Dopamine Agonists Dhimista Dareenka Qiimaha Kortex Orbitofrontal: Dareenka Khamaarka Qaaxada ee Cudurka Parkinson? (2009)

Neuropsychopharmacology. Qoraaga qoraaga; waxaa laga heli karaa PMC 2010 Dec 1.

Loo soo daabacay foomka ugu dambeeyey ee la sameeyay:

Neuropsychopharmacology. 2009 Dec; 34 (13): 2758 – 2766.
Lagu daabacay internetka 2009 Seb 9. doi: 10.1038 / sj.npp.npp2009124

PMCID: PMC2972251

GANACSIGA: CAMS1534

Thilo van Eimeren, 1,2,3 Bénédicte Ballanger, 1,3 Giovanna Pellecchia, 1,3 Janis M Miyasaki,2Anthony E Lang, 2 iyo Antonio P Strafella1,2,3, *

Macluumaadka qoraaga ► Xuquuqda daabacaadda iyo macluumaadka Shatiga ►

Nooca daabacan ee daabacan ee daabacaadda ayaa lagu heli karaa bilaash Neuropsychopharmacology

Eeg qoraalada kale ee PMC in culayskan maqaalkii la daabacay.

aan la taaban karin

Hanuunnada neerfaha ee qamaarka xanuunnada si wanaagsan looma fahamsana. Waxaa suuragal ah in lagu kasbado fahamka saameynta daawada ee habka abaalmarinta bukaanka qaba cudurka cudurka Parkinson (PD). Daaweynta loo yaqaan 'dopamine agonists' (DAs) waxay la xiriirtay khamaar cudurada ku dhaca bukaannada PD. Si kastaba ha noqotee, sida DAs ugu lug leeyahay horumarinta qaabkan balwadda lama oga. Waxaan tijaabinay mala awaalka ah in kicinta tonic ee dhakhaatiirta dopamine ay si gaar ah u qadarineyso nidaamka abaalmarinta dopaminergic adoo ka hortagaya hoos u dhaca ku dhaca gudbinta dopaminergic taasoo ku dhacda jawaab celin diidmo ah. Adigoo adeegsanaya sawir gacmeed muuqaal magnetic magnetic, waxaan bartay bukaanka PD inta lagu gudajiray sedex kalfadhi oo ah howl abaalmarin macquul ah si isdaba joog ah: dawada ka dib, daaweynta levodopa (LD), iyo kadib qiyaasta u dhiganta ee DA (pramipexole). Maxkamad kasta, qiimeynta saadaalinta abaalmarinta abaalmarinta waxaa lagu soo qaatay iyadoo la adeegsanayo natiijada, saamiga, iyo itimaalka. Pramipexole wuxuu si gaar ah u beddelay waxqabadka kortex orbitofrontal (OFC) laba siyaabood oo labadoodaba xiriir la leh khatarta kordhaysa ee qaadashada howlaha ka baxsan magnetka. Dhaqdhaqaaqyada ay ka soo baxaan natiijooyinka guud ahaan way ka sarreeyeen marka loo eego pramipexole marka la barbar dhigo LD ama dawada kabaxday. Intaa waxaa sii dheer, kaliya pramipexole ayaa si weyn hoos ugu dhigay xiriirinta tijaabada ah ee tijaabada ah iyadoo lagu qiimeeyo qiimaha qaladka saadaalinta. Daraasad dheeri ah ayaa laga soo saaray in tan ay sababtay khalkhalka liita ee tijaabooyinka khaladaadka xun ee saadaalinta abaalmarinta. Waxaan soo jeedineynaa in DAs ay ka hortagto joojinta gudbinta dopamine-ka sidaas darteedna ay curyaamiso saameynta xoojinta xun ee guuldarro. Natiijooyinkayaga la soo saaray ayaa kor u qaadaya su'aasha ah in khamaarka cudurada faafa uu qeyb ka noqon karo awoodda daciifka ah ee OFC si loo hago dabeecadda marka ay la kulmaan cawaaqib xumo.

Keywords: fMRI, jahwareerka xakameynta, dopamine agonist, abaalmarin, qabatin, xoojin

HORDHAC

Khamaarista - waa waqti aan dhib lahayn oo dadka badankood — waxay noqon karaan dabeecad qabatin ama dabeecad waxyeelo leh oo ku saabsan khamaarka jireed (PG). Si la mid ah qabatinka maandooriyaha, PG wuxuu leeyahay astaamo dulqaad, ka-tagid, ama ka-hortag (Ururka cilmi-nafsiga ee Mareykanka, 1994) waxaana badanaa loogu yeeraa 'qabatinka dabeecadda' (Potenza, 2008). In kasta oo PG, oo la mid ah qabatinka maandooriyaha, uu la xiriiray wax ka beddelidda nidaamka abaalmarinta dopaminergic, matalaadda qiimaha, iyo ka jawaab-celinta (Reuter et al, 2005; Steeves et al, 2009; Volkowet al, 2009), fikradaha waxqabadka neerfaha ee cudurka maskaxda ee 'PG' ayaa wali si fiican loo fahmay. Wadada loo maro fahamka PG, qadarin muuqata oo ku saabsan saameynta daawada ee nidaamka abaalmarinta ee bukaannada qaba cudurka cudurka Parkinson (PD) ayaa noqon kara astaan muhiim ah. Luminta ku-faafinta postpal dopaminergic ee PD waxay la xiriirtaa dabeecadda qaadashada halista ka hooseysa (Ragonese et al, 2003; Tomer iyo Aharon-Peretz, 2004). Si kastaba ha noqotee, bilawga daaweynta bedelka dopamine waxay la xiriirtay horumarinta PG (Seedat et al, 2000; Darawalka-Dunckley et al, 2003). In kasta oo, ilaa iyo imminka, xog-wareedyo aan ku filneyn oo waqti dheer la heli karo oo laga helayo talo bixin gaar ah oo daaweynta ah (dib u eegis eeg Galpern iyo Stacy, 2007), daraasadihii ugu dambeeyay waxay muujinayaan in khatarta ah in la sameeyo PG ay si gaar ah u korodho marka lagu daaweeyo agonists dopamine agonists (DAs) marka loo barbar dhigo daweynta la'aan DAs (Voon et al, 2006; Pontone et al, 2006; Weintraub et al, 2008). Isku soo wada duuboo, saamaynta qaadashada ayaan laga helin guud ahaan dadka bukaanka ah, halka bukaan-socodka shaqsiyeed ee PG, xaddiga qiyaasta daawada laga dheehan karo waa la arki karaa (Voon et al, 2006;Weintraub et al, 2008). In kasta oo sababaha weli go'aan loo gaarin, haddana waxaan u qaadaneynaa in, si loo horumariyo PG, kicinta dawooyinka guud ee wadaagga ah ee ku jirta dabeecadda aasaasiga ah ee bukaanka shaqsiga ah. Daraasadani waxay diiradda saareysaa suurtogalnimada dawooyinka guud ee dawooyinka dabiiciga ah iyadoo la baranayo cilladaha aan caadiga ahayn ee loo yaqaan 'DA-kax aan-ahayn ee abaalmarinta lagu sameeyo bukaanka PD.

Moodooyinka kombiyuutarka ee xisaabinta abaalmarinta, khaladka saadaalinta abaalmarinta (RPE) wuxuu matalaa farqiga u dhexeeya abaalmarinta la filayo iyo sida dhabta ah ee la helay (Sutton iyo Barto, 1998). Sii-daynta Dopamine ee neerons mesolimbic waxay ka tarjumaysaa qiimaha RPE si aad u wanaagsan. Khaladaadka togan ee saadaalinta abaalmarinta (sida 'ka wanaagsan wixii la filan karay') waxaa soo gudbiyay fadeexad wejiga 'dopamine neuron rasaas'Hollerman et al, 1998; Waelti et al, 2001). Dhanka kale, khaladaadka xun ee saadaalinta abaalmarinta (sida 'tan xun-wixii la filan karay') waxay horseedaan in la joojiyo wajiga firidhiga ee dopamine neuron (Schultz, 2002; Bayer et al, 2007). Sida DAs, oo ka duwan levodopa (LD), oo si kadis ah u kicineysa dhakhaatiirta dopamine, waxaan soo jeedineynaa in DAs laga yaabo inuu ka hortago joojinta gudbinta dopamine-ka sidaas darteedna uu curyaaminayo saameynta xoojinta xun ee luminta. In kasta oo saameyntan neurobehavioral ay si fiican u kordhineyso halista horumarinta PG, caddeyn toos ah oo xiriirkan ah ayaa jirta.

Halkan, waxaan ku baranay bukaannada PD iyada oo aan lahayn dawada beddelka dopamine (OFF), ka dib LD, iyo daaweynta Da 'ka dib markii ay ku ciyaarayeen ciyaarta' roulette 'inta lagu gudajiray muuqaalka firfircoonaanta magnetic (fMRI). Adeegsiga hawlo la mid ah, daraasadihii hore ee fMRI waxay si guul leh u qaabeeyeen waxqabadka nidaamka abaalmarinta dopaminergic adoo u adeegsanaya qiimeynta RPE sidii diiwaangeliyaha (Knutson et al, 2001; Yacubian et al, 2006). Waxaan xiiseyneynay (i) inaan ula jeedno isbeddelada dhaqdhaqaaqa ka dib ra'yi-celintii, iyo (ii) xiriirinta tijaabada-tijaabinta ah ee lagu qiimeeyo RPE -da oo ah tusaha howsha abaalmarinta maxalliga ah. Ka fogaanshaha saameynta dabeecadda ee jahwareersan inta lagu guda jiro fMRI, waxaan ku qiimeynay qadka qatarta qaadashada qadka tooska ah.

Iyada oo ku saleysan fikirka ah in DA ay ka hortagto gudbinta dopaminergic hoos u dhaca ee leh qiyamka RPE ee aan fiicnayn, waxaan saadaalinay in si ka duwan sida loo yaqaan 'PA iyo LD, DAs ay waxyar u kordhineyso celceliska firfircoonida iyo in ay quusto nidaamka abaalmarinta dhanka RPE. Waxaan sidoo kale qiyaasahay in abaalmarinta diidmada ay la xiriirto kororka dabeecadda qaadashada khatarta ah ee hawsha khadka tooska ah.

MATERIALS AND METHODS

Ka qaybgalayaashu

Sideed bukaan oo gacanta midig ah (da ', micnaheedu yahay ± SD: 56 ± 9 sano) oo leh heerka hore ee PD (mudada cudurka, waxaa loola jeedaa ± SD: 4 ± 3 sano) ayaa lagu qoray daraasadda. Daawooyinkooda anti-Parkinsonian waxaa ka mid ahaa isku darka LD (qiyaasta maalinlaha ah, oo macnaheedu yahay ± SD: 594 ± 290 mg) iyo pramipexole (qiyaasta maalinlaha ah, waxaa loola jeedaa ± SD: 2.3 ± 1.1 mg). Waxaan dooranay bukaannada aan taariikh u lahayn xaaladaha qalliinka maskaxda ku dhaca (oo ay ka mid yihiin niyad-jabka, waallida, ama wixii khalkhal dhanka xakameynta ah). Qiimaynta Beck depression II (waxaa loola jeedaa ± SD: 7 ± 5), Qiimaynta Montreal Cognitive Assetment (waxaa loola jeedaa NUM SD: 27 ± 2), iyo Barratt impulsivity Scale-11 (waxaa loola jeedaa NUM SD: 71 ± 10) ayaa loo isticmaalay in lagu qiimeeyo covert niyad-jabka, daciifnimada garashada, iyo dareenka shaqsiyeed, siday u kala horreeyaan. Dhammaan maaddooyinka oo dhan waxay bixiyeen oggolaansho qoraal ah oo la oggol yahay si ay uga qaybgalaan. Daraasada waxaa ogolaaday guddiga anshaxa cilmi baarista ee shabakada caafimaadka jaamacada, Toronto.

Bukaanka waxaa lagu bartey sedex kalfadhi oo ku saabsan fiidkiyo kaladuwan (1 – 3 toddobaad ka fog). Daaweynta bedelka Dopamine ayaa la hayey ugu yaraan 12 saac kahor kulan kasta. Amarka isku midka ah, bukaanka ayaa la bartay marka laga reebo dawada (OFF), kadib maaraynta afka ee LD (100mg LD + 25mg benserazide), ama qiyaasta u dhiganta ee DA (1mg pramipexole) (Jaantus 1a). Bukaan-socodka waxaa la geeyay hawl khatar-qaadis ah 37 ± 7 min ka dib maareyn daroogada, 21 NUM 5 min ka dib, qeybta mootada ee Unugga PD Rating Scale waxaa qiimeeyay khabiiro ku takhasusay cilladaha dhaqdhaqaaqa iyo 13 ± 2 min, gadaal xisaabinta maaliyadeed ee maaliyadeed. hawsha ayaa la qabtay intii lagu jiray dhacdada la xiriirta fMRI.

Naqshadeynta waxbarasho. (a) Ka dib markay habeennimadii ka baxaan dawada anti-Parkinsonian, bukaanada qaba cudurka loo yaqaan Parkinson's PD (PD) ayaa loo bartay si nidaamsan: dawada kabax (Off), ka dib daaweynta levodopa (LD), iyo kadib qiyaasta u dhiganta pramipexole ...

Qaadashada Khatarta Khatarta

Qaadashada Ballon Analog ee Qaadashada Halista ah waa cabiro fikir ahaan ku dhisan oo ah dabeecadaha qaadashada halista ee kaqeybgalayaashu ay ku badin karaan ama lumin karaan lacag (White et al, 2008). Kaqeybgalayaashu waxay kor u qaadayaan buufin lagu soo bandhigay shaashadda iyagoo gujinaya jiirka kombiyuutarka. Bamka kasta, miiska shaashadda wuxuu ku kordhayaa sentiyo 5. Ka dib tiro aan la saadaalin karin oo matoorro leh, buufinku wuu qarxi karaa, taasoo dhalisay luminta lacagtii ku ururtay miiska. Kaqeybgalayaasha soo saaray bambooyin badan (bambooyin celcelis ahaan la habeeyay) ayaa loo qaddariyo inay u janjeeraan inay galaan khataro (Lejuez et al, 2002). Waxaan ku tijaabinnay saameynta dawooyinka daraasadda kala duwanaanta (ANOVA) iyadoo la adeegsanayo STATISTICA ee Windows 6.0 (www.statsoft.com).

Hawsha Abaal-marinta ee suuragalka ah

Hawshan kumbuyuutareedku wuxuu u egyahay ciyaar roulette (Jaantus 1b). Ka dib markii aad ku orday wareegsan wareegga wareega ee wareega, kubad ayaa hoos u dhacday oo joogsatay 1 ee jeebka midabada 16 (4 mid kasta: jaale, casaan, buluug, cagaar). Kaqeybgalaha ayaa ku qiyaasay midabka jeebka kubadu inuu ku dhex istaagi lahaa isagoo dooranaya mid ka mid ah afarta ikhtiyaar ee: Kala badh tijaabooyinka, waa inuu kala doortaa afarta midab ee guuleysta (itimaalka guuleysiga, 0.25); qeybtii kale, waa inuu kala doortaa afarta sedex geesood ee midabada guuleysatey (itimaalka guuleysiga, 0.75). Tiirka tijaabada la bixiyay wuxuu ahaa 1 ama 5 doolar Kanada. Barnaamijka kumbuyuutarka wuxuu soo saaray kala-sooc hal-abuur ah ee qeybahaan tijaabinta ah (seddex nidaam oo horay loo sii diyaariyey ayaa loo adeegsaday si aan kala sooc lahayn). Go'aanka kaliya ee tijaabada ee ka-qaybgalaha ayaa ahaa ikhtiyaarka la dooran karo. Haddii kubaddu ay ku joogsato jeebka rinjiga mid ka mid ah midabada guuleystey, saami ayaa lagu guuleystay. Haddii kale, waa lumay. Si meesha looga saaro kala-duwanaanta sababta oo ah fursadda, isku xigga guusha iyo guuldarradu sidoo kale waa la sii daayay oo lagu daray qoraalka qoraalka ee kulankaas (barnaamijka wuxuu kubbadda ka dhigtay in kubaddu jeebka ka gasho). Isku dheelitirka bilowga wuxuu ahaa $ 20. Qaabka hore ee tijaabada ah ayaa lagu soo bandhigay saami (ama $ 1 qalin ama $ 5 biil) iyo xulashooyinka 2 s (Jaantus 1b, kor). Go'aanka waa in lagu gaadhaa gudaha soo socda ee 3 s (oo lagu muujiyey isugeynta tirada). Hadaan badhan la soo riixin intii lagu jiray wakhtigaas, barnaamijka wuxuu si aan kala sooc lahayn u xulay hal ikhtiyaar. Barnaamijku wuu istaagay haddii taasi dhacday seddex jeer oo isku xigta. Qeybta labaad ee tijaabada waxaa lagu soo saaray giraangiraha wareegaJaantus 1b, 2nd xaga sare). In kasta oo kubbaddu ku soconeyd agagaarka (8 s), saqafka ayaa lagu soo bandhigay bartamaha giraangiraha; xulashada la doortay iyo isku-dheelitirka ayaa lagu soo bandhigay ka hooseeya giraangiraha, iyo 0.5 s ka dib markii kubbaddu istaagtay, natiijada waxaa lagu soo bandhigay (3 s) bartamaha taayirka (calaamadda aljebrada iyo qadarka; khad cagaaran oo guuleysta; qalin casaan ah oo guuldarro ah) dheelitirkuna isu beddelay si isku mid ah (Sawirro 1b, 3rd xagga sare). Hadhaaga ugu dambeeya waxaa lagu bixiyay lacag caddaan ah.

Bukaannadu waxay ciyaarteen ciyaarta (Java 2 Platform Standard Edition 5.0; Sun Microsystems Inc, Santa Clara, CA) inta lagu gudajiray fMRI xiritaanka gulukoolada fiidiyowga waxayna muujineysaa go'aamada iyagoo riixaya badhamada sanduuqyada jawaabta ee la dhigo gacan kasta (sanaaduuqyada iyo gogolyada, Teknolojiyada Resonance, Los Angeles, CA, USA). Iyada oo taxane la sii qorsheeyay ee tijaabooyinka 280, dheelitirka $ marna kama uusan hoos dhicin 0 iyo dheelitirka ugu dambeeya wuxuu ahaa $ 8, $ 10, ama $ 12 (isbarbar dhig lagu sameeyay fadhiyada). Si looga fogaado daalka, ciyaarta waxaan ugu kala qaybinnay sagaal orod, mid walboo soconaya oo ah 9 min. Feejignaanta waxaa lagu qiimeeyay iyadoo la duubayo waqtiyada jawaabta iyo waxyaabaha laga bixi karo.

Moodellada RPE

Daraasadaha FMRI ee ku saabsan ka shaqaynta abaalmarinta, qiimayaasha RPE waxaa loo isticmaalay in lagu daydo xogta FMRI (O'Doherty et al, 2003; Yacubian et al, 2006), adoo u qaadanaya xiriir toosan oo udhaxeeya qiyamka RPE iyo heerka dhiiga-oksijiinka heerka-ku saleysan (BOLD) astaamaha aagaga gudashada maskaxda. Anagoo adeegsanayna howlo leh jaangooyooyin go'an, cad oo macquul ah iyo dusha sare, waxaan ku muujin karnaa qiimaha saadaalinta abaalmarinta sida soosaarka xisaabta saamiga iyo itimaalka guusha. Qiimaha RPE wuxuu matalaa faraqa udhaxeeya natiijada natiijada iyo qiimaha saadaalinta abaalmarinta (qiimaha natiijada − qiimaha saadaalinta abaalmarinta = qiimaha natiijada '(saamiga × itimaalka guusha)) ()Jaantus 1c).

fMRI Baaritaanka iyo Falanqaynta Xogta

Iyadoo la adeegsanayo iskaanka '3 T GE MRI scanner', echo planar T2 * sawirro miisaan culus leh oo la barbardhigo BOLD ayaa la helay XXX kasta s s sagaal meelood oo leh mugga 2.23. Muuqaalka-muuqaalka waxaa loo qaabeeyey inuu daboolo maskaxda hore, dhexda, iyo maskaxda. Cabbirka waxaa ku jira xaleefyo ah 245 oblique (30 mm, farqiga u jirin), cabbirrada duulimaadka diyaaradda waxay ahaayeen 3mm × 2 mm. Sawirada waxaa lagu farsameeyay oo la falanqeeyay iyadoo la isticmaalayo barnaamijyada barnaamijka 'SPM2' (http://www.fil.ion.ucl.ac.uk/spm). Labadii baaritaan ee ugu horreeyay ee socod kasta ayaa loo tuuray si loogu oggolaado in magnetization-si joogto ah loo sameeyo. Sawirada haray ayaa loo habeeyay sawirka koowaad oo si isdaba joog ah loogu qaabeeyey qaab muunad ah (MNI 305). Sawirada caadiga ah waxaa si isdaba joog ah loogula dhaqmay koronto Gaussian ah oo ah 8mm ugu badnaan nus-badh ah si loo yareeyo kala duwanaanshaha isugeynta anatomy iyo u suurtagelinta adeegsiga aragtida qormooyinka Gaussian.

Falanqaynta heerka koowaad waxaa loo sameeyay si gooni gooni ah maado kasta iyo gobol kasto oo dawooyin ah kuna saleysan moodada guud ee toosan (Friston et al, 1995). Beddelka maxalliga ah ee isbeddelada 'BOLD-signal' waxaa lagu qaabeeyey iyada oo la adeegsanayo dib-u-nooleyaal kala duwan oo loogu talagalay shaashadda (oo la keenay hawlqabadka jawaab-celinta hemodynamic) mid kasta oo ka mid ah dhacdooyinka soo socda: soo bandhigidda saamiga iyo xulashooyinka; badhanka saxaafadda; bilowga kubbada; natiijada. Sida tiirar dheeri ah oo ku jira shaxanka naqshadeynta, waxaa loola jeedaa qiyamka RPE ee la saxay ayaa la soo saaray iyada oo ah kalkaaliye gaar ah oo sharxaya isbeddelka BOLD-signal inta lagu jiro natiijada. Sawirro iska soo horjeeda oo keli ah (mawduuc kasta, xaalad dawadeed, iyo kalfadhiga) ee isbarbardhiga tooska ah ee ka tarjumaya natiijooyinka cad ee la keenay isbeddelka BOLD (mid ka mid ah diiwaan-galiyaha munaasabadda) iyo isku-dheelitirka isbeddelkan oo leh qiime RPE ah (mid ka mid ah diiwaan-hayihii RPE) ayaa galay tallaabooyin-soo-celinno kala duwan oo ANOVAs leh arrimaha 'mowduuca' (heerarka 8) iyo 'daawooyinka' (heerarka 3; Off, LD, DA) si loo sameeyo isbarbardhiga codka-caqliga ah ee isbeddelka calaamadaha BOLD-maxalliga ah. Waxaan tixgelinay heerka ugu hooseeya ee tirakoobkap<0.05 (ka dib sixitaanka heerka baadhista beenta ah) inay muhiim tahay (Genovese et al, 2002).

Intaa waxaa sii dheer, waxaan baarnay macquulnimada dabeecadda ee saamaynta lagu arkay falanqaynta kor ku xusan. Gaar ahaan, waxaan dooneynay inaan aragno bal in waxyeellada 'DA' ay la mid tahay dabeecadda qaadashada halista ee magnet-ka ee qatarta Ballon-analog. Si taas loo gaaro, waxaan soo bandhignay dhibco shaqsi ah ee ka-baxsan magnet-ka halista ah (bambooyin isku-habeysan oo isku-hagaajin ah) oo ah isuduwaha dhaqdhaqaaqa ee labada ANOVAs (hal falanqeyn hal qiimeyn, is-dhexgalka arrinta 'dawada').

Natiijooyinka

Dhibcaha Mootada iyo Dhaqanka

Sidii la filaayay, buundooyinka mootada ee Iskeelka Qiimeynta PD oo la wanaajiyey labadaba LD (19.6 ± 7.9) iyo DA (21.5 ± 9.2) marka la barbar dhigo OFF (27.5 ± 9.9) t-tests: DA vs. DAN p<0.01; LD vs. DAN p<0.01; DA vs. LD p= 0.16). Daawada wax saameyn ah kuma yeelan talaabooyinka feejignaanta ee howlaha FMRI. Wakhtiyada jawaabta (waxay ka dhigan yihiin ± SD: XXXXX ± 1270 ms; LD 300 ± 1329 ms; DA 419 ± 1250 ms) iyo jawaabaadka (waxay ka dhigan tahay ± SD: XEX 349 ± 9.75 ms; LD 5.2 ± 9.25 ms; DA 5.6 ± 9.75 ms; ) kama duwana xaaladaha u dhexeeya (waqtiyada jawaabta: F (3.1, 2) = 21, p= 0.90; Tixraacyada jawaabta: F (2, 21) = 0.03, p= 0.97). Daawooyinka sidoo kale si weyn umay saameynin natiijooyinka halista qaadashada ee Ballon analog halis-qaadashada ah F (2, 21) = 0.2, p= 0.98; celcelis celcelis ahaan bamgareynta la habeeyay ± SD: XADKA 37.6 ± 11.4ms; LD 38.1 ± 14.4ms; DA 38.8 ± 10.8ms.

Waxqabadka Jawaab-celinta

Soo bandhigida natiijooyinka per se isbeddelo ayaa laga sameeyay signalka BOLD ee kujira dhowr shabakadood. Kordhinta ayaa lagu arkay shabakad laba geesood ah oo iskuxiran (cortex visual: x= −18 / 18, y= -93, z= 6 / 0 mm; cerebellum: x= −30 / 30, y= −66 / −57, z= −27 / −21 mm; putamen: x= −21 / 24, y= −3 / 6, z= −3 / 0 mm; aagga muruqyada: dillaacyada: x= −12 / 12,y= 6 / 8, z= 45 / 44 mm; kiliyaha 'preventtor premotor cortex': x= −55 / 45, y= 3 / 6, z= 45 / 36 mm). Hoos udhac ayaa laga helay cortex-ka dusha sare ee dhabbaha kalfoofka 'corpus callosum'x= 0,y= 39, z= 0 mm) iyo kiliyaha hore ee hordhaca (x= 0, y= 57, z= 0 mm).

Markaad fiirineyso saameynta daawada, saameyn weyn oo ku saabsan isbeddelka sababay isbeddelka-BOLD-signal wuxuu kaliya laga helay kortex orbitofrontal bidix (OFC) (Shaxda 1). T-tests waxay muujisay in celceliska celceliska BOLD ka dib natiijooyinku ay ka sarreeyeen xaalada DA marka loo eego heerka LD ama OFF (Shaxda 1). Falanqaynta wadahadalada, xaaladda DA ayaa si weyn u xoojisay xiriir wanaagsan oo ka dhexeeya celceliska tirada bambooyinka la hagaajiyay iyo isbeddelada muuqda ee ay keentay BOLD-signal ee bidixda bidix ee OFC (Shaxda 1).

Saamaynta Pramipexole (DA) ee ku saabsan Dhaqdhaqaaqa Jawaab-celinta

Geedi socodka Abaalmarinta

Xidhiidh adag oo adag oo lala yeesho tijaabinta tijaabada ah ee RPE-da ayaa laga helay aagagga aagagga bartilmaamedka ah ee habdhiska dhiig-yaraha ee mesolimbic (dopaminergic system)Jaantus 2a iyo b; Shaxda 2). Qeybta ventral striatum, labada dawooyinka dopaminergic (LD / DA) ayaa si isku mid ah u naaqusay abaalmarinta maxalliga ah marka loo barbar dhigo OFF (Jaantus 3a iyo b; Shaxda 2). Dhanka OFC, si kastaba ha noqotee, kaliya DAs aad ayey u yareeyeen abaalmarinta maxalliga ah (Jaantus 3c iyo d; Shaxda 2). Falanqaynta covariance oo leh natiijooyinka qaddarka qaddarka qadka tooska ah waxay muujisay in xaaladda DA ay si weyn u xoojisay xiriir xun oo ka dhexeeya celceliska tirada bambooyinka la hagaajiyay iyo abaalmarinta maxalliga ah ee bidix ee bidixda OFC (Shaxda 2).

Jaantuska 2

Dib-u-Abaal marin haynta iyada oo aan dawo la helin (DAMBAR). (a) Tusaalaha xiriirka ka dhexeeya celceliska jawaab celinta BOLD inta lagu gudajiro natiijada iyo abaalmarinta saadaalinta saadaalinta (RPE) qiimeynta qeybta maareynta maaddada. (b) Falanqaynta kooxda: xiriir wanaagsan oo togan ...

Jaantuska 3

Saamaynta daawada dopaminergic ee ku saabsan hawsha abaalmarinta. (a) Qiyaasta isdhaafka iyo 90% kalsoonida dhexdhexaadka ee cabudhinta qiyamka saadaalinta tijaabada ee tijaabada ah (RPE) ee marinka wareega (x= -9,y= 21, z= −6 mm). DAN, oo aan lahayn dopaminergic ...

Saamaynta Daawooyinka Dopaminergic ee ku Saabsanaanta Abaalmarinta

Isku soo wada duuboo natiijooyinka OFC labadaba - oo ah kordhinta macnahiisu waa jawaab celin kadib jawaab celintii iyo tirtiriddii iswaafaqsanayd ee qiimayaasha RPE-qof ayaa soo gabagabeyn kara in weynaanta korodhka laxiriira DA ee dhaqdhaqaaqa OFC ay kuxirantahay qiimaha RPE. Marka la eego tijaabooyinka qiimayaasha RPE ee aan fiicnayn, DAs waxaa laga yaabaa inay kordhisay dhaqdhaqaaqa OFC illaa xad ka badan tijaabooyinka leh qiyamka RPE ee togan. Si loo xaqiijiyo fikirkaan, waxaan sidoo kale baaris ku sameynay macnaha jawaabihii keenay natiijooyinka ee la xiriira qiyamka RPE ee qaabka guud. Si kastaba ha noqotee, maaddaama isku-duwayaasha farqiga ugu weyn ee labada isbarbardhiggu aysan dhammaantood ahayn isku-darka (firfircoonida ka dhalata natiijada: z= −18; Abaalmarinta abaalmarinta: z= −3), waxaan ka soo saarnay qiimayaasha macnaha min halbeega 10mm, ee udhexeysa labada maxima (x= -24, y= 42, z= −10). Marka loo eego DAMBURKA, DA waxay si gaar ah u kordhisay dhaqdhaqaaqa orbitofrontal ee tijaabooyinka qiimeynta RPE ee aan wanaagsaneyn (Jaantuska 4).

Jaantuska 4

Isbeddellada BOLD-signal ee bidix dambe ee orbitofrontal kiliyaha (10mm sphere xudunta u ah) x= -24,y= 42, z= −10) ee laxiriirta abaalmarinta qiyamka saadaalinta iyada oo aan la isticmaalin dawada (OFF) iyo kadib pramipexole (DA). Marka loo eego OFF, DA gaar ahaan ...

DHIBAATOOYINKA

Raadinta ugu weyn ee daraasaddeena ayaa ah in kicinta tonic dopaminergic kicinta ah ee DAs ee bukaannada PD ay si gaar ah u yareeyeen abaalmarinta hawlgalka ee qaybta dambe ee 'OFC' iyadoo la kordhinayo waxqabadka inta lagu jiro khaladaadka xun ee saadaalinta abaalmarinta. Aqoonteenna, tan waxay metelaysaa caddeyntii ugu horreysay ee taariikheed ee ahayd in DAs laga yaabo inuu hoos u dhigo xoojinta taban ee barashada ku saleysan jawaab-celinta iyadoo laga hortagayo hoos u dhac ku yimaadda waxqabadka synaptik ee ku dhaca khaladaadka xun ee saadaalinta abaalmarinta. Arinta daran, helitaankani wuxuu ahaa mid dawooyin gaar ah leh, maadaama looma arag ka dib markii maamulka LD-kaas oo taa bedelkeeda la rumeysan yahay inuu kor u qaadayo kicinta firfircoonida ee dhakhaatiirta dopaminergic. Fikradan ayaa ku soo beegmaysa iyada oo si gaar ah u kordhaysa khatarta si loo horumariyo PG bukaannada PD-da laga daaweeyayVoon et al, 2006; Pontone et al, 2006; Weintraub et al, 2008).

Korjoogteynteena waxay la jaanqaadeysaa moodooyinka hadda ee naqshadeynta iyo xogaha saxda ah ee barashada xoojinta ku tiirsanaanta dopamine (Frank et al, 2004, 2007; Cools et al, 2006). Bukaannada PD ee aan la daaweyn waxay muujiyeen waxbarasho ku saleysan jawaabcelin taban oo hawlo kala duwan ah (Frank et al, 2004; Shohamy et al, 2004; Cools et al, 2006). In kasta oo natiijooyinka qaar ay muujinayaan in bukaannada aan la daweyn laga yaabo inay si gaar ah ugu liidato xagga barashada ka soo-celinta togan (Frank et al, 2004; Cools et al, 2006), cadaymo la taaban karo oo ku saabsan saamaynta xun ee daaweynta bedelka dopamine ee barashada jawaab celinta taban waxay umuuqataa mid joogto ah (Cools et al, 2006; Frank et al, 2007). Marka loo eego moodalka kombiyuutarka ee ay soo jeediyeen Frank iyo asxaabtiisa, jabinta wejiyada ee dopamine ka dib abaalmarino lama filaan ah waxay ku kacaysaa saameyn xoojin ah iyagoo dhiirigelinaya aqbalayaasha D1 (Frank et al, 2004). Dhanka kale, ciqaab lama filaan ah ama abaalmarin la celiyay ayaa horseedaya xoojin taban iyadoo hoos loo dhigayo ku-meel-gaarnimada calaamadaynta D2. Joogteynta kicinta tonic ee dhakhaatiirta daawada dopamine-sida daawada DA - sidaas awgeed waxay kor u qaadi kartaa saameynta dhexdhexaadinta D1 (tusaale xoojinta togan). Dhanka kale, waxay ka hortegi kartaa hakinta calaamadaha D2 ee calaamadaha waxayna taasi u horseedi kartaa curyaaminta barashada falcelinta xun. Natiijooyinkayagu waxay tilmaamayaan saameyn weyn oo dambe, taas oo si fiican loogu sharixi karo xulashada D2 / D3 ee pramipexole (Seeman, 2007). Xaqiiqdii, firfircoonida natiijada ee OFC way ka sarreysay DA oo saameynta kobcinta waxay umuuqatay inay ka weyneyd khasaaraha lama filaanka ah marka loo eego guulaha aan la fileynin, taas oo yareynaysa isku xirnaanta qiyamka RPE. Si kastaba ha noqotee, xaqiiqda ah in qaabkeennu ka duwan yahay midka loo isticmaalay daraasadaha Frank iyo saaxiibbada la shaqeeya waxay matalaan god muhiim ah (Frank et al, 2004, 2007). Waxaa intaa dheer, tixgalinta aragti ahaan ee kale waa in kicinta tonic ee astaamaha kaydiyayaashu ay yareyn karaan isku xirnaanta qiimaha RPE iyadoo la xakameynayo rasaas ka imaatinka nebironka dopaminergic neurons.

Natiijooyinkayagu waxay tilmaamayaan dhowrista qaraabada ee hawlgalinta abaalmarinta bukaannada PD ee aan la dawayn, halka LD iyo DA labadaba ay yareeyeen abaalmarinta hawlgallada marinnada marinnada dhiigga iyo OFC. Tani waxay xaqiijineysaa aragtida ah in daaweynta dopamine bedelka, dib u soo celinta heerarka dopamine ee qeybta muruqa ee loo yaqaan 'dorsal putamen' sidoo kale ay la imaan karto xad gudub xad dhaaf ah oo xagga garashada ah (dorso-med caudate) iyo limbic (ventral striatum, nucleus accumbens) qaybo. (Sawaaxil et al, 2000; Cools et al, 2001; Cools, 2006).

Waxqabadka firfircoonaanta neerfaha ka hor natiijadu ma saameyn ku yeeshay howsha neerfaha ee neuronal-ka ee qiyamka RPE ee gobollada dawooyinka kaladuwan? Maadooyinka caafimaad ahaan yar yari, qofku wuxuu runtii filan lahaa xidhiidh ka dhexeeya dhaqdhaqaaqa marinka kaadida iyo saadaalinta qiimaha. Waa in la ogaadaa, si kastaba ha noqotee, in saameyntani ay aad uga khiyaano badan tahay xiriirka ka dhexeeya RPE (Yacubian et al, 2006). Falanqayn horudhac ah oo ku saabsan xogteena, maanaan ka helin cilaaqaad noocaas ah xaalad kasta oo xagga dawooyinka ah (DAMBUR, LD, DA). Xaqiiqdii, qofku ma qaadan karo inuu cilaaqaadkaasi sii ahaanayo PD. Daraasad dhowaan la sameeyay oo lagu sameeyay bukaannada PD ka dib markay ka baxeen dawada, waayeelka iyo xakamaynta dhalinyarada ee caafimaadku waxay muujiyeen in inkasta oo howsha RPE ay u muuqato mid ilaa xad la ilaaliyay, bukaanada PD iyo kontoroolka waayeelka waxay muujinayaan astaamo saadaal ah oo liita.Aqoonyahanet al, 2007). Marka la eego dabeecadda khaldan ee xiriirkaan kaqaybgalayaasha da'da yar, khasaaraha qaraabadan ee xiriirkaan waayeelka iyo bukaannada PD, iyo xiriir la'aanta noocaas ah daraasaddeena, waxaan u qaadaneynaa in saameynta dammaanad-qaadku ay noqon karto oo keliya tiro aan laga fiirsan karin.

Daraasaddan ayaa sidoo kale laga yaabaa inay saameyn muhiim ah ku yeelato khamaarlayaasha cudurada ku dhaca ee aan lahayn PD.Reuter et al (2005) helay in kala duwanaanta dhaqdhaqaaqa marinka hawada ka dib markii togan vsjawaab celinta maaliyadeed ee taban ayaa ku yaraatay khamaarlayaasha cudurada ku dhaca ee la xiriira kontoroolka caafimaadka qaba. Sida qorayaashu tilmaameen, wali waa in la sii faahfaahiyo, inta ay la egtahay helitaankani wuxuu ka yimid jawaabcelin xasaasi ah iyo wixii ka soo baxa, ama jawaabihii loo adkeeyay ee khasaaraha. Natiijooyinkayaga waxay kor u qaadayaan su'aasha ah in PG lala xiriirin karo awoodda daciifka ah ee OFC si loo hago dabeecadda markii ay cawaaqib xumo la kulmaan.

Sida lagu qeexay hordhaca, waxaa jira laba sababood oo waaweyn oo lagu barbardhigo natiijooyinkayaga kuwa la xiriira kuwa maandooriyaha. Marka hore, shuruudaha baarista ee hadda ee PG iyo isku-daridda maandooriyaha (Ururka cilmi-nafsiga ee Mareykanka, 1994). Midda labaad, dhowr daraasadood oo dhowaan muuqaallo muuqaal ah oo ku saabsan maandooriyaha maandooriyaha ayaa hoosta ka xariiqay doorka muhiimka ah ee wadooyinka mesolimbic dopaminergic (Garavan et al, 2000; Volkow et al, 2004; Goldstein et al, 2007). Qofka qabatinka ah, qiimaha loo nisbeeyay dhacdooyinka qaarkood ama baaqyada ayaa u muuqda in la beddelay (Garavan et al, 2000; Ahmed et al, 2002; Grigson iyo Twining, 2002). Waxaa jira caddayn la taaban karo oo ah in OFC ay dhexdhexaadinayso u qalmida qiimeynta isla markaana ay qayb muhiim ah ka tahay go'aan qaadashada la qabsiga (Tremblay iyo Schultz, 1999; Knutson et al, 2000;Breiter et al, 2001; Elliott et al, 2003; Valentin et al, 2007). Runtii, daraasad dhowaan la sameeyay ee isticmaaleyaasha cocaine ayaa xaqiijisay ku lug lahaanshaha qaybta dambe ee 'OFC' ee tilmaam la'aanta liita ee qiimeynta jawaab celinta (Goldstein et al, 2007). Xakameynta maaddooyinka lagu qiimeeyo guusha sare in ka badan guulaha hoose, halka in kabadan nus maaddooyinka maandooriyaha maandooriyaha ay ku qiimeeyeen guulihii si isku mid ah. Soo helitaankan ayaa si weyn la xiriiriyay dhaqdhaqaaqyo sarreeya, oo aan nidaamsanayn oo lacag loogu talagalay qaybta dambe ee OFC. Natiijooyinkayagu waxay soo jeediyeen in DAs bukaannada PD ay u wareegaan qaybta dambe ee 'OFC' xagga sare, dhaqdhaqaaqyo aan nidaamsanayn ka dib falcelinta maaliyadeed - sahamin si muuqata ugu eg kuwa lagu sameeyay maandooriyaha maandooriyaha.

In kasta oo saameynaha DA ee dhexdhexaadka ku ah shaqada OFC ee dambe ay la xiriirto isbedello qaraabo ah oo ku yimid qaadashada hawsha qadka tooska ah, maamulka pramipexole wax saameyn toos ah ah kuma lahan ah ku yeelan karaan dhaqanka, iyagoo dib u soo celinaya natiijooyinka hore ee tabaruceyaasha caafimaad qabka ah (Hamidovic et al, 2008). Si kale haddii loo dhigo, saamaynta neerfayaasha ee DAs lagama yaabo inay xoog u weynaato inay runtii wax ka beddesho dabeecadda qof kasta. Laakiin maxaa dhacaya, haddii kicinta dawadan ay la falgasho nuglaanta shaqsiga? Hoos udhaca helitaanka karbaashka 'D2 receptors' waa dabeecad la xiriirta qabatinka maandooriyaha (Volkow et al, 1997). Waxa xiisaha lihi, waxaan dhawaan helnay in hoos udhaca helitaanka dhakhaatiirta 'D2 receptors' ay sidoo kale kala soocaan bukaanada PD ee leh PG bukaanka PD ee aan laheyn PG (Steeveset al, 2009). Mid ayaa laga yaabaa inuu qiyaasayo in shakhsiyaadka leh hoos u dhaca cufnaanta soo dhoweynta D2, faragelinta DAs ee barashada 'falcelinta xun ee dhexdhexaadinta' D2. Si kastaba ha noqotee, qofku ma xukumi karo in u nuglaanta shaqsiyadeed ee lagu hormarinayo qabatinka dabeecadda sidoo kale waxay ka timaadaa farsamooyinka neurobehavioral ee aan la xiriirin daawada mesolimbic dopamine. Maqnaanshaha hawl dibedda ah (yacni si xor ah u dhaqdhaqaaqa maskaxda), bukaannada PD ee la kulma astaamaha PG-ga culus ee waqtiga daraasadda waxay muujiyeen sii kordheynta udgoonnada maskaxda ee qaab dhismeedka dopaminergic mesolimbic, laakiin sidoo kale gudaha insula, hippocampus, iyo amygdala (Cilia et al, 2008). Daraasado dheeraad ah ayaa looga baahan yahay aaggan si loo kala sooco sifooyinka saadaalin kara nuglaanta qaab aan caadi ahayn oo neerfaha ah taas oo laga yaabo inay isu beddesho mar haddii PG ay u xoojiso dhaqan ahaan.

Isku soo wada duuboo, waxaan bixinaa cadeymo muujinaya in kicinta tonic ee dhaqaatiirta hore ee daawada dopamine ay dhaawici karto dabeecada xoojinta jirka (gaar ahaan taban) xoojinta qiimeynta iyadoo laga hortagayo hoos udhaca dhaqdhaqaaqa cortical synaptic ee dhaca falcelinta taban. Natiijooyinkayagii soo baxay ayaa kor u qaadaya su'aasha, in PG ay qayb ahaan noqon karto awoodda daciifka ah ee OFC si loo hago dabeecadda marka ay cawaaqib xumo la kulmaan.

Si kastaba ha noqotee, waxaa jira dhowr xaddidan oo daraasadeena ah oo laga yaabo inay caqabad ku noqoto gabagabadayada. Marka hore, marka la eego in natiijada ka soo baxday daraasaddeena ay meteleyso hab dawooyinka dawooyinka guud ah, waxaa laga yaabaa inaysan noqon kicinta kaliya ee PG ee bukaannada nugul ee qaba PD. Marka labaad, oo leh fMRI, waxaan ku cabiray isbeddelada oksijiinta dhiigga. In kasta oo ay tani u adeegsan karto tilmaan-bixin ku saabsan dhaqdhaqaaqa synaptik, daraasaddan ma baarayso wejiga hore ee dhakhaatiirta dopamine-ka tooska ah (tusaale ahaan adeegsiga radioligands bartilmaameedka dhakhaatiirta dopamine) oo sidaas darteed, kama soo qaadan karno go aan gaar ah oo ku saabsan neurotransmittersters ku lug leh. Saddexaad, waxaan baarnay howsha jawaab celinta-madax-bannaan ee waxqabadka. In kasta oo aan si aan toos ahayn ugu xiriirineyno natiijooyinka natiijooyinka qaddarka qaddar-qadashada tooska ah, ma soo uruurin wax caddeyn dheeraad ah oo toos ah oo ku saabsan muhiimadda hab-dhaqan ee dhimis la'aanta dambe ee OFC. Xaddidyada dheeriga ah waa cabirka muunad yar oo yar iyo halista cilaaqaadka wareega ee leh tillaabooyinka aan la sii kala soocin karin (Kriegeskorte et al, 2009). Daraasadaha mustaqbalka ayaa laga yaabaa inay awood u yeeshaan inay si toos ah u sharaxaan doorka hore ee gudbinta dopaminergic hore ee gudbinta jawaab-celinta taban iyo qiimeynta faragelinta daawooyinka ee DAs ama yaraanta khaaska ah ee qamaarayayaasha cudurka.

Mahadnaq

Waxaan u mahadcelineynaa shaqaalaha qeybta sawirka caafimaadka (gaar ahaan Adrian Crawley) iyo xarunta Xanuunada Dhaqdhaqaaqa (qaasatan Rosalind Chuang, MD iyo Thomas Steeves, MD) oo ka mid ah kaalmada ay ka gaysteen daraasada. Shaqadan waxaa qayb ahaan taageeray deeq ka timid Machadka Kanada ee Daraasaadka Caafimaadka (MOP-64423 to APS) iyo Safra Foundation. APS waxaa taageera Machadka Cilmiga Baadhitaanka Caafimaadka ee Abaalmarinta Baarayaasha Dambi Baarayaasha.

Qoraalada

SAXIIX:

Qorayaashu ma sheegaan khilaafka danta.

tixraacyada

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