Ukufunyanwa kweNoveli Relies kwi-Dopaminergic Signaling: Ubungqina obuvela kwi-Apomorphine's Impact kwi-Novelty N2 (2013)

UMauricio Rangel-Gomez,^1,* UClayton Hickey,¹ Therese van Amelsvoort,² Pierre Bet,³ kwaye UMartijn Meeter¹

Ulwazi loMbhali ► Iinqununu zeSihloko ► Ulwazi lobunikazi kunye neelayisensi ►

Yiya e:

Abstract

intshayelelo

Ukukwazi ukuphendula ngokuchanekileyo nangokukhawuleza kwi-stimuli yenoveli kuxhomekeke kwi-cascade yeendlela ze-neurological eziphantsi kombono, ingqalelo, ukufunda kunye nenkumbulo. [1]. Nangona into entsha yovuselelo ifumene uphononongo oluninzi, akukaqinisekwa ukuba kwenzeka njani ukufunyanwa kwezinto ezintsha, zeziphi izakhiwo ezibandakanyekayo, kwaye zeziphi iinkqubo ze-neurotransmitter ezingenelelayo.

Iimpawu eziNxulumene noMsitho (ERP) zifaneleke ngokufanelekileyo ukuqonda iindlela ze-neuromodulatory zokusetyenzwa kwezinto ezintsha. Izivuseleli zenoveli zihlala zifuna amacandelo amabini e-ERP ngokulandelelana: into entsha ye-N2 yangaphambili (N2b ePritchard kunye nabalingane [2] icandelo le-N2), kunye ne-P3, eyayanyaniswa nokunikezelwa kwengqwalasela kuvuselelo lwenoveli. [3], [4]. I-N2 ngokuqhelekileyo ibonakala ibonisa ukusetyenzwa okubandakanyekayo ekubhaqweni okuzenzekelayo kunye nokuqatshelwa kwenoveli evuselelayo [5], [6], kwaye icandelo lincitshiswe kakhulu emva kokuphinda-phinda okukodwa kokuvuselela inoveli [7]. Iye yahlulwa yangamacandelo amathathu: i-N2a, i-N2b kunye ne-N2c [2]. Ezi zihambelana ne-mismatch negativity (N2a), i-N2 yangaphambili okanye i-novelty N2 (N2b) kunye ne-N2 yangasemva (N2c; [8]). I-N2a/i-mismatch negativity ine-fronto-central ephezulu yokusabalalisa kwaye kucingelwa ukuba ibonise impendulo ye-neural ezenzekelayo kwi-auditory outlier. [9], [10], ngelixa i-N2b ikholisa ukwandulela icandelo le-P3a kwaye iqhele ukufunwa kumsebenzi obonakalayo oddball. [11], [12]. Eli candelo lamva lithathwa njenge semiautomatic, kuba lifunyaniswa yi-oddball stimuli kungakhathaliseki ukubaluleka komsebenzi. [5], [6]. I-N2c, eqhele ukwandulela icandelo le-P3b, inxulunyaniswa nemisebenzi yokuhlelwa [13].

Icandelo le-P3 likwahlulwe ngokwamacandelo amabini: i-fronto-central ye-P3a (okanye i-novelty P3) kunye ne-centro-parietal P3b. I-P3a inxulunyaniswe novavanyo lwenoveli yokuvuselela isenzo esilandelayo sokuziphatha kwaye ibekwe ukuba ibe ngumqondiso wendlela yokutshintsha ingqalelo. [14] kunye nesalathiso sokuphazamiseka [15]. I-P3b kunokuba kunjalo isalathise iinkqubo ezinxulumene nokuqondwa kwentsingiselo yovuselelo kunye nokubaluleka. [4], [7]. Ngokuhambelana noku, i-P3b iphuculwe ukwenzela ukuvuselela okuhambelana nezigqibo okanye iimpendulo zamva [16].

Izifundo ezininzi ze-pharmacological ziye zasebenzisa i-N2 kunye ne-P3 ukuphonononga isiseko semolekyuli yokufunyanwa kwezinto ezintsha, ubukhulu becala ngamachiza achaphazela uluhlu olubanzi lwee-neurotransmitters. USoltani kunye noKnight [17], kuphononongo olubanzi loncwadi, cebisa ukuba i-amplitude ye-oddball-elicited P3 ixhomekeke ekusebenzeni kwee-monoamines ezininzi, ngakumbi i-dopamine kunye ne-norepinephrine. Ngokungqinelana noku, uGabbay kunye noogxa bakhe [18] yafumanisa ukuba i-d-amphetamine, i-dopamine engakhethiyo kunye ne-norepinephrine agonist, iguqula i-P3a, i-N100 kunye nokuhlengahlengiswa kwe-negativity (RON) i-reactivity kwi-novel stimuli. Abathathi-nxaxheba abanomdla kwi-d-amphetamine babonise i-P3a enkulu ye-amplitude, i-amplitude eyancipha i-N100 kunye nokunciphisa i-amplitude ye-RON emva kwe-d-Amphetamine, xa kuthelekiswa nabathathi-nxaxheba abangakhethiyo ichiza.

Ungenelelo oluthe kratya oluthe ngqo lwe-pharmacological lusetyenzisiwe kuphando ngezilwanyana okanye kwizifundo apho izigulana zivavanywa kwiimeko kunye nangaphandle kweyeza. Kwi-schizophrenia, enxulunyaniswa nokungasebenzi kakuhle kwinkqubo ye-dopamine, ukungahambelani kwe-negativity (MMN) kuyancipha xa izigulana zifumana unyango lwe-neuroleptic oluvimba iindlela ze-dopaminergic. [19]. Kuphononongo nge-Parkinson's disease (PD) izigulana ulawulo lwe-L-Dopa okanye i-dopaminergic agonists aluzange lutshintshe izinto ezikhethwayo ezintsha, njengoko luvavanyiwe ngumsebenzi wesikrelemnqa oxhobileyo. Nangona kunjalo, oku kufunyanisiweyo kunzima ukutolika ngenxa ye-comorbidity kwisampulu, ebandakanya izigulana ezinokuziphatha okunyanzelekileyo. [20].

Olunye uphononongo lusebenzise indlela yonxibelelaniso, apho ukusebenza kwimimandla ethile kunye ne-neurotransmitter gene polymorphisms inxulunyaniswe nezalathisi zokusetyenzwa kwezinto ezintsha. Idatha esebenzayo yeMagnetic Resonance Imaging (fMRI) ibonisa umsebenzi omtsha-onomdla kwiindawo ze-mesolimbic ezityebileyo ze-dopamine njenge-substantia nigra kunye ne-ventral tegmental area. [21]. Iipolymorphisms zofuzo ezinxulumene nokufumaneka kwe-dopamine (COMT) kunye noxinaniso lwe-D2 receptors (ANKK1) zifunyenwe zimodareyitha ukusetyenzwa kwezinto ezintsha, kangangokuba i-P3a ephezulu yeamplitude inxulumene nebhalansi yezi zintlukwano zimbini. [22]. Ijene encoding yabathuthi be-dopaminergic (DAT1) nayo ibonakaliswe ekubhaqweni kwento entsha yomsebenzi. [23]. Ezi zifundo zicebisa ukuba ukufumaneka okuphezulu kwe-dopaminergic kuphucula ukubonwa kunye nokuqhubekela phambili kovuselelo lwenoveli. Ukongeza, i-P3a amplitude iyancitshiswa xa amanqanaba e-dopamine ephantsi, njengoko kubonisiwe kwizifundo ezinezigulane ze-Parkinson's disease. [24], [25].

Nangona kunjalo, kuphononongo lwakutsha nje uKenemans kunye noKähkönen [26] Cebisa ukuba isiphumo sokukhohlisa kwe-dopamine kwizinto ezinxulumene nezinto ezintsha, njenge-MMN kunye ne-P3, ibuthathaka, kwaye eyona mpembelelo iphambili ye-dopamine ikukusetyenzwa kwe-subcortical ehambelana nokujongwa kwengxabano. Aba babhali baphinda bacebise ukuba umphumo we-dopamine uxhomekeke kwi-receptor, kwaye ukuba i-agonism ye-D1 / D2 i-receptors ibandakanyeka ngokukhawuleza kweenkqubo zokuqonda.

Nangona ubungqina buxoxiwe ngasentla bucebisa umsebenzi we-dopamine ekusetyenzweni kwezinto ezintsha, ubume obuchanekileyo bale ndima ayikacaci. Kungenzeka ukuba i-dopamine isebenze ukwenza i-neural novelwano kuvuselelo lwenoveli, ngaloo ndlela idlala indima ebalulekileyo ekubhaqweni kwezinto ezintsha [27]. Kungenjalo, umsebenzi owenziwe yinto entsha kwimimandla yengqondo ye-dopaminergic inokubonisa okulandelayo asabela kuvuselelo lwenoveli, isalathiso sokuphendula kwengqondo kwiziganeko zokusingqongileyo ezinokuthi zihambelane nokuziphatha [28].

Kuphononongo lwangoku sisebenzisa inkqubo ye-dopamine ngolawulo lwe-D1/D2 i-apomorphine ye-agonist kunye nokulinganisa izinto ezinxulumene ne-ERP. Le ndlela isenza sikwazi ukwahlula indima ye-dopamine ekuqhubeni izinto ezintsha [29], [30]. Abathathi-nxaxheba bagqibe iiseshoni ezimbini zovavanyo, enye ilandela ulawulo lwe-apomorphine kunye nolawulo olulandelayo lwe-placebo ye-saline. Ukuze unqume ukubandakanyeka kwe-D1 / D2 ye-receptor kwi-processing entsha siye saba nabathathi-nxaxheba abagqibezela umsebenzi we-von Restorff kwiseshoni nganye ngelixa i-electroencephalogram irekhodwa. Kulo msebenzi, abathathi-nxaxheba bafunda uluhlu lwamagama, amanye awo agqamayo ngenxa yefonti eyodwa kunye nombala. Ezi kamva zikhunjulwe ngcono [31] ngenxa yobutsha babo [32].

Uphononongo olukhoyo lwe-ERP lokusetyenzwa kwezinto ezintsha luthande ukusebenzisa 'oddball' iiparadigms kunomsebenzi we-von Restorff. Kumsebenzi oqhelekileyo we-oddball impendulo ye-physiological kwi-infrequent non-standard stimuli iyahlolwa. Lo msebenzi ufuna ukuba abathathi-nxaxheba baphendule kwithagethi ethile enikezelwa ngokulandelelana kwezivuseleli ezikwaqulethe izivuseleli zenoveli ezingaqhelekanga, ezingenamsebenzi. Sisebenzise umsebenzi we-von Restorff ongaqhelekanga ngezizathu ezibini. Okokuqala, ibonelela ngesalathiso sokuziphatha sokusetyenzwa kwezinto ezintsha, ezizezi, amazinga okukhumbula izivuseleli zenoveli. Okwesibini, utshintsho olubangelwa yinto entsha ekukhunjulweni lubandakanya umlinganiselo wempembelelo yobutsha kwinkumbulo nasekufundeni. Njengoko kuphawuliwe ngasentla, uphononongo lwangoku lwakhuthazwa ngumbono wokuba i-dopamine inokuchaphazela ukufunda ngendima yayo ekubhaqweni kwezinto ezintsha, kwaye umdla wethu osisiseko kukuba ubutsha buba nefuthe njani ekufundeni nakwinkumbulo. Ke ngoko sikhethe ukusebenzisa umsebenzi ovumela umbono wendlela ubutsha obuzichaphazela ngayo ezi nkqubo zilandelayo zokuqonda (jonga kwakhona [33], [34].).

Ukuba i-dopamine D1/D2 receptor activation yonyusa ubuntununtunu bobuchopho kwinto entsha, ulindelo lwethu yayikukuba ukuvuselelwa kwe-dopamine receptors okubangelwa yi-apomorphine kuya kudala into entsha enkulu ye-N2 kumagama efonti yenoveli. Ukuba i-dopamine ibandakanyeka kwimpendulo yengqondo elandelayo, oku kufuneka kuboniswe kumacandelo amva njenge-P3a, kodwa i-N2 kufuneka ingachaphazeleki.

iziphumo

Idatha yokuziphatha

Umzobo 1 ibonisa ukuchaneka kokukhumbula njengomsebenzi wefonti entsha (inoveli / umgangatho) kunye nemeko yeziyobisi (i-apomorphine/i-placebo). Ukuchaneka okuqhelekileyo kuzo zonke iimeko zeziyobisi kumagama anoveli kwakuyi-30.2% kwaye kumagama aqhelekileyo ama-27.3%. Uhlalutyo lweenkcukacha-manani luthathe uhlobo lokulinganisa ukulinganisa ngokuphindaphindiweyo ukuhluka (RM ANOVA) kunye nezinto ezintsha kunye nemeko yeziyobisi. Oku akuvezi siphumo siphambili semeko yeziyobisi (F_1,25 = 2.27, p = 0.143), akukho mpembelelo iphambili yezinto ezintsha (F_1,25 = 2.02, P = 0.174), kodwa, ngokugqithiseleyo, intsebenziswano phakathi kwezinto (F_1,25  = 4.32, p = 0.048). Umahluko olandelelweyo ubonise ukuba ukusebenza kwenoveli yamagama efonti ibingcono kunaleyo yamagama asemgangathweni wefonti kwimeko ye-apomorphine (t₂₅ = 2.61, p = 0.015), kodwa akukho mahluko ukhumbulayo phakathi kwefonti yenoveli kunye namagama asemgangathweni kwimeko ye-placebo (t₂₅ = 0.12, P = 0.913). Qaphela ukuba amanani eenkcukacha-manani kolu tshintsho lucwangcisiweyo lubonisa amaxabiso akrwada, angalungiswanga.

 

Umzobo 1

Idatha yokuziphatha. Ukuchaneka (%) kuboniswe kwi-axis ye-y, kwaye imivalo icwangciselwe inoveli kunye ne-standard stimuli, zombini phantsi kwe-apomorphine kunye ne-placebo.

Idatha ye-ERP

Njengoko amagama asezantsi efonti engakhange afune i-N2 ecacileyo (jonga indawo yolawulo yasekunene ye Umfanekiso we2) sichonge icandelo le-N2 ngokusekwe kwimpendulo yovuselelo lwefonti yenoveli (jonga indawo yolawulo esekhohlo ye Umfanekiso we2). Ngokuvisisana noncwadi olukhoyo [6], i-N2 yayiyeyona nto iphezulu kwiindawo ze-electrode eziphambili ezihambelana ngokumalunga ne-Fz kunye ne-FCz kwi-10-10 ye-electrode yokubiza amagama. Imizobo eboniswe kuyo Umzobo 2 bonisa amandla arekhodiweyo kwii-electrodes ze-midline malunga nokulingana ne-electrode Fz kunye ne-Cz ye-electrodes ye-10-10 inkqubo.

 

Umzobo 2

I-ERPs ekhutshwe yinoveli kunye ne-standard stimuli emva kokulawulwa kwe-apomorphine kunye ne-placebo, kwi-electrodes Fz kunye ne-Cz.

Njengoko kubonisiwe kwiphaneli ephezulu ekhohlo ye Umzobo 2, i-N2 eqatshelweyo kwimeko ye-apomorphine yayingaphambili kwaye inkulu xa ifunwa ngamagama efonti yenoveli. I-N2 igqithe ngecandelwana elivumelanayo, i-P2, yona ngokwayo ifikelela incopho ye-180 ms. Nangona kunjalo, ukuhanjiswa komhlaba kunye nokwahluka okubonwayo kwe-latency phakathi kweziyobisi kunye neemeko ze-placebo zikhomba uhlengahlengiso oluthile lwe-N2.

Siqale uhlalutyo lwamanani ngokuvavanya ukuthembeka kwe-N2 latency shift. Oku kwaphunyezwa ngokusetyenziswa kwenkqubo ye-jackknifed bootstrap apho i-N2 iqala ukubambezeleka yachazwa njengomzuzu apho eli candelo lafikelela kwi-50% yobukhulu bayo be-amplitude (bona [35].) Olu hlalutyo lubonise ukuba ukuqala kwe-N2 kungaphambili kwimeko ye-apomorphine (166 ms) kunemeko ye-placebo (176 ms; t₂₅ = 2.19, p = 0.041).

Njengoko sinikwe le pateni uhlalutyo lwethu lwe-N2 amplitude lusekwe kumaxesha ahlukeneyo e-latency kwi-apomorphine kunye neemeko ze-placebo. Kwimeko nganye, sibale intsingiselo yeamplitude ejongwa kwisithuba se-20 ms esisekelwe kwincopho ye-N2. [36]. Ngaloo ndlela, i-N2 yemeko ye-apomorphine yachazwa njenge-amplitude ephakathi phakathi kwe-156 kunye ne-176 ms, kunye nemeko ye-placebo phakathi kwe-166 kunye ne-186 ms. Iziphumo zibonise i-N2 enkulu ngokuthembekileyo ekuphenduleni kwi-novel font stimuli kwi-apomorphine kunemeko ye-placebo (t₂₅ = 2.88, p = 0.008). 'Yabona 1 Table.

 

1 Table

Inkcazo yovavanyo lolawulo, oluyilelwe ukuvavanya isiphumo sobungakanani ekubonakalisweni kwamacandelo e-ERP aboniswe kolu xwebhu.

Asizange siqaphele ukungafani okubangelwa ngamachiza kwi-amplitude ye-P3a (~250-350 ms. I-post-stimulus). Ngokwahlukileyo, iP3b ecelwe ngamagama anoveli efonti ibonakala incinci kwimeko ye-apomorphine (iphaneli ephezulu ekhohlo ye Umzobo 2). I-Peak P3b amplitude yabonwa kwiindawo ze-electrode zangasemva, kwaye uhlalutyo lwamanani lwalusekelwe ngokufanelekileyo kwintsingiselo enokuthi ibonwe ukusuka kwi-350-450 ms post-stimulus kwi-electrode ebekwe kwindawo ehambelana neleyibhile ye-Cz kwi-10-10 montage. Olu hlalutyo lubonakalise ukuhla okuthembekileyo kwi-P3b amplitude echazwe ngamagama anoveli efonti kwimeko ye-apomorphine xa kuthelekiswa nemeko ye-placebo (t₂₅ = 2.37, p = 0.026).

ingxoxo

Siphande indima ye-dopamine D1/D2 receptor activation ekusetyenzweni kovuselelo lwenoveli. Ukulandela ulawulo lwe-D1/D2 agonist apomorphine siye saba nabathathi-nxaxheba benza umsebenzi wokukhumbula obandakanya unikezelo lwenoveli-font yegama elithi stimuli. I-EEG yarekhodwa ngelixa abathathi-nxaxheba begqibezela umsebenzi kwaye sahlula i-novelty-induced anterior N2 kunye ne-P3a ERP amacandelo.

Ngenxa yokuba i-N2 yangaphambili iye yanxulunyaniswa nokubhaqwa kwentshayelelo entsha [5], [6], kwaye kucingelwa ukuba isalathise isenzo sothungelwano lokubona into entsha ebekwe ubukhulu becala kwi-cortex yangaphambili [37], [38], inokusetyenziswa njengesalathiso sokufunyanwa kwezinto ezintsha ngaphakathi komongo wongenelelo lwamayeza oluchaphazela inkqubo ye-dopamine. Umsebenzi okhoyo ucebisa ukuba i-dopamine ibandakanyeka ekubhaqweni kwezinto ezintsha [23], kwaye ngokukodwa kunye nesantya seenkqubo zokuqonda [26]. Ukuba i-D1 / D2 i-activation ye-receptor idlala indima ebalulekileyo ekubonweni kwezinto ezintsha, ukulindela kwethu kukuba i-apomorphine kufuneka ibe nempembelelo ephawulekayo kwi-N2 yangaphambili. Ngokuhambelana noku, eli candelo lalilikhulu ngokuthembekileyo kwaye ngaphambili kwimeko ye-apomorphine.

Okubalulekileyo, impembelelo ye-apomorphine kwi-N2 yangaphambili echongiweyo kuphononongo lwethu iyathelekisa neziphumo ze-apomorphine ezibonwe kumsebenzi wangaphambili. Ngokomzekelo, kwiRuzicka et al. [29] Ukulawulwa kwe-apomorphine kwizigulane zika-Parkinson kubangele ukuba i-N2 kunye ne-P3 ekhutshwe yi-auditory target stimuli ibe ncinane kwaye ibe mva kunezo zichazwe kwiimeko ezingekho phantsi kweziyobisi. URuzicka et al. igqibe kwelokuba i-apomorphine icothisa iinkqubo zokuqonda ezisisiseko socalucalulo kunye nokwahlulahlulwa (jonga kwakhona [29], [39], [40]), njengoko kubonwa emva kokulawulwa kwe-levodopa kwizigulane zikaParkinson (umz. [41)]. Kulo mxholo ukukhawuleza kunye nokukhulisa i-N2 ebonakala kwiziphumo zethu kuyamangalisa: i-apomorphine ibonakala inefuthe ngokukodwa kwi-N2 eyenziwa yinto entsha echasene ngokuthe ngqo nokucotha ngokubanzi okubonwa kwi-N2 kunye ne-P3 kwizifundo zangaphambili.

Ngokuhambelana nalo msebenzi wangaphambili obonisa umphumo ophazamisayo jikelele we-apomorphine, sifumene ukunciphisa ngokubanzi kwi-P3 amplitude - ngakumbi kwi-P3b - xa abathathi-nxaxheba babephantsi kwempembelelo yeziyobisi (bona Umzobo 2). Ezi ziphumo azihambelani nobungqina bemfuza bangaphambili, obunxulumene nomsebenzi ophuculweyo we-dopaminergic kunye nokunyuka kwe-amplitude ye-P3a. [42]. Ebusweni bayo, oku kunokucebisa impembelelo engalunganga yechiza kwindlela yokuqaphela kunye ne-mnemonic eboniswe yi-P3. Nangona kunjalo, kuhambelana nezinye iziphumo kuncwadi [40], iziphumo zethu zibonise ukuba akukho budlelwane phakathi kwe-catecholomine-induced P3 ukuhluka kunye nokusebenza kokuziphatha. I-Apomorphine eneneni yayinokuthenjwa luncedo impembelelo kwinkumbulo yamagama efonti yenoveli.

Le pateni icebisa ukuba ukwahluka ekukhunjulweni kwamagama efonti yenoveli - isiphumo se-von Restoff - sibonakaliswa kwi-N2 yangaphambili, hayi i-P3, kwaye ke ibonisa utshintsho kwi-neural ubuntununtunu kwizinto ezintsha kuneenkqubo ezizayo zokuqonda. Oku kuhambelana neqela lezinto ezifunyenweyo kwilebhu yethu ebonisa ukwahlukana phakathi kobukhulu be-P3 kunye nethuba lokuba igama lefonti yenoveli liya kukhunjulwa. [43]. Ukungabikho okubonakalayo kwaso nasiphi na isiphumo sechiza kwi-P3a kunokubonakalisa impembelelo edibeneyo yeempembelelo zechiza ezimbini ezifanayo: kwelinye icala i-apomorphine inokwenza ukunyusa i-P3a amplitude ngokwandisa uvakalelo kwizinto ezintsha (njengoko kucetyisiwe kwiziphumo zangoku ze-N2), esinye isandla i-apomorphine inokusebenza ukunciphisa i-P3a amplitude ngempembelelo yayo embi ebanzi kwi-amplitude yamacandelo e-ERP.

Njengoko kuphawuliwe ngasentla, umsebenzi okhoyo ubonisa ukuba i-apomorphine inempembelelo ephazamisayo ngokubanzi kwi-cognition, kodwa iziphumo zethu zibonisa ngokucacileyo ukuba iququzelela iindlela zokufumanisa izinto ezintsha ezifakwe kwi-N2 yangaphambili. Oku kuhambelana neengcamango zeRedgrave kunye neGurney [27], abathi inoveli, izivuseleli ezingalindelekanga zibangela ukukhawuleza, ukukhutshwa kwe-dopamine ngokuzenzekelayo. Indima yolu kukhululwa iya kuba kukwazisa ezinye iindawo zobuchopho kwisehlo senoveli yokusingqongileyo, kunye nokuququzelela ukufundwa kwezi zivuseleli kunye neempendulo ezinokuthi zibangele ukubonakala kwazo. Ubutsha ngale ndlela buba ngundoqo kwi-plasticity yokuziphatha-ukuseta iqonga, nge-dopamine, yokufunda.

Njengoko kubonakala kwi Umzobo 2, icandelo le-N2 eliqatshelwe kolu phononongo ligqithana kunye necandelo le-P2 le-ERP, kwaye iziphumo zethu zinokubonisa ngokufanelekileyo indibaniselwano yeziphumo kula macandelo mabini. Zombini i-N2 kunye ne-P2 zenzeke ngexesha elinye le-latency kwaye kunzima ukuzohlula (ngaphandle kwe-polarity) njengoko ubukhulu becala zinovakalelo kubuchule obufanayo bovavanyo kwaye zinembonakalo yomhlaba efanayo. Zibonakala zibonisa umsebenzi kwiijenereyitha ezisondeleyo emzimbeni, ukuba azikho kwizakhiwo zobuchopho ezifanayo (njengoko bekuya kwenzeka ukuba umahluko wepolarity ubungenxa yokugotywa kwecortical).

Nangona kunjalo, akunakwenzeka ukuba ukwahluka kwi-P2 kunokuphendula kuphela kwiziphumo zethu. Okokuqala, i-amplitude ye-P2 ebangelwe ziifonti eziqhelekileyo ayizange iphenjelelwe yi-apomorphine, ngokuhambelana neziphumo ezikhoyo ezibonisa ukuba i-P2 isengozini yokufaneleka komsebenzi kunokuba ibe yinto entsha. [44]. Okwesibini, akunakwenzeka ukuba i-N2 yokutshintshwa kwe-latency shift ingenziwa ngotshintsho kwi-P2. I-N2 licandelo le-frequency ephezulu kakhulu kule datha, ngelixa i-P2 iyeyesiqhelo esisezantsi (kwaye iza kudibana ne-P3a). Ukwahlukahlukana kolu tshintsho olusezantsi lwe-positive-polarity complex akunakwenzeka ukudala utshintsho kwincopho ye-N2 ephezulu.

Siphakamisa ukuba iziphumo zangoku zibonisa umahluko kwi-N2 yangaphambili, kodwa enye indlela yokutolika inokuba kukuba ukuqhatha kwethu kovavanyo kuchaphazela ukungahambelani kakuhle. [45], [46]. Nangona kunjalo, izifundo zangaphambili zibonisa ukuba i-dopamine ayinayo impembelelo kwisizukulwana okanye ekumodareyithweni kwe-MMN [47]. Ngaphezu koko, iijeneretha ze-MMN ezibonakalayo zibonakala zibekwe kwi-cortex yangasemva, kunye nobuninzi beendawo ze-occipital. [48] endaweni yeendawo ezingaphambili ezibonakala kwiziphumo zethu.

Ngoko ke siphetha ukuba i-apomorphine inempembelelo ekuqhubekeni kwezinto ezintsha njengoko zifakwe kwi-N2 yangaphambili. I-Apomorphine ngokuqhelekileyo icingelwa ukuba inempembelelo ye-agonistic kwi-D1 / D2 receptors, ehambelana nombono wokuba umsebenzi owandisiweyo kwinkqubo ye-dopamine inokunxulunyaniswa nokunyuka kobuntununtunu bokuvuselela inoveli. Nangona kunjalo, imigqaliselo emibini kufuneka iqhotyoshelwe kulo mbono. Okokuqala, akukacaci ukuba i-apomorphine kwidosi ephantsi isebenza njenge-agonist, okanye kunokuba ngumchasi osebenzayo ngempembelelo yayo kwi-autoreceptors. [49], [50]. Esi siphumo sichasayo sicetyiswe njengengcaciso yeziphumo eziyingozi zengqondo kwizigulana zeParkinsonian. [51], [52], kodwa kusafuneka iboniswe ngokugqibeleleyo. Kuphononongo lwethu, i-apomorphine yayingenayo impembelelo kwimemori esisiseko, kodwa iphuculwe ngokukhethayo inkumbulo yenoveli. Umbono wokuba umchasi we-dopamine uya kudala le pateni kunzima ukudibanisa nayo nayiphi na iakhawunti yethiyori yangoku. Ngokwahlukileyo, ukuba loo apomorphine isebenze njenge-agonist, olu phuculo lokuziphatha luhambelana kakhulu nombono wokuba i-dopamine ibandakanyeka ekubhaqweni kwezinto ezintsha.

Okwesibini, utoliko lwethu lusekwe kwingcinga yokuba eyona ndlela iphambili yokwenziwa kovavanyo yinto entsha yovuselelo. Amagama efonti yeNoveli nawo ohlukile kumagama asemgangathweni wefonti kwiimpawu ezibonakalayo zombala, ubungakanani kunye nodidi lwefonti, ezinokuthi zithiyori zidlale indima ekuveliseni iimpendulo ezihlalutywe apha. Nangona kunjalo, akunakwenzeka ukuba ezi mpawu zibonakalayo zingenza iimpendulo ezifana ne-N2 kunye ne-P3a, kwaye oku kwakulawulwa kwimeko yobukhulu kuvavanyo lokulawula. Ngaphaya koko, ukwahluka kwezi ntlobo zento yovuselelo alubonisi lunxulumano kunye notshintsho kumsebenzi we-dopamine-rich midbrain nuclei. [53].

Ukuqukumbela, iziphumo zethu zibonisa ukuba ukulawulwa kwe-D1/D2 agonist apomorphine kukhokelele ekuphuculweni kokubonwa kwe-stimuli enombala wenoveli, ifonti, kunye nobukhulu, njengoko kubonisiwe ekuqaleni kwangaphambili kunye nokwanda kwe-amplitude yecandelo langaphambili le-N2 ye-ERP. Kulwazi lwethu, esi sisifundo sokuqala ukubonisa ukuba ukusebenza kwe-D1/D2 receptors ngokukhethayo kwandisa ubuntununtunu bengqondo kwizinto ezintsha. Indima yolu buntununtunu bandisiweyo inokuba kukuququzelela ukufundwa kolwakhiwo lwenoveli yovuselelo kunye neempendulo ezinxulumene nazo. Ngokuhambelana noku, sifumene ukuba izinto zenoveli zikhunjulwa ngcono emva kokusebenza kwe-D1 / D2 receptor.

Inkqubo yovavanyo

Inkqubo kunye ne-Stimuli

Umzobo 3 ibonisa umboniso wesicwangciso seseshoni yovavanyo. Njengoko i-apomorphine inemizuzu engama-40 ukuya kuma-50 yokunyuka kwexesha, ngoko ke uvavanyo luqale kwimizuzu engamashumi amane emva kokutofwa [52], [55]. Sisebenzise umsebenzi wokufunda ngomlomo olungisiweyo we-von Restorff apho amagama aboniswe ngefonti eqhelekileyo namagama anikezelwe ngefonti yenoveli afundwayo aze akhunjulwe kamva. Amagama efonti yenoveli adla ngokukhunjulwa ngcono kunamagama efonti eqhelekileyo [31]. Umelo olucwangcisiweyo lomsebenzi luboniswe kwi Umzobo 3. Yayibandakanya isigaba sokufunda, isigaba sokukhumbula, kunye nesigaba sokugqibela sokuqondwa, kodwa ukusebenza ngexesha lenqanaba lokugqibela lokuqondwa kwakusesilingini kwaye ziziphumo kuphela ezisuka kwisigaba sokukhumbula esixutyushwayo ngezantsi.

 

Umzobo 3

Ukumelwa okucwangcisiweyo kweseshoni yovavanyo kunye nomsebenzi (cutout).

Ngethuba lesigaba sokufunda, abathathi-nxaxheba banikwe uluhlu lwezibizo eziphathekayo ze-80 kwisiNgesi, kunye nobude begama obuhluka phakathi kwe-5 kunye ne-10 yamagama. Kwasetyenziswa izintlu ezimbini ezahlukeneyo, olunye kwiseshoni yovavanyo nganye, ngolandelelwano lwezi zintlu ngokungqinelanisiweyo kuzo zonke izifundo. La mazwi yayingalawo ayeqeshwe nguVan Overschelde noogxa bakhe [56], incediswa sisichazi-magama.

Amagama akuluhlu ngalunye anikwe mhlawumbi ngefonti eqhelekileyo (iCourier New, izihlandlo ezingama-60) okanye ifonti enoveli (izihlandlo ezingama-20). Amagama efonti yeNoveli anombala oguquguqukayo (omnye wemibala elishumi enokwenzeka, kunye nombala ngamnye ophinda kabini kuluhlu), uhlobo lohlobo oluguquguqukayo (olwahlukileyo kwigama ngalinye lenoveli kuluhlu), kunye nobukhulu obukhulu.

Uluhlu ngalunye luboniswe kabini kwiseshoni yokuvavanya nganye, kungekho tshintsho kulandelelwano, ifonti, okanye umbala, kwaye abathathi-nxaxheba bathatha ikhefu elifutshane emva komboniso wokuqala. Amagama abonakaliswe embindini wescreen esingwevu (ubukhulu obungama-21″) ekuma-80 cm phambi kwesihloko, kangangokuba amagama aqhelekileyo (ubungakanani befonti 17) athobe nge-2.5 ukuya ku-5 i-engile yokubonwayo, ngokuxhomekeke kubude begama, kunye nenoveli. amagama (ubukhulu befonti 30) 5.7 ukuya ku-9.6 degrees of visual angle.

Ulingo ngalunye luqale ngokunikezelwa komnqamlezo wokulungiswa kwesithuba esingakhethiyo se-400 ukuya kwi-500 ms (ukuhanjiswa okufanayo). Igama liye laboniswa embindini wesikrini kwaye lahlala libonakala kwi-3500 ms.

Kwinqanaba lokufunda, abathathi-nxaxheba bayalelwa ukuba bafunde amagama. Kwinqanaba le-cued recall phase, abathathi-nxaxheba banikwa i-cues ye-40 yamagama afundwe ngaphambili (amagama angama-20 anoveli kunye ne-random 20 yamagama aqhelekileyo - ayingawo onke amagama asemgangathweni athathwe ukunciphisa ubude bomsebenzi). I-Cues yayiquka oonobumba ababini bokuqala begama ngalinye, banikezelwa enye ngexesha ngokulandelelana okungahleliweyo, kwaye abathathi-nxaxheba bagqibezela igama elifundisiweyo ngokuchwetheza oonobumba abaseleyo. Igama ngalinye kulawo afundisiswayo lalinendibaniselwano ekhethekileyo yoonobumba ababini bokuqala.

Ukongeza kwi-stimuli yegama elibonakalayo, ngexesha lesigaba sokufunda i-stimulus yokuva yanikezelwa emva kokubonakala kwegama ngalinye emva kwekhefu. Ikhefu phakathi kokubonakala kunye nokuvalelwa kokuqala kukhethwe ngokungenamkhethe ukusuka kulwabiwo olufanayo lwe-817 ukuya kwi-1797 ms. Izandi zaziziindidi ezimbini; nokuba yithowuni esezantsi ye-'beep' (2.2 KHz, 300 ms), eyathi yanikezelwa kulingo lwama-58 kwangama-80, okanye ikliphu yesandi eyohlukileyo yolingo (300 ms), eyathi yanikezelwa kulingo lwama-22 kwangama-80. Kwakungekho budlelwane phakathi kwe-auditory stimuli kunye namagama abonakalayo, kwaye abathathi-nxaxheba bayalelwa ukuba bangazihoyi izandi. Isishukumiso sokuva sibandakanyiwe kuyilo lovavanyo ukuvelisa umlinganiselo ozimeleyo wokusetyenzwa kwezinto ezintsha, kodwa, ngokuhambelana nezinye iziphumo ezilandelayo kwilebhu yethu, akukho bungqina kwidatha yokwahlulahlula iithowuni ezisemgangathweni kunye neziqeshana zesandi ezizodwa kwaye oku kukhohlisa ayixoxwanga ngokubhekele phaya.

Ingxelo Yenkxaso

I-MM ixhaswa ngemali yinkxaso ye-VIDI 452-09-007 evela kwi-NWO. I-CH ixhaswa ngemali yi-VENI isibonelelo 016-125-283 evela kwi-NWO. Abaxhasi bemali babengenayo indima ekuyilweni kokufunda, ukuqokelela idatha kunye nohlalutyo, isigqibo sokupapasha, okanye ukulungiswa kombhalo wesandla.

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