Aberrant zosindikiza zizindikiro zopanga zisankho: Achinyamata otchova njuga amawonetsa kuti hypticensisticistic cortico-bereatal gambles

• Sofie V. Gelskov^{a, b,,,,} ,
• Kristoffer H. Madsen^{a, c},
• Thomas Z. Ramsøy^{a, d, 1},
• Hartwig R. Siebner^{a, e, 1}

yani: 10.1016 / j.neuroimage.2016.01.002

  Tsegulani

Mfundo

• Ochita masewera othamangitsana akuwonetsa kuyankha kwamtundu wa U kukhala wamanjenje komanso kubwezeretsa.
• Hypersensitivity iyi imapezeka mu cortico-striatal network, mwachitsanzo, caudate ndi DLPFC.
• Kumvetsetsa kweneku kungapange chisonyezo cha neural chizere cha kutchova juga.
• Zomwe tikuyembekeza mtsogolo pa netiweki ndi njira zokhudzana ndi zotsatira zake zikukonzekera.

Kudalirika

Kutchova juga kwachisawawa ndimavuto osokoneza bongo omwe amakhala ndi chidwi chosagwirizana ndi kutchova juga ngakhale atakumana ndi zovuta. Chimodzi mwazidziwitso za kutchova njuga kwachikhalidwe ndizosasokoneza komanso kusankha koopsa, komwe kwalumikizidwa ndi kukokoloka kwa zigawo zaubongo zokhudzana ndi mphotho monga gawo la porral striatum. Komabe, maphunziro am'mbuyomu adapereka zotsatira zotsutsana pamtunduwu, zikuwonetsa kukhudzika kapena kuchepa kwa phindu la ndalama. Kulongosola komwe kungachitike ndikuti ubongo wa njuga ukhoza kukhala kuti ukunena molakwika zaubwino ndi mtengo wake pakuyeza zomwe zingachitike, osati zopindulitsa ndi zotayika pa gawo limodzi. Kuti tithane ndi nkhaniyi, tidasanthula ngati njuga zam'magazi zimagwirizanitsidwa ndi zochitika zokhudzana ndi ubongo pazisankho zomwe zimalemera phindu la zotheka pakuwonongeka. Omwe anali otchova njuga komanso anthu athanzi labwino amaganiza zamatsenga pomwe amalola kapena kukana kutchova njuga mosiyana ndi makumi asanu ndi makumi asanu mwayi wopambana kapena wotayika. Mosiyana ndi anthu athanzi, otchova njuga amawonetsa mawonekedwe oyankha a U omwe akuwonetsa kubetchera kwa chidwi kwambiri komanso kothandiza kwambiri pa intaneti ya cortico-striatal network kuphatikizapo dorsolateral pre mbeleal cortex ndi caudate nucleus. Tsambali limakhudzidwa ndi kuwunika zochitika zadzidzidzi, kuwunika zomwe zachitika posachedwa ndikuyembekezera zotsatira zake. Kuwonongeka kwa maukonde awa, makamaka kwa kubetchera mopambanitsa chifukwa cha zovuta zazikulu, kumapereka chidziwitso chazachilendo chazomwe zimayambira njuga zam'magazi potengera mayanjano operewera pakati pa machitidwe a njuga ndi momwe zimakhudzira ndalama.

Keywords

• Kupanga zisankho;
• Njuga zachikhalidwe;
• Cortico-striatal hypersensitivity;
• fMRI;
• Kutaya kotayidwa;
• mphoto

Introduction

Kutchova juga kwachisokonezo ndimavuto amisala omwe amakhala ndi malingaliro osatsutsika ofuna kutchova juga ndalama ngakhale zitakhala zovulaza. Ndi kuchuluka kufalikira kwa 1-2% m'magawo ambiri azungu (Welte et al., 2008 ndi Wardle et al., 2010), vutoli limabweretsa vuto lalikulu pagulu ndi laumunthu. Kutchova juga kwachikhalidwe kwayesedwa ngati chizolowezi chogonana ndipo kumagawana zizindikiritso zambiri zamagulu osokoneza bongo monga kusiya, kulekerera, komanso chidwi chachikulu (Petry, 2007 ndi Leeman ndi Potenza, 2012).

Kupanga zisankho mwangozi ndi chidziwitso chofunikira kwambiri cha kutchova juga kwa matenda. Zowonadi, otchova juga amalekerera kwambiri ngozi.Clark, 2010 ndi Ophulika et al., 2013), ndi njuga ya pathological yalumikizidwa ndi kusintha kwa madera a dopaminergic omwe amalumikizidwa ndi mphotho, chiwopsezo, komanso kusunthira, monga ventral striatum ndi ventraledial prefrontal cortex (vmPFC) (van Holst et al., 2010, Limbrick-Oldfield et al., 2013 ndi Potenza, 2014). Komabe, pomwe maphunziro ena apeza hypokuyambitsa kwa mesolimbic mphoto njira poyankha kuyembekezera kapena zotsatira za mphotho ( Reuter et al., 2005, de Ruiter et al., 2009 ndi Balodis et al., 2012), kafukufuku wina wanena hyperkuyambitsa njira yomweyo kulandira mphotho yomwe ikuyembekezeka ( van Holst et al., 2012 ndi Worhunsky et al., 2014), zotayika zomwe zimayembekezeredwa (Romanczuk-Seiferth et al. 2015,, kapena njuga zazingwe ( Crockford et al., 2005 ndi Goudriaan et al., 2010). Chochititsa chidwi, maphunziro a positron emission tomography (PET) sanawonetse kusiyana kulikonse pakati pa otchova njuga ndi kuwongolera athanzi pakukula kwa kutulutsidwa kwa driatri dopamine ( Joutsa et al., 2012 ndi Linnet et al., 2011) koma adawonetsa kuyanjana pakati pakumasulidwa kwa dopamine ndi kuwopsa kwa kutchova juga (Joutsa et al. 2012), ndi kumasulidwa kwa dopamine ndi chisangalalo cha njuga (Linnet et al. 2011). Njira zoyankhirazi zopanda tanthauzo zimawonekera munkhani ziwiri zazikuluzaku njuga zamatenda. Kumbali imodzi, chiphunzitso cholipirira mphoto chimaneneratu za dongosolo la mphotho yopatsa chidwi chifukwa chogwiritsa ntchito dopamine D2 receptor yomwe ikupezeka muzosokoneza bongo ( Blum et al., 1990 ndi Noble et al., 1991) ndi otchova njuga ( Akubwera ndi al., 1996 ndi Akubwera ndi al., 2001). Maso am'munsi a dopaminergic mu ubongo amakankhira otchova njuga kuti apeze mphotho zapamwamba, kuti athe kufikira gawo lomwe "mphotho yamasewera" imayambira mu ubongo. Komabe, chiphunzitsochi chimalosera za kukondera kolimba ku zinthu zosokoneza ( Robinson ndi Berridge, 1993 ndi Robinson ndi Berridge, 2008) kumatsogolera ku hypersensitivity m'ma dopaminergic. M'masewera otchova njuga, chidwi chofuna kutchova juga chimayamba chifukwa cha kutchova juga pamalonda, zomwe zingapose phindu la zolipiritsa zina ( Goldstein ndi Volkow, 2002 ndi Goldstein et al., 2007).

Izi zimatsimikizira kuti magwiridwe akunja a njuga wa patali sakhala osakhudzidwa. Ngakhale kafukufuku wosiyanitsa zilango za ndalama komanso mphotho zingathe kuthana ndi momwe malingaliro amasungidwira mu ubongo, samanena momwe zopindulitsa ndi zotayika zimaphatikizidwira pa njuga. Posachedwa, tidayamba ntchito ya kutchova njuga yomwe imayang'ana kuchuluka konse kwa phindu ndi kutayika kwakatundu palokha, komanso momwe zopezera ndi kutayika zimakhalira motsutsana wina ndi mzake pamasewera "osakanikirana" (phindu / kutaya) (Gelskov et al. 2015). Mukamayesa zopindulitsa ndi zotayika, anthu amakhala ndi chidwi kwambiri ndi zomwe zingachitike ngati atapeza phindu lofanana, lingaliro lomwe limadziwika kuti kutaya njira (Kahneman ndi Tversky 1979). Mwakuchita izi, anthu nthawi zambiri amakana kutchova njuga kwa 50 / 50 pokhapokha atapambana mozungulira kuwirikiza kawiri kuposa momwe angathere. Kafukufuku wam'mbuyomu wogwiritsa ntchito njuga zosakanikirana ndi omwe adachita nawo zathanzi adawona kuti kuwerengera kopindulitsa kwa phindu ndi kutayika kumakhudzana ndi mphotho zokhudzana ndi dopaminergic chandamale, makamaka porral striatum ndi vmPFC (Tom et al. 2007). Komabe, pamene njuga yonse ya phindu / yotayika itaganiziridwa (mwachitsanzo, phindu lomwe lingachitike, kutayika kwakothekera, komanso zotsatirapo zakupambana kapena kutaya), maphunziro ena apeza gawo lofunikira kwa amygdala posiya kutaya (De Martino et al., 2010 ndi Gelskov et al., 2015). Mu kafukufuku wapano, tinagwiritsa ntchito ntchitoyi pagulu la anthu omwe ali ndi vuto la kutchova njuga ngati njira yodziwitsira anthu kuti apange zisankho zabwino.

Posachedwa, kafukufuku wazikhalidwe adawona kuti otchova juga amalephera kwenikweni kuposa machitidwe owongolera (Ophwanya et al. 2012, komanso onaninso Giorgetta et al. 2014). Apa, tifunsa ngati njuga zam'magazi zitha kuwonetsa kuperewera kwa zopindulitsa pakuwonongeka pakupanga chisankho. Mu kafukufuku waposachedwa, tapeza kuti zochitika za amygdala ndi ventral striatum zimawonetsa kuchuluka kwa kutaya chidwi mwa omwe ali ndiumoyo wabwino ataganiza kuvomereza kapena kukana kutchova njuga kwambiri (Gelskov et al. 2015). Apa, tidagwiritsa ntchito njuga imodzi kufufuza momwe zisankho zimapangidwira ndikusinthana kwakuthupi pakati pa kutaya kutaya (kutanthauza kuti kutaya kapena kuchepa kwambiri), komanso ngati kutaya kutaya kumawonekeranso m'malo okhudzana ndi mphotho ya mesolimbic . Kuti tithane ndi mavutowa, tidagwiritsa ntchito fMRI ndi ntchito yotchova njuga momwe otenga nawo mbali anavomera kapena kukana kutchova juga mosakanikirana ndi kuchuluka kwakukulu pakati pa phindu lokwanira ndi kutaya. Kapangidwe kathu kabwino kamatipatsa mwayi kuti tiwone ngati amiseche omwe amatsata njirayi amaganiza moyenera komanso molakwika mosiyana ndi kuwongolera kwaumoyo komanso ngati kuphatikiza ziwonetsero za kupeza-kutaya mu zosankha za njuga zimayenderana ndi zochitika zosaopsa kumadera aubongo omwe akukhudzidwa popanga zisankho zofunikira.

Zofunika ndi njira

ophunzira

Amiseche amuna khumi ndi anayi, osakhala ndi mankhwala a pathological (amatanthauza zaka zaka: 29.43; SD: 6.05; osiyanasiyana: 20-40) ndi 15 maphunziro oyendetsa athanzi (onse amuna; amatanthauza zaka zaka: 29.87; SD: 6.06; osiyanasiyana: 21- 38) adalembedwanso makamaka phunziroli. Oyamba kutchova jambulawa poyambilira adasinthidwa koma osayikidwa nawo pasadakhale chifukwa sanamvetsetse ntchitoyi: Mmodzi amatenga nawo mbali povomera kubetcha, pomwe winayo akuganiza kuti kutchova juga onse kulipira kumapeto kwa gawo. Anthu otchova juga adawalembera kudzera kumalo achitetezo aku Danish kuti achite njuga zamatenda. Palibe wochita nawo omwe anali ndi zovuta zowonjezera zaumoyo kupatula njuga yamatenda yozunguliridwa motengera mayendedwe azachipatala a DSM-IV, Axis I (SCID-I, Kafukufuku wofufuza, mtundu wa odwala komanso osapirira; Choyamba et al. 2002), kuphatikizapo zovuta monga kugwiritsa ntchito mankhwala osokoneza bongo kapena kudalira. Kupezeka kwa kutchova juga kwa pathological kunatsimikiziridwa ndi kuyankhulana kwazomwe zimapangidwa module ya SCID ya juga ya pathological. Onse otchova juga anali ndi chithunzi cha South Oaks Gging Screen (SOGS) pamwambapa 5 (Gulu 1; Lesieur ndi Blume 1987; Mitundu yamaDanish ya SOGS ndi ma module a SCID adamasuliridwa ndi J. Linnet). Ophunzira adayang'aniridwa kuti athe kuyenderana ndi MR, mbiri yokhudzana ndi zovuta zam'mitsempha, ndikusayina ma fomu achidziwitso. Kafukufukuyu adavomerezedwa motsogozedwa ndi protocol ya KF 01-131 / 03, yoperekedwa ndi komiti ya zamalamulo wamba.

Gulu 1.

Demographic ndi neuropsychological mawonekedwe a ophunzira.

Zambiri: SOGS, Screen ya Oaks ya South Oaks; AUDIT, Kugwiritsa Ntchito Mowa Zizindikiro Kuyesa; WAIS, Wechsler Adult Intelligence Scale; BDI, Beck Depression Inventory; BIS-11, Barratt Impulsiveness Scale, 11th ed., GAD-10, Generalized Anx wasiwasi Disorder test; DOSPERT, Domain -pecific Risk-Kuchuluka pamlingo.

a

Mulingo wapamwamba kwambiri wamaphunziro (kugoletsa): 1 = Sukulu ya sekondale / yocheperako, 2 = maphunziro amanja ndi maphunziro, 3 = sekondale yapamwamba, 4 = digiri yaukadaulo, 5 = digiri ya bachelors kapena zina, 6 = masters degree.

b

Wotchova juga m'modzi sanamalize chiwonetsero cha AUDIT, m'modzi sanamalize kusuta ndi maphunziro. Phunziro limodzi silinamalize kufunsa kwa BIS-11.

c

Chiyeso chosaloledwa cha parametric chovomerezeka chomwe chimagwiritsidwa ntchito chifukwa chogawa zosazolowereka.

Zosankha pazithunzi

Ophunzira adayesedwa masiku awiri osiyana kupatula milungu iwiri. Pachigawo choyesa choyambirira, ophunzira adayezetsa ma neuropsychological, mafunso, ndi zoyankhulana (onani Gulu 1). Ophunzirawo adapatsidwanso 200 Danish Kroner (mwachitsanzo, ndalama zaku Danish, DKK, 1 DKK ≈ 0.16 US dollar), omwe adauzidwa kuti abweretse sabata yotsatira kukayesa fMRI ngati gawo lotchovera njuga.

Ntchito yotchova njuga komanso zoyambitsa

Pa gawoli la FMRI, ophunzira adachita nawo njuga, yomwe imawafunikira kuvomereza kapena kukana njuga zosakanikirana zofananira ndikupambana kapena kutaya (Chith. 1A). Poyeserera kulikonse, maphunziro amaperekedwa ndi tchati cha pie chomwe chingapindule kapena kutayika komwe kutayika, kutengera momwe zinthu ziliri (mwachitsanzo, "kutayika koyamba" kapena "kupeza kaye"). Pambuyo pakuwonetsera kosiyanasiyana (2-5 s), kuchuluka kwachiwiri kwamasewera osakanikirana kunaperekedwa ndipo omvera adaganiza zovomereza kapena kukana kutchova njuga pompano podina batani limodzi mwa ma scan. Zonsezi, "gawo lowonetsa kufotokozera" komanso "chigamulo" chotsatira zidasinthidwa mu magawo a 0.5 (ie, 2, 2.5, 3, 3.5, 4, 4.5, ndi 5 s) zabodza mosasamala kanthu kuyambira pachiyeso mpaka pamlandu. Malangizo adawerengedwa mokweza kwa omwe atenga nawo mbali, pomwe amaliza maphunziro awo kwakanthawi mpaka atadziwa bwino ntchitoyi. Ophunzira adauzidwa kuti palibe mayankho omwe angaperekedwe pazotsatira za kubetcha kamodzi mukamayang'ana, koma kuti atatha gawo la fMRI, kompyuta imasankha mabetcha awiri osasinthika: omwe anali Adalandira pagawo la njuga, "ikaseweredwa" ndipo omwe atenga nawo mbali akhoza kutaya ndalama kuchokera ku zomwe apatsidwa kapena kuwina ndalama zowonjezera, pomwe akana kubetcha, palibe juga ya 50 / 50 yomwe idaseweredwa. Ophunzira adauzidwa kuti azitsatira zomwe akumva komanso kuti palibe yankho lolondola kapena lolakwika.

Fanizo la 1. 

Kutchova juga mu sikani, matrix olimbikitsa, ndi machitidwe osankha. A) Paradigm yokhudzana ndi zochitika za fMRI; ophunzira adalandira kaye kutayika kapena phindu lomwe lingachitike (mwachitsanzo, kukula kwa "Chiwonetsero"). Kenako, ndalama ziwirizi zikawonetsedwa, ophunzira adasankha kuvomereza kapena kukana kutchova juga (mwachitsanzo, gawo la "Kusankha"). Nthawi zoyeserera (ITI) zidasiyanitsa mayesero. Chidziwitso: "kr" = "DKK". B) Mapu otentha okhala ndi mitundu yoimira magawanidwe a juga (phindu / kutayika). Stimuli inali ndi ma 64-mapangidwe owonongekera osiyana, omwe amafanana ndi 8 omwe angapeze phindu (68-166 DKK; zokulitsa za 14) ndi 8 zomwe zitha kutayika (34-83 DKK; zowonjezera 7). Kulemba mitundu kumawonetsera magawanidwe kuchokera kutsikitsitsa (0.82) kupita pamwamba kwambiri (4.9). Zopeza zonse / zoperewera zonse zidaperekedwa kawiri mosiyanasiyana, kamodzi mu "phindu loyamba" ndipo kamodzi "koyamba kutaya". C) Mamapu otentha okhala ndi mitundu yoimira mitundu ya otchova njuga (kumanzere) ndi zowongolera (kumanja). Kulemba mitundu kuchokera pakuda mpaka kufiyira mpaka chikasu mpaka choyera kumawonetsa kuchuluka kwa kutchova njuga (kwakuda koyera: 0-100%). D) Kutaya kwakanthawi kotsutsana, lambda (λ), kwa onse omwe akutenga nawo mbali. Onani kugawa koyenera. Kuyesa kosavomerezeka kwa parametric kunawonetsa chizolowezi chochepetsera kuchepa kwa otchova njuga poyerekeza ndi kuwongolera athanzi (P = 0.077).

Zosankha za zithunzi

Stimuli inali ndi njuga zosakanikirana zomwe zimaperekedwa pazandalama zachikaso ndi zofiirira ndi ndalama imodzi (mwachitsanzo, phindu ndi zotayika mu ndalama zaku Danish) zoperekedwa theka lililonse la tchati (Chith. 1A). Zoyeserera za 64 zidaphatikiza kuchuluka kwa phindu la 8 (68-166 DKK; in extension of 14 DKK), ndi 8 angataye ndalama (34-83 DKK; in extension of 7 DKK; onani kuchuluka / kutayika kwa matrix mu Chith. 1B). Juga zosakanikirana 64 zidaperekedwa kamodzi ngati "phindu loyamba" ndipo kamodzi "kutayika koyamba", ndikupereka mayesero okwana 128. Zoyeserera zilizonse zinali za imodzi mwamagawo 8, omwe amadziwika ndi tchati cha pie chomwe chimasinthidwa ndi 45 ° (0 ° -360 °) pagulu lirilonse. Chifukwa chake, ngakhale kuchuluka kulikonse (mwachitsanzo + 82 DKK) kunawonekera nthawi 16, kumangoperekedwa kamodzi pamalo omwewo pazenera pazofunikira (kupindula kapena kutayika koyamba), kuti tipewe kubwereza komwe kungachitike. Kuonetsetsa kuti maphunziro ali tcheru pantchitoyi ndikuwonjezera kuchuluka kwake pansi pa 1, tidawonjezera mayesero 18 ovuta kwambiri. Mayesowa anaphatikiza 3 phindu lochepa (ie, 34, 41, 48 DKK) ndi 3 zotayika kwambiri (ie, 138, 152, 166 DKK). Ophunzira onse adakana mayeso osachepera 89%, kuwonetsa kuti omvera adalabadira ntchitoyi (otchova njuga adakana 98% yamayeso onse ogwira; osiyanasiyana: 95-100%; owongolera adakana mayesedwe a 98.9% oyesa; osiyanasiyana 89-100 %). Panalibe kusiyana pamitundu yoyesedwa yoyeserera pakati pamagulu (P = 0.61, t (27) = 0.52, SD = 2.99). Pomaliza, tidawonjezera mayesero 24 "oyambira": ma chart opanda kanthu opanda ndalama (zindikirani kuti mayesero osagwira kapena zoyeserera zoyambira sizinagwiritsidwe ntchito pakuwunika kwamakhalidwe kapena kuphatikizidwa ngati regressors of interest). Stimuli adawonetsedwa ndikusindikiza mabatani ojambulidwa pogwiritsa ntchito pulogalamu ya E-Prime 2.0 (Psychology Software Tools, Pittsburgh, PA).

Kutengera zosankha za omwe akutenga nawo mbali pazoyeserera za 128, tidawerengera kuchuluka kwa kutayika, lambda (λ), poyika kusintha kwa mayankho pakuyankha kwa ophunzira aliyense (kuvomereza / kukana). Mosiyana ndi Tom et al. (2007), tidagwiritsa ntchito kuchuluka kwathunthu / kutayika kwa magwiridwe osakanikirana monga kudzipatula kuti tipeze gawo la "malire" a lambda mwa aliyense mwa omwe akutenga nawo mbali. Izi zidachitika chifukwa choganizira kwambiri kuchuluka kwa kutchova juga mu fMRI kusanthula, m'malo mopeza phindu limodzi ndi kutayika. Lambda adawerengeredwa ngati kuchuluka kwa kupeza / kutayika komwe kuthekera kovomereza kuyesedwa kunali kofanana ndi kuthekera kosavomereza kuyesedwa (mwachitsanzo 0.5).

Zithunzi zojambula zamaginito

Makina ogwirira ntchito ndi kapangidwe kake adapezeka pogwiritsa ntchito sikani ya Nokia Magnetom Trio 3 T MRI yokhala ndi mutu wa 8-channel. MRI yogwira ntchito yodalira mpweya (BOLD) inagwiritsidwa ntchito pogwiritsa ntchito T2 * -weighted echo-planar imaging sequence (mavoliyumu 295; magawo 41; 3 mm isotropic resolution; kubwereza nthawi: 2430 ms; nthawi ya echo: 30 ms; flip angle: 90 °; munda wowonera: 192 mm, ndege yopingasa) opangidwira kuzindikira chizindikiro cha BOLD mu orbitofrontal cortex (Deichmann et al. 2003). Magawo anali ozungulira mozungulira ndipo gawo loyang'ana pamakalata linali kutsogolo- kumbuyo. Dziwani kuti mawonekedwe awonedwe sanalole kufotokozedwa kwathunthu kwa parietal cortex. Makina owoneka bwino atatu am'magazi onse adapezeka pogwiritsa ntchito maginito a T1 okonzekereratu mwachangu (gradient echo (MPRAGE) kutsatira cholinga cholemba limodzi (1 mm ma isoxic voxels; FOV: 256 mm; kupeza matrix 256 × 256; TR: 1540; TE: 3.93 ms, nthawi yosinthira: 800 ms, ndi mbali yozungulira ya 9 °) ndikupanga template yofananira yamagulu yowonetsera mamapu ogwira ntchito pamanambala. Mavoliyumu awiri oyamba adatayidwa ngati zowunikira kuti mundawo ufike pokhazikika.

Kusanthula kwa deta ya fMRI

Zambiri za fMRI zidawunikidwa pogwiritsa ntchito pulogalamu ya SPM8 (Wellcome department of Cognitive Neurology). Kukonzekera koyambirira kunaphatikizanso kukonza kwa kagawo ka nthawi, kusintha kwakanthawi kwa chithunzi, kulembetsa mwadongosolo zithunzi, kukhazikika pazithunzi za EPI (mwachitsanzo, chithunzi cha MNI template; ma voxels a 2 × 2 × 2 mm), kuwongola pogwiritsa ntchito isotropic Kutalika kwa 8 mm m'lifupi mwa theka la Gaussian kernel, komanso kusefa kwakanthawi kochepa (mafupipafupi 1/128 Hz). Mitundu yofananira (GLM) ikuyerekeza kukula kwa 24-parameter Volterra ya 6 yoyeserera yoyenda yolimbitsa thupi, yomwe idaphatikizidwa ngati regressors opanda chidwi monga tafotokozera mu Friston et al. (1996). Tidaphatikizaponso ma regressor owonjezera oyesa kukoka, mayesero olakwika (mwachitsanzo, 250 ms> nthawi yoyankha> 2500 ms ndi mayesero opanda yankho) komanso "regressor" atolankhani awiri oyeserera kuyendetsa kwamagalimoto okhudzana ndi makina osindikizira zala. M'maphunziro asanu, mavoliyumu am'mutu sanatulutsidwe chifukwa chakuyenda mutu kwambiri (mwachitsanzo, mutu wapadziko lonse wopitilira 8 mm, mutu wakomweko wopitilira 2 mm), ndi DVARS (mwachitsanzo, mizu yotanthauza squared (RMS) imasinthira chizindikiro cha BOLD kuchokera voliyumu kupita voliyumu, pomwe «D» amatanthauza kotengera kwakanthawi kanthawi kochitika ndi «VARS» pamasinthidwe a RMS pama voxels omwe ali pamwambapa 5% amasinthira chizindikiro cha BOLD padziko lonse lapansi Power et al., (2012)).

Mwa aliyense pagululi, tinasinthana ndi siginito yokhudzana ndi BOLD pogwiritsa ntchito GLM, yomwe imatsimikizira gawo lakuwonetsa ndi gawo la chigamulo chilichonse (onani Chith. 1A). Chizindikiro cha BOLD posintha gawo lalikulu la magawikidwe agawika kukhala "pazochitika" ndi "zotayika," chilichonse chimafanizidwa ndi kuchuluka kwawo ngati magawo a parametric mzere. Zosintha za BOLD panthawi yopanga zisankho zidasinthidwa modabwitsa ndi chiwonongeko chokwanira kwambiri kuphatikiza gawo loyamba (kutanthauza kuti mzere) ndi lachiwiri (kutanthauza quadratic) pol polomomial mod (mwachitsanzo (phindu / kutayika)²). Ma regressor onse okondweretsa adawonetsedwa ndi canonical hemodynamic reaction function.

Dongosolo la munthu payekha polingalira kuti polosomial ikusintha kuti iwonongeke kenako idalowetsedwa m'magulu awiri osiyana. Kuyesa kwachiwiri komweku kunaphatikizanso kuwongolera komwe kumayambitsa kusokera (kutanthauza, lambda) monga covariate kutengera chiwonetsero cha kusiyanasiyana kwa kutayika kwakutaya. Mtundu wina wachiwiri wachiwiri ndi wophatikizira kuchuluka kwa SOGS monga chisonyezo cha kutha kwa kutchova juga. Kusiyana pakayankhidwe ka BOLD dera pakati pa otchova juga ndi kuwongolera kunayesedwa pogwiritsa ntchito mayeso a mayeso awiri. Pa gulu, masango amatengedwa kuti ndiofunika ngati aposa malire a P <0.05 imakonzedwa pakufananiza kambiri ndi kukonza zolakwika m'banja muubongo wonse (mwachitsanzo pagulu lamagulu), pogwiritsa ntchito cholowera P_{Zosasankhidwa} <0.001. Kuphatikiza apo, kutsegulira kwamitundu yosiyanasiyana m'magulu oyenera a ma cortico-limbic akuti akuti P_{Zosasankhidwa} <0.001. Ma Coordinates amawonetsedwa mumalo a MNI stereotactic space. Pofuna kuwunikira magulu akuluakulu a BOLD (ie caudate ndi DLPFC, Chith. 4) ndikuchita ziwonetsero zamitundu yayikulu malinga ndi zomwe munthu akuchita (mwachitsanzo, kukonza chiwembu chotayika mu amygdala ndi kutha kwa njuga mosavutikira, Chith. 5), tidapanga ma masomiki otengera zigawozi pogwiritsa ntchito WFU PickAtlas (Maldjian et al. 2003). Kwa masks omwe amaphimba mabwalo awiri am'kati, amygdala, ndi precuneus, timagwiritsa ntchito masensa "AAL" ofotokozedwera (Tzourio-Mazoyer et al. 2002), pogwiritsira ntchito mask ya DLPFC, tidapanga chigoba chophimba madera a Brodmann 8-10, 46, ndi frontal gyrus (MFG). Zindikirani kuti palibe imodzi mwazomwe zidagwiritsidwa ntchito pokonzera chilichonse chazotsatira za FMRI zomwe zalembedwa mulemba lalikulu kapena pagome.

Results

Chiwerengero cha anthu ndi ma neuropsychological

Zambiri za demographic ndi neuropsychological zalembedwa Gulu 1. Magulu sanasiyane kwambiri pankhani ya ukalamba, kudzipereka, nkhawa, kapenanso kudalira mowa. Komabe, otchova juga adawonetsa kudalira kosuta kwakutali, maphunziro apamwamba, kunyinyirika kwakukulu ndipo adasiyana m'njira momwe adazionera zoopsa poyerekeza ndi zomwe sizida njuga. Zofunikira, onse otchova juga anali ndi SOGS yoposa 5, zomwe zikusonyeza kuti onse anali mu pathological range (yapakatikati: 10; osiyanasiyana: 6-19). Mosiyana ndi izi, onse koma maulamuliro awiri owongolera adalemba 0 pamayeso omwewo (apakati: 0; osiyanasiyana: 0-3), osawonetsa mabvuto a juga.

Matenda okhumudwa ndi othandizirana kawirikawiri pamatcheni amiseche, ndipo mosalekeza, tidapezanso kuwonjezeka kwakukulu kwa zodandaulitsa mu gulu la njuga poyerekeza ndi gulu lolamulira. Komabe, panalibe kulumikizana pakati pa machitidwe a juga (mwachitsanzo, λ) ndi mbiri ya BDI mwa otchova juga (R = 0.2739, P = 0.3651).

Tidapezanso kusiyana kwakukulu pakugwira ntchito pamazigawo a WAIS omwe amafufuza mawu komanso chidziwitso chambiri ("chidziwitso"). Apanso, sitinapeze kuyanjana pakati pa njirazi ndi chikhalidwe cha njuga (mwachitsanzo, kulumikizana pakati pa chidziwitso cha WAIS ndi λ: R = 0.0124, P = 0.9679; ndi pakati pa mawu a WAIS ndi λ: R = 0.2320, P = 0.4456).

Zotsatira zamakhalidwe

Chith. 1C ikuwonetsa kugawa kwa kutchova njuga pamlingo wopatsidwa-kutayika kwa otchova juga ndi owongolera. Ochita nawo mbali nthawi zonse amakhala akuwonetsa kusowa kolowera: Adalandira njuga pokhapokha phindu lomwe lidapitilira kuchuluka kwa zotayika (ie lambda> 1). Otchova juga samakonda kutaya ndalama zambiri. Chiwerengero cha mayesero omwe adalandiridwa motsutsana ndi omwe adatchova njuga anali 65% vs. 35%, ndikuwongolera, 55% vs. 45%, koma kusiyanasiyana pakati pawo kunali kwakukulu m'magulu onse awiri: lambda wapakatikati mwa otchova njuga anali 1.45 (SD = 0.49; mean = 1.45; range: 0.56-2.59), ndi kugawa kotsimikizika kwa λ's (koyika kokwanira kwa 0.42), pomwe lambda wapakatikati pakuwongolera koyenera anali 1.82 (SD = 0.83; mean = 1.83; range: 1.01-3.83; skewness yabwino: 0.93). Chifukwa chake, kusiyana kwa lambda pakati pamagulu kumangofika pakufunika kwamalire (P = 0.077; T (27) = 1.47). Dziwani kuti kugawa kwa lambda sikunali kwachilendo (kuyesa kwa Shapiro-Wilks mwachizolowezi: P = 0.0353, W = 0.9218). Chifukwa chake tidagwiritsa ntchito mayeso osavomerezeka potengera kusinthanso (komwe kumadziwikanso kuti mayeso osasintha) kuti tione kusiyana kwa lambda pakati pa otchova njuga ndi kuwongolera koyenera. Chiwerengero cha mayendedwe omwe adagwiritsidwa ntchito anali 10.000.

Chiwerengero cha zolakwika zolakwika chinali chofanana ndi magulu. Ochita masewera monga gulu anali ndi mayesero olakwika a 30 (15 non -ankho, 15 mayankho mwachangu kapena mwapang'onopang'ono) ndi mayankho olakwika a 0-8 pamutu uliwonse. Nkhani zowongolera zopangidwa pazolakwitsa za 27 kwathunthu (16 yosayankha, 11 mayankho mwachangu kapena mwapang'onopang'ono) ndi mayesero olakwika a 0-8 pamutu uliwonse. Nthawi zoyankha zinalinso zofanana pakati pa magulu (P = 0.66; t (27) = 0.45; otchova juga: 927 ms; Sd = 240; zowongolera: 959 ms; Sd = 122). Zisankho zovomereza kapena kukana kutchova juga zinali zovuta kwambiri pomwe phindu ndi zotayika zinali zofananira. Izi zimawonetsedwa munthawi zoyankha, popeza magulu onse awiriwo adayankha pang'onopang'ono pamene mtunda wa Euclidian pakati pa chiwonetsero / kutaya kwa gulu ndipo gulu limatanthauza kuti lambda yatsika (otchova njuga: R = 0.15, P <0.001; amazilamulira: R = 0.15, P <0.001).

Kuchuluka kwazowoneka za ntchito za neural zomwe ziwonjezera kuchuluka kwa kutaya-kutaya

Mu gawo lopanga zisankho, gulu lalikulu la mabwalo awiri mu anterior cingulate cortex (ACC) ndi vmPFC (P <0.001; x, y, z = - 8, 40, 6; Z = 4.75; k = 759), kotekisi yapakati pa cingular cortex ndi pafupi ndi precuneus, (P <0.001; x, y, z = - 10, - 30, 52; Z = 4.43; k = 1933), ndi girus wapamwamba wam'mbuyo (SFG; P <0.001; x, y, z = 18, 38, 56; Z = 4.34; k = 633) adawonetsa kukwera kwakanthawi kwamayankho a BOLD okhala ndi chidwi chochulukirapo-kutaya magawo pakati pa onse omwe akutenga nawo gawo 29. Chith. 2 chikuwonetsa kuti kuwongolera kumeneku kunayendetsedwa makamaka ndi otchova njuga, omwe akuwonetsa kuwonjezeka pang'onopang'ono kwa kuyankha kwa BOLD ndi ziwonetsero zomwe zimakonda gawo la gawo la ACC (P <0.001; x, y, z = - 8, 36, 8; Z = 5.18; k = 518; Chith. 2A) ndi vmPFC yoyenera (P = 0.003; x, y, z = 8, 34, - 10; Z = 4.23; k = 307) komanso pakati pa cingulum / precuneus (P = 0.031; x, y, z = - 10, - 30, 52; Z = 4.40; k = 188), gyrus wotsika pang'ono / parahippocampus (P = 0.002; x, y, z = 34, 2, - 30; Z = 4.23; k = 329), ndi girus wa postcentral (P = 0.001; x, y, z = 62; - 20, 44; Z = 4.11; k = 356). Kuwongolera, komano, kunawonetsa masango obalalika m'malo osiyanasiyana (kumanzere kwa precuneus: P <0.001; x, y, z = - 6, - 58, 32; Z = 4.72; k = 1010; Chilankhulo cholondola: P = 0.002; x, y, z = 18; - 86, - 8; Z = 4.67; k = 332; cuneus wamanzere: P = 0.028; x, y, z = - 14, - 100, 10; Z = 4.27; k = 193; ndi kumbuyo kwamanja kumbuyo kwa cerebellum: P = 0.001; x, y, z = 42, - 70, - 34; Z = 4.09; k = 351) ndikutsegulira kwakukulu kumanzere a angular gyrus (P <0.001; x, y, z = - 48, - 60, 30; Z = 5.06; k = 433; Chith. 2B). Ngakhale sitinapezenso kuchepa kwakukulu pakuchita chidwi ndi kubetcha kokulira, sitinapeze zomwe zikuchitika pagulu lazoyang'anira (L: P <0.001, yosakonzedwa; x, y, z = - 32, 24, - 2; Z = 3.83; k = 74; R: P <0.001, yosakonzedwa; x, y, z = 42, 24, 4; Z = 3.64; k = 14). Poyerekeza maguluwa, palibe kusiyana kwakukulu komwe kunapezeka. Komabe, otchova juga adawonetsa chizolowezi chowonjezeka pakuchita ndi kutchova njuga zochulukirapo mu ACC yoyamba (P <0.001, yosakonzedwa; x, y, z = - 8, 36, 6; Z = 4.33; k = 98; Chith. 2C). Zotsatira zomwe zikuwonetsa kukhudzika kwa kuchuluka kwa kutayika kwakakuthengo pakuwonjezeka kwa ntchito za neural zowonjezera zimatha kupezeka mu Supplementary mkuyu. 1 ndi Supplementary Table 1.

Fanizo la 2. 

Mapu owerengera okhala ndi utoto t-mamapu: Madera aubongo omwe akuwonetsa ubale wabwino pakati pa kuyankha kwa BOLD ndikuwonjezera kuchuluka kwa kutaya kwa kutchova A) mwa otchova njuga, B) pakuwongolera, ndi C) kusiyanitsa magulu awiriwa. Pakusiyanitsa magulu, kuchititsa BOLD kuwulula kusiyanasiyana kwamalingaliro oyamba a ACC (otchova njuga> zowongolera). Mamapu atsekedwa P <0.001 (yopanda tanthauzo) ndikuwonetsedwa pagulu lodziwika bwino la anatomical template potengera zithunzi za T1.

Zosankha za zithunzi

Kuchulukana kwamasiku atatu mu ntchito za neural zowonjezera phindu

Kuphatikiza kwa BOLD chizindikiro kuchokera kwa onse omwe akutenga nawo mbali, malo ophatikizika am'mbuyo mwam'mphepete ndikuwonetsa kuwonjezeka kwapadera kwa ntchito za neural ndikuwonjezeka kwa ziwonetsero zopindulitsa mu dorsal SFG (P <0.001; x, y, z = 12, 24, 60; Z = 5.38; k = 1769). Zowonjezera zina zakusiyanaku zidaphatikizira kumanzere chakumaso chapakati (P <0.001; x, y, z = - 38, 10, 50; Z = 4.81; k = 605), gyri yamayiko awiri (L: P = 0.022; x, y, z = - 42, - 64, 40; Z = 4.24; k = 227; R: P <0.001; x, y, z = 52, - 56, 38; Z = 4.68; k = 488), kumanzere kwa girus wam'mbuyo wotsika (P = 0.004; x, y, z = - 42, 26, - 16; Z = 4.09; k = 330), ndi gyrus wotsika wolondola (P = 0.001; x, y, z = 66, - 14, - 22; Z = 4.30; k = 409). Monga momwe tawonetsera Chith. 3, kuwunika kosiyana kwa gulu lirilonse kukuwonetsa kuti izi zimangokhala zogwirizana ndi otchova njuga. Mu otchova juga, malo angapo aubongo adawonetsa kuwonjezeka kwamtundu umodzi ngati gawo la magawo, kuphatikiza mbali yayikulu ya kutsogolo kwa mbali ya kutsogolo kwa gyri wapakati komanso wapamwamba, komanso tsinde loyang'ana kumutu lophimba kumutu ndi thupi la mbali yakumanzere ndi yamanja nyukiliya (Chith. 3A; mndandanda wonse wothandizira ukhoza kupezeka Gulu 2). Mosiyana ndi izi, mbiri yamachitidwe mu zowongolera sizinawonetse kusintha kwamtundu uliwonse wa zochitika poonjezera kuwonjezeka kwa phinduChith. 3B; Gulu 2).

Fanizo la 3. 

Mamapu okhala ndi zikwangwani zojambula zamitundu yosiyanasiyana: Magawo a maubongo akuwonetsa ubale wabwino pakati pa mayankho a BOLD ndikuwonjezeka kwa kutchova njuga kwa A) otchova juga, a B), ndi C) osiyanitsa magulu awiriwa. Mamapu apunthwa P <0.001 (osakonza).

Zosankha za zithunzi

Gulu 2.

Zotsatira zakugwira ntchito kwa MRI: kuwonjezeka kwamkutu munthawi ya ntchito za BOLD ndikuwonjezeka kwa kutchova njuga.

P <0.05, FWE yakonzedwa pamlingo wamagulu.

⁎

Ma maxima am'deralo mkati mwa tsango ndi Z alama> 4.

Zosankha pazithunzi

Poyerekeza otchova juga ndi maulamuliro, tinapeza kuchuluka kwamphamvu kwambiri kwa zochitika za neural ndi kuchuluka kwa kutayika mu gawo lalikulu la zigawo zaubongo (Chith. 3C), kuphatikiza khola lalikulu la cortico-striatal cluster. Mkati mwa tsango ili, gawo lamanzere la caudate lidawonetsa kusiyana kwamphamvu kwambiri pamlingo wokhotakhota ndipo DLPFC lamanja limawonetsa gawo lamphamvu kwambiri pagulu. Mndandanda wonse wamgulu lachitetezo umaperekedwa Gulu 2. Zodziwikiratu, palibe magulu omwe adawonetsera kusintha kwamphamvu kwa ntchito za neural ndi kuchuluka kwakutayika pazowongolera poyerekeza ndi otchova njuga.

Tiyeneranso kudziwa kuti kuchuluka kwa magwiridwe a BOLD kumawonjezeka kukhala otchova njuga omwe amakonda kupulumuka omwe amatchova njuga ngakhale kuphatikiza BDI kapena kuchuluka kwa WAIS ngati ochita nawo mayeso achiwonetsero achiwiri (mwachitsanzo, kufotokozera za kukhumudwa, mawu kapena kuchuluka kwa chidziwitso) , zomwe zinali zosiyana pakati pa magulu malinga ndi mayeso amachitidwe, mwawona Gulu 1). Zotsatira, komwe zotsatira za kukhumudwa zawoneka kuti zikuwonjezereka mwa kuchuluka kwa zochitika za neural zowonjezereka, zitha kupezeka ku Supplementary Fig. 2.

Kuti tifotokozere momwe zimakhalira pakuwonekera kwa kusintha kwa chizindikiro cha BOLD panthawi yopanga zisankho, tinapatsa gawo lililonse la 64 kupeza-kutaya gawo mu imodzi mwa zigawo za 16 zoyandikana nawo mu positi hoc GLM. Pomwe timakonza chiwembu chilichonse mwama bins awa ngati ntchito yowonjezera phindu la kutaya, tinapeza kuti mawonekedwe a BOLD poyang'ana otchova juga anali mawonekedwe a U (Chith. 4B). Kuti tidziwe ngati mzere kapena mtundu wa kiyubiki anali woyenera kufotokoza momwe zimakhalira, tinayesa ngati kusiyanasiyana komwe kunanenedwa ndikuphatikiza ma polynomial terms (quadratic and cubic) ndikofunikira. M'masewera otchova njuga koma osawongolera, mtundu wophunzitsidwa bwino udatsimikizira kuti mawonekedwe oyikika ndi oyenera kufotokoza mtundu wa momwe amapotera, kuposa koyenera mzere. Dziwani kuti zomwe zikufotokozedwazi siziyenera kuwonedwa ngati zotsatira zosiyana, koma kungowunikira koonjezera kuti muwonetse momwe mawonekedwe akuwonekera a BOLD akuyimira.

Fanizo la 4. 

Kusintha koyesedwa kwa kuyankha kwa BOLD kumawonjezera kuchuluka kwa kutayika kwa otchova njuga. A) Mamapu okhala ndi ma parametric okhala ndi zikwangwani zowonetsa masango omwe ali ndi chidwi chapamwamba kwambiri pazakuwononga kopindulitsa komanso kosapindulitsa kwa otchova njuga poyerekeza ndi kuwongolera. Mamapu apunthwa P <0.001 sinakonzeke. Kuwonetsa zigawo zikuluzikulu ziwiri zosiyana pakati pa magulu, kutsekedwa kwa anatomical kwa caudate nuclei (pamwamba) ndi DLPFC (pansi) kumagwiritsidwa ntchito. B) Malo obalalikawa adakhazikitsidwa pa "post hoc" kusanthula kwa GLM komwe kumapangidwira zofanizira, komwe mapindu oyandikira-kutayika adalumikizidwa palimodzi kukhala 16 "mabini" (kuchuluka kwake kumawonetsedwa pa x-axis). The ax-axis imawonetsa zochitika zam'madera (monga momwe amayankhira BOLD poyankha 8-voxel mozungulira pachimake pachimake) mgawo la otchova njuga (ofiira) ndi owongolera (akuda). Mtundu wokhala ndi zisa zosonyeza kuti kuyambitsa kumafotokozedwa bwino ndi quadratic poyerekeza ndi ubale wofanana ndi phindu-kutaya chiwonetsero mumtambo wa caudate (P = 0.02) ndi DLPFC (P = 0.02) mwa otchova juga (gulu lakumanzere) koma osawongolera (gulu lamanja).

Zosankha za zithunzi

Zovuta zakuwonongeka kwa munthu payekha

M'magulu onse awiriwa, kuchuluka kwa njira yotayirira, yotchulidwa ndi gawo la malera, kumakulitsa chidwi chomvekera kwambiri cha magawo osakanikirana a magawo osakanikirana mu ubongo wam'magawo omwe ali ndi chiwonetsero chachikulu mu amygdala wamanja (P <0.001; x, y, z = 24, - 4, - 26; Z = 5.01; (K = 1988). Kupatula chiwonetsero chachikulu cha amygdala, zigawo zimaphatikizapo DLPFC / SFG (P <0.001; x, y, z = 32, 24, 56; Z = 4.86; k = 2372), kumanzere kwakanthawi kwakanthawi kochepa / parahippocampal gyrus (P <0.001; x, y, z = - 44, - 24, - 24; Z = 4.59; k = 1435), precuneus (P <0.001; x, y, z = - 4, - 62, 26; Z = 4.40; k = 1169), ndi vmPFC (P = 0.009; x, y, z = 8, 26, - 18; Z = 4.31; k = 281).

Mwa otchova njuga, kuchuluka kwa njira yotayika kumalumikizidwa ndi kukhudzika kwakukweza kuzowonjezera-kutayika mu dorsal frontal network yomwe ili ndi chiwonetsero chapamwamba mu DLPFC (Chith. 5A; onaninso Gulu 3 mndandanda wathunthu wa zoyambitsa). Njira yolumikizira masewerawa imafanana kwambiri ndi malo oyambira omwe akuwonetsa ntchito za U zomwe zikuwonjezeka komanso ziwonjezeka za anthu otchova njuga Chith. 3.

Fanizo la 5. 

Kusintha kwa ubale wa U pakati pa ntchito za neural ndi kuchuluka kwa kutayika kwa A) munthu kusiyanitsa kutayika ndi B) kuopsa kwa kutchova juga. A) Mamapu okhala ndi zikwangwani zojambula zamitengo zosonyeza kuchuluka kwa kutayika kwa munthu payekhapayekha (komwe kumawonetsedwa ndi mautchulidwe apamwamba) kunalimbitsa ubale womwe unapangidwa pakati pa zochitika za neural ndi magawo otchova njuga pamatayala a pathological (mapanelo amanzere) kapena maulamuliro (mapanelo amanja). Chithunzi chomwe chili pansipa chikuwonetsa ubale womwe ulipo pakati pa ziwonetserozo pakati pa ubale wapakati pa ntchito ya neural ndi kuchuluka kwa kutaya kwake (y-axis) ndi kutayika kwa kutayika kwapadera (x-axis) mu billetal amygdala (maulamuliro: P <0.001; R² = 0.83; otchova juga: P = 0.11; R² = 0.71). B) Pamwambapa: Mapu owerengera okhala ndi mitundu yosonyeza magulu awiri mwa precuneus, pomwe chidwi cha njuga zowopsa chimakulirakulira chifukwa cha kutchova juga kwa omwe amatchova njuga. Kumanja: Chiwembu chomwaza chikuwonetsa ubale wapakati (P = 0.016; R² = 0.63) pakati pamalingaliro amtundu wina wa ubale wofanana ndi U pakati pa chiŵerengero ndi zochitika za neural m'dera la precuneus (y-axis) ndi kuopsa kwa kutchova juga komwe kumawonetsedwa ndi ziwerengero za SOGS (x-axis). Zochitika zonse za BOLD ndizochita zonse zaubongo zomwe zimawonetsedwa pakhomo P <0.001 (osakonza).

Zosankha za zithunzi

Gulu 3.

Zotsatira zakugwira ntchito kwa MRI: zotsatira za kutayika kwakukhazikika pakuwonjezeka kwapachulukidwe ka zigawo za BOLD za zigawo limodzi ndi magawo a njuga.

P <0.05, FWE yakonzedwa pamlingo wamagulu.

⁎

Ma maxima am'deralo mkati mwa tsango ndi Z alama> 4.

Zosankha pazithunzi

M'mawongolero osagwiritsa ntchito njuga, makina owonera ndi owonetsa kumbuyo omwe adawonetsa kutchova juga kwambiri ngati ntchito yotaya kutaya, amygdala wamanja ali ndi kukula kwamphamvu kwambiri (Chith. 5A, pakati kumanja; Gulu 3). Kufananitsidwa mwachindunji kwa magulu awiriwa kunabweretsa kutaya mtima kwakanthawi kawonedwe ka mbiri muzochitika mu DLPFC kwa otchova juga poyerekeza ndi maulamuliro (Gulu 3), pomwe zotsatira za kutembenuka mtima kwakutayika pa zochitika za amygdala sizinali zosiyana kwambiri pakati pamagulu.

Mukakonza ubale wapakati pamalingaliro a BOLD ndikuyerekeza kutaya, kutaya kutaya munthu m'magulu oyendetsa bwino (koma osati otchova njuga) kunalimbitsa ubale womwe unapangidwa pakati pa zochitika za neural mu amygdala (Chith. 5A, graph pansi. Dziwani kuti izi zinathandiza kwambiri kupatula mutu womwe sunawonongeke kwambiri). Kupatula ma voxel ochepa mu amygdala wamanja (onani Chith. 5A, pakati pagulu), kutayika kwakutaya kwa otchova njuga sikunalumikizidwe ndi kusintha kwa amygdala panthawi yopanga chisankho.

Zovuta zakuya kwa njuga zamatenda

Tidafufuza ngati kuwopsa kwa kutchova juga kwa otchova juga monga momwe munthu aliyense wa SOGS adasinthira kuyankho lochokera ku U ku ziwonetsero zoopsa panthawi yopanga zisankho. Kusaka kwaubongo kwathunthu kwawonetsa kukulitsa kwamphamvu kwa ziwopsezo zoopsa kwambiri ndi kutchova juga kwakatundu wamitundu iwiri (P = 0.003; x, y, z = - 6, - 48, 40; Z = 4.59; k = 335; Chith. 5B, pamwamba gulu). Chifukwa chake, kulumikizana pakati pa zigawo za BOLD zimasintha m'dera lachigawo chimodzi (kuletsa zochitika m'derali kudzera pachiwonetsero chazithunzi) komanso kuzunza kwambiri njuga kunali kofunika kwambiri (Chith. 5B, graph yotsika).

Ubongo umayankha ku zopeza zomwe zingachitike kamodzi ndi kutayika

Popeza kuchuluka ndi kutayika kwa kutchova njuga kosakanikirana kunaperekedwa motsatizana pachiyeso chilichonse, tinatha kusintha kusintha kwa zigawo mu siginecha ya BOLD yolingana ndi phindu limodzi ndi zotayika (koma onaninso zokambirana za jittering yomwe imagwiritsidwa ntchito mu Kukambirana gawo). Munthawi yovotera iyi, tidayang'ana pakusiyana pakati pa gulu pakuyankha, kutayika, phindu lochulukirapo, ndikuwonongeka. Panalibe zosiyana pagulu pazosinthazi, koma tidapeza njira yomenyanirana yopita ku BOLD yokweza kwambiri pamitengo yomwe ingagwiritsidwe ntchito ndi otchova njuga poyerekeza ndi oyang'anira amygdala (L: P <0.001, yosakonzedwa; x, y, z = - 26, 2, - 22; Z = 3.19, k = 6; R: P <0.001, yosakonzedwa; x, y, z = 24, - 2, - 10; Z = 3.43; k = 7).

Kukambirana

Posiyanitsa kupanga zisankho zathanzi komanso zamaganizidwe ndi ntchito yosakanikirana ya kutchova juga, tinayezera zochitika zokhudzana ndi ntchito nthawi yakusankha njuga, zomwe zimapangitsa kuti ochita nawo malonda asagule phindu lomwe lingachitike chifukwa chotayika. Masewera otchova njuga, dorsal cortico-striatal network amawonetsa kukhudzika kwapamwamba kwamatenda kwambiri komanso chidwi kwambiri chofuna kutaya ndalama poyerekeza ndi magwiridwe antchito oyenera. Kulimbitsa kwambiri madera a corsal cortico-striatal kuti akhale olowa kwambiri kumawonetsa kuti ochita kutchova juga amaika mphamvu mopambanitsa pamalingaliro operekedwa ndi juga. Makamaka, kuyimitsidwa kotere kwa mawonekedwe a U pakuwonekera pamitunda ya njuga sikunawonedwe pamawu, kuwonetsa kuti kudziwika kwakanthawi kochepa kwambiri kumakhala chizindikiro cha neural cha njuga.

Chosangalatsa ndichakuti, mawonekedwe a U omwe amawoneka ngati ma neural pantchito yolimbirana kwambiri komanso yosangalatsa kwambiri sanawonetsedwe m'chigawo cha mphotho, monga cyral striatum kapena orbitof mbeleal cortex. M'malo mwake, zidawonetsedwa pamakina a dorsal cortico-striatal "Associative" kapena "Executive", kuphatikiza gawo la caudate ndi DLPFC. DLPFC yomwe idalembedwa ikuphatikiza gyri ya dorsal ndi mesial apamwamba komanso yapakatikati, yolingana ndi BA 6 / 8 / 9 ndi "9 / 46d" (Badre ndi D'Esposito, 2009 ndi Goldstein ndi Volkow, 2011). Ma dorsal cortico-striatal network amadziwika kuti akuchita nawo ntchito zowunikira zomwe zachitika posachedwa ndikuyembekezera zotsatira zawo (zowunika onani Yin ndi Knowlton 2006). Makamaka, gawo laumunthu la caudate lakhala likuthandizidwa pakukonzekereratu kwa zochitika zothandizira kuchitapo kanthu (zotsatira zantchito)Knutson et al., 2001, O'Doherty et al., 2004, Tricomi et al., 2004 ndi Delgado et al., 2005).

Zotsatira zathu zapano zikuwonetsa kuti dorsal cortico-striatal network imatenga gawo lofunikira pazisankho za njuga zopangidwa ndi otchova njuga. Kuwerengera kwambiri-kuwonongera kumadziwika kuti kumakhala kofunikira kwambiri malinga ndi zomwe mungakwanitse kuchita: phindu lomwe kubetcha ndilofunika, ndizofunikira kwambiri kuvomereza; Komanso, kubetchera kochuluka kwambiri, ndikofunika kwambiri kukana. M'mitu yathanzi, dorsal striatum yapezeka kuti ilandire kukondoweza kapena kukondoweza, m'malo mowonjezera mtengo wamagulu (Barta et al. 2013). Tidziwitsa kuti pamisamba yotchovera njuga, dorsal cortico-striatal network imakhala yotsika mtengo ndipo imalemera kwambiri izi pazomwe zimataya phindu kwambiri kuposa maphunziro apamwamba.

Malingaliro amakono azomwe zimayambitsa kuthana ndi njuga zam'magazi ndizokakamira kwawo m'njira yosavuta, polosera za hypo- kapena hypersensitivity ya ventral striatum ndi zigawo zina zamkati mwa dongosolo la mphotho monga vmPFC. Chifukwa chake, kafukufuku wam'mbuyomu wamiseche omwe adatchova juga adawonetsa kuchepa (Balodis et al. 2012) kapena kupititsidwa patsogolo (van Holst et al., 2012 ndi Worhunsky et al., 2014) kuyambitsa kwa cyral striatum panthawi yoyembekeza mphoto. Mu kafukufuku wapano, palibe kusiyana pakati pa zochitika za neural pakati pa otchova njuga ndi kuwongolera kosagwiritsa ntchito njuga zomwe zidatulukira mu njira yolipira mphotho pomwe adayang'ana kutayika kamodzi kapena ndalama pakaperekedwe ka gawo lalikulu kapena momwe zingapezere phindu ndi kutayika kwa mayendedwe osakanikirana mu gawo la chisankho. Amygdala yekha kumanja ndi kumanzere adawonetsa zomwe zingachitike poyambira mwamphamvu kuti athe kuchita bwino panthawi yoyamba. Mwanjira ina, lingaliro lovomera kapena kukana kutchova juga silimagwirizana ndi hyperensitivity ya mphotho. Kupeza koyipa kumeneku kumagwirizana ndi kafukufuku waposachedwa pomwe otchova juga adawonetsa kubwezeretsedwa kwapadera kwa njira zolipirira ndalama koma chidziwitso choperewera cha zomwe zikuneneratu zoyambitsa zolakwika (Sescousse et al. 2013). Kuperewera kwa njira yosasintha m'mabukuwa, komwe kungakhale ndi zotsutsana kapena kusakhudzana konse, zikuwonetsa kuti kufotokozera njuga zamatenda mwaukadaulo kapena kuwongolera kungakhale kosakwanira. Adanenanso kuti zosankha zomwe zimapezeka mu njuga zamatenda zimatha kutuluka pakusayanana pakati pa kayendedwe ka dopaminergic komwe kumakhudza magwiridwe olimbitsa miyendo ndi mbali zoyendetsedweratu, m'malo mwakusokoneza gawo limodzi patokha (Clark et al. 2013). Mmodzi mwa ochita bwino pa mabungwe a cortico-striatal loop ndi dorsal cortico-striatal loop, yomwe yalimbikitsidwa posankha zochita ndi kukonza zochitika zankhondo (Yin ndi Knowlton, 2006 ndi Seo et al., 2012). Dziwani kuti posankha zomwe zikuchitika pakalipano zimapangidwa malinga ndi kupezeka pakati pa zopeza ndi zotayika osati njira zotsatirika, kapena njira zowyembekezera. Ichi mwina ndi chifukwa chomwe timapeza madera omwe ali okhudzana kwambiri ndi kusankha kwa chinthucho (mwachitsanzo kuvomereza kapena kukana kubetcha), m'malo mwa malo omwe amakhalapo pakuyembekezera kapena kulandira zotsatira.

Apa, pakulamulira kosagwiritsa ntchito njuga, kutaya zinthu mosagwirizana ndi ntchito yotchova juga kumalumikizidwa ndi chidwi champhamvu kwambiri pazowonjezera-kutayika mu amygdala. Zotsatira izi zikugwirizana bwino ndi zomwe tapeza posachedwa mgulu lina la anthu athanzi (Gelskov et al. 2015), pomwe otenga nawo mbali ambiri adawonetsa kukhudzika kwa neural mu amygdala mpaka phindu lalikulu-kutaya kwa magwiridwe osakanikirana. Zotsatirazi zidapitilira ngakhale panali kusiyanasiyana pakati pa maphunziro. Omwe adasewera nawo omwe adasewera mu sikaniyo sanasinthe (mwachitsanzo, kugawa ndalama, kutalikirana, ndi kutulutsa zokopa, ndi zina zambiri). Komabe, njira zopezera ndalama zimasiyana pang'ono. Pakafukufuku waposachedwa, omwe adatenga nawo gawo adalandira ngongole zenizeni (200 DKK) zomwe adasunga kwa masabata 1-2 asanalowe nawo ngati gawo la njuga, pomwe kafukufuku wam'mbuyomu, omwe adatenga nawo gawo adakhulupirira kuti atha kutaya ndalama poyambira mphatso. Kusiyana kumeneku pamalingaliro amathandizidwe mwina kumatha kufotokozera chifukwa chake maphunziro olamulira athanzi mu kafukufuku wapano anali ocheperako pang'ono (medda lambda wa 1.82) poyerekeza ndi kafukufuku wathu wam'mbuyomu (median lambda wa 2.08). Ngakhale kusiyana pakati pa magulu awiri athanzi sikunali kofunikira (P = 0.18, testutation test), kusiyana kwa lambda pakati pa gulu lathanzi lakale ndi gulu la otchova juga kunali kwakukulu (P = 0.004, mayeso ovomerezeka). Kusiyana kwina koonekeratu pakati pa maphunzirowa ndi kusiyana kwa msinkhu, popeza gulu lolamulira lomwe lidalipo linali lakale kuti lifanane ndi otchova njuga (P = 0.0175, t (29) = 2.52; 2-mayeso t-mayeso). Komabe, ngati zilipo, kusiyana kumeneku kuyenera kuneneratu za lambda, popeza maphunziro athanzi lakale amakhala otayika kwambiri kuposa achichepere. Kuphatikiza apo, maphunziro awiriwa anali osiyana pang'ono ndi momwe amalingalira kutchova juga. Phunziro lathu lapitalo, tidapeza kuti amygdala anali ozindikira kusinthasintha kwakulandila poyerekeza ndi gawo linalake la "malire" (mwachitsanzo mphambu ya lambda, λ). Mtunduwu ukhoza kulingaliridwa ngati yankho la "V" lopangidwa ndi BOLD pakukula kowonjezeka, pomwe "malo otsika" a V anali λ-score. Ma regressor amizere iwiri adasanja muyeso uliwonse woyeserera kukhala wosakondera kapena wosakhazikika, malingana ndi momwe amasiyana ndi λ iliyonse (mwachitsanzo, magawanidwe osinthasintha <munthu aliyense λ <matchulidwe okopa). Komabe, mu kafukufuku wapano, sitinathe kuyika mtundu wathu pazambiri za λ, popeza ochepa omwe adatenga nawo gawo anali ndi ziwonetsero zambiri kwambiri kapena zochepa kwambiri. Chifukwa chake, tidagwiritsa ntchito phindu losawonongeka lomwe silinasinthidwe kuti tiwone kuyankha kwamitsempha pazowerengera zonse zopitilira (ie "U" -kuyankha koyankha kwa BOLD ku chiŵerengero). Dziwani kuti kugwiritsa ntchito mtundu wosiyana pang'ono wa quadratic kungakhale chifukwa chomwe sitinatchulenso zomwe amygdala amachita potchova njuga pamitu yathanzi. Zingakhale choncho kuti amygdala imayang'aniridwa ndi malire, λ, ndi kuyambitsa kwa amygdala mu kafukufuku wathu wakale zitha kukhala zokhudzana ndi kuphatikizidwa kwa λ-score mu regressor akulu. Kutanthauzira kumeneku kukugwirizana ndi kuti njira ziwirizi zowunikira zidawonetsa kuti kutaya njuga pamakhalidwe kumalumikizidwa ndikumverera kwakukulu kwa amygdala kuzotsatira zosasunthika komanso zotsogola kwambiri pakupanga chisankho. Kuphatikizidwa, zomwe zapezazi zikuwonetsa gawo lofunikira la amygdala posankha zosankha zoyipa mwa anthu athanzi.

Mwa otchova juga, kulumikizana pakati pa kutaya njira zomwe sizimayenderana ndi zochitika zamasewera pamitengo ya kutchova njuga kunawululira zochitika zosafunikira kwenikweni mu amygdala. M'malo mwake, zochitika zokhudzana ndi zisankho mu DLPFC zidasinthidwa ngati ntchito yotaya kutaya. Zotsatira zake zinali zamphamvu kwambiri kwa otchova juga poyerekeza ndi zowongolera. Chosangalatsa ndichakuti, izi zidafika pamalo amodzi mu DLPFC pomwe tidapeza mphamvu yayikulu kwambiri yoyerekeza kwambiri magawo omwe ali ndi kuwongolera. Izi zikuwonetsa kuti mu otchova juga, kuchuluka kwa njira yotayika sikumawonetsedwa ndi malo omwe akuneneratu zakumaso kapena kufunikira kwa kukondoweza monga amygdala ndi ventral striatum, koma m'malo mwake ndi zochitika mu DLPFC. Mwa chiwerengero ichi, zikuwoneka kuti gawo laling'ono lopanga zigawo zikuluzikulu limakhala ngati kukumbukira ntchito, kusinthitsa ntchito, ndikuyimira zochitika zotsatila (Elliott, 2003, Monsell, 2003 ndi Seo et al., 2012) ikuwonjezera amygdala pakulimbana ndi kutaya njuga mosiyanasiyana. Komabe, lingaliro ili likufunika kufufuzidwanso m'maphunziro a juga amtsogolo.

Chochititsa chidwi, tinapeza chizolowezi chofuna kutaya njuga pang'ono. Malinga ndi malingaliro azikhalidwe zacikhalidwe, momwe amachitila zinthu zosamveka bwino izi zimapangitsa kuti ochita juga azichita bwino kuposa kuwongolera. Komabe, nkhani yakusinthika kwakukhudzana ndi kusowa kwa zinthu zitha kutanthauza kuti kusankhana m'malingaliro kunakwaniritsa cholinga chotsogolera zosankha mwanzeru mukamaba chakudya. Zowonadi, kutaya kutaya kumanenedwa m'mbuyomu monga anyani a capuchin (Chen et al. 2006; koma onaninso Silberberg et al. 2008) kuwonetsa kuti kuphonya kutaya njira yoyendetsera bwino yochokera ku malingaliro yomwe ingakhale yozindikira kwambiri yolimbitsira chitetezo. Kafukufuku waposachedwa ndi Giorgetta et al. (2014) anapeza kuti otchova juga omwe anali m'magulu azachipatala pambuyo pake anali otayika kwambiri kuposa otchova juga omwe anali m'mbuyomu chithandizo. Chochititsa chidwi, adapeza kuti omwe amatchova juga monga gulu (paliponse momwe angalandire chithandizo) anali otayika kwambiri kuposa njira zoyenera. Mosiyana ndi izi, kafukufuku wam'mbuyomu wofufuza za kutaya mtima kwa otchova juga adapeza kuti otchova juga (kutanthauza osalandira mankhwalawa) adataya pang'ono poyerekeza ndi oyendetsa bwino (Ophwanya et al. 2012). Izi zimadzetsa funso ngati chithandizo chokwanira chitha kupangitsa kuti otchova njuga asatayike. Pakufukufuku wapano, otchova njuga adalembedwa kuchipatala, ndipo ambiri adachitapo lingaliro lazachipatala. Mwina, ichi ndi chifukwa chake sitinapeze kusiyana kwakukulu pakati pa otchova njuga komanso owongolera athanzi koma chokhacho cholowera.

Pomaliza, tidapeza kuti otchova juga omwe ali ndi zizindikiro zambiri zamtundu wa juga, monga momwe amawerengera ndi gawo la SOGS, anali ndi chidwi chambiri pozindikira kuchuluka kwa kutchova njuga. Precuneus ndi posterior cingate cortex nthawi zambiri zimapezeka poyankha ntchito zodzidziwitsira (onani ndemanga ndi Cavanna ndi Trimble 2006), ndipo kafukufuku waposachedwa wofufuza kudziletsa kwa otchova juga adawonetsa zizindikiro zamagetsi zamagetsi pamtunda wakumbuyo kwa cortex pogwiritsa ntchito MEG (Thomsen et al. 2013). Zizindikiro zobera izi zalumikizidwa ndi chowonadi chokhazikitsidwa kuti otchova juga wazamisala amavutika kwambiri ndi kudziletsa. Mu kuphunzira kwathu, kusinthasintha kwa zochitika zamagetsi ngati gawo la kutchova njuga kumawonetsanso njira zofananira zodziletsa. Komabe, malingaliro awa okhudzana ndi kugwira ntchito kwa njirayi mu njuga zamatenda akufunika kukonzedwa mwanzeru m'maphunziro amtsogolo.

Zotsatira zathu zinaulula mawonekedwe osinthika, ooneka ngati U pa zochitika zonse za caudate ndi DLPFC pomwe otchovera njuga amayesa kubetcha ndalama. Ngakhale mawonekedwe amtunduwu amayambira kuchitika mwangozi, koma osagwirizana, kusokonekera kwa magawo aubongo awa, atha kupangidwanso kuchokera pakusintha pakalumikizidwe. Kafukufuku wam'mbuyomu m'maphunziro athanzi adapereka umboni wokwanira wolumikizana pakati pa caudate ndi PFC, podalira zonse zogwira ntchito (mwachitsanzo. Robinson et al. 2012) komanso zomasulira (mwachitsanzo Verstynen et al. 2012) cholumikizira cha cortico-striatal. Ndikothekanso kuti njira zamiseche zimawonetsera kusintha kosiyanasiyana kwa kayendedwe ka gawo mu gawo lodziwika bwino la cortico-striatal.

Monga mmaphunziro ambiri ammbuyomu, tidangophatikiza maphunziro a amuna (mwachitsanzo van Holst et al., 2012, de Ruiter et al., 2009, Linnet et al., 2011 ndi Sescousse et al., 2013). Komabe, ngakhale kafukufuku wamatenda akuwonetsa kuti abambo akuimira anthu ambiri otchovera njuga (Kessler et al. 2008), njuga zamatenda zimakhudzanso azimayi. Chifukwa kafukufuku wasonyeza kusiyana pakati pa azimayi ndi abambo potengera zomwe amakonda monga kutchova njuga (mwachitsanzo, mitundu yamagetsi yokhayokha monga makina olowera vs. mitundu yambiri yochita nawo masewera olimbitsa thupi monga poker) ndi maziko osonkhezera (mwachitsanzo, kuthawa malingaliro osayenerana ndi machitidwe osaka malingaliro ; onani kuwunika kwa Raylu ndi Oei 2002,, zomwe zilipo sizingafanane ndi kuchuluka kwa akazi. Chifukwa chake, izi zikuyenera kufotokozedwanso ngati otchova juga achikazi angawonetse ziganizo zosiyanasiyananso pakupanga zisankho monga amiseche achimuna mu phunziroli.

Mfundo yosinthira maphunziro amtsogolo ndi kuchuluka kwa maphunziro a juga omwe aphatikizidwa mu kafukufukuyu (n = 14). Ngakhale kukula kwamagulu kunali kofanana ndi maphunziro am'mbuyomu a fMRI (Crockford et al., 2005, Reuter et al., 2005, Thomsen et al., 2013 ndi Balodis et al., 2012) ndipo odwala anali odziwika bwino, zikadakhala zabwino kuphunzira gulu lalikulu. Zowonjezera zina zimaphatikizapo njira yolankhulirana pakati pa zochitika zosangalatsa. Popeza kutchova juga mwachangu komanso mosasunthika kunayikidwa patsogolo, tidasankha kutulutsa zochitikazo, osatinso nthawi yoyeserera pakati pawo, ngakhale panali ITI ya 1.2 s pakati pagawo lililonse lopanga zisankho ndi chiwonetsero chachikulu kusowa kwa jitter pano kungathandizire kuti sitinapeze kusiyana pakati pamagulu munthawi yoperekera ukulu.

Mwapang'onopang'ono, tikuwonetsa kuti dorsal cortico-striatal network yomwe ikukhudzidwa ndi zochitika zothandizira kuchitapo kanthu - ikuwonetsa kukhudzika kwakukulu pakuwonjezeka kwambiri pa kutchova njuga. Mbiri yoyeserera ya U ku DLPFC ndi precuneus inali yokhudzana ndi kuchuluka kwa kutayika kwakanthawi kogwirira ntchito njuga komanso kuuma kwa njuga zamatenda. Zotsatira izi zimalimbikitsa kufufuza kwamtsogolo kuti zikuthandizire chidwi cha neuroimaging kuchokera pakulipiritsa kwapadongosolo mpaka kumadongosolo azisamba a dortal cortico-striatal in gological pathological.

Kuvomereza

Tikuthokoza ndi mtima wonse onse omwe atenga nawo mbali chifukwa cha nthawi yawo komanso Danish Center ya Ludomani chifukwa chokhazikitsa gulu la anthu otchova juga. Tikuthokoza Sid Kouider chifukwa cha ndemanga zothandiza pamwambapa ndi Christian Buhl potithandiza pa kusonkhanitsa deta. Ntchitoyi idathandizidwa ndi Danish Council for Independent Research in Social Sayansi kudzera pa ndalama zoperekedwa ndi Dr. Ramsøy ("Chisankho Neuroscience Project"; perekanso. 0601-01361B) ndi Lundbeck Foundation kudzera mu Zopereka Zabwino ("ContAct"; perekani. R59 A5399) kwa Dr. Siebner. Ntchito yochitidwa ndi Dr. Gelskov ku Laboratoire de Science Cognitives et Psycholinguistique imathandizidwa ndi zopereka za ANR (ANR-10-LABX-0087 ndi ANR-10-IDEX-0001-02). Scanner ya MR idaperekedwa ndi Simon Spies Foundation.

Zowonjezera A. Zowonjezera

Zowonjezera

Thandizani ndi mafayilo a DOCX

Zosintha

Zothandizira

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