Ho se sebetse ha corresx ea prefrontal ho lemalla: ho fumanoa ka mahlaseli a kotsi le ho ameha ka meriana (2011)

THUTO E TLAHANG

Rita Z. Goldstein1 & Nora D. Volkow

Tlhahlobo ea Tlhaho Neuroscience 12, 652-669 (November 2011) | Doi: 10.1038 / nrn3119

inahaneloang

Tahlehelo ea taolo ea tšebeliso ea lithethefatsi e bakoang ke bokhoba ba lithethefatsi qalong e ne e lumeloa hore e bakoa ke ho sitisoa ha mekotla ea meputso e meholo. Leha ho le joalo, lithuto tsa ho nahana ka boits'oaro bo bobebe li bonts'itse karolo ea bohlokoa ea karolo ea pele ea cortex (PFC) ka tatellano ea eona ea libaka tsa meputso ea litho le ho kenya letsoho mosebetsing oa tsamaiso e phahameng (mohlala, boits'oaro, tšobotsi ea tlhokomeliso le tlhokomeliso). Tlhahlobo ena e tsepamisa maikutlo ho lithupelo tse sebetsang tse entsoeng lilemong tse leshome tse fetileng tse ntlafalitseng kutloisiso ea rona ea ho nka karolo ha PFC tšebelisong ea lithethefatsi. Ho sitisoa ha PFC ho lemalleng bokhoba ba tahi ha e qobelloe feela ho sebelisa lithethefatsi empa e boetse e ikarabella bakeng sa boits'oaro bo bobe bo tsamaisanang le ts'ebeliso e mpe ea bolokolohi ba ho ikhethela.

SELELEKELA

Ho lemalla lithethefatsi ho kenyelletsa mokokotlo o khutlang oa ho tahoa, ho itlopa joala, ho khaotsa le ho lakatsa ho tlisoang ke ts'ebeliso e mpe ea lithethefatsi leha ho e-na le litlamorao tse mpe (sa feiga. 1). Lithethefatsi tse hlekefetsoang ke batho li eketsa dopamine potolohong ea moputso mme ho lumeloa hore li ba le litlamorao. Ka hona, lithuto tse ngata tsa tleliniking ea bokhoba ba tahi li tsepamisitse likarolo tsa midbrain dopamine (sebaka sa karolelano ea mokokotlo le substantia nigra) le meaho ea basal ganglia eo ba e ralileng ho eona (ventral striatum, moo li-nucleus accumbens li leng teng, le dorsal striatum), tse tsejoang hore li kenya letsoho moputsong, maemong le maemong a tloaelo1, 2, 3. Leha ho le joalo, lithuto tsa pele le tsa tliliniki li sa tsoa hlahisa leseli 'me li qalile ho hlakisa karolo ea preortal cortex (PFC) ho addiction4. Mekhahlelo e mengata e hlalositsoe ho PFC eo e leng ea mantlha bakeng sa tšebetso e nepahetseng ea methapo - ho akaretsa maikutlo, kelello le boits'oaro - mme seo se thusa ho hlalosa hore na hobaneng pherekano ea ts'ebeliso ea ts'ebetso ea PFC e ka ama mekhoa e mengata ea boits'oaro (Tafole ea 1).

Setšoantšo sa 1 | Liponahatso tsa boitšoaro ba IRISA syndrome ea bokhoba ba lithethefatsi.

Palo ena e bonts'a matšoao a mantlha a tlhekefetso ea bokhoba ba lithethefatsi - ho tahoa, ho itlopa joala, ho ikhula le ho lakatsa - e le sesupo sa boitšoaro ba ho sitisoa ke karabo le ho se sebetse hantle ka letsoalo. Ho itaola ka lithethefatsi ho ka lebisa taetsong, ho latela lithethefatsi, tekanyo le tekanyo ea ts'ebeliso, le lintho tse fapaneng ka bonngoe. Likarolo tsa ho itlopa lijo li qala ka lithethefatsi tse ling, tse kang koae ea koae, 'me ts'ebeliso ea lithethefatsi e ba e qobelloang - lithethefatsi tse ngata li sebelisoa' me ka nako e telele ho feta kamoo ho neng ho reretsoe - ho bonts'a boitšoaro bo fokolisitsoeng. Lithethefatsi tse ling (mohlala, nicotine le heroin) li amahanngoa le tšebeliso ea lithethefatsi tse fumanehang hangata. Kamora ho khaotsa ho sebelisa lithethefatsi tse feteletseng kapa tse pheta-phetoang, matšoao a ho khaola a hlaha, ho kenyelletsa ho haelloa ke ts'usumetso, ho anhedonia, maikutlo a seng monate le ho ntlafatsa khatello ea maikutlo hape. Litakatso tse feteletseng kapa takatso ea lithethefatsi, kapa tse ling, ts'ebetso tse ikatisang tse joalo ka khethollo ea maikutlo le likarabo tse boemo bo botle, li ka bula tsela ea ts'ebeliso e eketsehileng ea lithethefatsi leha motho ea lemaletseng a leka ho ithiba (sheba Lethathamo la 1 bakeng sa litšobotsi tsa bongaka tsa ho lemalla litheko maemong. ea iRISA le karolo ea PFC ho ho lemalla). Setšoantšo se fetotsoe, ka tumello, ho Ref. 7 © (2002) Mokhatlo oa American Psychiatric Association.

Tafole 1 | Mekhoa e amanang le cortex ea pele e sa sitisoeng ke lithethefatsi

Motheong oa liphumano tsa ho nahana le lithuto tse hlahang tsa thuto ea morao-rao5, 6, re hlahisitse maikutlo a 10 lilemong tse fetileng tse ileng tsa sitisa tšebetso ea PFC ho lebisa ho lefu la ho sitisoa ha karabo le litšitiso tsa lefutso (iRISA) ka ts'ebeliso ea tlhekefetso (sa feiga. 1) - letšoao leo e tšoauoang ka ho fana ka ho se sebetse ho feteletseng hoa lithethefatsi tse amanang le lithethefatsi le lithethefatsi, ho fokotseha ho utloahala ho matlafalitsoeng ntle le lithethefatsi le ho fokotsa bokhoni ba ho thibela boits'oaro bo bobe kapa bo sa tsamaiseng boitšoaro bo bobe ba7. Ka lebaka la mefokolo ena ea mantlha, ho batla lithethefatsi le ho nka ts'ebetso ea sepheo sa mantlha, ho etsahala ka lits'enyehelo tsa mesebetsi e meng8 le ho fihlela ka boits'oaro bo feteletseng ho fumana lithethefatsi9.

Mona re lekola lithuto tse inahaneloang ka karolo ea PFC ha e le temallo ho tloha lilemong tse leshome tse fetileng, re li kopanya mohlaleng oa iRISA ka sepheo sa ho fumana kutloisiso e kholo ea ho se sebetse ha PFC ka ho lemalla. Haholo-holo, ona ke tlhahlobo ea pele e hlophisehileng ea karolo ea libaka tse ikhethileng kahare ho PFC e sebetsang ka har'a methapo ea methapo-kutlo e sebetsang ka tlasa ts'ebetso ea ho lemalla. Re lekola lipatlisiso tsa positron emission tomography (PET) le lithuto tsa MRI (fMRI) tse shebileng likarolo tsa PFC tse kentsoeng ts'ebetsong ea lithethefatsi. Tsena li kenyelletsa orbitof Pambal cortex (OFC), anterior cingrate cortex (ACC) le dorsolateral prefrontal cortex (DLPFC) (bona Tafole ea 1 bakeng sa libaka tsa Brodmann; bona leseli la tlatsetso S1 (tafole) bakeng sa libaka tsa Brodmann tse sa buuoang ka lingoloa tse kholo). Re nka liphetho tsa lithuto tsena (sa feiga. 2) maemong a karolo eo PFC e e bapalang ho IRISA: pele, karabong ea litlamorao tse tobileng tsa lithahasello tse amanang le lithethefatsi le lithethefatsi; ea bobeli, karabong ea meputsong eo eseng ea lithethefatsi, joalo ka chelete; ea boraro, ts'ebetsong ea maemo a phahameng a tsamaiso, ho kenyelletsa taolo ea inhibitory; 'me ea bone ke tlhokomeliso ea bokuli. Re hlahisa mohlala o bonolo o thusang ho tataisa likhopolo tsa rona mabapi le karolo ea litlatsetso tse fapaneng tsa PFC ho endophenotype ea ts'ebeliso ea lithethefatsi (fig. 3), joalo ka ha ho hlalositsoe ka botlalo ka tlase. Bakeng sa lithuto tsa pele ho PFC ka bokhoba ba litlaleho kapa litlaleho tse tebileng tsa ts'ebetso ea PFC re fetisetsa 'mali ho litlhahlobo tse ling10, 11.

Setšoantšo sa 2 | Boithuto ba morao-rao bo mabapi le ts'ebetso ea PFC ho batho ba lemaletseng lithethefatsi.

Libaka tsa ts'ebetso (tse lekantsoeng ho sebelisoa MRI, positron emission tomography (PET) kapa single-Photon emission computer tomography (SPECT)) (Tlhahisoleseling ea tlatsetso S1 (tafole)) li reriloe sebakeng sa stereotaxic, se bonts'itsoeng sebakeng sa dorsal le ventral. karolo) le likarolo tsa morao-rao le tsa maikutlo (karolo e bohareng le karolo e tlase, ka tatellano) ea kelello ea motho. a | Liphetoho tsa ts'ebetso tse amanang le likarolo tsa neuropsychological ke ho lemalla. Libaka tsa preortal cortex (PFC) li bonts'a phapang ea tšebetso lipakeng tsa batho ba lemaletseng taolo le taolo e phetseng hantle nakong ea mesebetsi e kenyang tlhokomelo le mohopolo oa ho sebetsa (o bonts'itsoeng botala), ho nka liqeto (ho bonts'itsoeng ka leseli le leputsoa), taolo ea inhibitory (e bonts'itsoeng mosehla), maikutlo le ts'usumetso (e bonts'itsoe ka bofubelu), le cue reactivity le tsamaiso ea lithethefatsi (e bonts'itsoeng ka lamunu). Ntle le moo, libakeng tse ling tsa PFC mesebetsi e ikamahanya le tšebetso ea ts'ebetso kapa tšebeliso ea lithethefatsi (e bonts'itsoeng ka boputsoa bo lefifi). b | Liphetoho tsa ts'ebetso tse amanang le likarolo tsa bongaka tšebelisong, ho kenyelletsa ho tahoa le ho itlopa joala (ho bontšitsoe ka bofubelu; lithethefatsi li ne li sebelisoa ka nako ea lihora tsa 48 tsa thuto), ho lakatsa (ho bontšitsoe ka pinki; lithethefatsi li sebelisitsoe 1-2 libeke pele ho thuto) le ho tlohela (ho bontšitsoe ka pherese; lithethefatsi li ne li sebelisoa ho feta libeke tsa 3 pele ho thuto). Libaka tse bonts'itseng ts'ebetso lithutong tseo karolo ea bokhoba e neng e sa hlalosoe kapa e neng e ke ke ea khethoa li bonts'oa hape (e bonts'itsoe ka sootho). Hona le lithuto tse ts'oanang le tse bontšitsoeng ho a. Boithuto bo ne bo kenyelletsoa ha feela ho ka fanoa ka likhokahanyo tsa x, y le z mme haeba likhonteraka tsena li le kahare ho PFC grey; lithuto tseo ho tsona li-x, y le li-link tsa li ka keng tsa fumaneha kapa tsa ngolloa ka nepo li sa kenyelelitsoe. Lihokela tsohle tsa x, y le z li ile tsa fetoloa sebaka sa Talairach (e sebelisa GingerAle, kopo ea Java ea sefofane sa Meta-Analysis pele e rera. Multi-Level Kernel Density Analysisboxbox213, 214 e ile ea sebelisoa (bona Webosaete ea Univesithi ea Colorado CANLab; bona hape le leseli la tlatsetso S8 (setšoantšo)).

Setšoantšo sa 3 | Mohlala oa ho nka karolo ha PFC ho ts'ebetsong ea litheko.

Mohlala oa kamoo tšebelisano lipakeng tsa subparal cortex (PFC) e ka laolang liphetoho tse bang teng kelellong, maikutlong le boitšoarong. Mohlala o bontša kamoo liphetoho mesebetsing ea litlatsetso tsa PFC bathong ba lemaletseng li amanang le matšoao a mantlha a kliniki ea ho lemalla - joala le ho itlopa joala, le ho iketla le takatso - ho bapisoa le ts'ebetso ea PFC bathong kapa liphateng tse phetseng hantle. Mohlala o shebana haholo le taolo ea thibelo le maikutlo. Li-ovals tse putsoa li emela likaroloana tsa dorsal PFC (ho kenyeletsoa le dorsolateral PFC (DLPFC), dorsal anterior cingulate cortex (dACC) le gyrus e ka tlase e ka pele; bona Lethathamo 1) tse amehang taolong ea taolo e phahameng (mekhoa ea 'ho bata'). Li-ovals tse khubelu li emela likaroloana tsa ventral PFC (medial orbitofrontal cortex (mOFC), ventromedial PFC le rostroventral ACC) tse amehang lits'ebetsong tse iketsang, tse amanang le maikutlo ('hot'). Mesebetsi e amanang le lithethefatsi tse amanang le lithethefatsi (mohlala, ts'ebetso ea ho hlohlelletsa, ho batla lithethefatsi, leeme le ho batla lithethefatsi) tse laoloang ke litlhaloso tsena li emeloa ke meriti e lefifi le mesebetsi e sa amaneng le lithethefatsi (mohlala, boiteko bo tsitsitseng) bo emeloa ke meriti e bobebe . a | Boemong bo phetseng hantle, mesebetsi ea kelello e sa amaneng le lithethefatsi, maikutlo le boits'oaro pele (bo bonts'itsoeng ke mahe a maholo a 'mala o bobebe) le likarabo tsa othomathiki (maikutlo le mekhoa ea ts'ebetso e ka lebisang ho nkeng lithethefatsi) li hatelloa ke ho kenya letsoho ho tsoa ho PFC ea dorsal ( e bonts'itsoeng ke motsu o teteaneng). Kahoo, haeba motho ea phetseng hantle a pepesehetse lithethefatsi, boits'oaro bo fetelletseng kapa bo sa lokelang ba ho noa lithethefatsi bo thibeloa kapa bo emisoa ('Stop!'). b | Nakong ea takatso le ho tlohela, mesebetsi e amanang le lithethefatsi, maikutlo le boits'oaro li qala ho fifala mesebetsi e amanang le lithethefatsi, e baka likhohlano mabapi le tšebeliso ea lithethefatsi ('Emisa?'). Tlhokomeliso e theohileng le / kapa boleng bo abeloa tšusumetso e sa amaneng le lithethefatsi (e bonts'itsoeng ke li-ovary tse nyane tse khanyang leseli), mme phokotso ena e tsamaisana le boits'oaro bo fokolisitsoeng le anhedonia, reactivity ea khatello le matšoenyeho. Ho boetse ho na le keketseho (e bonts'itsoeng ke mahe a maholo a lefifi-moriti) ho khethollo ea lithethefatsi le takatso e matla ea takatso ea lithethefatsi le takatso ea lithethefatsi. c | Nakong ea botahoa le ho itlopa joala, ts'ebetso ea ts'ebetso e phahameng e sa amaneng le lithethefatsi (e bonts'itsoeng ke oval e nyane e putsoa) e hatelloa ke tlatsetso e ekelitsoeng (e bonts'itsoeng ke motsu o motenya) ho tsoa libakeng tse laolang mesebetsi e amanang le lithethefatsi, e 'chesang' (e kholo oval e khubelu e lefifi). Ka mantsoe a mang, ho na le phokotso e kenang e tsoang libakeng tsa taolo e nang le taolo e phahameng (e bonts'itsoeng ke motsu o mosesane o phunyeletsoeng), mme libaka tsa 'hot' li tla ho laola tlatsetso ea tlhaiso-leseling e phahameng. Kahoo, ho tsepamisa maikutlo ho fokotsa ho tsepamisa maikutlo linthong tse ling tse amanang le lithethefatsi, ho eketsoa ka matla le maikutlo a mantlha - joalo ka tšabo, khalefo kapa lerato - lia hlakoloa, ho latela moelelo le tšitiso ea motho ka mong. Phello ke hore boits'oaro bo ikemetseng bo susumetsoang, joalo ka ts'ebeliso e mpe ea lithethefatsi, mabifi le boitšoaro bo hlephileng, li atile haholo ('Tsamaea!').

Ha ba lekola Tlhatlhobo ena, babali ba hloka ho amohela liphetho tse ngata haholo, tse ka ipaka li ferekanya kaha liqeto tse hlakileng ha li fanoe kamehla. Sena ke 'nete haholoholo bakeng sa mesebetsi ea lehae: mohlala, na mokokotlo oa ACC le DLPFC li kentse letsoho karabong ea takatso kapa taolong ea takatso, kapa ka bobeli? Ho tseba hore na ke karolo efe ea PFC e buellanang le ts'ebetso e ka bang thata haholo, mohlomong ka lebaka la ho fetoha ha kelello le kutloisiso ea mesebetsi ena - ke hore, bankakarolo ba ka sebelisa maano a mangata ha ba etsa mesebetsi ea methapo ea kutlo, 'me litsamaiso tsa pele li bonahala li na le maemo a fetofetohang a ts'ebetso ho feta litsamaiso tsa mantlha tsa sensorimotor. Lilemo tse ling tse leshome tsa lipatlisiso li ka ipaka li le bohlokoa kutloisisong ea rona ea karolo ea PFC ho lemalleng lithethefatsi. Ho kopanya sephetho ho tsoa lithutong tsa pele ho nako le lithutong tsa kalafo ea bongaka, ho nahanoa ka likarolo tse ling tsa cortical le subcortical tse lemalloang - PFC e hokahane haholo le libaka tse ling tsa boko (bona Lebokose la 1 bakeng sa puisano ea lithuto tsa pele tse hlahlobang marang-rang ana molemong oa bokhoba) - le ho sebelisa likhomphutha ho etsa mohlala ho ka thusa ho tsoela pele ho hlalosa mesebetsi e ka bang teng ea kelello ho khetha libaka tsa PFC le ho matlafatsa kutloisiso ea rona ea ho nka karolo ha bona bokhobeng ba lithethefatsi. Tlhahlobo ea rona ke mohato o lebisang ntlheng ena.

Lebokose 1 | Liphetoho tse amanang le bokhoba ba khokahano le sebopeho sa PFC

Prefrontal cortex (PFC) e hokahane haholo le libaka tse ling tsa bokong le tsa subcortical tsa boko le marang-rang, ho kenyeletsoa le 'default mode network' (DMN) le 'dorsal attention network', tse amehang lits'ebetsong tsa taolo ea phethahatso joalo ka tlhokomelo le thibelo^{43, 155, 156}. Leha potso ea hore na marang-rang ana - le libaka tse ling tse amanang le boko - litlamorao tsa ho lemalla lithethefatsi li sa tsoa qala ho hlahlojoa, lithuto tsa khokahano ea mmuso tse phomotseng li se li bonts'itse ts'episo ho lipalo tse senolang ho teba ha lefu le sephetho sa kalafo. Mohlala, ho batho ba tsubang, ho tsuba koae ho amana haholo le ho lemalla ha koae. ho sebelisa patch ea nicotine ho matlafalitse haholo matla a khokahano ea litsela tse 'maloa tsa khokahano ea ACC, ho kenyelletsa le tsa meaho ea methapo ea methapo.¹⁵⁷. Ntle le moo, ho batho ba tsubang ba sa tsubeng, ho ntlafala ha matšoao a tlisoang ke nicotine ho ile ha amana le kamano e kopaneng pakeng tsa marangrang a taolo le DMN, ka khokahano e fetotsoeng ea tšebetso ka har'a DMN kenelletsoe moputsong¹⁵⁸. Boithuto ba morao tjena mabapi le ts'ebeliso ea bokhoba ba boko ba nicotine bo fetole mokhoa oa bohlokoa oa ho nahana ka bongata moo khokahanyo e hlahlojoang mabapi le ho tšepahala ha taba ea bohlooho le ho etsa ntho e ncha hape.^{159, 160}.

Matla a khokahano a amanang le marang-rang a marang-rang le ona a fokotsehile ho tse ling tse tlisoang ke lithethefatsi. Ho batho ba lemaletseng koae, rostroventral ACC (karolo ea DMN) e ne e na le khokahano e tlase le mpa ea bohareng, moo dopamine neuron e leng teng¹⁶¹, mme ho hlahisitsoe litholoana tse tšoanang lithutong tse ling¹⁶². Phokotso ea likhokahanyo tse sebetsang le tsona ho tlalehiloe ka temallo ea heroin¹⁶³, eo ho eona khokahano e neng e fetoloa ka mekhoa e amanang le lithethefatsi¹⁶⁴ hape e amanang le nako e telele ea tšebeliso ea heroin¹⁶⁵. Ho hlokahala lithuto tse ling ho tseba hore na khokahano ea naha ea phomolo e bolela esale pele ts'ebetso ea ts'ebetso, le hore na lithethefatsi tsa tlhekefetso kapa meriana e ka bang teng li ka fetola mehato ena joang, mohlala, na ts'ebeliso ea lithethefatsi e eketsa khokahano ea boko ba phomolo le ts'ebetso e susumetsoang ke mosebetsi kapa phomolo e phahameng kapa boemo ba mantlha bo ka amahanngoa le ts'ebetso e fokotsehileng ea mesebetsi? Lipotso tsena li bohlokoa hobane likarabo li tla thusa ho tseba lintlha tsa pheletso ea kliniki-ka mohlala, lethal dose ea meriana e ka theoloa ho ipapisitse le khokahanyo ea tšebetso ea naha ea phomolo.

Lithuto tsa ho nahana ka sebopeho li bonts'itse khatello ea boemo ba bokhubelu ba PFC kapa botenya ho pholletsa le batho ba lemalloang (ho fihlela tahlehelo ea 20%). Mohlala, liphofu tsa PFC li fokotseha, haholo ho dorsolateral PFC (DLPFC), li ngotsoe ho batho ba lemaletseng joala. Liphokotso tsena li amana le tšebeliso e telele ea joala^{166, 167} le ts'ebetso e mpe ea kholo¹⁶⁷, le ho phehella ho tloha likhoeli tsa 6-9 ho fihlela ho lilemo tsa 6 kapa ho feta tsa ho ila^{168, 169, 170}. Leha ho bile le liphetho tse hananang¹⁷¹, lithuto tse ngata ho batho ba lemaletseng koae^{172, 173, 174}, methamphetamine¹⁷⁵, heroin¹⁷⁶ (leha e le kalafong ea methadone^{177, 178}) le nikotine^{159, 160, 179, 180} tlaleha phokotso e tšoanang ea li-PFC tse theohileng - tse hlahelletseng ho DLPFC, ACC le orbitofrontal cortex (OFC) - tse amanang le nako e telele kapa ho teba ha tšebeliso ea lithethefatsi. Ho phehella ha liphetoho tsena tsa sebopeho ntle le pheletso ea tšebeliso ea lithethefatsi le ho tlohela nako e telele ho bontša tšusumetso ea lintho tse tlisoang pele ho boitšoaro bo tsitsitseng kapa tse tsitsitseng tse ka 'nang tsa etsa hore batho ba bang ba sebelise lithethefatsi le ho lemalla nakong ea ntlafatso.lebokose 3). Leha ho le joalo, litlolo tse joalo tsa moralo ha li bonoe ho basebelisi ba joala ba lilemong tsa bocha¹⁸¹ kapa matekoane¹⁸², e fanang ka tlhahiso ea hore litheko tsena tsa PFC e kanna ea ba litholoana tse tlisoang ke ho sebelisa lithethefatsi. Hore na e khetha ho lemalla kapa ke sesosa sa bokhoba, papali e joalo e tlase ea PFC, haholo ho medial OFC, e amana le ho etsa liqeto tse mpe.¹⁸³ ho ka lebisang liphellong tse mpe bophelong ba batho ba lemaletseng joala.

Litlamorao tse tobileng tsa ho pepesetsoa lithethefatsi

Mona, re lekola lithuto tse ileng tsa hlahloba litlamorao tsa lithethefatsi tse matlafatsang le tse sa susumetseng ts'ebetsong ea PFC (Tlhahisoleseling ea S2 (tafole)). Mohlala oa rona o bolela esale pele ntlafatso ea ts'ebetso ea lithethefatsi libakeng tsa PFC tse kenyelletsang lits'ebetso tse amanang le lithethefatsi - ho kenyelletsa likarabo tsa maikutlo, boits'oaro bo ikemetseng le ho nka karolo ha taolo ea maemo a holimo (mohlala, medial OFC (mOFC) le PFC ea ventra ka ho lakatsa, OFC ho tebello ea lithethefatsi, ACC ka hloko leeme le DLPFC ho theha mehopolo e amanang le lithethefatsi). E boetse e bolela esale pele hore ho fokotseha ho bakoang ke lithethefatsi mesebetsing e sa amaneng le lithethefatsi libakeng tsena tsa PFC, haholo-holo nakong ea ho lakatsa le ho itlopa lijo ho batho ba lemaletseng lithethefatsi, ho buisanoeng ka tlase (Fig. 3). Tumellanong le polelo e boletsoeng esale pele, tsamaiso ea koae e kenang kahare ho batho ba lemaletseng koae ka nako e sa lekanyetsoang e ile ea eketsa litlaleho tsa batho ba bangata le ba labalabelang, 'me haholoholo dikarabo tsa karabelo ea oksijene ea mali ea FMRI maemong a fapaneng a PFC subXions12, 13. Ho khahlisang ke hore tšebetso e neng e sebelisoa ka morao ka ho le letšehali la OFC, frontopolar cortex le ACC li ile tsa fetoloa ka tebello ea lithethefatsi (ke hore, ts'ebetso e ne e le kholo kamora ho lebelloa le ho tlisoa ka mokhoa o sa lebelloang oa koae), athe libaka tse katlase li arabetse ka kotloloho ho litlamorao tsa meriana ea koae. ho ne ho se na modulation ka tebello); tataiso e tobileng ea sephetho e fapana le sebaka sa phaello (ROI) 13. Thutong ea 18Fluorodyoxyglucose PET (PET FDG), tsamaiso ea lithethefatsi tse matlafatsang tsa methylphenidate (MPH) ho basebelisi ba cocaine ba mafolofolo li eketsehile tsoekere ea 'mele ea glucose metabolism14. Mona, ea morao ka ho le letšehali OFC e bonts'itse metabolism e kholo ho arabela ho sa lebelloang ho feta MPH e lebelletsoeng; mokhoa o fapaneng le oo oa BOLD phello ho thuto e kaholimo13 e kanna ea bonts'a maikutlo a fapaneng a nakoana a maikutlo a monahano (bona ka tlase).

Lithethefatsi tse matlafatsang li boetse li eketsa tšebetso ea PFC liphoofolong tsa liphoofolo. Mohlala, phallo ea mali a khubung ea tikoloho (rCBF) ho litšoene tse amanang le lithethefatsi tse tsoetseng pele litabeng tsa lithethefatsi e ile ea eketseha ho DLPFC kamora taolo e se nang khang le ho ACC nakong ea boits'oaro bo bobebe bo ikemetseng ba cocaine15, 16. Boithuto ba PET FDG ka sebopeho se tšoanang sa liphoofolo bo bontšitse hore boikoetliso ba koae bo eketsehile metabolism ho OFC le ACC ho isa tekanyo e kholo ha phihlello ea cocaine e ne e atolosoa ho feta nakong ea phihlello e neng e lekantsoe17 (hlokomela hore phihlello e atolositsoeng, empa e sa fihlelletsoe kapa e le khutšoane, ke e amanang le phetoho ho tloha tekanyo e tlase ho isa ho lithethefatsi tse feteletseng, joalo ka ha ho hlaha ho addiction18). Ka mokhoa o ts'oanang, tsamaiso ea cocaine ea intracerebroventricular ka har'a likhoto e bakile karabelo e kholo ea fMRI libakeng tse khethiloeng tsa boko, ho kenyelletsa le PFC19.

Ha ho kopanngoa hammoho, phello e ka sehloohong ea cocaine (le lintho tse ling tse khothatsang tse kang MPH) ho PFC ke ho eketsa ts'ebetso ea PFC, joalo ka ha e lekantsoe ke glucose metabolism, CBF kapa BOLD (leha ho le joalo boithuto bo sa tsoa etsoa, ​​cocaine e fokotsitse bophahamo ba mali ba "cC" ba cocaine ho litšoene tsa macaque20 ). Ha bolelele ba phihlello ea ts'ebeliso ea ts'ebeliso ea lithethefatsi le lithethefatsi e le mosebetsi oa PFC, keketseho ea tšebetso e etsahalang nakong ea ts'ebetso ea lithethefatsi e ka ba sesupo sa phetoho ea ts'ebetso ea phetoho e tsoang ho ts'ebeliso ea pele kapa ea nako le nako ea ts'ebeliso e tloaelehileng, joalo ka neuropsychological e amanang le lithethefatsi. lits'ebetso, ho kenyelletsa tebello e amanang le lithethefatsi (le likarabo tse ling tse nang le maemo), hatella kapa ho fifala ha mekhoa e amanang le lithethefatsi, joalo ka tebello ea - kapa tšusumetso ea ho latela lipheo tse amanang le lithethefatsi (sa feiga. 3).

Ho batho ba tsubang, ba tsubang, RCBF e ile ea fokotsoa ka mokokotlong oa dCC (A-DACC) mme sena se ne se amana le ho fokotseha ha litakatso kamora ho tsuba koae ea pele ea letsatsi21. Ho ile ha tlalehoa melaetsa e ts'oanang pakeng tsa rCBF ho OFC le ho lakatsa ka mor'a ho kenngoa ka lijoaline tse matla tsa heroin ho batho bao e leng li-heroin-wate22. Phapang pakeng tsa litlamorao tsa koae (le tse ling tse khothatsang) le mefuta e meng ea lithethefatsi ts'ebetsong ea PFC li ka bonts'a phapang litlamorao tse tobileng tsa lithethefatsi ho PFC le libakeng tse ling tsa boko (cannabinoid, mu opioid le li-nicotine receptors. bakeng sa matekoane, heroin le nikotini, ka ho latellana, li na le ts'oaetso e fapaneng ea boko ba tikoloho) kapa litebello tseo e seng tsa CNS (cocaine le methamphetamine li na le litlamorao tsa pherekano tse fapaneng le litlamorao tsa matekoane kapa joala), kapa li ka supa ho fapana hoa mekhoa lintlha (mohlala, hore na lithuto li hlahlobile boleng bo felletseng kapa bo amanang le mong ka bona) kapa 23. E kanna ea amana le litlamorao tsa litakatso tse tlisoang ke lithethefatsi: ka lithethefatsi tse kang koae, ho lakatsa ho batho ba lemalloang ho eketsa metsotso ea 10-15 kamora ho tsuba, athe lithuto tse boletsoeng ka holimo li fokotseha ka takatso ea takatso hang ka mor'a ts'ebetso ea nicotine kapa ea heroin. Ha e shebelloa ka leseli lena, 'me e lumellana le mohlala oa rona, sephetho se kopaneng se fana ka maikutlo a hore ha tšebeliso ea lithethefatsi e fokotseha ho lakatsa, sena se amahanngoa le ho fokotseha hoa ts'ebetso e amanang le lithethefatsi ea PFC, le ho fapana. Ka kopanelo le litheko tsena tse amanang le lithethefatsi, re ka lebella hore ts'ebetso ea PFC e sa amaneng le lithethefatsi e eketsehe, joalo ka ha ho le joalo (bona ka tlase).

Ho se lumellane pakeng tsa liphetho karolong ena, le nakong ea Tlhatlhobo ena, ho ka hlahisoa le liphapang lipakeng tsa mekhoa e fapaneng ea ho nahana - taba e lokelang ho ananeloa pejana ho Tlhahlobo ena. Mohlala, PET FDG e lekanya ts'ebetso ea glucose metabolic e atolositsoeng ho feta 30 min, athe fMRI BOLD le PET CBF e bonts'a liphetoho tse potlakileng mekhoeng ea ts'ebetso. Methati ena e boetse e fapana mehatong ea bona ea mantlha: ho ke ke ha khoneha ho theha motheo oa mantlha ka BOLD fMRI, athe ho ka khoneha ka PET le arterial spin labeling MRI. Phapang e 'ngoe e tloaelehileng lipakeng tsa lithuto ke boemo ba mantlha ba motho, mohlala, nako ea ho se thibele e ka ama mehato ea ho lakatsa le ho tlohela.

Likarabo mabapi le mekhoa e amanang le lithethefatsi

Bokaholimo ba ts'ebeliso ea lithethefatsi ke likarabo tse lumellanang le tšusumetso e amanang le sethethefatsi seo batho ba tloaetseng ho se etsa - joalo ka lintho tse sebelisoang ho fana ka lithethefatsi, batho ba rekang lithethefatsi kapa maikutlo ba reng nakong e fetileng ba ne ba imolohile kapa ba ts'oenyehile. ka tšebeliso ea lithethefatsi - e leng se khannang takatso ea ho sebelisa lithethefatsi le eo e leng bahlahisi ba bohlokoa ho khutla hape. Liphuputso tse entsoeng ka boqhetseke li hlahlobe likarabo tsena tse nang le maemo ka ho pepesa batho ba lemaletseng litheko tse amanang le lithethefatsi, mohlala, ka ho ba bontša litšoantšo tse amanang le lithethefatsi. Mona, re qala ka ho lekola lithuto tse bapisang karabelo ea PFC mabapi le ho pepesetsoa tlhahiso ea batho ba lemaletseng le taolo (Tlhahisoleseling ea S3 (tafole)), ebe re buisana ka lithuto tse ileng tsa hlahloba sephetho sa ho ila, tebello le ts'ebetso ea kelello ho karabelo ea PFC ho lithethefatsi Likhakanyo tse amanang le eona (Tlhahisoleseling ea tlatsetso S4 (tafole)). Re bolela esale pele hore bathong ba lemaletseng, likarabelo tsa PFC litekanyetsong tse amanang le lithethefatsi li etsisa likarabo tsa moriana ka boeona, ka lebaka la maemo, le hore ho kenella ho baka karabelo ea likarabo tse fanoeng ke lithethefatsi ho PFC.

Phello ea ho pepeseha hoa cue mosebetsing oa PFC. Le ha ho na le mekhelo24, 25, 26, lithuto tsa fMRI li tlaleha hore ha li bapisoa le taolo, batho ba lemaletseng lithethefatsi ba bonts'a likarabo tse ntlafalitsoeng tsa BOLD ho PFC ho likotsi tse amanang le lithethefatsi tse amanang le litekanyetso (Tlhahisoleseling ea tlatsetso ea S3 (tafole)). Liphetho tsena li tlalehiloe ho DLPFC e ka ho le letšehali, gyrus ea letsoho le ka lehlakoreng le ka letsohong le letšehali (sebaka sa Brodmann 34) ho batho ba bacha ba tsubang koae27, le ho DLPFC ea machabeng le ACC ka nako e khuts'oanyane ea li-alcohol tsa 28. Ho ile ha tlalehoa keketseho e tšoanang lithutong (ho kenyeletsoa lithuto tsa PET FDG) tsa batho ba lemaletseng koae ka ho shebella livideo tse amanang le koaeX29 le tsa batho ba tsubang haholo ba shebang livideo tse amanang le koae ha ba ntse ba sebetsana le koae30. Khafetsa, ha ho na liphapang pakeng tsa batho ba lemaletseng kapa ba sa lemalleng litekanyetso tse phahameng kapa tse khahlisang, kapa esita le karabelo e ikemetseng (mohlala, karabelo ea boitšoaro ea letlalo) ho li-cues31 tse amanang le lithethefatsi, tse fanang ka maikutlo a hore mehato ea neuroimaging e tebile ho feta ho khetholla sehlopha phapang lipotsong tse fumanehang maemong a amanang le lithethefatsi. Habohlokoa le ho feta, likarabo tse fuoeng tsa PFC tse kopantsoeng li kopantsoe le litakatso tsa ts'ebeliso ea lithethefatsi29, 'me li rerela ts'ebetso ea kamora nako e latelang mosebetsing oa ho amohela maikutlo31 le ts'ebeliso ea lithethefatsi 27 likhoeli hamorao32, e bonts'a hore mehato ena e na le bohlokoa ba tleliniki. Joalo ka ha ho ts'ebetso ea PFC e khahliloeng ke li-cues3 tse amanang le lithethefatsi (tse ileng tsa kenya tšebetsong libaka tse subcortical sebakeng sa29), litlamorao tsena li ka hlahisoa feela ha litumelo tse amanang le lithethefatsi li bonoa ka hloko, empa sena se hloka ho ithutoa ho ea pele.

Mohala o khahlehang oa lithuto o lekola ts'ebetso e amanang le PFC e amanang le cue nakong ea ho pepeseha ha lithethefatsi ka har'a lithethefatsi. Ho banna ba itšetlehileng ka heroin ba fumanang liente tsa heroin ha ba ntse ba shebella livideo tse amanang le lithethefatsi, CBF ho OFC e hokahane le takatso ea ho sebelisa lithethefatsi, le CBF ho DLPFC (Brodmann area 9) amanang le thabo22 (Tlhahisoleseling ea tlatsetso S2 (tafole)). Moelelong ona, hoa khahlisa ho tseba hore tatso feela ea joala (e bapisoang le lero la litchi) e ka eketsa ts'ebetso ea BOLD PFC ho lino tse tahang, mme karabelo ena e tsamaisana le tšebeliso ea joala le ho ts'oara35 mme mohlomong e tsamaisoa ke dopamine neurotransuction ho subcortical moputso oa potoloho36 . Ka lehlakoreng le leng, ho batho ba noang joala kapa ba tsubang, ba sa tsubeng, mesebetsi e amanang le cue e fokotsehile ka tahi kapa taolo ea nikotine. Ho fumana hona ho lumellana le ho fumana hore lithutong tse seng lithethefatsi, tsamaiso ea MPH e kenelletseng e fokotse metabolism libakeng tsa ProC tsa PFCNUMX (Box 37). Lithuto tsa nako e tlang li ka bapisa likarabo tsa PFC ka kotloloho ho litloaelo tse amanang le lithethefatsi ho batho ba sa its'epahalleng le ba its'epileng 'me ka ho etsa joalo ba lekola phello ea ho tahoa ho likarabo tse amanang le PFC. Ho nahana ka ho itlopa joala lithutong tse sebelisang tlhekefetso ea lithethefatsi ho ka ba molemo ho moralo oa lipuisano ho fokotsa boits'oaro bo khothalletsoang ke cue.

Lebokose 2 | Karolo ea dopamine le li-neurotransmitters tse ling

Li-receptor tsa Dopamine D2, tse hlalosoang ka mokhoa o tebileng libakeng tse tlasa subcortical tse kang midbrain le dorsal and ventral striatum, le tsona li abeloa ho pholletsa le preortal cortex (PFC). Letoto la lithuto tsa positron emission tomography (PET) le tlaleha ho fumaneha ka tlase ha striatal dopamine D2 receptor ho batho ba lemaletseng methamphetamine¹⁸⁴, cocaine³⁸ kapa joala¹⁸⁵, le bathong ba nang le botenya bo feteletseng¹⁸⁶, 'me liphokotso tsena li ne li amahanngoa le ts'ebetso ea metabolism ea metabolic e fokotsehileng ho orbitof Pambal cortex (OFC) le anterior cingulate cortex (ACC). Sena se fana ka maikutlo a hore tahlehelo ea dopamine e sebelisang li-receptor tsa D2 e ka tlatsa tse ling tsa bofokoli ba ts'ebetso ea pele e ka bonoang ho ts'enyo - mohopolo o tšehetsoang ke data ea pele ho bonts'a hore ho fumaneha ha dopamine D2 receptor ho ne ho amana le karabelo ea PFC ea moriana ho cocaine. - batho ba ahlotsoeng¹⁸⁷. Phokotso ea ho fumaneha ha li-stopat dopamine D2 hape ho tlalehiloe ho batho ba tsubang ba banna haholo, kamora ho tsuba ka mokhoa o tloaelehileng le kamora lihora tsa 24 tsa ho tsuba; maemong a teng, ho fumaneha ha dopamine D2 receptor ka hara naha e kopaneng ea ACC ho ne ho amana hampe le takatso ea ho tsuba (litumellano tse ntle li bonts'itsoe bakeng sa striatum le OFC)¹⁸⁸. Bopaki ba dopamine depletion ho dorsolateral PFC (DLPFC) le bona bo tlalehiloe ho sa foleng ba bacha ketamine basebelisi, le maemo a ho nyahama a ne a amana le tšebeliso e phahameng ea beke le beke ea lithethefatsi¹⁸⁹. Boithuto bo bong ba PET bo tlalehiloe ka mokhoa o hlakileng oa tokollo ea dopamine ka lebaka la taolo e kenang ea moriana o hlasimollang (mohlala, methylphenidate) ho ba hlekefetsang koae le lino tse tahang, ka ho fokotseha ho tšoanang ha boiphihlelo ba ho itlaleha ba ho ikutloa ba le holimo^{38, 185}.

E lumellana le datha ho tsoa lithutong tsa liphoofolo, liphetho tsena ho batho ba lemaletseng li supa ts'ebetso ea dopaminergic e sa bonahaleng - ea mantlha le ea ho arabela phephetso e tobileng - e amanang le ho lakatsa ho matla le ho teba ha ts'ebeliso. Karabo e sa hlabang ea dopamine e rerile esale pele e tla khetha khetho ea 'nete bakeng sa koae ho feta chelete ho batho ba lemaletseng koae, e leng ho fanang ka maikutlo a hore e ka' na ea etsa hore lithuto li boele li boele li phele hape.¹⁹⁰. Liphetho li boetse li bontša hore, ka ho laola boholo ba dopamine e eketseha ho striatum¹⁸⁵, OFC e nka karolo ea bohlokoa phetolong ea boleng ba bathusi; Ho sitisoa ha molao ona ho ka bakela boleng bo eketsehang bo hlahisitsoeng ka moputso oa lithethefatsi lithutong tse lemaletseng. Tumellanong le tlhahiso ena, metabolism ho medial OFC le Aral ea kahare ho bahlaseli ba koae e ile ea eketseha ka mor'a taolo e matlafatsang ea maikutlo, athe e ile ea fokotsoa ka taolo; keketseho ea metabolic ea tikoloho ho bahlorisi e ne e amahanngoa le takatso ea lithethefatsi³⁸.

Li-opioid tsa tlhaho le tsona li hokahanya likarabo tse khotsofatsang tsa lithethefatsi tse ngata tsa tlhekefetso, haholo-holo heroin, joala le nikotine. Tšebeliso e mpe ea lithethefatsi e amahanngoa le ho fokotseha ha tlhahiso ea li-opioids tsa endo native, e leng tšusumetso e ka kenyang matšoao a ho khaola, ho kenyeletsa dysphoria. Ho ithuta ho sebelisoa [¹¹C] carfentanil e bonts'itse hore batho ba hlekefetsang koae ba ne ba e-na le bokhoni bo phahameng ba PFC mu opiate receptor binding (e bonts'ang maemo a tlase a opioid ea maemo a tlase) ho feta taolo e ntle eo e seng lekhoba la tahi, le hore sena se ile sa phehella ho cortex ea ka pele le ACC ho feta libeke tsohle tsa 12¹⁹¹. Receptor e phahamisitsoeng ea opiate receptor e tlamang ho DLPFC le ACC pele kalafo e ne e amahanngoa le tšebeliso e kholo ea koae le nako e khuts'oanyane ea ho ila, mme o ile a khothalletsoa hore e be moetapele oa sephetho se nepahetseng sa kalafo ho feta ts'ebeliso ea mantlha ea lithethefatsi le joala.¹⁹². Liphello tse tšoanang li tlalehiloe ho banna ba lemaletseng joala¹⁹³, athe boemo ba 'mu (kapa kappa) opiate receptor bo khutlisetsoa morao ke methadone e sa foleng ho batho ba lemaletseng heroin¹⁹⁴.

Ho fokotsa bokhoni ba ho kopanya ba PFC bakeng sa radiotonin transporter radioligand ho tlalehiloe ho ba hlekefetsang methamphetamine¹⁹⁵, basebelisi ba bacha ba MDMA ea boithabiso¹⁹⁶ le ho hlaphoheng joala¹⁹⁷. Ho fumaneha ha transporter ea serotonin ho fokotsang ho ka bonts'a neuroadaptations ho eketsa synotic serotonin, empa e ka boela ea bonts'a tšenyo litsing tsa methapo ea kutlo ea serotonergic. Lits'ebetso tse ling tsa neurotransmitter tse laolang PFC ebile li kenelletse li-neuroadaptations tse etsahalang ka tšebeliso e mpe ea lithethefatsi ho liphoofolo tse sebetsang li kenyeletsa glutamate¹⁹⁸ le cannabinoid^{199, 200} litsamaiso. Leha ho le joalo, ho tla fihlela joale ha ho na lithuto tse phatlalalitsoeng tse nang le radiotracers ho tšoantšisa litsamaiso tsena bokhobeng ba batho.

Sheba Tlhahisoleseling ea tlatsetso S7 (tafole) bakeng sa kakaretso ea lithuto tse bapisang litsamaiso tsa neurotransmitter lipakeng tsa batho ba lemaletseng taolo le taolo e phetseng hantle.

Ts'ebetso ea PFC ho lintlha tse amehang e boetse e tlalehiloe litlamong tsa boitšoaro. Mohlala, banna ba batona ba neng ba bapala lipapali tsa inthanete nako e fetang lihora tse 30 ka beke ba bontšitse ts'ebetso ea BOLD ho OFC, ACC, medial PFC le DLPFC ha ba shebella litšoantšo tsa papali, mme lits'ebetso tsena li ne li tsamaellana le takatso ea ho bapala. Ka mokhoa o ts'oanang, ha o bapisoa le litaba tsa taolo, batho ba papali ea papali ea chelete ba shebelletseng livideo tsa papali ea chelete ba bonts'itse ts'ebetso e eketsehileng ho DLPFC e nepahetseng le gyrus39 e ka tlase, mme ts'ebetso ena e amana le takatso ea ho becha40. Ka lehlakoreng le leng, phuputso e 'ngoe ho batho ba bechang ba sa sebetseng e bonts'itse likarabo tse fokotsoang tsa moea o tsoang ka letsohong le letšehali la PFC BOLD ho hlola ho fapana le ho lahleheloa ke mosebetsi o kang oa papali ea chelete, mme boholo ba phokotso bo ne bo tsamaellana le bohale ba bokhoba ba papali ea chelete, joalo ka ha ho hlahlojoa lipotso tsa papali ea chelete. Litsela tse fapaneng tsa phetoho ea ketsahalo (li-hyperactivations le li-hypoactivations ha li bapisoa le taolo) li kanna tsa tsamaisoa ke ROI (mohlala, ho holofala ho amanang le mosebetsi oa PFC hangata ho bonoa mme ho thoe ke karolo ea 'network e sa feleng' 41) , liphapang tsa takatso (takatso e tlalehiloe ho Refs 42, 43, 39 empa eseng Ref. 40), liphapang tsa mosebetsi kapa lintlha tsa mokhoa, tse akaretsoeng qetellong ea karolo ena.

Mathata a khetholloang ke taolo e sa sebetseng ea ts'ebeliso ea lijo a boetse a amahanngoa le ts'ebetso e sa tloaelehang ea PFC ho li-cue. Sena ha se lebelloe, ka lebaka la hore mathata ana le bokhoba ba tahi li kenyelletsa ho sekisetsa ho ts'oanang le lipotong tsa neuronal44, ho kenyelletsa le ho fokotseha ha ho fumaneha ha striatal dopamine D2 receptor45. Mohlala, basali ba nang le anorexia kapa bulimia ba shebang feela litšoantšo tsa lijo (ha ba bapisoa le litšoantšo tse sa amaneng le lijo) ba bonts'itse likarabo tse eketsehileng tsa fMRI BOLD ho PFC46 ea ventromedial ventrom. Ha li bapisoa le bakuli ba nang le bulimia, bakuli ba nang le anorexia ba bontšitse ts'ebetso e kholo ea tokelo ea OFC ho arabela linepe tsa lijo, mohlomong e leng se amang sebaka sena ka boits'oaro bo fetelletseng; Ka lehlakoreng le leng, ts'ebetso ea DLPFC e setseng litšoantšong tsena e ile ea fokotseha ho bakuli ba nang le bulimia ha e bapisoa le taolo e phetseng hantle, mohlomong e amang sebaka sena tahlehelo ea taolo ea ho ja lijo46. Phuputsong e 'ngoe, basali ba banyane ba nang le mathata a ho ja, empa ba sa laole lihlooho, ba bonts'itse ts'ebetso ea PFC e tsoang ka lehlakoreng le letšehali nakong ea khetho ea lentsoe le lebe ka ho fetesisa ho tsoa litsing tsa lentsoe tse amanang le' mele (ha li bapisoa le nakong ea khetho ea lentsoe le sa nke lehlakore ho tloha mantsoe a sa nke lehlakore) 47. Liphapang tse joalo ha lia ka tsa bonoa ka mantsoe a mabe ka kakaretso, a bontšang hore ts'ebetso ea sebaka sena e tsamaisoa ke mantsoe a amanang haholo le lithahasello tsa sehlopha sena sa mokuli. Ha ho nkuoa hammoho le sephetho ho batho ba bapalang papali ea chelete ba hlalositsoeng kaholimo ho 42, likarabo tsa PFC tse tsoang ka ntle ho 'mele li ka latela bohlokoa ba maikutlo a ho tšoenyeha ka ho fetesisa ho bakuli bao ho buuoang ka bona (ke hore, ho hapa kapa ho qoba tahlehelo bakeng sa batho ba nang le bolotsana ba ho becha, setšoantšo sa' mele bakeng sa batho ba nang le Mathata a ho ja le mekhoa e amanang le lithethefatsi bakeng sa batho ba lemaletseng lithethefatsi) mme e ka sebetsa e le sepheo sa ho latela lits'ebetso tsa kalafo bokhobeng, joalo ka ha ho sa tsoa hlahisoa48, 49.

Phello ea ho ila, litebello le ho kena lipakeng tlhokomelong ea motho. Mona, re fana ka tlhahiso ea hore ho kenella ha kelello le ho qeta nako e telele ho fihlelle likarabo tse tlisoang ke PFC, le hore tebello e amanang le lithethefatsi le ho ila nako e khuts'oane ho na le litlamorao tse fapaneng. Tšusumetso ea ho tlohela nako e khuts'oanyane mosebetsing o amanang le PFC e ithutile haholo litabeng tsa bokhoba ba nicotine (Tlhahisoleseling ea tlatsetso S4 (tafole)). Phuputsong e arolang ea ho ngola MRI, ho se ts'oaroe ha hora ea 12 ho batho ba tsubang ho eketse litakatso, CBF ea lefats'e le CBF ea tikoloho ho OFC, mme e fokotse CBF ho PFC e nepahetseng, ka liphetoho tsa CBF ho li-ROI tsohle tse tsamaellanang le litakatso le matšoao a ho tlohela50. Reacuction e ntlafalitsoeng ea cue ena e boetse e tlalehiloe nako e teletsana ea ho itima lijo - ho fihlela matsatsi a 8 ho DLPFC, ACC le botlaaseng bo ka pele bo tlase ho basali ba tsubang51 - hape e amana hantle le ho lakatsa52. Leha ho le joalo, lithuto tse ling li tlaleha hore ha ho na tšusumetso ea ho ila ts'ebetso ea CC e khothalletsoang ke CC. Sena se kanna sa hlahisoa ke lintlha tse ling tse bakang phapang e kholo litlamorao, joalo ka tebello ea ho tsuba qetellong ea thuto53. Kannete, joalo ka ha ho tšohliloe ka holimo54, tebello feela e ka etsahalla litlamorao tsa tšebeliso e mpe ea lithethefatsi ts'ebetsong ea PFC ho batho ba lemaletseng. Boithuto boo ho bona mefuta eohle e meraro - tebello ea taolo ea lithethefatsi, ho pepesetsoa litšebelisanong tse amanang le lithethefatsi le ho ila - e hlahlojoa ka litlamorao tse kholo le tšebelisano 'moho ts'ebetsong ea PFC li ka ba molemo, haholoholo haeba li kenyeletsa disampole tse kholo. Matla a nakoana a PFC cac reactivity e boetse e ntse e lokela ho hlahlojoa lithutong tse telele, ho lekola motho a le mong nakong eohle ea nako e telele ea ho itima lijo.

Mohala o ts'episang oa lipatlisiso o hlahloba ho feto-fetoha ha boitšoaro ha cue reaction. Mohlala, karolo bakeng sa mOFC ho hatelleng takatso ea maikutlo e bontšitsoe ke lipatlisiso tse tsoang thutong ea morao-rao ea PET ho basebelisi ba koae. Ho labalabela ho eketseha ka mor'a ho shebella video ea lintho tse amanang le koae, le maemo a ho lakatsa a amanang le tsoekere ea glucose ho PFC55 ea medial. Habohlokoa, ha barupeluoa ba ne ba laetsoe - pele ba shebella video - ho thibela takatso ea takatso, metabolism ho MOFC e nepahetseng e fokotsehile, mme sena se ne se amahanngoa le ts'ebetso ea ts'ebetso e nepahetseng e ka tlase ea frontal gyrus (sebaka sa Brodmann 44), e leng sebaka sa bohlokoa taolong ea thibelo. Ho batho ba tsubang ba tsubang lisakerete tsa kalafo, taelo ea ho hanela ho tsilatsila ha ba ntse ba shebella livideo tse amanang le ho tsuba e ne e amahanngoa le ts'ebetso ea DLPFC le ACC, leha e ne e sa lebelloa, ts'ebetso ena e ne e tsamaisana hantle le ho lakatsa ho tsuba56. Phuputso ea morao-rao e bonts'a hore tataiso ea phetoho ea ts'ebetso le ho ikamahanya le takatso ea litakatso e ka fetoloa ka leano la boitšoaro le sebelisoang ho hatella takatso. Thutong ena e khahlehang, ba tsubang koae ba laetsoe ho nahana ka litlamorao tsa nako e telele le tsa nako e telele tsa ho ja tšusumetso e bonts'itsoeng litšoantšong (tse amanang le koae tse amanang le koae tse amanang le lijo) 57. Ho nahana ka litlamorao tsa nako e telele ho ne ho amahanngoa le ts'ebetso e eketsehang libakeng tsa PFC tse amanang le taolo ea kelello (DLPFC le gyrus e tlase) le ts'ebetso e fokotsehileng libakeng tsa PFC tse amanang le ho lakatsa (mOFC le ACC). Ntle le moo, takatso ea ho itlaleha e ile ea fokotseha ha lithuto li nahana ka litlamorao tsa nako e telele, 'me li ne li tsamaellana hampe le ts'ebetso ho DACC le DLPFC. Tlhahlobo ea bohokahanyi e bonts'itse hore kamano e pakeng tsa ts'ebetso e eketsehang ho DLPFC le ho fokotseha ho amanang le melaoana e ne e se ea bohlokoa kamora ho kenyelletsa mosebetsi o fokotsehileng oa "ventral striatum" mohlaleng ona. Leha ho le joalo, lithuto tsa preclinical tse sebelisang lisebelisoa tsa ho tlatsa kapa tsa optogenetic li hlokahala ho utloisisa hamolemo tšebelisano ea PFC le seterral ea ho hatella likarabo. Ho nkuoa hammoho, liphetho tsa lithuto tse sebelisang mekhoa ea boits'oaro ho hatella ho lakatsa ho fana ka ts'ehetso molemong oa rona o kopantsoeng (sa feiga. 3), e khethollang lipakeng tsa libaka tsa PFC tse tsamaisang boiteko ba ho se lemohe ba taolo le taolo ea thibelo ea lithethefatsi (DLPFC, dACC le gyrus e tlase). tse bontshang ho ameha ka maikutlo a amanang le lithethefatsi, litakatso le boits'oaro bo hatellang (mOFC le ventral ACC).

Ho akaretsa, ho pepesehela litloaelong tse amanang le lithethefatsi ho etsisa litlamorao tsa taolo e tobileng ea lithethefatsi ts'ebetsong ea PFC ho batho ba lemaletseng lithethefatsi, leha ho le joalo, tšusumetso ea nako ea ho ila le tebello ea ts'ebeliso ea lithethefatsi (le lits'ebetso tse amanang le tsona tse kang ho theha mehopolo e amanang le lithethefatsi) , le liphallelo tsa bona tse ikhethang mosebetsing oa PFC, li ntse li lokela ho hlahlojoa ka mehlala e meholo. Ka ho holisa lithuto tsa ho sebetsa hape ka cue ho kenyelletsa mesebetsi e meng ea neuropsychological, le ka ho lekola tataiso ea lihokelo pakeng tsa tšebetso ea PFC le lintlha tse tobileng tsa mohlala (mohlala, ho lakatsa), bohlokoa ba ts'ebetso ea libaka tse itseng tsa ts'ebetso ea PFC bo lemaletseng. Khothaletso e 'ngoe ea lithuto tsa nako e tlang mabapi le ho sebetsa hape ke ho tsamaisa lipapiso ka kotloloho lipakeng tsa (mohlala, ho ithiba ha ho bapisoa le ho satiety) le maemo a mosebetsi (mohlala, lithethefatsi tse khahlanong le ho se nke lehlakore) le ho etsa likamano tsa kelello ka liphetoho tse fapaneng tsa boitšoaro. Boithuto ba nako e tlang bo ka bapisa nako le mokhoa oa ts'ebetso ea PFC kamora ho pepeseha ha lithethefatsi tse mpe le ho latela ho pepesehela litekanyetso tse maemong tse tšoanang lithutong tse ts'oanang. Boithuto ho batho ba sa lemalloang bo ka sebelisoa ho lekola tšusumetso ea ho hloka (mohlala, lijo) le litlhoko tse potlakileng (mohlala, tlala, takatso ea thobalano le sepheo sa ho fihlella) ho PFC cue reacaction. Mohlala, ho taolo e nyane ea bophelo bo botle, ho lakatsa lijo tse nahanoang - tse susumetsoang ke lijo tse matlafatsang - ho ne ho amahanngoa le ts'ebetso libakeng tse 'maloa tsa maoto le tsa parisane, ho kenyelletsa ACC (Brodmann sebakeng sa 24) 58.

Ho bohlokoa ho hlokomela hore kaha ha re so hlahlobe lingoliloeng tse tsoang ka hare ho terri - mme ka hona lipapiso tse tobileng li ke ke tsa etsoa lipakeng tsa PFC le likarabo tse ikhethileng mabapi le maikutlo ana - re ke ke ra nyenyefatsa, leha ho ka ba joalo ka hore sena ke hore, ts'ebetso ea PFC ka boeona e ka kenya letsoho ho litlamorao tse khotsofatsang tsa lithethefatsi le mekhoa ea lithethefatsi.

Likarabo tsa meputso eo e seng ea lithethefatsi

Re fana ka tlhahiso ea hore ho batho ba nang le ts'ebeliso ea lithethefatsi, ts'ebetso ea PFC ho arabela moputsong o sa amaneng le lithethefatsi e khahlano le liphetoho tsa ts'ebetso tsa PFC tse supang ts'ebetso e amanang le lithethefatsi (feiga. 3). Haholo-holo, ho batho ba lemaletseng lithethefatsi ba leng maemong a ho lakatsa, ho tahoa, ho khaola kapa ho ikoalla kapele, maikutlo a PFC ho fumana meputso e sa amaneng le lithethefatsi, e tla bontšoa haholo ha ho bapisoa le lithutong tse phetseng hantle tse sa lemaletseng joala. Kannete, ho fokotseha ha maikutlo ho meputso e sa amaneng le lithethefatsi ke phephetso ntlafatsong ea kalafo ea bakuli ba nang le mathata a tšebeliso ea lithethefatsi. Ka hona, ho bohlokoa ho ithuta hore na batho ba lemaletseng lithethefatsi ba arabela joang ho ba khothalletsoang bao eseng ba lithethefatsi.

Boikutlo bo fokotsehileng joalo ba moputso o amanang le lithethefatsi bo hlalositsoe e le moelelo o tloaelehileng59. Tlhalosong ena, ts'ebeliso ea lithethefatsi khafetsa le e phahameng e lebisa liphetohong tse matlafatsang tsa boko tse fokotsang ts'ebetsong ea hedonic le ts'ebetso ea tšusumetso ('moputso'), ho fapana le ho matlafatsa sistimi e hanyetsang (mohanyetsi kapa 'anti-moputso' )60. Ts'ebetso ena e ts'oana le mamello, moo kutloisiso ea moputso e fokotsehang. E hapuoe hape ke khopolo-taba ea mohanyetsi e hlahisitsoeng ke Slomon le Corbit61, 62, e hlalosang matla a nakoana a likarabo tsa maikutlo tse hanyetsanang; mona, matlafatso a fosahetseng (ka mohlala, ho hula) a hlola matlafatso a matla (mohlala, a susumetsoang ke lithethefatsi) phetohong ea ts'ebeliso ea lithethefatsi ka linako tse ling ho ba lemalla. Ts'ebetso ena e bohlokoa molemong oa phetolo ea maikutlo le taolo ea maikutlo, eo, ha maikutlo a hlalosoang e le 'linaha tse matlafatsoang ke batšehetsi'63, li tlameha ho senyeha bokhobeng ba lithethefatsi, haholo nakong ea ts'ebetso ea leeme e kang ho lakatsa le ho itlopa joala.

Anhedonia ke tšobotsi e hlalosang ts'ebeliso ea ts'ebeliso ea lithethefatsi64, le mekhoa ea pherekano e kholo ea khatello ea maikutlo - e kenyeletsang anhedonia e le letšoao la mantlha - e kopane le batho ba bangata ba lemaletseng lithethefatsi (ka mohlala, 50% ea batho ba lemaletseng koaeXXUMUMX). Kamano e matla lipakeng tsa mathata a ts'ebeliso ea maikutlo le ts'ebeliso ea lithethefatsi ha e felle feela ho khatello ea maikutlo65; mohlala, khatello ea maikutlo ke ntho e ka bang kotsi bakeng sa ho khutla hape ha lithethefatsi66. Leha ho le joalo, lipatlisiso mabapi le hore na ho fetoloa ha maikutlo ho fetohileng ho ameha joang mathateng a tšebeliso ea lithethefatsi ho bokhachane67, 68, joalo ka ha ho tšohliloe ka tlase (Tlhahisoleseling ea tlatsetso S69 (tafole)).

Chelete ke sesebelisoa se sebetsang se sa sebetseng, se mahareng le se akaretsang se fumanang boleng ba sona ka tšebelisano 'moho,' me se sebelisoa thutong ea maikutlo maikutlong a batho a letsatsi le letsatsi; Ts'ebetso e sekiselitsoeng ea moputso ona e kanna ea supa mokhoa o mobe oa ho ithuta sechabeng ka ho lemalla. Bofokoli bo joalo, bo khethollehileng ka ho fetesisa ka lebaka la boleng bo matla ba ho susumetsa le ho tsosa bo atisang ho amahanngoa le moputso ona, ho ka tiisa mohopolo oa hore bokhobeng, lipotoloho tsa moputso oa boko li 'koeteloa' ke lithethefatsi, leha e le monyetla oa ho ba le khaello e seng e ntse e le teng ts'ebetsong ea moputso le eona e ke ke ea qheleloa ka thoko.

Phuputso e 'ngoe ea fMRI e batlile hore na batho le litsamaiso tse lemaletseng koae ba arabetse joang ha ba amohela moputso oa chelete bakeng sa ts'ebetso e nepahetseng tlhokomelong e tsitsitseng le mosebetsing oa khetho e qobelloang70. Ho taolo, moputso oa chelete o tsitsitseng (phaello e neng e sa fapana ka har'a li-block block le tse neng li ka tsejoa esale pele) e ne e amahanngoa le moetlo oa morao-rao oa OFC ho arabela ka mokhoa o hlophisitsoeng (ketsahalo e nyolohileng ka monotonically ka palo: phaello e phahameng> phaello e tlase> ha ho na phaello), athe DLPFC le rostral ACC li arabetse ka ho lekana ho chelete efe kapa efe ea chelete (phaello e phahameng kapa e tlase> ha ho na phaello). Moetso ona o tsamaellana le karolo ea OFC ho sebetsaneng le moputso o lekanyelitsoeng, joalo ka ha ho tlalehiloe ho bao e seng batho71 le lithuto tsa batho72, 73, 74, 75, 76, hape le karolo ea DLPFC e lebisitsoeng ho77. Lihlooho tse lemaletseng Cocaine li bonts'itse lipontšo tse fokotsehileng tsa fMRI ka letsohong le letšehali la OFC bakeng sa leruo le phahameng ha li bapisoa le taolo ebile li ne li sa tsotelle phapang lipakeng tsa meputso ea chelete ka letsohong le letšehali la OFC le DLPFC. Ho makatsang ke hore, halofo e fetang ea batho ba lemaletseng koae ba lekantsitse boleng ba chelete eohle ka ho lekana (ke hore, US $ 10 = US $ 1000) 78. Liphesente tse mashome a robeli a metso e mehlano tsa phapang ea litekanyetso tsena li ka bakoa ke likarabo tsa morao-rao tsa OFC le karolelano ea medial frontal gyrus (le amygdala) moputsong oa chelete lihloohong tse lemalloang. Leha liphuputso tsena li hloka ho phetoa ka boholo ba mehlala le ka mesebetsi e hlokolosi, leha ho le joalo ba fana ka maikutlo a hore batho ba bang ba lemaletseng koae ba kanna ba fokotsa kutloisiso ho liphapang tse amanang le boleng ba meputso. Ho 'batalatsa' ho joalo ha gradient e nkoang e le matla ho ka ipapisa le boleng bo holimo kapa leeme ho meputso ea hanghang (joalo ka setlhare se fumanehang) 79 le theolelo ea meputso e meholo empa e liehile80, 81, ka hona e fokotsa ts'ebetso e matlafatsang ea ts'ebetso. Liphetho tsena e kanna ea ba ea bohlokoa kalafong kaha ho matlafalitsoe hoa chelete maemong a laoloang hantle ho bonts'itsoe ho ntlafatsa ho ithiba ha lithethefatsi82, hape ho kanna ha ba le bohlokoa ho profeta sephetho sa kliniki. Tumellanong le mohopolo ona, sechabeng se tšoanang, boemo ba ts'ebetso ea maiketsetso ea DACC mosebetsing moo ts'ebetso e nepahetseng e neng e lefuoa ka mokhoa o lekanang le tšebeliso ea koae khafetsa, athe degree ea rostroventral ACC (e fetelang ho mOFC) hypoactivation e tsamaellanang le mosebetsi- Ho susumetsoa ke takatso ea khatello. Ho ne ho e-na le mokhatlo o fapakaneng oa li-PFC ROI tsena tse nang le cue reactivity bohareng ba likokoana-hloko tse lemaletseng koae empa eseng lithutong tsa taolo, tse amang likarolo tsena tsa ACC taolong ea likarabo tsa lithethefatsi tse iketsang83.

Ho ke ho hlokomeloe hore lithutong tse hlalositsoeng ka holimo, lithuto ha lia botsoa ho khetha pakeng tsa meputso ea chelete. Re bolela esale pele hore khetho e tla latela ts'ebetso e tšoanang (khetho ea moputso o tlase) litulong tse phetseng hantle ho feta ho batho ba lemaletseng, bao re lebelletseng ho bonts'a ho feto-fetoha ha maemo (ho khetha lithethefatsi ho feta tse ling tse khothalletsang), haholo-holo nakong ea ho lakatsa le ho itlopa joala. . Boithuto bo lumellang lithuto ho khetha lipakeng tsa li -forforter li entsoe haholo liphoofolong tsa mosebetsi. Liphuputso tsena li bonts'itse hore, ha ho fanoa ka khetho, liphoofolo tse pepesitsoeng lithethefatsi li khetha lithethefatsi ho feta novelty85, boits'ebetso bo lekaneng ba bo-mme le lijo86, 87, 88, li bonts'a hore ho pepeseha lithethefatsi ho ka fokotsa boleng bo ananeloang ba meputso ea tlhaho, esita le tse e hlokahala bakeng sa ho pholoha. Phuputsong ea morao-rao e entsoeng ke motho eo ho eona lithuto li ka hapang koae kapa chelete, batho ba tsubang ka linako tse ling ba ne ba khothalletsoa ho fumana chelete ho feta ho tsuba, athe batho ba tsubang ba itšepang ba ne ba etsa boiteko bo tšoanang ba ho hapa chelete kapa ho tsuba koae. Sehlopha se tšoanang ka ts'ebelisano ea moputso se ile sa bonoa ka ho le letona la OFC, DLPFC ea bobeli mme sa tloha ACC, hoo ka linako tse ling batho ba tsubang libaka tsena ba bonts'a ts'ebetso e phahameng ho susumetsa moputso oa chelete ho feta ho susumetsa ho hakana ka moputso oa koae, athe ba tsubang ba its'epileng ba bonts'itse ha ho na phapano ea bohlokoa tšebetsong e joalo ea boloi e lebelletsoeng. Libaka tsena li boetse li bonts'itse ts'ebetso e phahameng ho chelete ka linako tse ling ho fapana le ho batho ba tsubang ba89.

Liphetho tsena, hammoho le sephetho sa boits'oaro litlhahlobong tsa neuropsychological ho batho ba lemaletseng koae XXUMX, 91 (bona le Box 92), li kenya letsoho kutloisisong ea rona ea hore na likhetho tsa moputso o lekanang li ka fetoha joang tšebelisong e joalo ka khetho ea lithethefatsi e hlolisang le ('me ka linako tse ling e feta) khetho bakeng sa bathusi ba bang, ka ho fokotseha ho hoholo hoa bokhoni ba ho abela litheolelo tse amanang le litheolelo tse amanang le lithethefatsi.

Reacciation ea maikutlo.

Liphuputso tse 'maloa tse hlahlojoang kaholimo li bapisitse likarabo tsa PFC ho tse sa ameheng empa li tsosa maikutlo a maikutlo ka likarabo ho tse amanang le kameho (mohlala, tse amanang le lithethefatsi) 25, 26, 28, 46, 47 (Tlhahisoleseling ea tlatsetso S3 (tafole)) . PFC e ne e sa sebetse hantle ha e arabela litšoantšo tse tsoang mefuteng eohle ea maikutlo lithutong tse lemaletseng joala28, PFC e ka pele e ne e se na boikaketsi ho arabela litšoantšo tse monate ho batho ba lemaletseng heroine26, le ho bakuli ba nang le mathata a ho ja likarabo tsa PFC litšoantšong tse khelohileng li ne li tloaelehile46, 47. Kahoo, ho fapana le se boletsoeng esale pele ke mohlala oa rona (Setšoantšo sa 3), ho ne ho se na phapang karabong ea PFC lipakeng tsa lithuto tse amanang le lithethefatsi le tse amang maikutlo empa e se tse amanang le lithethefatsi ho tse ling tsa lithuto tsena. Sephetho sena, le ho fapana ha liphetho, ho ka bakoa ke - hara lintlha tse ling - palo e nyane ea lithuto, liphapang lipakeng tsa lithuto (joalo ka boholo ba mehlala, sethethefatsi se ka sehloohong sa tlhekefetso le nako ea ho ithiba) le kutloisiso ea mehato e sebelisitsoeng. Liphuputso tsa nako e tlang li tla una molemo ka ho sebelisa lirekoto tse amanang le liketsahalo kapa electroencephalography, tse nang le tharollo e phahameng haholo ho feta fMRI kapa PET.

Setšoantšo se hlakileng se hlaha ha lithuto li kenyelletsa tšebetso ea maikutlo mesebetsing ea kelello-boits'oaro (Tlhahisoleseling ea S5 (tafole)). Mohlala, ha ho hlokahala ho lumellana le protagonist letotong la likarete, e 'ngoe le e' ngoe e bonts'ang pale e khuts'oane, batho ba lemaletseng methamphetamine ba fane ka likarabo tse fokolang ntle le taolo ea potso ea "ke eng e tla etsa hore motho ea ka sehloohong a ikutloe a le betere?" 93. Ha ho bapisoa le ho laola lithuto, batho ba lemaletseng hape ba bonts'itse hypoactivation ho OFC (le hyperactivation ho DLPFC) ha ba araba potso ena. Ntle le thuto e le 'ngoe ho batho ba lemaletseng lithethefatsi tsa heroinXXUMUM, lithuto tse ling tse tšoanang li boetse li tlaleha liphapang lipakeng tsa lihlopha tse lemaletseng le ho laola likarabelo tsa PFC mesebetsing e hlokang ho sebetsoa ha maikutlo a maikutlo joalo ka lifahleho, mantsoe kapa maemo a rarahaneng. Mohlala, ha banna ba lemaletseng joala ba taolo ba matla a mahlano a sefahleho, lipuo tse mpe li ne li amahanngoa le ts'ebetso e tlase ho ACC ea leqele empa ts'ebetso e phahameng ho DLPFC le dacC e nepahetseng e bapisoa le li-control94. Ntle le moo, ha ho bapisoa le taolo e phetseng hantle, basebelisi ba cocaine ba bonts'a li-ACC le dorsomedial PFC hypoactivations ha ba ntse ba etsa mosebetsi oa khethollo ea lengolo nakong ea tlhahiso ea litšoantšo tse monate (tse sa nke lehlakore) le li-hyperactivations ho DLPFC e kopaneng nakong ea tlhahiso ea lintho tse sa thabiseng (tse khahlisang) pictures95. Ka mokhoa o ts'oanang ha ho bapisoa le taolo e phetseng hantle, batho ba tsubang matekoane ba bontšitse li-ACC hypoactivations le tokelo ea DLPFC le litsobotsi tse tlase tsa boemo bo tlase ba karabelo ha ba hlahisa sefahleho se koatileng se koatileng (khahlanong le lifahleho tse sa jeleng paate); Karabelo e nepahetseng ea ACC e tsamaellana hantle le khafetsa ea tšebeliso ea lithethefatsi le likarabo tse ikhethileng tsa ACC tse tsamaellanang le maemo a moroto oa cannabinoid le tšebeliso ea joala96. Ka lehlakoreng le leng, dacC ea ka ho le letšehali e ne e le sesole sa methati e itšetlehileng ka methapo ea methamphetamine ha e bapisoa le taolo ha e ahlola maikutlo a sefahleho ka mosebetsi o amang (ho ahlola sebopeho sa lipalo) mme sena se ne se amana le lehloeo le boits'oaro bo ikemetseng ho lithuto tse lemalloang97.

Ha ho kopantsoe hammoho, lithuto tsena li bontša hore DLPFC e sebetsa haholo nakong ea ts'ebetso ea maikutlo ho batho ba lemaletseng ho bapisoa le litaba tsa taolo, haholoholo bakeng sa maikutlo a mabe. ACC e bonts'a liphetho tse tsoakaneng, leha e na le lithuto tse ngata tse bonts'ang boikaketsi ho feta ho hloka botsitso. Ho ka etsahala hore ts'oaetso e matla ea DLPFC e kanna ea lefella boikaketsi ba ACC, bo ka hlalosang ho haella ha phapang ts'ebetsong ea ts'ebetso lipakeng tsa batho ba sebelisang hampe lithethefatsi le taolo e nepahetseng boholo ba lithuto tsena. Boitšoaro bo fosahetseng le / kapa ba ho nkeha maikutlo bo ka bonoa nakong ea liphephetso tse matla tsa maikutlo tse kang khatello ea maikutlo, takatso kapa mesebetsi e thata ho feta. Ho hlakile hore mesebetsi ea libaka tsena malebana le mofuta o sisintsitsoeng (Setšoantšo sa 3) e hloka ho utloisisoa hantle. Ho ka etsahala hore, ka ho hira pele ho ts'ebetso ea ts'ebetso e phahameng ea li-PFC (e buelletsoeng ke DLPFC), ts'usumetso e mpe ea maikutlo e eketsa kotsi ea ts'ebeliso ea lithethefatsi ho batho ba lemaletseng lithethefatsi, haholo-holo maemong a behang khatello e eketsehileng mehloling e fokolang ea taolo ea kutloisiso. Tlhaloso ena e tsamaellana le tlholisano lipakeng tsa lits'ebetso tse amanang le lithethefatsi le tse sa amaneng le lithethefatsi le lipakeng tsa lits'ebetso tsa 'ho bata' le 'ho chesa' ka mohlala (Setšoantšo sa 3c).

Leha lithuto tse 'maloa tse boletsoeng kaholimo li sebelisitse lits'oants'o tse mpe tsa valenced, potso e sa feleng ke hore na kutloisiso e fetotsoeng ho batho bao e seng makhoba a lithethefatsi e boetse e sebetsa ho ba matlafatsang ba fosahetseng joalo ka tahlehelo ea chelete. Boithuto liphoofolong bo bonts'a hore bafo ba 'lemaletseng' ba bonahatsa ho phehella ha lithethefatsi le haeba sethethefatsi se amana le ho fumana ts'oaetso ea motlakase99. Ho batho, hypoactivation ka ventrolateral PFC e nepahetseng ho batho ba tsubang nakong ea tahlehelo ea chelete, le ho batho ba papali ea chelete nakong ea phaello ea chelete, ho tlalehiloe 100 (Tlhahisoleseling ea Tlatsetso S5 (tafoleng) Leha lithuto tse ling li hlokahala ka ho hlaka, moelelo oa phokotso ea kutlo ho batho ba matlafatsang bokhoba ba tahi o na le litlamorao tse ntle le, ntle le tse matlafatsang (joalo ka li-voucher le litokelo), li-reinforcers tse mpe (joalo ka ho koalloa teronkong) ba sebelisang lithethefatsi hampe. Mehato e ka ntlafatsoa ka ho khetha mofuta o sebetsang ka ho fetisisa le lethal dose. Liphuputso tsa nako e tlang li ka thusa ho netefatsa hore na batho ba lemaletseng joala ba ka sebelisa lithethefatsi hobane ba boreha habonolo, ba ferekane, ba koatile kapa ba tšohile, mohlomong ka lebaka la ts'ebetso e fetotsoeng ea PFC. Moeli o tlase oa ho ba le efe kapa efe ea maikutlo ana, kapa ho hloleha ho boloka boits'oaro bo tataisoang ke sepheo (mohlala, ho phethela mosebetsi o bora) ha o na le maikutlo ana, ho ka amahanngoa le taolo e holofetseng ea thibelo (ke hore, ho susumetsoa ke maikutlo) joalo ka ha ho hlahlojoe ka tlase. Ho batho ba lemaletseng k'hok'heine, mesebetsi ea PFC e tloaetse ho fana ka puo khafetsa ea ts'ebetso e khothatsang e matlafatsang101, e ka bang tekanyo ea ts'itiso e sitoang ea boiteko mme ea baka ho se nke karolo ho lekaneng mesebetsing ea kalafo.

Taolo ea inhibitory ea ho lemalla

Ho lemalla lithethefatsi ho tšoauoa ka ho senyeha ho bonolo, empa ho atile, ho nahanisisa maikutlo ho ka potlakisang tsela ea eona, ho ts'osetsa ho ithiba ka nako e telele 102 kapa ho eketsa mokhoa oa kalafo103, 104. PFC e bohlokoa bakeng sa lits'ebetso tse ngata tsa ts'oaetso, ho kenyeletsoa tlhokomelo, mohopolo oa ho sebetsa, ho nka liqeto le ho lieha litheolelo (Letlapa la 105), tseo kaofela li sekiselitsoeng ho batho ba lemaletseng lithethefatsi, joalo ka ha li hlahlojoe kae kapa kae1. Mosebetsi o mong oa bohlokoa oa kutloisiso ea PFC ke boits'oaro, 'me mona re tsepamisitse maikutlo ho karolo ea PFC ts'ebetsong ena ea bokhoba (Tlhahisoleseling e tlatselletsang S106 (tafole)). Boitaolo bo bolela, hara tse ling tsa ts'ebetso, ho bokhoni ba motho ba ho tataisa kapa ho emisa boits'oaro, haholoholo ha boits'oaro bo ka se be hantle kapa bo be molemo, kapa bo nkuoe e le ntho e fosahetseng ho e etsa. Sena se amana le bokhoba ba tahi, leha ho na le tlhokomeliso ea litlamorao tse bohloko tsa lithethefatsi (bona le karolo e ka tlase mabapi le tlhokomeliso ea mafu ka bokhoba ba tahi), batho ba lemaletseng lithethefatsi ba bonts'a bokhoni ba ho thibela tšebeliso e mpe ea lithethefatsi. Taolo e holofetseng ea thibelo, eo e leng ts'ebetso ea mantlha ea boits'oaro, e kanna ea kenya letsoho ho kenelletseng liketsong tsa botlokotsebe molemong oa ho fumana sethethefatsi, le ho theha taolo e senyehileng ea maikutlo a mabe, joalo ka ha ho boletsoe kaholimo. Mathata ana a ka beha batho kotsing ea ho lemalla lithethefatsi. Tumellanong le litlaleho tsa pejana6, boitšoaro ba bana nakong ea lilemo tse leshome tse qalang tsa bophelo bo bolela esale pele ho itšetleha ka lithethefatsi lilemong tsa bona tsa leshome tsa bophelo107.

E-ea / u sa ee le ho emisa lipontšo tsa nako ea karabelo.

Mesebetsi eo hangata e sebelisoang ho lekanya taolo ea inhibitory ke mosebetsi oa ho ea / ho se ee le mosebetsi oa ho emisa ka lets'oao la ho emisa (SSRT). Mosebetsing oa ho ea / ho se ee, batho ba lemaletseng koae ba bontšitse liphoso tse ngata tsa ho se sebetse le komishene ho feta taolo mme hona ho hlahisitsoe ka hypoactivation ho dACC nakong ea liteko tsa ho emisa109. Phuputsong e 'ngoe, phokotso ea boitšoaro ba inhibitory ho basebelisi ba koae e ile ea eketsoa ke mosebetsi o mongata haholo oa ho hopola; hape, hypoactivation ea dACC e ne e amahanngoa le ts'ebetso e fokolang ea mosebetsi110. Ka mokhoa o ts'oanang, banna ba lemaletseng heroine ba bonts'itse linako tse fokolang tsa karabelo mosebetsing / ho se ee, hammoho le hypoactivation ho ACC le medial PFC111. Liphetho tse tsoang ho SSRT li thata haholo ho li hlalosa. Mohlala, ACC e ne e le tšibollo nakong ea katleho e thibelitsoeng ha e bapisoa le litšitiso tse sa atlehang tsa karabo ho banna ba lemaletseng koae, mme ts'ebetso ea bona ea boits'oaro e ne e ts'oana le ea control112. ACC e ne e boetse e na le tšibollo nakong ea phetoho e hlokolosi ea boitsoaro 'me e nka monyetla oa ho kenya ts'ebetsong lino tse tahang, haholo lithutong tse nang le takatso e matla ea joala ka nako ea fMRI scan113. Ka lehlakoreng le leng, ACC e ne e le mofere-fere nakong ea liphoso tsa thibelo113, mohlomong hobane lithethefatsi tse tahiloeng li sebelisitse tlhokomelo e kholo ho lekola letšoao la ho emisa ho feta taolo - ts'ebetso e amanang le ACC. Ts'ebetso e ntseng e eketseha libakeng tse ling tsa PFC e boetse e tlalehiloe ho ba tsubang ka mor'a ho tsuba ka mor'a ho tsuba ka hora ea 24, empa (ho fapana le tebello ea ts'ebetso e eketsehileng ea ts'ebetso ea tikoloho) e fokotsehile114 (Tlhahisoleseling ea tlatsetso S4 (tafole)).

Phapang e kholo ea liphetho tse tsoang lipatlisisong tsena e kanna ea bakoa ke liphapang tse hlahlobong, mofuta oa papiso le phapang ea tšebetso lipakeng tsa lihlopha, ntle le tse ling tse fapaneng. Leha ho le joalo, ho hlaha mokhoa oo dACC e nang le ts'usumetso nakong ea mesebetsi ena ea taolo ea thibelo, mme ts'ebetso ena ea kelello e amanang haholo le ts'ebetso e sa sebetseng, haholoholo le linako tse khutšoane tsa ho ila. Ts'ebetso e lebelletsoeng ea kelello-boits'oaro e ka fokotsa ts'ebeliso ena. Mohlala, ho fana ka leseli ka ho ruta (joalo ka ho fana ka temoso ea teko e tlang ea ho se tsamaee) taolo e ntlafatsang ea inhibitory mosebetsing oa ho ea / ho se ee, mme sena se ne se kopantsoe le ts'ebetso e ntlafalitsoeng ea ACC ho batho ba lemaletseng methamphetamineX. Litšebelisano tse joalo tsa kelello le boits'oaro li ka sebelisoa e le boikoetliso ba neano bo kopanetsoeng 'me li kopantsoe le taolo e tšoanang ea lithethefatsi, joalo ka ha ho hlalositsoe ka tlase.

Mesebetsi ea Stroop.

 Taolo ea inhibitory e ka boela ea hlahlojoa ho sebelisoa 'mala-lentsoe Stroop task116. Ts'ebetso e fokolang butle le liphoso tse ling nakong ea liteko tse sa nepahalang mosebetsing ona ke letšoao la ho hloka taolo ha PFC. Patlisiso e entsoeng ka neuro e bonts'itse hore dACC le DLPFC li kentse letsoho mosebetsing ona117, 118, 119, ka likarolo tse ikhethileng bakeng sa libaka tsena ho khethollano ea li-dacC le resolution (DLPFC) 120.

Boithuto bo sebelisang mofuta oa li-stroop tsa mebala ho batho ba lemaletseng bokhoba ba litlaleho li hlahisa liphetho tseo hangata li lumellanang le tse tlalehiloeng kaholimo. Mohlala, ba hlekefetsang koae ba ne ba na le CBF e tlase ho dacC ea leqele le DLPFC e nepahetseng nakong ea liteko tse sa nepiseng letho ha li bapisoa le liteko tse kopanetsoeng, athe ACC e nepahetseng e bontšitse mokhoa o fapaneng; ho feta moo, ts'ebetso ea ACC e nepahetseng e ne e amana hantle le cocaine use121 (Tlhahisoleseling ea S6 (tafole)). Ho banna ba sebelisang matekoane, CBF e tlase nakong ea mosebetsi ona e tlalehiloe libakeng tse 'maloa tsa PFC, ho kenyelletsa le ACC ea morao-rao, ventCosial PFC le DLPFC122. Lithuto tse itšetlehileng ka Methamphetamine li boetse li bonts'itse li-hypoactivations khokahanong ea taolo ea inhibitory, ho kenyelletsa dACC le DLPFC ha ba ntse ba etsa mosebetsi ona123. E lumellana le tšusumetso ea ho ila mosebetsi mosebetsing oa ho ea / ho se ee - tlalehiloeng ka holimo114, ba tsubang lisakerete ba ileng ba lekoa kamora ho ts'oara hora ea 12 ba ile ba fokotsa linako tsa karabelo, mme ba ntlafatsa dACC le ho fokotsa likarabo tse nepahetseng tsa DLPFC litekong tse sa sebetseng ka 'mala-lentsoe Stroop task124 (Tlhahisoleseling ea tlatsetso S4 (tafole)). Habohlokoa le ho feta, tlhahlobo ea fMRI e bonts'itse ts'ebetso ea ts'ebetso ea PFC ea ventromedial (libaka tsa Brodmann 10 le 32) nakong ea polelo-lentsoe mosebetsi oa Stroop o ile a etsa libeke tsa 8 pele ho ts'ebetso ea phekolo e ile ea bolela esale pele sephetho sa kalafo ho batho ba lemaletseng koae.

Mofuteng o mong oa maikutlo oa mosebetsi ona, mantsoe a 'mala a nkeloa sebaka ke mantsoe kapa litšoantšo tse amanang le sebaka seo motho a itseng a amehileng ka sona, joalo ka mantsoe a amanang le joala bakeng sa batho ba lemaletseng joala. Leha liteko tsa Stroop tsa khale le tsa maikutlo li kenyelletsa tlhoko ea ho hatella likarabo ho tlhaiso-leseling e nyarosang ha ka nako e ikhethileng e boloka tlhokomelo ho thepa e khothatsang e hlokahalang ho phethela mosebetsi, ke mosebetsi oa maikutlo oa Stroop feela o sebelisang kamano ea maikutlo joalo ka moferekanyi. Moralo o joalo oa maikutlo oa Stroop o kanna oa tsoela pele ho arola tšebetso e fetotsoeng ea PFC bokhobeng: na e ka khonahala ho mofuta o fe kapa o fe oa likhohlano kapa e etsahala ka kotloloho nakong ea likhohlano tse amanang le lithethefatsi?

Phuputso ea fMRI ho basebelisi ba matlafatsang e bonts'itse ho tsotella mantsoe a amanang le lithethefatsi: batho ba lemaletseng, empa ba sa laoloe, ba bonts'a tlhokomelo e hlakileng ho mantsoe a amanang le lithethefatsi (a lekantsoeng joalo ka karabelo ea maikutlo a mahareng a mebala e khethiloeng ka nepo ea mantsoe a amanang le lithethefatsi ho tlosa tumello karabelo ea karabelo ea mebala e khethiloeng ka nepo ea mantsoe a se nang lehlakore), e neng e kopantsoe le likarabo tse ntlafalitsoeng ka lehlakoreng le letšehali la PFC. Likarabo tse joalo ha lia ka tsa bonoa bakeng sa 'mala-lentsoe Stroop task126. Ka mokhoa o ts'oanang, linepe tse amanang le lithethefatsi li holisa likarabo tsa dACC tsebong e amanang le ts'ebetso ho batho ba tsubang koae. Liphumano tsena li fana ka maikutlo a hore ts'ebelisong, lisebelisoa tse eketsehileng tsa tlase li hlokahala ho tsepamisa mohopolo mesebetsing e amanang le lithethefatsi e le teng ka lintho tse ka e sitisang (ka hona, e le leeme) nakong ea mosebetsi. Ho loantšana le liphetho tsena le tse ling127 ke lithuto ho basebelisi ba koae ba hona joale, moo mantsoe a amanang le lithethefatsi a neng a sa amane le ts'ebetso e liehang kapa liphoso tse ling tsa128, 83. Phapang ena e ka amana le moralo oa mesebetsi kapa boemo ba ho batla kalafo ba barupeluoa; re bolela esale pele hore ntoa e ntlafatsang lipakeng tsa mantsoe a amanang le lithethefatsi le mantsoe a sa jeleng paate e tšoaea batho ba lekang ho ila lithethefatsi. Bopaki ba phello e joalo ho ba tsubang ba tsubang haufinyane bo phatlalalitsoe129.

Litlamorao tsa taolo ea lithethefatsi nakong ea mesebetsi ea taolo ea inhibitory.

Ho haelloa ke taolo ea maikutlo le taolo ea thibelo ho batho ba lemaletseng le ho ntlafatsa ts'ebetso ea PFC ka taolo e otlolohileng ea lithethefatsi (bona kaholimo le tlhaiso-leseling e tlatselletsang S2 (tafole)) hammoho li ka tšehetsa mohopolo oa ho iphekola131, 132. Ho latela khopolo-taba ena, ho itšebetsa ka lithethefatsi - le keketseho e amanang le ts'ebetso ea PFC - ntlafatsa likhaello tsa maikutlo le kutloisiso tse teng ho batho ba lemaletseng lithethefatsi. Phello e joalo ea ho iphekola e kile ea amoheloa ke sechaba sa kalafo, joalo ka ha ho pakoa ke ho sebelisa methadone (e leng opioid ea maiketsetso) joalo ka kalafo e tloahelehileng ea agonist bakeng sa ts'epahalo ea heroine. Phuputsong ea fMRI, ho shebella likhopolo tse amanang le heroine ho ne ho amahanngoa le takatso e fokolang nakong ea kamora 'tekanyetso ho feta nakong ea tekanyetso ea methadone ea pele ho batho ba lemaletseng heroine,' me ho fokotseha ho tšoanang likarabong tse amanang le maikutlo ho tse peli tsa OFC133 (Tlhahisoleseling e tlatselletsang S4 (tafole)). Ts'ehetso ea matla e qala ho bokella bakeng sa phello e ts'oanang ho batho ba lemaletseng koae. Mohlala, koae e kenang methapong (e eketsang li-extracellular dopamine level) ho basebelisi ba k'hok'heine e ntlafalitse taolo ea thibelo mosebetsing oa ho ea / ho se tsamaee, mme sena se ne se amahanngoa le tloaelo ea ts'ebetso ea ACC le ts'ebetso e ntlafalitsoeng ea ts'ebetso ea DLPFC nakong ea mosebetsi134. Intravenous MPH (eo hape e eketsang li-extracellular dopamine level) ka mokhoa o ts'oanang e ntlafalitse ts'ebetso ho SSRT ho batho ba hlekefetsang k'hok'heine, 'me sena se ne se hokahane hantle le ts'ebeliso e amanang le ts'itiso ea cortex e ka pele e kahare e ka morao mme e hokahane hampe le ts'ebetso ho PFC e tsoang ka har'a mali. kamora MPH, ts'ebetso libakeng ka bobeli e bonts'itse tloaelo ea ho tloaela maemo a tloaelehileng135. Phuputso ea PET e bonts'itse hore MPH ea molomo e fokolitse metabolism e fokotsehileng libakeng tsa limbic brain - ho kenyeletsoa lateral OFC le DLPFC - tse ileng tsa latela ho pepesetsoa likhopolo tse amanang le cocaine ho batho ba lemaletseng cocaine136. E boetse e fokolitse liphoso tsa khomishene, mokhoa o tloaelehileng oa ho se ts'oenyehe, nakong ea ts'ebetso ea maikutlo e amanang le lithethefatsi, ho batho ba lemaletseng koae le ho laola, le ho batho ba lemaletseng phokotso ena e ne e amahanngoa le ho ts'oaroa hoa ts'ebetso ho rostroventral ACC (e atoloha ho mOFC) le DACC; Ts'ebetso e amanang le mosebetsi oa DACC pele tsamaiso ea MPH e hokahanngoa le ts'ebeliso e nyane ea ts'ebeliso ea joala137 (Setšoantšo sa 4). Leha e ntse e lokela ho ithutoa hore na litla-morao tsa MPH li kenya letsoho joang litlamorao tsa eona tsa 'ho tloaela' basebelisi ba koae, ha li kopantsoe liphetho tsena li fana ka maikutlo a hore litlamorao tse matlafatsang tsa dopamine tsa MPH li ka sebelisoa ho thusa liphetoho tsa boits'oaro ho batho ba lemaletseng lithethefatsi ( mohlala, ntlafatsa boits'oaro), haholo haeba kalafo ea MPH e kopantsoe le mehato e ikhethileng ea kutloisiso.

Setšoantšo sa 4 | Tšusumetso ea methylphenidate ea molomo ho ts'ebetso ea cortex ea anterior le ts'ebetso ea ho lemalla joala ba koae.

Methylphenidate e ntlafatsa likarabo tse sebetsang tsa MRI e kopanya likarabo le ho fokotsa liphoso tsa khomishene ho tsebiso e ikhethileng ho batho ba nang le ts'ebeliso ea koae. a | 'Mapa oa axial oa libaka tsa cortical o bonts'itseng likarabo tse ntlafalitsoeng ho methylphenidate (MPH) ha li bapisoa le placebo ho batho ba lemaletseng koae. Libaka tsena ke dorsal anterior cingrate cortex (dACC; libaka tsa Brodmann 24 le 32) le rostroventromedial ACC (rvACC) e atolohang libakeng tsa medial orbitof Pambal cortex (mOFC; Brodmann libakeng tsa 10 le 32). Maemo a bohlokoa (Lintlha tse ngata tsa tšebetso) li ngotsoe ka mebala (e bontšitsoe ke sekala sa mebala). b | Khokahano pakeng tsa lets'oa la BOLD (e hlahisitsoeng e le% sign change from placebo) rvACC extending to the mOFC (x = −9, y = 42, z = −6; Brodmann libakeng tsa 10 le 32) nakong ea ts'ebetso ea mantsoe a amanang le lithethefatsi le ho nepahala mosebetsing oa fMRI (ka bobeli ke lintlha tse fumanehang: MPH minus placebo). Lithuto ke batho ba 13 ba nang le mathata a tšebeliso ea koae le 14 li-control. Setšoantšo se hlahisoa hape ka tumello ho Ref. 215 © (2011) Macmillan Publishers Ltd. Litokelo tsohle li sirelelitsoe.

Re lokela ho hlokomela hore litlamorao tsa dopamine agonists mabapi le ho rarolla mathata a amanang le ts'ebetso ea kelello maikutlong kapa maikutlong a kelello, li ka latela mohlala oa tšebeliso e mpe ea lithethefatsi126 kapa liphapang tse ling, tse kang ho itaola le tšebeliso ea lithethefatsi bophelo bohle. lula u lokela ho ithutoa ka mehlala e meholo ea mehlala. Hape, li-probes tse se nang dopaminergic (mohlala, cholinergic kapa AMPA receptor agonists) li ka fana ka lipehelo tse ling tsa pharmacological bakeng sa kalafo ea ts'ebeliso ea koae ea cocaine138.

Ka kakaretso, sephetho sa liphuputso ho taolo ea thibelo ea lithethefatsi bokhobeng ba lithethefatsi se fana ka maikutlo a hore ho na le dacC hypoactivity le taolo e fokolang ea thibelo ho batho ba lemaletseng lithethefatsi. Ts'ebetso e ntlafalitsoeng ea PFC e tlalehiloe ka mor'a ho tlohela nakoana, ho pepesetsoa litloaelo tse amanang le lithethefatsi le lithethefatsi ka boeona (kapa li-pharmacological agents tse tšoanang). Leha ho le joalo, leha ho pepesetsoa lithethefatsi ho boetse ho amahanngoa le ts'ebetso e ntle mesebetsing ena ea kelello, ho ithiba ka nakoana le ho pepesehela litloaelo tse amanang le lithethefatsi ho na le sephetho se fapaneng le ts'ebetso ea mosebetsi. E shebiloe moelelong oa mofuta oa tlhahiso e boletsoeng (sa feiga. 3), leha lithethefatsi tsa tlhekefetso li fana ka liphallelo tsa nakoana, ho ikoetlisa ka nako e telele le lithethefatsi tsena ho na le litlamorao tsa nako e telele - meeli e fokotsitsoeng ea taolo ea thibelo le tšitiso e amanang le maikutlo - e kanna ea se ke ea felisoa ka ho ithiba nakoana, hape ho tloaeloang ho nchafatsoa ha ho pepesetsoa mekhoa e amanang le lithethefatsi. Ho tloaela mesebetsi ena, ho sebelisa ts'ebetso ea bophelo bo botle ba bongaka le boits'ebetso - ho kopantsoe le ba khothalletsoang - e lokela ho ba sepheo kalafong ea ho lemalla.

Tlhokomeliso ea lefu le lemallo

Bokhoni ba ho utloisisa lefatše la rona le kahare (ho kenyelletsa ho kenella empa ho fetela ho taolo e phahameng ea maikutlo, tšusumetso le boits'oaro) bo its'etleha ho PFC. Ka lebaka la bofokoli ba tšebetso ea PFC ho batho ba nang le bokhoba ba tahi bo hlahlobiloeng kaholimo, ho ka etsahala hore tlhokomeliso e thibetsoeng ea boholo ba boits'oaro kapa tlhoko ea kalafo e ka tiisa se neng se reoa ke 'ho hana' bokhoba ba lithethefatsi - ke hore , khopolo ea hore mokuli ea lemaletseng lithethefatsi o khona ho utloisisa ka botlalo likhaello tsa hae empa a khetha ho e hlokomoloha e ka ba phoso. Ho joalo, liphuputso li sa tsoa fana ka maikutlo a hore batho ba lemaletseng lithethefatsi ha ba tsebe hantle hore na bokuli ba bona bo boima hakae (ke hore, ho batla ha bona lithethefatsi le boits'oaro le litlamorao tsa hona) mme sena se kanna sa amahanngoa le likhaello marangrang a taolo139.

Liphuputso tse 'maloa li fane ka bopaki ba karohano lipakeng tsa boithati le boits'oaro ba' nete bokhobeng. Mohlala, taolong e phetseng hantle lebelo le ho nepahala ha likarabo bakeng sa boemo bo phahameng ba lichelete ha li bapisoa le ho se nke lehlakore mosebetsing oa tlhokomelo o matlafatsoang ka mokhoa o qobelloang o neng o lefshoa le ho itlaleha ha hao mosebetsing. Ka lehlakoreng le leng, litlaleho tsa lihlooho tsa k'hok'heine tsa ho nka karolo mosebetsing li ne li khaotsoe mesebetsing ea tsona ea 'nete, e bonts'a ho se lumellane lipakeng tsa boits'oaro bo itlalehang le boits'oaro bo susumetsoang ke sepheo. Ho sebelisa mosebetsi o sa tsoa hlahisoa moo barupeluoa ba khethileng litšoantšo tseo ba li ratang mefuteng e mene ea litšoantšo ebe ba tlaleha seo ba nahanang hore ke mofuta oa bona oa litšoantšo o khethiloeng70, phapang pakeng tsa ho itlaleha le khetho ea 'nete - e bonts'a temohisiso ea boits'oaro ba khetho ea motho - e ne e le e matla ka ho fetisisa ho basebelisi ba hajoale ba k'hok'heine, leha e ne e boetse e bonahala ho basebelisi ba itšireletsang, bao e neng e amana le bona khafetsa khafetsa ka tšebeliso ea cocaine ea91.

Mochini oa motheo oa karohano ena e kanna ea ba ho se kopane ha likarabo tsa boits'oaro le boits'oaro nakong ea ho ithuta ho feto-fetohang, joalo ka ha ho bonts'itsoe hore ho etsahetse kamora ho tsoa lesioning ho litšoene140. Ho na le bopaki bo bong ba li-neural-boits'oaro bo fapaneng le ho batho. Thutong e ka bang teng e amanang le ketsahalo e sebelisang mosebetsi o tlalehiloeng kaholimo ho 70, lihlooho tsa taolo li bonts'itse likarabo tsa motlakase le linako tsa karabelo maemong a chelete e phahameng ha li bapisoa le boemo ba ho se nke lehlakore, mme mehato ena e 'meli ea tlhokomelo e susumetsoang e ne e amana. Mokhoa ona ha oa ka oa bonoa sehlopheng se lemaletseng k'hok'heine, moo ho nang le bokhoni ba ho arabela ka nepo ho chelete (ke hore, ho fetoha hoa boits'oaro ho matlafatso ena), ho amanang hampe le makhetlo a ts'ebeliso ea koae ea morao-rao141. Phuputso e 'ngoe e bontšitse hore, mosebetsing oa papali ea chelete, likhetho tsa lithuto li ne li tataisoa ke liphoso tsa' nete le tse iqapetsoeng, athe batho ba tsubang lisakerete ba ne ba tataisoa feela ke liphoso tseo ba li entseng, leha liphoso tse iqapetsoeng li bakile likarabo tse matla tsa methapo ea kutlo142, hape e supa ho ikarohanya le neural-boits'oaro bokhobeng. Mofuteng o hlahisitsoeng (setšoantšo sa 3), mochini ona o emeloa ke phokotso e tlisoang ke libaka tse laoloang ke ts'ebetso ea maikutlo le likarabo tse maemong a phahameng.

Habohlokoa, ho batho karohano ena ea boits'oaro e ka netefatsoa ka ho bapisa litlaleho tsa bakuli le tsa ba fanang ka tsebo137 joalo ka litho tsa lelapa kapa bafani ba kalafo, kapa ka mehato e ikemiselitseng ea ts'ebetso litlhahlobong tsa methapo ea kutlo143. Ho bohlokoa ho hopola hore mehato ea ho itlaleha e fana ka leseli la bohlokoa ho likhaohano tse joalo, empa ha ho fanoa ka meeli ea litlaleho tsa hau, nts'etsopele ea mehato e mengata ea kutloisiso le tlhokomeliso e bohlokoa bakeng sa lipatlisiso le merero ea bongaka. Mehato e 'meli e ts'episang ke tlhokomeliso ea liphoso mme e ama ho ts'oana. Tlhokomeliso ea liphoso mosebetsing oa ho ea / oa ho ea e fumanoe e fokotsoe ho batho ba hlekefetsang matekoane ba banyenyane mme sena se ne se amahanngoa le phokotso ho DLPFC ea mahaeng le ACC e nepahetseng, le ts'ebeliso e kholo ea lithethefatsi ea hona joale144. Lithutong tse itšetlehileng ka methamphetamine, PFC e kenang ka hare ho naha e ne e se na maikutlo nakong ea tšusumetso e tšoanang mme sena se ne se amahanngoa le alexithymia145 e itlalehang haholo. Ha tlhokomeliso e ntlafetseng ea ts'ebeliso e mpe ea lithethefatsi e boletse esale pele ho ithiba ho fihlela selemo se le seng kamora kalafo ea lino tse tahang1, mohala ona o ntseng o hola oa lipatlisiso o ka matlafatsa kutloisiso ea rona ea ho khutlela mokhoeng oa lithethefatsi, ka mohlala, ho ntlafatsa mekhoa ea ho kenella e teng hona joale, ka ho lebisa tlhokomelo batho ba lemalloang ba fokotsitseng tlhokomeliso ea bona bakeng sa mehato e lumellanang.

Meeli ea ho ithuta le mekhoa ea nako e tlang

Lintho tse ka sehloohong tse hlahisang Tlhahlobo ena ke tsepamiso ea rona ho PFC ka litšenyehelo tsa ho se kenye likarolo tse ling tsa bokong ba cortical le likarolo tse sa bonahaleng. Moralo o tšehetsang ts'ebetso e phahameng ea taolo le taolo ea holimo-tlase o rarahane mme ho nahanoa hore o kenyelletsa marang-rang a ts'ebetso a kenyelletsang, ho kenyelletsa le PFC, libaka tse ling tse kang parietal cortex e phahameng, insula, thalamus le cerebellum147. Ka lebaka leo, hape e fuoe meeli ea tlhaho ea lithuto tse amanang le tšibollo ea batho, tšebeliso ea ho hloka toka e lokela ho qojoa - ke hore, PFC e kanna ea se ke ea tsamaisa bofokoli bo hlalositsoeng tekong ena. Boithuto ba meta-bokamoso boo ho bona ho senyehileng ha marang-rang a ts'ebetso ea ts'ebeliso ea lithethefatsi ntle le tšebeliso ho lokelang ho ts'oaroa ka litholoana tse tsoang lipatlisisong tsa mechini ho liphoofolo tse sebetsang.

Taba e hlokomelehang e nang le lipatlisiso tse ngata tse hlahlojoang tse mabapi le ts'ebeliso ea bona ea tšebetso ea ROI e reng ka linako tse ling e haelloa ke litlhahlobo tse matla tsa lipalo tsa tlhahlobo ea kelello eohle. Mohlala, ho hlola litaba tsa matla a tlase, sephetho se tlalehiloeng ka linako tse ling se lekanyetsoa ho tlhahlobo ea kamora ho hoc libakeng tse bonts'itseng liphetho tsa bohlokoa ho lithuto tsohle ho maemo ohle a mosebetsi; Tlhahlobo ea kelello ka botlalo (ka mohlala, sehlopha kapa mofuta oa ts'usumetso) kapa litlamorao tsa tšebelisano, kapa lihokelo tsa ho etsa mosebetsi kapa tsa lipetlele tsa kliniki ha li etsoe hangata. Ka hona, liphetho tse joalo tsa ROI li ka emela phoso ea Mofuta oa I empa li ka boela tsa fetoa ke likarolo tsa bohlokoa tsa neural tse kenyellelitsoeng ketsahalong e entsoeng tlasa lipatlisiso, mohlala, ho lakatsa kapa taolo ea ho lakatsa. Mokhoa oa ho fokotsa meeli ea tlhahlobo ea kamora ho hoc ke ho etsa tlhahlobo ea kelello ka bobeli le ho sebelisa ROI148, 149, e ka thusang ho ntlafatsa nomenclature ea ROIs lithutong tsohle. Litaba tse ling tse tloaelehileng li amana le tlhahiso e sa phethahalang ea data ea 'nete (joalo ka ho se fane ka moelelo le phapang, kapa ho se fane ka mahlaseli ha a fana ka tlaleho), e ka hlakisang tataiso ea phello (activation le deactivation), e ka eketsang phapang e teng ho Liphetho tse phatlalalitsoeng (mohlala, hyperactivation e ka bua ka ts'ebetso e phahameng kapa deactivations tse tlase ho tloha tlase). Ka kakaretso, tšimo ena e tla una molemo ho tloha maemong a ts'oanang - a lits'ebetso tse amanang le ho nahana, mesebetsi, sekaseko le sebopeho sa thuto - tse tla nolofalletsa ho hlalosoa ha se fumanoeng. Boemo ba maemo bo boetse bo bohlokoa bakeng sa ho lumella ho hokahanngoa ha li-setshelo tsa data ho tsoa li-laboratories tse fapaneng - ho hlophisoa ha lintlha joalo ho tla bohlokoa haholo lithutong tsa liphatsa tsa lefutso tse ikemiselitseng ho utloisisa puisano lipakeng tsa liphatsa tsa lefutso, nts'etsopele ea boko, ts'ebetso ea boko le litlamorao tsa lithethefatsi lits'ebetsong tsena. Mohlala, ho boptjoa ha lisebelisoa tse kholo tsa ho nahana ka mokhoa oa ho nahana ho tla ba bohlokoa ho utloisisa hore na liphatsa tsa lefutso tse tsamaeang le ho lemalla ho lemalla li ka ama kelello ea motho joang kamora ho tšebeliso e mpe ea lithethefatsi. Ho feta moo, bokhoni ba ho kopanya li-data tse kholo tsa ho nahana - joalo ka ha bo sa tsoa etsoa bakeng sa litšoantšo tsa MRI tsa phomolo e sebetsang e kopanyang150 - e tla lumella kutloisiso e ntlafalitsoeng ea ts'ebeliso ea ts'ebeliso ea kelello ea hore nakong e tlang e ka sebetsa e le biomarker ho tataisa kalafo.

Le ha ho na le mekhelo e seng mekae (e hlahisang PFC e nepahetseng, haholo-ACC le DLPFC, ts'ebetsong ea phumano ea thibelo) lintlha tse hlahlojoang mona ha li na mohlala o hlakileng o bonts'ang liphetoho tsa morao-rao tsa boko ho batho ba lemaletseng. Leha ho le joalo, lateralization e ne e se sepheo sa lipatlisiso ho e 'ngoe ea lithuto tse lekiloeng. Kaha ho na le bopaki ba ho senyeha ha morao nakong ea ho ts'oara menoana ho tlhekefetso ea koaeX151, lithuto tse etsang lipatlisiso tsa patlisiso ea PFC ka kotloloho ho iRISA ka ho lemalla lia hlokahala. Ntle le moo, ho na le liphapang tse hlakileng tsa bong mabapi le karabo ea lithethefatsi le phetoho ea ho ts'oara joala, 'me lithuto tsa monahano li eketsa kutloisiso ea rona mabapi le likarolo tsa botona le botšehali tsa boko ba motho. Leha ho le joalo, ho fihlela joale, lithuto tse 'maloa tse laoloang hantle li tsepamisitse maikutlo phapusing ea botona le botšehali boemong ba PFC bokhobeng; ho fapana le hoo, lithuto tse ngata li sebelisa lithuto tsa basali kapa tsa banna (boholo ba banna). Boithuto bo boetse bo hlokahala ho hlahloba litlamorao tse ka fetohang tsa litsobotsi tse ling; e khahlisang haholo ke litlamorao tsa mathata a kopantsoeng le 'mele (ka mohlala, khatello ea maikutlo e ka mpefatsa le ho fokola ha batho ba lemaletseng lithethefatsi152) le ho tsitsinyeha ha tšebeliso ea lithethefatsi le nako ea ho se ts'oarelle (mohlala, cocaine e kanna ea theola kapa ea koahela ho lematsa kherehloa153 kapa ho senyeha hoa maikutlo ha Cocaine - batho ba ikhethileng). Boithuto ba nako e telele bo tla thusa ho hlahloba litaba tsena, tse bohlokoa haholo ho ba lahlang lithethefatsi ka ts'epo ea hore ts'ebetso ea PFC e tla fola. Ntle le moo, ho bapisa lipakeng tsa mefuta e fapaneng ea lintho tse hlekefelitsoeng ho ka lumella phapang pakeng tsa lintlha tse ikhethileng ho lithethefatsi tse ling ho tsoa linthong tse ka tloaelehileng bathong bohle ba ho lemalla. Sebakeng sa ho phekola heterogeneity ea liphetoho tsa tlhaho le boitšoaro le tšebeliso ea lithethefatsi joalo ka lerata, lithuto li ka e hlahloba ka sepheo sa ho araba lipotso tsa bohlokoa: na ho se sebetse ha PFC ho iRISA ho hlahelle haholo ho batho ba bang ba lemaletseng ho feta ho ba bang? Na ho iphekola ho sebelisa lithethefatsi ho nkela batho ba bang ho feta ho batho ba bang? Tšebeliso ea lithethefatsi tsa koae ka morbid, e leng taolo ho feta mokhelo (mohlala, lino tse ngata tse lemaletseng joala hampe) li ama neurobiology ho lemeng? Moelelo oa phapang ee ho phello ea kalafo le ho hlaphoheloa ke ofe? Habohlokoa ka ho fetisisa, re ka sebelisa liphetho tsa laboratori joang ho ts'ebetso ea PFC ho kenya letsoho ho tsebisa moralo oa ho kenella ka mokhoa o sebetsang oa kalafo?

Kakaretso le sephetho

Ka kakaretso, lithuto tsa neuroimaging li senotse mokhoa o hlahang oa ho se sebetse ha PFC ho batho ba lemaletseng lithethefatsi tse amanang le litholoana tse mpe - ts'ebeliso e ngata ea lithethefatsi, ts'ebetso e mpe le ho feta ea ts'ebetso ea PFC le monyetla o moholo oa ho oela hape. Ho batho ba lemaletseng lithethefatsi, ts'ebeliso e atileng ea PFC ha ba noa k'hok'heine kapa lithethefatsi tse ling le ha ho hlahisoa litlhahiso tse amanang le lithethefatsi li nkeloa sebaka ke boiketsiso bo atileng ba PFC nakong ea ho pepesehela mathata a phahameng a maikutlo le a kelello le / kapa nakong ea ho khaotsa nako e telele ha e sa ts'oaroe. Likarolo tsa PFC tse amanang haholo le bokhoba ba tahi li kenyelletsa boits'oaro (ke hore, taolo ea maikutlo le taolo ea thibelo) ho felisa liketso tse seng molemo ho motho ka mong, boits'oaro le tlhokomelo ea ts'usumetso e matla e hlokahalang ho kenella morerong o susumetsoang ke sepheo. boitšoaro, le boits'oaro. Leha ts'ebetso lipakeng tsa libaka tsa PFC e hokahane haholo ebile e fetoha habonolo, hoo tikoloho e ngoe le e ngoe e kenang mesebetsing e mengata, PFC ea dorsal (ho kenyeletsoa DACC, DLPFC le gyrus e tlase e ka pele) e kentsoe letsoho haholo taolong ea holimo-tlase le mesebetsing ea meta , PFC ea ventromedial (ho kenyeletsoa le subgenual ACC le mOFC) taolong ea maikutlo (ho kenyeletsoa maemo le ho fana ka tšusumetso ho lithethefatsi le lits'oants'o tse amanang le lithethefatsi), le PFC ea ventrolateral le lateral OFC litloaelong tsa karabelo e ikemetseng le ho se tsotelle (Tafole ea 1). Ho se sebetse hoa libaka tsena tsa PFC ho ka kenya letsoho kholisong ea takatso, ts'ebeliso e qobelloang le 'ho hana' ho kula le tlhoko ea kalafo - matšoao a khethollang bokhoba ba lithethefatsi. Ho se sebetse ha PFC maemong a mang ho ka etella tšebeliso ea lithethefatsi pele mme ha fana ka ts'oaetso ea ho ba le mathata a ts'ebeliso ea lithethefatsi (Box 3). Ho sa tsotelehe hore na ho na le lebaka lefe, sephetho sa lithuto tsa neuroimaging tse hlahlojoang mona se fana ka maikutlo a monyetla oa hore li-biomarker tse khethehileng li ka lebisoa molemong oa ho kenella. Mohlala, mohlomong lintho tse sa tloaelehang tsa PFC li ka sebelisoa ho khetholla bana le bacha ba ka ruang molemo haholo ho tsoa boitekong bo matla ba ts'ebeliso e mpe ea lithethefatsi, mme mohlomong meriana e ka ntlafatsa likhaello tsena mme ea thusa batho ba lemaletseng ho kenella kalafong ea tlhabollo.

Lebokose 3 | Tlokotsi le tšebeliso ea lithethefatsi pele

Boithuto ba hore na ho ka ba le tlokotsi pele ho tlokotsi - joalo ka ho pepesetsoa lithethefatsi, nalane ea lelapa kapa li-polymorphisms tse khethiloeng le litšebelisano tsa bona - ts'ebetso ea ts'ebetso ea preortal cortex (PFC) e bohlokoa bakeng sa moralo oa ts'ebetso ea ho kenella nakong e tlang le boiteko ba ho thibela; Lithuto tsena li totobatsa bohlokoa ba ho shebella barekisi ba lihlahisoa tse hlakileng tsa tlokotsi ea ts'ebeliso ea lithethefatsi le bokhoba ba tsona. Mohlala, ho fokotseha ho phallo ea mali a khohlela a lefatše ka bophara (CBF) (−10%), le ntlafatso ea CBF ho dorsolateral PFC (DLPFC) (9%) le anterior cingulate cortex (ACC) (12%) ho tlalehiloe lilemong tsa bocha tse nang le boima ba 'mele. prenatal cocaine e pepesitsoeng²⁰¹. PFC e matlafatsang e boetse e tlalehiloe ho basebelisi ba bacha ba MDMA²⁰², matekoane²⁰³ kapa joala²⁰⁴ nakong ea mosebetsi oa ho ea / ho se ee, tseo ba neng ba li etsa ka tloaelo (Tlhahisoleseling ea tlatsetso S6 (tafole)). Ka mokhoa o ts'oanang, ha ho bapisoa le ho laola bana le bana ba neng ba e-na le batsoali ba joala empa ba inehetse, bana ba neng ba e-na le batsoali ba joala 'me ba le kotsing ea ho nooa (ba thathamisitsoeng ho latela boemo ba bothata ba ho noha nakong ea bocha) ba ne ba e-na le hypCactive tokelo dorsomedial PFC bilateral orbitof Pambal cortex (OFC) e ne e le kelello, leha ho ne ho sena phapang ea boitšoaro ha u bala mantsoe a maikutlo ka khutso. Hoo e ka bang sampole eohle, ho hloka matla hoo ha PFC ho ne ho amana le matšoao a kantle ho naha le ka mabifi²⁰⁵ (Tlhahisoleseling ea tlatsetso S5 (tafole)). Ka hona, liphetoho tse joalo ts'ebetsong ea PFC li kanna tsa tlama ka nako e khuts'oane (joalo ka ha ho bonahatsoa ke ts'ebetso e lekanang ea ts'ebetso), empa ka nako e telele li ka khothaletsa tlhekefetso ea lithethefatsi le bokhoba ho batho bana, leha sena se ntse se lokela ho netefatsoa.

Mochine o bakang bofokoli bo joalo ho, kapa o fanang ka ts'ireletso khahlanong le, ho ts'oara lithethefatsi ho ka kenyelletsa ho fetoloa ha dopaminergic neurotransmission. Mohlala, ho fumaneha ha li-dopamine D2 receptor le metabolism ea PFC ea tikoloho e ne e phahame ho litho tse fokolang, tse sa amehang tsa malapa a joala ho feta lithutong ntle le nalane e joalo ea malapa, e leng se fapaneng le sephetho se atisang ho tlaleheloa ho batho ba lemaletseng lithethefatsi (lebokose 2;; bona Tlhahisoleseling ea tlatsetso S7 (tafole))²⁰⁶. Batho ba nang le nalane ea malapa ea ts'ebeliso e mpe ea joala ba tlaleha maikutlo a tlase, mme sena se ne se amana le ho fumaneha ka tlase ha drietal dopamine D2 receptor fumaneha le metabolism e tlase ea OFC. Ka hona hoa etsahala hore kholo ea dopamine D2 receptor e fumanehang le ts'ebetso ea metabolic e ntlafalitsoeng ho PFC ho batho ba nang le nalane ea malapa ea tšebeliso e mpe ea joala e eketse boemo ba maikutlo bo botle - leha ho le joalo sena se ile sa lula se le ka tlase ho boemo maemong a taolo e phetseng hantle - ho maemo a ka bang le ona o ile a sireletsa batho bana khahlanong le bokhoba ba ho lemalla. Hape hoa etsahala hore maemo a hlokehang bakeng sa ts'ireletso ea ts'ireletso e joalo, le hore maemo a tlase (mohlala, khatello e sa feleng) a ka pepesetsa batho ba tšoanang le lithethefatsi hamorao bophelong, empa sena se ntse se lokela ho hlalosoa lithutong tse telele. Mechine e meng, joalo ka dysmorphology ea boko²⁰⁷, e kanna ea ba ea bohlokoa molemong oa ho fana ka monyetla oa ho lemalla.

Menehelo ea liphatsa tsa lefutso e ka re behang kotsing ea ho lemalla le eona e bohlokoa. Mohlala, basebelisi ba bang ba kamehla ba matekoane a bang le likotsi tsa mofuta oa mofuta oa "cannabinoid receptor 1" (CB1) kapa mafura acid amino hydrolase 1 (FAAH; enzyme e fanang ka tšebeliso ea "cue" e amanang le lithethefatsi libakeng tse ling tsa li-PFC.²⁰⁸. Taba ea bohlokoa ke hore, mofuta o joalo oa tšebelisano ea tikoloho o ka sebelisoa ho bolela esale pele boitšoaro bo kotsi ba nako e tlang. Mohlala, keketseho ea selemo sa 1 selemong sa banana ba lilemong tsa bocha ba phetseng hantle se ka boleloa esale pele ka ts'ebetso ea hamorao ea OFC e khothalletsoang ke lithahasello tse amanang le lijo, empa feela ho bajari ba kotsi ea dopaminergic alleles dopamine receptor D4 (DRD4) 7-repeat allele or the DRD2 TaqIA A1 allele²⁰⁹. Boithuto ba morao-rao bo boetse bo fana ka maikutlo a hore tšebelisano lipakeng tsa li-polymorphisms le lelapa - ho kenyeletsoa prenatal - ho pepesetsoa lithethefatsi ho ka susumetsa nts'etsopele ea OFC^{210, 211}. Mohlala, phuputso ea morao-rao e bonts'itse hore medial OFC (mOFC) grey taba ea molumo e fetotsoe ke monoamine oxydase A genotype, hoo maemo a tlase a mofuta ona a ileng a tsamaisa litaba tsa bohlooho ba MOFC a fokotseha ho batho ba lemaletseng koae.²¹², 'me sena se ne se amana le tšebeliso e telele ea koae.

Links

LINTHO TSE FUMANEHANG

• Leqephe la lapeng la Rita Z. Goldstein

• Leqephe la lehae la Brookhaven National Laboratory Neuropsychoimaging Group

• Setsi sa Naha sa Ts'ebeliso e Mpe ea Tebeliso ea Lithethefatsi

• Webosaete ea Univesithi ea Colorado CANLab

Liteboho

Phuputso ena e ne e tšehelitsoe ke lithuso tse tsoang Setsing sa Naha sa US sa Tlhekefetso ea Lithethefatsi (R01DA023579 ho ea ho RZG), lenaneo la Intramural NIAAA le Lefapha la Matla, Ofisi ea Patlisiso ea Bioloji le Tikoloho (bakeng sa tšehetso ea meralo ea motheo). Re leboha tlatsetso ea AB Konova ho moralo oa setšoantšo sa 2. Re tlameha ho leboha basekaseki ba rona bao litlhaloso tsa bona li ileng tsa ananeloa haholo 'me tsa tataisa ntlafatso ea rona ea sengoloa sa pele.

Phatlalatso ea lithahasello

Bangoli ha ba phatlalatse lithahasello tsa lichelete.

Lintlha tse eketsehileng

Tlhahisoleseling e tlatselletsang e tsamaea le pampiri ena.

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