Abstract
Phezu kwako nje ukufuna ngokucacileyo ukuyeka, amakhoboka exesha elide azifumana engenamandla okuxhathisa iziyobisi, nangona esazi ukuba ukusebenzisa iziyobisi kusenokuba likhondo eliyingozi. Ukungangqinelani okunjalo phakathi kolwazi olucacileyo lweziphumo ezibi kunye neepatheni zokuziphatha ezinyanzelekileyo zibonisa ungquzulwano lwengqondo / lokuziphatha oluluphawu oluphambili lokukhobokisa. I-Neurobiologically, umsebenzi owenziwe ngokwahlukileyo kwi-cue subregion ezahlukeneyo, kunye nokunxibelelana kwe-dopamine ejikelezayo ukusuka kwimimandla ye-ventral striatal ukuya kwimimandla ye-dorsal, idlala indima ebalulekileyo ekufuneni iziyobisi. Nangona kunjalo, indlela yokusebenza edibanisa le ngqalelo ye-neuropharmacological kunye nengxabano ekhankanywe ngasentla kwengqondo / yokuziphatha ayaziwa. Apha sinika ingcaciso esesikweni yokubala yokungangqinelani kwengqondo okubangelwa sisiyobisi ebonakala “kwimpazamo ezichazayo” yabasebenzisa iziyobisi. Sibonisa ukuba iziyobisi ezikhobokisayo ngokuthe ngcembe zivelisa impembelelo ekhuthazayo ekufuneni iziyobisi kwiinkqubo ezikwinqanaba elisezantsi lesiqhelo, ngaphandle koxabiso oluphantsi lokuqonda kolu kuziphatha. Le pathology ivela ngaphakathi kwesakhelo sokufunda esomelezwa ngokwenqanaba eliphezulu xa ukuvezwa okungapheliyo kwiyeza kuvelisa imiqondiso ye-pathologicaly eqhubekayo ye-dopamine. Ngaloo ndlela iyeza liqweqwedisa i-dopaminergic spirals ethi ikhuphe imiqondiso yokuqinisa i-ventro-dorsal cortico-striatal hierarchy. I-Neurobiologically, ithiyori yethu ibalelwa kuphuhliso olukhawulezileyo lwe-dopamine efflux yeziyobisi kwi-ventral striatum kunye nempendulo yokulibaziseka kwi-dorsal striatum. Ithiyori yethu ikwabonisa indlela le patheni yokuphendula ixhomekeke ngokunzulu kwi-dopamine spiring circuitry. Ngokwendlela yokuziphatha, isakhelo sethu sichaza ukungakhathali ngokuthe ngcembe kokufuna iziyobisi kwizohlwayo ezinxulumene neziyobisi, into ethintela iziphumo zeziyobisi, kunye nokuthanda okuzingileyo kweziyobisi kunomvuzo wendalo ngamakhoboka. Imodeli icebisa ukuqikelelwa okunokuvavanywa nangaphaya koko, ibeka inqanaba lokujonga umlutha njenge-pathology yeenkqubo zokwenza izigqibo zenqanaba eliphezulu. Lo mbono uhambelana nokutolikwa kwendabuko kokulutha njengonxibelelwano phakathi kweenkqubo zesigqibo esiziqhelileyo kunye neenjongo.
Citation: I-Keramati M, i-Gutkin B (2013) I-Hierarchy yeSigqibo esingalinganiyo kwi-Addicts ephuma kwi-Drug-Hijacked Dopamine Spiraling Circuit. PLoS ENYE 8(4): e61489. doi:10.1371/journal.pone.0061489
umhleli: UAllan V. Kalueff, kwiYunivesithi yaseTulane Medical School, eUnited States yaseMelika
I funyenwe: NgoJanuwari 4, 2013; Zamkelwa: Matshi 10, 2013; Yashicilelwe: Aprili 24, 2013
Copyright: © 2013 Keramati, Gutkin. Eli linqaku elivulekileyo lokufikelela lisasazwe phantsi kwemiqathango yeLayisensi ye-Creative Commons Attribution, evumela ukusetyenziswa okungathintelekiyo, ukuhanjiswa, kunye nokuveliswa kwakhona kuyo nayiphi na indlela, ngaphandle kokuba umbhali wokuqala kunye nomthombo banikwe ikhredithi.
Inkxaso: Olu phononongo luxhaswe ngemali evela kwiFrontiers du Vivant, i-French MESR, i-CNRS, i-INSERM, i-ANR, i-ENP kunye ne-NERF. Abaxhasi bemali babengenayo indima ekuyilweni kokufunda, ukuqokelela idatha kunye nohlalutyo, isigqibo sokupapasha, okanye ukulungiswa kombhalo wesandla.
Injongo yokunyanzela: Ababhali baye bavakalisa ukuba akukho mfuno ekhuphisanayo.
intshayelelo
"Siye savuma ukuba asinamandla phezu komlutha wethu-ukuba ubomi bethu abunakulawuleka" itsho imfundiso yokuqala ye-Narcotics Anonymous 12-step program. [1]. Oku kubonisa indlela amakhoboka angenamandla azifumanisa ngayo xa kuziwa ekuchaseni iziyobisi, nangona esazi ukuba ukuthatha iziyobisi linyathelo elingalunganga. [2]-[4]. Ngapha koko, uphawu lokukhobokisa kukunyanzeliswa ukufuna amachiza nokuba iindleko zeziphumo ezibi ezicacileyo. [5]. Ukutyikitywa kokuziphatha okunjalo kwe-pathological kubonakala kuvavanyo olulawulwayo apho amakhoboka abonisa uphawu "lwempazamo ezichazayo": ukungangqinelani phakathi kwempendulo enamandla yokuziphatha ngokubhekiselele kukhetho olunxulumene neziyobisi kunye nexabiso eliphantsi eliphantsi lokuba umlutha uxela ichiza. [4], [6], [7]. Xa kudityaniswa nelahleko yokulawulwa kwengqondo ethintelayo ekuziphatheni, emva kokuvezwa ixesha elide kwiziyobisi, lo mahluko phakathi kwezicwangciso zokuqonda kunye nemikhwa edityanisiweyo kunokubangela ukuguquka ukusuka kwisiqhelo ukuya kwisinyanzelo sokuziphatha kokufuna iziyobisi. [8].
Ukuphulukana nolawulo lwengqondo kunye nempazamo ozichazayo ukuza kuthi ga ngoku kuye kwayibaleka ingcaciso esisiseko ngeemodeli ezisemthethweni zokulutha. [9]-[13]. Iithiyori ezidlulileyo zokuba likhoboka leziyobisi, ubukhulu becala zibekwe ngaphakathi kwesakhelo sokufunda, jonga umlutha njengemeko ye-pathological yokufunda umkhwa (ukuvuselela-impendulo) inkqubo. [9]-[13]. I-hypothesis ephambili emva kwazo zonke ezo modeli kukuba isiphumo sekhemesti yeziyobisi kwi-dopamine signing, ekucingelwa ukuba ithwele umqondiso wokufundisa we-stimulus-response, ikhokelela ekomelezeni ngokuthe ngcembe kwemibutho enjalo. Esi siphumo sikhokelela kwimikhwa enyanzelekileyo yokufuna iziyobisi. Ngelixa lo mbono uncitshisiweyo wokulutha ubambe imiba ethile yento eyenzekayo, ukuvumelana okukhulayo kuncwadi lokulutha kubonisa ukuba iinkqubo ezininzi zokufunda zibandakanyeka kwi-pathology. Kuphela ngumfanekiso ontsokothileyo obandakanya ukuqonda kwengqondo, kunye neenkqubo ezikwinqanaba elisezantsi lokuziqhelanisa, onokuchaza iindlela ezahlukeneyo zokuziphatha ezinjengomlutha. [8], [14].
Kweli phepha, samkela indlela yokufunda yokuqinisa ngokwemigangatho [15] apho izigqibo zimelwe kumanqanaba ahlukeneyo e-abstraction, kwi-cognitive-to-motor hierarchy. Sicinga ukuba i-cascade yokufunda exhomekeke kwi-dopamine idibanisa amanqanaba olawulo kunye [16]. Siphinde sicinge ukuba amachiza okuxhatshazwa ngokwekhemisti aqweqwedisa indlela yonxibelelwano phakathi kwamanqanaba okukhutshwa. Ngokusekwe kwezi ngcinga, sibonisa ukuba ingxelo exeliweyo ye-cognitive dissonance kwi-addiction iphuma ngaphakathi kwesakhelo sokufunda esomelezwa ngokwenqanaba eliphezulu xa ukuvezwa kweziyobisi okungapheliyo kuphazamisa ukufunda ngexabiso kulo lonke ulawulo lwesigqibo. Olu phazamiseko lukhokelela ekuxatyisweni okugqithisileyo kokhetho lwamachiza kwiinkqubo zesiqhelo ezikwinqanaba elisezantsi kwaye yiyo loo nto iqhuba indlela yokuziphatha yokukhangela iziyobisi. Emva koko siye sibonise ukuba "akuthandwa" kodwa ukufuna iziyobisi okunyanzelekileyo kunokuchazwa njengeenkqubo zokuqhelwa kweziyobisi ezikumgangatho ophantsi olawula ukuziphatha, ngelixa iinkqubo eziphilileyo zengqondo kumanqanaba aphezulu okumela zilahlekelwa kulawulo lokuziphatha. Ngaphaya koko, sibonisa ukuba imodeli ecetywayo inokuphendula kubungqina bamva nje malunga nokulibaziseka kophuhliso lweziyobisi-elicited dopamine efflux kwi-ventral vs. dorsal striatum, ngokulandelelana, kunye nokuxhomekeka kwale pateni kwi-dopamine spiraling circuitry.
Impahla nenkqubo
Iziqendu
Ngokuhambelana noncwadi lwengqondo olutyebileyo lwezengqondo, ukufunda kwethu ukomelezwa kwenqanaba eliphezulu [15], [18] Isicwangciso-nkqubo sithatha ukuba isicwangciso sokuqonda esingabonakaliyo esifana “nokwenza iti” sinokophulwa ngokolandelelwano lwezenzo ezikwinqanaba elisezantsi: amanzi abilayo, ukubeka iti embizeni, njl. njl. ulawulo (Umzobo 1A). I-Neurobiologically, amanqanaba ahlukeneyo olawulo lwesigqibo ukusuka kulwazi ukuya kumanqanaba emoto amelwe ecaleni kwe-rostro-caudal axis yesekethe ye-cortico-basal ganglia (BG) [19]-[21]. Le sekethi yenziwe ngamacandelo ahlukeneyo avalelekileyo avaliweyo phakathi kwecortex yangaphambili kunye ne-basal ganglia. [22], [23] (Umzobo 1B). Ngelixa iilophu zangaphambili zingaphantsi kokumelwa okungaphaya kwezenzo, iilophu zecaudal, eziqulathe i-sensory-motor cortex kunye nedorsolateral striatum, zibandakanya imikhwa yomgangatho ophantsi. [19]-[21].
Umzobo 1. Intlangano ye-hierarchical yokuziphatha kunye nesekethe ye-cortico-BG.
A, Umzekelo wesigqibo soluhlu lwezinto ezimbini ezizezinye: iziyobisi vs. ukutya. Ikhondo ngalinye lesenzo limelwe kumanqanaba ahlukeneyo okutsalwa, ekucingelwa ukuba afakwe kwiikhowudi ezahlukeneyo ze-cortico-BG. Ukufuna uhlobo ngalunye kwezi zimbini zomvuzo kunokulandela isohlwayo esinomlinganiselo we-16. B, Uqhagamshelo lwe-Glutamatergic olusuka kwiindawo ezahlukeneyo zangaphambili kwiprojekthi ukuya kwiindawo eziphantsi kwe-striatal kwaye emva koko iprojekthi ibuyele kwi-PFC nge-pallidum kunye ne-thalamus, yenza iilophu ezininzi ezihambelanayo. Ngenethiwekhi ye-striato-nigro-striatal dopamine, imimandla ye-ventral ye-striatum inefuthe kwezona ndawo zininzi ze-dorsal. i-vmPFC, i-ventral medial prefrontal cortex; I-OFC, i-orbital cortex yangaphambili; I-dACC, i-cortex yomqolo ongaphambili we-cingulate; I-SMC, i-sensory-motor cortex; I-VTA, indawo ye-ventral tegmental; I-SNc, i-substantia nigra pars compacta. Umzobo 1B Ilungiswe ukusuka kwireferensi yama-21.
I-doi: 10.1371 / journal.pone.0061489.g001
Ngaphakathi kolu jikelezo, umsebenzi wephasic we-midbrain dopamine (DA) neurons ebonisa imiqondiso ye-striatum impazamo phakathi kwemivuzo eqikelelweyo kunye nefunyenweyo, ngaloo ndlela ithwele ulwazi oluqinisayo lwempendulo. [24]. Olu qikelelo lwe-DAergic lwenza uqhagamshelo olujikelezayo oludibanisa imimandla engaphezulu ye-ventral ye-striatum ukuya kwimimandla ethe kratya ye-dorsal ngokubizwa ngokuba yi-"spiraling" yoqhagamshelwano. [25]-[27] (Umzobo 1B). Ngokusebnzayo, umbutho onjalo okhokelela phambili odibanisa i-rostral kwi-caudal cortico-BG loops ivumela ukudityaniswa okuthe ngqo ukusuka kwi-coarse ukuya kwi-final representation. Ngokufanelekileyo, i-spirals ye-DA icingelwa ukuba ibonelele nge-neurobiological substrate yokuqhubela phambili ulungelelwaniso lwempazamo yokuxela kwangaphambili ngamanqanaba aphezulu olawulo (ukufaka ikhowudi kulwazi olungabonakaliyo malunga nexabiso leendlela zokuziphatha). Le mpazamo iye isetyenziswe ukuhlaziya amaxabiso entshukumo kumanqanaba aneenkcukacha [16]. Ngamanye amazwi, i-DA spirals ivumela amanqanaba ovavanyo lwengqondo (abstract cognitive level of valuation) ukukhokela ukufundwa kwiinkqubo zokuvandlakanywa kwezenzo ezineenkcukacha.
Umzobo wethiyori
Ngokwethiyori yokubala yokuqinisa ukufunda [28] (RL), i-arhente (kwimeko yethu umntu okanye isilwanyana) sifunda ukwenza ukhetho olunolwazi ngokuhlaziya ixabiso eliqikelelweyo langaphambili, , kwisigaba ngasinye sesenzo selizwe, , xa umvuzo ifunyanwa yi-arhente ngexesha njengesiphumo sokwenza isenzo kwimeko yomxholo (uvuselelo) . Ixabiso ihlaziywa ngekhompyutha isiginali yempazamo yoqikelelo lomvuzo. Lo mqondiso awuxhomekeke kuphela kumvuzo ofunyenwe ngoko nangoko (), kodwa nakwixabiso lelizwe elitsha i-arhente ephela kuyo, emva kokuba isenzo senziwe. Ichazwa ngu , lo msebenzi wexabiso wexesha eliphambili umela isixa sembuyekezo yexesha elizayo isilwanyana esilindele ukuyifumana kwimeko yesiphumo, , ukuya phambili. Impazamo yoqikelelo ingabalwa ngale nxaki ilandelayo:
Ngokucacileyo, isiginali yempazamo yoqikelelo ibala umahluko phakathi kwento elindelweyo kunye nexabiso elivuzayo lesenzo. Kulwakhiwo lwesigqibo soluhlu, nangona kunjalo, kunokuba sifunde i -amaxabiso ngokuzimeleyo kumanqanaba ahlukeneyo, amanqanaba angaphezulu abstract anokwenza umqondiso wokufundisa ubalwe kumanqanaba asezantsi. Kuba amanqanaba aphezulu olawulo oluphezulu amele ukumelwa okungaphaya kokungalindelekanga kokusingqongileyo, ukufunda kwenzeka ngokukhawuleza kuloo manqanaba. Oku kungenxa yomlinganiselo ophantsi wokumelwa okungabonakaliyo kokuziphatha: isicwangciso sentshukumo sinokumelwa njengenyathelo elinye (umlinganiselo omnye) kwinqanaba eliphezulu lolawulo oluphezulu kunye nezenzo ezineenkcukacha ezininzi (imilinganiselo emininzi) kumanqanaba asezantsi. yoluhlu lwemigangatho. Ixabiso lenqanaba eliphezulu lesi sicwangciso-senzo siya kufundwa ngokukhawuleza xa kuthelekiswa namanqanaba aneenkcukacha apho iimpazamo zomvuzo ziya kufuna ukubuyisela umva onke amanyathelo acacisiweyo. Ngaloo ndlela, ukulungiswa kwamanqanaba asezantsi ngolwazi lwexabiso ukusuka kumanqanaba aphezulu kunokukhawulezisa ukudibanisa kwezi xabiso. Enye indlela esebenzayo ngokweenkcukacha-manani yokwenza oko kukucinga ukuba ukwenza ikhompuyutha yesiginali yempazamo yoqikelelo kwi -th level of abstraction, , umsebenzi wexabiso elongezelelweyo okwexeshana, , ivela kwinqanaba eliphezulu lokutsalwa, [16]:
Ukugcina okugqibelele, i-equation 2 ingasetyenziselwa ukubala impazamo yoqikelelo kuphela xa intshukumo yokugqibela emiselweyo yokhetho olungekhoyo lwenziwa (jonga uMfanekiso S1 kwi. Ifayile yeS1). Kwezinye iimeko, ukufunda ngexabiso kumanqanaba ahlukeneyo kwenzeka ngokuzimeleyo, njengakwi-equation 1. Kuzo zombini ezi meko, umqondiso wokufundisa usetyenziselwa ukuhlaziya amanani angaphambili kwinqanaba elingqinelanayo:
(3)
apho lizinga lokufunda. Olu hlobo lolwabelwano lolwazi lwamanqanaba aphakathi lubonakala ngokwebhayoloji njengoko lubonakalisa ubume obujikelezayo besekethe ye-DA, ithwala ulwazi phantsi koluhlu lwemigangatho kwicala le-ventro-dorsal. Kwangaxeshanye, ukukhokelwa ngamanqanaba angaphaya kwengqondo kukhawulezisa ukufunda, kuthomalalisa umgangatho ophezulu wokufunda ngexabiso kumanqanaba aneenkcukacha. [16].
Kweli phepha sibonisa ukuba intsebenziswano phakathi kwenguqulelo elungisiweyo yemodeli ephuhliswe kuyo [16] kunye neziphumo ezithile ze-pharmacological zokusetyenziswa kakubi kweziyobisi kwinkqubo ye-dopaminergic inokubamba idatha enxulumene nokulutha kwizikali ezahlukeneyo zohlalutyo: inqanaba lokuziphatha kunye nenqanaba le-neurobiological. Okokuqala, imodeli entsha izisa ingcaciso ebambekayo enokubakho yeendlela ezininzi zokuziphatha ezinxulunyaniswa nokuba likhoboka leziyobisi (umz. impazamo ozichazayo. [4], [6], [7]). Okwesibini, sinokuphendula uluhlu olubanzi lobungqina malunga nokuguquguquka kokukhutshwa kwe-dopamine ekhutshwe ngamachiza [17].
Siyitshintsha imodeli eboniswe kuyo [16] ngoku Landelayo. Senza imodeli isebenze ngakumbi malunga nomthamo wememori yokusebenza ngokutshintsha kunye , kwi-equation 2, ekubeni amaxabiso amabini edibana kwinqanaba elifanayo elizinzileyo (jonga uMfanekiso S2 Ifayile yeS1, kwisiseko sokubala kunye ne-neurobiological):
Apha, lukhetho olucacileyo kwaye sisenzo sokugqibela samandulo kulandelelwano lokuziphatha olugcwalisa ngokupheleleyo olu khetho. Ngokufanayo, lixabiso elivuzayo le , equka (ixabiso elivuzayo le ).
Okubaluleke kakhulu, iziyobisi ezahlukeneyo ezisetyenziswa kakubi ngabantu zabelana ngepropathi esisiseko yokwandisa i-pharmacological concentration ye-dopamine ngaphakathi kwe-striatum. [29]. Ngokufanelekileyo, sidibanisa le mpembelelo ye-pharmacological yechiza ngokongeza i-bias efanelekileyo, , (bona kwakho [9]-[12]) kumqondiso wempazamo yoqikelelo oluthwalwa yi-dopamine neurons (jonga umfanekiso we-S3 kuyo Ifayile yeS1, kwisiseko sokubala kunye ne-neurobiological):
apha ibamba isiphumo esithe ngqo se-pharmacological yechiza kwinkqubo ye-DA, kunye lixabiso layo lokuqinisa ngenxa yeziphumo ze-euphorigenic (bona Ifayile yeS1 ngolwazi olongezelelweyo).
Ngelixa ii-equations 3 kunye ne-5 kunye zichaza indlela yokubala ukuhlaziya ixabiso kwimodeli yethu, sikwacinga ukuba indlela yokhuphiswano olusekwe ekungaqinisekisini imisela inqanaba lokukhupha elilawula ukuziphatha. Oku kukhuthazwa yindlela ecetywayo kwi [29] kulamlo phakathi kweenkqubo zesiqhelo nezijoliswe kwiinjongo. Ngokubhekiselele koku, kwinqanaba ngalinye lesigqibo, kuphela inqanaba lokutsalwa ngeyona ngqiniseko iphakamileyo ekuqikeleleni ixabiso lokhetho lilawula ukuziphatha. Nje ukuba eli nqanaba lenze isigqibo sokuthatha isenzo, onke amanqanaba asezantsi olawulo luya kuthunyelwa leli nqanaba liphezulu ukuphumeza isenzo esikhethiweyo njengolandelelwano lweempendulo zeemoto zangaphambili (bona Ifayile yeS1 ngolwazi olongezelelweyo; Umzobo S4 kwi Ifayile yeS1; Umzobo S5 kwi Ifayile yeS1). Ekufumaneni ingxelo yembuyekezo evela kokusingqongileyo, amaxabiso kuwo onke amanqanaba ayahlaziywa. Le ndlela yolamlo esekelwe ekungaqinisekisini iqikelela ukuba njengoko iinkqubo ezingabonakaliyo zibhetyebhetye ngakumbi, zinekhono eliphezulu lokuqikelelwa kwexabiso ngexesha lamanqanaba okuqala okufunda kwaye ngaloo ndlela, ukulawula ukuziphatha kwezi zigaba. Nangona kunjalo, njengoko amanqanaba abstract esebenzisa umboniso orhabaxa wokusingqongileyo (umz. ngenxa yokuqulatha inani elincinane lemisebenzi yesiseko), amandla awo okuqikelelwa kwexabiso lokugqibela akachanekanga njengalawo amanqanaba aneenkcukacha. Ngamanye amazwi, emva koqeqesho olubanzi ukuqiniseka okuhambelana namaxabiso aqikelelweyo kusezantsi kumanqanaba asezantsi olawulo xa kuthelekiswa namanqanaba aphezulu. Ke ngoko, ngokufunda okuqhubelekayo, amanqanaba asezantsi olawulo oluphezulu athathela kulo ulawulo lokhetho lwezenzo, njengoko ukungaqiniseki kwabo kuncipha kancinci kancinci. Oku kuvumelana nemigca emininzi yobungqina obubonisa ukulawulwa okuqhubekayo kwe-dorsal phezu kwe-ventral striatum kulawulo lokufuna iziyobisi (kunye nokufuna imbuyekezo yendalo) [8], [30], [31].
iziphumo
Ukungahambelani koqingqo-maxabiso oluphezulu kuvela phantsi kweziyobisi kodwa hayi imbuyekezo yendalo
Ngokuchaseneyo nemodeli yangaphambili yokomeleza ukufunda okusekwe kwimodeli yokukhobokisa [9]-[13] ezisekelwe kwindlela yesigqibo-nkqubo enye, i-akhawunti yethu yakhelwe phezu kwenkqubo-sikhokelo yeenkqubo ezininzi zokunxibelelana. Ngenxa yoko, nangona umfuziselo wesiphumo sechiza kwisiginali yempazamo yoqikelelo kwimodeli yethu iyafana nedlulileyo. [9]-[12], kuphumela kwimiphumo eyahlukileyo ngokusisiseko. Ukonyuka kwe-dopamine okwethutyana kweziyobisi konyusa impazamo yokuqikelela kwangoko kwinqanaba ngalinye lolawulo kwaye ngenxa yoko, ingenisa umkhethe, , ekudluliselweni kolwazi ukusuka kwelinye inqanaba lokutsalwa ukuya kwelinye, ecaleni kwendlela erhabaxa ukuya kwi-fine yolawulo. Olu tyekelo lubangela ixabiso le-asymptotic lokufuna iziyobisi kwinqanaba elinikiweyo iiyunithi eziphezulu kunomnye umaleko ongabonakaliyo (Umzobo 2B). Ukuqokelelwa kwezi zintlukwano ecaleni kwe-rostro-caudal axis iqhubela phambili ngokuqhubekayo iyantlukwano ebalulekileyo kwixabiso leendlela zokuziphatha zokufuna iziyobisi phakathi kwezinto eziphezulu kunye nezisezantsi zolawulo lwemigangatho. Ngaloo ndlela, nangona kulandelwa isohlwayo esinamandla, ixabiso lokuziphatha okuhambelana neziyobisi lihlala lilungile kwi-loops yemoto ephantsi, ngelixa liba libi kumanqanaba okuqonda. Ngamanye amagama, imodeli iqikelela ukuba ukuqokelelana kwesiphumo seziyobisi kwi-spirals ye-DA yonyusa ixabiso lokufuna iziyobisi kwimikhwa yenqanaba lemoto ukuya kwi-amplitude ephezulu kangangokuba nesohlwayo esinamandla sendalo asiyi kukwazi ukusehlisa ngokwaneleyo. Sicebisa ukuba oku kucacisa ukungangqinelani phakathi kovavanyo lokuqonda kunye nomgangatho ophantsi wokuziphatha okunxulumene neziyobisi kumakhoboka. Ngamanye amazwi, sicebisa ukuba ukufuna ichiza elinyanzelekileyo kunye nokwehliswa kakhulu kwe-elasticity kwiindleko ezinxulumene noko kuvela kwimpembelelo yekhemesti yechiza lokuqweqwedisa indlela exhomekeke kwi-dopamine ehambisa ulwazi phakathi kwamanqanaba olawulo lwezigqibo.
Umzobo 2. Ukukhuthaza ukutya vs. ichiza kumanqanaba ahlukeneyo okukhutshwa (iziphumo zokulinganisa).
Kwizilingo zokuqala ze-150 apho kungekho sohlwayo silandela umvuzo, ixabiso lokufuna imbuyekezo yendalo kuwo onke amanqanaba aguqukela kwi-10 (A). Kwimeko yeziyobisi, nangona kunjalo, isiphumo esithe ngqo se-pharmacological yechiza (, isethwe kwi) iziphumo zexabiso le-asymptotic kwinqanaba ngalinye ukuba libe iiyunithi eziphezulu kunezo zomgangatho omnye ophezulu wokutsalwa (B). Ke, xa kulandelwa sisohlwayo, ngelixa iilophu zokuqonda ngokuchanekileyo zinika ixabiso elibi kukhetho lokufuna iziyobisi, iilophu zomgangatho wemoto zifumanisa ukufuna ichiza kunqweneleka (ixabiso elilungileyo). Iigophe kulo mzobo zibonisa ukuguquguquka kwamaxabiso kwisilwanyana "esinye" esifanisiweyo kwaye ke, akukho lucazululo lwamanani olusebenzayo.
I-doi: 10.1371 / journal.pone.0061489.g002
Ngelixa iziyobisi, kwimodeli yethu, zikhokelela kumaxabiso okungalinganiyo kuwo onke amanqanaba, ixabiso lembuyekezo yendalo liguqukela kwixabiso elifanayo kuwo onke amanqanaba, ngenxa yokunqongophala kwefuthe elithe ngqo le-pharmacological kwindlela yokubonisa i-DA.). Ngenxa yoko, akukho kungangqinelani okanye ukuxabisa kakhulu kumanqanaba aneenkcukacha kuya kuqwalaselwa kwimeko yembuyekezo yendalo (Umzobo 2A). Ukuxabisa kakhulu iimpendulo zokufuna iziyobisi kumanqanaba asezantsi olawulo kufuneka kubangele ukhetho olungaqhelekanga lwamachiza ngaphezu kwembuyekezo yendalo, kunye nokubandakanyeka kakhulu kwimisebenzi enxulumene neziyobisi.
Ukuphendula okwahlukileyo kwe-dopamine kwi-ventral ngokuchasene ne-dorsal striatum kwiimpawu ezinxulumene neziyobisi
I-Neurobiologically, iindima ezahlukileyo zemimandla ephantsi yokulala ekufumaneni nasekuboniseni indlela yokuziphatha yokufuna iziyobisi ithathe indawo ephambili kuphando lokulutha. Ubungqina obuguqukayo obuvela kwimizila eyahlukeneyo yophando bucebisa ukuba utshintsho lokuziphatha ukusuka ekuzonwabiseni ukuya kusetyenziso olunyanzelekileyo lweziyobisi lubonisa utshintsho lwe-neurobiological lokuxabisa ukusuka kwi-ventral ukuya kwi-dorsolateral striatum. [8], [33], [34], ehambelana nokutshintsha ukusuka kwingqiqo ukuya kumanqanaba aneenkcukacha kumzekelo wethu. Ngokungqinelana nemodeli yethu, i-DA ejikelezayo inethiwekhi edibanisa i-ventral ukuya kwimimandla eqhubekayo ye-dorsal ye-striatum iboniswa ukudlala indima ebalulekileyo kolu tshintsho. [25].
Kuphononongo oluphambili lwamva nje uWilluhn et al. [17] ivavanye ipateni yokukhutshwa kwe-dopamine ekuphenduleni kwizinto ezinxulumene neziyobisi kwi-ventral kunye ne-dorsolateral striatum yeempuku kwiiveki ezintathu zokufumana i-cocaine. Ukusebenzisa i-voltammetry ye-scan ekhawulezayo ye-cyclic, eyona nto ibalulekileyo yayikukuba i-DA efflux eyenziwe nge-cue kwi-ventral striatum ivela nasemva koqeqesho oluncinci kakhulu. Ngokwahlukileyo, i-dorsolateral striatum ibonise i-cue-triggered DA efflux kuphela emva koqeqesho olubanzi, kwaye uphuhliso lwale pateni yokukhulula lwanyamalala xa i-ventral striatum ibonakaliswe kwi-ipsilateral hemisphere.
Kuba isisombululo sexeshana se-voltammetry ekhawulezayo yokuskena sithatha ukuguquguquka okungaphantsi koxinzelelo, iphethini ephawulweyo ye-DA efflux kufuneka ibalulwe kuphawu lwe-DA "phasic" kwaye ke, kuphawu lwempazamo yokuxela kwangaphambili, ngokwethiyori ye-RL ye-dopamine. [24]. Ngokutsho kwethiyori ye-RL, umqondiso wempazamo yokuqikelela ekujongeni uvuselelo olungalindelekanga ulingana nexabiso elivuzayo eliqikelelwa sisivuseleli. Ke ngoko, ukukhutshwa kwe-DA okubangelwa yicue kuyalingana nexabiso elixelwe kwangaphambili yile cue.
Ngokubhekiselele koku, isakhelo sethu soluhlu lwemigangatho sibonelela ngengcaciso esesikweni yepateni yokwahluka kwe-ventral ngokuchasene ne-dorsal striatal striatal DA efflux exeliweyo [17]. Ixabiso eliqikelelweyo sisica esinxulunyaniswa neziyobisi kumanqanaba okuqonda abstract yolawulo lolawulo nyuka ngokukhawuleza kumanqanaba okuqala oqeqesho (Umzobo 2B), ngenxa yobukhulu obuphantsi bengxaki yokufunda kumanqanaba aphezulu okuthatha izinto. Ngenxa yoko, imodeli yethu ibonisa ukuba i-DA efflux eyenzelwe i-cue kufuneka ijongwe kwi-ventral striatum nasemva koqeqesho olulinganiselweyo (Umzobo 3). Kumanqanaba angaphezulu okumelwa, nangona kunjalo, inkqubo yokufunda iyacotha (Umzobo 2B), ngenxa yobukhulu obuphezulu besithuba sengxaki, kunye nokuxhomekeka ekufundeni kumanqanaba angaphezulu angabonakaliyo ngokusebenzisa i-DA spirals. Ngenxa yoko, i-DA efflux eyenzelwe i-cue kwi-dorsolateral striatum kufuneka ikhule kancinci kwaye ibonakale kuphela emva koqeqesho olubanzi (Umzobo 3).
Umzobo 3. I-Dopamine efflux kwiindawo ezahlukeneyo eziphantsi kwe-striatal ukuphendula kwiimpawu ezinxulumene neziyobisi (iziphumo zokulinganisa).
Ngokuhambelana nedatha yovavanyo [17], imodeli ibonisa (ikholamu yasekhohlo) ukuba ukuphendula kwiimpawu ezinxulumene neziyobisi, kuya kubakho i-dopamine efflux kwi-ventral striatum, emva koqeqesho olulinganiselweyo nolubanzi. Kwimimandla engaphantsi kwe-dorsolateral, nangona kunjalo, i-DA efflux ekhutshiweyo iya kukhula ngokuthe ngcembe ngexesha lokufunda. Imodeli iqikelela (ikholamu yesibini ukusuka ekunene) ukuba oku kulibaziseka kophuhliso lwe-DA efflux kwi-dorsal striatum kuxhomekeke kuqhagamshelo lwe-serial oluxhomekeke kwi-DA oludibanisa i-ventral ne-dorsal striatum. Oko kukuthi, njengesiphumo sokuqhawula i-spirals ye-DA, ngelixa impendulo ye-DA e-cue-elicited ihlala injalo kwi-ventral striatum, yehla kakhulu kwi-dorsolateral striatum. Ngapha koko, imodeli iqikelela (ikholamu yesithathu ukusuka ekunene) iziphumo ezifanayo ze-DA efflux kwi-dorsolateral striatum kwimeko ye-lesioned ventral striatum. Okokugqibela, ukuba emva kokudityaniswa okubanzi kweziyobisi kwizilwanyana ezingagungqiyo, isohlwayo silandela ichiza, imodeli iqikelela (ikholamu yasekunene) ukuba isiphumo esinxulumene neziyobisi sikhokelela ekuthinteleni umlenze we-ventral we-DA spirals, nasemva koqeqesho oluncinci. Kweminye imimandla yedorsal, nangona kunjalo, i-DA efflux yehla ngokucothayo ngexesha lokufunda, kodwa iya kuhlala inethemba, nasemva kokubhanqa okubanzi kwesohlwayo esohlwaywa ngamachiza. Idatha echazwe kulo mzobo ifunyenwe kwisilwanyana "esinye" esifanisiweyo kwaye ngoko, akukho lucazululo lwamanani olusebenzayo.
I-doi: 10.1371 / journal.pone.0061489.g003
Ngapha koko, imodeli yethu icacisa ubungqina kwi [17] ukuba ukulibaziseka kophuhliso lwe-DA efflux kwi-dorsolateral striatum kuxhomekeke kwi-ventral striatum (Umzobo 3). Kwimodeli yethu, isilonda esilingeneyo esilingeneyo se-ventral striatum (inqanaba lokuxatyiswa kwe-abstract kwimodeli) linciphisa kakhulu ixabiso eliqikelelweyo leyeza kumanqanaba aneenkcukacha kwi-ipsilateral hemisphere kwaye ke, yehla kakhulu inqanaba le-DA efflux. Ukuze senze umzekelo wesilonda se-ventral striatum, silungisa nje ixabiso lazo zonke izivuseleli kwinqanaba eliphezulu leqela ukuya kwiqanda.
Ngokufanayo, imodeli yethu iqikelela ukuba ukuphuhliswa kwe-phasic DA yokubonisa kwi-dorsolateral striatum kuxhomekeke kwimfezeko ye-DA spiraling circuit (Umzobo 3). Ngapha koko, ukuqhawuka konxibelelwano kwisekethe ejikelezayo ye-DA kwimodeli yethu kunciphisa unxibelelwano kuwo wonke amanqanaba okutsalwa, nto leyo ethintela ukuqokelelwa komkhethe owenziwe ngamachiza kumqondiso wokomeleza, ecaleni kwamanqanaba olawulo lwezigqibo. Ukwenza umzekelo wokuqhawulwa koqhagamshelo kwi-DA exhomekeke kwisekethe yesiriyali ye-ventral ukuya kwi-dorsal striatum, sibamba inqanaba ngalinye lokutsalwa ukubala umqondiso wempazamo yengqikelelo kwindawo (njengakwi-equation 3), ngaphandle kokufumana ixabiso lelizwe elihambele phambili okwexeshana ukusuka phezulu ngokukhawuleza. inqanaba lokuthatha.
Ngaphaya koko, imodeli iqikelela ukuba ipateni ye-DA efflux ye-cue-elicited iya kutshintsha ukuba emva koqeqesho olubanzi kunye ne-cocaine kunye ne-cocaine ehambelana neendlela, njengoko kuvavanyo olungasentla, umntu uqala ukubhangqa ukuhanjiswa kwe-cocaine ngesohlwayo esinamandla. Siqikelela ukuba i-DA efflux ekuphenduleni i-cocaine ehambelana ne-cocaine kufuneka yehle ngokukhawuleza ngaphantsi kwesiseko kwi-ventral striatum. Kwi-dorsolateral striatum, nangona kunjalo, ukukhutshwa kwe-DA kwe-cue kufuneka kuhlale ngaphezulu kwesiseko (Umzobo 3) ngokulibaziseka okunokwenzeka okulibaziseko. Oku kubonisa ukunika ixabiso elivumayo le-subjective kwi-stimulus yeziyobisi kumanqanaba aneenkcukacha, ngaphandle kokubi (ngaphantsi kwesiseko) amaxabiso kumanqanaba okuqonda. Kuyaphawuleka ukuba oku kuqikelelwa kuxhomekeke kwingcinga yokuba isohlwayo siphathwa yingqondo njengomvuzo ongalunganga. Le ngcinga iyinto ephikisanayo: ixhaswa ngokucacileyo zizifundo zovavanyo [35], ukanti kwaxutyushwa ngenye indlela ngabanye [14], [36]. Ngaphandle kolu qikelelo, eminye imiba yemodeli ayixhomekeke ekubeni isohlwayo sifakwe ngekhowudi yi-dopamine okanye yenye inkqubo yokubonisa.
Irejimeni yoqeqesho esetyenziswa nguWilluhn et al. [34] ayandiswa ngokwaneleyo ekuveliseni isinyanzelo sokuziphatha ekufuneni iziyobisi, ebonakala ngokungabi naluvelwano kwizohlwayo ezinxulumene neziyobisi. [37], [38]. Ke, umbuzo ophambili ekufuneka uphendulwe yintoni ubudlelwane phakathi kokulibaziseka kokuphuhliswa kwempendulo ye-DA kwi-DLS, kunye nophuhliso lwasemva kwexesha lokuphendula okunyanzelekileyo. Ngokwemodeli yethu, ukuziphatha okunyanzelekileyo kufuna kungekuphela nje ukuxatyiswa okugqithisileyo kokukhethwa kweziyobisi kumanqanaba aphantsi olawulo, kodwa kunye nokudluliselwa kolawulo lokuziphatha ukusuka kwingqondo engabonakaliyo ukuya kwiinkqubo zesiqhelo ezisezantsi. Ubungakanani bexesha lezi nkqubo zimbini zixhomekeke ngokuyinxenye omnye komnye: inkqubo yoqikelelo olungaphezulu ixhomekeke kwisiginali yempazamo yokuxela kwangaphambili, ngelixa ukuhanjiswa kolawulo lokuziphatha nako kuxhomekeke ekungaqiniseni okunxulumene noqikelelo lwexabiso. Yiyo loo nto, ukuxatyiswa okugqithisileyo kweempawu ezinxulumene neziyobisi kumanqanaba aphantsi olawulo lwemigangatho kungandulela ukutshintshwa kolawulo kwindlela yokuziphatha ukusuka phezulu ukuya ezantsi kuluhlu lwemigangatho. Izikali zexesha ngqo ezi nkqubo zimbini zixhomekeke kwireyithi yokufunda nakwingxolo ekhoyo kumanqanaba ahlukeneyo, ngokulandelelanayo (jonga Ifayile yeS1 ngolwazi olongezelelweyo). Ngamanye amazwi, kusenokwenzeka ukuba i-cue-induced dopamine efflux kwi-DLS inokukhula kakhulu ngaphambi kokuba kubonakaliswe indlela yokuziphatha enyanzelekileyo.
Iimpembelelo zokuziphatha zokuxatyiswa okungangqinelaniyo kumachiza xa kuthelekiswa nembuyekezo yendalo
Ngokuziphatha, kwimodeli yethu, ukuba isohlwayo sidityaniswe neziyobisi kumanqanaba okuqala okusebenzisa iziyobisi ngokuzithandela, ixabiso elingabonakaliyo lempendulo yokufuna iziyobisi liba libi ngokukhawuleza. Kucingelwa ukuba ukufuna iziyobisi kulawulwa ngamanqanaba angekho ngqiqweni kula manqanaba okuqala, uphononongo olubi olungelulo lokhetho lwechiza lwenza ukuba umntu angakwazi ukuphinda afumane inyathelo lesenzo. Oku kuya kuthintela ukudityaniswa kokukhethwa okunamandla kwinqanaba elisezantsi ngamachiza ekuhambeni kwexesha. Ke, imodeli icacisa ukuqina kokhetho lwechiza kwiindleko ngexesha lamanqanaba okuqala okusetyenziswa kweziyobisi, kodwa hayi emva kokusetyenziswa okungapheliyo. Ngokungaguqukiyo, iimodeli zezilwanyana zokukhobokisa zibonisa ukuba ukungavani kweempendulo zokufuna iziyobisi kwiziphumo ezinobungozi ezinxulumene neziyobisi kukhula kuphela emva kokuzilawula ixesha elide kweziyobisi, kodwa kungathintelwa ukusetyenziswa kweziyobisi. [37], [38]. Ngokuchaseneyo nethiyori yethu, iimodeli zangaphambili zokubala zokulutha [9], [10] zichasene ngokuthe ngqo nalo mzimba wobungqina, kuba ziqikelela ukuba iziphumo ezibi zokuziphatha ezilandela ngokukhawuleza ukusetyenziswa kweziyobisi, azinampembelelo zikhuthazayo nakwinqanaba lokuqala lokufumana iziyobisi (bona Ifayile yeS1 ngolwazi olongezelelweyo).
Imodeli yethu iqhubela phambili ukwenzeka kwesiphumo sokuthintela kwiziphumo zamachiza [39]. Ukuvinjwa yinto yokumisela imeko apho ukudibanisa kwangaphambili kwe-stimulus A kunye nesiphumo sithintela ukubunjwa kobudlelwane phakathi kwe-stimulus eyahlukileyo ye-B kunye neso siphumo kwisigaba soqeqesho esilandelayo, apho zombini i-A kunye ne-B zinikezelwa phambi kokunikezelwa kwesiphumo. [40]. Iziphumo zokulinganisa imodeli yethu kuyilo lovavanyo lwePavlovian (bona Ifayile yeS1 ngolwazi olongezelelweyo kuguqulelo lwePavlovian lomzekelo) lubonisa ukuba kuzo zombini iimeko zembuyekezo yendalo kunye neziyobisi, xa ixabiso eliqikelelweyo kwinqanaba elithile lolawulo lifikelela kwisimo salo esizinzileyo (kunokuba likhule ngokungenamda), akukho kufunda ngakumbi okwenzekayo apho. inqanaba, ukusukela ukuba isignali yempazamo yengqikelelo yehlile ukuya kwiqanda (Umzobo 4). Ke, ukudibanisa inkuthazo entsha kunye nomvuzo osele uxelwe kwangaphambili kuya kuthintelwa. Ubungqina bokuziphatha obubonisa umphumo wokuthintela ohambelana neziyobisi kunye nabaqinisekisi bendalo [39] isetyenziswe njengengxoxo enkulu yokugxeka imodeli ye-computational ecetywayo ngaphambili ye-dopamine [9]. Apha sibonise ukuba ukugxila kubume be-hierarchical yokumelwa kunye ne-dorsal-ventral spiraling dopamine loop umbutho unokuphendula ngedatha yokuvala, ngaloo ndlela uthintele oku kugxekwa (bona Ifayile yeS1 ngolwazi olongezelelweyo).
Umzobo 4. Ukuthintela umphumo wendalo vs. imbuyekezo yeziyobisi.
Imodeli iqikelela ukuba ukuthintela kwenzeka kwimivuzo yendalo (A) kunye neziyobisi (B), kuphela ukuba ixesha loqeqesho lokuqala "lubanzi", kangangokuba i-stimulus yokuqala iqikelele ngokupheleleyo ixabiso lesiphumo. Emva koqeqesho "oluphakathi", amanqanaba okuqonda aguquguqukayo aqikelele ngokupheleleyo amaxabiso kwaye ngaloo ndlela, athintele ukufunda okungakumbi. Nangona kunjalo, ukufunda kusasebenza kwiinkqubo ezikwinqanaba elisezantsi xa inqanaba loqeqesho lwesibini (ukunikezelwa ngaxeshanye kwazo zombini izivuseleli) siqala. Ke, imodeli yethu iqikelela ukuba uqeqesho lokuqala oluphakathi kuvavanyo oluthintelayo olunemivuzo yendalo luya kukhokelela ekungahambelani kwengqondo / kokuziphatha. Idatha echazwe kulo mzobo ifunyenwe kwisilwanyana "esinye" esifanisiweyo kwaye ngoko, akukho lucazululo lwamanani olusebenzayo.
I-doi: 10.1371 / journal.pone.0061489.g004
Njengoko bekutshiwo ngaphambili, imigca emininzi yobungqina ibonisa ukulawulwa okuqhubekayo kwe-dorsal phezu kwe-ventral striatum kulawulo lokuziphatha ngexesha lokufunda. [8], [31], [32]. Ukutolikwa kwimvelaphi yobo bungqina, ixabiso elingalungelelananga lokukhangela iziyobisi kulo lonke ulawulo lukwachaza iinzame ezingaphumelelanga zamakhoboka okunciphisa ukusetyenziswa kweziyobisi emva kwamava exesha elide ngechiza, xa ulawulo kukhetho olunxulumene neziyobisi lutshintshile lusuka kwingqondo ukuya kwesezantsi- iinkqubo zenqanaba lesiqhelo. Oku kuphakama kweenkqubo ezilawulwa ngamachiza ngokwemvelo kukhokelela ekuziphatheni ngokungaguqukiyo kwiindleko ezinxulumene neziyobisi (ukufuna iziyobisi okunyanzelekileyo), mhlawumbi kukhatshwa nempazamo ozichazayo. Kwimeko yembuyekezo yendalo, nangona kunjalo, imodeli yethu iqikelela ukuba nangona i-inelasticity yokuziphatha inyuka ngexesha lokufunda, njengoko kungekho xabiso-ukungahambelani kukhula kuwo wonke amanqanaba olawulo, izohlwayo ezinxulumene nomvuzo ziya kuthi ekugqibeleni zithintele ukufuna umvuzo.
Imodeli yethu igxile kuvavanyo lwezenzo kuluhlu lwesigqibo "ekucingelwa ukuba sinikwe", kwaye ishiya ecaleni indlela iinketho ezingabonakaliyo kunye neendlela ezisezantsi ezihambelanayo ezifunyenwe ekuqaleni ngexesha lophuhliso. Ukufumanisa ulawulo lwesigqibo kucetywa ukuba kube yinkqubo esezantsi ukuya phezulu, ephunyezwe ngokudibanisa iintshukumo ezilandelelanayo zomgangatho ophantsi kunye nokwakha iinketho ezingaphaya kwengqondo. [41]. Le nkqubo, ekucingelwa ukuba idlula kwi-dorsal ukuya kwi-ventral striatum, ikwicala elichaseneyo lendlela yokhuphiswano ecetywayo apha, yokulawula indlela yokuziphatha.
ingxoxo
Ubungqina obukhulayo bobungqina bendima yokwahluka kwemimandla eyahlukeneyo yokulala ekukhotyokisweni budla ngokutolikwa kwisakhelo senkqubo yesiqhelo kunye ne-dichotomy. [8], [14], [34]. Indlela yokwenza izigqibo ngokoluhlu oluphezulu esiyisebenzisayo apha iyahambelana neeakhawunti zenkqubo ezimbini. Ngelixa inkqubo yenkqubo-mbini ijongene ne-algorithms ezahlukeneyo (imodeli-free vs. imodeli-base [30]) ukusombulula ingxaki enye, isakhelo se- hierarchical RL siqwalasela kumelo olwahlukeneyo lwengxaki enye kumanqanaba ahlukeneyo othatho lwexeshana. Kwithiyori, mhlawumbi isiqhelo okanye i-algorithm ejoliswe ekujoliswe kuyo inokusombulula nganye yezi zibonakaliso ezahlukeneyo zengxaki. Kwimodeli yethu, ukuqokelelwa kocalucalulo olubangelwa ngamachiza ngaphezulu kwe-DA spirals kwenzeka kwindawo apho i-algorithm yoqikelelo lwexabiso ingenamodeli (ukufunda umkhwa). Nangona kunjalo, oku akuthinteli ubukho benkqubo esekwe kwimodeli esebenza kumanqanaba aphezulu olawulo. Umntu unokubandakanya ngokulula ixabiso elixhomekeke kwi-PFC-exhomekeke kwinjongo-ejolise kwinjongo kunye nenkqubo yesigqibo kwimodeli ngokucinga ukuba izenzo kumanqanaba aphezulu okukhutshwa zivavanywa yinkqubo ejoliswe kwiinjongo. Ngelixa olo nxunguphalo alutshintshi uhlobo lweziphumo ezithiwe thaca kulo mbhalo-ngqangi, ukuguquguquka kwawo okongezelelekileyo ekuchazeni omnye umba wokulutha kushiywe kwizifundo ezizayo. Enyanisweni, kwimodeli yethu, kungakhathaliseki ukuba kukho inkqubo ethe ngqo yenjongo okanye ayikho, ukungafani kwixabiso le-asymptotic lokufuna iziyobisi phakathi kwezinto ezimbini ezigqithisayo zolawulo lukhula kunye nenani lamanqanaba ezigqibo ezilawulwa yinkqubo "yesiqhelo". .
Ngokokukhanya kwethiyori yethu, ukuphinda kuphinde kujongwe njengokuvuselelwa kwemikhwa ye-maladaptive eleleyo yenqanaba lemoto, emva kwexesha lokongamela amanqanaba okuqonda. Ngapha koko, umntu unokucinga ukuba ngenxa yonyango lokuqonda (kumakhoboka omntu) okanye ukupheliswa ngenkani (kwimizekelo yezilwanyana zokuziyeka), ixabiso eliphezulu lokufuna iziyobisi kwinqanaba elineenkcukacha lolawulo alicinywa, kodwa libe lilele ngenxa yokungalali. ukutshintsha ulawulo ubuyele kumanqanaba okuqonda. Kuba indlela yokuziphatha enxulumene neziyobisi inobuntununtunu kwiziphumo ezibi kumanqanaba angabonakaliyo, kungoko ukufuna iziyobisi kunokuphetshwa ukuba nje iinkqubo zokuqonda ezikwinqanaba eliphezulu zilawula indlela yokuziphatha. Umntu unokude acinge ukuba iinkqubo ezithandwayo zamanyathelo ali-12 (umzekelo, i-Alcoholics Anonymous, iNarcotics Anonymous, njl. njl.) zisebenza ngokuyinxenye ngokufuna ukuba abathathi-nxaxheba bavume ukungangqinelani kwendlela yabo yokuphila enxulumene neziyobisi, ngaloo ndlela bexhobisa amanqanaba okuqonda abstract ukuba asebenzise ulawulo olucacileyo phezu kwabo. ukuziphatha. Iimeko ezicinezelayo okanye ukuchaneka kwakhona kwiziyobisi (i-priming) kunokucingelwa njengemingcipheko eyenza buthathaka ukongamela amanqanaba angabonakaliyo ngaphezulu kokuziphatha, okunokubangela ukuvela kwakhona kweempendulo zokufuna iziyobisi (ngenxa yexabiso elifihlakeleyo eliphezulu elingenangqondo. ).
Isishwankathelo, siphakamisa i-akhawunti ehambelanayo yeziganeko ezininzi, ezibonakala zingafani zokukhotyokiswa ziziyobisi. Imodeli yethu ibonelela nge-akhawunti eqhelekileyo yedatha malunga neendima ezihlukeneyo ze-ventral vs. dorsal striatal circuits ekufumaneni iziyobisi kunye nokusebenza komkhwa, kunye nendima ekhethiweyo yoqhagamshelwano lwe-DA oluqhubela phambili kwiziphumo zeziyobisi ngokuchasene nabaqinise bendalo. Okona kubaluleke kakhulu, sibonisa indlela i-pathology eyenzelwe iziyobisi kwi-ventral-to-dorsal DA imiqondiso ethoba ulwazi olukhuthazayo phantsi kolawulo lwengqondo enokukhokelela kwiyantlukwano phakathi kwezimo zengqondo zomlutha malunga nokufuna iziyobisi kunye nento abayenzayo ngokwenene. Ngokucacileyo, imodeli yethu ayifuni, kwaye ayenzelwanga, ukunika ingxelo epheleleyo yokukhotyokiswa ziziyobisi. Ukucacisa eminye imiba engachazwanga yokulutha kufuna ukudibanisa nezinye iinkqubo ezininzi zobuchopho ezibonakaliswe ukuba zichatshazelwa ziziyobisi zokuxhatshazwa. [42]. Indlela yokudibanisa iinkqubo ezinjalo kuthungelwano olusesikweni lokubala ihleli ingumxholo wophando olungaphaya.
Ukuxhasa ulwazi
Umzobo S1,Isampulu yesigqibo soluhlu olunamanqanaba amahlanu okutsalwa. Umzobo S2, Isekethe ye-neural ehambelanayo kwezi zintathu zixoxiwe nge-algorithms yokufunda ngexabiso sisakhiwo sesigqibo soluhlu. A, Ukusebenzisa i-algorithm ye-TD-learning (i-equation S7), isignali yephutha lokubikezela kwinqanaba ngalinye le-abstraction ibalwa ngokuzimeleyo kwamanye amanqanaba. B, Kumzekelo ocetywayo nguHaruno noKawato (4) (i-equation S8), ixabiso lexesha eliphakamileyo lexesha livela kwinqanaba eliphezulu lokukhupha. C, kwimodeli yethu (i-equation S9) ixabiso lexesha eliphakamileyo lexeshana lithatyathelwa indawo ngokudityaniswa komvuzo kunye nexabiso le-Q lesenzo esenziweyo kwinqanaba eliphezulu lokukhupha. Umzobo S3, Imodeli yethu iqikelela iindawo ezahlukeneyo zesenzo samachiza kwisekethe yokufunda umvuzo: iisayithi ze-1 ukuya kwi-3. Iziyobisi ezichaphazela indawo ze-4 ukuya kwi-6, ngokuchaseneyo, aziyi kubangela iipatheni zokuziphatha kunye ne-neurobiological eziveliswa ngokulinganisa imodeli yamachiza, kodwa iya kuvelisa iziphumo ezifanayo kwimeko yembuyekezo yendalo. Umzobo S4, Umsebenzi osetyenziselwa ukulinganisa indlela yokhuphiswano olusekwe ekungaqinisekisini phakathi kwamanqanaba olawulo lolawulo lokuziphatha. Umzobo S5, Iziphumo zokulinganisa, ezibonisa utshintsho oluthe chu kulawulo kwindlela yokuziphatha ukusuka phezulu ukuya kumanqanaba asezantsi olawulo. Q(imiz,a) kwaye I-USA) bonisa ixabiso eliqikelelweyo kunye nokungaqiniseki kwezibini zezenzo zikarhulumente, ngokulandelelanayo.
I-doi: 10.1371 / journal.pone.0061489.s001
(PDF)
Imibulelo
Siyabulela uS. Ahmed noP. Dayan ngeengxoxo ezibalulekileyo, kunye noM. Reinoud, D. Redish, N. Daw, E. Koechlin, kunye no-A. Dezfouli ngokubeka izimvo kwi-manuscript.
Umbhali Wemivuzo
Uyilwe kwaye wayila imifuniselo: MK. Wenza imifuniselo: MK. Uhlalutye idatha: MK BG. Ii-reagents ezinikezelweyo / izixhobo / izixhobo zokuhlalutya: MK. Ubhale iphepha: MK BG.
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