Mesolimbic sebōpeho se setle sa batho ba baholo (2007)

Cereb Cortex. 2007 Dec;17 (12): 2940-8. Epub 2007 Mar 23.

Bunzeck N1, Schütze H, Khoeli S, Kaufmann J, Düzel S, Heinze HJ, Düzel E.

inahaneloang

Ho tsofala ho tloaelehileng ho amana le tahlehelo ea methapo ea methapo sebakeng sa dopaminergic midbrain (substantia nigra / ventral tegmental sebakeng seo, SN / VTA), e leng sebaka se sa tsoa kenella ts'ebetsong ea rialo ea susumetsang e le karolo ea netweke ea mesolimbic ho kenyelletsa hippocampus. Mona, re hlalositse ho senyeha hoa sebopeho se amanang le lilemo tsa sisteme ea mesolimbic re sebelisa tekanyo ea phetiso ea matla a khoheli (MTR) mme re e kopantseng le likarabo tsa mesolimbic hemodynamic (HRs) ho tsosa maikutlo a manyane. Batho ba baholo ba mashome a mabeli a motso o mong ba phetseng hantle ba lipakeng tsa lilemo tse 55 ho isa ho tse 77 ba entse pono e sa bonahaleng ea ho khetholla mesolimbic HRs hore e se ke ea hlola e e-ba teng ka seoelo, pherekano e mpe ea maikutlo, le ho tsepamisa maikutlo ka ho sebelisa monahano o matla oa matla a khoheli. Ba HRs ba ka SN / VTA e nepahetseng le hippocampus e nepahetseng ho tse ncha ba ile ba hokahanngoa ka nepo ka SN / VTA MTR le hippocampus MTR empa eseng amygdala MTR. Leha ho le joalo, HR ea amygdala ho maikutlo a mabe a valence a amanang le amygdala MTR empa eseng le MTR ho SN / VTA kapa hippocampus. Liphetho li theha kamano ea ts'ebetso ho ts'ehetsa ts'ebetso ea hippocampal-SN / VTA ea mesolimbic novelty ka ho bonts'a hore ts'ebetso ea hemodynamic ho SN / VTA le hippocampus bakeng sa bocha li angoa ke khethollo e amanang le lilemo tsa meaho ena.

Mantsoe a bohlokoa

Selelekela

Ho na le bopaki bo fetolelang ba hore dopamine e bapala karolo e seng feela ho matlafatsong oa ho ithuta empa hape le ho sebopeho sa memori sa episodic se itšetlehileng ka hippocampus.Lisman le Mohau 2005). Ho liphoofolo, dopamine e khothalletsa bokhoni ba nako e telele ba hippocampal (Otmakhova le Lisman 1996; Li et al. 2003; Lemon le Manahan-Vaughan 2006) le khatello ea maikutlo ea nako e telele (Lemon le Manahan-Vaughan 2006) tikolohong ea CA1 mme e ntlafatsa ho ithuta ho itšetlehileng ka hippocampus (Gasbarri le al. 1996; Bach et al. 1999; Lemon le Manahan-Vaughan 2006). Ts'ebeliso ea Intrahippocampal ea li-dopaminergic agents (joalo ka amphetamine) e ntlafatsa mohopolo oa sebaka ka mesebetsi ea methapo ea metsi (Packard le al. 1994). Li-entraventricular liente tsa antoponist ea dopamine e khethiloeng li lebisa ho bolulo bo senyehileng ba boits'oaro ha liphoofolo li khutlisetsoa tikolohong ea lipalesa tsa pele (Lemon le Manahan-Vaughan 2006). Mo bathong, diphetogo tsa pathological mo dopaminergic system di ka amanngwa le makoa a memori (Backman et al. 2000).

Bopaki bo sebetsang ba anatomical bakeng sa karolo ea dopaminergic midbrain ho episodic encoding bo tsoa liphumantsong tsa morao-rao tsa tšebetso ea matla a matla a matla a molumo (fMRI). Ts'ebetso e amanang le moputso ea sebaka sa substantia nigra / ventral tegmental (SN / VTA), sebaka seo mesolimbic dopaminergic neuromodulation e qalileng ho sona, se amahanngoe le ntlafatso ea memori ea nako e telele ea hippocampus e itšetlehileng ka nako e telele mme mohlomong e kopane (Wittmann le al. 2005; Adcock et al. 2006). Ts'ebetso e amanang le mpa ea bongoana e boetse e hlaha ntle le moputso (Schott le al. 2006). Tlatsetso ea anatomical ea hore karabelo ena e sebetsang ea SN / VTA e amana le dopaminergic neurotransuction e matlafalitsoe ke bopaki ba morao-rao bo bontšang hore profil e amanang le ts'ebetso sebakeng sena e fetoloa ke palo e sebetsang ea tandem pheta polymorphism ho dopamine transporter (DAT1) mofuta (Schott le al. 2006).

Ho 'nile ha fanoa ka maikutlo a hore kamano e sebetsang pakeng tsa SN / VTA le hippocampus e tsamaisoa ke ts'usumetso e ncha e ncha (Lisman le Mohau 2005). Melemo ea "coding dopaminergic" midbrain neuron ka har'a liphoofolo le eona e arabela linthong tse ncha le tse etsahalang ha lintho li fetoha ntle le ho tiisa.Schultz 1998). Re sebelisa fMRI, haufinyane re hlokometse hore le SN / VTA ea motho e nka bohato ba ho hlasimolla, ha mekhoa e meng e khathollang e kang ho se tloaelehe (kapa ho kheloha ha maemo), maikutlo a mabe a maikutlo, kapa sepheo sa mohopolo o tloaelehileng.Bunzeck le Duzel 2006). Lintlha tsena li fana ka bopaki bo tšehetsang mofuta oa morao-rao o bonts'ang ts'ebetso ea hippocampal-SN / VTA e sebetsanang le ts'ebetso ea bohlanya le ho ngolisa litaba (Lisman le Mohau 2005). Ba hlakisa hore ha ho sa na moputso o hlakileng, ts'ebetso ea loop ena e tsamaisoa ke lipale tse ncha tsa maikutlo ho fapana le mefuta e meng ea ts'usumetso ea matla. Hammoho le bopaki bo boletsoeng bo hokahanya tšebetso ea SN / VTA le khouto e atlehileng ea ts'oaetso leha ho se na moputso (Schott le al. 2006), liphumano tsena li fana ka khokahano lipakeng tsa likarabo tse ncha ho hippocampal-SN / VTA le katleho ea mohopolo oa episodic.

Dopaminergic neurotransuction e feta diphetohong tse amanang le dilemo tse loketseng mohopolo oa episodic. Lintlha tsa botho tsa motho li supa ho fokotseha ho amanang le lilemo tse 3% ho dopamine D1 (Seman et al. 1987; Cortes le ba bang. 1989; Rinne le al. 1990) le li-receptor tsa D2 (Seman et al. 1987) ka lilemo tse leshome. Ho SN, ho na le tahlehelo ea methapo ea kutlo ea dopaminergic ea 6% ka lilemo tse leshome le motsoakong oa karolo ea 2 ea bongaka le XNUMX% karolong e latelang ea moea (Fearnley le Lees 1991). Kahokahanyo ea antemortem fluorodopa positron emission tomography le lipalo tsa cell cell ea postmortem ho SN, tahlehelo ea methapo e ne e lekana hantle le phokotseho ya ho fumaneha ha dopamine (striatal dopamine) (Snow le al. 1993). Ho batho ba baholo ba baholo, liphoso tse mohopolong oa episodic li hlahisoa hantle ke li-receptor tsa D2 ho feta ka lilemo (Backman et al. 2000).

Mofuta oa hippocampal-SN / VTA o bolela esale pele hore boholo ba karabelo ea SN / VTA ea motho le hippocampus ho bocha ho batho ba baholo ba lokela ho ikemiselitsoe ka kopanelo ke botshepehi bo ka hara SN / VTA le hippocampus. Ho fapana le hoo, ho latela hore amygdala ha e kenye letsoho ka kotloloho ts'ebetsong ea bohloka ea hippocampal-SN / VTA (Lisman le Mohau 2005; Bunzeck le Duzel 2006), leha likarabo tse nyane tsa hippocampal kapa SN / VTA ha lia lokela ho kopanngoa le botsitso ka har'a amygdala. Re lekile mohopolo ona ka ho sebelisa mokhoa o tšoanang o mocha oa tlhaiso-leseling o ileng oa hlahisa likarabo tse hlakileng tsa hemodynamic (HRs) ho SN / VTA le hippocampus ho batho ba baholo ba banyenyane (Bunzeck le Duzel 2006) sehlopheng sa batho ba baholo ba phetseng hantle. Ho ts'epahala ha sebopeho sa SN / VTA, hippocampus, le amygdala tsa bohle ba neng ba nka karolo li ile tsa lekanngoa ho sebelisoa ho nahana ka phepelo ea matla a khoheli (MTI).

Phetisetso ea maqhubu ka har'a lithane e amana le phapanyetsano ea matla a proton pakeng tsa protocol ea metsi a tsamaeang le liprothone tse sa sebetseng ka macromolecule (Wolff le Balaban 1989). Ho fihlela MTI, matla a khoheli a proton ea macromolecular e sarafalitsoe hanyane ka tšebeliso ea mochini o nepahetseng oa motlakase nakong ea monahano o boima oa proton. Ho sebelisana ha liprothone tsena tse nang le likarolo tse ngata tsa moea tse nang le liprothone tsa metsi a mobile libakeng tsa tsona tse haufi, ho na le letšoao la metsi le bonoang litšoantšong. Phokotso ena ea lets'oao e ipapisitse le thepa ea lisele tse joalo ka mohopolo, sebopeho le / kapa chemistry ea li-macromolecule, le litaba tsa metsi hammoho le likarolo tsa tatellano ea litšoantšo. Haeba ho na le mehato e 'meli e latellanang ka (tumellano ea phetisetso ea motlakase [MTT]) ntle le (ha ho na phetiso ea khoheli ea matla a khoheli), sekhahla se bitsoang seo se bitsoang magnization transfer ratio (MTR) se ka baloa voxel ka motheo oa voxel ho latela: MTR = (MTT - MT) / MTT.

Phokotso ea Hippocampal ea MTR e tlalehiloe ho lefu la Alzheimer's (Hanyu, Asano, Iwamoto, et al. 2000; Hanyu, Asano, Kogure et al. 2000) le ho isa tekanyong e tlase ho 'dementia ea' mele ea Lewy (Hanyu et al. 2005). Pathophysiology e ikhethileng e tlatselletsang ho fokotsoa ha MTR hippocampal maemong ana ha e e-so hlake, empa phokotso ea MTR ho bakuli ba nang le lefu la ts'abo ea methapo e fana ka lintlha tse ling. Ba fana ka maikutlo a hore phokotso ho MTR e ka bonoa le haeba mekhoa e meng ea ho nahana, joalo ka T2- le T1Monahano o bobebe, ha o bonts'e ho sa tsotelleng ho etsang hore o amehe ka ho khetheha ha o fumana litlolo tsa pele tsa litho tse tloaelehileng tse kenyelletsang taba e tšoeu (Iannucci le al. 2000; Traboulsee et al. 2002; Audoin le ba bang. 2004; Fernando et al. 2005) le cortical (Fernando et al. 2005) hammoho le taba e tebileng ea bohlooho (Audoin le ba bang. 2004). Phokotso ea MTR litabeng tse tšoeu tse tloaelehileng li ka ba teng ka lebaka la ho eketsoa ke mohopolo, ho ruruha ha methapo ea kutlo, ho bolaoa hoa moea (demyelination)Rademacher et al. 1999), le tahlehelo ea letsoalo la axonal (van Waesberghe et al. 1999) hammoho le litlhapa tsa masapo (Fazekas et al. 2005). Phokotso ea MTR litheko tse tloaelehileng tsa bohlooho li ka hlaha ka lebaka la transsynaptic morphological abnormality secondary to the afferent demions lisi, mme monyetla ona o sa tsoa ts'ehetsoa ke ho fumana hore MTR ea pono ea cortical e fokotsehile kamora ketsahalo e ikhethileng ea "neuritis" ea "optic"Audoin le ba bang. 2006). Ho khahlisang ke hore bakuli bana le bona ba fokotsetse li-MTR ho hippocampus, gypus e phahameng ea nakoana, leselicular lei, le ho fana ka maikutlo a hore MTR e amehile ka ho fetoloa ha neuronal le ho fokola ha moriana oa tlhaho o amanang le litaba tsa bohloeki ka mor'a lintho tse bobebe tse amanang le taba e amanang le tšoeu.Audoin le ba bang. 2006).

Ho fokotsehile ha MTR ho bakuli ba nang le lefu la Parkinson (PD) (Eckert le ba bang. 2004; Seppi le Schocke 2005). Lebaka la phokotso ea SN MTR ho PD ha le utloisisoe ka botlalo. PD e tšoauoa ka mokhoa o ikhethileng oa ho fokotsa dopaminergic, li-neurones tse nang le li-neurones tsa SN (par compacta). Neuromelanin ke "macromolecule" e sa koaheleng e fanang ka 'mala o moputsoa ho SN. Tahlehelo ea methapo ea kutlo hammoho le ho senyeha ha "neuromelanin macromolecule scaffolding"Fasano et al. 2006) e ka lebisa phokotso ea MTR. Hoa nahanoa hore mekhoa ena e ka boela ea lebisa ho fokotseng ha MTR ho batho ba baholo ba phetseng hantle ba se nang matšoao a PD.

Kamora nako, ho batho ba baholo ba phetseng hantle, MTR ea cortex e bonts'a kamano e mpe le lilemo, mme phokotso e amanang le lilemo e matla ho feta ea taba e tšoeu, a fana ka maikutlo a hore MTR e ela hloko liphetoho tse amanang le lilemo tsa meaho ea litaba tse putsoa (Ge et al. 2002; Fazekas et al. 2005; Benedetti le al. 2006). Leha ho le joalo, datha mabapi le kamano pakeng tsa MTR le ts'ebeliso ea kelello ea botsofaling li haella (mohlala, Deary et al. 2006), hape, ho na le tsebo ea rona, ha ho na data e fumanehang mabapi le liphetoho tse amanang le lilemo tsa MTR tsamaisong ea mesolimbic.

Lisebelisoa le mekhoa

Lihlooho

Batho ba baholo ba mashome a mabeli a motso o mong ba phetseng hantle, ba nang le letsoho le letona (lilemo tse 55-77; ho bolela lilemo tse 65.3; ho kheloha ho tloaelehileng [SD] = lilemo tse 6.3; basali ba 11 le ba batona ba 10) ba ile ba ngolloa ho nka karolo ho lefeng phuputsong, e ileng ea amoheloa ke komiti ea melao ea boitšoaro ea lehae ea Univesithi ea Otto-von-Guericke ea Magdeburg, Jeremane. Ho ea ka tlaleho ea boits'oaro, ha ho le ea mong oa lithuto eo ea neng a e-na le nalane ea khatello ea maikutlo, ea kelello kapa ea mathata a bongaka kapa a mathata a leha e le afe a bongaka. Lithuto tsohle li fumane lintlha ka har'a mofuta o tloaelehileng ho Geriatric Depression Scale (GDS [Yesavage JA et al., 1982]; bolela GDS = 1.4, SD = 1.1; GDS ≤ 4 bakeng sa lithuto tsohle; Li-GDS li tloha ho 0–15; lintlha tse phahameng tse fetang 11 li bonts'a khatello ea maikutlo) le Examination ea Mini-Mental State (MMSE [Folstein ME le al., 1983]; bolela MMSE = 29.5, SD = 0.75; MMSE ≥ 28 bakeng sa lithuto tsohle; MMSE e tsoa ho 0-30; tse ngata tse ka tlase ho 25 ke li-pathological). Ho feta moo, lithuto tsohle li ne li na le khatello e tloaelehileng ea mali, 'me ha ho le e' ngoe ea tsona e neng e le motenya (ho bolela index ea boima ba 'mele = 27.1, SD = 5.1). Ha ho kopanngoa le litlaleho tsa boits'oaro, lipotso le tlhahlobo ea bongaka li bontša bophelo bo botle ba lilemo. Bakeng sa ho lekola hore na ho na le phokotso e amanang le lilemo ho MTR, re kenyelletse data ea anatomical ea MRI ho batho ba baholo ba 24 (lilemo tsa lilemo: lilemo tse 21-30; bolela = lilemo tse 23.25; SD = lilemo tse 2.21; basali ba 16 le ba batona ba 8). Ha ho le ea mong oa batho bana ba baholo ea ileng a tlaleha nalane ea mathata a methapo ea kelello, ea mafu a kelello kapa a bongaka kapa a mathata a leha e le afe a bongaka.

Moralo oa Teko le Mosebetsi

Lithuto tsa khale li phethile li-block tse 8 tsa paradigm e fetotsoeng ea pono e tlalehiloeng ho Bunzeck le Duzel (2006). Sebakeng ka seng, ho ne ho e-na le litekanyetso tse 80, li-oddbb tse lebisitsoeng, li-oddborts tse 10 tse sa nke lehlakore, litumellano tse 10 tsa maikutlo, le litlaleho tse 10 tse nyarosang, tse hlahisang kakaretso ea likhetho tse 10 ka sehlopha sa oddball tlhahlobong eohle.Feie. 1A). Ho qoba ho lula kahare ho mekhahlelo mme re lumelle kakaretso ea seo re se fumaneng ka mekhahlelo e fapaneng ea maikutlo a bonoang, re ile ra hlahisa litšoantšo tsa sefahleho sa banna karolong e le 'ngoe ea setšoantšo le litšoantšo tse bonts'ang maemo a kantle karolong e' ngoe (ho hanyetsana le lithuto tsohle). Re khethile mekhahlelo ena ho e-na le litšoantšo tse sa hlakoheng ho etsa hore tlhahlobo ea tšusumetso e sebetse ka mokhoa o loketseng. Tsusumetso ea sepheo e hlahisitsoe pele ho seboka sa liteko tsa 4.5, 'me lithuto li ne li hlokoa ho etsa mochini o bonolo o tobaneng le o mong le o mong oa tlhahlobo ea bona ea letsoho le letona. Ha ho likarabo tsa makoloi tse amanang le sehlopha leha e le sefe sa tse ling tsa khothalletso. Nakong ea teko, litšoantšo li ile tsa hlahisoa bakeng sa 500 ms tse lateloang ke sefapano se sesoeu sa sefahleho se tšoeu holima molala o motšo (boleng ba bohlooho = 127) ba sebelisa interstimulus interval (ISI) ea 2.7 s. ISI e ne e soetsoe pakeng tsa −300 le + 300 ms (e tsamaisoa ka mokhoa o tšoanang). Tlhophiso ea susumetso e ntlafalitsoe bakeng sa katleho mabapi le ho hakanya li-HR tse amanang le tšusumetso (Hinrichs et al. 2000).

Setšoantšo sa 1. 

Moetso oa khale, mokhoa oa teko (A), le phaello ea thepa ea FMRI (B). Papatsong e sa tloaelehang, re sebelisitse maikutlo a tloaelehileng, litheko tse sa lebelloang, litheko tse sa nke lehlakore, litheko tse mpe tsa maikutlo le litlaleho tse nyarosang tsa lipalo-lipalo li supa khafetsa (ho%). Ka halofo e le 'ngoe ea liteko re ile ra hlahisa litšoantšo tsa lifahleho tsa banna le halofo e' ngoe ea kantle. Taelo eo e ne e hanyetsanoa ka lithuto tsohle. Bakeng sa bophahamo bo bong le bo bong ba fMRI, ho ile ha nkuoa liseke tse 24 tse tšoanang le moqomo oa mpa o koahelang SN / VTA, hippocampus, amygdala, likarolo tsa cerebellum le cortex ea pele.B).

Liphetoho tsohle li nkuoe ho Bunzeck le Duzel (2006). Moriri o harelaneng le litsebe tsa lifahleho li ile tsa tlosoa ka maiketsetso, 'me likarolo tse ka ntle li ne li sa kenyeletse lifahleho. Litšoantšo tsohle li ne li soeufalitsoe ka mokhoa o hlakileng li le boleng bo bofubelu ba 127 le SD ea 75. Litšoantšo li ne li supiloe bohareng ba skrineng, 'me barupeluoa ba li shebile ka seiponeng se kentsoeng holim'a coil, ba beha setšoantšo sa mahlakore hoo e ka bang 8 °. Litšoantšo li nkuoe mehloling e fapaneng (lifahleho tse sa nke lehlakore: "Pokello ea litšoantšo tsa kelello ho Stirling," http://pics.psych.stir.ac.uk/; lifahleho tse mpe tsa maikutlo: [Ekman le Friesen 1976]; le boemo bo sa thabiseng ba maikutlo: mokhoa oa machaba oa papali o amohelehang [Lang et al. 2001]). Setšoantšo se sa rateheng sa maikutlo se bonts'a kotsi e mpe e mpe ea koloi (ntle le batho). Ts'ebetso ea tlhahlobo ea sepheo e ile ea hlahlojoa ka ho sekaseka sekhahla sa ho otla (likarabo tse nepahetseng ho sepheo) le sekhahla sa alamo ea bohata (likarabo ho linepe tsa nontarget).

Mekhoa ea fMRI

Joalokaha Bunzeck le Duzel (2006), fMRI e ile ea etsoa mochining oa MRI oa 3-Tesla whole-body (LG Magnetom Trio, Erlangen, Jeremane) e nang le echo planar imaging (EPI) e sebelisa coil ea hlooho ea li-8. Protocol ea Acquisition le tlhaiso ea data li ne li le joalo ka Bunzeck le Duzel (2006). Slices e ne e nkuoa e tšoana le ts'ebetso ea ts'ebetso ea ts'ebetso ea kelello ka mokhoa o sa tloaelehang le o kenyelletsoeng. Sebokeng se sebetsang, 24 T2* Litšoantšo tse se nang boima (EPI tatellano) (EPI) molumo ka bongata ka phallo ea mali - li ile tsa fumaneha ka bongata (boholo ba matrix: 64 × 64; 24 cm ka molumo; tšimo ea pono [FoV]: 192 × 192 mm; qeto ea sekhahla: 3 × 3 × 3 mm; lekhalo = 0.3 mm; nako echo [TE] = 30 ms; phetetso ea nako [TR] = 1500 ms; le flip angle = 75 °). Likarolo tsena li ne li koahetse hippocampus, amygdala, le brainstem (ho kenyelletsa diencephalon, mesencephalon, lipone, le medulla oblongata) le likarolo tsa "cortex" ea pele.Feie. 1B). Bakeng sa sehlooho ka seng sa khale, tlhaiso-leseling e sebetsang e fumanoe mananeong a ho lekola a 4 a nang le meqolo ea 440 ka nako. Ho ile ha fumanoa meqolo e meng e tšeletseng ka nako e ngoe le e ngoe qalong ea seboka se seng le se seng se sebetsang 'me hamorao ea lahloa ho tsoa tlhahlobisong ho lumella matla a khoheli a mmuso. Litšoantšo tsa boko bo felletseng ba sehlooho ka seng li ile tsa bokelloa ke T1Mekhahlelo ea ho hlaphoheloa ha boima ba 'mele - e hlophisitsoeng EPI (IR-EPI) (boholo ba matrix: 64 × 64; maseke a 60; FoV: 192 × 192 mm; qeto ea sebaka: 3 × 3 × 3 mm; lekhalo = 0.3 mm; TE = 33 ms ; TI = 1450 ms; le TR = 15000 ms).

Bakeng sa batho ba baholo le ba baholo, a T1setšoantšo sa anatomical se nang le boima ba 'mele (tatellano ea 3D e senyehileng ea li-gradient-echo; boholo ba matrix: 256 × 256; lilae tse 124; FoV: 250 × 250 mm; qeto ea sebaka 0.98 × 0.98 × 1.5 mm; TE = 8 ms; TR = 24 ms; le flip angle = 30 °) le litšoantšo tse boima ba proton tse 2 (tatellano ea spin-echo; boholo ba matrix: 256 × 256; likhae tse 48; FoV: 250 × 250 mm; qeto ea sebaka: 0.98 × 0.98 × 3 mm; TE = 20 ms; le TR = 2600 ms) li fumanoe bakeng sa boko ba sehlooho ka seng. Setšoantšo se le seng se nang le boima ba proton se fumanoe ka pulse e lokisang (1200 Hz off-resonance, 16 ms) e hlahisang setšoantšo sa MT (Feie. 2A) ngoe e ile ea nkuoa ntle le pulse e lokiselitsoeng ea sefahleho e bakang setšoantšo sa UMT (Feie. 2B). Kamora nako, limmapa tsa MTR bakeng sa thuto ka 'ngoe (Feie. 2C) li ne li baloa ho latela equation e latelang: MTR = (UMT - MT) / MTT. Ho ntlafatsa ho tsebahatsoa ha SN / VTA le khubu e khubelu, litšoantšo tsa MT tsa lithuto tsohle tse 21 li ile tsa hlophisoa ka nepo ho template e tloaelehileng ea Montreal Neurological Institute (MNI) e fanoeng ke SPM99 mme ea karolelanoa ka lithuto ho etsa template ea MT ea ba baholo sehlopha sa lithuto (Feie. 2D). Le ha sebaka sa SN / VTA se ka arohanngoa habonolo le meaho e potileng ho litšoantšo tsa MT e le mola o khanyang, khubu e haufi ea eona e bonahala e le lefifi (Feie. 2A,D). Ka bobeli T1Setšoantšo sa-anatomical -weighted le setšoantšo sa boima ba proton-weight bo ile ba hlahlojoa ho sebelisoa 1.5-Tesla whole-body MRI System (Signa Horizon LX, General Electric, Waukesha, WI).

Setšoantšo sa 2. 

Litšoantšo tsa Anatomical MR. Bakeng sa thuto e 'ngoe le e' ngoe ea litšoantšo tsa "proton density" tse peli li ile tsa fumanoa: setšoantšo se le seng sa proton se nang le pulse e lokiselitsoeng ho hlahisa setšoantšo sa MT (A) le setšoantšo sa bobeli sa proton ntle le setšoantšo se phetheselang se hlahisang setšoantšo sa UMT (B). Litšoantšo tseo ka bobeli li sebelisitsoe ho bala setšoantšo sa MTR sa sehlooho (C) (bona Lisebelisoa le Mekhoa), e neng e sebelisetsoa ho supa bots'epehi ba lithuto tsa SN / VTA, hippocampus le amygdala. Litšoantšo tsohle tsa MT tsa khale tsa lithuto tsa khale li ile tsa aroloa ka lebaka la template ea MT ea sehlopha (D), e neng e sebelisetsoa ho etsa activation kahare ho SN / VTA (e potiloeng ka botala) le khubelu khubelu (e pota-potiloeng ka bofubelu).

Lintlha tsa fMRI li ne li ntlafalitsoe li bile li hlahlobisisoa ka lipalo Bunzeck le Duzel (2006) ka mekhoa e metle ea metara e akaretsang (Friston et al. 1994) o sebelisa sephutheloana sa software sa SPM99 (Lefapha la Wellcome of Cognitive Neurology, University College, London, UK) le MATLAB 6.1 (The MathWorks, Inc., Natick, MA). Litšoantšo tsohle tse sebetsang li ile tsa lokisoa bakeng sa phapang e sa tloaelehang-le sengoathoana mabapi le selae sa bohareng se fumanoeng ka nako, se lokisoe bakeng sa liemahale tse tsamaeang ka molumo oa molumo oa pele, 'me sa fetoloa ka mokhoa o tšoanang maemong a tloaelehileng T1'Mapa oa template ea' mapa oa lipalo-palo ("Ashburner le Friston 1999). Tloaelo e ile ea bonoa ka ho khopisa thuto ea anatomical IR-EPI ho template ea SPM le ho sebelisa mekhahlelo ena litšoantšong tse sebetsang. Litšoantšo li ile tsa hlophisoa bocha ho ea 2 × 2 × 2 mm mme ea ntlafatsoa ka isotropic 4-mm e bophara bo felletseng halofo ea boholo ba Gaussian kernel. Lintlha tsa fMRI tsa letoto la nako li ne li tlhotliloeng ka mokhoa o fetisisang (khaola li-120 s) mme lefats'e ka bophara li phahamisitsoe ho li-voxel le lisekeleng nakong e ngoe le e ngoe ea thuto. Sebopeho sa lipalo-palo bakeng sa sehlooho ka seng se ne se sebetsoa ka ho sebelisa tšebetso ea karabelo ea kananete le lihlahisoa tsa eona tsa nakoana (Friston et al. 1998). Ho hapa lits'oants'o tse amanang le metsamao e amanang le metsamao, li-covariate tse 6 thutong e ngoe le e ngoe li ne li kenyellelitsoe (liphetolelo tse 3 tsa 'mele o thata le li-3 tse fetotsoeng ho tloha pusong ea pele). Litlamorao tse ikhethileng tsa tikoloho li ile tsa lekoa ka ho sebelisa phapanyetsano ea mela ho thuto e ngoe le e ngoe le maemo a fapaneng. Litšoantšo tse fapaneng tse hlahisitsoeng li ile tsa hlahisoa tlhahlobisong ea litla-morao tsa boemo ba bobeli. Mohlala o mong ke ona t-liteko li sebelisitsoe litšoantšong tse fumanoeng molemong oa molumo oa sehlooho ka seng le maemo a fapaneng. Ha re fuoa likhopolo-taba tsa pele, liphetho li ile tsa thibeloa P <0.005 (e sa nepahala) le k = 3 voxel. Ho netefatsa bokhoni ba kemolo ea SN / VTA le likarabo tsa khubu ea khubelu, limmapa tsa ts'ebetso li ne li hloiloe holima template ea MT. Tikoloho ea tlhaho ea tšebetso ea tšebetso e ka ntle ho mpa ea bohareng e ile ea hlahlojoa mabapi le maemo a tloaelehileng a boemo ba leholimo bo phahameng ka ho sebelisa limmapa tsa SPM ho template ea phepo e tloaelehileng (MNI) e fanoeng ke SPM99.

Ho lekola litlamorao tsa liphetoho tsa sebopeho sa sisteme ea mesolimbic ts'ebetsong ea bohlanya, hippocampus le amygdala li hlalositsoe e le libaka tse khahlisang (ROI) sebelisa motho ka mong T1Litšoantšo tse se nang boima, 'me SN / VTA ROI e ne e hlalosoa e sebelisa setšoantšo se le seng sa MT. Kamora nako, li-ROI li ile tsa fetisetsoa setšoantšong se le seng sa MTR, 'me boleng ba bohlokoa (ho li-voxels) ho ROI e' ngoe le e ngoe bo ile ba nkuoa ka lebaka la SN / VTA MTR, hippocampus MTR, le amygdala MTR. Boemong ba bobeli bo bonolo ba regression e sekaseka lilemo, SN / VTA MTR, hippocampus MTR, le amygdala MTR li ile tsa kenngoa e le li-regressors bakeng sa papiso ea phaello (mohlala, oddballs e seng molaong le li-oddballs tse sa nke lehlakore).

Results

Ka boitšoaro, 92.1% (SD = 2.1) ea lipehelo tsohle li fumanoe ka nako ea mokhoa oa ho arabela oa 558 ms (SD = 68), mme ke feela 2.32% (SD = 2.1) ea litlelase tsohle tse ntlafatsang tse arabiloeng ka bohata e le liphofu.

Thutong ea pele ea tlhaiso-leseling ea li-fMRI, li-HRs tse bohareng ba mpa li ile tsa hlahlojoa bakeng sa maemo a fapaneng a phaello. Limmapa tsa Statistical parametric li bonts'a hore kahara bo-mahareng, mofufutso (buka ea maiketsetso e ts'oanang le li-oddballs tse sa nke lehlakore) o phahamisitse karabelo e hlahelletseng ho SN / VTA e nepahetseng.Feie. 3A-C, Tlhokomelo ea Lethathamo la S1A) empa ho haella ka sethe (litekanyetso tse sa nke lehlakore tsa litekanyetso le litekanyetso) le maikutlo a mabe a maikutlo a fosahetseng (maikutlo a mabe a maikutlo a sa lumellaneng le litheko tse sa nke lehlakore) ha a a ka a etsa joalo. Boemong ba lipalo ba P = 0.005 (uncorcheded) sepheo (sepheo sa oddballs vs. oddballs tse sa jeleng paate) e ne e amahanngoa le ts'ebetso e matla ho pholletsa le bo-maqhubu bohle ho kenyeletsa le SN / VTA e kopanetsoeng habeli. Leha ho le joalo, monyako oa P = 0.05 (e lokisitsoe), ke khubu e khutsitseng e khubelu feela (Feie. 3H) e hlahisitse ts'ebetso (Tafole ea tlatsetso S1D).

Setšoantšo sa 3. 

Mekhoa ea ts'ebetso ea FMRI. Ts'ebetso ea Novelty (li-oddballs tse ncha vs. oddballs tse sa nke lehlakore) e ne e amahanngoa le ts'ebetso ho SN / VTA (A-C), hippocampus, le parahippocampal cortex (D, E). Li-valence tse mpe tsa maikutlo (li-oddballs tse mpe tsa maikutlo le li-oddbb tse sa nke lehlakore) li hlahisitse amygdala e nepahetseng (F) le ho se tloaelehe (ho sa tloaelehang ha litheko (li-oddballs tse bapileng le litekanyetso) li ile tsa kenya tšebetsong hippocampus (G). Maqhama a mabeli a nyarosang a maikutlo le ho haella ha lia ka tsa kenya tšebetsong SN / VTA. Targetness (sepheo sa li-oddballs vs. oddballs tse sa tsejoeng) se qalile mookotla oa bofubelu ba leqele (H). Limmapa tsa ts'ebetso li ntlafalitsoe ka matla template ea MT ho (A, B, C., 'me H) (Bona Lisebelisoa le Mekgwa) le ho T1Boko bo tloaelehileng ba MNI ho (D,E,F, 'me G). Limmapa tsa ts'ebetso li ne li thibetsoe P = 0.005 (e sa hlophisitsoeng) ntle le ho tsoa ho (H) li-activation li ne li thibetsoe P = 0.05 (e lokisitsoe).

Bophelong bohle bo fuperoeng, lipale tsa tšusumetso tse matla li ne li amahanngoa le karabelo e matla ea bonngoe hippocampus (Feie. 3D,E) le parahippocampal cortex (Feie. 3D le Tafole e Ntle ea S1A). Litlamorao tse mpe tsa maikutlo (maikutlo a fosahetseng a makatsang) le maikutlo a sa nke lehlakore) a hlahisitse ts'ebetso ho amygdala e nepahetseng (Feie. 3F, le Tafole e Ntle ea S1B), ho se lekane (litloaelo tse sa nke lehlakore tsa litheko le litekanyetso) li ile tsa kenya tšebetsong hippocampus (Feie. 3G) le habeli tsa parahippocampal cortex (Letlapa la tlatsetso la S1C), le ho tsepamisa mohopolo ho ne ho amahanngoa le ts'ebetso libakeng tse ngata tsa bophahamo bo sa lekanyetsoang ho kenyeletsa hippocampi ka bobeli. Leha ho le joalo, ka monyako o hlokisang botsitso (P = 0.05, e lokisitsoe), mokhoa oa ts'ebetso oa ho tsepamisa mohopolo o ne o behelletsoe ka tharollo e nepahetseng ea letsopa, thalamus, patortal infotale e ka pele, bilatesal basal ganglia, ts'ebetso ea naha e kenang, ging e nepahetseng, le lets'ollo le letšehali (Letlapa la tlatsetso la S1D). Kamora nako, bohloka, ho haella, le sepheo empa eseng maikutlo a mabe a maikutlo a ile a kenya tšebetsong libaka tse 'maloa kahare ho cortex ea pele (Supplementary Tafole S1).

Tlhahlobo ea MTR

Tlhatlhobo ea khokahanyo kahare ho sehlopha sa batho ba baholo (likamano tsohle tse tlalehiloeng ke likamano tse peli tsa Pearson ntle le ha ho boletsoe ka tsela e ngoe) le mefuta ea SN / VTA MTR, hippocampus MTR, amygdala MTR, le lilemo li senotse kamano e ntle lipakeng tsa SN / VTA MTR le hippocampus MTR (r = 0.542, P = 0.011) empa ha ho khokahano lipakeng tsa mefuta e meng e fapaneng (Lethathamo 1). Ho tsoela pele ho lekola litlamorao tsa botsofali liphetohong tsa sebopeho, SN / VTA MTR le hippocampus MTR li ile tsa bapisoa lipakeng tsa batho ba baholo ba 24 le ba baholo ba 21 ba sebelisang mehlala e ikemetseng T-etona. Ho bile le phokotso ea bohlokoa ea SN / VTA MTR ho batho ba baholo ba baholo (ba metsero e 'meli, likhato tsa tokoloho [df] = 43, P = 0.008, T = 2.8), ha ho ne ho ena le mokhoa feela (makhetlo a mabeli, df = 43, P = 0.17, T = 1.4) bakeng sa phokotso ea hippocampus MTR (Feie. 4).

Setšoantšo sa 4. 

Papiso ea MTR pakeng tsa bacha le batho ba baholo ba baholo. Le ha SN / VTA MTR e ne e phahame haholo ka palo ea batho ba baholo ba banyenyane (papiso e nang le marapo a mabeli, P = 0.008, T = 2.8) (e bontšitsoe ke naleli), hippocampi MTR e ne e sa fapana haholo lipakeng tsa batho ba babeli empa e ne e rata ho phahama ka mohlala oa batho ba baholo ba banyenyane (papiso e nang le marapo a mabeli, P = 0.17, T = 1.4). Liphoso tsa liphoso li bonts'a phoso e tloaelehileng ea moelelo.

Lethathamo 1 

Coefficients (pearson mabapi le khokahano ea) pakeng tsa SN / VTA MTR, hippocampus MTR, amygdala MTR, le lilemo

Bakeng sa ho lekola kamano lipakeng tsa ts'ebetso ea boqapi le botsitso ba sebopeho-joalo ka ha ho bonts'itsoe ke MTR-le ts'ebetso e ncha le lilemo, tlhahlobo e bonolo ea khatello ea maikutlo bakeng sa pherekano e sa tloaelehang ('li-oddballs tse ncha vs. oddballs tse se nang lehlakore') li entsoe ka li-regressor SN / VTA MTR, hippocampus MTR, amygdala MTR le lilemo. SPMs e senoletse hore SN / VTA MTR e amana hantle le mohono oa HR ho SN / VTA (Feie. 5A) le hippocampus e nepahetseng (Tafole ea tlatsetso S2A), hippocampus MTR e lumellane hantle le mocha oa HR ho hippocampus e nepahetseng (Feie. 5F le Supplementary Tafole S2B), 'me lilemo li ne li hokahanngoe hampe le buka e sa tloaelehang ea HR ho hippocampus (Supplementary Tafole S2C). Ho ne ho se na kamano pakeng tsa amygdala MTR le litaba tse ncha tsa HR ho hippocampus kapa SN / VTA (Tafole ea S2D ea Tlatsetso).

Setšoantšo sa 5. 

Likamano lipakeng tsa li-HR le li-MTR tse amanang. Novelty HR in SN / VTA (A) amanang hantle le SN / VTA MTR (B) le hippocampus MTR (C) empa eseng lilemoD) kapa amygdala MTR (E). Ka hippocampus (F), HR e ncha e lumellana hantle le SN / VTA MTR (G), hippocampus MTR (H) le hampe ka lilemo (I) empa eseng ka Amygdala MTR (J). Limmapa tsa ts'ebetso li ntlafalitsoe haholo holima template ea MT (A) kapa T1Boko bo tloaelehileng ba MNI (F) le ho thijoa ha P = 0.005 (e sa lokang). Marena a bontša phetoho e kholo ho *P = 0.05 kapa **P = 0.01 - ns e khutsufatso "ha e bohlokoa" (P > 0.05).

Tlhahlobo e haufinyane ea voxel e phahameng ho SN / VTA (Feie. 5A) (X le Z = 0, −14, −12) e bonts'ang khokahano lipakeng tsa HR e ncha le SN / VTA MTR le voxel e phahameng haholo hippocampus (Feie. 5F) (10, −2, 24) tse bonts'ang khokahano lipakeng tsa HR tse ncha le hippocampus MTR ka nako eo li ile tsa etsoa. HR e sa tloaelehang ho SN / VTA e hokahane hantle eseng feela le SN / VTA MTR (Feie. 5B) empa hape le hippocampus MTR (Feie. 5C), ha e bonts'ane le lilemo (Feie. 5D) kapa amygdala MTR (Feie. 5E). HR e sa tsebeng letho ka hippocampus e nepahetseng (Feie. 5F) amanang hantle feela eseng feela ka hippocampus MTR (Feie. 5H) empa hape le SN / VTA MTR (Feie. 5G), ha e ntse e bonts'a kamano e mpe le lilemo (Feie. 5I), hape ha ho khokahano le amygdala MTR (Feie. 5J). Ntle le moo, hippocampus HR le SN / VTA HR ho litaba tse ncha li hokahane hantle (r = 0.375, P = 0.047, e le 'ngoe-tailed), empa ho ne ho sena khokahano lipakeng tsa amygdala HR ho bocha le SN / VTA HR kapa hippocampus HR ho litaba tse ncha (ka bobeli P > 0.39). Kamanong e latelang e sa lekanyetsoang e sebelisang lilemo joalo ka taolo ea taolo, likamano lipakeng tsa bocha HR ho SN / VTA le SN / VTA MTR (r = 0.62, P = 0.004), HRS ea boqhetseke ho SN / VTA le hippocampus MTR (r = 0.48, P = 0.03), ha a na litaba tsa HR hippocampus le SN / VTA MTR (r = 0.43, P = 0.055), le HR ea bohlano ho hippocampus le hippocampus MTR (r = 0.63, P = 0.003) e lutse e le ea bohlokoa kapa e atametse boemo ba bohlokoa (bo-HR ba bo-hippocampus le SN / VTA MTR).

Kamano ea ts'ebetso pakeng tsa SN / VTA MTR le hippocampal MTR ha e na monyetla oa ho ba sesupo sa ts'ebetso ea lefats'e e amanang le bohlooho kapa e tšoeu ka hore SN / VTA MTR kapa MT ea hippocampal ha e bonts'ane le kamano le 'mala oa lefats'e kapa bophahamo ba taba e tšoeu ea batho ba baholo ba baholo (kaofela P litekanyetso> 0.3). Meqolo ea lefatše ka bophara ea bohlooho le bosoeu e ile ea ntšoa ho ipapisitsoe le taba T1Setšoantšo se nang le boima bo sebelisang likarolo tse tloaelehileng tsa bokong ba SPMAshburner le Friston 2000).

Bakeng sa ho sekaseka litšobotsi tsa HR ho amygdala bakeng sa litumellano tse mpe tsa maikutlo, ho hlahlojoa bonolo ho hlahloba ho sebelisa "likhopolo tse nyarosang tsa maikutlo le litumellano tse sa nke lehlakore" le li-MTR tse fapaneng le lilemo tse joalo ka li-regressor li ile tsa etsoa. Ha ho le e 'ngoe ea litlhahlobo tsena tsa SPM e senotseng khokahano ea bohlokoa molemong oa bohlokoa oa 0.005 (o sa hlophisoa). Leha ho le joalo, tlhahlobo e haufinyane ea HR ea tlhoro e phahameng kahare ho amygdala e nepahetseng bakeng sa maikutlo a mabe a maikutlo (X le Z = 28, 0, −22; bona Tafole ea Tlatsetso S1B) le amygdala e nepahetseng ea MTR e senole khokahano lipakeng tsa lintho tse peli tse fapaneng ka mokhoa o le mong oa taolo e le ngoe (r = 0.376, P = 0.046, e le 'ngoe-tailed). Ka lehlakoreng le leng, HR ea hloahloeng ena e phahameng ea maikutlo a fosahetseng ha a ka a lumellana le SN / VTA MTR, hippocampus MTR, kapa lilemo (kaofela P > 0.34).

Ho fapana le seo re se boneng morao tjena ho bacha ba phetseng hantle (Bunzeck le Duzel 2006)) Ho fapana le boqhetseke, leha ho le joalo, sepheo sa HRs ea li-voxel tsena ha ea ka ea lumellana le SN / VTA MTR (P ≥ 0.5) empa e hokahane hampe le linako tsa karabelo ea moetsi ho lipheo (r = -0.42, P = 0.056). Ntle le moo, litaba tsa khale tsa HR ho SN / VTA ha lia ka tsa lumellana le nako ea karabelo (r = 0.16, P = 0.5), mme ho ne ho sena khokahano lipakeng tsa SN / VTA HR ho fihlela sepheo le lilemo (P ≥ 0.5).

Puisano

Mofuta oa hippocampal-SN / VTA o bolela esale pele hore boholo ba karabelo ea SN / VTA ea motho le hippocampus ho bocha ho batho ba baholo ba lokela ho ikemiselitsoe ka kopanelo ke botshepehi bo ka hara SN / VTA le hippocampus. Ho fapana le hoo, ho fanoa ka hore amygdala ha e kenye letsoho ka kotloloho ho hippocampal-SN / VTA novelty processing, likarabo tsa hippocampal kapa SN / VTA ha lia lokela ho ameha ke ho tšepahala kahare ho amygdala. Ona ke ona mohlala oo re o boneng. Ha re nahana ka li-MTR tsa SN / VTA, amygdala, le hippocampus, re hlokometse kamano e khethiloeng-kamano pakeng tsa SN / VTA le hippocampus bakeng sa ts'ebetso e ncha. Likarabo tsa Novelty ho SN / VTA le hippocampus li ile tsa hokahanngoa, 'me li ne li hokahanngoa le li-MTR tsa tsona tse fapaneng (Feie. 5B,H). Habohlokoa le ho feta, likarabo tsa lipale tse qabolang tsa hippocampal li ne li boetse li amana le MTR ea SN / VTA (Feie. 5G), 'me likarabo tse ncha tsa SN / VTA li ne li hokahane le MTR ea hippocampus (Feie. 5C). Kamano ena e kopaneng ea sebopeho-ha e na monyetla oa ho bonts'a phello e sa reroang ea liphetoho tsa MTR hobane MTR ea amygdala e ne e sa tsamaellane le karabelo e ncha ea SN / VTA (Feie. 5E) kapa hippocampus (Feie. 5J). Leha ho le joalo, ho ne ho e-na le khokahano e fokolang pakeng tsa li-MTR ho amygdala le HR ho maikutlo a mabe a maikutlo ho amygdala ha ho sena khokahano efe kapa efe le liphetoho tsa MTR ho SN / VTA le hippocampus. Liphumano tsena tsa kamano ea sebopeho se ikhethileng ka har'a SN / VTA le hippocampus bakeng sa ts'ebetso ea bohlanya li fana ka ts'ehetso e matla bakeng sa thekiso ea hippocampal-SN / VTA ts'ebetsong ea bohlanya (Lisman le Mohau 2005).

SN / VTA MTR ea batho ba baholo ba baholo e ne e le tlase haholo ho feta sehlopheng sa rona sa taolo ea bacha (Feie. 4), ho fana ka maikutlo a hore lintho tseo re li fumaneng li feta tlhahisong ea maikutlo ebile li bohlokoa ho utloisisa liphetoho tse amanang le lilemo tsa memori. Leha ho le joalo, phokotso ena ea SN / VTA MTR ho batho ba baholo ba baholo ha ea ka ea fetolela tumellano lipakeng tsa lilemo le MTR thutong ea rona. Tlhaloso e 'ngoe e hlakileng ea sena ke lilemo tse fokolang tsa sampole tsa lithuto tsa rona tsa khale. Ho tsejoa, ho etsa mohlala, hore, hippocampal volumes le tsona ha li bonts'ane le maemo a lilemo tsa disampole tse moqotetsane (Szentkuti et al. 2004; Schiltz le al. 2006) empa bonts'a khokahano le mehlala e simolohang ho tloha ho 20s ho isa ho 80s (Raz le Rodrigue 2006). Ho ka nahanoa hore ka bongata ba lilemo tse qalang lilemong tsa bo-20 ho isa lilemong tsa bo-80, ho fumana ha rona phetoho e kholo ho batho ba baholo ho tla fetolela tumellanong lipakeng tsa lilemo le SN / VTA MTR.

Seo re se fumaneng se phahamisa potso ea hore na liphetoho tsa sebopeho le tšebetso ho SN / VTA le hippocampus li amana ka mokhoa o loketseng. Lintlha tsa Anatomical li rata monyetla o joalo. Taba ea mantlha, merero ea SN / VTA ka kotloloho ho hippocampus (Lisman le Mohau 2005). Taba ea bobeli, le ha hippocampus e sa sebetse ka kotlolloho ho SN / VTA, ke eona e ka sehloohong le mohlomong tšimoloho ea lets'oao le sa tloaelehang ho SN / VTA (Lisman le Mohau 2005). Lebaka ke hore libaka tse ling tsa nakoana tsa maikutlo li bile le tšusumetso ho bonoeng bocha (Brown le Aggleton 2001), joalo ka perorthinal cortex, li na lipalo tse fokolang haholo ho "ventral striatum"Friedman et al. 2002) ka hona ha ho lumeloe ho fana ka pontšo e sebetsang ea boqapi ho SN / VTA (Lisman le Mohau 2005).

Joalo ka ho batho ba baholo ba phetseng hantle (Bunzeck le Duzel 2006), SN / VTA e ne e arabela ka mokhoa o hlakileng ho susumetsa maikutlo bocha ho feta ho seoelo kapa maikutlo a mabe a maikutlo. Leha ho le joalo, ho fapana le seo re se fumaneng ho batho ba baholo ba phetseng hantle (Bunzeck le Duzel 2006), SN / VTA e ntlafalitsoe haholo ke sepheo le karabelo ea eona e tsamaeang le makoloi ho batho ba baholo. HR ho fihlela sepheo sa eona e ne e amana hantle le nako ea karabelo, e fana ka tlhahiso ea hore kabo ea lisebelisoa tse sebetsanang le SN / VTA molemong oa ho etsa karabelo ea boitšoaro litekanyong li ka bonts'a mekhoa e mamellehang bakeng sa mathata a koloi e bobebe. Re lokela ho hlokomela, leha ho le joalo, hore ka tekanyo e phahameng ea lipalo-palo re bone mohlala o tšoanang oa boleng bo kahare le bohareng ba mahareng joaloka ho batho ba baholo ba phetseng hantle (Bunzeck le Duzel 2006). Haholo-holo, ka har'a mpa ea bohareng, likarabo tsa ho tsepama li ne li hokahantsoe le khubu e khubelu (Feie. 3H). Ka hona, ho bonahala eka kabo ea SN / VTA hore e arabeloe ho batho ba baholo ba phetseng hantle e bontša phetoho e lekanang haholo ho batho ba baholo ba nang le linako tse fokolang tsa karabelo empa eseng phetoho ea boleng ho karabelo ea sebopeho sa bokhachane. Thutong ea morao-rao ea posmortem ea methapo ea methapo ea SN, batho ba baholo ba phetseng hantle ntle le PD ba bontšitse tahlehelo ea methapo ho SN, mme tahlehelo ena e ne e tsamaellana le matšoao a bonolo a parkinsonia a joalo ka bradykinesia le gait ho leka-lekana (Ross et al. 2004). Ho ka etsahala hore linako tse liehang ho arabela li bonts'a bradykinesia e bonolo, eo ka nako e 'ngoe e amanang le ho khanna ho ea SN / VTA molemong oa ho etsa phello. Habohlokoa, ho tlameha ho hlokomeloe hore e ntse e lokela ho khethoa hore na ke mosebetsi o hlokang "palo ea kelello" kapa "ngoliso ea kelello" ea merero ha ho se na karabelo e fetang ea koloi e ka lebisang ho bohareng ba HR bohareng ho fihlella liphofu tsa bacha. le ho batho ba baholo ba baholo.

Hippocampus le amygdala tsa batho ba baholo ba baholo li ile tsa bonahala li boloka thepa ea bona ea likarabo e bonoang ho batho ba baholo ba phetseng hantle (Strange le Dolan 2001; Yamaguchi et al. 2004; Crottaz-Herbette le al. 2005). Joalo ka ho batho ba baholo ba banyenyane (Bunzeck le Duzel 2006), hippocampus e ne e le khetho e fokolang ho feta SN / VTA hobane e arabile ho hongata (Feie. 3D,E) hammoho le seoelo (Feie. 3G). Ka lehlakoreng le leng, amygdala, e ne e le setereke feela se ileng sa arabela ka mokhoa o hlakileng ho tlatsueho e mpe ea maikutlo (Feie. 3F). Boithuto ba pejana ho batho ba baholo ba baholo bo bontšitse hore lifahleho tse nang le tšabo tse ntšo ha li bapisoa le sefahleho se tloaetseng ho se nke lehlakore li amahanngoa le ts'ebetso e matla ea amygdala ho batho ba baholo ba phetseng hantle (Wright le ba bang. 2006). Tlhahiso-leseling e teng hona joale e tiisa sepheo sena ka ho bontša hore ho batho ba baholo ba phetseng hantle ho na le ts'ebetso e matla ea bo-amygdala ho tloaelo e tšosang ea sefahleho (lifahleho le lits'oants'o) ha li bapisoa le maikutlo a tloaelehileng a sefahleho (lifahleho le maemo).

Boithuto bo 'maloa ba pejana bo fuputse phetoho tse amanang le lilemo ts'ebetsong ea boqhetseke ba sebelisa menyetla e amanang le liketsahalo (ERPs). Ha ba lumelloa ho fana ka tlhokomelo ea boithaopo litšoantšong tse sa bonahaleng tsa litšoantšo nakong ea ho shebella ka boithatelo, batho ba baholo ba sebetsang ka mokhoa o phahameng ha ba na letšoao la likarabo tse amanang tse nyane tse amanang le P300 (Daffner le ba bang. 2006). Ha e le hantle, maqhubu a bona a P300 a ka ntlafatsoa le ho fana ka tlhahiso e fanang ka maikutlo a susumetsang haholoanyane lithutong tse ncha tsa batho ba baholo (Daffner le ba bang. 2006). Khopolo ena e lumellana le lithuto tsa lesion tse fanang ka maikutlo a hore bo-ralitaba ba pele-pele bo nka karolo molatong oa ntho e ncha ea P300 (Soltani le Knight 2000) le hore batho ba baholo ba phetseng hantle ba lula ba bonts'a hemispheric lateralization mesebetsing ea kelello joalo ka encoding ea episodic mohlomong e bonts'a lits'ebetso tsa mats'eliso a matla (Dolcos et al. 2002). Lintlha tsa rona li tsamaisana le ak'haonte e joalo ea lithuto tsa ERP tsa ts'ebetso ea bohlanya kaha li bonts'a likarabo tse nyane tsa mesolimbic novelty ho batho ba baholo ba nang le SN / VTA e fokolang le hippocampi. Ho ka etsahala hore batho ba baholo ba baholo ba iphetetse bakeng sa likarabo tse fokolisitsoeng tsa mesolimbic novelty ka ho ikemisetsa ka matla ho etella pele lithutong tse ncha. Haeba ho joalo le haeba karabo ea bohlanya ea P300 ho batho ba baholo ba baholo e amana le ho tataisoa joalo ka boiteko, motho a ka bolela esale pele hore P300 e ncha lithutong tsena e lokela ho eketseha ka ho eketseha ka ho fokotseha ha MTR ho SN / VTA le hippocampus. Habohlokoa, sena se nka hore bots'epehi ba cortex ea pele nakong ea botsofali bo tloaelehileng bo lumella matšeliso a ho fokotseha ha ts'ebetso ea mesolimbic. Leha ho le joalo, sena ha se na ho ba joalo haeba ho na le khokahano pakeng tsa tahlehelo ea ts'ebetso ea mantlha ea cortical le mesolimbic e sebetsang le / kapa bots'epehi.

Sesebelisoa se phetoa hantle haholo ho batho ba baholo ba phetseng hantle ke ts'ebetso e felileng ea ntho e ncha ea P300 ka ho pheta-pheta (Friedman et al. 1998; Daffner le ba bang. 2006; Weisz le Czigler 2006). Lintlha tsa rona li bonts'a hore likarabo tsa lipalesa tsa mesolimbic li fokotsehile ha li bapisoa le liphetoho tsa sebopeho ho SN / VTA le hippocampus, empa ha re e-so ithute ka litaba tsa hore li-oddballs tse ncha lithutong tsa rona ha li a phetoa. Lintlha tsa rona ka hona ha li nke lehlakore mabapi le monyetla oa hore ntle le hore o fokotsehe ka li-MTR tse tlase ho SN / VTA le hippocampus, likarabo tse sa tloaelehang libakeng tsena le tsona li bontša ho fokotseha ha tikoloho.

Ntle le lobe ea nakoana, lirekoto tse fapaneng tsa elektronike, lithuto tsa bakuli (Baudena et al. 1995; Daffner le ba bang. 2000,, le lithuto tsa ho nahana ka (Opitz et al. 1999; Clark et al. 2000ba totobalitse karolo ea li-cortices tsa pele le tsa orbitofrontal (Busa et al. 2002) ts'ebetsong ea bohlanya (Yamaguchi et al. 2004). Le ha li-HRs ho ea bocha, ho haella, le ho tsepamisa maikutlo li ne li fapane hole le palo ea rona ea lipono tse fokolang, karolo ea karolo e ka pele ho ts'ebetso ea bocha e feta mohloling oa pampiri ena. Bophahamo bo felletseng ba thepa bo hlokahala ho lekola kamano ea ts'ebetso lipakeng tsa li-cortices tsa pele le tsa orbitofrontal le meetso ea mesolimbic nakong ea ts'ebetso e ncha.

Ho akaretsa, mohlala oa liphetoho tse amanang le lilemo le tšebetso tse shebiloeng mona ka har'a sistimi ea mesolimbic e fana ka ts'ehetso bakeng sa ts'ebetso ea hippocampal-SN / VTA ea ts'ebetso ea bohloka. Ha joale ho tlameha ho tsejoa hore na liphetoho tsa sebopeho le tšebetso ho loop ena li ama ts'ebetso ea memori ea episodic joang ho batho ba baholo. Ho feta moo, liphumano tsena li fana ka maikutlo a hore batho ba baholo ba nang le li-SN / VTA MTR tse tlase le likarabo tse fokotsang tsa mesolimbic ho li-novelty ba ka rua molemo ho nkeng dopaminergic. The dopamine precursor levodopa (L-DOPA) e nkuoa haholo ebe e fetoloa ke dopaminergic neurons ebe e ntšoa ka phasal. Ka hona, L-DOPA ke setlhare se khahlisang ka ho khetheha ho ntlafatsa phasic dopamine ho araba bonyatsi. E se e bontšitsoe ho matlafatsa ho ithuta ha mantsoe a macha ka ho pheta-pheta ho batho ba baholo ba phetseng hantle (Knecht et al. 2004; Breitenstein le al. 2006) le ts'ebetso ea ho hopola mantsoe (Newman et al. 1984) hammoho le ho hlophisoa ha mohopolo oa koloi lithutong tsa khale tse phetseng hantle (Floel et al. 2005, 2006). Ho hlokahala lithuto tsa Pharmacological ho hlahloba melemo ea L-DOPA le dopamine agonists ho batho ba baholo ba nang le li-MTR tse tlase ho SN / VTA.

Boitsebiso bo Eketsehileng

Lintho tse tlatsetsang li ka fumaneha ho http://www.cercor.oxfordjournals.org/.

lumela hore baa fokola

Boithuto bona bo tšehelitsoe ke lithuso ho tsoa ho Deutsche Forschungsgemeinschaft (Klinische Forschergruppe "Kognitive Kontrolle," TP1) le BMBFT (CAI) ho tsoa Univesithing ea Magdeburg. Re leboha Michael Scholz bakeng sa thuso ka moralo oa fMRI le Ulrike Malecki le Ana Blanco bakeng sa thuso ea ho fumana data. Khohlano ea ThahaselloHa ho ea phatlalalitsoeng.

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