Mekhoa e fetohang ea ho kenngoa ha boko boemong ba lijo le li-cocaine ho ba hlekefetsang k'hok'heine: ho kopana le li-receptors tse hlaselang D2 / D3 (2015)

Dardo Tomasi, Ph.D.,^*,1 Gene-Jack Wang, MD,¹ Ruiliang Wang, Ph.D.,² Elisabeth C. Caparelli, Ph.D.,³ Jean Logan, Ph.D.,⁴ 'me Nora D. Volkow, MD^1,3

Cocaine, ka ts'ebetso ea eona e sebelisang dopamine (DA), e sebelisa mekhoa e etsang litlhohonolofatso tsa tlhaho. Leha ho le joalo, boholo ba marang-rang a sebetsanang le meputso ea tlhaho le ea lithethefatsi le hore na ho na le phapang ea DA e amanang le tlhekefetso ea cocaine e susumetsa marang-rang ana ha a etsoa lipatlisiso ho batho. Re lekantse likarabo tsa boikoetliso ba boko ho lijo le k'hok'heine tse nang le fMRI, le li-receptor tsa D2 / D3 ho striatum e nang le [¹¹C] raclopride le PET ka 20 ba sebetsang hampe ka cocaine. Ha li bapisoa le likhetho tse sa nkeheng, lijo le li-cocaine li ntse li kopanela li-cerebellum, li-orbitofrontal, li-cortices tse ka tlaasana le tsa pele ho nako le li-insula le cuneus e senyehileng le mekhoa e tsitsitseng ea marang-rang (DMN). Lipontšo tsena tsa fMRI li ne li lekana le li-receptor tse hlaselang D2 / D3. Ho na le k'hok'heine e tsotehang le lijo tsa lijo hape tse emisitsoeng ho ventral striatum le hypothalamus. Ha li bapisoa le lijo tsa lijo, likhahla tsa cocaine li hlahisoa ka tlase ho insula le postyral gyrus, le ho se sebetse habonolo hypothalamus le libakeng tsa DMN. Ho ts'ebetsoa libakeng tsa cortical le cerebellum ho eketsehile ka ho lekanang le valence ea cues, mme ho ts'ebetsong ho lijo tse ling ka li-cortices tse ling tsa 'meleng le tsa orbitofrontal le tsona li eketsehile ho latela boima ba' mele. Nako e telele ho pepeseha ha cocaine ho ne ho amahanngoa le ho fokotsa matla ho bobeli ba occipital cortex le cerebellum, e ka bonang ho fokotseha ha li-receptor tsa D2 / D3 tse amanang le ho kula. Liphuputso tsena li bonts'a hore likhahla tsa cocaine li etsa hore ho be le litsela tse tšoanang, le hoja li sa ts'oane, litsela tse etsoang ke tse amoheloang ke lijo le hore li-receptor tse hlaselang D2 / D3 li arabela likarabo tsena, li fana ka maikutlo a hore ho hlahisa li-cocaine tse sa foleng ho ka susumetsa kutloisiso ea bokooa eseng lithethefatsi feela empa le lijo tse ling.

Lihlooho

Barupeluoa ba ithutoang e ne e le banna ba 20 ba sebetsang ka cocaine ba hlekefetsang (lilemo tse 46.4 ± 3.3; lilemo tse 12.8 ± 1.4 tsa thuto; 'mele oa letšoao (BMI) oa 26 ± 4 kg / m²; bolela ± SD). Barupeluoa ba ile ba hiroa ho tsoa lipapatsong libotong tsa sechaba, likoranteng tsa lehae le ka molomo. Lihlooho tsohle li fane ka tumello e ngotsoeng e nang le tsebo joalo ka ha e amohetsoe ke Boto ea lehae ea Boto ea Setsi (Komiti ea Univesithi ea Stony Brook ea Patlisiso e Amanang le Lithuto tsa Batho, CORIHS), mme ba ile ba hlahlojoa ka lebaka la ho ba sieo ha mafu a bongaka, mafu a kelello kapa methapo. Setsebi sa kelello sa bongaka se ile sa etsa lipuisano tse hlophisitsoeng hantle tse neng li kenyelletsa Lipuisano tse hlophisitsoeng tsa Kliniki bakeng sa DSM-IV Axis I Disorders [mofuta oa lipatlisiso (Pele, le al. 1996; Ventura, et al. 1998)] le Tlhekefetso ea Tlhekefetso ea Lithethefatsi (McLellan, et al. 1992).

Liteko tse tloaelehileng tsa laboratori (mohlala, electrocardiogram, lab ea mali le skrine ea moroto) li ile tsa etsoa nakong ea ketelo ea ho lekola ho netefatsa litekanyetso tsa ho kenyelletsa / ho kenyelletsa thuto. Litaba tsa banna li ne li kenyelelitsoe haeba ba ne ba le 1) ba khona ho utloisisa le ho fana ka tumello e nang le tsebo; o ne a e-na le 2) DSM IV e fumanoeng bakeng sa ts'ehetso e sebetsang ea cocaine 3) bonyane nalane ea lilemo tse 2 ea ts'ebeliso e mpe ea koae e sebelisang bonyane ligrama tse 3 tsa koae / beke; 4) ts'ebeliso e kholo ea cocaine ka tsela e tsubang kapa ea iv, le 5) e sa batleng kalafo ea cocaine. Bafo ba ne ba qheleloa ka thoko haeba ba ne ba na le 6) nalane ea hajoale kapa e fetileng ea lefu la methapo le simolohileng bohareng kapa lefu la kelello ho kenyelletsa tšebeliso e mpe ea joala kapa lithethefatsi ho fapana le cocaine le nicotine, 7) maemo a phahameng a ho tšoenyeha, ho tšoha, khatello ea kelello, ntle le ba amanang le tšebeliso e mpe ea koae; 8) bokuli ba hajoale ba bongaka bo ka amang ts'ebetso ea boko; 9) nalane ea hajoale kapa e fetileng ea lefu la pelo le methapo ho kenyelletsa lefu la pelo le khatello e phahameng ea mali kapa lefu la endocrinological; 10) ho sithabela hlooho le ho lahleheloa ke kelello> Metsotso e 30; 11) nalane ea hlooho ea hlooho ea methapo; 12) lisebelisoa tsa tšepe kapa tse ling tse hanyetsang MRI.

Lihlooho tse leshome le metso e meraro li ne li tsuba lisakerete (lilemo tse 17 ± 7 tsa tsuba; 8 ± 7 lisakerete ka letsatsi). Baithuti bohle ba ne ba e-na le moriana o motle bakeng sa li-cocaine matsatsing a mabeli a thuto, e bontšang hore ba sebelisitse k'hok'heine nakong ea lihora tsa 72 pele ho moo.

Coteine-cue le video-cue video paradigms

Libuka tse peli tsa li-romantic paradigms li sebelisitsoe thupong ea hona joale ea fMRI. Mosebetsi oa khatiso ea video ea nako e telele ea 6 (cueine)Setšoantšo sa 1A le 1B) e entsoe ka k'hok'heine e ts'eletseng, ho se nke lehlakore ka makhetlo a tšeletseng le ho laola 6 (skrine e ntšo e nang le sefapano sa setsi sa ho lokisa), metsotsoana e meng le e meng ea 20 e tšoarellang ka nako e telele e bile e hlaha ka tatellano e sa tloaelehang. Lihlopha tsa cocaine li ne li e-na le lihlopha tsa video tse sa pheta-phetoang tse bontšang lipapali tse neng li etsa hore ho rekisoe, ho lokisetsa le ho tsuba ha cocaine e neng e hatisitsoe pele (Volkow, et al. 2006; Volkow, et al. 2010b). Lihlopha tse sa jeleng paate li ne li e-na le mosebetsi o tloaelehileng oa tsamaiso / oa theknoloji e le ho laola lintho.

  

Setšoantšo sa 1

A: Li-video tse hlahisoang ke li-cocaine (cocaine), li-cocaine kapa li-video epochs (20 metsotsoana e telele) li bontša lipapali tse neng li reka ho reka, ho lokisetsa le ho tsuba ha cocaine ...

Ka mokhoa o ts'oanang, mosebetsi oa khatiso oa video oa nako e telele oa 6 o ne o entsoe ka 'lijo' tse tšeletseng, 'tse sa nke lehlakore' tse tšeletseng (mosebetsi o tloaelehileng oa tsamaiso / theknoloji) le 6 'taolo' (nako e khubelu e nang le sefapano sa ho lokisa), metsotsoana e meng le e meng ea 20 e tšoarellang. le ho hlaha ka tatellano e sa tloaelehang. Lihlopha tsa lijo li ne li e-na le likarolo tse sa pheta-phetoang tsa video tse sa tsoa hatisoa (Wang, et al. 2013), e bontšang litšoantšo tsa ho sebeletsa le ho sebelisoa ha lijo tse lokiselitsoeng ho itokisetsa ho ja lijo (ie, meatballs, pasta, omelets, burger, pancakes).

Litaba li ne li laeloa hore li shebe skrine ka ho tsoelang pele 'me li tobetse konopo ea karabo ka letsoho le letona le letona neng le neng ha li rata likarolo tsa lipapali. Liqhetsoana tsa video tsa maqheka li ile tsa tlalehoa ka tlung 'me li bolokiloe mofuteng oa Audio Video Interleave ka basebetsi ba libaesekopo tsa libuka tsa Brookhaven National Laboratory. Lifilimi tsena tsa maqheka li ile tsa hlahisoa ho lihlooho tsa MRI-compatible goggles (Resonance Technology Inc., Northridge, CA) e hokahaneng le k'homphieutha ea motho. Software ea ho bontsa e ne e ngotsoe ka lipuo tsa Visual Basic le C sephuthehong sa Visual Studio (Microsoft Corp., Redmond, WA) 'me e ne e lumellane hantle le thekiso ea MRI e sebelisoang ka katleho.

Lijo le li-cocaine valence

Ha lihlooho tse ling li ntse li hatelletse konopo ea karabo nakong ea lijo, k'hok'heine le / kapa linako tse sa jeleng lipolotiki ha li ntse li rata litšoantšo tse bontšitsoeng lipapaling tse fapaneng. Palo ea lisebelisoa tsa konopo e ne e sebelisetsoa ho lekanya li-valence tse amanang ka tekanyo ho tloha 0 ho ea 10. Haholo-holo, palo ea mechine ea khatiso nakong ea lijo (f), se nke lehlakore (n) le ho laola mokhoa oa motheo (b) nako e 'ngoe ea video e hlahisitsoeng ka lijo e ne e sebelisetsoa ho ipapisa lijo = f / (f + n + b) Le ho se jele paate = n / (n + f + b) li-valence tse amanang le video ea lijo-thollo. Ka mokhoa o ts'oanang, palo ea mechine ea khatiso nakong ea cocaine (c) linako tse ling li ne li sebelisetsoa ho lekanyetsa k'hok'heine = c / (c + n + b) hammoho le ho se jele paate = n / (n + c + b) liphahlo nakong ea video ea cocaine-cue. Hlokomela hore li-valence tsa lijo le li-cocaine ke mehato e tloaelehileng e nang le likamano tse sa lumellaneng le valence e sa nkeheng, le hore b (palo ea mechine ea li-button nakong ea motheo oa motheo oa ho lokisa) e bonts'a lerata la lerata le ho fokotsa ho se lumellane ho fosahetseng pakeng tsa li-valence tsena ho tloha ho se hokahanngoa ho sa nepahetseng.

MRI e fumanoang ka boitsebiso

Lihlooho li hlahlobiloe letsatsing pele ho thuto ho leka ho qoba tšebeliso ea lithethefatsi bosiung ba pele ho thuto. Ba ile ba tlisoa ho Guest Guest Facility ho Brooven National Laboratory ho 5: 00PM, moo ba neng ba ja lijo tsa mantsiboea 'me ba hlola bosiung boo. Hoseng ho hlahlamang, pakeng tsa 8: 00AM le 8: 30AM, bafo ba bona ba ne ba e-na le hoseng lijo tsa hoseng tse nang le metsi le bagel, roll kapa lijo-thollo ho itšetlehile ka seo ba se ratang. Ho ts'oaroa ha bono ho li-cocaine, li-food and cue neutral li ile tsa hlahlojoa pakeng tsa 9: 00AM le 10: 00AM ka makhetlo a mabeli ho matsatsi a fapaneng a lithuto tsa 2, libeke tsa 2 li arohane. Tlhophiso ea tlhahiso ea livideo tsa lijo-le tsa cocaine e ne e le lihlooho tse ngata. XMUMX-Tesla eohle body Varian (Palo Alto, CA) / Siemens (Erlangen, Jeremane) MRI scanner e nang le T4 * -eighted shot-echo planar imaging (EPI) sekhetho se lekaneng (TE / TR = 2 / 20 ms, xNUMX-mm sekhahla sa sekhahla, sekhahla sa 1600-mm, likhahla tsa 4 tse nyenyane, 1 × 35 matrix boholo, 64 × 64 mm² Qeto ea sefofaneng, 90 ° -flip angle, lintlha tsa nako ea 226, bandwidth ea 200.00 kHz) ka sampling ea sampling le ho koaheloa hohle ha boko ho sebelisitsoe ho bokella litšoantšo tse sebetsang tse nang le phapano ea mali-oxygenation-level-dependent-BOLD). Padding e ne e sebelisetsoa ho fokotsa motsamao. Ts'ebetso ea sehlooho e ile ea beoa leihlo hang kamora hore fMRI e ngoe le e ngoe e sebetse e sebelisa algorithm ea k-space motion detection algorithm (Caparelli, et al. 2003) e ngotsoeng ka Interactive Data Language (IDL; ITT Litsela tsa Boitsebiso bo Bonahalang, Boulder, CO). Li-earplugs (-28 dB khatello ea molumo oa khatello ea molumo; Aearo Ear TaperThat 2; Aearo Co., Indianapolis, IN), li-headphones (-30 dB khatello ea molumo oa khatello ea molumo; Molaoli XG MRI Mochine oa lisebelisoa, Moqapi oa theknoloji, Inc., Northridge, CA) le mokhoa o "khutsitseng" oa ho fumana chelete o ile oa sebelisoa ho fokotsa ts'ebetso ea ho kena-kenana le lerata la mochine nakong ea fMRI (Tomasi, le al. 2005). Litšoantšo tse sa tloaelehang li ne li bokelloa ho sebelisoa mahlakore a mararo a mahlakore a mararo a T1 a fetoletsoeng ka tsela e tšoanang (TE / TR = 7 / 15 ms, 0.94 × 0.94 × 1.00 mm³ sekhahla sa mahlaseli, thuto ea 256 le mehato ea 192-96-encode-phase-encoding, nako ea scan ea 16 metsotso) le sekhetho se nang le boima ba hyperecho (TE / TR = 2 / 0.042), bolelele ba 10, 16 × 256 boholo, likaroloana tsa 256, 30 × 0.86 mm² ka sefofaneng sa sefofane, 5 mm thickness, ha ho lekhalo, nako ea X scan ea Min) ho laola mekhoa e sa tloaelehang ea boko.

Tlhahlobo ea Data

Mekhoa ea ho lokisa mokhoa oa ho pheta-pheta e fokotsang letšoao-tahlehelo ea maiketsetso ho EPI e ne e sebelisetsoa ho tsosolosa litšoantšo (Caparelli le Tomasi 2008). Lintlha tse 'nè tse qalang tsa ho bapala li lahliloe ho qoba liphello tse se nang tekanyo pontšo ea fMRI. Lenane la liphuputso la mapolesa la SPM8 (Setsi sa Tlhokomelo sa Wellcome sa Neuroimaging, London, UK) se sebeliselitsoe lits'ebetso tse latelang. Tlhaloso ea setšoantšo e ne e etsoa ka 4^th mosebetsi oa boipheliso B-spline ntle le ho lekanya le ntle le ho loantša; hlooho ea hlooho e ne e le tlaase ho liphetolelo tsa 2-mm le liphetolelo tsa 2 bakeng sa lintlha tsohle. Sebaka sa maemo a tloaelehileng sebakeng sa stereotactic Institute ea Montreal Neurological (MNI) se ile sa etsoa ka phetoho ea 12-parameter e fetoletsoeng ka nako e telele, litlhaloso tse ling tsa 16-nonlinear le boholo ba voxel ea 3 × 3 × 3 mm³ le template ea SPM8 EPI e tloaelehileng. Sebaka sa ho khantša sepakapaka se ne se etsoa ka ho sebelisa kernel ea Gaussia e kholo-halofo ea XMUMX-mm (FWHM). Likarabo tsa fMRI nakong ea li-paradigms tsa lipapali tsa video li ne li hakanngoa li sebelisa mokhoa o tloaelehileng o lekaneng (Friston, le al. 1995) le sebopeho sa marang-rang se nang le li-controller tsa 2, ho etsa mohlala oa ho qalella ha 20sec nako e telele ea cocaine / lijo le linako tsa khale tsa 20sec tse sa nke lehlakore (Setšoantšo sa 1B), ea khotsofatsoa ka ho feta (HRF) le ho feta-palo (motlakase oa ho khaola: 1 / 800 Hz). Ka hona, limmapa tse fapaneng tsa 2 tse bontšang liphetoho tsa% BOLD-fMRI ho tloha setsing sa pele (sefahleho se setšo se nang le sefapano sa ho lokisa) se bakoang ke cocaine / lijo le lijo tse sa nke lehlakore li ile tsa fumanoa mofuteng o mong le o mong oa fMRI bakeng sa taba ka 'ngoe.

Tlhahlobo ea liteko e tšepahala

Ho tšepahala ha likarabo tsa boikopanyo ba boko ho lihlopha li ile tsa hlahlojoa bakeng sa voxel e 'ngoe le e' ngoe ea litšoantšo e sebelisang mehato e le 'ngoe e kopaneng ea intraclass correlation (Shrout le Fleiss 1979).

Ka ho khetheha, ICC (3,1) e entsoe ka bokong ho ea ka-lihlooho (BMS) le ho fokotseha (EMS) e bolela litekanyetso tsa litekanyetso tse ngotsoeng bakeng sa voxel ka 'ngoe e sebelisa IPN test-retest ea tšepahala matlab toolbox (http://www.mathworks.com/matlabcentral/fileexchange/22122-ipn-tools-for-test-retest-reliability-analysis) le limmapa tse fapaneng tsa fMRI tse amanang le cocaine / lijo tse tsoang lihloohong tsohle le mananeo (k = 2). Hlokomela hore coefficients ea ICC (3, 1) e tsoa ho 0 (ha e tshepehe) ho 1 (ho tšepahala ka ho phethahetseng).

PET ea ho hlahloba

Metsotso e mashome a mararo kamora ho hlahlojoa ha MRI (hoo e ka bang metsotso ea 60 kamora qetellong ea fMRI) lihlooho li ile tsa e-ba le PET ea ho hlahloba ho fumaneha ha li-receptors tsa DA D2 / D3 bokong. Re ne re sebelisa tomograph ea HR + (tharollo 4.5 × 4.5 × 4.5 mm³ bophara bo feletseng ba halofo, boholo ba 63) ka [¹¹C] raclopride, radiotracer e tlamellanong le li-receptor tsa DA D2 / D3, le mekhoa e hlalositsoeng pele (Volkow, et al. 1993a). Ka bokhutšoanyane, lisebelisoa tsa tlhahiso li qalile hang ka mor'a ho kenngoa ha 4-8 mCi (mosebetsi o itseng oa 0.5-1.5 Ci / μM). Litekanyetso tse mashome a mabeli tsa tlhahiso ea matla li ile tsa fumanoa ho tloha nakong ea ente ho fihlela metsotso ea 54. Sampuli ea arteria e ne e sebelisetsoa ho lekanyetsa kakaretso ea carbon-11 le e sa fetoheng [¹¹C] raclopride ka lero la mali. Bophahamo ba matla ba kabo (DV), bo tsamaellanang le litekanyo tsa tekano ea karolelano ea methapo ea methapo ea radiotracer ho ea ea methapo ea mali ea eona, e ne e hakanyetsoa bakeng sa voxel e ngoe le e ngoe e sebelisa mokhoa oa ho sekaseka lits'oants'o bakeng sa lits'ebetso tse fetoloang tse sa hlokeng sampole ea mali (Logan J 1990). Litšoantšo tsena li ile tsa hlophisoa ka mokhoa oa sebaka sa MNI stereotactic li sebelisa SPM8 'me tsa sebelisoa hape ho sebelisa li-voxels tsa 2-mm isotropic. Setšoantšo sa MNI sa tloaelo, se neng se entsoe pele ho sebelisoa litšoantšo tsa DV ho tsoa ho lithuto tse 34 tse phetseng hantle tse fumanoeng ka [¹¹C] raclopride le mokhoa o tšoanang oa PET oa ho hlahloba (Wang, et al. 2011), e ne e sebelisetsoa morero ona. DV ratios, e lumellanang le bokhoni bo sa khonehang ba ho tlama (BP_ND) ka voxel e 'ngoe le e' ngoe, e ile ea fumanoa ka normalizing matla a litšoantšo tsa DV ho eona ho cerebellum (libaka tse ka ho le letona le tse nepahetseng-tsa thahasello). Atlas ea Automated Anatomical Labeling (AAL)Tzourio-Mazoyer, et al. 2002) e ne e sebelisetsoa ho fumana likarolo tsa MNI tsa litsi tsa boima bakeng sa putamen le caudate; litsamaiso tsa bohareng tsa moeli pakeng tsa caudate le putamen li khethiloe bakeng sa striral striatum. Ka lebaka leo, mask a masotomic (maseru) a nang le volume 1 ml (voxels ea 125 imaging) e ne e lebisitsoe ho putamen [xyz = (± 26, 8, 2) mm], ho hlaphoheloa [xyz = (± 12, 12, 8) mm] le ventral striatum [xyz = (± 20, 10, -12) mm] ho lekanya ho fumaneha ha kakaretso ea li-receptor tsa D2 / D3 bakeng sa motho ka mong libakeng tsena tse hlaselang (Setšoantšo sa 2A).

  

Setšoantšo sa 2

A: Ho itokolla ho ka holimo ho maikutlo a MRI axial ka boko ba motho bo bonts'ang hore ho na le li-receptors tsa DA D2 / D3 tse latellaneng. PET le raclopride [11C] e ne e sebelisetsoa ho lekanya lipalo tsa ho tsamaisa tse amanang le litekanyetso tsa cerebellum, tse tšoanang ...

Lipatlisiso tsa sethathamo

Tsela e le 'ngoe ea ho hlahloba sekhetho sa mefuta-futa ka SPM8 ka lilemo, BMI le lilemo tse ngata tsa cocaine tse sebelisang cocaine (ANCOVA) li ne li sebelisetsoa ho hlahloba bohlokoa ba li-signals tse sebelisang boko bo tloaelehileng le tse fapaneng le lihlahisoa tse sa jeleng, tsa lijo le tsa cocaine. Lipatlisiso tsa SPM8 tsa khatello ea maikutlo li ne li sebelisoa hape ho hlahloba mokhatlo o ts'oanang oa boitsebiso ba boko ba bokooa le boteng ba D2 / D3 receptor (BP_ND) ka caudate, putamen le ventral striatum, hammoho le lilemo tse sebelisoang ke cocaine, valence ea cue le BMI hohle lihloohong. Tlhaloso ea lintlha e behiloe joaloka P_FWE <0.05, e lokisitsoe bakeng sa papiso e mengata le khopolo ea tšimo e sa reroang le khalemelo ea liphoso tse bohlale ho ba lelapa sehlopheng. Sekhahla se etsang sehlopha sa P <0.005 le boholo bo tlase ba sehlopha sa li-voxels tse 200 li sebelisitsoe molemong ona. Mokhoa o tloahelehileng oa Bonferroni oa lipapiso tse ngata o ile oa sebelisoa hape ho laola palo ea litlhahlobo tse ikemetseng tsa khatello ea maikutlo ea SPM. Pc <0.05 ea boemo bo thata ba sehlopha se hlophisitsoeng ka nako e le 'ngoe e ikarabellang bakeng sa litokiso tsa Bonferroni le litokiso tse felletseng tsa boko ba FWE li sebelisitsoe molemong ona.

E sebetsang ROI-e hlahloba

Ts'ebetso ea bono le lihlopha tsa ho khaotsa ho hlahlojoa li ile tsa hlahlojoa ka ho eketsehileng le tlhahlobo ea sebaka-ea-thahasello (ROI) ho khetholla bafuputsi ba ka 'nang ba susumetsa lisebelisuoa tse matla tsa ho tsamaisana, le ho tlaleha litekanyetso tsa bobeli ka molumo o kang oa ho ts'oanela ho shebahala (mohlala, (Worsley, et al. 1992)) ho e-na le litekanyetso tsa tlhōrō ea voxel tse bohlokoa. Molumo oa lihlahisoa tsa metsi o ne o hakanyetsoa hore o sebelisa ho bala ka tšohanyetso tšimong ka SPM8 e le palo e haufi le lik'hilograma FWHM = 12.7 mm, 12.3 mm, 13.1 mm. Kahoo, mask a isotropic a 9-mm a nang le li-voxels tsa 27 (0.73 ml) a hlalosoa libakeng tsa liketsahalo tse sebetsang tsa ho ts'oanela ho sebetsa / ho thibela likarolo tse ling ho tlosa palo ea% BOLD ho tloha limmapa tse fapaneng tse fapaneng. Li-mask tsena li ile tsa bōptjoa 'me tsa tsepamisoa ke li-coordinates tse tobileng tse thathamisitsoeng ho tsona Lisebelisoa tsa 1--44.

  

Lethathamo 1

Tlhaloso ea li-statistical bakeng sa lihlopha tse sebelisoang ke boko tse neng li atisa ho sebelisoa ke cocaine (C) le lijo (F) litšoantšo tse bapisoang le ho se jele paate (N) cues.

  

Lethathamo 4

Tlhaloso ea lintlha tsa likamano pakeng tsa likarabo tsa fMRI tse tloaelehileng bakeng sa lijo (F) le cocaine (C) cues le lilemo tsa cocaine, ho rata likarolo tse ngata le boima ba 'mele (BMI).

boitshwaro ja

Li-valence li ne li le tlase bakeng sa mekhoa e sa jeleng paate ho feta bakeng sa lijo kapa li-cocaine (P <10^-6, t> 7.4, df = 19, t-teko e kopantsoeng; Setšoantšo sa 3A) empa ha ea ka ea fapana ka lijo le k'hok'heine. Ho bile le khokahano e mpe lipakeng tsa lihlooho pakeng tsa valence ea mekhoa e sa jeleng paate le ea li-cocaine / lijo, joalo ka ha lithuto li rata li-cocaine / lijo hanyane ka hanyane li sa rateng mekhoa e sa jeleng paate (R <- 0.8, P < 0.0001, df = 18, Pearson khokahano; Setšoantšo sa 3B).

  

Setšoantšo sa 3

Likarabo tsa boitšoaro nakong ea lipapali tsa video tsa tlhaho. A: Lihlooho li ne li laeloa ho hatisa konopo ea karabo ha ba rata likarolo tsa sebaka seo. Palo ea mechine ea li-button e ne e sebelisetsoa ho fumana hore na litaba li ne li rata cocaine, lijo le ...

Li-receptors tsa Striatal DA D2 / D3

Kakaretso ea phumaneho ea li-receptor tsa DA D2 / D3 ho li-ROI tsa striatal e ne e phahame bakeng sa putamen ho feta bakeng sa caudate, le bakeng sa caudate ho feta bakeng sa ventral striatum (P <10^-9, li-hemispheres tse le letšehali le tse nepahetseng li lekanya boholo). Ho fumaneha ha li-receptor tsa D2 / D3 ho striatum ha hoa ka ha bontša hore ho na le likamano tse kholo le botsofali, BMI, bothata kapa ho ba le valence ea cues.

Ts'ebetso ea boko

Ha li bapisoa le motheo oa ho lokisa, ho se nke lehlakore e hlahisitsoeng ka makhetlo a mabeli ka bophahamo ba occipital, li-fusiform le tse phahameng ka ho fetisisa li-gyri (BAs 19 le 6), cerebellum (posterior lobe), e tlase e fokolang ea cortex (BA 40), e tlase e sebetsang ka tlaase ho opculum (BA 44) le hippocampus, libaka tsa marang-rang (DMN) libaka (cuneus, precuneus le gyrus ea angular) (P_FWE <0.0005; Setšoantšo sa 4).

  

Setšoantšo sa 4

Tlhaloso ea setšoantšo ea ho sebelisoa ha boko (bohlasoa bo bofubelu) / ho khaotsa (likarolo tse bofubelu-motsoako) litšoantšong tsa maiketsetso tse amanang le li-epochs tsa motheo tsa ho lokisa, tse fetisetsoang ponong ea lateral le ea mongobo ea cerebrum le ho shebella pono ea cerebellum.

Ha li bapisoa le motheo oa ho lokisa, li-cocaine cues e hlahisitsoeng ka makhetlo a mabeli ka li-calcarine le likarolo tse tlase tsa li-parietal cortices (BAs 18 le 40), fusiform (BA 19), li-precentral (BA 6) le li-gyri tse ka hare-hare (BA 44), le hippocampus, le ts'ebetso e kopanetsoeng linaheng tse ling tsa DMN (cuneus, mahlaseli a mabeli, cingulum ea morao-rao le gyrus e nyenyane) (P_FWE <0.0005; Setšoantšo sa 4).

Ha li bapisoa le motheo oa ho lokisa, lijo tsa lijo (BA 18), li-poreetorm gyrus (BA 19), li-poroetal cortex (BA 38), tlase e ka tlaasana ea operculum (BA 40), OFC (BA 45) le hippocampus, le ts'ebetso ea linaha tse peli ka lekhetlo la bobeli (ACC), RVACC, BAs 11, 10 le 11), cuneus (BAs 32 le18), precuneus (BA 19) le gyrus e nyenyane (BA 7) (P_FWE <0.0005; Setšoantšo sa 4).

Tlhahlobo ea liteko e tšepahala

Tlhatlhobo ea ICC ea tlhaiso-leseling ea tlhahlobo ea fMRI ea tlhahlobo ea liteko e bonts'a ts'epahalo ho isa tekanyong e phahameng bakeng sa likarabo tsa BOLD-fMRI litsing. Ka ho khetheha, lipontšo tsa fMRI ho rvACC, occipital cortex, ventral striatum, cerebellum, operculum e ka pele e ka pele, postcentral, precentral le tlase tlase gyri, cuneus, precuneus le gular ea angular e ne e na le ICC (3,1)> 0.5 (Setšoantšo sa 5).

  

Setšoantšo sa 5

Limmapa tsa Intraclass correlation (ICC), tse fanoang ka pono ea lateral le ventral ea cerebrum le pono ea ho pota-pota ea cerebellum, e bontšang ho tšepahala ha matšoao a fMRI. Likarolo tsa voxel tsa ICC (3,1) li ile tsa baloa ho tsoa likarabong tsa BOLD-fMRI ho lijo le k'hok'heine ...

Mokhoa o tloaelehileng oa ts'ebetso bakeng sa lijo le li-cocaine

Li-cocaine le lihlahisoa tsa lijo li hlahisitse ho sebetsa ho feta ho se nke lehlakore ka cerebellum, gyri e ka tlaasana le ea pele-pele, OFC le li-insula, le tlhahiso e tlase ho feta ho se nke lehlakore ka ventral striatum, rvACC le calcarine cortex (P_FWE <0.0005; ANCOVA; Setšoantšo sa 6 'me Lethathamo 1).

  

Setšoantšo sa 6

Tlhaloso ea lintlha tsa boikopanyo ba boko bo sebetsang ho cocaine le lijo tse amanang le tse ling tsa lipolotiki tse sa nke lehlakore tse hlahisoang ke maikutlo a axial a boko ba motho. Mohlala oa SPM8: ANCOVA. Mebala ea mebala e na le lintlha tse ngata.

Mekhoa e sebetsang ka ho khetheha ea lijo le li-cocaine

Litlhaku tsa Cocaine li hlahisitse matla a mangata ho feta ho se nke lehlakore ka tlaase ho pele le occipital, parahippocampal le gyri ea postcentral le cerebellum, le ho theoha ho feta ho se nke lehlakore libakeng tse bonts'ang, li-cortex, OFC, rvACC, post-insula, li-paralentral le grey, putamen le ventral striatum (sebaka sa NAc) (P_FWE <0.05, ANCOVA; Letlapa le tlatsetsang S1, Lifeiga tsa 6 'me Le7) .7). Ka mokhoa o ts'oanang, lijo tse hlahisoang ke lijo li hlahisa matla a mangata ho feta ho se nke lehlakoreng la gyrus ea postcentral, temporal pole e tlaase le holimo ka holimo ho cortex, insula le cerebellum, le ho theoha ho feta ho se nke lehlakore ka mahlakoreng a mahlo a mahlo a mahlo, a precuneus, a cuneus, a methapo ea occipital grey, ventral striatum, hypothalamus le bo-midbrain [sebaka sa ho ba le tekano (VTA) le substantia nigra (SN); P_FWE <0.01; Letlapa la S1 'me Setšoantšo sa 7].

  

Setšoantšo sa 7

Tlhaloso ea likhapiso tsa likarabo tse fapaneng tsa ho kenyelletsa likarolo tse fanoang ka maikutlo a axial a boko ba motho. Mohlala oa SPM8: ANCOVA. Mebala ea mebala e na le lintlha tse ngata.

Ha li bapisoa le lijo tsa lijo, likhahla tsa cocaine li hlahisoa ka tlaase ho insula le postyral gyrus, ho fokotseha ka tlaase ho hypothalamus, precuneus le posting cingulum le ho ts'ebetsong ho holimo nakong ea bohareng ba nakoana le cortex e fokolang (Lethathamo 2;; P_FWE <0.005; Setšoantšo sa 7). Ka lehlakoreng le leng ha ho bapisoa le litlhapi tsa cocaine, lijo tse hlahisang lijo li hlahisitse ts'ebetso e khōloanyane ho hypothalamus / midbrain le ka mor'a cingulum ka morao 'me ba thibela hore ho be le li-cingulum tsa morao-rao moo li-cocaine li li entseng.

  

Lethathamo 2

Tlhaloso ea li-statistical bakeng sa lihlopha tse sebetsang tsa boko tse ileng tsa sebelisoa ka tsela e sa tšoaneng ke cocaine, lijo le mahlakore a sa nke lehlakoreng.

Tlhaloso ea Striatal D2 / D3 e fumanoang le ho sebelisoa ha boko

Re ile ra hlahloba setsoalle se kopanetsoeng pakeng tsa ts'ebetso ea boko le li-receptor tsa D2 / D3 ka boipheliso bakeng sa li-corsate le li-putamen le ventral striatum hobane libaka tse sa tšoaneng tsa striatum li bontšitse litekanyetso tse sa tšoaneng tsa cortical, 'me li na le liphello tse fapaneng tsa mohopolo libakeng tsa bokooa tse amehang ka taolo ea boitšoaro (Grahn, et al. 2008), ts'ebetso ea botšepehi le ts'ebeliso ea moputso (Volkow, et al. 2011b). Ho ne ho e-na le likamano tse bohlokoa pakeng tsa ho fumaneha ha li-receptor tsa DA D2 / D3 ho striatum le likarabo tse tloaelehileng tsa ho sebelisana ka morero oa lijo le li-cocaine (P_FWE <0.05; Lethathamo 3; Setšoantšo sa 2B le 2C). Ka ho khetheha, ho eketsehile BP_ND e ne e amahanngoa le ho matlafatsoa ka matla ho hippocampus le parahippocampus, rvACC le OFC, le ho fokolloa ha matla ho cuneus, e phahameng ka ho fetisisa ka pele ho gyrus le caudal dorsal ACC (cdACC). BP e eketsehileng_ND ka putamen e ne e amahanngoa le ho matlafatsa ka matla ho OFC, midbrain, cerebellum le holimo ka holimo le parahippocampal gyri le ho fokola ka matla ho cdACC le bohareng ba pele gyrus, cuneus le occipital e mengata le lipilisi tse ling. Litloaelano tse tloaelehileng le BP_ND ka caudate le putamen ba ile ba pholoha litokiso tse eketsehileng tsa Bonferroni bakeng sa palo ea likhahla tsa BP (Pc <0.05, boemo ba sehlopha bo lokisitsoeng bokong bo felletseng ka tokiso ea FWE le bakeng sa liphetoho tse tharo tsa BP ka mokhoa oa Bonferroni). Keketseho ea BP_ND ka ventral striatum e ne e amahanngoa le ho matlafatsoa ka matla maemong a tlase a tlaase le a phahameng a holimo, li-paralentral lobule, gyrus ea postcentral le gyrus ea precentral le ho fokolisa matla ka ho etsa khalase. Leha ho le joalo, litloaelano tse tloaelehileng le BP_ND ka ventral striatum ha aa ka a phela litokisetso tse eketsehileng tsa Bonferroni bakeng sa palo ea li-regression tsa BP. Litšebelisano tsena li ne li sa tšoane haholo le k'hok'heine le lijo tsa lijo (Setšoantšo sa 2C). Litekanyetso tsa li-correlation bakeng sa caudate le putamen li ne li kenella haholo ka occipital cortex, cdACC le rvACC (Setšoantšo sa 2B). Litekanyetso tsa li-correlation tsa ventral striatum ha lia ka tsa bontša ho kopana ho hoholo le tse ling bakeng sa caudate le putamen.

  

Lethathamo 3

Tlhaloso ea likhetho bakeng sa likamano pakeng tsa likarabo tsa fMRI tse tloaelehileng bakeng sa lijo (F) le cocaine (C) cues le ho fumaneha ha li-receptors tsa DA D2 (D2R) ka caudate, putamen le ventral striatum.

Mekhatlo e nang le boemo bo sa foleng, likarabo tsa boitšoaro le BMI

Tlhaloso ea linear e hlahloba litloaelano tse senotsoeng pakeng tsa kopano e kopanetsoeng e sebelisoang ke lijo le li-cocaine, lilemo tsa lilemo tsa ho sebelisa cocaine le li-valence tsa lijo le li-cocaine (P_FWE <0.05; Lethathamo 4; Setšoantšo sa 8). Ka ho khetheha, ho pepeseha ha cocaine nako e telele ho ne ho amahanngoa le ho ts'ebetsoa ho fokolang sebakeng sa cluster se neng se e-na le calcarine cortex e nepahetseng le cerebellum e nepahetseng le e letšehali ho tse ling tsa lijo le tsa cocaine (Lethathamo 4, Setšoantšo sa 8). Li-valence tse ntseng li eketseha bakeng sa lijo le li-cocaine li ne li amahanngoa le ho eketsa ts'ebetsong ho ea tlaase le ho phahama ka nako e telele le e bohareng le e tlaase ea nakoana, le cerebellum le gyrus ea postcentral, le ho theoha ka tlaase ho cuneus bakeng sa cocaine le lijo. Ho phaella moo, BMI e holimo e ne e amahanngoa le ho eketsa ts'ebetso ea lijo ho OFC (BA 11) le gyrus ea postcentral (P_FWE <0.05; Lethathamo 4; Setšoantšo sa 8). Mekhatlo ena e tloahelehileng e sebelisang lilemo tse ngata tsa ts'ebeliso ea cocaine, valence ea cue le BMI e pholohile litokiso tse ling tsa Bonferroni bakeng sa palo ea likhetho (Pc <0.05).

  

Setšoantšo sa 8

Mefuta ea likarolo pakeng tsa ketso e tloaelehileng ea cocaine le lijo tse nang le lijo le BMI, valence ea cue le lilemo tse sebelisang cocaine le ho sebelisana ha tsona (Valence ∩ Lilemo tsa tšebeliso ea cocaine), tse nang le maikutlo a latellanang le a mongobo ka bothata ba lefu le ho robala ...

Li-receptor tsa D2 / D3 le ts'ebetso ea boko

Ho fumaneha ha methapo ea DA D2 / D3 ho striatum e ne e amahanngoa le ts'ebetso ea boko ho cocaine le lijo. Hoa thahasellisa hore, le hoja litšebelisano tsa likamano li ne li tšoana le cocaine le lijo tse ling, mekhatlo e momahaneng pakeng tsa ho fumaneha ha li-receptor e hlaselang D2 / D3 le likarabo tsa BOLD li ne li e-na le karolo e kholo bakeng sa caudate and putamen (dorsal striatum) empa lebala la sephahla le ne le bontša mokhoa o khethollang. Liphuputso tsena li lumellana le karolo ea tsamaiso ea DA le ea li-receptor tsa D2 / D3 ho khutlisetsa lihlahisoa ho lijo le lithethefatsi (Salamone le Correa 2012) 'me ka karolo e ikhethang eo ho etsoang ka eona le sebaka se senyehileng sa naha ho fetola likarabo tsa lipotso (Di Ciano, et al. 2008).

Mohlala oa likamano pakeng tsa li-receptor tse hlaselang D2 / D3 le ho kenyelletsa BOLD li kenyeletsa libaka tsa cortical (parietal cortex) le cerebellum, e leng libaka tsa boko bo nang le maemo a tlase a amohelang D2 / D3 receptors (Mukherjee, et al. 2002). Mokhoa ona o atileng oa likamano o ka 'na oa bonahatsa karolo eo modemone ea D2 / D3 e nang le li-neurone ka statum e nang le liketsahalo tsa cortical ka litsela tsa tsona tsa thalamo-cortical (Haber le Calzavara 2009). Ka lebaka leo, matla a kopano pakeng tsa li-receptor tsa D2 / D3 le ts'ebetso ea BOLD sebakeng se fanoeng se tla bontša karolo ea ho khetholla ha basebelisi ba D2 le ba amohelang D3 ba bonts'ang likhokahano ho marang-rang a loketseng a cortical le a subcortical a sebelisitsoeng ke cues.

Karolo ea li-receptor tsa D2 / D3 ha li ntse li sebelisoa hape lijong le lithethefatsi li lumellana le liphuputso tsa pele tsa bophelo. Ka ho khetheha, ho sebelisa PET le [¹¹C] raclopride rōna le ba bang re bontšitse hore ho pepesehela lithethefatsi ho eketsa dopamine ka mor'a ho pepesa k'hok'heine (Volkow, et al. 2006; Wong, et al. 2006), amphetamine (Boileau, et al. 2007) le heroin (Zijlstra, et al. 2008) cues. Lithuto tsa mahlale le haloperidol le amisulpiride li boetse li bontšitse hore thibelo ea D2 / D3 e amohelehang e fokotsa khethollo e matla ho li-heroin tse lemalang batho ba heroin (Franken, et al. 2004), 'me e lumellana le ts'ebetso ea ho tsuba litlhapi ho ACC le PFC ho batho ba tsubang (Luijten, et al. 2012) le ho noa joala ho ACC le OFC ka lino tse tahang (Hermann, le al. 2006). Ka hona, liphihlelo tsa rona le tsa ba bang (Saunders le Robinson 2013) e bontša hore karolo ea DA, ka karolo e itseng ho feta li-receptors tsa D2 empa ho ka etsahala hore ebe le li-receptor tsa D3, li na le karolo ea bohlokoa mosebetsing oa ho sebetsana le lithethefatsi le lijo. Ho fapana le lithuto tsa rona tsa pele (Wang, et al. 2001), BP e hlaselang_ND e ne e sa amane le BMI thutong ea hajoale, e ka bonts'ang liphapang lipakeng tsa mehlala. Haholo-holo, athe thuto ea hajoale e kenyelletsa feela karoloana e nyane ea batho ba batenya ho tlola (3/20 lihlooho tse nang le BMI> 30 kg / m²;; Libaka tsa BMI: 20-35 kg / m²) 'me kaofela ha bona e ne e le bahlaseluoa ba k'hok'heine, lithuto tsa rona tsa pele li kenyeletsa 10 ka matla ho se sebelise lithethefatsi hampe batho ba nang le BMI e kholo ho feta 40 kg / m² (fapaneng: 42-60 kg / m²) le 10 bophelo bo botle bo sa sebeliseng lithethefatsi hampe (range: 21-28 kg / m²).

Sebopeho se tloaelehileng

Ho khetholla lipotoloho tsa boko bo feteletsoeng tse nkiloeng ke lijo le lithethefatsi li ka thusa ho tseba mekhoa ea phekolo e ka thusang batho ba lemaletseng lithethefatsi le batho ba feteletseng. Litlhohonolofatso tsa tlhaho li lokolla dopamine mokhoeng oa ventral, oo ho lumeloa hore o tla beha liphello tsa bona tse putsang. Leha ho le joalo ka ho pepesehela khafetsa moputso oo dopamine e eketsehang ho fetisoa ho tloha moputsong ho tse ling tse bolelang esale pele (Schultz, et al. 1997), e leng se etsang hore ho be le koloi e susumetsang e hlokahalang bakeng sa ho netefatsa boitšoaro bo hlokahalang bakeng sa tšebeliso ea moputso (Pasquereau le Turner 2013). Ho pepesa hangata lithethefatsi tsa tlhekefetso ho boetse ho fella ka boemo ba boemo bo botle. Ka tsela ena, likarabo tsa boemo ba lijo le lithethefatsi li fetola ts'usumetso ho susumelletseha ho ba le maikutlo a hlalosang moputso (Berridge le Robinson 2003).

Ho thahasellisang re bontša hore libaka tsa dopaminergic tse thibelang ho hlahella litabeng tsa moputso, ho kenyelletsa le ventral striatum (ho ea ho lijo le lithethefatsi) le hypothalamus le midbrain (ho ea lijo tsa lijo) ha li bapisoa le likarolo tse sa nke lehlakore (Lethathamo 2 'me Setšoantšo sa 4), e lumellanang le mekhoa e thibelang ea DA ho batho bao e seng li-primates (Bophirimela le Grace 2002) le ho batho (Volkow, et al. 2010b) le ka keketseho ea DA ts'ebetsong e latelang ea lithethefatsi ho bahlaseli ba k'hok'heine (Volkow, et al. 2006) le lijo tse fanang ka taolo (Volkow, et al. 2002). Lithethefatsi tsohle tse nang le lithethefatsi li eketsa DA mokhoeng oa ventral (NAc) (Koob 1992), 'me liphello tsa bona tse putsang li amahanngoa le tsena e eketseha ho lokolloa ha DA (Drevets, et al. 2001; Volkow, et al. 1999b; 2009 e Bohlale). Lijo li ka boela tsa eketsa DA ho tsoa kahare ho li-ventatum (de Araujo, et al. 2008; Norgren, et al. 2006) 'me li na le moputso o matla (Lenoir, et al. 2007). Ka lehlakoreng le leng, cerebellum le insula, li ile tsa bontša ho matlafatsa k'hok'heine le lijo ho e-na le ho se nke lehlakore (Lethathamo 2 'me Setšoantšo sa 4). Liphuputso tsena li lumellana le ts'ebetsong ea cerebellum le insula nakong ea temo ea maikutlo litlamong tsa tlala (Haase, et al. 2009) le ka cerebellar (Grant, le al. 1996) le ts'ebetsong ea batho ba nang le lik'hemik'hale tsa cocaine ba pepesehileng likheo tsa cocaine (Wang, et al. 1999). Ho feta moo, ha ba hlaseloa ke li-cocaine, bahlaseluoa ba cocaine ba ile ba laela ho thibela takatso ea bona ea ho thibela lihlekehleke tsena (Volkow, et al. 2010a), 'me tšenyo ea insula e ka senya ho lemalla tsuba ea sakerete (Naqvi, et al. 2007). Ka sebele sehlekehlekeng sena se ntse se nkoa e le sehlahlo se ka sehloohong sa ho lemalla ho lemalla ho lemalla litabeng tsa lithethefatsi.Naqvi le Bechara 2010). Liphello tsa rona li fapane le tse fumanoang ke likhoto tse koetliselitsoeng ho kopanya monko o monate le ho fumaneha ha li-reinforcer (li-cocaine tse se nang mokokotlo / mouth sucrose), tse bonts'ang mosebetsi o fapaneng oa bokooa ho NAc bakeng sa cocaine ho feta sucrose (Liu, et al. 2013). Phapang ena e ka 'na ea bonahatsa phapang lipakeng tsa mefuta-futa (ho lemalla batho ka litoeba tse tšoaetsanoang le k'hok'heine), tšebeliso ea monko o khahlanong le litšoantšo le likhohlano ho tsoa liphellong tsa manonyeletso a sebelisetsoang lithuto tsa litoeba.

Ts'ebetso ea Cerebellar e ne e le matla bakeng sa k'hok'heine le lijo tse fapaneng ho feta tse sa nke lehlakore, tse lumellanang le lipatlisiso tsa pele tse bontšang karolo ea karolo ea cerebellum ho ithuta ka moputso (Thoma, le al. 2008), mohopolo o bakoang ke cocaine (Carbo-Gas, et al. 2013) le ho laola mesebetsi ea visceral le taolo ea phepo ea lijo (Haines, et al. 1984). Ts'ebetso ea Cerebellar lijong le li-cocaine li fokotsehile ka lilemo tse ngata tsa tšebeliso ea cocaine (Lethathamo 4). Tlhahiso ena e tsamaellana le likarabo tsa boko tse fokolang tsa boko ha li bapisoa le taolo (Bolla, et al. 2004; Goldstein, et al. 2009; Hester le Garavan 2004; Li, et al. 2008; Moeller, et al. 2010; Volkow, et al. 2010b), le ka lipatlisiso tsa rona tse fetileng tse bontšang hore keketseho ea methapo ea methapola ea cerebellar e ileng ea hlokomeloa ka mor'a hore ho be le phephetso ka lithethefatsi tse matlafatsang (methylphenidate) li amana le ho fumaneha ha li-receptor tse hlaselang D2 / D3 (Volkow, et al. 1997a), tse atisang ho fokotseha ha ba hlekefetsang k'hok'heine (Martinez, et al. 2004; Volkow, et al. 1993b; Volkow, et al. 1990).

Ha li bapisoa le litloaelo tse sa nkeheng, li-cocaine / lijo tsa lijo li boetse li etsa hore ho be le ts'ebetso e eketsehileng ka lateral OFC, likarolo tse tlase tsa pele le tsa pele ho nako le ho thibela matla ho rvACC, libaka tsa precuneus le tse bonahalang (Lethathamo 1). Liphuputso tse fetileng li bontšitse hore ha li bapisoa le lihlahisoa tse sa nkeheng, li-cue tsa lijo li etsa hore e be tsa bohlokoa ts'ebetso likarabo tsa insula, li-cortex, li-parietal le li-cortices tse bonahalang (Cornier, et al. 2013), le bana ba kotsing ea ho ba botenya haholo ba bonts'a matla haholoanyane ho lijo tse fumanehang ka hare ho cortex (Stice, et al. 2011). Ho feta moo, insula ea ka hare, le tlase e ka tlaasana le OFC li kopanngoa le striatum ka litekanyetso tsa cortico-striatal modulated ke DA (Haber 2003) le ho phetha boikarabelo ba bohlokoa ho thibela ho thibela tšebetso, ho etsa liqeto, tsamaiso ea maikutlo, ho susumetsa le ho ba le boikutlo bo matla (Goldstein le Volkow 2002; Phan, et al. 2002; Volkow, et al. 1996). Ho feta moo, OFC bohlooho bo bongata bo bongata bo bonts'a likamano tse fosahetseng le BMI ho lemalla li-cocaine le litsamaiso hammoho le lilemo tse sebelisang cocaine ho lemalloa ke cocaine (Smith, et al. 2013), e ka boela ea bonahatsa liphello tsa cocaine libakeng tse nang le meputso ea tlhaho joaloka OFC.

Mefuta e fapaneng ea marang-rang

Litlhaku tsa Cocaine li hlahisitse ts'ebetso e matla haholo ea fMRI ka cerebellum, occipital le prefrontal cortices le ts'ebetso e kholo ho rvACC le ho hlasela holimo ho feta ho se nke lehlakore. Liphuputso tsena li lumellana le keketseho e amanang le litakatso tse amanang le litakatso tsa PFC, li-lobe tsa nakoana le cerebellum (Grant, le al. 1996) le ka ho fokotseha ha metsoli ea ventral striatum (Volkow, et al. 2010b) 'me ho phalla ha mali ho fokotseha ka basal ganglia (Childress, le al. 1999) ho lemalloa ke cocaine nakong ea li-codiine-cue stimulation paradigms.

Li-cue tsa lijo li hlahisitse ts'ebetso e matla haholo ea fMRI ho feta ho se nke lehlakore lihlahantsing tsa li-insula, li-cortices le tse bonahalang, le ho thibela ho eketsehileng ho rvACC, hypothalamus, midbrain le primax cortex, precuneus le gyrus. Le hoja litlhapi tsa cocaine ha lia ka tsa etsa hore BA 43 (k'hemik'hale e tloaelehileng; Lethathamo 2) ka holimo ho lihlooho, likarabo tsa fMRI lijong tsa lijo ka BA 43 li ne li le bohlokoa (Lethathamo 2) 'me ka tsela e nepahetseng e tsamaisana le ho fumaneha ha batho ba DA D2 / D3 mecheng ea ventral striatum (Setšoantšo sa 2C), e leng se neng se tla fana ka maikutlo a ho feto-fetoha ha dopaminergic sebakeng sena sa boko. Ts'ehetso ea sena e ne e le likamano tse kholo pakeng tsa likarabo tsa ts'ebetso ea fMRI ka cortex ea boithabiso le valence ea cue lijo (Lethathamo 4), kaha DA e lekanya bohlokoa ba meputso ea lijo (Volkow, et al. 2012b).

Ho se ts'ebetsoe libakeng tsa morao-rao tsa DMN ho ne ho e-na le lijo tse ngata ho feta tsa li-cocaine. Ts'ebetsong ea DMN e amahanngoa le moloko oa mehopolo ea boipheliso nakong ea ho lelera kelellong (Mason, le al. 2007) mme ts'ebetso ea eona e hlahisa nakong ea ts'ebetsong ea mesebetsi e hlokang tlhokomelo e hlokang tlhokomelo (Fox, et al. 2005). Habohlokoa, tekanyo ea ts'ebetso ea DMN nakong ea tlhokomelo e hlokang mesebetsi ea tsebo e fapana hohle mesebetsing (Tomasi, le al. 2006), mohlomong ho bonahatsa tekanyo ea ho tlosoa ha mehopolo ea boipheliso. Ka hona, ho fokolloa ha DMN ho fokolang bakeng sa likheo tsa cocaine ho feta bakeng sa lijo tsa lijo ho ka bonahatsa tekanyo e phahameng ea menahano ea nakoana nakong ea li-cocaine ho feta nakong ea lijo. Sena se ka bonahatsa phapang e sa tšoaneng ea ho lokolloa ha dopamine lipakeng tsa lijo le li-cocaine hobane ho eketseha ha DA ho amahanngoa le ts'ebetso ea DMN (Thanos, et al. 2013; Tomasi, le al. 2009). Tšebelisano e fosahetseng e pakeng tsa li-receptor tsa D2 / D3 ka dorsal striatum le likarabo tsa fMRI ka cuneus, e le hore maemo a phahameng a ho amohela li-receptor e kholoanyane ho thibela cuneus, e lumellana le karolo e thibelang ea DA ho DMN (Thanos, et al. 2013; Tomasi, le al. 2009).

BOLD-fMRI e bonts'a tlhatlhobo ena e ne e sa fapane ka ho feletseng matsatsing a thuto, ho fana ka maikutlo a ho fapana ho fapaneng ka hare ho-ho feta pakeng tsa lihlooho. Ho feta moo, ts'ebetso ea ho hlahloba lits'ebeletso tsa ts'ebetso ea ts'ebetso e ne e tšoana le ea mekhoa e tloaelehileng ea ho sebetsana le mesebetsi ea fMRI e sebelisang mekhoa e thibetsoeng (Bennett le Miller 2013). Ha e le hantle, ho tšepahala ha matšoao a fMRI ho fapane le 0.4 (ho tšepahala ho itekanetseng) ho ea ho 0.8 (ho tšepahala ho phahameng), hape ho fana ka maikutlo a ho fokotsa ho feto-fetoha ha bokooa ba bokooa lijong le li-cocaine bakeng sa ka hare-taba ho feta mehato e pakeng tsa lihlooho.

Ha re fetola liphello tsa rona re ile ra nahana hore ho ka etsahala hore ebe batho ba hlekefetsang ba ts'oaetsano ea k'hok'heine ba ka 'na ba ameha haholo-holo litabeng tsa moputso (moputso oa tlhaho le oa lithethefatsi), e leng se ka tlatsetsang bothateng ba bona ba ho lemala (Saunders le Robinson 2013). Ho feta moo, liphelong tsa rona, valence ea likheo tsa cocaine e amana le valence ea lijo, e lumellanang le kutloisiso e tloaelehileng ho kakaretso cue reactivity (Saunders le Robinson 2013). Ka tsela eo, re ke ke ra kenyeletsa monyetla oa hore phapang eo re e bonang ho bahlaseli ba cocaine e ka 'na ea e-ba teng pele ho ts'ebeliso ea bona ea lithethefatsi' me e ka 'na eaba e entse hore e be kotsing ea ho sebelisoa hampe ka cocaine. Tabeng ena, e ka be e lakatseha ho kenyelletsa sehlopha sa taolo ho hlahloba hore na liphello li bakoa ke eng ho lijo le li-cocaine ho batho ba lemalang le batho bao e seng makhoba le ho bona hore na kutloisiso ea bona ho lijo e boetse e fapane pakeng tsa lihlopha. Re fana ka maikutlo a hore ho se tšoane ha likarabo tsa boitšoaro le ts'ebetso ea boko bo hlahisoang ke lijo tse fanoang ke li-cocaine e ka ba kholo ho feta lits'ebetso ho feta bakeng sa bahlaseli ba cocaine. Ho feta moo, re ne re sebelisa [¹¹C] raclopride, e nang le limmapa tsa D2 / D3, mme e ka ba tse lakatsehang ho sebelisa radiotracers e neng e tla re thusa ho khetholla pakeng tsa monehelo oa li-receptor tsa D2 le tsa ba amohelang D3. Hape, [¹¹C] raclopride e ela hloko tlhōlisano ho DA e sa mameleng (Volkow, et al. 1994), kahoo re ke ke ra tseba hore na mokhatlo o nang le ts'ebetso ea boko bo bontša phapang pakeng tsa li-receptors tsa D2 / D3 kapa tlhōlisano ea dopamine le radiotracer bakeng sa ho tlama litsamaiso tsa D2 / D3. Leha ho le joalo, kaha rona le ba bang re 'nile ra bontša hore bahlaseluoa ba k'hok'heine ba fokotseha ho lokolloa ha DA (Volkow, et al. 2011b) ho ka etsahala hore ho se tšoane ha bokhoni ba boko bo bontša likarolo tse fapaneng tsa li-receptor tsa D2 / D3 ho striatum. Ho phaella moo, lenaneo la fMRI le qalile ho hlahloba PET ka metsotso ea 60 mme e ka eketsa ho lokolloa ha DA ka nako e telele, ho fokotsa ka mokhoa o tsitsitseng BP_ND mehato. Leha ho le joalo, ho eketseha ha ho lokolloa ha DA ho bakoang ke lintlha tse potlakileng le tse khutšoanyane (metsotso ea 2-3) (Erhardt, et al. 2002) ka hona ho lebelloa hore ho lokolloa ha DA ho tla be ho khutletse boleng ba pele ka nako ea mokhoa oa PET oa ho hlahloba. Leha ho le joalo, hobane re ke ke ra tiisa hore ha ho na letho, DA e lokolloa nakong ea fMRI ke ntho e ferekanyang thutong ea rona.

Liphello tsa rona li bonts'a hore lijo le li-cocaine li na le marang-rang a tloaelehileng a amoheloang ke li-receptor tsa DA D2 / D3 tse akarelletsang cerebellum, insula, tlaase ka tlase, OFC, ACC, somatosensory le occipital cortices, ventral striatum le DMN. Lijo tsa lijo li hlahisitsoe matla ts'ebetso likarabo ho feta cocaine tse hlahang li-insula tsa posterior le gyrus ea postcentral, ho thibela ho feta libakeng tsa DMN le libakeng tsa hypothalamic le ho fokotseha ho fokolang ka likortices tsa nakoana le tsa parietal. Likarabo tsa ts'ebetso ea bongobo lijong le li-cocaine libakeng tsa prefrontal le tsa temporal cortical tse amanang le meputso ea meputso e eketsehileng le valence ea cues 'me e amana le li-receptors tsa D2 / D3; e lumellanang le substrate e tloaelehileng ea neuronal bakeng sa boleng ba litlhapi tsa tlhaho le lithethefatsi tse fokotsoang ka mokhoa oa D2 / D3 o amohelanoang lipakeng ho lemalla.

Mosebetsi ona o ile oa finyelloa ka tšehetso ea Mekhatlo ea Sechaba ea Tlhekefetso ea Joala le Tlhekefetso ea Lithethefatsi (2RO1AA09481).

Bangoli ha ba tlalehe litabeng tsa lichelete kapa litabeng tse ka 'nang tsa e-ba le thahasello.

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