Ukusetyenziswa kwe-Mesolimbic ekuveliseni abantu abadala (2007)

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

UBunzeck N1, USchütze H, Stallforth S, Kaufmann J, UDüzel S, U-Heinze HJ, UDüzel E.

Abstract

Ukuguga okuqhelekileyo kunxulunyaniswa nelahleko ye-neuronal kwindawo ye-dopaminergic midbrain (indawo ye-substantia nigra / ye-ventral tegmental, SN / VTA), mmandla osandula ukufakwa ekuqhubeni inoveli yenkuthazo njengenxalenye yenethiwekhi ye-mesolimbic kubandakanya ne-hippocampus. Apha, sichaze ubungakanani obunxulumene nobume bokudalwa kwenkqubo ye-mesolimbic kusetyenziswa umda wokudluliselwa kwemagnethi (MTR) kwaye siyidibanisa neempendulo ze-mesolimbic hemodynamic (HRs) ukukhuthaza ubungendawo. Amashumi amabini ananye abantu abadala abaphilile abadala phakathi kwe-55 kunye ne-77 iminyaka enza ipadadball ebonakalayo evumela ukwahlula i-HRs ye-mesolimbic ibe yinto yokungaqhelekanga kwizinto ezinqabileyo, ukungahambisani nemvakalelo engathandekiyo, kunye nokujolisa ekusetyenzisweni komfanekiso wemagneti resonance. Ii-HRs kwi-SN / VTA yasekunene kunye ne-hippocampus esekunene kwinto entsha yayilungelelaniswe kakuhle nge-SN / VTA MTR kunye ne-hippocampus MTR kodwa hayi i-amygdala MTR. Nangona kunjalo, i-HR ye-amygdala ukuya kwi-valence engathandekiyo yeemvakalelo edibene ne-amygdala MTR kodwa hayi nge-MTR kwi-SN / VTA okanye i-hippocampus. Iziphumo zimisela ulwalamano-lomsebenzi ubudlelwane ekuxhaseni i-hippocampal-SN / VTA loop ye-mesolimbic novelty processing ngokubonisa ukuba i-hemodynamic activation kwi-SN / VTA kunye ne-hippocampus yobuntshatsheli ichaphazeleka ngokukhethekileyo kukungqinelani kobudala obuhambelana nezi zinto.

Amagama abalulekileyo

intshayelelo

Kukho ubungqina obuguqukayo bokuba i-dopamine idlala indima kungekuphela nje ekuqiniseni ukufunda kodwa nakwimemori ye-episodic exhomekeke kwi-episodic.I-Lisman kunye neGrace 2005). Kwizilwanyana, i-dopamine inyusa amandla e-hippocampal yexesha elide (I-Otmakhova kunye neLisman 1996; Li et al. 2003; I-lemon kunye neManahan-Vaughan 2006kunye noxinzelelo lwexesha elide (I-lemon kunye neManahan-Vaughan 2006) kwindawo ye-CA1 kunye nokuphucula ukuxhomekeka kwe-hippocampus-(I-Gasbarri et al. 1996; Bach et al. 1999; I-lemon kunye neManahan-Vaughan 2006). Ukusetyenziswa kwe-Intrahippocampal agents ye-dopaminergic agents (njenge-amphetamine) kuphucula inkumbulo yendawo kwimisebenzi ye-maze (UPackard et al. 1994). I-Intraventricular injections ye-dopamine ekhethiweyo ye-D1 / D5 receptor antagonists ikhokelela kwimeko yokungalungiseki kokuziphatha okucaphukisayo xa izilwanyana ziphinde zabuyiselwa kwimeko yangaphambili yenoveli (I-lemon kunye neManahan-Vaughan 2006). Kubantu, utshintsho lwe-pathological kwinkqubo ye-dopaminergic lunokunxulunyaniswa nokusilela kwememori (Umntu obuyela umva et al. 2000).

Ubungqina obusebenzayo be-anatomical yendima ye-dopaminergic midbrain kwi-episodic encoding ivela kwiziphumo zophando lwamandla e-resonance imaging (fMRI) yakutshanje. Ukuvuselela okunxulumene nomvuzo we-substantia nigra / ventral tegmental ndawo (SN / VTA), ummandla apho isiseko se-mesomimbic dopaminergic neuromodulation simsuka, sinxulunyaniswa nokwenziwa kwememori ye-hippocampus exhomekeke kwixesha elide kunye nokwenziwa kwendibaniselwano.U-Wittmann et al. 2005; Adcock et al. 2006). Ukwenza intsebenzo enxulumene nokubola okwenzeka embindini yenzeke ngokuzimela komvuzo (USchott et al. 2006). Isalathiso se-anatomical sokuba le mpendulo yokusebenza ye-SN / VTA inxulumene ne-dopaminergic neurotransuction iqiniswe bubungqina bemvelo obutsha obubonisa ukuba iprofayili yokuvula enxulumene nokufakelwa kule ndawo iguqulwe ngenani elisebenzayo lokuguquguquka kwe-tandem ephindaphindiweyo kwi-dopamine transporter (DAT1) uhlobo (USchott et al. 2006).

Kucetyisiwe ukuba ubudlelwane obusebenzayo phakathi kwe-SN / VTA kunye nehippampus buqhutywa kukuvuselela okuthile (I-Lisman kunye neGrace 2005). I-dopaminergic dbaminergic midbrain neurons yemivuzo kwizilwanyana ikwaphendula kwinto entsha kunye nakwindawo yokuhlala xa imeko iba yinto eqhelekileyo ngaphandle kokuqiniswa (ISchultz 1998). Sisebenzisa i-fMRI, kutshanje saphawula ukuba ikwakhona iSN / VTA yomntu ephendula kwinkuthazo entsha, ngelixa ezinye iindlela zokuvuselela ezinjengokungaqhelekanga (okanye umxholo ophambeneyo), ukungahambelani okuhle ngokweemvakalelo, okanye ukujolisa kwishukumisi esiqhelekileyo asisebenzi kakuhle (I-Bunzeck kunye ne-Duzel 2006). Olu lwazi lubonelela ubungqina bokuxhasa imodeli yakutshanje ebonisa ukuphakanyiswa kwe-hippocampal-SN / VTA kunye nokusetyenziswa kwe-inch (I-Lisman kunye neGrace 2005). Bacacisa ukuba kwimeko yokungabikho komvuzo obonakalayo, ukusebenza kwale nto kuqhutywa yinto yokuvuselela inkanuko kunokuba zikho ezinye iindlela zokuvuselela amandla. Kunye nobungqina obukhankanyiwe ngaphambili obumanyanisa umsebenzi we-SN / VTA kunye nekhowudi ephumeleleyo nangona kungekho mvuzo (USchott et al. 2006), ezi zinto zifunyanisiweyo zicebisa unxibelelwano phakathi kweempendulo zobunqabileyo kwi-hippocampal-SN / VTA kunye nokwenziwa ngempumelelo kwememori ye-episodic.

I-dopaminergic neurotransuction ifumana iinguqu ezinxulumene nobudala ezifanelekileyo kwimemori ye-episodic. Idatha ye-autopsy yomntu ibonisa ukwehla okunxulumene nobudala be-3% kwi-dopamine D1 (USeeman et al. 1987; Cortes et al. 1989; Rinne et al. 1990) kunye nee-receptors ze-D2 (USeeman et al. 1987) ishumi leminyaka. Kwi-SN, kukho ilahleko ye-dopaminergic neurons ye-6% kwishumi ngalinye kwisahlulo se-medial kunye ne-2% kwinxalenye yomva we-venral (Fearnley kunye neLees 1991). Ngokudityaniswa kwe-antemortem fluorodopa positron emission tomography kunye ne-postmortem neuronal cell count in the SN, ilahleko ye-neuronal yayihambelana ngokuncipha nokuhla kokufumaneka kwe-dopamine ye-striatal (Ikhephu et al. 1993). Kwabantu abadala abadala, iintsilelo kwimemori ye-episodic zibalwa kungcono yi-D2 receptor binding kunokubudala (Umntu obuyela umva et al. 2000).

Imodeli ye-hippocampal-SN / VTA icingela ukuba ubukhulu bempendulo ye-SN / VTA yomntu kunye ne-hippocampus ukuya nezinto ezintsha kubantu abadala kufuneka zimiselwe ngokudibeneyo ngokunyaniseka ngaphakathi kwe-SN / VTA kunye ne-hippocampus. Ngokwahlukileyo, inikezwe ukuba i-amygdala ayifaki galelo ngokuthe ngqo kwi-hippocampal-SN / VTA novelty process (I-Lisman kunye neGrace 2005; I-Bunzeck kunye ne-Duzel 2006), akukho zimpendulo ze-hippocampal okanye ze-SN / VTA akufuneki zidityaniswe kunye nokuthembeka ngaphakathi kwi-amygdala. Sivavanye le hypothesis sisebenzisa ipharobigm efanayo yokufumana impendulo yeHemodynamic (HRs) kwi-SN / VTA kunye nehippampus kubantu abadala abancinci (I-Bunzeck kunye ne-Duzel 2006) kwiqela labantu abadala abasempilweni. Ukunyaniseka kobume be-SN / VTA, hippocampus, kunye ne-amygdala yabo bonke abathathi-nxaxheba kulinganiswa kusetyenziswa umzobo wokudluliselwa kwemagnetism (MTI).

Ukuhanjiswa kwe-Magnetisis kwizicubu kunxulumene notshintshiselwano ngemagnethi yeproton phakathi kweeprotokholi zamanzi eselfowuni kunye neeproteni ezinganyanzelekanga zii-macromolecule (I-Wolff kunye neBalaban 1989). Ukufezekisa i-MTI, i-magnetization ye-macromolecular proton igcwele ngokugqibeleleyo isebenzisa ngokufanelekileyo i-off-resonance irradiation ngexesha lokuqina komgangatho we-proton. Unxibelelwano lwale mimandla icoconic yahluthwa ngokuthe ngcembe ngeeprotokholi zamanzi eselfowuni kwindawo yazo ejikelezileyo engqonge umqondiso wamanzi oqwalaselweyo kwimifanekiso. Oku kuncitshiswa komqondiso kuxhomekeke kwiipropathi zezicubu ezinje ngoxinzelelo, ulwakhiwo kunye / okanye ikhemistri yee-macromolecule, kunye nomxholo wamanzi kunye nemilinganiselo yokulandelelana kwemifanekiso. Ukuba i-2 imilinganiselo elandelelana kunye (nokudluliselwa kwemagnethi [MTT]) nangaphandle (akukho lutshintsho lwemagnethi [UMT]) ukuhanjiswa kwemagneti kufunyenwe, oko kubizwa ngokuba ngumlinganiselo we-magnetization (MTR) ungabalwa kwi-voxel ngokwe-voxel ngokwe: MTR = (UMT - MT) / MTT.

Ukuncitshiswa kwe-Hippocampal ye-MTR kuye kwaxelwa kwisifo se-Alzheimer's (Hanyu, Asano, Iwamoto, et al. 2000; Hanyu, Asano, Kogure et al. 2000) kwaye ukuya kwinqanaba elincinci kwi-Lewy body dementia (Hanyu et al. 2005). I-pathophysiology ekhethekileyo exhasa ulungiso lwe-MTR kwi-hippocampal kwezi meko ayikacaci, kodwa ukunciphisa kwe-MTR kwizigulana ezine-sclerosis ezininzi kubonelela ngemeko ethile. Bacebisa ukuba ukunciphisa kwe-MTR kunokujongwa nokuba ezinye iindlela zokucinga, ezinje T2- kwaye T1Ukuqiqa okunobunzima, bonisa ukungahambi ngendlela eyenza ithathe ingqalelo ngakumbi ekufumaneni ubuchwephesha bokuqala bezicubu ezibonakala rhoqo kubandakanya umba omhlophe (U-Iannucci et al. 2000; Traboulsee et al. 2002; Audoin et al. 2004; UFernando et al. 2005) kunye ne-cortical (UFernando et al. 2005) kunye nemicimbi engwevu ejulile (Audoin et al. 2004). Ukuncitshiswa kwe-MTR kwinto emhlophe eqhelekileyo ebonakala ngathi inokubakho ngenxa yokwanda kokuqaqamba, ukuvuvukala kwe-perivascular, demyelination (Umthengisi et al. 1999), kunye nelahleko yokuxinana kwe-axonal (van Waesberghe et al. 1999) kunye nokuthuka okunyanzelisiweyo (UFazekas et al. 2005). Ukuncitshiswa kwe-MTR kwinto eqhelekileyo ebonakala ingwevu kungabangelwa kukuphambuka kwesifo se-transsynaptic morphological to les affilint demions, kwaye oku kungenzeka kuxhaswe kukufumanisa ukuba ukubonwa kwe-MTR ye-cortical kuncitshisiwe emva kwesigameko esingafaniyo se-opic neuritis (Audoin et al. 2006). Okubangela umdla kukuba, ezi zigulana ziye zacutha ii-MTR kwi-hippocampus, i-tempic gyrus, i-lenticular nuclei, kunye ne-cerebellum, iphakamisa ukuba i-MTR inomdla ekuguqukeni kwe-transsynaptic neuronal degeneration kunye ne-cortical synaptic morphological change into eqhelekileyo-ebonakalayo emveni kokuvela kwezilonda ezihambelana nemicimbi emhlophe.Audoin et al. 2006).

Ukuncitshiswa kwe-MTR kuye kwaqwalaselwa kwakhona kwi-SN kwizigulana ezinesifo sika-Parkinson's (PD) (U-Eckert et al. 2004; I-Seppi kunye neSchocke 2005). Isizathu sokuncitshiswa kwe-SN MTR kwi-PD asiqondakali kakuhle. I-PD ibonakaliswa ngokunyula okukhethiweyo kwe-dopaminergic, i-neuromelanin-equkethe i-neurones ye-SN (i-paractacta). I-Neuromelanin yi-macromolecule emnyama engatyibilikisi ebonisa umbala omnyama kwi-SN. Ukuphulukana kwe-Neuronal kunye nokuwohloka kwesikroba se-neuromelan macromolecule scaffolding (UFasano et al. 2006) kungakhokelela ekunciphiseni kwe-MTR. Kucingelwa ukuba zombini iindlela zinokuthi zikhokelele ekunciphiseni kwe-MTR kubantu abadala abasempilweni nabangenazo iimpawu zonyango ze-PD.

Okokugqibela, kubantu abadala asebekhulile asempilweni, i-MTR ye-cortex ibonisa ukunxibelelana okungathandekiyo kunye nobudala, kunye nokuncitshiswa okunxulumene nobudala bomelele kunokwento emhlophe, ndicebisa ukuba iMTR inovakalelo lweenguqu ezinxulumene nobudala kulwakhiwo lwezinto ezingwevu (UGe et al. 2002; UFazekas et al. 2005; UBenedetti et al. 2006). Nangona kunjalo, idatha kulwalamano phakathi kweMTR kunye nokusebenza kwengqondo ekwaluphaleni kunqabile (umzekelo, UDeary et al. 2006), kwaye kukho, kulwazi lwethu, akukho datha ekhoyo malunga notshintsho olunxulumene nobudala be-MTR kwinkqubo ye-mesolimbic.

Impahla nenkqubo

I zifundo

Amashumi amabini ananye, abantu abadala abanempilo, abanesandla sasekunene (iminyaka yobudala: iminyaka ye-55-77; kuthetha = iminyaka ye-65.3; ukuphambuka okuqhelekileyo [SD] = iminyaka eyi-6.3; amabhinqa angama-11 kunye namadoda angama-10) aye aqeshwa ukuze athathe inxaxheba kuhlaziyo, olwamkelweyo Ikomiti yokuziphatha kwimimandla yaseOtto-von-Guericke Dyunivesithi yaseMagdeburg, eJamani. Ngokwengxelo yokuziphindezela, akukho namnye kwizifundo owayenembali ye-neurological, psychiatric, okanye ukuphazamiseka kwezonyango okanye naziphi na iingxaki zonyango ezikhoyo. Zonke izifundo zifumene amanqaku kumgangatho oqhelekileyo kwiGeriatric Depression Scale (GDS [I-Yesavage JA et al., 1982]; kuthetha i-GDS = 1.4, SD = 1.1; I-GDS ≤ 4 yazo zonke izifundo; I-GDS isusela kwi-0-15; Amanqaku aphezulu ngaphezu kwe-11 abonisa uxinzelelo) kunye noVavanyo lweMental-Mental State (MMSE [UFolstein ME et al., 1983]; kuthetha i-MMSE = 29.5, SD = 0.75; I-MMSE ≥ 28 yazo zonke izifundo; I-MMSE isusela kwi-0-30; Amanqanaba asezantsi kune-25 asemathambo). Ngapha koko, zonke izifundo zazinoxinzelelo lwegazi oluqhelekileyo, kwaye akukho nanye kuzo eyayiyetyebileyo (kuthetha ukuba isilinganiselo somzimba = 27.1, SD = 5.1). Ithathiwe kunye, iingxelo zokuzazisa, iincwadana zemibuzo, kunye neemviwo zonyango zibonisa iminyaka efanelekileyo yezempilo. Ukuvavanya ukuba ingaba kukho ukunciphisa okunxulumene nobudala kwi-MTR, sibandakanya idatha ye-anatomical MRI evela kubantu abadala abancinci be-24 (inqanaba lobudala: iminyaka ye-21-30; kuthetha = iminyaka ye-23.25; SD = iminyaka ye-2.21; amabhinqa angama-16). Akukho namnye kwaba bantu badala osele efumene imbali ye-neurological, psychiatric, okanye ukuphazamiseka kwezonyango okanye naziphi na iingxaki zonyango ezikhoyo.

Uyilo lovavanyo kunye nomsebenzi

Izifundo ezindala zigqibe iibhloko ze8 zeparadigm ebonakalayo eguqulelweyo ekunikwe ingxelo ngayo I-Bunzeck kunye ne-Duzel (2006). Kwibhloko nganye, bekukho imigangatho ye-80, i-10 ekujongwa kuyo izinto ezingaziwayo, i-10 oddballs ezingathathwanga, i-10 oddballs, kunye ne-10 inoveli oddballs, ivelisa itotali ye80 iklasi nganye ye-oddball kulo lonke uvavanyo.Ikhiwane. 1A). Ukuthintela ukuhlala kwindawo ekhethekileyo kunye nokuvumela ukwenziwa ngokubanzi kwezinto esizifumeneyo ngokweendidi ezahlukeneyo zokubonakalayo, sibonisa imifanekiso yobuso bamadoda kwisiqingatha seseshini kunye nemifanekiso ebonisa iindawo ezingaphandle kwenye inxenye (ezichasene nezifundo). Sikhethe ezi ndidi endaweni yemifanekiso engaqhelekanga. Inkuthazo ekujoliswe kuyo yaziswa ngaphambi kweseshoni yovavanyo ye-4.5 s, kwaye izifundo zacelwa ukuba zenze iqhosha lokucinezelela ngokulula kukubonakala kwalo kamva kulingo kusetyenziswa umnwe wabo wesalathiso ekunene. Akukho zimpendulo zemoto zidibene nolunye udidi lweeklasi zokuvuselela. Ngexesha lokuvavanywa, imifanekiso yenziwa ye-500 ms yalandelwa ngumnqamlezo omhlophe wokulungiswa kwimvelaphi engwevu (ixabiso lempunga = 127) kusetyenziswa i-interstimulus interval (ISI) ye2.7 s. I-ISI yaqhutywa phakathi kwe-−300 kunye ne-300 ms (kwahanjiswa ngendlela efanayo). Umyalelo wesikhuthazo wenziwa wasebenza ngempumelelo ngokubhekisele kuqikelelo lwe-HRs enxulumene nokukhuthaza (IHinrichs et al. 2000).

Umzobo 1. 

Isiseko, uyilo lokulinga (A), kunye nokufunyanwa kwesilayidi se-FMRI (B). Kwipadigm ye-oddball, sisebenzise isivuseleli esemgangathweni, ii-oddbball, ii-oddbb ezingathathi hlangothi, i-oddballs ezingathandekiyo ngokweemvakalelo, kunye nee-oddballs zenoveli-amanani abonisa ukuvela rhoqo (kwi%). Kwisiqingatha esinye sokuvavanywa siveze imifanekiso yobuso bamadoda nakwelinye icala elingaphandle. Lo myalelo wawunxamnye nezifundo zonke. Kwivolumu nganye ye-fMRI, izilwanyana ze-24 zafunyanwa zangqinelana nobungqimba obugubungela i-SN / VTA, hippocampus, amygdala, amacandelo e-cerebellum, kunye ne-preortal cortex (B).

Zonke izinto ezishukumisayo zazithatyathwe I-Bunzeck kunye ne-Duzel (2006). Iinwele ezityebileyo kunye neendlebe zobuso zasuswa ngobuchule, kwaye izibonisi zangaphandle azibandakanyi ubuso. Yonke imifanekiso yayiwempuzekile kwaye yahlelwa ngokwexabiso elingwevu le127 kunye ne-SD ye75. Imifanekiso yayiqikelelwa embindini wesikrini, kwaye abathathi-nxaxheba bayibukela kwisipili esinyuswe phezu kwekhoyili yentloko, isusa i-angle ye-8 °. Imifanekiso yathathwa kwimithombo eyahlukeneyo (ubuso obungathathi hlangothi: "Ukuqokelelwa kweMifanekiso yePsycht ekuShukumiseni," http://pics.psych.stir.ac.uk/; ubuso obungathandekiyo ngokweemvakalelo: [I-Ekman kunye neFriesen 1976]; kunye nemeko yeemvakalelo engalunganga: inkqubo yemifanekiso ethandekayo yamanye amazwe [Lang et al. 2001]). Umfanekiso ongemva komfanekiso obonakalayo ubonise ingozi yemoto engalunganga (ngaphandle kwabantu). Ukusebenza kokufunyanwa kweethagethi kwavavanywa ngokuhlalutya inqanaba lokubetha (iimpendulo ezichanekileyo kwithagethi) kunye nereyithi ye-alam yobuxoki (iimpendulo kwimifanekiso engacacanga).

Iindlela ze-fMRI

Njengoba I-Bunzeck kunye ne-Duzel (2006), I-fMRI yenziwa kwinkqubo ye-MN ye3-Tesla yomzimba wonke (INokia Magnetom Trio, Erlangen, Germany) nge-echo planar imaging (EPI) isebenzisa i-coil ye-8-channel coil. Umgaqo wokufunyanwa kunye nohlalutyo lwedatha lwalunjalo I-Bunzeck kunye ne-Duzel (2006). Izicengca zifunyanwe zangqinelana nenkqubo yobuchopho kwicala elingaqondakaliyo-nelichaphazelekileyo. Kwiseshoni yokusebenza, i-24 T2* Imifanekiso enobunzima (ulandelelwano lwe-EPI) ngevolumu ene-oxygen oxygenation level-kuthelekiswa ukuxhomekeka kwafunyanwa (ubungakanani be-matrix: 64 × 64; 24 izilayi ngomthamo; indawo yokujonga [FoV]: 192 × 192 mm; isisombululo somhlaba: 3 × 3 × 3 mm; i-gap = 0.3 mm; ixesha echo [TE] = 30 ms; ukuphindaphinda kwexesha [TR] = 1500 ms; kunye ne-flip angle = 75 °). Ezi voluyitha zagubungela i-hippocampus, i-amygdala, kunye ne-brainstem (kubandakanya i-diencephalon, i-mesencephalon, iipuni, kunye ne-medulla oblongata) kunye neenxalenye zecortex yangaphambili kunye ne-cerebellum (Ikhiwane. 1B). Kwisifundo ngasinye esidala, idatha esebenzayo yafunyanwa kwiiseshoni zokuskena ezi-4 eziqulathe imiqulu engama-440 ngeseshoni nganye. Amanqaku amathandathu ongezelelweyo kwiseshoni nganye afunyenwe ekuqaleni kweseshoni nganye yokusebenza kwaye emva koko alahlwa kuhlalutyo ukuvumela uzinzo lukarhulumente oluzinzileyo. Imifanekiso yesifundo ngasinye sengqondo yaqokelelwa ngu T1Ukulungiswa kwakhona kwe-inversion-weighted-EPI (IR-EPI) ukulandelelana (ubungakanani be-matrix: I-64 × 64; i-60 izilwanyana; i-FoV: 192 × 192 mm; isisombululo somhlaba: 3 × 3 × 3 mm; gap = 0.3 mm; TE = 33 ms I-TI = 1450 ms; kunye ne-TR = 15000 ms).

Kubantu abadala abancinci nabadala, a T1-umzimba otyebileyo we-anatomical (ulandelelwano lwe-3D lwe-gradient-echo ulandelelwano; ubungakanani bematrix: 256 × 256; 124 slices; FoV: 250 × 250 mm; spatial resolution 0.98 × 0.98 × 1.5 mm; TE = 8 ms; TR = 24 ms; and flip i-angle = 30 °) kunye ne-2 yeproton density-weighted images (ulandelelwano lwe-spin-echo; ubungakanani beMatrix: 256 × 256; 48 izilayi; I-FoV: 250 × 250 mm; isisombululo sendawo: 0.98 × 0.98 × 3 mm; TE = 20 ms; kunye ne-TR = 2600 ms) zafunyanwa kwingqondo nganye yesifundo. Umfanekiso omnye wobunzima be-proton obufunyenwe nge-pulse ye-saturation (1200 Hz off-resonance, 16 ms) ekhokelela kumfanekiso we-MT (Ikhiwane. 2A) kwaye enye yafunyanwa ngaphandle kokucwangciswa kwepuliti yokugcwalisa okubangela umfanekiso weMTT (Ikhiwane. 2B). Emva koko, iimephu zeMTR kwisifundo ngasinye (Ikhiwane. 2C) zabalwa ngokokulingana okulandelayo: MTR = (MTT - MT) / MTT. Ukuphucula ukwaziwa kwe-SN / VTA kunye ne-nucleus ebomvu, imifanekiso ye-MT yazo zonke izifundo ze-21 ezindala yenziwa yahlelwa ngokwethala leMetreal Neurological Institute (MNI) ithemplethi eyanikezelwa yi-SPM99 kunye ne-avareji kuzo zonke izifundo ukwenza itemplate ye-MT endala iqela lezifundo (Ikhiwane. 2D). Ngelixa indawo yengingqi ye-SN / VTA inokwahlula ngokulula kwizakhiwo ezijikelezileyo kwimifanekiso ye-MT njengomtya oqaqambileyo, isunukeli ebomvu esondeleyo ibonakala mnyama (Ikhiwane. 2A,D). Zombini ezi T1-Imifanekiso ye-anatomical-weighted kunye ne-proton density-weighting imifanekiso yaskena kusetyenziswa i-1.5-Tesla whole-body MRI System (Signa Horizon LX, General Electric, Waukesha, WI).

Umzobo 2. 

Imifanekiso ye-Anatomical MR. Kwisifundo ngasinye se-2 proton density imifanekiso ifunyenwe: umfanekiso omnye wokuxinana kwiproteni yokulala ulungiselela ukugcwalisa okukhokelela kumfanekiso we-MT (A) kunye nomfanekiso wesibini we-proton density image ngaphandle kokulungiselela ukugcwaliseka kokugcwalisa okukhokelela kumfanekiso weMTT (B). Yomibini le mifanekiso yayisetyenziselwa ukubala umfanekiso we-MTR yesifundo (C) (jonga izixhobo kunye neendlela), ezazisetyenziselwa ukumisela ubunjani bezinto ze-SN / VTA, i-hippocampus, kunye ne-amygdala. Yonke imifanekiso emidala yezifundo ze-MT zibekwe ngokomndilili zikhokelela kwitemplate yeqela le-MT (D), ebisetyenziselwa ukwenza indawo isebenze ngaphakathi kwi-SN / VTA (ijikelezwe luhlaza) kunye neneyukhi ebomvu (ijikelezwe ebomvu).

Idatha ye-fMRI yaphuculwa kwaye yahlalutywa ngokwezibalo njenge I-Bunzeck kunye ne-Duzel (2006) yindlela yemodeli esekwe ngokubanziUFriston et al. 1994) usebenzisa isoftware ye-SPM99 yesoftware (iSebe le-Wellcome of Cognitive Neurology, University College, London, UK) kunye neMATLAB 6.1 (I-MathWorks, Inc., Natick, MA). Yonke imifanekiso esebenzayo yayilungisiwe ngenxa yokungaqhelekanga-kunye nesilikheyike sokungqinelani kwesilayi esisezantsi esithe satholwa ngexesha, salungiswa ukwenziwa kwezinto zakudala ngokulungiswa komthamo wokuqala, saza salungiswa ngokwendawo yesiqhelo T1Imephu yeetemplate zamanani asemgangathweni obunzima (SPM)I-Ashburner kunye noFriston 1999). Ukuqheleka kwafezekiswa ngokujija isifundo se-anatomical IR-EPI kwitemplate ye-SPM kunye nokusebenzisa ezi paramitha kwimifanekiso esebenzayo. Imifanekiso yatshintshwa yenziwa i-2 × 2 × 2 mm kwaye yatyibilika nge-isotropic 4-mm epheleleyo-ububanzi besiqingatha sobuninzi beGaussian kernel. Idatha ye-fMRI yedatha yexesha yayicocwe kakhulu (isikiwe i-120 s) kwaye yandiswa kwihlabathi liphela ngaphezulu kwee-voxels kunye nokuskena kwiseshoni nganye. Imodeli yeenkcukacha-manani kwisifundo ngasinye yabalwa ngokusebenzisa impendulo ye-canonical function kunye neziphumo zayo zokwexeshana (UFriston et al. 1998). Ukubamba i-arhente ezinxulumene nentshukumo ezinxulumene nentshukumo, i-6 covariates ngeseshoni nganye ibandakanyiwe (ukuguquguqulwa komzimba we-3 kunye nokujikeleza kwe-3 kumiselwe kulungelelwaniso lokuqala). Iziphumo zemeko ezithile zommandla zavavanywa ngokusetyenziswa kokwenza umahluko kumgca ngamnye kwisifundo ngasinye kunye neemeko ezahlukeneyo. Imifanekiso ephambili ebangelwe yangeniswa kuhlalutyo lweziphumo zenqanaba lesibini. Apha, enye isampulu t-izilingo zazisetyenziselwa imifanekiso efunyenwe kwiseti yesifundo ngasinye kunye neemeko ezahlukeneyo. Ngokunikwa kwethu ii-hypotorius zangaphambili, iziphumo zithintelwe P <0.005 (engachanekanga) kunye k = I-voxel ye-3. Ukuqinisekisa ubunyani bendawo ye-SN / VTA kunye neempendulo ze-nucleus ezibomvu, iimephu zokuvula zaphakanyiswa kwitemplate ye-MT. Indawo eyaziwa njenge-anatomical Localization ye-activation ebalulekileyo ngaphandle kwe-midbrain yavavanywa ngokubhekisele kumgangatho osemgangathweni we-atereo-atlas ngu-superimposition yeemephu ze-SPM kwithemplethi yengqondo esemgangathweni (MNI) ebonelelwe yi-SPM99.

Ukuvavanya iimpembelelo zotshintsho olwakhiwo lwenkqubo ye-mesolimbic kulwakhiwo olungenanto, i-hippocampus kunye ne-amygdala zachazwa njengemimandla yenzalo (ROI) kusetyenziswa umntu T1Imifanekiso enobunzima, kunye ne-SN / VTA ROI yachazwa kusetyenziswa umfanekiso ngamnye we-MT. Emva koko, ii-ROIs zatshintshelwa kumfanekiso ngamnye we-MTR, kunye nexabiso lexabiso (kwi-voxels) ye-ROI nganye yakhutshwa ngenxa ye-SN / VTA MTR, hippocampus MTR, kunye ne-amygdala MTR. Kwinqanaba lesibini lokuphononongwa ngokulula kwinqanaba lokuhlalutya ubudala, i-SN / VTA MTR, hippocampus MTR, kunye ne-amygdala MTR zangeniswa njengama-regressors kuthelekiso lomdla (umzekelo, i-oddballs zenoveli kunye nee-oddballs ezingathathi hlangothi).

iziphumo

Ngokuziphatha, i-92.1% (SD = 2.1) yazo zonke iithagethi zabonwa ngexesha lokuphendula kwe-558 ms (SD = 68), kwaye yi-2.32% kuphela (SD = 2.1) yazo zonke ezinye iiklasi zokuphakanyiswa ezaphendulwa ngobuxoki njengeethagethi.

Kuhlalutyo lwedatha yokuqala ye-fMRI, i-HRs ephakathi kwe-midbrain yavavanywa kwiimeko ezahlukeneyo zenzala. Imephu zobume beparametric zibonisa ukuba ngaphakathi kobusika, ivuselela inoveli (i-oddballs ezinqabileyo vs. i-oddbb engathathi hlangothi) iphakamise impendulo ebonakalayo kwi-SN / VTA eyiyo (Ikhiwane. 3A-C, Unyango lweS1A eyongeziweyo) kodwa kunqabile nge-se (imigangatho engathathi hlangothi vs. imigangatho) kunye nokuchaphazeleka okungathandekiyo ngokweemvakalelo (imizwa engathandekiyo yeemvakalelo ngokudibana nee-oddballs ezingaqhelekanga) azange. Kwisibalo sedatha P = 0.005 (engalunganga) ukujolisa (ukujongwa kwe-oddballs ngokuchasene ne-oddballs ezingathathwanga) kudityaniswa nokuvuselelwa okuqinileyo kuyo yonke i-midbrain kubandakanya i-biliveal SN / VTA kunye ne-nortus red nucleus. Nangona kunjalo, kumda we P = 0.05 (ilungisiwe), yindawo kuphela ebomvu engasukiyo (Ikhiwane. 3H) kwatyhileka ukusebenza (iTheyibhile eyoKongezelelweyo ye-S1D).

Umzobo 3. 

Iipatheni ze-FMRI zokuvula. Ukulungiswa kwenoveli (inoveli oddballs vs. i-oddballs ezingathathi hlangothi) yayanyaniswa nokwenza kusebenze kwi-SN / VTA (A-C), hippocampus, kunye neparhippocampal cortex (D, E). I-valence engathandekiyo yeemvakalelo (ii-oddballs ezingathandekiyo ngokweemvakalelo nxamnye nee-oddbb ezingathathi hlangothi) zenziwe zasebenza i-amygdala elungileyo (F) kunye nokunqongophala (ukungathathi cala kwemigangatho ngokuchasene nemigangatho) esebenze kwi-hippocampus (G). Zombini ukungahambi kakuhle ngokweemvakalelo nokunqabiseka akuzange kusebenze i-SN / VTA. Ujoliso (ekujoliswe kuko ngokungathandabuzekiyo vs. oddballs ezingalawulekiyo) zenziwe zasebenza i-nucleus ebomvu yasekhohlo (H). Imephu zokusebenza zaphakanyiswa kwitemplate ye-MT kwi- (A, B, C, yaye H) (Jonga izixhobo kunye neendlela) kwi T1Ubunzima obuqhelekileyo be-MNI kwi (D, E, F, yaye G). Imephu zokusebenza zazithintelwe P = 0.005 (ayilunganga) ngaphandle kwa (H) I-activation ibithintelwe P = 0.05 (ilungisiwe).

Kuyo yonke ivolumu esklweyo, ukukhuthaza inoveli yempembelelo inxulunyaniswa nempendulo eqinileyo yamazwe amabini kwi-hippocampus (Ikhiwane. 3D,E) kunye ne-parahippocampal cortex (Ikhiwane. 3D kunye neTafile eyongezelelweyo i-S1A). I-valence engathandekiyo yeemvakalelo (imizwa engathandekiyo yeemvakalelo ezingafaniyo kunye ne-oddbb engathathi hlangothi) i-activation elungile kwi-amygdala elungileyo (Ikhiwane. 3F, kunye neTafile eyongezelelweyo i-S1B), ukunqabiseka (imigangatho engadibaniyo kunye nemilinganiselo) esebenze kwi-hippocampus yasekhohlo (Ikhiwane. 3G) kunye neparparpocampal cortex yamazwe amabini (iTheyibhile yokuXhaswa kweS1C), kunye nokujolisa kugxunyekwe nokunxulunyaniswa kwimimandla emininzi yevolumu yophononongo olunenxalenye kubandakanya zombini hippocampi. Nangona kunjalo, kumgaqo olondoloze ngakumbi (P = 0.05, ilungisiwe), ipatheni yokuqalisa kokujolisa yayithintelwe kwikheyiphu yasekunene, ishiya thalamus, ilizwe elingaphantsi le-cortex yangaphambili, i-bilaral basal ganglia, i-bilateral insula, i-cingate gyrus yangakwesobunxele, kunye ne-postyrral gyrus (i-supplementary Table S1D). Okokugqibela, ukungaqhelekanga, ukunqabiseka, kunye nokujolisa kodwa hayi ukungabi natyala ngokweemvakalelo kusebenze imimandla eliqela ngaphakathi kwecortex yangaphambili (Itheyibhile yokuXhasa iX SUMNUMX).

Uhlalutyo lweMTR

Uhlalutyo lokunxibelelana ngaphakathi kwiqela labantu abadala (lonke unxibelelwano oluchaziweyo lulungelelwaniso olunemisila emibini ngaphandle kokuba kuchazwe ngenye indlela) kunye nezinto eziguquguqukayo SN / VTA MTR, hippocampus MTR, amygdala MTR, kunye nobudala butyhile unxibelelwano oluqinisekileyo phakathi kwe-SN / VTA MTR kunye nehippocampus MTR (r = 0.542, P = 0.011) kodwa akukho lungelelwano phakathi kwezinye izinto eziguquguqukayo (1 Table). Ukuqhubeka nokuvavanya iziphumo zokuguga kutshintsho lolwakhiwo, i-SN / VTA MTR kunye ne-hippocampus MTR zathelekiswa phakathi kwabadala abangama-24 kunye nabadala abangama-21 basebenzisa isampulu ezimeleyo T-i. Kwakukho ukuncitshiswa okukhulu kwe-SN / VTA MTR kubantu abadala abadala (ezimbini-umsila, idigri yenkululeko [df] = 43, P = 0.008, T = 2.8), ngelixa bekukho kuphela imeko (ezimbini-tailed, df = 43, P = 0.17, T = 1.4) yokwehliswa kwe-hippocampus MTR (Ikhiwane. 4).

Umzobo 4. 

Ukuthelekisa kwe-MTR phakathi kwabancinci kunye nabantu abadala. Ngelixa i-SN / VTA MTR yayiphezulu kakhulu kuninzi lwabantu abadala abancinci (ukuthelekiswa kwemisipha emibini, P = 0.008, T = 2.8) (iboniswe yinkwenkwezi), i-hippocampi MTR ayikhange ihluke kakhulu phakathi kokubini kwabemi kodwa ithambekele ekubeni phezulu kwisampulu yabantu abadala abancinci (uthelekiso oluneempawu ezimbini, P = 0.17, T = 1.4). Imida yempazamo ibonisa impazamo esezantsi yentsingiselo.

1 Table 

I-Coefficients (ulungelelwaniso lwePearson) kulungelelwaniso phakathi kwe-SN / VTA MTR, hippocampus MTR, amygdala MTR, kunye nobudala

Ukuvavanya ubudlelwane phakathi kokulungiswa kwezinto kunye nokuthelekiswa nolwakhiwo-njengoko kubonakalisiwe yi-MTR-kunye nokusetyenziswa kwezinto ezinobudala kunye nobudala, uhlalutyo olucacileyo lokungaqwalaselwa kwezinto ezintsha ('inove oddballs vs. oddballs') zenziwa kusetyenziswa ii-regressors SN / VTA MTR, hippocampus MTR, amygdala MTR kunye nobudala. Ii-SPM zabhengeza ukuba i-SN / VTA MTR inxibelelana kakuhle nothotho lwe-HR kwi-SN / VTA (Ikhiwane. 5A) kunye ne-hippocampus elungileyo (iTheyibhile yokuXhasa iS2A), iHippocampus MTR idibene kakuhle nokuthetha okutsha kwiHippocampus elungileyo (Ikhiwane. 5F kunye neTafile eyongezelelweyo i-S2B), kwaye ubudala badityaniswa kakubi kunye nobuncinci be-HR kwi-hippocampus elungileyo (iTheyibhile yokuXhasa iS2C). Kwakungekho lungelelwano phakathi kwe-amygdala MTR kunye nokubonakalayo kweHR nokuba yeyiphi na iHippocampus okanye i-SN / VTA (Itheyibhile yokuXhaswa kweS2D).

Umzobo 5. 

Ulungelelwaniso phakathi kwe-HRs kunye nee-MTR ezinxulumene nento. I-Novelty HR kwi-SN / VTA (A) enxulumene kakuhle ne-SN / VTA MTR (Bkunye ne-hippocampus MTR (C) kodwa hayi ubudala (D) okanye i-amygdala MTR (E). Kwi-hippocampus (F), ubugcisa obutsha be-HR buhambelana kakuhle ne-SN / VTA MTR (G), hippocampus MTR (H) nokungathandani ngeminyakaI) kodwa hayi nge-amygdala MTR (J). Imephu zokusebenza zaphakanyiswa kwitemplate yeqela leMT (A) okanye T1Ubungakanani obuqhelekileyo be-MNI kwengqondo (F) kwaye wabekwa kwi P = 0.005 (ayilunganga). Ii -sterster zibonisa ulungelelwaniso olubalulekileyo e *P = 0.05 okanye **P = 0.01-ns izifinyezo "azibalulekanga" (P > 0.05).

Uvavanyo olusondeleyo lwencopho ye-voxel kwi-SN / VTA (Ikhiwane. 5A) (x, y, z = 0, −14, −12) ebonise unxibelelwano phakathi kobunewunewu HR kunye ne-SN / VTA MTR kunye ne-voxel ephezulu kwi-hippocampus (Ikhiwane. 5F) (I-10, −2, 24) ebonisa ulungelelwaniso phakathi kwe-HR kunye ne-hippocampus MTR yenziwa emva koko. Iarhente yexesha elizayo kwi-SN / VTA ilungelelaniswe kakuhle kungekuphela nge-SN / VTA MTR (Ikhiwane. 5B) kodwa kunye ne-hippocampus MTR (Ikhiwane. 5C), ngelixa libonisa ukungahambelani kunye nobudala (Ikhiwane. 5D) okanye i-amygdala MTR (Ikhiwane. 5E). I-HR engaqhelekanga kwi-hippocampus elungileyo (Ikhiwane. 5F) edibene kakuhle hayi nge-hippocampus MTR (Ikhiwane. 5H) kodwa nange-SN / VTA MTR (Ikhiwane. 5G), ngelixa ibonisa unxibelelwano olungelulo ngobudala (Ikhiwane. 5I), kwaye akukho kunxibelelana nge-amygdala MTR (Ikhiwane. 5J). Ngaphaya koko, i-hippocampus HR kunye ne-SN / VTA HR kwizinto ezintsha zilungelelaniswe kakuhle (r = 0.375, P = I-0.047, itayara enye), kodwa akubangakho nto inxibelelanayo phakathi kwe-amygdala HR to novelty and SN / VTA HR or hippocampus HR to novelty (zombini P > 0.39). Kumdibaniso olandelayo okwahlukileyo usebenzisa ubudala njengokuguquguquka kolawulo, unxibelelwano phakathi kwento entsha ye-HR kwi-SN / VTA kunye ne-SN / VTA MTR (r = 0.62, P = 0.004), ubuqhetseba kwi-HR kwi-SN / VTA kunye ne-hippocampus MTR (r = 0.48, P = 0.03), ubuqhetseba kwi-HR kwi-hippocampus kunye ne-SN / VTA MTR (r = 0.43, P = 0.055), kunye ne-HR eyaziwayo kwi-hippocampus kunye ne-hippocampus MTR (r = 0.63, P = I-0.003) ihleli ibalulekile okanye isondela kwinqanaba lokubaluleka (inqaku le-HR kwi-hippocampus kunye ne-SN / VTA MTR).

Ubume besakhiwo-Umsebenzi phakathi kwe-SN / VTA MTR kunye ne-hippocampal MTR alunakulindeleka ukuba ubonakalise inkqubo ye-grey-ehambelana nobudala okanye inkqubo emhlophe njenge-SN / VTA MTR okanye iMHR yehippampal ayibonisanga unxibelelwano kunye ngwevu yehlabathi okanye ivolumu emhlophe yemicimbi yabantu abadala abadala (bonke P amaxabiso> 0.3). Ubungakanani bomhlaba wonke ongwevu nomhlophe kwimiba ekhutshiweyo yakhutshwa ngokusekwe kwisifundo T1-Umfanekiso onobunzima usebenzisa ii-algorithms zobuchopho obuqhelekileyo ze-SPM (I-Ashburner kunye noFriston 2000).

Ukwenzela ukuhlalutya iimpawu zabasebenzi kwi-amygdala yeemvakalelo ezingathandekiyo ngokweemvakalelo, ucazululo olulula lokuhlalutya lusebenzisa umahluko "okhoyo ngokweemvakalelo okungahambelani neearhente ezingathathi hlangothi" kunye nee-MTRs ezahlukileyo kunye nobudala njengabenzi bobuhlanga. Akukho nalunye kolu hlalutyo lwe-SPM oluveze ulungelelwaniso olubalulekileyo kwinqanaba lokubaluleka kwe-0.005 (engalunganga). Nangona kunjalo, ukuvavanywa ngokusondeleyo kwe-HR yencopho ye-voxel ngaphakathi kwe-amygdala efanelekileyo ye-valence engathandekiyo yeemvakalelo (x, y, z = 28, 0, −22; bona i-Tafile yeThebhile ye-S1B) kunye ne-amygdala elungileyo ye-MTR ityhile unxibelelwano phakathi kwezi zinto zixabisekileyo kwinqanaba elinye lomsila wokubaluleka (r = 0.376, P = 0.046, itayara enye). Ngokuchasene noko, i-HR kule ndawo iphakamileyo ye-voxel kwi-valence engathandekiyo yeemvakalelo ayizange ihambisane ne-SN / VTA MTR, hippocampus MTR, okanye ubudala (konke P > 0.34).

Ngokungafaniyo nokuqaphela kwethu kutshanje kubantu abadala abasempilweni.I-Bunzeck kunye ne-Duzel 2006), ukufunyanwa okujolisiweyo kunye nempendulo yeemoto ezihambelana noko yayanyaniswa ne-HR eyaziwayo kabini kungekuphela kwi-nucleus ebomvu kodwa kunye ne-SN / VTA, kubandakanya ezo voxels ze-SN / VTA ezibonise iimpendulo eziphezulu kwinto entsha. Ngokungafaniyo nobunewunewu, nangona kunjalo, ukujolisa kwii-HRs kwezi voxels akuzange kuhambelane ne-SN / VTA MTR (P ≥ 0.5) kodwa ulungelelwaniso olubi namaxesha okusabela kwesihloko kwiithagethi (r = -0.42, P = 0.056). Ngaphaya koko, ubugcisa obutsha kwi-SN / VTA khange buhambelane nexesha lokuphendula (r = 0.16, P = 0.5), kwaye kwakungekho nxibelelaniso phakathi kwe-SN / VTA HR ekujolise kuyo kunye nobudala (P I-0.5).

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Imodeli ye-hippocampal-SN / VTA ibikezela ukuba ubukhulu bempendulo ye-SN / VTA yomntu kunye ne-hippocampus ukuya kwinto yokufunda kubantu abadala kufuneka igqitywe ngokudibeneyo ngokunyaniseka ngaphakathi kwe-SN / VTA kunye ne-hippocampus. Ngokwahlukileyo, kuba i-amygdala ayifaki galelo ngqo kwi-hippocampal-SN / VTA kwinto entsha yokuphendula, akukho ziimpendulo ze-hippocampal okanye ze-SN / VTA mazingachaphazeli ukuthembeka ngaphakathi kwi-amygdala. Yiyo kanye ipateni esiyiqapheleyo. Xa sijonga ii-MTR ze-SN / VTA, i-amygdala, kunye nehippampus, siqwalasele ulwalamano olukhethayo-ulwalamano phakathi kwe-SN / VTA kunye ne-hippocampus yokulungisa izinto ezintsha. Iimpendulo ze-Novelty kwi-SN / VTA kunye ne-hippocampus zadityaniswa, kwaye zalungelelaniswa nee-MTRs zazo (Ikhiwane. 5B,H). Okubaluleke ngakumbi, iimpendulo zendlela yobunyangi be-hippocampal yaphinda yahambelana noMTR we-SN / VTA (Ikhiwane. 5G), kunye neempendulo zezobugcisa kwi-SN / VTA zidityaniswe ne-MTR ye-hippocampus (Ikhiwane. 5C). Olu lungelelwaniso lolungelelwaniso-lomsebenzi alunakulubonakalisa umphumo ongaxelwanga womda wotshintsho lweMTR kuba i-MTR ye-amygdala yayingahambelani nempendulo yobudenge nokuba yeyiphi i-SN / VTA (Ikhiwane. 5E) kunye nehippampus (Ikhiwane. 5J). Nangona kunjalo, kukho unxibelelwano olungenamandla phakathi kwe-MTRs e-amygdala kunye ne-HR ukuya kwi-valence engathandekiyo ngokweemvakalelo e-amygdala xa kungekho naluphi na unxibelelwano notshintsho lweMTR kwi-SN / VTA kunye nehippampus. Ezi zinto zifunyanisiweyo zendlela ekhethiweyo yokwakha-intsebenzo ngaphakathi kwe-SN / VTA kunye ne-hippocampus yokusetyenziswa kwezinto ezintsha zibonelela ngenkxaso eqinileyo kwi-hippocampal-SN / VTA loop ekuqhubeni izinto ezintsha (I-Lisman kunye neGrace 2005).

I-SN / VTA MTR yabantu abadala abadala yayiphantsi kakhulu kuneqela lethu lolawulo lolutsha (Ikhiwane. 4), ukucebisa ukuba iziphumo zethu zidlula ngaphaya kolungelelwaniso kwaye zihambelana nokuqonda utshintsho olunxulumene nobudala kwimemori. Nangona kunjalo, oku kuncitshiswa kwe-SN / VTA MTR kubantu abadala asitolikanga kunxibelelaniso phakathi kweminyaka yobudala kunye neMTR kwisifundo sethu. Enye inkcazo ebonakalayo koku luluhlu olunqabileyo lweminyaka yesampulu yezifundo ezindala. Kuyaziwa, umzekelo, ukuba imiqolo ye-hippocampal nayo ayibonisi ulungelelwaniso nobudala kwiisampulu zobudala obuxineneyo (Szentkuti et al. 2004; Schiltz et al. 2006) kodwa bonisa unxibelelwano kunye neesampuli ezisusela kwii-20s ukuya kwii80s (I-Raz kunye neRodrigue 2006). Kucingelwa ukuba ngomgangatho wobudala oqala kwii-20s ukuya kuthi ga kwi-80s, ukufumana kwethu ukuncitshiswa kwabantu abadala kuya kuguqulela kulungelelwaniso phakathi kweminyaka yobudala kunye ne-SN / VTA MTR.

Iziphumo zethu ziphakamisa umbuzo wokuba ngaba utshintsho kunye nolwakhiwo kwi-SN / VTA kunye ne-hippocampus zinxulumene ngokufanelekileyo. Idatha ye-Anatomical iyayithanda into enjalo. Okokuqala, iiprojekthi ze-SN / VTA ngqo ziye kwi-hippocampus (I-Lisman kunye neGrace 2005). Okwesibini, nangona i-hippocampus ingaphumeli ngqo kwi-SN / VTA, eyona nto iphambili kwaye mhlawumbi iyintsingiselo yomqondiso ongenanto kwi-SN / VTA (I-Lisman kunye neGrace 2005). Kungenxa yokuba eminye imimandla yokwexeshana ethe yachukunyiswa kukufunyanwa kwezinto (UBrown kunye no-Aggleton 2001), njenge-perirhinal cortex, ineengqikelelo ezibuthathaka kakhulu kwi-ventral striatum (UFryman et al. 2002) kwaye ke akukholeleki ukuba banikezela isibonakaliso esisebenzayo sonyulu kwi-SN / VTA (I-Lisman kunye neGrace 2005).

Njengakwantu abadala abasempilweni.I-Bunzeck kunye ne-Duzel 2006), i-SN / VTA yayiphendula ngakumbi kubuvuseleli obutsha kunokunqabileka okanye ubugqwirha obungathandekiyo. Nangona kunjalo, ngokungafaniyo neziphumo zethu zangaphambili kubantu abadala abasempilweni abadala (I-Bunzeck kunye ne-Duzel 2006), I-SN / VTA yenziwa ngamandla ngokujolisa kunye nokuphendula kwayo ngemoto kubantu abadala. Inkqubo yokujolisa kwi-HRT yayihambelana ngokungahambelani nexesha lokuphendula, iphakamisa ukuba ukwabiwa kwezixhobo zokusebenza ezinxulumene nezinto zeSN / VTA zokwenza iimpendulo zokuziphatha kwiithagethi kunokubonakalisa iindlela zokubuyisa kwiingxaki zemoto ezihamba kancinci. Kufuneka kuqatshelwe, nangona kunjalo, kumgangatho ophezulu wokugcina amanani sibukele imodeli efanayo yomgangatho ngaphakathi nangaphandle kwebhulabhu njengakwantu abadala abasempilweni.I-Bunzeck kunye ne-Duzel 2006). Ngokukodwa, ngaphakathi kumbindi wobushushu, iimpendulo ezijolisiweyo zaxhonywa kwi-nucleus ebomvu (Ikhiwane. 3H). Ke ngoko, kubonakala ngathi ukwabiwa kwe-SN / VTA kwiimpendulo zokujolisa kubantu abadala abasempilweni kubonakalisa utshintsho oluninzi ngakumbi kwabo bantu badala banamaxesha okusabela kodwa notshintsho olwenziweyo ekuphenduleni kwebanga lokuhamba. Kuphengululo lwamva nje lwe-postmortem ye-SN ye-neuronal density, abantu abadala abanempilo ngaphandle kwe-PD babonisa ukulahleka kwe-neuronal kwi-SN, kwaye le lahleko yahambelana neempawu ezibuthathaka ze-parkinsonia ezinje nge-bradykinesia kunye nokungalingani kwe-gait (URoss et al. 2004). Kuyenzeka ukuba amaxesha okusabela acothayo abonise i-bradykinesia ethambileyo, ethi ke yona idityaniswe nomqhubi owonyukayo oya kwi-SN / VTA kwilinge lokuhlawulwa. Ngokubalulekileyo, kuya kufuneka kuphawulwe ukuba kuya kuhlala kugqitywe ukuba ngaba umsebenzi lowo ufuna "ukubalwa kwengqondo" okanye "ukubhaliswa kwengqondo" kweethagethi kungabikho mpendulo ininzi yemoto kuya kukhokelela kubunini obuhlukileyo be-midbrain kwiithagethi kulutsha. nakubantu abadala abadala.

I-hippocampus kunye ne-amygdala yabantu abadala asebekhulile babonakala begcina iipropathi zabo zeempendulo ezijongwe kubantu abadala abasempilweni.Emangalisayo kunye neDolan 2001; Yamaguchi et al. 2004; UCrottaz-Herbette et al. 2005). Njengakwantu abadala abancinci (I-Bunzeck kunye ne-Duzel 2006), i-hippocampus yayikhetheke kancinci kune-SN / VTA kuba iphendula kwinto entsha (Ikhiwane. 3D,E) kunye nokunqongophala (Ikhiwane. 3G). I-amygdala, kwelinye icala, yayingowona mmandla uphendule kakhulu kwi-valence engathandekiyo yeemvakalelo (Ikhiwane. 3F). Izifundo zangaphambili kubantu abadala abadala zibonakalise ukuba inoveli yobuso eyoyikisayo xa ithelekiswa nobuso obungathathi hlangothi inxulunyaniswa nokusebenza okuqinileyo kwe-amygdala kubantu abadala abadala abanempilo (UWight et al. 2006). Idatha yangoku yandisa oku kufumaniswayo ngokubonisa ukuba kubantu abadala abasempilweni abadala bakwakhona nokusebenza okuqinileyo kwe-amygdala ukuya kukoyikiswa (ubuso nobuso) xa kuthelekiswa nokukhuthaza ukungathathi hlangothi (ubuso nobuso).

Uninzi lwezifundo zangaphambili ziphande ngotshintsho olunxulumene nobudala kwinto yobunkunkqele ekusebenziseni ubuchule obunxulumene nomsitho (i-ERPs). Xa bavunyelwe ukuba banikezele ingqalelo ngokuzithandela kwimifanekiso yokubonakalayo yenoveli ngexesha lokujonga okuzenzekelayo, abantu abadala abadala abasebenza kakhulu ababonakalisi uphawu lokuncipha kwe-P300 yeempendulo ezinqabileyo (Umqeshwa et al. 2006). Ngapha koko, i-P300 amplopes yazo inokuphuculwa mhlawumbi icebisa ukuzama ngakumbi ukulandela intshayelelo yenoveli kubantu abadala abadala (Umqeshwa et al. 2006). Le ngcinga iyahambelana nezifundo zesifundo esicebisa ukuba i-cortex yangaphambili yangaphambili ithathe inxaxheba kwisizukulwana sezinto ezinqabileyo ze-P300 (I-Soltani kunye ne-Knight 2000) kwaye ukuba abantu abadala abadala abaphilile bahlala bebonakalisa u-hemispheric lateralization kwimisebenzi yokuqonda efana nokufaka i-episodic encinciUDolcos et al. 2002). Idatha yethu iyahambelana neakhawunti enjalo yezifundo ze-ERP zokwenza izinto ezinobunkunkqele njengoko zibonisa ukunciphisa iimpendulo ze-mesolimbic inoveli kubantu abadala abadala abane-SN / VTA kunye ne-hippocampi engacacanga. Kunokwenzeka ukuba abantu abadala abadala bafumane ukuphendulwa kwe-mesolimbic novelty majibu ngokunyanzela okungxamisekileyo kwangaphambili kokuguqula inoveli. Ukuba yinyani kwaye ukuba impendulo eyi-P300 yempendulo ebubini kubantu abadala iyahambelana nokuziqhelanisa nokuzimisela okunjalo, umntu unokuxela kwangaphambili ukuba i-P300 yokufunda kwezi zifundo kufuneka inyuke ngokunyuka ngokuncipha kwe-MTR kwi-SN / VTA kunye ne-hippocampus. Ngokubalulekileyo, oku kuthatha ukuba ukuthembeka kwecortex yangaphambili ngexesha lokuguga kwesiqhelo kuvumela imbuyekezo yokuncipha kokusebenza kwe-mesolimbic. Nangona kunjalo, oku akunakuba kunjalo ukuba kukho unxibelelwano phakathi kokuphulukana nomsebenzi wangaphambili we-cortical kunye ne-mesolimbic kunye / okanye ingqibelelo.

Ukuphindaphindwa okuhle okuphindaphindiweyo ekusebenzeni kwezinto ezintsha kubantu abadala abasempilweni kukuphazamiseka kwendawo entsha ye-P300 ngokuziphindaphinda.UFryman et al. 1998; Umqeshwa et al. 2006; I-Weisz kunye ne-Czigler 2006). Idatha yethu ibonisa ukuba iimpendulo ze-mesolimbic novelty ziphendulwe ngokunxibelelene notshintsho lolwakhiwo kwi-SN / VTA kunye ne-hippocampus, kodwa asifundanga ngendawo yokuhlala ngenxa yokuba i-oddballs ezinoveli kuphando lwethu aziphindwanga. Idatha yethu ke ngoko ayithathi cala ngokubhekisele kokuncitshiswa kwe-MTRs esezantsi kwi-SN / VTA kunye ne-hippocampus, iimpendulo zobuntshatsheli kwezi ndawo zikwabonisa ukwehla kwezindlu.

Ngaphandle kwe-lobe yexeshana, uluhlu olubanzi lwerekhodi ye-electrophysiological, izifundo zezigulana (UBaudena et al. 1995; Umqeshwa et al. 2000), kunye nezifundo zokucinga (I-Opitz et al. 1999; UClark et al. 2000) bayiqaqambisile indima yendibano yecala eliphambili nelingaphambiliUmgaqo et al. 2002) ekusebenzeni kwezinto ezintsha (Yamaguchi et al. 2004). Ngelixa ii-HRs zisekutsha, kunqabile, nasekujoliseni iinto zahlukile ngokwendlela yethu yokulinganisa, indima ye-cortex yangaphambili ekusebenzeni kwento engaphaya komda weli phepha. Umthamo opheleleyo wokufumana uyimfuneko ukuvavanya ubudlelwane bokusebenza phakathi kwe-cortices zangaphambili kunye ne-orbitofortal kunye nezakhiwo ze-mesolimbic ngexesha lokuprinta.

Ukushwankathela, ipatheni yenguqu ehambelana nobudala kunye nokutshintsha kokusebenza apha kwinkqubo ye-mesolimbic inikezela ngenkxaso kwi-hippocampal-SN / VTA loop yokuphawula izinto ezintsha. Ngoku iya kuhlala imiselwe ukuba iinguqu kunye nokusetyenzwa kolu tshintsho kuchaphazela njani ukusebenza kwememori ye-episodic kubantu abadala. Ngapha koko, ezi ziphumo zibonisa ukuba abantu abadala abadala abane-SN / Vta MTRs eziphantsi kunye nokuncipha kweempendulo ze-mesolimbic zokungena kwezinto ezinokutsha banokufumana izibonelelo endaweni yokufumana indawo. I-dopamine precursor levodopa (L-DOPA) ithathwa kakhulu kwaye iguqulwe nge-dopaminergic neurons kwaye emva koko ikhutshwe ngokwe-phasically kwi-synaptic cleft, ngelixa i-dopamine agonists iya kusebenzisa ngakumbi i-tonic activation ye-postynaptic dopamine receptors. Ke, i-L-DOPA sisidakamizwa esinomdla ngokukodwa ukukhuthaza ukukhutshwa kwe-phasic dopamine ekuphenduleni kwinto entsha. Sele ibonakalisiwe eyandisa ukufunda isigama esitsha ngokuziphindaphinda kubantu abadala abasempilweni (U-Knecht et al. 2004; UBreitenstein et al. 2006) nokulungisa inkumbulo yamagama (Newman et al. 1984) kunye nokwenziwa kwememori yeemoto kwizifundo ezindala ezinempilo (I-Floel et al. 2005, 2006). Izifundo ze-Pharmacological ziyafuneka ukuvavanya izibonelelo ze-L-DOPA kunye ne-dopamine agonists kubantu abadala abadala abane-MTRs esezantsi kwi-SN / VTA.

Izinto ezongezelelweyo

Izinto ezongeziweyo ziyafumaneka kwi http://www.cercor.oxfordjournals.org/.

Imibulelo

Olu phononongo luxhaswe zizibonelelo ezivela kwiDeutsche Forschungsgemeinschaft (Klinische Forschergruppe "Kognitive Kontrolle," TP1) kunye neBMBFT (CAI) kwiDyunivesithi yaseMagdeburg. Sibulela uMichael Scholz ngoncedo loyilo lwe-fMRI kunye no-Ulrike Malecki kunye no-Ana Blanco ngoncedo lokufumana idatha. Ukugqubana kwemidlaAkukho namnye obhengeziweyo.

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