛ࡁ࡞࠸ࠋࡢⅬࡋ࡚ࡣࠊ IHF ࢆ㝶ព⦰࡛࠾ࡇ࡞ࡗࡓࡇࡀ࠶ࡿࠋTBS ࡸ PAS ࡛ࡣ➽⦰ࡼࡾྍረᛶ ኚࡀᾘኻࡍࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿࠋᅇ⏝࠸ࡓ IHF ࡢ᪉ἲࡣ I3 ࢆㄏᑟࡍࡿࡓ ࡵ➽ࢆᙅ⦰ࡉࡏ࡚࠾ࡇ࡞ࡗࡓ[21]ࠋ➽⦰ࡣ QPS ࡛ࡣྍረᛶ࠼ࡿᙳ㡪ࡣ ࡑࢀࡁࡃ࡞࠸ࡢሗ࿌ࡶ࠶ࡾ[125]ࠊᅇࡢᐇ㦂⏝࠸ࡓ➽⦰ࡣᐇ㦂⤖ ᯝ῝้࡞ᙳ㡪ࡣ࠼࡞ࡗࡓ⪃࠼ࡓࠋ 93 ࡉࡽࠊࣄࢺ࡛⬻༙⌫㐠ື㔝㛫ㄪ⠇ࢆ◊✲ࡍࡿ㝿ࡣࠊᖺ㱋[126]ࠊඃ༙ ⌫㠀ඃ༙⌫ࡢ₯ᅾⓗ࡞㐪࠸[74, 75, 76, 77, 78]ࢆ⤡ᅉᏊࡋ࡚⪃៖ࡍࡿᚲ せࡀ࠶ࡿࠋࡇࡢ◊✲࡛ࡣࠊ࡚ࡢཧຍ⪅ࡣྑࡁ࡛࠶ࡾࠊࡑࡢࡓࡵඃ༙⌫ ࡽ㠀ඃ༙⌫ࡢᙳ㡪ࢆࡳࡓࠋ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢᖺ㱋ඃഃࡢᙳ㡪 ࡣࠊᑗ᮶ࡢㄢ㢟࡛࠶ࡿࠋࡉࡽࠊᛶᕪࡶࡲࡓ⤡ᅉᏊ࡞ࡿྍ⬟ᛶࡀ࠶ࡾࠊࡇ ࢀࡶࡲࡓ᳨ウㄢ㢟࡛࠶ࡿ[77, 127]ࠋ⿕㦂⪅ࡢேᩘࡀ㝈ࡽࢀ࡚࠸ࡿࡇࡶ㝈⏺Ⅼ࡛ ࠶ࡿࠋᅇ࣏ࢪࢸࣈฟࡓ⤖ᯝࡣࠊᑡேᩘ࡛ࡶ⤫ィᏛⓗ᭷ព࡞⤖ᯝࡀฟࡓ ࡓࡵࠊேᩘࡼࡿᙳ㡪ࡣᑡ࡞࠸⪃࠼ࡽࢀࡿࡀࠊ࠸ࡃࡘࡢࢿ࢞ࢸࣈฟࡓ ⤖ᯝࡣேᩘࡢᑡ࡞ࡉࡀᙳ㡪ࡋࡓྍ⬟ᛶࡶ࠶ࡿࠋࡲࡓࠊIHI ࡸ IHF ࡀ⬻ᱱࢆࡋ ࡓࡶࡢ࡛࠶ࡿ▱ࡽࢀ࡚ࡣ࠸ࡿࡶࡢࡢࠊQPS ࡼࡿᑐഃࡢᙳ㡪ࡀ⬻ᱱ࡛ࡣ࡞ ࡃูࡢ⓶㉁ୗࢆࡋ࡚࠸ࡿྍ⬟ᛶࡶࡣྰᐃ࡛ࡁ࡞࠸ࠋࡑࡢࡓࡵࡣ⬻ᱱ ↓ᙧᡂࡢᝈ⪅࡛ࡢ⤖ᯝࡀཧ⪃࡞ࡿᛮࢃࢀࡿࠋࡇࢀࡽᵝࠎ࡞ᅔ㞴࡞Ⅼࡶ࠶ࡿ ࡀࠊࣄࢺ࠾ࡅࡿ⬻ᱱࡢ࣓࢝ࢽࢬ࣒ࡑࡢㄪ⠇ᶵᗎࡘ࠸࡚ࠊࡉࡽ࡞ࡿ◊✲ࡀ ᚲせ࡛࠶ࡿ⪃࠼ࡽࢀࡓࠋ ࡲࡵࡿࠊᕥ M1 ࡢ QPS-5 ࡣᑐഃࡢྑ M1 ࡢ MEP ቑࢆࡶࡓࡽࡋࡓࠋ ᕥЍྑ M1 ࡢ SIHI IHF ࡶቑࡋࠊIHF ࡀྑ M1 ࡢ MEP ኚ᭷ព┦㛵ࡋࡓࠋ ࡇࢀࡽࡢ⤖ᯝࡽࠊᑐഃࡢ LTP ᵝຠᯝࡢⓎ⌧ࡣࠊ⬻ᱱࢆࡋࡓ⬻༙⌫㐠ື 㔝㛫ㄪ⠇ຠᯝ㛵㐃ࡋ࡚࠸ࡿ⪃࠼ࡽࢀࡓࠋ 94 ࠙⤖ㄽࠚ ➨ 1 ❶࡛ࡣࠊMCI ᝈ⪅࠾࠸࡚ TMS ࡼࡿ IHI ࡀ␗ᖖ࡛࠶ࡿࡇࢆึࡵ࡚♧ ࡋࠊ⬻ᱱᶵ⬟ࡢ㞀ᐖࢆ♧၀ࡋࡓࠋIHI ࡶ⓶㉁㛫ࡢ㐠ື㔝ᢚไࢆ♧ࡍ SAI ࡶ␗ᖖ࡛࠶ࡾࠊṇᖖ࡛࠶ࡗࡓ⓶㉁ෆᶵ⬟ẚ㍑ࡋ࡚ࠊ⓶㉁㛫ᶵ⬟ࡀ␗ᖖ࡞ࡾ ࡸࡍ࠸ࡶ⪃࠼ࡽࢀࡓࠋࡇࢀࡽ㧗ḟᶵ⬟௨እࡢ㞀ᐖࡶ᪩ᮇࡽฟ⌧ࡍࡿࡇࡀ ㄆ▱ᶵ⬟㞀ᐖࡢ≉ᚩࡢ୍ࡘ࡛࠶ࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡓࠋඃ༙⌫㠀ඃ༙⌫ ᳨࡛ᰝ⤖ᯝࡀ␗࡞ࡿྍ⬟ᛶࡸࠊྠ୍ᝈ⪅࡛ࡢ⤒ኚࡘ࠸࡚ࡣᚋ᳨ウࡀᚲ せ⪃࠼ࡽࢀࡓࠋ ➨ 2 ❶࡛ࡣࠊIHI SAI ࡘ࠸࡚ࠊࡑࢀࡒࢀ┦ᢚไࡀࡳࡽࢀࡿࡇࢆゎ᫂ࡋ ࡓࠋࡇࢀࡣࠊࡇࢀࡲ࡛ SAI SICI ࡸ SAI LICI ࠸ࡗࡓᢚไ⣔ᅇ㊰࠾࠸࡚ ࡶ┦ᢚไస⏝ࡀࡳࡽࢀ࡚࠾ࡾࠊᢚไ⣔ᅇ㊰ࡼࡿ⬻ෆࡢ㐣࡞ᢚไࢆ㜵ࡄ⏕ ⌮ⓗ࡞ᶵᵓ࡛࠶ࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡓࠋᮏᐇ㦂࡛ࡣࠊࡇࡢ┦స⏝ࡘ࠸่࡚ ⃭ᙉᗘ౫Ꮡᛶ࠸࠺᪉ἲ࡛ヲ⣽࡞᳨ウࢆ࠾ࡇ࡞࠸ࠊ่⃭ᙉᗘࡀᙉ࠸ሙྜࡢࡳࡇ ࡢ┦ᢚไࡀࡳࡽࢀࡿࡇࢆ♧ࡋࡓࠋ୍᪉ࠊ่⃭ᙉᗘࡀᙅࡃࠊ༢⊂࡛ࡣᢚไࡀ ぢࡽࢀ࡞࠸≧ែ࡛ࡣࠊ┦స⏝ࡀᏑᅾࡋ࡞ࡗࡓࠋ⚄⤒ᅇ㊰㛫ࡢ┦స⏝ࡘ ࠸࡚ࡣࠊࡇࢀࡲ࡛ࡶከᩘሗ࿌ࡉࢀ࡚࠸ࡿࡀࠊᅇ♧ࡋࡓࡼ࠺࡞่⃭ᙉᗘ౫Ꮡᛶ 95 ࡢሗ࿌ࡣࡇࢀࡲ࡛࡞ࡃࠊᚋࡢ㢮ఝ◊✲ࡢཧ⪃࡞ࡿ⤖ᯝᛮࢃࢀࡓࠋIHI SAI ࠸࠺ 2 ࡘࡢ⓶㉁ࡽ M1 ࡢㄪ⠇ᶵ⬟㛫ࡢ┦స⏝ࡢᏑᅾࡀ᫂ࡽ࡞ ࡾࠊ⚄⤒ᝈ࡛ࡢ⤖ᯝࡢゎ㔘ࡸ่⃭ධࡼࡿ⓶㉁㛫ㄪ⠇ࡢኚࢆゎ㔘ࡍࡿୖ ࡛㔜せ࡞▱ぢ࡛࠶ࡗࡓࠋ ➨ 3 ❶࡛ࡣࠊ⬻ྍረᛶㄏᑟ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡢᙳ㡪ࡘ࠸࡚ᐇ㦂ࢆ ࠾ࡇ࡞࠸ࠊ⬻ྍረᛶㄏᑟࡀᑐഃ M1 ࡶཬࡪࡇࠊࡑࢀྠ⬻༙⌫㐠ື㔝 㛫ㄪ⠇ࡶኚࡍࡿࡇࢆ♧ࡋࡓࠋᅇࡢᐇ㦂࡛ࡣࠊࡇࢀࡲ࡛ࡢඛ⾜◊✲ࡣ␗ ࡞ࡾࠊ⬻༙⌫㐠ື㔝㛫ㄪ⠇ࡋ࡚ࠊಁ㏻⣔㸦IHF㸧ᢚไ⣔㸦IHI㸧ࡢ୧᪉ࢆ ᣦᶆࡋࡓࡇࡀ≉ᚩⓗ࡛࠶ࡗࡓࠋ࠸ࡎࢀࡢᣦᶆࡶኚࡋࡓࡇࡽࠊ⬻ᱱ⥺ ⥔ࢆࡋ่࡚⃭ᑐഃࡢ M1 ࠾࠸࡚ࡶࢩࢼࣉࢫྍረᛶࡀኚࡋࡓࡇࡀ♧၀ ࡉࢀࡓࠋࡇࢀࡲ࡛ࡢ⬻༞୰࠾ࡅࡿ༙⌫㛫ᑐ❧ࣔࢹ࡛ࣝࡣࠊIHI ࡢࡳࢆࡑࡢᶵᗎ ࡋ࡚⪃࠼࡚࠸ࡓࡀࠊᅇࡢ⤖ᯝࡽࡣಁ㏻⣔࡛࠶ࡿ IHF ࡢᏑᅾࡶ⪃៖ࡍࡿᚲ せࡀ࠶ࡿ⤖ㄽࡋࡓࠋࡇࢀࡣࠊື≀ᐇ㦂࡞࡛♧ࡉࢀ࡚࠸ࡿ⬻ᱱ࠾ࡅࡿ⯆ዧ ᛶࢩࢼࣉࢫࡢ㔜せᛶࡶ୍⮴ࡋ࡚࠸ࡿ⪃࠼ࡽࢀࡓࠋIHF ࡘ࠸࡚ࡣࠊ⚄⤒ᝈ ࡛ࡶࡇࢀࡲ࡛࠶ࡲࡾ᳨ウࡉࢀ࡚࠾ࡽࡎࠊᚋὀ┠ࡍࡁㄪ⠇ᶵ⬟࡛࠶ࡿ⪃࠼ ࡽࢀࡓࠋࡉࡽࠊࡇࡢᐇ㦂࠾࠸่࡚⃭ᑐഃྍረᛶኚࢆཬࡰࡏࡿྍ⬟ᛶࢆ ♧ࡋࡓࡀࠊࡇࢀࡣ⬻ᱱࢆࡋࡓࣄࢺ㐠ືᶵ⬟ㄪ⠇࠾࠸࡚ࠊ༢࡞ࡿ่⃭ഃࡢ⯆ 96 ዧᛶࡢኚࡢ⤖ᯝࡼࡗ࡚ᑐഃḟⓗ࡞ᙳ㡪ࡀ⏕ࡌࡿࡔࡅ࡛ࡣ࡞ࡃࠊᑐഃ༙ ⌫┤᥋ኚࢆㄏᑟ࡛ࡁࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡓࠋࡋࡋࠊ่⃭᪉ἲࡼࡗ࡚ࡑ ࡢຠᯝࡢⓎ⌧ࣃࢱ࣮ࣥࡀ␗࡞ࡗࡓࡾࠊྠࡌ่⃭᪉ἲ࡛ࡶಶேࡼࡾຠᯝࡀ␗࡞ ࡗࡓࡾࡍࡿࡇࡶ▱ࡽࢀ࡚࠾ࡾࠊᚋࡣࡇࡢࡼ࠺࡞Ⅼࡶὀ┠ࡋ࡚◊✲ࢆࡍࡍ ࡵ࡚࠸ࡃᚲせࡀ࠶ࡿ⪃࠼ࡽࢀࡓࠋᐇ㝿ࡢᝈ⪅࡛ࡣࠊᖖ⪅␗࡞ࡿⅬࡶከࡃࠊ ⮫ᗋᛂ⏝ࡣᢏ⾡ⓗ࡞ᅔ㞴ࡶక࠺ࡀࠊᚋࡣࠊࡇࡢࡼ࠺࡞ㄢ㢟ࢆඞ᭹ࡋࠊࣜࣁ ࣅࣜࢸ࣮ࢩࣙࣥ࡞⤌ࡳྜࢃࡏࡓ◊✲ࢆ࠾ࡇ࡞࠺ࡇ࡛ࠊ⒪ධ᪉ἲࡢ᪂ ࡓ࡞㛤Ⓨࡘ࡞ࡀࡿࡇࡀᮇᚅࡉࢀࡓࠋ ᮏ◊✲࡛ࡣࠊ⬻ᱱࢆࡋࡓࣄࢺ㐠ືᶵ⬟ㄪ⠇ࡘ࠸࡚ TMS ࢆ⏝࠸࡚ከゅⓗ ᳨ウࡍࡿࡇࢆ┠ⓗࡋࡓࡀࠊ◊✲ࢆ㏻ࡌ࡚ࠊIHI ࡢኚࡀᝈࡢデ᩿ࡸែᶵ ᗎࡢゎ᫂ᙺ❧ࡘྍ⬟ᛶࢆ♧၀ࡋࠊ⓶㉁㛫ㄪ⠇ᶵᵓࡘ࠸࡚᫂ࡽࡋࡓࠋࡲ ࡓࠊ㐠ື㔝ࡢ㛗ᮇຠᯝㄏᑟ㐠ື㔝㛫ㄪ⠇ࡢ㛵㐃ࢆ᫂ࡽࡋࠊᚋࡢࣜࣁࣅ ࣜࢸ࣮ࢩࣙࣥ࡞ࡢ⮫ᗋᛂ⏝ࡢ⌮ㄽⓗᇶ┙ࡘ࡞ࡀࡿ⤖ᯝࢆ♧ࡋࡓࠋ≉ IHF ࠸࠺ࡇࢀࡲ࡛ㄪࡽࢀ࡚࠸࡞ࡗࡓ㐠ື㔝㛫ㄪ⠇ᶵ⬟ࡢ㔜せᛶࢆ♧ࡋࠊᚋ ὀ┠ࡍࡁㄪ⠇ᶵ⬟࡛࠶ࡿࡇࢆ♧ࡋࡓࠋࡇࡢࡼ࠺⬻ᱱࢆࡋࡓ㐠ືᶵ⬟ㄪ ⠇ࡘ࠸࡚ᖜᗈࡃ␗࡞ࡗࡓゅᗘࡽࡢゎ᫂ࢆ┠ᣦࡋࠊ࠸ࡎࢀࡢᐇ㦂ࡽࡶࠊ⬻ ᱱࢆࡋࡓ㐠ືᶵ⬟ㄪ⠇ࡘ࠸࡚᪂ࡓ࡞▱ぢࢆᚓࡿࡇࡀ࡛ࡁࡓࠋ 97 ࠙ᘬ⏝ᩥ⊩ࠚ 1. 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