I-Orbitofrontal Cortex Decision Ukwenza Futhi Isidakamizwa Somuthi (2006)

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Uhlobo lokugcina oluhleliwe lomshicileli luyatholakala at I-Trends Neurosci

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abstract

I-cortex ye-orbitof Pambal, njengengxenye ye-cortex yangaphambili, ifakwa umfutho emsebenzini wokuphatha. Kodwa-ke, ngaphakathi kulesi sifunda esibanzi, i-orbitof Pambal cortex ihlukaniswa ngephethini yayo eyingqayizivele yokuxhuma nezindawo zokufunda ezibalulekile ezihlangene ze-subcortical, ezifana ne-basolateral amygdala kanye ne-nucleus accumbens. Ngokwalesi sixhumanisi, i-orbitofrontal cortex ibekwe endaweni eyodwa ukusebenzisa ulwazi oluhlangene ukufezekisa ikusasa, futhi isebenzise inani lemiphumela ebonwayo noma elindelekile yokuqondisa izinqumo. Lokhu kubuyekezwa kuzodingida ubufakazi bamuva nje obuxhasa lesi siphakamiso futhi kuzobhekwa nobufakazi bokuthi ukulahleka kwalesi siginali, njengomphumela wezinguquko ezibangelwa yizidakamizwa kule mibuthano yobuchopho, kungahle kube nesizathu sokwenza izinqumo okungalungile okubonisa ukuthi umlutha wezidakamizwa.

Isingeniso

Amandla ethu wokwenza okulindelwe mayelana nokufisa noma inani lemicimbi ezayo kungenzeka ngaphansi komzwelo nokuziphatha kwethu. Eqinisweni, imisebenzi emibili ebanzi yabiwe ngokuhlangene ngokwakhiwa kwalokho okulindelwe. Ngakolunye uhlangothi, okulindelwe kuqondisa indlela esiziphatha ngayo ngokushesha, kusivumele ukuba siphishekele izinjongo futhi sigweme ukulimala okungase kube khona. Ngakolunye uhlangothi, okulindelwe kungaqhathaniswa nemiphumela yangempela yokwenza lula ukufunda ukuze indlela yokuziphatha kwesikhathi esizayo ibe nokuguquguquka. Yomibili le misebenzi idinga ukuthi imininingwane mayelana nemiphumela elindelekile igcinwe kwimemori ukuze iqhathaniswe futhi ihlanganiswe nolwazi mayelana nesimo sangaphakathi nezinhloso zamanje. Inqubo enjalo yokuhlanganisa iveza isibonakaliso esizobhekisa kulo njengokulindelekile komphumela, igama elisetshenziswa isikhathi eside abafundisi bezenkolo ukuthi babhekisele ekumeleleni kwangaphakathi kwemiphumela okungenzeka ukuthi ilandele isenzo esithile [1]. Ukuphazamiseka kwesiginali enjalo kungalindeleka ukuthi kudale ubunzima obukhulu, emikhakheni yomibili yokwenza izinqumo eziguqukayo futhi ufunde emiphumeleni emibi yezinqumo. Kulesi sibuyekezo, okokuqala sichaza ubufakazi bamuva bokuthi i-orbitofrontal cortex (OFC) idlala indima ebalulekile esizukulwaneni nasekusetshenzisweni kokulindelwe kwemiphumela. Ngemuva kwalokho, sizoxoxa ngobufakazi bamuva nje ukuthi izinqumo ezingalungile ezibonisa ukuthi umlutha wezidakamizwa zibonisa, ngokwengxenye, ukuphazamiseka kwalesi siginali ngenxa yezinguquko ezibangelwa izidakamizwa e-OFC nasezindaweni zobuchopho ezihlobene.

Umsebenzi we-Neural ku-OFC nokuziphatha okuncike ku-OFC kukhombisa iqhaza elibalulekile le-OFC esizukulwaneni sokulindelwa kwemiphumela

Amandla wokugcina ulwazi ukuze lusetshenziswe, luhlanganiswe nolunye ulwazi bese lusetshenziselwa ukuqondisa indlela yokuziphatha luye lwachazwa ngokuhlukahlukene njengokusebenza kwenkumbulo, ukubhala noma ukumelela, futhi kuncike ngokunamandla kwi-cortex yokuqala [2]. Ngaphakathi kwe-cortex yangaphambili, i-OFC, ngokuxhumana kwayo nezindawo ezinemilenze, isendaweni eyingqayizivele ukunika amandla ulwazi oluhlangene mayelana nemiphumela noma imiphumela yokufinyelela imemori yokumelwa (Ibhokisi 1). Ngempela inani elandayo locwaningo libonisa ukuthi isixhumi esilinganayo se-neural senani elilindelekile lemiphumela likhona futhi mhlawumbe senziwe ku-OFC. Isibonelo, izifundo zabantu ze-neuroimaging zibonisa ukuthi izinguquko zokugeleza kwegazi ku-OFC ngesikhathi sokulindelwa kwemiphumela elindelekile futhi lapho inani lomphumela olindelwe liguqulwa noma lingathunyelwa [3-6]. Lokhu kusebenze kubonakala kukhombisa inani lokukhuthaza lezi zinto futhi kuyabonakala lapho lolo lwazi lusetshenziselwa ukuqondisa izinqumo [7]. Le miphumela iphakamisa ukuthi ama-neurons ku-OFC akhuphula umsebenzi lapho imininingwane enjalo icutshungulwa. Ngakho-ke, umsebenzi we-neural ku-OFC owandulela umvuzo owandulelayo noma wezijeziso uyanda, ngokuvamisile kuboniswa amanani wokugqugquzela wale miphumela [8-11]. Isibonelo, lapho izinkawu zethulwe ngezimpawu ezibonakalayo ezidwetshwe ngemivuzo ethandwayo ehlukile, ama-neurons kumoto we-OFC ngokungakhethi ngokuya ngokuthi umphumela olindelekile ungumvuzo owuthandayo noma ongafuneki ngaphakathi kwalelo bhulokhethi lesivivinyo [10]. Ngaphezu kwalokho, uRoesch no-Olson [11] muva nje ukhombisile ukuthi ukudubula ku-OFC kulandelela amanye amamethrikhi athile wevelu yemiphumela. Isibonelo, ama-neurons asha ngomlilo ngokuhlukile ukuze athole umvuzo ngokuya ngosayizi wawo obulindelekile, isikhathi esilindelekile esidingekayo ukusithola kanye nemiphumela engemihle yokuphikisa ehambisana nokuziphatha okungafanele [11,12].

Ibhokisi 1. I-anatomy yesiyingi se-orbitofrontal ngamagundane nezimpawu

URose noWoolsey [53] siphakamise ukuthi i-cortex yokuqala ingachazwa ngokuqagelwa kwe-mediodorsal thalamus (MD) kunokuba kube yi-'stratiographic analog' [54]. Le ncazelo ihlinzeka ngesisekelo sokuchazwa kwezindlu ezisetshenziswa kuqala ezindlini zazo zonke izinhlobo. Kodwa-ke, ukufana okusebenzayo nokusebenzayo okuchaza kahle izindawo ezenzelwe abantu (Umzekeliso I waleli bhokisi).

Ku-rat, i-MD ingahlukaniswa ngezigaba ezintathu [55,56]. Ukuqagela okuvela ezingxenyeni ezikhethekile zezindondo neze-MD kuchaza isifunda esifaka izindawo ezi-orbital kanye ne-ventral and dorsal agranular cortices infular [55-58]. Lezi zifunda ze-MD ziklelinye zithola okuqondana ngqo kusuka e-amygdala, medial temporal lobe, ventral pallidum nasendaweni ye-ventral ehlukanisiwe, futhi zithola okokufaka okuvela ku-piriform cortex [55,56,59]. Le ndlela yokuxhumana ifana naleso se-MD esisendaweni ephakathi nendawo, esichaza ukuhlukaniswa kwangaphambili kwe-orbital ngezigaba zokuqala [60-62]. Ngakho-ke, isifunda esichaziwe endaweni ye-orbital ye-rat prefrontal cortex kungenzeka sithola okokufaka okuvela ku-thalamus efana kakhulu nokufika kwe-cortex ye-orbital yangaphambili. Ngokusekelwe, ngokwengxenye, kule ndlela yokufaka, izinkundla zokuqagela zezindondo zezindondo nezisendaweni ephakathi nendawo ezindaweni eziphansi zecort preortal cortex ziye zahlongozwa njengokuzazisa esifundeni se-orbitof Pambal [55,57,63-65]. Lezi zindawo ezinama-rodents zifaka phakathi i-dorsal ne-ventral agranular insort cortex, kanye nezindawo ze-lateral nezangaphakathi ze-orbital. Lo mqondo we-rat orbitofrontal cortex (OFC) awuhlanganisi i-cortex ye-medial noma ye-ventromedial orbital, elele odongeni lwe-medial ye-hemisphere. Lesi sifunda sinamaphethini wokuxhumana ne-MD nezinye izindawo ezifana kakhulu nezinye izifunda odongeni lwezindondo.

Olunye uxhumano olubalulekile luqokomisa ukufana phakathi kwamanani we-OFC ne-prC ye-OF. Mhlawumbe okuphawuleka kakhulu ukuxhumana kokubuyisana nenkimbinkimbi yesakhiwo se-amygdala (ABL), isifunda okucatshangwa ukuthi sibandakanyeka ezicini ezihlobene noma ezishukumisayo zokufunda [66-74]. Okwakamuva, lokhu kuxhumana kudluliselwe ekuchazeni ukufana okuthile kokuhlukunyezwa kokuziphatha okubangelwa ukulimala kwe-OFC noma i-ABL [14,17,75-77]. Ukuxhumeka okubuyisanayo phakathi kwe-amygdala ye-basolateral nezindawo eziku-rat ofC, ikakhulukazi i-agranular insular cortex [58,78-80], phakamisa ukuthi ukusebenzisana phakathi kwalezi zinhlaka kungabaluleka ngokufanayo ukuze kulawulwe imisebenzi yokuziphatha kumagundane. Ngaphezu kwalokho, kuzo zombili amagundane nezinduna, i-OFC ihlinzeka ngokuqagela okuqine okuqongelelwe kuma-nucleus accumbens, okudlula ngokufakwa ngaphakathi kwizakhiwo ze-limbic ezifana ne-ABL ne-subiculum [81-84]. Ukujikeleza okuqondile okuxhuma i-OFC, izinhlaka ze-limbic kanye ne-nucleus accumbens kuveza ukufana okuhlaba umxhwele kuzo zonke izinhlobo zezilwane eziphakamisa ukufana kokusebenzelana kokusebenza phakathi kwalezi zinto ezinkulu zebanga [81,84,85].

Umdwebo I

Ifayela elingaphandle eliphethe isithombe, umzekeliso, njll. Igama le-nto nihms52727f4.jpg

Ubudlelwano be-Anatomical be-OFC (eluhlaza okwesibhakabhaka) kumagundane nezinkawu. Ngokusekelwe kuphethini yabo yokuxhumana ne-mediodorsal thalamus (MD, eluhlaza okotshani), i-amygdala (i-orange) ne-striatum (epinki), izindawo ezise-orbital nezama-agranular insular ezingaphakathi kwe-rat preortal cortex ziyasizakala embonini ye-OFC yangaphambili. Kuzo zombili lezi zinhlobo, i-OFC ithola okokufaka okuqinile okuvela kuma-sensor cortices kanye nemininingwane ehlobene ne-amygdala, bese ithumela umphumela ohlelweni lwezimoto nge-striatum. Ibhokisi ngalinye libonisa isigaba esibonisa ukumelana. Izifinyezo ezingeziwe: i-AId, i-dorsal agranular insula; I-AIv, i-insral agranular insula; c, maphakathi; CD, caudate; LO, i-orbital ye-lateral; m, indondo; I-NAc, i-nucleus accumbens core; i-rABL, i-rostral basolateral amygdala; I-VO, i-ventral orbital, kufaka phakathi izifunda ezi-ventrolateral kanye ne-ventromedial orbital; I-VP, i-ventral pallidum.

Umsebenzi olindelekile ubonakala njengesici esivamile somsebenzi wokudubula e-OFC kuyo yonke imisebenzi eminingi lapho izehlakalo zenzeka ngokulandelana, futhi ngenxa yalokho, i-oda (Ibhokisi 2). Okubalulekile, noma kunjalo, lezi zimpendulo ezikhethiwe zingabonakala ngaphandle kwezimpawu zokubonisa uphawu, futhi zitholakala njengoba izilwane zifunda ukuthi izinkomba ezithile zibikezela umphumela othize. Ngamanye amagama, lo msebenzi wokukhetha umelela ukulindelwa kwesilwane, kususelwa kulwazi, yemiphumela engahle ibe khona. Lezi zici ziboniswa ku Umfanekiso we-1, ekhombisa ukuphendula kweningi labantu be-OFC neurons okurekhodwe kumagundane njengoba befunda futhi beguqula izinkinga zokwahlulela iphunga le-nov [8,9,13]. Kulomsebenzi olula, amagundane kumele afunde ukuthi iphunga elilodwa libikezela umvuzo emthonjeni oseduze we-fluid, kanti elinye iphunga libikezela isijeziso. Ukuqala kokufunda, ama-neurons e-OFC aphendula kokunye kepha hhayi komunye umphumela. Ngaso leso sikhathi, ama-neurons nawo aqala ukuphendula elindele umphumela wawo awuthandayo. Ngokwezifundo eziningi, i-15-20% yama-neurons e-OFC ithuthukise lo msebenzi kulo msebenzi, yadubula ilindela ukuthi kube ne-sucrose noma i-quinine isethulo [8,9,13]. Umsebenzi kulolu hlanga lwe-neural lubonisa inani lemiphumela elindelekile, eligcinwe kulokho esikuchaze lapha njengememori yokumelela.

Ibhokisi 2. Umsebenzi we-Orbitof Pambal unikeza isiginali eqhubekayo yenani lemicimbi ezayo

I-orbitof Pambal cortex (OFC) ikulungele ukusetshenziswa kolwazi oluhlangene ukubikezela bese isayina inani lemicimbi yesikhathi esizayo. Noma umbhalo oyisisekelo walesi sibuyekezo ugxile emsebenzini ngezikhathi zokubambezeleka ngaphambi kwemivuzo yokuhlukanisa lesi siginali, ukunwetshwa okunengqondo kwalokhu kungqubuzana ukuthi umsebenzi ku-OFC ufaka lesi siginali kuwo wonke umsebenzi. Ngakho-ke, i-OFC ihlinzeka ngokuhlaziya okuningwayo ngenani elilinganayo lesimo samanje nangezifundo ezenziwayo ezingacatshangelwa.

Le ndima ibonakala emsebenzini wokudubula we-OFC neurons ngesikhathi sokusampula kwezimpawu zokucatshangelwa komvuzo noma isijeziso [86-88]. Isibonelo, kumagundane aqeqeshelwe ukwenza umsebenzi wobandlululo onamaphutha ayisishiyagalombili, lapho amaphunga amane ahlotshaniswa nomvuzo kanti amakha amane ahlotshaniswa non-umvuzo, ama-neuron we-OFC athonywa kakhulu ukubaluleka kokuhlobana kwephunga kunokuphathwa ubunikazi bephunga langempela [87]. Ngempela uma ubunikazi bephunga benziwa abunangqondo, ama-neuron we-OFC azosinaka lesi sici sokuzwa sentambo. Lokhu kuboniswe nguRamus no-Eichenbaum [89], oqeqeshe amagundane kumphunga ayisishiyagalombili oqhubekayo obambezela ukungalingani-kuya-isampula, lapho ukwakhiwa okuhlobene okuhlobene nomvuzo akuyona ubuwena bephunga kepha kunalokho ukufana 'komdlalo' noma 'okungafani nomdlalo' phakathi kwentambo eku kwecala lamanje nelandulele. Bathole ukuthi i-64% yama-neurons aphendulayo abandlulula lo mqhathaniso-wokungalingani nomdlalo, kuyilapho i-16% kuphela eyadubula ngokukhetha komunye wephunga.

Yize noma ukudubula okukhetha u-cue kuye kwahunyushwa njengokufaka okuhlanganisiwe, siphakamisa ukuthi lo msebenzi we-neuronal empeleni umelela ukuhlolwa okuqhubekayo kwemiphumela engase ibe khona yesilwane. Ngakho-ke, ukudubula okukhethiweyo kwalezi zinzwa akumane kuveze iqiniso lokuthi ikhebula elithile liye lahlanganiswa ngokuthembekile ngomphumela othile esikhathini esedlule, kepha kunalokho libonisa ukwahlulela kwesilwane esinikezwe izimo zamanje ezithi, ngokubamba lolo lwazi oluhlangene, kuholele kulowo mphumela esikhathini esizayo. Lesi sahlulelo sifanekiselwa njengenani lalowo mphumela othize ohlobene nezinjongo noma izifiso zangaphakathi, futhi lokhu okulindelwe kuvuselelwa njalo. Ngakho-ke, ukudubula ku-OFC kukhombisa ngampela inani elilindelekile lesimo esilandelayo esizokhiqizwa sinikezwe impendulo ethile, noma ngabe leso simo siyisiqiniseko esiyinhloko noma simane siyisinyathelo esiya kuleyo nhloso yokugcina. Ngokuhambisana nalesi siphakamiso, ukubuyekezwa kwezincwadi kukhombisa ukuthi ukufaka ikhodi ku-OFC kwehlukanisa ngokweqiniso imicimbi eminingi, ngisho naleyo isuswe ekulethweni kwemivuzo yangempela, uma ihlinzeka ngemininingwane ngamathuba omvuzo wesikhathi esizayo (Umdwebo I waleli bhokisi). Isibonelo, ekuqeqeshweni kokubandlulula ngephunga, i-OFC neurons umlilo ilindele i-nose-poke eyandulela isampula sephunga. Ukuphendula kwalezi zinzwa kuhluka ngokuya ngokuthi ukulandelana kwezivivinyo zakamuva [87,90] noma indawo [91] ibikezela amathuba aphezulu womvuzo.

Umdwebo I

Ifayela elingaphandle eliphethe isithombe, umzekeliso, njll. Igama le-nto nihms52727f5.jpg

Umsebenzi we-Neural e-OFC ngokulindela imicimbi yezilingo. Ama-Neurons ku-rat ye-OFC aqoshwa ngenkathi kwenziwa iphunga lesishiyagalombili, le-Go-NoGo harufu lokubandlulula. Umsebenzi okhonjwe ngama-neurons ama-orbitofrontal amane abonisiwe, avumelaniswa emicimbini emine eyehlukene yemisebenzi (a-d). Umsebenzi uboniswa ngefomethi e-raster phezulu nanjenge-histogram yesikhathi somcimbi ezansi kwephaneli ngalinye; amalebula ngaphezulu kwesibalo ngasinye akhombisa umcimbi wokuvumelanisa nanoma yiziphi izehlakalo ezenzeka ngaphambi noma ngemuva kokuqala kokukhanya (i-LT-ON), iphunga (i-OD-POK), isiqalo sephunga (OD-ON), i-poke yamanzi (i-WAT-POK) noma ukulethwa kwamanzi (WAT-DEL). Izinombolo zikhombisa inani lezilingo (n) kanye nenani le-spikes ngomzuzwana. Ama-neurons amane ngalinye laxosha ngokuhlangana nomcimbi ohlukile, kanti ukudubula kuleyo nyobu ngakunye kwakhuphuka kulindelwe lowo mcimbi. Kuguqulwe, ngemvume, kusuka ku- [87].

Umfanekiso we-1 

Ukusayinwa kokulindelwe kwemiphumela ku-orbitof Pambal cortex. Amabha amnyama akhombisa impendulo ezivivinyweni ezibandakanya umphumela owuthandayo wama-neurons esigabeni sokulandela ngemuva. Amabha amhlophe akhombisa impendulo kumphumela ongathandwa. Umsebenzi uvumelaniswe ...

Ngemuva kokufunda, la ma-neurons azoqalwa ukusebenza yizinkomba ezibikezela imiphumela yazo ayithandayo, ngaleyo ndlela esayina umphumela olindelekile ngisho nangaphambi kokuba kwenziwe impendulo. Lokhu kubonakala ekuphenduleni kwesibalo sabantu kuvezwe Umfanekiso we-1, obonisa umsebenzi ophakeme, ngemuva kokufunda, ukuphendula iphunga elinobuhlungu elibikezela umphumela oncamelayo wabantu be-neuronal. Lezi zimpawu zingavumela isilwane ukuthi sisebenzise okulindelwe kwemiphumela engase iholele izimpendulo kuzimpawu kanye nokwenza lula ukufundela lapho okulindelwe kwephulwa.

Umbono wokuthi i-OFC iqondisa indlela yokuziphatha ngokubonisa ukulindelwa kwemiphumela ihambisana nemiphumela yokulimala kwe-OFC ngokuziphatha. Le miphumela ibonakala ngokujwayelekile lapho impendulo efanele ingakwazi ukukhethwa kusetshenziswa izinhlangano ezilula, kepha kunalokho kudinga ukuthi okulindelwe komphumela kuhlanganiswe ngokuhamba kwesikhathi noma ukuqhathaniswa phakathi kwezinye izimpendulo. Isibonelo, abantu abalimele i-OFC abakwazi ukuhola indlela yokuziphatha ngokusekelwe kwimiphumela yezenzo zabo emsebenzini wokugembula we-Iowa [14]. Kulesi msebenzi, izikhonzi kufanele zikhethe kumakhadi wamakhadi anemivuzo ehlukahlukene nezinhlawulo ezimelwe kumakhadi. Ukwenza izinqumo ezinhle, izifundo kumele zikwazi ukuhlanganisa inani lale mivuzo nezinhlawulo ezahlukahlukene ngokuhamba kwesikhathi. Abantu abanomonakalo we-OFC ekuqaleni bakhetha ama-decks athola imivuzo ephezulu, okubonisa ukuthi bangasebenzisa izinhlangano ezilula ukuqondisa ukuziphatha ngokosayizi womvuzo; kodwa-ke, ziyehluleka ukuguqula izimpendulo zazo ukuze zibonise izinhlawulo ezinkulu ezenzeka kwesinye isikhathi kulezo zakhiwo. Ukuhlanganisa imininingwane mayelana nesikhathi, izinhlawulo ezibonakala ngokuthile kuzokwenziwa lula ngekhono lokugcina inani ngenani lemiphumela elindelekile kwimemori yokumelele ngemuva kokhetho olwenziwe, ukuze ukwephulwa kwalokhu kulindelekile (izinhlawulo ezithile ngezikhathi) kungabonakala. Lokhu kusilela kuthandeka ekushintsheni okushintshiwe okuboniswe kumagundane, ezinkawu nakubantu ngemuva kokulimala kwe-OFC [15-21].

Leli khono lokubamba imininingwane mayelana nemiphumela elindelwe kumemori yokumelela nayo iye yabuzwa ocwaningweni lwakamuva lapho izifundo zenze izinqumo phakathi kwezifiso ezimbili ezibikezela ukujeziswa noma umvuzo kumazinga ahlukahlukene okungenzeka [22]. Kwenye ingxenye yalolu cwaningo, izifundo zanikwa impendulo ngokubaluleka komphumela abangazange bawukhethe. Izifundo ezijwayelekile zikwazile ukusebenzisa le mpendulo ukuguqula imizwa yazo ngokuthanda kwazo futhi zifunde ukwenza izinqumo ezingcono ezivivinyweni ezizayo. Isibonelo, umvuzo omncane wabenza bajabule ngokwengeziwe lapho bazi ukuthi bagweme inhlawulo enkulu. Abantu abanomonakalo we-OFC bakhombise izimpendulo ezijwayelekile ezingokomzwelo emvuzweni nasezijezisweni abazikhethile; kodwa-ke, impendulo ngomphumela ongakhethiwe ibingenamthelela emizweni yabo noma ekusebenzeni kwabo okulandelayo. Okusho ukuthi, babejabule lapho bethola umvuzo, kepha bebengajabule ngokwengeziwe uma beziswa ukuthi bavikele nenhlawulo enkulu. Lokhu kukhubazeka kuhambisana nendima ye-OFC ekugcineni imininingwane ehlobene kwimemori yokumelela ukuqhathanisa okulindelwe kwemiphumela. Ngaphandle kwalesi siginali, abantu ngeke bakwazi ukuqhathanisa inani elilinganayo lemiphumela ekhethiwe nengashintshiwe bese behluleka ukusebenzisa lolu lwazi lokuqhathanisa ukulungisa imizwa futhi benze lula ukufunda.

Yize lezi zibonelo ziveza, ukubonakaliswa okuqonde ngqo kwendima ebalulekile ye-OFC ekwakheni okulindelwe kwemiphumela ukuqondisa izinqumo kuqhamuka emisebenzini yokuqinisa amandla okusiza. Le misebenzi ihlola ukulawulwa kokuziphatha ngokufanekiselwa kwangaphakathi kwenani lomphumela olindelekile. Isibonelo, kwinguqulo ye-Pavlovian yale nqubo (Umfanekiso we-2), amagundane aqale aqeqeshelwe ukuhlobanisa i-cue elula nokudla. Ngemuva kokuphendula okunesimo kumisiwe ekukhanyisweni, inani lokudla liyancipha ngokuyihambisa ngokugula. Kamuva, esivivinyweni sabaphenyi, okokukhanya okukhanyayo kuphinde kuvezwe esimisweni sokuqothula esingavuzwanga. Izilwane ezitholakele ukugula kokugula zidla okuncane ekukhombeni kunokulawula okunganelwanga amandla. Ngokubalulekile, lokhu kwehla kokuphendula kubonakala ekuqaleni kweseshini futhi kuncishisiwe ekunciphiseni okuvamile ekuphenduleni okuvela ekufundeni okuqothulayo phakathi neseshini. Lokhu kwehla kokuqala kokuphendula kumele kubonise ukusetshenziswa kwesethulo sangaphakathi senani lamanje lokudla kuhlangene nenhlangano yokudla yokukhanya kokuqala. Ngakho-ke, imisebenzi yokugcizelela yokuqinisa inikezela isilinganiso esiqondile samandla okukhohlisa nokusebenzisa okulindelwe komphumela ukuqondisa indlela yokuziphatha.

Umfanekiso we-2 

Imiphumela yezilonda ze-neurotoxic ze-orbitof Pambal cortex (OFC) ekusebenzeni emsebenzini wokuqinisa amandla we-reinforcer. (A) Amagundane wokulawula namagundwane anezilonda zangaphakathi ze-neurotoxic ze-OFC ziqeqeshelwe ukuhlobanisa isivuseleli esinempilo (CS, ukukhanya) ne ...

Amagundane anezilonda ze-OFC ahluleka ukukhombisa noma yimuphi umphumela wokudonswa kwemali kokuphendula okukhonjwe kule paradigm, naphezu kokuma okujwayelekile nokuncipha komphumela [23]. Ngamanye amagama, bayaqhubeka nokuphendula okukhanyayo bese bezama ukuthola ukudla, noma kungeke bakudle uma kwethulwa (Umfanekiso we-2). Ngokubalulekile, amagundane akhishwa yi-OFC akhombisa amandla ajwayelekile okucima izimpendulo zawo ngaphakathi kweseshini yokuhlola, abonisa ukuthi ukusilela kwabo akubonisi ukungakwazi okuvamile ukuvimbela izimpendulo ezinemibandela [24]. Esikhundleni salokho, i-OFC inendima ethize yokulawula izimpendulo ezinemibandela ngokuya kwezethulo zangaphakathi zenani elisha lomphumela olindelekile. Ngakho-ke, izilonda ze-OFC ezenziwe ngemuva kokufunda ziyaqhubeka zithinta ukusebenza kulo msebenzi [25]. Imiphumela efanayo iye yabikwa ezinkomeni eziqeqeshelwe ukwenza inguqulo yalomsebenzi [19].

Amagundane anezilonda ze-OFC akhombisa nezinguquko ze-neurophysiological ezifundeni ezansi nomfula ezihambisana nokulahleka kokulindelwa kwemiphumela. Kokunye ukuhlola [26], izimpendulo zaqoshwa kusuka kumayunithi owodwa ku-basolateral amygdala, indawo ethola ukuqagela okuvela e-OFC, ekufundeni kwamagundane nokubuyisa ubandlululo lwenephunga lomsebenzi owenziwe ngaphambili. Ngaphansi kwalezi zimo, izilonda ze-OFC ziphazamise ukudubula okulindelwe okuvame ukubonwa e-amolgal basy. Ngaphezu kwalokho, ngaphandle kokufaka kwe-OFC, ama-neurons we-basolateral amygdala abe esekhetha kancane kancane, ikakhulukazi ngemuva kokuba izinhlanganiso zomphumela we-cue-back zabuyiselwa. Ukushumeka okuhambisana kancane kancane ku-basolateral amygdala ngenxa yezilonda ze-OFC, ikakhulukazi ngesikhathi sokushintshwa, kuyahambisana nomqondo wokuthi ukulindelwa kwesiphetho kusiza ukufunda kwezinye izinhlaka, ikakhulukazi lapho okulindelwe kwephulwayo njengoba kunjalo ngokubuyela emuva. Ngakho-ke, i-OFC ibonakala ikhiqiza futhi imele okulindelwe kwemiphumela okungabalulekanga nje ekuqondisweni kokuziphatha ngokwalokho okulindelwe ngekusasa, kodwa futhi nekhono lokufunda ukwephulwa kwalokhu okulindelwe. Ngaphandle kwalesi siginali, izilwane zihlanganyela ekuziphatheni okungahambi kahle, eziqhutshwa yizindlela ezisetshenziswayo kanye nemikhuba yokuphendula ivuseleli, kunokuba ziveze umbono noma umphumela.

Ukuziphatha okuluthayo kanye nokulindelwe komphumela

Okutholakele kamuva nje kukhombisa ukuthi lo mbono womsebenzi we-OFC unokuningi ongakunikeza ukuqonda kokuluthwa yizidakamizwa. Ngokuya kwe- Incwadi Yokuhlola Nezibalo Zezinkinga Zengqondo [27], ukuxilongwa kokuxhomekeka kwento kudinga ukuthi umuntu abonise ukungakwazi ukulawula indlela yakhe yokufuna izidakamizwa, yize kunemiphumela emibi. Ukuziphatha okunjalo okuluthayo kubonakaliswa ngokuhlukile njengokucindezelayo, okuphoqayo, okuphikelelayo noma okulawulwa yizinto ezihlobene nezidakamizwa. Ngaphezu kwalokho, kuvame ukubonwa yize kunesifiso esishiwo salokho abayimilutha sokuyeka. Ngakho-ke, ukuxilongwa kokuncika kwento kudinga iphethini yokuziphatha efana neyamagundane angama-OFC akhona, izinkawu nabantu.

Ngenxa yalokho, umlutha wezidakamizwa uhlotshaniswa nezinguquko kusakhiwo nomsebenzi we-OFC. Isibonelo, ucwaningo lokucabanga ngemilutha luveze ngokungaguquki ukonakala kokuphuma kwegazi e-OFC [28-33] (ngesibuyekezo esihle kakhulu, bona [34]). I-Alcohol kanye nemilutha ye-cocaine ibonisa ukwehliswa kwezilinganiso eziyisisekelo zokuqalwa kwe-OFC ngesikhathi sokuhoxa okucashile ngisho nangemva kokuhlala isikhathi eside. Ngakolunye uhlangothi, lapho kuvezwa izinkambo ezihlobene nezidakamizwa, imilutha ikhombisa ukweqisa kwe-OFC ehambelana nezinga lokufisa abalibonayo. Lezi zinguquko zihambisana nokulimazeka ekuziphatheni okuncike ku-OFC kwezilutha zemithi [35-39]. Isibonelo, abahlukumeza utshwala nabasebenzisa i-cocaine bakhombisa okufanayo, noma kungenzima kangako ngokwesilinganiso, ukuphazamiseka emsebenzini wokugembula ochazwe ekuqaleni, njengoba kwenza abantu abanezilonda ze-OFC. Ngokufanayo, ezinye izivivinyo zelebhu zokwenza izinqumo ziveze ukuthi abahlukumezi be-amphetamine bathatha isikhathi eside futhi mancane amathuba okuba bakhethe ukhetho oluzuzisa kakhulu kunolulawulo. Kepha ingabe lezi zinto ezisilelayo zibonisa ubungozi obukhona ngaphambili bokulutha kwabanye abantu? Noma ingabe zingumphumela we-neuroadaptations wesikhathi eside obangelwa izidakamizwa? Futhi uma kunjalo, akhombisa ushintsho esakhiweni futhi / noma asebenza ngaphakathi kwe-OFC, noma ingabe awumphumela woshintsho kwenye indawo kumanethiwekhi e-corticolimbic alingisa imiphumela yezilonda ze-OFC?

Ukuze uphendule le mibuzo, kuyadingeka ukuthi uphendukele kumamodeli wezilwane, lapho izidakamizwa eziluthayo zingahanjiswa ngendlela elawulwayo ngokumelene nesizinda sofuzo esimisiwe nesizungezile. Inani elikhulayo lezifundo manje selikhombisa ukuthi ukuchayeka isikhathi eside ezidakamizweni eziluthayo - futhi ikakhulukazi ama-psychostimulants - kuholela ekuguqukeni kwengqondo okuhlala isikhathi eside nokuziphatha [40-50]. Ngokubalulekile le miphumela ibonwa ngokujwayelekile izinyanga ngemuva kokuyekiswa nasezilungiselweni zokuziphatha ezingahambisani nokuchayeka kwezidakamizwa, kuyahambisana nomqondo wokuthi izidakamizwa eziluthayo ziguqula imijikelezo yobuchopho ebalulekile kulawulo olujwayelekile lokuziphatha. Muva nje, izifundo eziningana zikhombisile imiphumela ku-OFC. Isibonelo, amagundane aqeqeshelwe ukuzilawula ngokwawo amphetamine amasonto ambalwa kubikwe ukuthi akhombisa ukwehliswa kwesibalo sokuqaqanjelwa komgogodla e-OFC inyanga eyodwa kamuva [46]. Ngaphezu kwalokho, la amagundane ahlangabezana nezidakamizwa akhombise ukulungiswa kabusha kwama-dendrites awo ngokuphendula ukuqeqeshwa kwensimbi. Lokhu okutholakele kuphawuleka ikakhulukazi ngokukhanya kokuqina komgogodla okuye kwabikwa ngaphambili ku-cialex ye-medial predomal cortex, i-nucleus accumbens nakwezinye izindawo ngemuva kokwelashwa nge-psychostimulants [41]. Ngakho-ke, phakathi kwalezi zifunda ze-corticolimbic, i-OFC ibonakala ihlukile ekuboniseni ubufakazi bokwehla kwe-synaptic plasticity ngemuva kokuvezwa kwezidakamizwa.

Ukwehla kwamandla eplastiki ku-OFC kungalindeleka ukuthi kube nomthelela emisebenzini exhomeke ku-OFC. Ngokuhambisana nalesi sinqobelo, amagundane anikezwe inkambo yamasonto amabili yokwelashwa nge-cocaine ikhombisa ukungalawuleki okungapheli kokuziphatha okuncike ku-OFC. Ngokuqondile, lezi zilwane azikwazi ukusebenzisa inani lemiphumela ebikezelwe ukuqondisa indlela yazo yokuziphatha. Kokunye ukuhlola [51], amagundane anikezwa imijovo yecocaine yansuku zonke amasonto amabili. Esikhathini esingaphezulu kwenyanga kamuva, la magundane ahlolwa emsebenzini wokubandlulula i-Go-NoGo. Kulesi msebenzi, amagundane afunda ukuya ethekwini elingamanzi ukuze athole i-sucrose ngemuva kokuhogela iphunga elilodwa futhi agodle ukuya ethekwini elilodwa loketshezi ukugwema i-quinine ngemuva kokuhogela iphunga lesibili. Amagundane aphathwe yi-cocaine afunde lokhu kubandlulula ngezinga elifanayo nangezilawuli eziphathwe ngosawoti, kepha ahluleka ukuthola ukubandlulula ngokushesha njengoba kwaba njalo nokulawula. Ukushoda okufanayo kubuye futhi kuboniswe emaphalamende anikezwa ukufinyelela okuhlala isikhathi eside kwe-cocaine [43]. Ukushoda okunjalo okuguqukayo kuwuphawu lwezilwane nabantu abangama-OFC abakhishwe inyumbazana [15-21], lapho kucatshangwa ukuthi kukhombisa ukungakwazi ukuguqula isimilo esisunguliwe ngokushesha okukhulu. Siphakamisa ukuthi indima ye-OFC ekusekeleni lokhu kuguquguquka okusheshayo ihambelana nokubaluleka kwayo kokusayina okulindelwe kwemiphumela [26]. Ngesikhathi sokufunda okuguqukayo, ukuqhathanisa kwalesi siginali nomphumela wangempela, oguquliwe kuzokhiqiza amasiginali wephutha abalulekile ekufundeni okusha [1]. Ngaphandle kwalesi siginali, amagundane akhishwa yi-OFC angafunda kancane. Njengoba sesivele sidingida, i-neurophisiological lunglate yalokhu kufunda okuncane isanda kukhonjiswa ekufakweni okuhlanganisa okungaguquki kokuhlangana kwama-basolateral amygdala neurons kumagundane angama-OFC akhishwa [26].

Ukulahleka kwalesi siginali kuyabonakala nakwisivivinyo sesibili lapho amagundane aphathwa khona nge-cocaine amasonto amabili abese ehlolwa emisebenzini yokudonswa kwezidakamizwa yasePavlovian echazwe ekuqaleni [24]. Futhi, ukuhlolwa kwenziwa cishe inyanga eyodwa ngemuva kokwelashwa kokugcina kwe-cocaine. Lawa magundane abonise ukujongwa nokwejwayelekile kokujwayelekile, futhi futhi aqede aphendule ngokujwayelekile esigabeni sokugcina sokuhlolwa; kepha amagundane aphethwe yi-cocaine awazange akhombise ukwehla okujwayelekile okuzenzakalelayo ukuphendula kulokho okubikezelayo. Lokhu kusilela (Umfanekiso we-3) Kufana nokushoda ngemuva kwezilonda ze-OFC kulo msebenzi (Umfanekiso we-2). Lokhu okutholakele kuhambisana nokungakwazi ukukhombisa inani lomphumela olindelekile. Impela, ngoba kulo msebenzi akukho okucacayo maqondana nezethulo ezidingekayo ekulameni ukusebenza okujwayelekile, ukusilela okuchazwe lapha kukhomba ngokungalingani ekulahlekelweni kokulindelwe kwemiphumela kumagundane aphathwe i-cocaine.

Umfanekiso we-3 

Imiphumela yokwelashwa kwe-cocaine ekusebenzeni komsebenzi we-reinforcer devaluation (Umfanekiso we-2). Amagundane aphethwe i-saline- ne-cocaine aqeqeshelwe ukuhlanganisa isivuseleli esinempilo (i-CS, ukukhanya) nesivuseleli esingavunyelwe (i-US, ukudla). (A) Ngaphezu kwamabhulokhi wesikhathi amane, ...

Ukulahleka kwale ndlela esindayo kuzobanga ubungako bemilutha yokuqhubeka nokufuna izidakamizwa, yize kunemiphumela emibi engenakugwemeka yokuziphatha okunjalo, ngoba kuzobenza bangakwazi ukufaka lolu lwazi olubikezelayo ekwenzeni kwabo izinqumo futhi mhlawumbe ngeke bakwazi ukufunda kusuka isipiliyoni esiphindaphindwayo sale miphumela emibi. Noma ezinye izinhlelo zobuchopho zingabandakanyeka futhi, izinguquko ezibangelwa izidakamizwa kulolu phawu oluthembele ku-OFC ngokwazo zingasiza ngamandla ekuguqukeni kusuka ekuziphatheni okuqondile okuqondiswe kunhloso kuya ekuphenduleni okuphoqelelayo. Lolu shintsho lukhombisa ushintsho kubhalansi phakathi kwalezi zindlela zokuncintisana zokulawula indlela yokuziphatha. Ukuchazwa okunjalo kuzobambelela ekuziphatheni okuluthayo kokulutha izidakamizwa, futhi nokutholakele kwakamuva kumamodeli ezilwane athile omlutha lapho amagundane angavumeli ukuziphatha okufuna izidakamizwa, noma ngabe imiphumela emibi yenziwa iphikisana nalokhu kuziphatha [45,47].

Ukuphetha amazwi

Sibuyekeze okutholakele kwakamuva ukuxhasa isiphakamiso sokuthi i-OFC ibalulekile ekubonakaliseni inani lemiphumela noma imiphumela elindelekile. Siphinde saxoxa ngokuthi lo mbono ungabaluleka kanjani ekuqondeni i-pathology esekela umlutha wezidakamizwa. Vele lemibono iphakamisa eminye imibuzo eminingi. Uma i-OFC ikhiqiza amasiginali maqondana nemiphumela elindelekile, kubalulekile ukuba uqonde ukuthi izindawo ezisezansi komfula zisebenzisa kanjani lezi zimpawu - ezilwaneni ezijwayelekile, ngaphezu kwalezo ezidalulwe ezidakamizweni eziluthayo. Siphakamise ukuthi i-basolateral amygdala ingahle ibandakanyeke kanjani [26]; kodwa-ke, ukuqonda iqhaza elenziwa yilezi zisibonakaliso ku-nucleus accumbens - nokuthi baxhumana kanjani nokunye kokufakwa kwe- 'limbic' - kungahle kube kufaneleke kakhulu ukuqonda ukulutha. Ama-laboratories amaningana asebenza kanzima ukuxazulula lezi zinkinga ezibalulekile. Ngaphezu kwalokho, kuzobaluleka ukukhombisa ukuthi ngabe izinguquko ekuziphatheni okuncike ku-OFC ngemuva kokuvezwa kwezidakamizwa empeleni zibonisa umsebenzi oshintshiwe wamangqamuzana noma we-neurophysiological ku-OFC, njengoba kusikiselwe idatha yokuqopha yokuqala [52], noma kungenjalo ukuthi zingabonisa ushintsho kwenye indawo kwisifunda, njengama-nucleus accumbens, indawo ende ethambekele ekuluthweni. Futhi-ke, noma yimuphi umfuziselo wesilwane unesifo kuphela uma usikisela ikhambi lokushintshwa kwezifo. Lokhu kunzima esimweni sezilonda kodwa kungenzeka ukuthi kwenzeke ubuciko obuvela ekuvezweni kwezidakamizwa. Kodwa-ke, kusazobonwa ukuthi kungenzeka yini ukwenziwa ngamakhambi ukwenza ngokwejwayelekile le ndlela futhi mhlawumbe kube yiluphi uhlobo lokuqhathaniswa nama-molecule noma ama-neurophysiological akhonjwa ezilwaneni eziphathiswe izidakamizwa. Silindele ukuthi lezi zinkinga nezinye eziningi zizodingidwa eminyakeni ezayo (Ibhokisi 3).

Ibhokisi 3. Imibuzo engaphendulwanga

  1. Izindawo ezansi nomfula - ikakhulukazi ama-nucleus kukusanya - zisebenzisa amasiginali maqondana nemiphumela yokulindelwe evela e-OFC? Lolu lwazi luhlanganiswa kanjani nokunye okokufaka kwe- 'limbic' kuma-accumbens?
  2. Ngabe ushintsho ekuziphatheni okuncike ku-OFC ngemuva kokuvezwa kwezidakamizwa kungaxhunyaniswa noshintsho kokuhlosiwe kwamangqamuzana noma i-neurophysiological ngaphakathi kwe-OFC? Noma ingabe lokhu kushiyeka kokuziphatha kubonisa ushintsho kwenye indawo kumasekethe wokufunda?
  3. Ngabe izinguquko ezihlobene nezidakamizwa ekuziphatheni noma kwezinye izimpawu zingabuyiselwa emuva ngokuziphatha noma kwezezokwelapha?
  4. Ngabe ushintsho olusebenzayo ku-OFC noma amasekethe wokufunda ahlobene ahlukile ezilwaneni ezinikezwe okuphikisanayo nokuhlangenwe nakho kwezidakamizwa okungekho okuphikisanayo? Futhi uma kunjalo, ingabe umehluko unethonya elibucayi ekuziphatheni?
  5. Ngabe ushintsho ku-OFC underlie behaviour kwizidakamizwa zokuluthwa izidakamizwa zokufuna izidakamizwa okuphoqelekile futhi ziphinde zibuye? Futhi kungenzeka yini ukuthi zibaluleke kakhulu ekuqaleni kwenguquko yokuluthwa umlutha, zikhuthaze ukusetshenziswa kwezidakamizwa okuqhubekayo ngaphambi koshintsho lwezimo zezimali, ezihambisana nokufinyelela isikhathi eside, zibe nomthelela?

Ukuvuma

Ucwaningo lwethu lwalwesekwa izibonelelo ezivela ku-NIDA (R01-DA015718 to GS), NINDS (T32-NS07375 to MRR) and NIDCD (T32-DC00054 to TAS).

Okubhekwayo

I-1. I-Dickinson A. Umbono wokulangazelela kwesimo sezilwane. Ku: Klein SB, Mowrer RR, abahleli. Imibono Yokufunda Yesikhashana: Isimo SasePavlovian kanye Nesimo Sokufunda Kwendabuko. I-Erlbaum; I-1989. I-pp. 279-308.
I-2. IGoldman-Rakic ​​PS. Ukujikeleza kwe-cortex yangaphambili yangaphambilini nokulawulwa kokuziphatha ngememori emelele. Ku: Mountcastle VB, et al., Abahleli. I-Handbook of Physiology: I-Nervous System. V. American Physiology Society; I-1987. I-pp. 373-417.
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