Kuphatikizidwa kwa machitidwe a ubongo kupita ku zakudya ndi mankhwala a cocaine mu owononga cocaine: kucheza ndi D2 / D3 receptors (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 ndi Nora D. Volkow, MD^1,3

Cocaine, pogwiritsa ntchito dopamine (DA), ikugwiritsa ntchito njira zomwe zimapereka mphotho zachilengedwe. Komabe, kuchuluka pakati pa magulu omwe amapanga mphotho ndi mankhwala osokoneza bongo komanso ngati chizindikiro cha DA chogwiriridwa ndi mankhwala a cocaine chimakhudza magulu amenewa sichinafufuzidwe mwa anthu. Tinayeza mayankho okhudza ubongo ndi zakudya za cocaine ndi fMRI, ndi D2 / D3 receptors mu striatum ndi [¹¹C] raclopride ndi PET mu 20 omwe amagwiritsa ntchito mankhwala osokoneza bongo a cocaine. Poyerekeza ndi zandale, chakudya ndi cocaine zimagwiritsidwa ntchito kwambiri, zomwe zimapangidwira, zowonongeka, zowonongeka komanso zowonongeka ndi cuneus komanso njira zosasinthika (DMN). Zizindikiro za fMRIzi zinali zofanana ndi zofunkha D2 / D3. Chokalika chododometsa ndi chakudya chachitsulo chinachotsanso ventral striatum ndi hypothalamus. Poyerekeza ndi chakudya, mankhwala a cocaine amapangidwa m'munsi mwa insula ndi postyral gyrus, komanso kuchepa pang'ono mu hypothalamus ndi madera a DMN. Kugwira ntchito m'madera a cortical ndi cerebellum kuwonjezeka molingana ndi valence ya cues, ndi kuika chakudya ku zigawo zofanana ndi zomwe zimapangidwira m'matumbo komanso zina zothamanga. Kupezeka kwa cocaine nthawi yaitali kunkagwirizanitsidwa ndi kutsekedwa kochepa m'magulu awiri a occipital ndi cerebellum, zomwe zingawonetse kuchepa kwa D2 / D3 receptors zogwirizana ndi matenda. Zotsatirazi zikuwonetsa kuti mankhwala a cocaine amachititsa kuti zikhale zofanana, ngakhale kuti sizikufanana, njira zowonjezera ndi zakudya komanso kuti odwala D2 / D3 amalandira mayankhowa, kuwonetsa kuti kutentha kwa cocaine kungakhudze ubongo wanu osati mankhwala okhaokha komanso chakudya.

Ophunzira

Ophunzirawo anali 20 omwe amagwira ntchito molakwika ndi cocaine (amuna 46.4 ± 3.3); zaka 12.8 ± 1.4 za maphunziro; thupi lalikulu index (BMI) la 26 ± 4 kg / m²; amatanthauza ± SD). Ophunzirawo adalembedwa pamalonda otsatsa malonda, m'manyuzipepala am'deralo komanso pakamwa. Maphunziro onse adapereka chidziwitso chovomerezeka chovomerezedwa ndi Institutional Review Board (Komiti ya Stony Brook University pa Kafukufuku Wokhudza Anthu, CORIHS), ndipo adawunikidwa kuti apeze matenda azachipatala, amisala kapena amitsempha. Katswiri wazamisala adachita zoyankhulana mwapadera zomwe zidaphatikizapo Structured Clinical Interview ya DSM-IV Axis I Disways [kafukufuku wofufuza (Choyamba, et al. 1996; Ventura, et al. 1998)] ndi Addiction Severity Index (McLellan, et al. 1992).

Mayeso oyeserera a labotale (mwachitsanzo, electrocardiogram, lab lab and screen mkodzo) adachitidwa paulendo wowunikira kuti awonetsetse kuphatikizira / kusiyanitsa kafukufukuyu. Mitu yamwamuna idaphatikizidwa ngati anali 1) amatha kumvetsetsa ndikupereka chidziwitso; anali ndi 2) DSM IV yodziwika kuti imadalira mankhwala osokoneza bongo a cocaine; 3) osachepera mbiri yazaka 2 yogwiritsa ntchito mankhwala osokoneza bongo a cocaine pogwiritsa ntchito magalamu atatu a cocaine / sabata; 3) kugwiritsa ntchito mankhwala osokoneza bongo a cocaine posuta fodya kapena iv, komanso 4) osafuna chithandizo cha cocaine. Omwe sanatengeredwe ngati anali ndi 5) mbiri yakale kapena yam'mbuyomu yamatenda am'magazi oyambira kapena matenda amisala kuphatikiza kumwa mopitirira muyeso kapena kudalira mowa kapena mankhwala osokoneza bongo kupatula cocaine ndi chikonga, 6) kuchuluka kwa nkhawa, mantha, psychosis, kupatula omwe amagwirizana ndi nkhanza za cocaine; 7) matenda azachipatala omwe angakhudze ubongo; 8) mbiri yapano kapena yam'mbuyomu yamatenda amtima kuphatikiza matenda amtima komanso kuthamanga kwa magazi kapena matenda a endocrinological; 9) kupwetekedwa mutu ndikutaya chidziwitso> Mphindi 10; 30) mbiri yakumutu kwam'mimba; 11) zopangira zazitsulo kapena zotsutsana ndi MRI.

Mitundu khumi ndi itatuyi inali yosuta fodya (17 ± 7 zaka za kusuta, 8 ± 7 ndudu pa tsiku). Ophunzira onse anali ndi mchere wokhala ndi cocaine m'masiku onse ophunzira, posonyeza kuti agwiritsira ntchito cocaine pa maola oyambirira a 72.

Zotsatira za Cocaine ndi kanema wa zakudya zomwe zimawoneka ngatidididims

Mapulogalamu awiri a mavidiyo a paradigms adagwiritsidwa ntchito pa phunziro la FMRI. Ntchito yopititsa patsogolo mavidiyo ya 6 ya long cocaine (Chizindikiro 1A ndi 1B) idapangidwa ndi cocaine sikisi, sita osalowerera ndale ndi 6 (mawonekedwe wakuda omwe ali ndi mtanda wopangira malo), nthawi iliyonse yachidule ya 20 ndikuchitika mwachisawawa. Mapulogalamu a cocaine anali ndi zigawo zosagwiritsanso kanema zomwe zimaonetsa kugula, kukonzekera, ndi kusuta kwa cocaine zomwe zinatulutsidwa kale (Volkow, et al. 2006; Volkow, et al. 2010b). Nthawi zosalowerera ndale zinkakhala zochitika nthawi zonse zowonongeka / ntchito zamakono monga zolamulira zinthu.

  

Chithunzi cha 1

A: Mavidiyo omwe amachititsa kuti ntchitoyi ikhale yogwira ntchito, imakhala yopanda ndale komanso yopanda mavidiyo a cocaine kapena masewero a chakudya (20 masekondi ambiri). Kuwonetsera zithunzi zomwe zimagula kugula, kukonzekera, ndi kusuta cocaine (cocaine) ...

Mofananamo, ntchito yopititsa patsogolo mavidiyo ya 6 yomwe imatenga nthawi yayitali idapangidwa ndi "chakudya" chachisanu ndi chimodzi, 6 'osalowerera ndale' (ntchito yachizolowezi ya ntchito / luso) ndi 6 'kulamulira' nthawi yochepa ya 20 masekondi ndipo zimachitika mwadongosolo. Nthawi zakudya zinali ndi zigawo zosagwiritsa ntchito mavidiyo zomwe zatulutsidwa posachedwapa (Wang, et al. 2013), zomwe zikuwonetsera masewero olimbikitsa kudya (ie, meatballs, pasta, omelets, burger, zikondamoyo).

Nkhanizo zidalangizidwa kuti ziziwonerera pulogalamuyo pang'onopang'ono ndikusindikiza batani loyankhidwa ndi thumba lawo lakumanja pamene ankakonda zochitikazo. Zidutswa za vidiyo zomwe zinkapezeka pakhomo ndi kusungidwa mu Audio Video Interleave format ndi ogwira ntchito pavidiyo pa Brookhaven National Laboratory. Mavidiyo awa adakambidwa pa nkhani za MRI-compatible goggles (Resonance Technology Inc., Northridge, CA) yogwirizana ndi makompyuta. Pulogalamuyi inalembedwa m'zilankhulo za Visual Basic ndi C mu phukusi la Visual Studio (Microsoft Corp., Redmond, WA) ndipo idagwirizanitsidwa bwino ndi kupeza kwa MRI pogwiritsa ntchito pulling pulse.

Zakudya za cocaine valence

Pamene nkhanizo zinkagwira ntchito pang'onopang'ono pa chakudya, cocaine ndi / kapena nthawi zosalowerera zina zomwe zimakonda kwambiri zomwe zimawonetsedwa pazithunzizo. Chiwerengero cha makina a batani chinkagwiritsidwa ntchito poyerekeza zivalo zofanana kuchokera mu 0 mpaka 10. Mwachindunji, chiwerengero cha batani chimaphatikizira pa chakudya (f), ndale (n) ndi kuyang'anira maziko oyamba (b) nthawi yowonetsera kanema ya chakudya idagwiritsidwa ntchito kuwerengera chakudya = f / (f + n + b) Ndi kulowerera ndale = n / (n + f + b) zivomezi zofanana ndi kanema ya zakudya. Mofananamo, chiwerengero cha makina osindikizira pa cocaine (c) nthawi zinkagwiritsidwa ntchito kuti ziwerengere cocaine = c / (c + n + b) komanso kulowerera ndale = n / (n + c + b) ma valences pa kanema ya cocaine. Onani kuti chakudya ndi cocaine valence ndi zovomerezeka mayendedwe omwe ali osagwirizana ndi valentical nevral, ndi kuti b (chiwerengero cha makina osindikizira pa nthawi yoyambira) kumakhala phokoso la phokoso ndipo amachepetsa kugwirizana kosagwirizana pakati pa ma valences kuchokera ku mgwirizano wolakwika.

MRI data kupeza

Mutuwo unayang'anitsitsa-tsiku lomwe lisanayambe phunziroli pofuna kuyesetsa kupewa kugwiritsa ntchito mankhwala usiku womwewo usanayambe kuphunzira. Iwo anabweretsedwa ku Guest Guest Facility ku Brookhaven National Laboratory ku 5: 00PM, kumene iwo ankakhala chakudya chamadzulo ndikugona usiku wonse. Mmawa wotsatira, pakati pa 8: 00AM ndi 8: 30AM, anthuwa anali ndi kadzutsa kakang'ono kamene kali ndi madzi ndi bagel, roll kapena tirigu malingana ndi zomwe amakonda. Kugwiritsira ntchito ubongo kuti likhale cocaine cues, chakudya ndi ndale sizinayesedwe pakati 9: 00AM ndi 10: 00AM kawiri pa 2 masiku kuphunzira, masabata 2 kupatula. Kukonzekera kwa mavidiyo a mavidiyo ndi zakudya za cocaine kunali kovuta pa maphunziro. A 4-Tesla thupi lonse Varian (Palo Alto, CA) / Siemens (Erlangen, Germany) Kujambula kwa MRI pogwiritsa ntchito T2 * -wotetezedwa-kujambula zithunzi zofanana (EPI) (TE / TR = 20 / 1600 ms, 4-mm chidutswa, 1-mm kusiyana, magawo a 35, 64 × 64 matrix kukula, 3.125 × 3.125 mm² Kusintha kwa ndege, 90 ° -flip angle, 226 time time, 200.00 kHz bandwidth) wokhala ndi mayendedwe apakompyuta ndikuwunika ubongo wonse adagwiritsidwa ntchito kusonkhanitsa zithunzi zogwira ntchito mosiyana ndi magazi-oxygenation-level-dependent (BOLD). Padding idagwiritsidwa ntchito kuchepetsa kuyenda. Kuyenda kwamutu kunayang'aniridwa nthawi iliyonse fMRI ikatha kugwiritsa ntchito k-space motion detection algorithm (Caparelli, et al. 2003) lolembedwa mu Interactive Data Language (IDL; ITT Zowonetsera Zowonongeka, Boulder, CO). Pulogalamu yamakono (-28 dB yovuta kuthamanga kwachangu; Aearo Ear TaperPamene 2; Aearo Co., Indianapolis, IN), makutu (-30 dB phokoso loyendetsa mphamvu; Commander XG MRI Chowombera, Resonance Technology Inc., Northridge, CA) ndi Njira yopezera kugula "yogula" inagwiritsidwa ntchito kuchepetsa kusokonezeka kwa phokoso la phokoso pa fMRI (Tomasi, ndi al. 2005). Zithunzi zosawerengeka zinasonkhanitsidwa pogwiritsira ntchito T1 yolemera zitatu-dimensional modified driven kufanana Fourier kusintha kusintha mapangidwe (TE / TR = 7 / 15 ms, 0.94 × 0.94 × 1.00 mm³ Kusintha kwa malo, maulendo axial, masewero a 256 ndi 192 × 96-encoding steps steps, 16 Mphindi nthawi yopima) ndi kusintha modified T2-hyperecho sequence (TE / TR = 0.042 / 10 masekondi, echo kutalizera = 16, 256 × 256 matrix kukula, zigawo za 30, 0.86 × 0.86 mm² kukonza ndege, 5 mm thickness, palibe kusiyana, 2 min scan nthawi) kuti athetse makhalidwe aakulu a ubongo.

Data Processing

Njira yowonetsera njira yomwe ikuchepetsera chiwonetsero chowonetseratu ku EPI chinagwiritsidwa ntchito popanganso chithunzi (Caparelli ndi Tomasi 2008). Mfundo zoyambirira zazing'onoting'ono zinatayidwa kuti zisawononge zotsatira zosagwirizana ndi chizindikiro cha fMRI. Mapulogalamu ofotokoza mapepala a SPM8 (Wellcome Trust Center ya Neuroimaging, London, UK) anagwiritsidwa ntchito pofufuza. Kuwonetsera kwazithunzi kunkachitika ndi 4^th digiri B-spline ntchito popanda kuyeza ndi popanda kugwedeza; Kusuntha kwa mutu kunali kochepa kuposa Mabaibulo a 2-mm ndi ma 2 ° -zosinthira pa zokopa zonse. Kukhazikika kwa malo kumalo osungirako malo a Montreal Neurological Institute (MNI) ankagwiritsidwa ntchito pogwiritsa ntchito 12-parameter kusintha ndi regularization, kusintha kwa 16-nonlinear ndi kukula kwa voxel ya 3 × 3 × 3 mm³ ndi sewero la SPM8 EPI. Kuwongolera kwapakati kunkachitika pogwiritsa ntchito kernel ya Gaussian ya XWUMX-mm yochuluka kwambiri (FWHM). FMRI amayankha panthawi yomwe mafilimu amawongolera mafilimu amayerekezera kuti amagwiritsa ntchito chitsanzo chofanana (Friston, ndi al. 1995) ndi kapangidwe kamene kamakhala ndi 2, poyendetsa kayendetsedwe ka 20sec yaitali cocaine / nyengo ya chakudya ndi nthawi ya 20sec yaitali yomwe siilimbana nawo.Chithunzi 1B), atsegulidwa ndi otsika (HRF) ndi high-pass (maulendo odulidwa: 1 / 800 Hz). Motero, mapu osiyana a 2 omwe amasonyeza kusintha kwa chizindikiro cha BOLD-fMRI kuchokera pazomwe zimayambira (tsamba lakuda lokhala ndi mtanda) chifukwa cha cocaine / cue chakudya ndi ndale sizinapezeke pa fMRI iliyonse pa phunziro lililonse.

Kukhazikika kwa retestdi kudalirika

Kudalirika kwa mayankho ogwira ubongo ku maulendowa anayesedwa pa voxel iliyonse ya imaging pogwiritsa ntchito njira ziwiri zosakanikirana zosiyana (Chiphuphu ndi Zowopsya 1979).

Makamaka, ICC (3,1) imapangidwe mu ubongo ponena za masewero ena (BMS) ndi zotsalira (EMS) zikutanthawuza mawerengedwe apakati pa voxel iliyonse pogwiritsa ntchito IPN-retest yodalirika matlab toolbox (http://www.mathworks.com/matlabcentral/fileexchange/22122-ipn-tools-for-test-retest-reliability-analysis) ndi mapu osiyana a fMRI ofanana ndi cocaine / cue chakudya kuchokera ku maphunziro onse ndi magawo (k = 2). Onani kuti ICC (3, 1) coefficients amachokera 0 (palibe kudalirika) kwa 1 (kudalirika kwathunthu).

PET kuyesa

Mphindi makumi atatu mutatha kuwunika kwa MRI (pafupi ndi 60 maminiti pambuyo pa mapeto a fMRI) maphunzirowa anafufuza PET kuti apeze mapepala a DA D2 / D3 mu ubongo. Tinagwiritsa ntchito tomograph ya HR + (yankho la 4.5 × 4.5 × 4.5 mm³ m'lifupi lonse theka-maximum, magawo a 63) ndi [¹¹C] raclopride, radiotracer imene imamanga DAXXUMUM / D2 receptors, ndi njira zomwe zanenedwa kale (Volkow, et al. 1993a). Mwachidule, zowonongeka zinayambika mwamsanga pambuyo pa jekeseni wa 4-8 mCi (ntchito yapadera 0.5-1.5 Ci / μM). Zithunzi makumi awiri zowonjezera zowonjezera zinapezeka kuchokera nthawi ya jekeseni mpaka maminiti 54. Chitsanzo chogwiritsira ntchito chogwiritsira ntchito chinkagwiritsidwa ntchito kuti chiwerengero cha carbon-11 ndi chosasinthika [¹¹C] raclopride mu plasma. Kuchulukitsa kwa magawidwe (DV), komwe kumafanana ndi muyeso wofanana wa kuchuluka kwa minofu ya radiotracer mpaka kuchuluka kwa madzi am'magazi ake, amayerekezeredwa pa voxel iliyonse pogwiritsa ntchito njira yosanthula ya machitidwe osinthika omwe safuna sampuli yamagazi (Logan J 1990). Zithunzizi zidasinthidwa mwapadera kudera la MNI stereotactic pogwiritsa ntchito SPM8 ndikuyesanso pogwiritsa ntchito ma voxels a 2-mm isotropic. Chikhalidwe cha MNI, chomwe chidapangidwa kale pogwiritsa ntchito zithunzi za DV kuchokera pamitu 34 yathanzi yomwe idapezeka ndi [¹¹C] raclopride ndi njira yomweyi ya PET kusanthula (Wang, et al. 2011), idagwiritsidwa ntchito paichi. DV yofanana, yomwe ikugwirizana ndi mphamvu yosagwiritsiridwa ntchito (BP_ND) mu voxel iliyonse, anapezedwa ndi normalizing kuchuluka kwa zithunzi za DV kwa izo mu cerebellum (kumanzere ndi kumanja zigawo-za-chidwi). Atalimu Yodziwika Anatomical Labeling (AAL) atlas (Tzourio-Mazoyer, et al. 2002) anagwiritsidwa ntchito kupeza malo a MNI a malo osowa kwambiri a putamen ndi caudate; malo ozungulira pakati pa caudate ndi putamen adasankhidwa kwa ventral striatum. Choncho, masotikisi (cubic) masks ndi voliyumu 1 ml (125 imaging voxels) ankakhazikitsidwa pa putamen [xyz = (± 26, 8, 2) mm], zovuta [xyz = (± 12, 12, 8) mm] ndi ventral striatum [xyz = (± 20, 10, -12) mm] kuti azindikire kupezeka kwa ma D2 / D3 receptors kwa munthu aliyense m'madera oterewa (Chithunzi cha 2A).

  

Chithunzi cha 2

A: Kubwezera zomwe zingatheke kuwona MRI ya axial yokhudzana ndi ubongo waumunthu ukuwonetsa kupezeka kwa alandira DA D2 / D3 mu striatum. PET ndi raclopride [11C] idagwiritsidwa ntchito powerengera mabuku ofalitsa okhudzana ndi chikhalidwe cha cerebellum, zomwe zikugwirizana ...

Kusanthula kusanthula

Njira yodziwongolera njira zosiyana pakati pa SPM8 ndi zaka, BMI komanso zaka za cocaine ntchito (ANCOVA) amagwiritsidwa ntchito kuyesa kufunika kwa chizindikiro chodziwika bwino cha ubongo kumalo osalowerera, chakudya ndi cocaine. Zolemba za SPM8 zofufuza zapamwamba zimagwiritsidwa ntchito poyesa mgwirizanowu wamagwiridwe okhudza ubongo ndi kupezeka kwa D2 / D3 receptor (BP_ND) mu caudate, putamen ndi ventral striatum, komanso zaka za cocaine ntchito, cue valence ndi BMI pa maphunziro. Chiwerengero cha chiwerengero chinayikidwa monga P_FWE <0.05, yokonzedwa poyerekeza kangapo ndi malingaliro am'munda osasinthika komanso kukonza zolakwika m'banja pagulu lamagulu. Khomo lopanga masango P <0.005 ndi kukula kochepa kwamagulu kwama voxels 200 adagwiritsidwa ntchito pazolinga izi. Njira yosamalirira ya Bonferroni yofananizira kangapo idagwiritsidwanso ntchito kuwongolera kuchuluka kwa kusanthula kwa SPM kodziyimira pawokha. Pc <0.05 yolimba yolumikizana yomwe nthawi yomweyo imakonza zowongolera za Bonferroni ndikuwongolera kwathunthu kwa ubongo kwa FWE idagwiritsidwa ntchito pachifukwa ichi.

Kugwiritsa ntchito ROI-kumafufuza

Kugwiritsa ntchito ubongo ndi masewera osokoneza anafufuzidwa kwambiri ndi chigawo cha-chidwi (ROI) kufufuza kuti azindikire anthu omwe angapangitse kusanthula kwakukulu, komanso kufotokozera mavoti omwe amawoneka mofanana ndi kufanana kwachithunzi (mwachitsanzo, kukonza zinthu, kapena "kutsitsa" (Worsley, et al. 1992)) m'malo mosiyana kwambiri ndi ma voxel. Mtengo wa chotsitsacho unkayesa kugwiritsa ntchito kuwerengeka kwachisawawa mu SPM8 monga chiwindi chapafupi ndi Cartesian FWHM = 12.7 mm, 12.3 mm, 13.1 mm. Choncho, masikiti a 9-mm isotropic omwe ali ndi ma voxels a 27 (0.73 ml) adatanthauzidwa pa malo ogwira ntchito / kusokoneza / masankhulidwe ochotsako kuti atenge chizindikiro cha% BOLD kuchokera ku mapu a mitundu yosiyanasiyana. Masikiti awa adalengedwa ndipo amayimilira pamabuku ogwirizana omwe atchulidwapo Matebulo 1--44.

  

Gulu 1

Chiwerengero cha chiwerengero cha magulu opangira ubongo omwe nthawi zambiri ankalimbikitsa cocaine (C) ndi chakudya (F) cue poyerekeza ndi ndale (N) cues.

  

Gulu 4

Chiwerengero cha chiwerengero cha mgwirizano pakati pa mafirimu a fMRI ku chakudya (F) ndi cocaine (C) cues ndi zaka za cocaine, zomwe zimakonda chiwerengero cha thupi ndi chiwerengero cha thupi (BMI).

Makhalidwe

Valence anali ochepa pamalingaliro osalowerera ndale kuposa chakudya kapena mankhwala a cocaine (P <10^-6, t> 7.4, df = 19, t-mayeso awiri; Chithunzi cha 3A) koma sizinasiyane pankhani yazakudya ndi cocaine. Panali kulumikizana kolakwika pakati pamitu pakati pa valence ya zomwe sizilowerera ndale ndi zomwe zimachitika ndi cocaine / zakudya, kotero kuti momwe maphunzirowo amakondera mankhwala a cocaine / chakudya pomwe samakonda zomwe sizinachitike (R <- 0.8, P < 0.0001, df = 18, Pearson malumikizidwe; Chifaniziro cha 3B).

  

Chithunzi cha 3

Mayankho a zikhalidwe pa nthawi yokopa mavidiyo. A: Nkhanizo zinalangizidwa kuti azikankhira pakani phokoso loyankhidwa pamene ankakonda zochitikazo. Chiwerengero cha makina a batani anagwiritsidwa ntchito kuti adziwe momwe nkhanizo zimakhudzira cocaine, chakudya ndi ...

Odwala Striatal DA D2 / D3

Kupezeka kwapakati pa DA D2 / D3 receptors mu ma striatal ROI anali okwera kwambiri kwa putamen kuposa caudate, komanso kwa caudate kuposa kwa ventral striatum (P <10^-9, ma hemispheres akumanzere ndi olondola amawerengeka). Kupezeka kwa madokotala a D2 / D3 mu striatum sanasonyeze mgwirizano waukulu ndi zaka, BMI, chiwerengero kapena valence ya cues.

Kugwiritsa ntchito ubongo

Poyerekeza ndi maziko oyambirira, osalowerera ndale Pulogalamu yapamwamba yomwe imagwiritsidwa ntchito pakati pa magetsi, pakati pa magetsi, mafinya ndi apamwamba kwambiri (BAs 19 ndi 6), kuperewera (poseri lobe), kuchepa kwapayetal cortex (BA 40), otsika kwambiri opaleshoni opculum (BA 44) ndi hippocampus Dera la DMN (cuneus, precuneus ndi greyrus) (P_FWE <0.0005; Chithunzi cha 4).

  

Chithunzi cha 4

Zomwe zimatanthawuza kuti ubongo umasinthidwa (red-yellow) mayankho omveka (magulu a blue-cyan) ku mavidiyo otchuka okhudzana ndi nthawi zoyambira, zomwe zimagwiritsidwa ntchito pazithunzi zowonongeka komanso zozizwitsa za cerebrum.

Poyerekeza ndi maziko oyambirira, mankhwala a cocaine (BA 18), chithunzithunzi (BA 40) ndi griri yapakatikati (BA 19), ndi hippocampus, ndi kuchitapo kanthu pakati pa madera a DMN pambuyo pake (cuneus, zozizwitsa, chingulum pambuyo pake ndi gyrus ang'on) (P_FWE <0.0005; Chithunzi cha 4).

Poyerekeza ndi maziko oyambirira, cue chakudya BA 18), gyrus (BA 19), nthawi yochepa yapamwamba (BA 38), ochepa parietal cortex (BA 40), otsika kwambiri opaleshoni opculum (BA 45), OFC (BA 11) ndi hippocampus, ndi maiko awiri omwe amalephera kugwira ntchito mu rostral / ventral ACC (rvACC, BAs 10, 11 ndi 32), cuneus (BAs 18 ndi19), precuneus (BA 7) ndi gyrus angular (BA 39) (P_FWE <0.0005; Chithunzi cha 4).

Kukhazikika kwa retestdi kudalirika

Kuwunika kwa ICC kwamayesero obwereza a fMRI akuwonetsa kudalirika kokwanira pamayankho a BOLD-fMRI pamalingaliro. Makamaka, ma FMRI mu rvACC, occipital cortex, ventral striatum, cerebellum, operculum yakutsogolo, postcentral, precentral komanso otsika kutsogolo gyri, cuneus, precuneus ndi angular gyrus anali ndi ICC (3,1)> 0.5 (Chithunzi cha 5).

  

Chithunzi cha 5

Mapu a ICC (correlation correlation) (ICC), operekedwa pazithunzi zam'mbuyo ndi zozizwitsa za ubongo ndi kuwonetsera kosavuta, powonetsa kudalirika kwa zizindikiro za fMRI. Ma voxel a ICC (3,1) amawerengedwa kuchokera ku mayankho a BOLD-fMRI ku chakudya ndi cocaine ...

Njira zowonjezera zowonjezera chakudya ndi cocaine

Cocaine ndi zakudya zapamwamba zimapangitsa kuti anthu asamalowe m'malo mosiyana ndi omwe saloŵerera m'ndendemo, kutsika kwapakati ndi kutentha kwapakati, OFC ndi insula, komanso kutsekemera m'malo mochita zinthu mosiyana kwambiri ndi ventral striatum, rvACC komanso calcarine cortex (P_FWE <0.0005; ANCOVA; Chithunzi cha 6 ndi Gulu 1).

  

Chithunzi cha 6

Zomwe zizindikiro za ubongo zowathandiza kuti ubongo uyanjanitse ndi cocaine ndi zakudya zomwe zimagwirizana ndi zomwe sizilowerera ndale zomwe zimachitika pa ubongo wa munthu. Mchitidwe wa SPM8: ANCOVA. Mabala ojambulidwa ndi ma t-scores.

Zomwe zimayambitsa zowonjezera chakudya ndi cocaine

Mankhwala a Cocaine amapangitsa kuti anthu azichita bwino kwambiri kusiyana ndi maulendo osaloŵerera m'zinthu zapakati pazomwe zimakhala zochepa kwambiri, zogwiritsira ntchito parahippocampal ndi griri ya postcentral ndi cerebellum, komanso kuchepetsa kutsekemera kuposa maulendo osaloŵerera m'zinthu zooneka bwino, zolembera, OFC, rvACC, posture insula, lobule m'mapiri ndi greyrus, putamen ndi ventral striatum (malo a NAc) (P_FWE <0.05, ANCOVA; Mapepala Owonjezera S1, Mafanizo 6 ndi And7) .7). Mofananamo, chakudya chimapangitsa kuti anthu asamalowetseke m'malo omwe amalowerera m'mizinda yam'mbuyo, nthawi yamtengo wapatali komanso yapamwamba kwambiri. ndi midbrain [malo olowera kumtunda (VTA) ndi substantia nigra (SN); P_FWE <0.01; Gulu la S1 ndi Chithunzi cha 7].

  

Chithunzi cha 7

Zomwe zikutanthauza kusiyana kwa mayankho okhudzana ndi zomwe zimachitika pa maganizo axial a ubongo wa munthu. Mchitidwe wa SPM8: ANCOVA. Mabala ojambulidwa ndi ma t-scores.

Poyerekeza ndi chakudya, mankhwala a cocaine amapangidwa m'munsi mwa insula ndi postyral gyrus, kuchepa kwa hypothalamus, precuneus ndi posting cingulum ndi kutsegulira kwambiri m'kati mwa gyrus pakati ndi parietal cortex (Gulu 2; P_FWE <0.005; Chithunzi cha 7). Mosiyana poyerekeza ndi mankhwala a cocaine, zizindikiro za chakudya zinapangitsa kuti anthu asamangidwe kwambiri mu hypothalamus / midbrain ndi pambuyo pa cingulum ndipo iwo anasiya ma chingulum omwe amachititsa kuti mankhwalawa asinthe.

  

Gulu 2

Zomwe zimagwiritsidwa ntchito pamagulu opangira ubongo omwe amachitidwa mosiyana ndi cocaine, chakudya ndi ndale.

Kupezeka kwa Striatal D2 / D3 kupezeka ndi ubongo

Tinawonanso mgwirizano pakati pa ubongo ndi D2 / D3 amalandira pokhapokha chifukwa cha zovuta zowonongeka ndi putamen ndi ventral striatum chifukwa zigawo zosiyana za striatum zasonyeza njira zosiyana za cortical, ndipo zimakhala ndi zotsatira zosiyana pamagulu a ubongo okhudzana ndi khalidwe labwino (Grahn, et al. 2008), kulandira mphamvu ndikupindula mphoto (Volkow, et al. 2011b). Panali mgwirizano wofunika kwambiri pakati pa kupezeka kwa DAXX / D2 receptors mu striatum ndi machitidwe omwe amagwirizanitsa ntchito zomwe zimaperekedwa ndi chakudya ndi cocaine (P_FWE <0.05; Gulu 3; Chizindikiro cha 2B ndi 2C). Makamaka, kuwonjezeka kwa BP_ND Pogwiritsa ntchito mphamvu ya hippocampus ndi parahippocampus, rvACC ndi OFC, komanso kufooketsa mphamvu mu cuneus, mkulu wa gyrus ndi caudal ACCOR (cdACC). Kuchuluka kwa BP_ND mu putamen ankagwirizanitsidwa ndi mphamvu yowonjezereka mu OFC, midbrain, cerebellum ndi apamwamba kwambiri ndi parahippocampal gyri ndipo ali ndi mphamvu yolimbikitsidwa mu cdACC ndi pakati pa gyrus yoyamba, cuneus ndi occipital ndi lingual gyri. Misonkhano yeniyeni ndi BP_ND mu caudate ndi putamen adapulumuka kuwongolera kowonjezera kwa Bonferroni kwa kuchuluka kwa kusintha kwa BP (Pc <0.05, mulingo wamagulu womwe udakonzedwa muubongo wathunthu ndi kuwongolera kwa FWE komanso kusintha kwa BP katatu ndi njira ya Bonferroni). Kuchuluka kwa BP_ND mu ventral striatum ankagwirizanitsidwa ndi mphamvu zowonjezereka komanso zapamwamba zowonongeka, phokoso lapacentral, gyrus yapamtunda ndi gyrusitanti ndi zofooka zomwe zimagwiritsidwa ntchito. Komabe, mayanjano ogwirizana ndi BP_ND mu ventral striatum sanapulumutse mayesero owonjezera a Bonferroni kwa chiwerengero cha kusintha kwa BP. Zolumikizizi sizinali zosiyana kwambiri ndi cocaine ndi cue chakudya (Chithunzi cha 2C). Zolumikizidwe zofanana zogwiritsira ntchito zida zowonjezera zimakhala zofunikira kwambiri mu occipital cortex, cdACC ndi rvACC (Chifaniziro cha 2B). Mchitidwe wogwirizana kwa ventral striatum sunasonyeze kuti ndizofunika kwambiri ndi zomwe zimapangidwira.

  

Gulu 3

Chiwerengero cha chiwerengero cha mgwirizano pakati pa mafirimu a fMRI ku chakudya (F) ndi cocaine (C) cues ndi kupezeka kwa DA D2 receptors (D2R) mu caudate, putamen ndi ventral striatum.

Macheza ndi maonekedwe, makhalidwe ndi ma BMI

Kugwiritsa ntchito kayendedwe ka mitsempha kumagwirizanitsa maubwenzi omwe amapezeka pakati pa kugwiritsiridwa ntchito ndi chakudya ndi cocaine, chiwerengero cha zaka za cocaine ndi zizindikiro za zakudya ndi cocaine (P_FWE <0.05; Gulu 4; Chithunzi cha 8). Kwenikweni, kutayika kwa cocaine yaitali kunagwirizanitsidwa ndi kuchepetsedwa kochepa m'dera la masango omwe anali ndi calcarine cortex yolondola ndi cerebellum yoyenera ndi yamanzere ku zakudya zonse ndi mankhwala a cocaine (Gulu 4, Chithunzi 8). Kuwonjezeka kwa valence kwa chakudya ndi cocaine cues kunagwirizanitsidwa ndi kuwonjezeredwa kuwonjezereka mu otsika ndi apamwamba parietal ndi pakati ndi lowerior cortices nyengo, cerebellum ndi gryrus poststral, komanso poyambitsa cuneus kwa cocaine ndi chakudya cues. Kuwonjezera apo, BMI yowonjezereka ikugwirizanitsidwa ndi kuwonjezereka kwa chakudya ku OFC (BA 11) ndi gyrus (Post_FWE <0.05; Gulu 4; Chithunzi cha 8). Mabungwe olumikizana awa omwe akhala akugwiritsa ntchito mankhwala osokoneza bongo a cocaine, cue valence ndi BMI adapulumuka kuwongolera kowonjezera kwa Bonferroni kuchuluka kwa kubwerera m'mbuyo (Pc <0.05).

  

Chithunzi cha 8

Mchitidwe wogwirizana pakati pa kachitidwe kake ka cocaine ndi zakudya za BMI, valence yamtengo wapatali komanso zaka za cocaine ntchito (Valence ∩ Zaka za cocaine ntchito), zomwe zimagwiritsidwa ntchito pazomwe zimagwiritsidwa ntchito pang'onopang'ono komanso m'maganizo mwawo. ...

D2 / D3 receptors ndi kuchitidwa ubongo

Kukhalapo kwa DA D2 / D3 receptors mu striatum kunagwirizanitsidwa ndi ubongo poyambitsa cocaine ndi chakudya chakudya. Chochititsa chidwi n'chakuti, ngakhale kuti mgwirizanowu unali wofanana ndi cocaine ndi chakudya, mayanjano ophatikizapo pakati pa D2 / D3 kupezeka kwapadera ndi mayankho a BOLD anali nawo kwambiri kwa caudate and putamen (dorsal striatum) koma statum striatum inasonyeza chitsanzo chosiyana. Zotsatirazi zimagwirizana ndi gawo la DA ndi ma D2 / D3 receptors pochita zowonjezera ku chakudya ndi mankhwala osokoneza bongo (Salamone ndi Correa 2012) komanso ndi udindo wapadera umene dera lopweteketsa ndi lachitukuko likuchita posintha mayankho (Di Ciano, et al. 2008).

Chitsanzo cha mgwirizano pakati pa mapulogalamu obereka D2 / D3 ndi opangira BOLD amaphatikizapo malo a cortical (parietal cortex) ndi cerebellum, zomwe zili m'madera a ubongo omwe ali otsika kwambiri a D2 / D3 receptors (Mukherjee, et al. 2002). Mchitidwe wochuluka wa mgwirizanowu ukhoza kuwonetsera gawo lomwe D2 / D3 amalandira omwe ali ndi neurons mu striatum ali mu cortical ntchito kudzera thalamo-cortical malingaliro (Haber ndi Calzavara 2009). Choncho, mphamvu ya mgwirizano pakati pa ma D2 / D3 receptors ndi kuikidwa kwa BOLD kudera linalake zingasonyeze njira yowonongeka ya obwezera D2 ndi D3 obvomerezedwa akufotokozera zowonongeka pa malo ogwirizana ndi othandizira omwe akugwirizana nawo.

Udindo wa D2 / D3 receptors pakugwirizanitsa ndi chakudya ndi mankhwala okhudzana ndi mankhwala akugwirizana ndi zomwe anapeza kale. Makamaka, pogwiritsa ntchito PET ndi [¹¹C] raclopride ife ndi anthu ena tawonetsa kuti kuyandikira mankhwala osokoneza bongo kumapangitsa kuti dopamine ikhale yowonjezereka potsatira mankhwala a cocaine (Volkow, et al. 2006; Wong, et al. 2006), amphetamine (Boileau, et al. 2007) ndi heroin (Zijlstra, et al. 2008) cues. Maphunziro azachipatala ndi haloperidol ndi amisulpiride awonetsanso kuti D2 / D3 receptor blockade amachepetsa chidwi cha heroin cues mu heroin ovuta (Franken, et al. 2004), ndipo amaonetsetsa kuti akusuta fodya mu ACC ndi PFC mwa anthu osuta fodya (Luijten, et al. 2012) komanso kumwa mowa mu ACC ndi OFC mowa (Hermann, ndi al. 2006). Motero, zomwe tapeza pamodzi ndi za ena (Saunders ndi Robinson 2013) amasonyeza kuti DA, mwa mbali kudzera mwa obvomerezeka a D2 koma mwinamwake komanso ovomerezeka a D3, ali ndi udindo wapadera pokonza mankhwala ndi mankhwala. Kusiyana ndi maphunziro athu apitayi (Wang, et al. 2001), BP yopweteka_ND sanalumikizidwe ndi BMI mu kafukufuku wapano, yemwe angawonetse kusiyana pakati pa zitsanzo. Makamaka, pomwe kafukufuku wapano akuphatikizapo kagawo kakang'ono ka anthu onenepa kwambiri (maphunziro a 3/20 omwe ali ndi BMI> 30 kg / m²; Mtundu wa BMI: 20-35 makilogalamu / m²) ndipo onsewa anali owononga mankhwala a cocaine, zomwe tinaphunzira kale zinaphatikizapo 10 kwambiri osati mankhwala osokoneza bongo omwe ali ndi BMI yaikulu kuposa 40 kg / m² (zosiyana: 42-60 kg / m²) ndi 10 wathanzi wosagwiritsira ntchito mankhwala osokoneza bongo (zosiyana: 21-28 kg / m²).

Makompyuta ambiri

Kuzindikiritsa maulendo a ubongo omwe akugwedezeka omwe amachitidwa ndi zakudya ndi mankhwala osokoneza bongo angathandize kupeza njira zothandizira mankhwala omwe angapindule onse oledzeretsa ndi olemera kwambiri. Mphoto zachilengedwe zimamasulidwa dopamine mu ventral striatum, yomwe imakhulupirira kuti izi zimapindulitsa kwambiri. Komabe pobwereza mobwerezabwereza ku mphotho yomwe dopamine ikuwonjezeka imachotsedwa ku mphotho yopita ku cues yomwe imalosera iwo (Schultz, et al. 1997), motero kumayambitsa kuyendetsa galimoto yofunikirako yofunika kuti zitsimikizidwe kuti ndizofunika kuti mupindule (Pasquereau ndi Turner 2013). Kuwonetsedwa mobwerezabwereza ndi mankhwala osokoneza bongo kumabweretsa chikhalidwe. Mwanjira iyi, mayankho ogwirizana ndi chakudya ndi mankhwala amachititsa kuti chilimbikitso chikhale cholimbikitsana chomwe chikulingalira mphotho (Berridge ndi Robinson 2003).

Chochititsa chidwi timasonyeza kuti madera a dopaminergic omwe amachititsa kuti asapangidwe ndi mphoto, kuphatikizapo ventral striatum (kwa zakudya ndi mankhwala osokoneza bongo) komanso hypothalamus ndi midbrain (kuti azidya chakudya) poyerekeza ndi ndale.Gulu 2 ndi Chithunzi cha 4), zomwe ziri zogwirizana ndi zoletsedwa za DA muzinthu zosakhala za anthu (West ndi Grace 2002) ndi anthu (Volkow, et al. 2010b) komanso kuwonjezeka kwa DA mu ndondomeko zotsatirazi za mankhwala osokoneza bongo ku cocaine abusers (Volkow, et al. 2006) ndi zakudya zomwe zikuwongolera (Volkow, et al. 2002). Mankhwala osokoneza bongo amachulukitsa DA mu ventral striatum (NAc) (Koob 1992), ndipo zotsatira zake zopindulitsa zimagwirizana ndi izi kuwonjezeka kwa DA kumasulidwa (Drevets, et al. 2001; Volkow, et al. 1999b; 2009 yanzeru). Zakudya zikhoza kuwonjezera DA mu ventral striatum (de Araujo, et al. 2008; Norgren, et al. 2006) ndipo ali opindulitsa kwambiri (Lenoir, et al. 2007). Komabe, cerebellum ndi insula, zikuwonetseratu kuti zimakhala zolimba kwambiri ku cocaine ndi zakudya zomwe sizinalowerere kuzinthu zina.Gulu 2 ndi Chithunzi cha 4). Zotsatirazi zikugwirizana ndi kuyambitsidwa kwa cerebellum ndi insulu nthawi ya chilakolako cha chilakolako cha njala (Haase, et al. 2009) komanso ndi cerebellar (Grant, ndi al. 1996) ndi kuchitapo kanthu mwachisawawa a cocaine omwe amadziwika ndi mankhwala a cocaine (Wang, et al. 1999). Komanso, akakhala ndi mankhwala a cocaine, owononga mankhwala osokoneza bongo amachititsa kuti chilakolako chawo chisawonongeke.Volkow, et al. 2010a), ndipo kuwonongeka kwa insulu kungasokoneze kuledzera kwa kusuta fodya (Naqvi, et al. 2007). Zoonadi, insuluyo ikudziwika kuti ndi yovuta kwambiri yokhala ndi chizoloŵezi cha mankhwala osokoneza bongo.Naqvi ndi Bechara 2010). Zotsatira zathu zimasiyana ndi zomwe zimapezeka mu makoswe ophunzitsidwa kuti azigwirizana ndi fungo lokhazika mtima pansi (cocaine / mouth sucrose), zomwe zimasonyeza ntchito zosiyanasiyana za ubongo ku NAc kwa cocaine kusiyana ndi sucrose (Liu, et al. 2013). Kusiyana kumeneku kungayambitse kusiyana pakati pa mitundu (anthu osokoneza bongo ndi makoswe omwe amagwiritsidwa ntchito ku cocaine), kugwiritsa ntchito fungo losiyana ndi maonekedwe ndi zovuta kuchokera ku zotsatira zopweteka kwambiri zomwe zimagwiritsidwa ntchito pophunzira.

Kukonzekera kwa cerebellar kunali kolimba kwambiri kwa cocaine ndi chakudya m'malo mwa ndale, zomwe zikugwirizana ndi maphunziro apitayi omwe amasonyeza ntchito ya chidziwitso cha maphunziro (Thoma, ndi al. 2008), kukumbukira kwa cocaineCarbo-Gas, et al. 2013) ndi mu lamulo la ntchito za visceral ndi kudyetsa (Haines, et al. 1984). Kutsegula kwa cerebellar kwa zakudya ndi mankhwala a cocaine kunachepetsedwa ndi zaka zambiri za cocaine ntchito (Gulu 4). Izi zikugwirizana ndi mayankho ofooka a ubongo wa poyerekeza ndi zowongolera (Bolla, et al. 2004; Goldstein, et al. 2009; Hester ndi Garavan 2004; Li, et al. 2008; Moeller, et al. 2010; Volkow, et al. 2010b), ndi zomwe tafufuza kale zomwe zikuwonetsa kuti kuwonjezeka kwa mankhwala osokoneza bongo omwe amachitidwa pambuyo pa vuto ndi mankhwala osokoneza bongo (methylphenidate) akugwirizana ndi kupezeka kwa D2 / D3 receptor (Volkow, et al. 1997a), omwe amachepetsa kuchepa kwa cocaine opondereza (Martinez, et al. 2004; Volkow, et al. 1993b; Volkow, et al. 1990).

Poyerekeza ndi zandale, cocaine / cue chakudya chinapangitsanso kuwonjezereka kowonongeka kwa OFC, malo ochepetsedwa ndi oyang'aniridwa ndi oyang'anizana ndi am'mbuyo komanso kuchitapo kanthu kowonjezereka mu rvACC, malo owonetsetsa ndi maonekedwe (Gulu 1). Kafukufuku wammbuyo awonetsa kuti poyerekeza ndi zigawo zandale, chakudya cha chakudya chimapangitsa kuti zikhale zofunika kutsegulira mayankho a insula, coratex yowona, ya parietal ndi yowonekera (Cornier, et al. 2013), ndi ana omwe ali pangozi yowonjezera kunenepa amasonyeza kuti ali ndi mphamvu zowonjezera ku zakudya zomwe zimapezeka mu khungu (somatosensory cortex)Stice, et al. 2011). Kuwonjezera pamenepo, insula yam'kati, ndi yotsika yapansi ndi OFC imagwirizanitsidwa ndi striatum ndi zizindikiro za cortico-striatal zomwe DA (Wogwira 2003) komanso kusewera maudindo ofunika kuwongolera, kupanga ziganizo, malamulo okhudza maganizo, zolimbikitsa komanso zolimbikitsa (Goldstein ndi Volkow 2002; Phan, et al. 2002; Volkow, et al. 1996). Kuwonjezera pamenepo, OFC imvini yolemba mawu imasonyeza kuwonana kolakwika ndi BMI mu mankhwala osokoneza bongo ndi cocaine komanso zaka za cocaine zomwe zimagwiritsidwa ntchito ku cocaine (Smith, et al. 2013), zomwe zingathenso kuwonetsa zotsatira za cocaine m'madera omwe ali ndi madalitso a chilengedwe monga OFC.

Mitundu yosiyanasiyana

Makhalidwe a Cocaine anapanga mphamvu zowonjezereka za fMRI mu cerebellum, occipital ndi prefrontal cortices ndi kuchitapo kanthu mu rvACC ndi ventral striatum kusiyana ndi ndale. Zotsatirazi zikugwirizana ndi kuwonjezereka kwa kaganizidwe kokhudzana ndi chilakolako cha PFC.Grant, ndi al. 1996) komanso ndi kuchepa kwa kagayidwe ka ventral striatum (Volkow, et al. 2010b) ndipo ubongo wamagazi umachepa mu basal ganglia (Childress, ndi al. 1999) mu cocaine oledzera pa cocaine-kukopa mapulogalamu paradigms.

Zolemba za chakudya zimapangitsa kuti ntchito ya FMRI ikhale yolimba kwambiri kusiyana ndi kusaloŵerera m'zinthu zonyamulira m'madzi, mabala odyera komanso owonetsa zithunzi, komanso kuchitapo kanthu mu rvACC, hypothalamus, midbrain ndi primary visual cortex, precuneus ndi gyrus angular. Ngakhale kuti mankhwala a cocaine sanayambe kuchititsa BA 43 (chogwirira ntchito; Gulu 2) kwambiri pamitu yonse, mayankho a fMRI ku chakudya cha BA 43 anali ofunika kwambiri (Gulu 2) ndipo zimagwirizanitsidwa bwino ndi kupezeka kwa DA D2 / D3 receptors mu ventral striatum (Chithunzi cha 2C), zomwe zingagwiritsidwe ntchito mofanana ndi dopaminergic dera la ubongo. Kutsimikizira izi ndizogwirizana kwambiri pakati pa mayankho okhudzana ndi fMRI mu caltex yogula ndi valence cue chakudyaGulu 4), popeza DA ikuwonetsa phindu la chakudya chambiri (Volkow, et al. 2012b).

Kusokonekera m'madera a DMN apamwamba kunali kwakukulu kwa chakudya kusiyana ndi mawu a cocaine. Kugwira ntchito kwa DMN kwakhala kugwirizana ndi chiyambi cha malingaliro odzidzimutsa podutsa malingaliro (Mason, et al. 2007) ndipo kuchitapo kanthu kwake kumachitika panthawi yazidziwitso zofunikira zokhudzidwa (Fox, et al. 2005). Chofunika kwambiri, mlingo wa kuchitidwa kwa DMN panthawi yomwe mukufunira ntchito zamaganizo zimasiyana pakati pa ntchito (Tomasi, ndi al. 2006), mwinamwake kusonyeza kukula kwa maganizo odzidzimutsa. Motero, kuchepa kwa DMN kuchepa kwa mankhwala a cocaine kusiyana ndi kudya chakudya kungathe kuwonetsa kukula kwakukulu kwa malingaliro amodzi pa nthawi ya cocaine kusiyana ndi nthawi ya chakudya. Izi zikhoza kusonyeza kusiyana pakati pa dopamine kumasulidwa pakati pa chakudya cha cue ndi cocaine chifukwa DA akuwonjezeka ndi DMN deactivation (Thanos, et al. 2013; Tomasi, ndi al. 2009). Kugwirizana kolakwika kunaphatikizapo pakati pa ma D2 / D3 receptors mu zovuta zowonongeka ndi magwiridwe a fMRI mu cuneus, kotero kuti apamwamba kwambiri omwe amalandira mpata waukulu kwambiri wa kuphulika kwa cuneus, akugwirizana ndi ntchito yoletsera ya DA mu DMN (Thanos, et al. 2013; Tomasi, ndi al. 2009).

BOLD-fMRI yomwe ikuyimira mu phunziro ili siinali yosiyana kwambiri ndi masiku onse ophunzirira, kutanthauza kuchepetsa kusiyana pakati pa- maphunziro. Kuwonjezera apo, kuyembekezera kuyesayesa kumayesedwa koyambitsanso njira zowonongeka zomwe zinapangidwa ndi zolembazo zinali zofanana ndi zomwe zimagwira ntchito moyenera fMRI ntchito zomwe zimagwiritsidwa ntchito (Bennett ndi Miller 2013). Kwenikweni, kudalirika kwa zizindikiro za fMRI zinachokera ku 0.4 (kudalirika modalirika) ku 0.8 (kudalirika kwambiri), komanso kuwonetsa kuti kusintha kwa ubongo kumapangitsa kuti zakudya ndi zakumwa za cocaine zikhale zosiyana-siyana kusiyana ndi magawo ena.

Potanthauzira zotsatira zathu tinaganiza kuti mwina anthu omwe amagwiritsa ntchito mankhwala osokoneza bongo angakhale okhudzidwa kwambiri ndi malipiro (zachilengedwe ndi mphotho), zomwe zingachititse kuti azisokonezeka (Saunders ndi Robinson 2013). Kuwonjezera apo, mu zotsatira zathu zizindikiro za cocaine zimagwirizanitsidwa ndi valence ya chakudya cues, mofanana ndi chidziwitso chodziwika kuti chidziwitso cha reactivity (Saunders ndi Robinson 2013). Choncho sitingathe kupatulapo kuti kusiyana komwe timayang'ana mwa owononga mankhwala a cocaine kungakhale koyambirira kugwiritsa ntchito mankhwala osokoneza bongo ndipo zikhoza kuwapangitsa kukhala ovuta kuwononga mankhwala osokoneza bongo. Pachifukwa ichi, zikanakhala zosangalatsa kuyika gulu lotsogolera kuti liwonetsetse momwe zowonjezera zowonjezera zowonjezera chakudya ndi mankhwala a cocaine omwe ali osokoneza anthu osagwiritsidwa ntchito mosamala komanso kudziwa ngati chidziwitso chawo cha chakudya chimasiyana pakati pa magulu. Ife tikulemba kuti kusiyana komweko mu mayendedwe a khalidwe ndi ubongo wa ubongo woperekedwa ndi zakudya zomwe zimadya ndi cocaine zikhoza kukhala zazikulu kwambiri pa zowononga kusiyana ndi owononga a cocaine. Komanso, tinagwiritsa ntchito [¹¹C] raclopride, yomwe imapanga kupezeka kwa D2 / D3 kupezeka, ndipo zikanakhala zabwino kugwiritsa ntchito radiotracers zomwe zingatithandize kusiyanitsa pakati pa zopereka za D2 receptors ndi za D3 receptors. Komanso,¹¹C] raclopride amavomerezana ndi mpikisano ku DA yosagonjetsa (Volkow, et al. 1994), kotero sitingadziwe ngati mgwirizano ndi ubongo wamatsenga umasiyana ndi ma D2 / D3 okhudzidwa ndi masewera kapena mpikisano wa dopamine ndi radiotracer kuti amangirire kulandirira D2 / D3. Komabe popeza ife ndi anthu ena takhala tikuwonetsa kuti owononga mankhwala a cocaine amasonyeza kuchepetsedwa kwa DA (Volkow, et al. 2011b) zikutheka kuti kusiyana kwa ubongo kumabwereza maulendo osiyanasiyana a D2 / D3 receptors mu striatum. Kuonjezera apo, gawo la FMRI lisanayambe kuwunika kwa PET ndi maminiti a 60 ndipo zikhoza kuwonjezeka kumasulidwa kwa DA kosatha, mochepetsera kuchepetsa BP_ND miyeso. Komabe, kuwonjezeka kwa DA kumasulidwa kumene kumayambira ndi cues ndi yofulumira komanso yochepa (2-3 maminiti) (Erhardt, et al. 2002) ndipo kotero ziyembekezeredwa kuti DA adzamasulidwa ku nthawi yoyamba ndi nthawi ya PET kufufuza njira. Komabe, popeza sitingavomereze kuti kulibe, DA kumasulidwa pa fMRI ndizovuta kwambiri pa phunziro lathu.

Zotsatira zathu zikuwonetsa kuti chakudya ndi cocaine zimagwiritsidwa ntchito mofanana ndi DA D2 / D3 receptors zomwe zimaphatikizapo cerebellum, insula, otsika patsogolo, OFC, ACC, somatosensory ndi occipital cortices, ventral striatum ndi DMN. Zakudya za chakudya zinapangidwa mwamphamvu kutsegulira mayankho oposa cocaine m'malo otchedwa posterior insula ndi gyrus postcentral, kutalika kwambiri m'madera a DMN ndi hypothalamic ndi kutsegulira m'makonzedwe am'nyengo ndi parietal. Mayankho okhudza ubongo ndi chakudya cha cocaine m'madera oyandikana ndi maulendo amtundu wambiri omwe amaphatikizapo mphotho ndiwonjezeredwa ndi valence ya cues ndipo amagwirizanitsidwa ndi D2 / D3 receptors; zogwirizana ndi gawo lofala la neuronal gawo la mtengo wa mankhwala achilengedwe ndi mankhwala omwe amatsitsimutsa kudzera mwa D2 / D3 receptor chizindikiro chosokoneza choledzeretsa.

Ntchitoyi inakwaniritsidwa ndi kuthandizidwa ndi National Institutes of Alcohol Abuse and Alcohol (2RO1AA09481).

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