Mchitidwe wa kutchova njuga ndi kutchova njuga mu matenda a Huntington (2014)

Carla Kalkhoven¹, Cor Sennef¹, Ard Ngale¹ ndi Ruud van den Bos^2*

• ¹Chardon Pharma, Herpen, Netherlands
• ²Dipatimenti ya Organicalal Animal Physiology, Gulu la Sayansi, Radboud University Nijmegen, Nijmegen, Netherlands

Matenda a Huntington (HD) ndi matenda amtundu, neurodegenerative, omwe amakhudza mwachindunji ma neurons a njira yosalunjika, zomwe zimapangitsa kutsika kwapang'onopang'ono kwa mgwirizano wama minofu ndikuwonongeka kwa kuwongolera kwamalingaliro ndi kuzindikira. Chosangalatsa ndichakuti kudziwiratu kwa kutchova juga kwa matenda a m'magazi ndi zina zomwe zimapangitsa kuti pakhale kusokonezeka m'mabwalo amtundu wa cortico omwe amakhudzidwa ndi HD, ndikuwonetsa zofananira zokhudzana ndi disinhibition, kuphatikiza kusintha kwa kulanga ndi mphotho, kusakhazikika, komanso kulephera kulingalira zabwino zazitali zopindulitsa kwakanthawi kochepa. Odwala onse a HD komanso otchova njuga amawonetseranso zofooka zofananira pakuchita zisankho zowopsa, monga Iowa Kutchova Juga Task (IGT). Izi zofanana zikusonyeza kuti odwala HD ndi gulu lomwe lingakhale pachiwopsezo cha zovuta zamatchova njuga. Komabe, mavuto oterewa amangowoneka mwa odwala HD. Mukuwunikaku, tikufuna kudziwa kuopsa kwa kutchova njuga kwa HD, komanso machitidwe aubongo. Makamaka chifukwa cha kuwonjezeka kwa mwayi wotchova njuga wopezeka pa intaneti, ndikofunikira kumvetsetsa zoopsa izi ndikupereka chithandizo choyenera cha wodwala moyenerera. Kutengera ndi zomwe zapezeka mu neuropathological ndi chikhalidwe, tikupangira kuti odwala HD sangakhale ndi chizolowezi chowonjezereka chofunafuna ngozi ndikuyamba njuga, koma kuti atha kukhala ndi mwayi wowonjezeka akangoyamba kuchita njuga. Chifukwa chake, zochitika zamtsogolo komanso zamtsogolo za kuthekera kwa kutchova juga pa intaneti komanso zokhudzana ndi zosokoneza bongo zomwe zikugwirizana ziyenera kuyang'aniridwa mosamala, makamaka kwa magulu omwe ali pachiwopsezo ngati odwala HD.

Introduction

Matenda a Huntington (HD) ndi matenda amtundu wa neurodegenerative, wobadwa mwanjira yotchuka kwambiri. Matendawa amadziwika ndi ma motor omwe amapita patsogolo, ozindikira komanso azikhalidwe, zomwe nthawi zambiri zimawonekera pakati pa 30 ndi 50 wazaka, ndipo zimayambitsa kufa msanga mu 10-20 zaka matenda atayamba. HD imayambitsidwa ndi kusintha kwa mtundu wa Huntingtin (HTT), komwe kumapangitsa kuti mapuloteni awonjezeke, kusinthanso njira zingapo zam'magazi, ndipo pamapeto pake kufa. Kuwonongeka kwa Neuronal kumachitika koyambirira mu striatum (caudate nucleus ndi putamen), komwe kumakhudza njira za cortico-striatal zomwe zimathandizira kuyendetsa ntchito zamagalimoto ndi kuzindikira (Reiner et al., 2011; Vonsattel et al., 2011). Pamalo oyendetsa galimoto, njira zowonongeka izi zimanenedwa ngati kusunthika kosasinthika (chorea), pomwe odwala akuwonetsa / odwala omwe ali ndi vuto laukadaulo, ophatikizira ena mwa kukakamira, kusawerengera pachiwopsezo komanso kulephera kuyimitsa maphunziro oyipa kanthu (Hamilton et al., 2003; Duff et al., 2010b). Zizindikiro zofananira komanso zodziwika zimawoneka mwa zizolowezi zokhudzana ndi zinthu kapena zochitika zina (Newman, 1987; Rosenblatt, 2007; Iacono et al., 2008). Chifukwa chake, zitha kuyembekezeredwa kuti odwala HD ali pachiwopsezo chokhala ndi mavuto osokoneza bongo. Ma paradigms opanga zisankho mu ma labotale alimbikitsanso kuchepa kwa kupanga zisankho zowopsa kwa odwala otsogola a HD (mwachitsanzo, Stout et al., 2001), ndipo njuga zamatumbo zawonedwa mwangozi m'gululi la odwala (De Marchi et al., 1998). Komabe, zomwe zapezazi ndizosowa, ndipo zodabwitsa ndizoti kafukufuku ochepa adayang'ana mwachindunji zizindikiro ndi zotsatira za, mwachitsanzo, kudziletsa kwakanthawi mu HD.

Mukubwereza uku tikuti odwala a HD atha kukhala gulu lowopsa pobweretsa njuga zovuta. Choyamba, kutchova juga kovuta kumadziwika ndi kuthekera kwa maphunziro kusiya njuga ngakhale mavuto azachuma, aumwini kapena akatswiri. Kutengera ndi kusokonezeka kwa mitsempha ndi mawonekedwe amachitidwe mphamvu yakuyimitsa njuga imawoneka kuti yatsika kapena palibe kwa odwala HD. Kachiwiri,, chifukwa cha kuthekera kwakuthekera kwakutchova juga komanso kuwonjezeka kwa kutchova njuga kwachilamulo ndi kovomerezeka (onani, Griffiths, 2003), titha kuyembekezera kuti kuwonjezeka kwa mavuto amtundu wa juga kuwonjezeka m'zaka zikubwerazi. Kuchulukitsa kufalikira kungayike pachiwopsezo magulu omwe ali pachiwopsezo, monga odwala HD, omwe sanadziwike pachiwopsezo chotere.

Mwambiri, kusintha mikhalidwe yakunja ndi njira zamankhwala kumatha kukhala ndi zotsatira zosayembekezereka komanso zosafunikira pamachitidwe a wodwala, makamaka mu zovuta za minyewa. Zotsatira zoterezi zimasowa mosavuta ngati zizolowezi sizimapangidwanso. Izi zikuwonetsedwa bwino ndi vuto la matenda a Parkinson, pomwe kuyambitsidwa kwa mankhwala osokoneza bongo ndi dopamine agonists kunayambitsa zovuta zowongolera monga kubetcha kovutikira, kugula, kudya, ndi hypersexuality, chifukwa chakuchulukitsa kwa mesolimbic dopaminergic system (Dodd et al., 2005; Witjas et al., 2012; Weintraub et al., 2013). Komabe, zotsatirazi sizinadziwike mpaka patadutsa zaka zambiri kuchokera pakubweretsa njira zochizira dopamine agonist kuphatikiza kusintha kwa zochitika zokhudzana ndi (kupezeka kwa) kugula, kudya, kugonana, intaneti, ndi kutchova juga. Izi zikuwonetsa kuti kuunikiranso za ngozi zomwe zili pachiwopsezo ndikofunikira kuti athe kupereka chithandizo chokwanira komanso chitsogozo kwa odwala akakhala kuti akusintha.

Apa, tifufuza mbiri ya matenda a HD mokhudzana ndi kusuta, mavuto a juga, komanso zosankha zopanga chisankho. Mu Gawo HD: Neuropathology, Zizindikiro, ndi Kupita Patsogolo, kupita patsogolo kwa zisonyezo za HD kudzakambidwa pokhudzana ndi kusokonezeka m'mabwalo amtundu wa cortico omwe akukhudzidwa ndikuphunzira ntchito, kumva kulanga, ndikuwongolera / kuzindikira. Mu Gawo Kutenga Mwangozi ndi Pathological Kutchova Njuga mu HD, mbiri ya neurobiological ya odwala HD idzakambidwa pamayendedwe otchovera njuga komanso kuyesedwa koyeserera kochita kupanga zisankho komanso kupanga zisankho, monga Iowa Kutchova Juga Task (IGT) ndi Kampasi ya Kutchova Juga Task (CGT). Mu Gawo Kukambirana, tikambirana momwe kuwonekera kwa ngozi za njuga kumatha kubweretsa malingaliro pa odwala HD ndi omwe amawasamalira momwe angathanirane ndi nkhaniyi komanso omwe angapewe mavuto ena. Tikufunanso kudziwa mafunso omwe sanayankhidwe, omwe angayambike ngati poyambira kafukufuku wamtsogolo pakupezeka ndi chiwopsezo cha zovuta za njuga kwa odwala HD.

HD: Neuropathology, Zizindikiro, ndi Kupita Patsogolo

Mechanisms ya Neurobiological

HD imayambitsidwa ndi CAG yosasunthika (trinucleotide; cytosine-adenine-guanine) yobwereza mtundu wama HTT, yomwe imatsogolera pakupanga mapuloteni a huttin (Htt) ophatikizidwa ndi polyglutamine (polyQ)MacDonald et al., 1993). Kuchuluka kwa kubwezeretsa kwa trinucleotide kumalumikizidwa molingana ndi msinkhu wa matendaSnell et al., 1993; Stine et al., 1993). Odwala ambiri a HD ali ndi 40-55 yobwereza yomwe imayambitsa chisokonezo chachikulu cha akuluakulu, pomwe kufotokozera mobwerezabwereza kwa 70 kumabweretsa vuto la achinyamata. Anthu omwe ali ndi zochepa kuposa 35 CAG zobwereza mtundu wa HTT sizitulutsa HD. Ngakhale njira zomwe HD pathogeneis imakhalirabe yosadziwika ndipo sizingakambidwe mwatsatanetsatane pano, zimakhudzana ndikupanga mapuloteni omwe amaphatikizidwa ndi polyQ yowonjezera Htt, komanso kuyanjana kwa mutant Htt ndi mapuloteni ambiri omwe akukhudzidwa ndi metabolism yamphamvu, mapuloteni ndi vesicle mayendedwe, ndi kayendedwe ka gene (Li ndi Li, 2004; Jones ndi Hughes, 2011). Kubwezeretsedwa kwa ma cell munthawiyo kumapangitsa kuti ma neuronal asinthe chifukwa cha zinthu zina zomwe zimaphatikizira chisangalalo ndi apoptosis.

Kuwonongeka kwa Neuronal koyambirira kumangolekeredwa ku basal ganglia, komwe ma spiny neurons apakati mu striatum (caudate nucleus ndi putamen) amakhudzidwa makamaka (Vonsattel ndi DiFiglia, 1998; Kassubek et al., 2004). Striatum imalandira athandizira ake osangalatsa kwambiri (glutamatergic) kuchokera kumadera a cortical, pomwe amalandila kulowetsa dopaminergic kuchokera ku substantia nigra. Striatum ili ndi zotheka ziwiri (GABA-ergic) zotulutsa: njira yolunjika ndi yosadziwika (Chithunzi 1A). Ma striatal neurons a polojekiti yotsogolera njira yolowera mkati mwa ma globus pallidus (GPi), omwe nawonso amakhala ndi ziwonetsero zoletsa mpaka thalamus. The thalamus imapereka chidziwitso chachikulu cha zokondweretsa. Chifukwa chake, kugwira ntchito kwa njira yolumikizana yotsogola kumalepheretsa ntchito ya GPi, yomwe imatulutsa disinhibort thalamocortical, potero imathandizira kuyendetsa ndi kuzindikira. Njira yosadziwika yokhazikika, kumbali ina, imapita ku GP (GPe), yomwe imatumiza zowerengetsa ku subthalamic nucleus (STN). STN imatumiza zotsatsira ku GPi. Chifukwa chake, kuyambitsa njira yosakhala yokhazikika yotsata njirayi kumapangitsa kuti STN iyambe kugwira ntchito, yomwe imalepheretsa zochitika za thalamocortical, kupondaponda kuyenda ndi ntchito zamunthu. Kusintha kwakhalidwe kumachitika chifukwa (chocheperako) chochita m'njira yolunjika komanso yosadziwika. Pathology munjira yosadziwika ndi yofunikira ku HD ndipo imasokoneza kayendetsedwe ka kayendetsedwe ka kayendedwe ka magalimoto komwe kumapangitsa kuti kuchepa kwa kuwongolera kuyendetsa kayendetsedwe ka magalimoto ndi machitidwe (Chithunzi 1B; Albin et al., 1989; Alexander ndi Crutcher, 1990).

 

Chithunzi 1. (A) Njira yosavuta yopanga mabungwe a cortico-basal ganglia network (kotakata, malo okhalamo, pallidal ndi thalamic) yowonetsa njira zowunjika komanso yosalunjika mu ubongo wabwinobwino. (B) Kusintha kwatsatanetsatane kwa msewu wosalunjika (X) mu HD kumabweretsa kuchepa kwamphamvu pakuwongolera zochitika za cortical. GPe: kunja kwa globus pallidus; GPi: mkati globus pallidus; STN: subthalamic nucleus. Red: inhibitory (GABA) njira, Blue: zisangalalo (glutamate) njira.

Malo ozungulira a Cortico-basal ganglia, omwe amalumikizana pakati pa madera a cortical, malo olimba, madera a pallidal ndi madera a thalamic, adakonzedwa m'njira yofananira yopereka ntchito zosiyanasiyana mu bungwe lakhalidwe. Ndemanga zambiri zabwino zimakhalapo pamalumikizidwe ndi magawo azigawo (mwachitsanzo, Alexander et al., 1986, 1990; Alexander ndi Crutcher, 1990; Yin ndi Knowlton, 2006; Verny et al., 2007; Yin et al., 2008; Haber ndi Knutson, 2010; Sesack ndi Grace, 2010), timangowunikira zinthu zochepa zomwe zili zoyenera kuwunika kwathu. Choyamba, polankhula mokakamiza ku dorsal to the ventral topographical organised in all cortical and striatal dalipo. Chifukwa chake, malo oyambira a dorsal amayanjanitsidwa ndi malo a dorsal striatal pomwe malo oyambira kwambiri am'mbali amayanjanitsidwa ndi madera ena abata (kuphatikiza ma nucleus). Chachiwiri, mabwalo atatu oyenda bwino amatha kufotokozedwa. Dongosolo la sensorimotor limazungulira sensorimotor striatum (putamen) ndi sensorimotor cortices zomwe zimagwirizanitsidwa ndi kuphedwa kwa khalidwe la motor. Dongosolo la Associative / cactitive control limaphatikizapo dorsolateral prefrontal cortex, anterior cingulate cortex, and Associative striatum (caudate nucleus). Izi ndizofunikira makamaka pakuwongolera oyang'anira, mwachitsanzo, zimakhudzidwa ndikuwongolera kuzindikira, kulinganiza ndi kukumbukira kukumbukira. Kuphatikiza apo zimakhudzidwa ndikulimbikitsa kusinthasintha kwakanthawi kachitidwe kosinthika ndikulimbikitsa kapena kuletsa (kulanga) machitidwe ogwiritsira ntchito, mwachitsanzo, machitidwe a machitidwe, omwe amaphunziridwa mogwirizana ndi chilengedwe (Kravitz et al., 2012; Paton ndi Louie, 2012). Dongosolo la limbic limaphatikizira orbitof mbeleal cortex, ventromedial prefrontal cortex, amygdala, ndi limbic striatum (nucleus accumbens). Gawo lino ndilofunikira makamaka pakuwunika phindu la chikumbumtima, kuonetsera mphotho yomwe ikuyembekezeredwa kapena kulangidwa kwa chikondwerero chomwe chikubwera, kusankha kapena chochitika, kayendetsedwe ka malingaliro, ndi kuphunzira kosinthasintha (kosangalatsa)O'Doherty et al., 2001; Rushworth et al., 2007; van den Bos et al., 2013b, 2014).

Pathology mu HD imawonedwa mu putamen ndi caudate nucleus (Vonsattel ndi DiFiglia, 1998; Kassubek et al., 2004; Vonsattel, 2008; Vonsattel et al., 2011; Hadzi et al., 2012). Kuphatikiza apo, m'malo onsewa ma atrophy amatsata mawonekedwe, kuyambira kumadera akumata ndi kumatanthwe ndikupita kumadera am'kati ndi otetemera pamene matendawa akupita (Vonsattel ndi DiFiglia, 1998; Kassubek et al., 2004; Vonsattel, 2008). Komabe atrophy yoyambirira yawonekeranso mu ma nucleus accumbens ndi globus pallidus m'maphunziro ena (van den Bogaard et al., 2011; Sánchez-Castañeda et al., 2013). Pomwe kusokonezeka m'madongosolo a sensorimotor (putamen) kumatha kukhala kogwirizana ndi chizindikiro chagalimoto, kusokonezeka kwa mayanjano / gawo lodziwika bwino (caudate nucleus) kungakhale kokhudzana ndi kusweka kwa ntchito, ndikuyambitsa kuchepa, mwachitsanzo, kukumbukira kukumbukira kwa odwala oyambirira a HD (Lawrence et al., 1996; Bonelli ndi Cummings, 2007; Wolf ndi al., 2007). Kusokonezeka mu gawo la nthambi zam'manja, monga chifukwa cha atrophy koyambirira kwa maukosi a nucleus, kumatha kukhala kokhudzana ndi mphwayi ndi kukhumudwa (Bonelli ndi Cummings, 2007; Unschuld et al., 2012). Kupita patsogolo kwapang'onopang'ono mu striatum kumatha kudzetsa kusokonezeka motsatana kwa mabwalo a cortico-striatal. Mwachitsanzo, nyukiliya ya porral caudate imakhalanso gawo la mbali ya orbitofrontal, yomwe imakhudzidwa pamene matendawa akupita patsogolo. Kuwonongeka kwa dera lino kukugwirizana ndi kudziletsa (Bonelli ndi Cummings, 2007). Pambuyo pake, kufalikira kumatha kufalikira kumadera ena aubongo, kuphatikiza mbali zina za basal ganglia (madera a pallidal ndi thalamus), hippocampus, amygdala ndi cortical madigiri omaliza a matendawa.

Ponseponse, HD imadziwika ndi kuwonongeka kwina kwa maselo a striatal neurons omwe ali munjira yolunjika. Matendawa akamakula, chiwonetsero cha ma striatum chikufalikira motsatira mawonekedwe a caudal-rostral ndi dorsal-ventral gradient ndikuyambitsa kusokonezeka kwakukulu kwa mabwalo a cortico-striatal. Kuwonongeka kwa ulamuliro wa inhibitory m'mabwalo awa kumakhudzana mwachindunji ndi kupita patsogolo kwa chizindikiritso cha magalimoto, kuzindikira ndi mawonekedwe mu HD, monga tafotokozera pansipa.

Zizindikiro za HD

HD imadziwika ndi mawonekedwe osiyanasiyana opita patsogolo a mota, ozindikira komanso amakhalidwe. Zizindikiro zoyambirira zimakonda kukhala ndi zaka zapakati, ndikukula kwakanthawi kwa 40, ngakhale ochepa odwala amadwala HD, yomwe imayamba zaka za 20 zisanachitike. Popeza zomwe matendawa amakula ndikukula kwa HD ana ali osiyana kwambiri ndi vuto lokhala ndi vuto loyambika, tikambirana za gulu lomaliza la odwala pakuwunika uku. Chimodzi mwazizindikiro zoyambirira kuonekera mu HD ndi chorea (vuto la kusayenda kwina), ndipo kupezeka kwa matenda nthawi zambiri kumachitika pambuyo poti matenda ayamba.Shannon, 2011). Kafukufuku wina, komabe, amafotokoza kusintha kosadziwika bwino komanso kosakhazikika kwa matendawa asanafike, ndipo momwe zimachitikira komanso kupitilira kwa zizindikiro za HD kumakhalabe nkhani. Komabe, ndemanga zingapo zamatenda a HD zilipo (Roos, 2010; Anderson, 2011; Shannon, 2011).

Zizindikiro zamagalimoto

Zizindikiro zamagalimoto zimayamba kuonekera kumayambiriro kwa HD, ndipo nthawi zambiri zimakhala woyamba zizindikiro kuzindikirika mu labotale komanso abale oyambira odwala HD.de Boo et al., 1997; Kirkwood et al., 1999, 2001). Zosokoneza zamagalimoto zikuwoneka ngati kuyamba kugwira ntchito pakulakwitsa poyankha (Smith et al., 2000), yogwirizana ndi gawo la kayendedwe ka cortico-striatal mota mu sensorimotor kuphunzira ndi kuwongolera (Graybiel et al., 1994). Zizindikiro zoyambirira za nthenda yamagalimoto nthawi zambiri zimakhala zozungulira (chorea) mwachitsanzo, minofu ya nkhope, zala ndi zala ("kusinkhana"), Hyperreflexia, ndikusunthika kotulutsa mtima (Young et al., 1986; Shannon, 2011), zomwe zimabweretsa kuwoneka wamba kosapumira komanso kuuma mtima kwa odwala oyambirira a HD. Kusuntha kwachilendo kumeneku kumakhala kachilendo ndipo nthawi zambiri kumakhala kosadziwika poyamba, koma kumayamba kuwonjezeka pang'onopang'ono mpaka kufalikira kwa minofu ina yonse pakapita nthawi. Zizindikiro zina zoyambirira zamagalimoto zimaphatikizira kuchepa kwa ma saccadic kapena akuchedwa.Peltsch et al., 2008) ndi dysarthria (Ramig, 1986; Young et al., 1986). Dysarthria, vuto la kulankhula, limadzetsa kuvuta kwa mawu komanso kusuntha kwa mawu, zomwe zimapangitsa kuti mawu azikhala osavuta kumvetsetsa. Dysphagia (kumeza zovuta) imawonedwa mwa odwala ambiri omwe ali ndi vuto lofika pakati pamatenda, ndipo amayamba kukula pang'onopang'ono mpaka odwala sangathenso kudya osakhudzidwa ndipo nthawi zambiri amafunikira chubu chodyetsa kumapeto kwa HD (Heemskerk ndi Roos, 2011). Zizindikiro zina zamagetsi, zomwe sizikhala choreic zomwe zimadziwika kawirikawiri pakati pa matenda opatsirana zimaphatikizira zovuta zovuta za gait, kusakhazikika kwa mtima, ndi dystonia (minyewa yomwe imayamba chifukwa cha minyewa yomwe imayambitsa pang'onopang'ono kubwereza kosakhazikika komanso kupweteka kwakanthawi), komwe kumakhala koyenda nthawi zambiri ndi kugwa pafupipafupi (Koller ndi Trimble, 1985; Tian et al., 1992; Louis et al., 1999; Grimbergen et al., 2008). Kuuma ndi bradykinesia (kuchepa kwa kayendedwe ka zinthu ndi kuzizira) nthawi zina kumawonedwa, koma kumangolekeredwa pamilandu ya ana aang'ono (HD)Bittenbender ndi Quadfasel, 1962; Hansotia et al., 1968). Zizindikiro zamagalimotozi ndizogwirizana ndi kusokoneza kwa sensorimotor (ndi Associative / cognitive control) cortico-striatal circuits zomwe zimakhudzidwa kwambiri ndi HD.

Zochitika zaumoyo komanso zamisala

Mavuto amachitidwe mu HD amatha kukhala ovuta komanso ovuta kufotokozera, ndipo kupezeka kwawo ndi kuyambira kumasiyana kwambiri pakati pa anthu. Kuphatikiza apo, nthawi zina zimakhala zovuta kusiyanitsa kusokonezeka kwa chikhalidwe ndi kuthana ndimatenda osautsa (Caine ndi Shoulson, 1983). Chiwerengero cha kafukufuku chomwe chawonetsa machitidwe mu HD ndichoperewera, ndipo chifukwa chake palibe chidziwitso chochepa pakukula kwawo pamatendawa (van Duijn et al., 2007). Zizindikiro zomwe zimafotokozedwa pafupipafupi komanso mwatsatanetsatane mu HD ndizosakwiya, kupanda chidwi, komanso kukhumudwa, zomwe zimachitika ndi kuchuluka kwa pafupifupi 50% (Caine ndi Shoulson, 1983; Folstein ndi Folstein, 1983; Craufurd et al., 2001; Kirkwood et al., 2001; van Duijn et al., 2007, 2014; Tabrizi et al., 2009). Nthawi zonse kukwiya komanso kusamverako nthawi zina kumawonedwa mwa anthu omwe ali ndi HD.Tabrizi et al., 2009; van Duijn et al., 2014,, komanso kuvutika maganizo kwanenedwa kumayambiriro azachipatala (Shiwach, 1994; Julien et al., 2007; Epping et al., 2013). Zizindikiro zothandizirazi ndi zina mwazizindikiro zoyambirira zamagalimoto zoyambirira kuzindikiridwa ndi achibale oyamba (Kirkwood et al., 2001). Zizindikiro zokhudzana ndi chidwi, zomwe zimayamba pang'onopang'ono panthawi yamatendawa, zimaphatikizapo kusowa kwa mphamvu, chilimbikitso ndi kudzipereka, kuchepa kupirira komanso mtundu wa ntchito, kusowa bwino, kusadzisamalira komanso kupweteketsa mtima (Craufurd et al., 2001; Kirkwood et al., 2001). Zizindikiro zakukhumudwitsa zakhala zikugwirizana ndi kuchuluka kwa zochitika mu ventromedial prefrontal cortex (Unschuld et al., 2012). Kusokonekera kumalumikizidwa ndi vuto la orbitof mbeleal dysfunction, lomwe limayambitsa kuchepa kwamphamvu pakuyankha kwamalingaliro amygdala (Klöppel et al., 2010).

Zizindikiro zina, zamavuto amisala omwe amawonedwa mu HD ndi nkhawa, kusokonezeka-kukakamiza, mania, zodziwikiratu monga zodandaula, monga paranoia, kuyerekezera zinthu m'maganizo, ndi chinyengo (Caine ndi Shoulson, 1983; Folstein ndi Folstein, 1983; Craufurd et al., 2001; Kirkwood et al., 2001; van Duijn et al., 2007). Zizindikiro izi sizichitika mpaka pakatikati kapena mochedwa matendawa, ngakhale akuti amadziwika kuti amakumana ndi HD odwala (Duff et al., 2007). Matenda olembetsa kwambiri agwirizanitsidwa ndi kuwonongeka kwa orbitof mbeleal cortex ndi anterior cingate cortex, pomwe schizophrenia, vuto lomwe limaphatikizapo kuchepa pakukonzekera, kulinganiza ndi chidwi, likugwirizana ndi kukomoka kwa mtima kwapambanitsa.Tekin ndi Cummings, 2002).

Akuti zizindikiro zambiri zamisala mu HD zimakhala gawo la matenda otsogola kapena osokoneza bongo, omwe ali ndi zizindikiro monga kusasamala, kusakwiya, kudziwitsa, kuperewera, kuzindikira, komanso kupilira.Lyketsos et al., 2004; Rosenblatt, 2007,, zomwe nthawi zambiri zimawonedwa mwa odwala HD (Hamilton et al., 2003; Duff et al., 2010b). Kutengedwa palimodzi, mabukuwa akuwonetsa kuti kuyambika ndi kupita patsogolo kwa zisonyezo zamtundu wa HD ndikosazindikira, matenda omwe amachitika pafupipafupi komanso asanayambike, pomwe nkhawa, zovuta zowoneka bwino, komanso zizindikiro zama psychotic sizachilendo ndipo zimachitika pambuyo pake matendawa. . Zizindikiro zamisala izi zimagwirizanitsidwa ndi kusokonezeka kwa mabwalo a miyendo ndi Associative / cortitive control cortico-striatal omwe amakhudzidwa kwambiri ndi HD.

Zizindikiro zakuzindikira

Kutsika kwamtundu wamadzi ndi gawo lina lofunika la matenda a HD. Kafukufuku wambiri adayang'ana makamaka pakupezeka kwa chizindikiritso cha magawo am'mbuyomu komanso matenda oyamba a HD, m'chiyembekezo chodzapeza matendawa oyambira matenda (obwerezedwanso mu Papp et al., 2011; Dumas et al., 2013). Zambiri, zotsatira zake zikuwonetsa kuti kusintha kwa kuzindikira kovuta kutha kuwonedwa mpaka zaka za 5-10 lisanayambike zizindikiro zagalimoto zokhala ndi njira zokwanira. Kafukufuku wina adapeza kuti, pakuwoneka koyambirira komanso koyambirira kwamankhwala a HD, pafupifupi 40% ya odwala akukumana kale ndi zovuta za kuzindikira pang'ono (vuto logwirizana ndi kuchepa kwa kukumbukira, osakwaniritsa njira yodziwira matenda a dementia; Duff et al., 2010a). Komabe, si kafukufuku onse amene amathandizira izi:Blackmore et al., 1995; Giordani et al., 1995; de Boo et al., 1997; Kirkwood et al., 2001). Mwambiri, mabukuwo amavomereza kuti kukonza mauthenga ndi kuthamanga kwa psychomotor zimakhudzidwa makamaka koyambira (Rothlind et al., 1993; Kirkwood et al., 1999; Verny et al., 2007; Paulsen et al., 2008). Zovuta zina zomwe zimawonedwa poyambilira zimaphatikizanso mavuto omwe ali ndi chidwi,Jason et al., 1988; Rothlind et al., 1993; Foroud et al., 1995; Lawrence et al., 1996; Hahn-Barma et al., 1998; Verny et al., 2007; Paulsen et al., 2008; Tabrizi et al., 2009; Papp et al., 2011; Stout et al., 2011). Kusintha kwazindikiritso kwawonedwa mwa odwala oyambira matenda (Jason et al., 1988), panthawi yomwe masinthidwe owonjezereka amakhala operewera, pomwe kuphunzira kobwerera kudakali komweko (Lawrence et al., 1996). Chifukwa chake, odwala akadali okonzanso kufunika kwa kupatsidwanso mphamvu ndikuphunzira zovuta zatsopano zolimbikitsira pamlingo womwewo (mwachitsanzo, mawonekedwe kapena mtundu), koma ali ndi mavuto osunthira chidwi chawo pamlingo wina (mwachitsanzo, kuchokera pa mtundu mpaka mawonekedwe) monga zimafunikira ntchito yatsopano kuti mulandire mphotho. Pambuyo pake matendawa, kuzindikira kusinthasintha komanso kupirira zimachititsanso kuti odwala HD asamve bwino.Josiassen et al., 1983; Lange et al., 1995). Kukula kwa zizindikirozi kumayenderana ndi kusakhazikika kwa dorsolateral presetal circuit kumayambiriro kwa matendawa, popeza kusintha kosinthika kwakukhazikika kumayendetsedwa ndi dorsolateral prefrontal cortex, pomwe kuphunzira kobwerera kumayendetsedwa ndi orbitof mbeleal cortex (Dias et al., 1996; McAlonan ndi Brown, 2003). Zovuta zina zoyambirira zimaphatikizaponso kusayenda bwino, kusayenda bwino, kusalingalira bwino, komanso kuchepa kwamakhalidwe ndi malingaliro (Watkins et al., 2000; Paradiso et al., 2008; Duff et al., 2010b). Disinhibition yaonedwa kale m'magulu oyamba a HD, omwe magwiridwe ake amakhala ophatikizika ndi ntchito zomwe zimafunikira zoletsa zoyambitsa zamphamvu koma zosayenera (Holl et al., 2013). Pomaliza, maphunziro angapo apeza kuti odwala preclinical HD amakhala ndi vuto lozindikira zomwe sizili bwino monga mkwiyo, kunyansidwa, mantha komanso chisoni. Kuzindikira kwamthupi kumachepa pang'onopang'ono, ndipo kumatha kufalikira ku mavuto osavomerezeka m'magawo oyambira matenda.Johnson et al., 2007; Tabrizi et al., 2009; Labuschagne et al., 2013). Izi phenotype ikugwirizana ndi kukomoka kwa orbitofrontal cortex, yomwe imakhudzidwa ndikuwonetsa zambiri zazokhudza mtima komanso mphotho (Henley et al., 2008; Ille et al., 2011).

Kafukufuku wokhala ndi mitundu ya zinyama za HD akuwonetsanso kuwonongeka kwazindikiritso kwa omwe amawonera odwala. Ngakhale si maphunziro onse omwe amapeza zovuta kuzindikirika (Fielding et al., 2012), zomwe zapezedwa mu rat ndi mbewa za HD zimaphatikizapo nkhawa, kuchuluka kwa kuyankha pamalingaliro oyipa, ndi zovuta pakubweza kwaphunziro ndi njira zosinthira (Faure et al., 2011; Abada et al., 2013). Kafukufuku wina adapeza zolakwika zoyambirira pakubweza kusinthaku kusanachitike kwa zizindikiro zamagalimoto mumtundu wa makoswe a HD (Fink et al., 2012). Chosangalatsa ndichakuti, nyama za HD zimawoneka kuti zimachita chidwi kwambiri ndi zomwe zimapangitsa kuti munthu azikhala wopanda nkhawa, pomwe odwala amasonyezanso kuchepa kwa malingaliro. Pakadali pano sizikudziwika ngati izi zikuwonetsa kusiyana pantchito yomwe ikuperekedwa (kuzindikira momwe mukumvera molimbana ndi mayankho pamagulu owopseza), zosiyana zokhudzana ndi mitundu pazotsatira zamatenda kapena kusiyana kwakukulu pakati pa mtundu wa makoswe ndi mkhalidwe wa munthu. Mwambiri, kafukufuku mu odwala komanso mitundu ya zinyama za HD akuwonetsa kuti magwiridwe antchito osiyanasiyana amatha kuzindikira kale HD. Zovuta zoyambirira zimaphatikizira kuchepa kwa chidwi, kukumbukira, kusinthasintha, kuzindikira, komanso kuzindikira. Pakadali pano, odwala nthawi zambiri amalephera kuzindikira za kuzindikira kwawo (kuchepa) kwa kuzindikira kwawo (Hoth et al., 2007). Popita nthawi, Zizindikiro zimazindikira pang'onopang'ono, zomwe zimayamba kudwala kwambiri. Ngakhale kupezeka kwa zizindikiro kumakhala kofanana ndi kuwonongeka motsatizana kwa mabungwe oyanjana / ozindikira komanso ma limbic cortico-striatal circuits, motero, ntchito zina zomwe zimagwirizana ndi gawo la limbic zimathanso kukhudzidwa kale koyambirira kwa HD.

Kutsiliza

Magalimoto, zikhalidwe ndi kuzindikira mu HD zaphunziridwa kwambiri m'mbuyomu, ndipo pitilizani kukhala mutu wokondweretsa chifukwa cha kusiyanasiyana kwakukulu pakupezeka kwa chizindikirochi komanso kuyambika kwa zizindikirozi kwa odwala. Mwambiri, zikhalidwe ndi kuzindikira zimagwirizana ndi magawo atatu amkhalidwe azikhalidwe: chidwi, kusowa kwaudindo, komanso kudziwitsa. Kuphatikiza kwa zizindikirozi nthawi zina kumatchedwa "Executive dysfunction syndrome". Zizindikiro zonsezi zimakhudzana ndi kuchepa m'mabwalo a cortico-striatal okhudza orbitof mbeleal cortex, dorsolateral prefrontal cortex ndi anterior cingulate cortex. Monga tafotokozera pamwambapa, maphunziro a neuropathological awona kuchepa pang'onopang'ono kwa striatum mu dorsal kuti ventral malangizo kwa odwala HD. Ngakhale maganizidwe azikhalidwe komanso ozindikira agwirizana pang'onopang'ono ndikuwonongeka kwapang'onopang'ono kwa mabwalo a cortico-striatal, zomwe zikuwonetsa zomwe zikuwoneka zikuwoneka kuti zikuyambitsa zambiri kuposa momwe zikuyembekezeredwa potengera momwe amaonera. Kukhazikika ndi kupitilira kwa zikhalidwe za kuzindikira ndi kuzindikira mu HD ndizopambana kwambiri, kuwonetsa kuti kuwonongeka kwa zigawo zocheperako kumatha kukhala kosiyana kwambiri komanso kufalikira koyambirira kwa HD kuposa momwe mumaganizira kale. Malingaliro awa amathandizidwa ndi umboni wochokera ku maphunziro angapo oyerekeza zoyeserera (Thieben et al., 2002; Rosas et al., 2005; van den Bogaard et al., 2011).

Kutenga Mwangozi ndi Pathological Kutchova Njuga mu HD

Kutchova Njuga

Ngakhale anthu ambiri amatha kutchova njuga, zitha kukhala vuto lalikulu kwa ena, pamene akupanga mitundu ya zinthu zoterezi. Kutchova juga kwachikhalidwe kumadziwika ndi kulakalaka kochuluka kwa kutchova njuga ngakhale zotsatilapo zomveka zachuma, zanu komanso ntchito. Posachedwa adayikidwa ngati nkhodwe mu DSM-V, popeza imafanana kwambiri ndi mavuto obwera chifukwa cha kugwiritsa ntchito mankhwala osokoneza bongo mu njira zonse za diagnostic ndi neuropathology (van Holst et al., 2010; Clark ndi Goudriaan, 2012). Kutchova njuga kwachikhalidwe kudzakhala koyamba komanso kokhako ka “chizolowezi” chodziwika pagulu "Kugonjera ndi Mavuto Ena ”. Komabe, ziyenera kudziwidwa kuti kusiyana kumakhalapo pakati pa kuzolowera zinthu zama psychoactive ndi kuzolowera kutchova juga. Choyamba, kulakalaka kwabwino kwa zinthu zosokoneza bongo kumakhalapo pakudya zinthu zomwe zimadziwika, pomwe kukhutitsa mtima wofuna kutchova juga kungakhale ndi zotsatira zosatsimikizika chifukwa ndalama zingapindulidwe kapena ayi, pokhapokha ngati ndichita kutchova juga pachokha. ngati ntchito yosangalatsa. Chifukwa chake, kutchova njuga kwa m'magazi kumatha kukhala kokulirapo pankhani iyi komanso zotsatira zosatsimikizika kuposa kugwiritsidwa ntchito molakwika. Dziwani kuti kusinthika kwa zotsatira, kuphatikiza zonse ziwiri komanso kuwonongeka, kungakhale kofunikira kwambiri pakukonda kutchova juga, chifukwa kumapereka njira yolimbitsira, yomwe ndi njira yamphamvu kwambiri yopangira zinthu / zamagulu akale (Sharpe, 2002; Fiorillo et al., 2003). Chachiwiri, zinthu zama psycho zingasinthe kwambiri ntchito mu ubongo ndi zotumphukira zamagetsi kuposa kutchova juga, chifukwa cha zochitika zawo zamankhwala pamachitidwe angapo a neurotransmitter, ndikufulumizitsa njira zowonjezera, ndikupangitsa kugwiritsa ntchito mankhwala osokoneza bongo kukhala njira yamphamvu kwambiri yosokoneza bongo.

Njira zomwe zimayambira njuga ndizovuta ndipo zimakhudza zigawo zambiri zaubongo ndi ma neurotransmitter machitidwe (obwerezedwanso mu Raylu ndi Oei, 2002; Goudriaan et al., 2004; Potenza, 2013). Kukhazikika kwa kusokoneza bongo kwayenderana ndi kuchepetsedwa kwa ma dopamine D2 receptors mu striatum, omwe amagwira ntchito pophwanya malingaliro kuti alepheretse kumasulidwa kwa dopamine. Zotsatira zazikulu za dopaminergic pathways zimawonjezera chidwi kuti zitheke, kulimbikitsidwa, komanso kulimbikitsidwa kwamakhalidwe oyenera (Volkow et al., 2002; Di Chiara ndi Bassareo, 2007). Kusintha kwachindunji komwe kumachitika pamene njuga zamatsenga zimayamba kuphatikizira kukondoweza kwa kutchova njuga (van Holst et al., 2012) ndikuwonetsetsa chidwi chazomwe zimayenderana ndi njuga (Ophulika et al., 2011a,b). Kuphatikiza apo, otchovera njuga achepetsa kuwongolera zochitika pamakhalidwe, monga momwe zimasonyezedwera ndi kuchepa kwa magwiridwe antchito, kuyambitsa chidwi, komanso kukonda kubwereza mphotho zomwe zimachedwa pantchito za neurocognitive (Goudriaan et al., 2004; Ophulika et al., 2012a; van den Bos et al., 2013a).

Ochita kutchova juga amalephera kuchita bwino poyerekeza ndi kuwongolera pazomwe zimapangitsa kuti pakhale chisankho chantchito (mwachitsanzo, Cavedini et al., 2002; Brand et al., 2005; Ophulika et al., 2012b; bwereza: Ophulika et al., 2013). Kuwonongeka koyipa kumeneku sikudalira ngati ntchito zili ndi malamulo omveka bwino opambana ndi zotayika monga Game of Dice Task (Brand et al., 2005) kapena ngati maphunziro ayenera kuphunzira poyesa-ndi-zolakwika zomwe kusankha kumakhala kothandiza pamapeto pake, monga IGT (Cavedini et al., 2002; Ophulika et al., 2012b; onani Gawo Kupanga Chochita Mwangozi ndi Odwala a HD pa Ntchito Zamalonda mwatsatanetsatane wa ntchitoyi). Komabe, kuopsa kwa kutchova juga kunaphatikizidwa ndi kugwira ntchito popanga zisankho zomwe sizikudziwika ngati zotsatira zake sizikudziwika (IGT) kuposa ntchito zomwe zili ndi malamulo omveka bwino (Ophulika et al., 2012b). Kuwona uku ndikosangalatsa poyerekeza kuti m'maphunziro abwinobwino theka lachiwiri la IGT pomwe maphunziro aphunzira zochitika mwadzidzidzi amafanana ndi ntchito zomwe zili ndi malamulo omveka bwino. Zonsezi palimodzi, izi zikuwonetsa kuti kusokonezeka kwa kutchova juga kwa zisankho pakutha kupanga chisankho kungachitike chifukwa chakuchepa kwa kayendetsedwe kazigawo, komwe kumakhala kogwirizana ndi malamulo omveka bwino, komanso kusokonezedwa kwa mphotho ya kukwiya (kutengeka), komwe kumakhudzana ndi kuyesedwa ndi cholakwika kuphunzira kuwunika kwa nthawi yayitali pakusankha (van den Bos et al., 2013a, 2014). Kuphatikiza apo, zikuwonetsa kuti kusokonezeka kwakumapeto kwake kungakhale chinthu chofunikira kwambiri pakukulira kwa njuga.

Kuchokera pamaphunzirowa zikuwonekeratu kuti kuwongolera kwa ma neurobiological popanga njuga zamatenda kumayambitsa kusokonezeka m'magulu awiri oyanjana / ozindikira komanso ozungulira.van den Bos et al., 2013a). Zotsatira zake, otchovera njuga akuwonetsa kuchepetsedwa kudziwongolera, kuwonetsa chidwi, ndi chidwi chowonjezeka, zonse zomwe ndizinthu zokhudzana ndi kudziletsa (Iacono et al., 2008). Mwayi woti munthu ayambe kusuta m'moyo wake, komabe, zimadaliranso pazinthu zina zambiri, monga zomwe adakumana nazo asanabadwe ndi zoopsa zomwe zingachitike m'chilengedwe.

Kutchova Njuga kwa HD: Umboni wa Epidemiological

Ndi kuchuluka kowonjezereka kwa mwayi woperekedwa ndi intaneti, palinso kuwonjezeka kwa mwayi wa njuga za pa intaneti zomwe zili zovomerezeka komanso zosaloledwa m'zaka zaposachedwa. Izi zomwe zimapezeka mosavuta ndipo nthawi zambiri zimakhala zosagwiritsidwa ntchito mosasamala zitha kukhala pachiwopsezo kwa aliyense yemwe ali ndi vuto lotchova juga, koma osagwirizana nawo (Griffiths, 2003). Odwala a HD ndi amodzi mwa magulu omwe njuga za pa intaneti zingakhale pachiwopsezo chotere, chifukwa kudziletsa mwazinthu zina (zomwe zimafala kwambiri pamatendawa) ndikofunikira kwambiri pakulimbikitsa bongo.Iacono et al., 2008). Zowonadi, monga tafotokozera pamwambapa, odwala HD amawonetsa zizindikiro zingapo za kupewetsa matenda, monga kukwiya, kusokoneza poyankha, komanso kuchepetsedwa kuzindikira kwam'maganizo, kumayambiriro kwa matendawa. Zizindikiro zina zomwe zawonedweratu mu HD, ndipo zimatha kuchititsa chidwi cha odwala kupanga zisankho zomveka, ndikusinthika kwachidziwitso, kupirira, kusalingalira bwino, komanso kuchepa kuzindikira. Kupatula izi zodziwikiratu pakati pa odwala HD ndi otchovera njuga, magulu onse awiriwa amawonetsa zodabwitsazi komanso zodabwitsazi pamagawo ofanana a cortico-striatal.

Poona kufanana kumeneku pakati pa otchova juga a m'matenda ndi odwala HD, titha kuyembekezera kuti zovuta za kutchova njuga ziwonjezereka pakati pa odwala HD poyerekeza ndi kuchuluka wamba. Komabe, Kafukufuku amodzi yekha mpaka pano adanenapo za kubedwa kwa ma genetic m'mabanja aku Italy omwe ali ndi HD (De Marchi et al., 1998). M'banjali, anthu awiri adapezeka kuti ali ndi juga wazaka zapakati pa 18, asanachitike zizindikiro za HD. Kafukufuku wina wofufuzira sanafotokoze za nkhaniyi, ngakhale kuti kupanga zisankho molakwika, kusankha pachiwopsezo, komanso kuweruzidwa koyipa kwawonetsedwa kuti zikuika pachiwopsezo kwa odwala HD omwe amasankha zofunikira pamoyo ndi zochitika zachuma (Klitzman et al., 2007; Shannon, 2011). Momwemonso, malipoti pazinthu zokhudzana monga kugwiritsa ntchito mankhwala osokoneza bongo komanso kugwiritsa ntchito mankhwala osokoneza bongo pa intaneti zikusowa m'mabuku apano a HD pathology. Pakadali pano, sizikudziwika ngati kusowa kwa malipoti a mavuto amtundu wa juga m'mabuku a HD kwachitika chifukwa cha kusayang'anira izi, kapena ngati kulibe kutchuluka kwa njuga pakati pa odwala HD. Zifukwa zingapo zimalongosola chifukwa chake zovuta zotere sizinanenedwe pafupipafupi. Choyamba, ngakhale kuchuluka kwa kutchova njuga kwachulukitsidwa mu HD, izi zimangokulira odwala ochepa. Kuphatikiza ndikuti chiwerengero cha anthu okhudzidwa ndi HD chokha ndichoperewera, izi zitha kuchititsa kuti mavuto azitchova njuga asayerekezedwe ngati vuto linalake pagulu la odwala. Kachiwiri, kusowa kwa mavuto amtundu wa njuga mu HD kumatha kukhala kwokhudzana ndi kulephera kapena kusafuna kwa odwala kuchoka mnyumbamo chifukwa cha zovuta zamoto ndikuwona pafupipafupi malingaliro osonyeza chidwi komanso kukhumudwa. Asanafike pa kutchova juga pa intaneti, izi zitha kuti zidalepheretsa odwala HD kuti azikachezera malo otchova njuga monga kasino. Pomaliza, unyamata umaoneka ngati nthawi yovuta kwambiri yolimbana ndi mavuto otchova njuga (van den Bos et al., 2013a,, pomwe odwala HD ambiri samayamba kuwonetsa zofooka zokhudzana ndi disinhibition mpaka pambuyo pa moyo. Komabe, chifukwa cha zochita za achinyamata zokhudzana ndi intaneti, atha kukhala ndi machitidwe achisangalalo monga kutchova juga pa intaneti, zomwe zimayamba kukhala vuto pamene zizindikiro za HD ziwonekera pambuyo pake. Chifukwa chake, ngakhale malo omwe odwala njuga-omwe akuwoneka kuti ali pachiwonetsero mwina sanalimbikitse machitidwe otere m'mbuyomu, zikuwonekeratu kuti kupezeka kwina ndi kupezeka kwa mwayi wa njuga kunyumba kungasinthe kuchuluka kwa mavuto okhudzana ndi kuchuluka kwa HD .

Kupanga Chochita Mwangozi ndi Odwala a HD pa Ntchito Zamalonda

Ntchito zantchito nthawi zambiri zimagwiritsidwa ntchito poyesa zowoneka bwino komanso zamakhalidwe pazovuta zamitsempha. Kuti mumvetsetse momwe amathandizira ndikuchepetsa zovuta zomwe zimapangitsa kuti pakhale chisankho ndikuchita zangozi, ntchito zingapo zapangidwa, kuphatikiza IGT (Bechara et al., 1994) ndi CGT (Rogers et al., 1999). Pa IGT, ophunzira amapatsidwa makadi anayi amakhadi. Amawalangizidwa kusankha makhadi kuchokera ku ma desk awa, omwe amatha kupambana nawo kapena kutaya ndalama; cholinga cha ntchitoyi ndikupambana ndalama zambiri momwe mungathere. Zovomerezeka zimasiyana wina ndi mzake pafupipafupi komanso kuchuluka kwa zomwe amapambana komanso kutayika. Awiri mwa awa ndi ma "zoyipa", omwe amachititsa kuti zonse zitheke m'kupita kwa nthawi, ndipo ziwiri ndizabwino ", zomwe zimatsogolera phindu lonse. Ophunzirawo sanapatsidwe izi, komabe, ndipo akuyenera kudziwa kuti ndi mitundu iti yomwe imakhala yopindulitsa kwambiri pazesaku. Mwachizolowezi, athanzi, ophunzira amaphunzira bwino malamulo a ntchitoyi atatha kuchuluka kwa zitsanzo, ndipo pamapeto pake amayamba kukonda mapezowo. Komabe, pali kusiyanasiyana kwakukulu pakati pa magwiridwe antchito ngakhale pakati pa omwe atenga nawo gawo laumoyo, kuphatikiza mwachitsanzo kusiyana pakati pa zogonana (van den Bos et al., 2013b). Pa CGT, otenga nawo mbali amaperekedwa ndi mzere wamabokosi a 10 a mitundu iwiri yosiyanasiyana, ndipo akuyenera kupanga chisankho chobisika momwe bokosi lamtundu wabisika. Ayenera kubera ngongole pakudalira kwawo pa chisankhochi. Mu ntchitoyi, zidziwitso zonse zoyenera zimaperekedwa kwa omwe akutenga nawo mbali pazoyeserazi, ndipo ziyeso ndizodziyimira pawokha, motero zimachepetsa kukumbukira kukumbukira ndi kuphunzira. Ntchito zonse njuga ndizokhazikitsidwa bwino, ndipo IGT imavomerezedwa ngati njira yoyenera yopanga zisankho zenizeni (Buelow ndi Suhr, 2009,, pomwe CGT ndi yofunikira makamaka pakuwerenga popanga zisankho pokhapokha pophunzira.

Odwala a HD adayesedwa pa Iowa ndi Kampasi ya Kutchova Njuga Task. Pakufufuza ndi odwala apakati pamagulu, Stout et al. (2001) anapeza kuti ntchito pa IGT idachepetsedwa poyerekeza ndi maphunziro wamba. Kusiyana kwa magwiridwe antchito kunawonekera gawo lachiwiri la ntchitoyi; komwe maphunziro nthawi zambiri amayamba kuwonetsa zokonda za madigiri abwino, odwala HD amapitilizabe kusankhapo zina zoyipa. Izi zikusonyeza kuti odwala HD mwina sanaphunzire kuti ndi ma desiki ati omwe anali opindulitsa, kapena anapitiliza kusankha makhadi pamalo oyipa ngakhale atadziwa izi. Olembawo adazindikira kuti ambiri mwa omwe adachita nawo gawo la HD adawonetsa kuti amadziwa kuti madekitala ena anali ovuta, komabe akupitilizabe kusankha makhadi pamiyalayo, kuwonetsa kuti odwala HD amatha kuphunzira malamulo a ntchitoyi, koma sangathe kukhazikitsa njira yabwino yosankhira kuyankha pa zilango za aliyense payekha komanso mphotho yake. Komabe, kugwiritsidwa ntchito kochepetsetsa kunapezeka kuti kumakhudzana ndi kukumbukira kukumbukira ndi malingaliro, zomwe zimapangitsa olemba kulingalira kuti odwala HD sangakhale ndi vuto lophunzira kapena kukumbukira zotsatira zazitali zosankha makadi kuchokera pagulu linalake. Odwala a HD nawonso adakwera kwambiri pochotsa ma disinhibition kuposa zowongolera zathanzi, koma izi sizinaphatikizidwe ndi magwiridwe antchito. Potsatira njira yomweyo Stout ndi anzawo, ndikufanizira mitundu itatu yamaganizidwe ofotokozera kufooka kwa odwala HD, ndipo adapeza kuti izi zidafotokozedwa bwino ndikusokonekera pakukumbukira ndikuwonjezeranso kusasamala ndi kusakhudzidwa (Busemeyer ndi Stout, 2002). Kuyipa kwa odwala HD pa IGT kungakhalenso kokhudzana ndi kuchepetsedwa kwa kutayika kwa odwalawa, komwe kumapezeka poyesa mayendedwe apakhungu pakhungu la IGT (Campbell et al., 2004). Kupeza kumeneku kumagwirizana ndi kuvutika kwamtunduwu kwa odwala omwe ali ndi HD (Johnson et al., 2007; Ille et al., 2011,, ndikuwonetsa kuti sangakhale omvera pazachilango zazikulu, motero sangapatuke pamakalata oyipa. Makamaka gawo lachiwiri la IGT limafunikira kutha kupondereza zinthu zosafunikira poyankha kulanga, pakulimbikitsa njira zopindulitsa (de Visser et al., 2011; van den Bos et al., 2013b, 2014).

Maphunziro ena owerengeka adayesa kupanga zisankho zowopsa kumayambiriro kwa HD, koma sizinapeze zovuta pakuchita kwa odwalawa pa IGT kapena CGT (Watkins et al., 2000; Holl et al., 2013). Chifukwa chake, zikuwoneka kuti zofooka pakupanga chisankho ndi chiopsezo cha zovuta zamtundu wa juga sizimakula mpaka magawo apakati a matendawo. Komabe, maphunziro awa adapeza zovuta m'machitidwe omwe amafunikira kukonzekera ndi kulepheretsa kuyankha koyambirira kwa odwala oyambirira a HD. Zikuwoneka kuti odwala HD amayamba kukhala ndi zovuta zobisika, zoletsa, kuzindikira, kuzindikira, ndikukumbukira. Mwa odwala ena izi zimatha kubweretsa mavuto pamavuto ndi kupanga zisankho koyambirira kwa matendawa, koma odwala HD ambiri samakhala ndi zovuta posankha zochita mpaka atakwanitsa kukhala pakati.

Njira za Neurobiological Zokuchita Kupanga Ku HD

Njira zachikhalidwe za Neurobiological zomwe zimapanga chisankho chachilendo mu IGT

Njira zama neurobiological zomwe zimapangira chisankho mu IGT zaphunziridwa bwino ndikufotokozedwa (onani,. Bechara et al., 2000; Doya, 2008; de Visser et al., 2011; van den Bos et al., 2013b, 2014). Kuchita mwadongosolo ntchito imeneyi kumafunika kulumikizana pakati pa mabwalo a miyendo ndi yolumikizana / yolumikizana. Zochita mu gawo la miyendo zimaganiziridwa kuti ndizambiri pantchito yoyamba ya IGT, pomwe imakhudzidwa ndikuwunika, kuyankha mphoto ndi kulangidwa, komanso kuphunzira zofunikira pazotsatira zazifupi komanso zazitali zazisankho mu ntchito (Manes et al., 2002; Clark ndi Manes, 2004; Achinyamata ndi Farah, 2005; Gleichgerrcht et al., 2010; de Visser et al., 2011; van den Bos et al., 2014). Dera loyang'anira / lozindikira, ndizofunikira kwambiri gawo lachiwiri la IGT, pakafunika kukakamiza mayankho omvera pamalipiro ndi zilango pazopindulitsa kwa nthawi yayitali, kulimbikitsa mayendedwe opindulitsa ndikuwongolera njira zoyipa (Manes et al., 2002; Clark ndi Manes, 2004; Achinyamata ndi Farah, 2005; Gleichgerrcht et al., 2010; de Visser et al., 2011; van den Bos et al., 2014).

Zovuta za neurobiological mu IGT popanga zisankho mu HD

Popeza njira zopangira zisankho mu IGT zimaphatikizapo kulumikizana kwa mabwalo a miyendo ndi othandizira / ozindikira olimba a cortico-striatal, sizosadabwitsa kuti odwala HD ali ndi vuto lochita izi. Chimodzi mwazowonera za Stout ndi anzawo ndikuti chiwopsezo chotayika pakuchita zisankho chimachepetsedwa mwa odwala HD (Campbell et al., 2004). Izi zikugwirizana ndizotsatira kuti odwala awa amakhala ndi vuto lozindikira malingaliro osalimbikitsa, ndipo atha kufotokozedwa ndi zosokoneza mu orbitof mbeleal cortex (Ille et al., 2011). Cortex ya orbitof mbeleal ndiyofunikira pakukhudza mtima, ndipo imayendetsedwa mitu yofananira poyankha zilango ndi mphotho pakuchita chisankho (O'Doherty et al., 2001). Kupeza kwina Stout et al. (2001) ndikuti magwiridwe antchito a HD pa IGT amalumikizana ndi kuchepa kwa malingaliro ndi malingaliro a nthawi yayitali pa Mattis Dementia Rating Scale. Kulephera kuphunzira kapena kukumbukira komwe ndimadongosolo omwe amapindulitsa pakapita nthawi yayitali kumatha kuphatikizidwa ndi kuchepa kwa zochitika zamagulu ogwirizanitsa / ozindikira, omwe amafunikira kukonzekera kwanthawi yayitali komanso kuwongolera kuwongolera (Manes et al., 2002; Clark ndi Manes, 2004; Achinyamata ndi Farah, 2005; Gleichgerrcht et al., 2010). Izi zikugwirizana komanso zoperewera panjira yosakhudzika mu HD, popeza kafukufuku waposachedwa akuwonetsa kuti njira yosalunjika ndiyofunikira kuti pakumveka kuwalanga mukaphunzitsidwe kophunzitsira (Kravitz et al., 2012; Paton ndi Louie, 2012). Kusazindikira zakutsogolo zotsatira za chisankho kungayambitsenso kusokonezeka kwa vuto laling'ono la cortex, popeza vuto lofananira limawonedwa kwa odwala omwe awonongeka pamalo oyambitsawa (Bechara et al., 1994). Chifukwa chake, kuchepa kwa ntchito kwa odwala HD pa IGT kumatha kuchitika chifukwa cha kuphatikizika kwa masokosi ophatikizira a cortico-striatal omwe amakhala ndi orbitof mbeleal cortex, ventromedial prefrontal cortex ndi dorsolateral prefrontal cortex. Izi zimabweretsa kutsitsa kuyankha kumalangidwe mgawo loyamba la ntchitoyi, ndikulephera kuphunzira kuti ndi magulu ati omwe amakhala opindulitsa kwa nthawi yayitali, kulinganiza moyenera, ndikukhomerera mayankho osafunikira mu gawo lachiwiri la IGT.

Kukambirana

HD ndi Njuga ya Pathological: Zowopsa Ziti?

Kusintha kofananira kwa mawonekedwe amoto, kutengeka, komanso kuzindikira kwa HD kumachitika chifukwa cha kulimba pang'onopang'ono kwa striatal atrophy komwe kumakhudza magawo osiyanasiyana a cortico-striatal. Ngakhale kuyambika ndi kupita patsogolo kwa zikhalidwe ndi kuzindikira kumawoneka kuti ndizopambana kwambiri, magalimoto oyendetsa galimoto ndi ozindikira amathandizidwadi kumayambiriro kwa matendawo, pomwe ma limbic circ amakhudzidwa pambuyo pake. Chosangalatsa ndichakuti kudziwika kwa mitsempha ya juga ya pathological ndi zikhalidwe zina zimaphatikizapo kusokonezeka m'mabwalo amodzi a cortico-striatal omwe amakhudzidwa ndi HD. Ngakhale izi ndizofanana, komabe, m'mabuku azachipatala HD sinakhale yogwirizana ndi njuga zamatsenga kapena machitidwe ena osokoneza bongo. Kafukufuku amodzi yekha mpaka pano wafotokoza banja lomwe mavutidwe a juga adachitika m'mabanja angapo okhudzidwa ndi HD (De Marchi et al., 1998). Timalingalira kuti zizindikiro zamagalimoto a odwala, komanso zaka zawo komanso malo omwe amakhala, zingakhale kuti zawalepheretsa kuyamba njuga, ngakhale atakhala otanganidwa kwambiri ndi zovuta zotere. Kumbali ina, kuvutika maganizo komwe kumapezeka kawirikawiri kumayembekezeredwa kukulitsa kukhudzidwa ndi chiwopsezo cha mavuto a njuga, kutengera maphunziro a kulumikizana (Clarke, 2006). Kulongosola kwinanso kwa kusawona kwa mavuto amtundu wa juga mu HD kungakhale kokhudzana ndi kusiyanasiyana komwe kumayambitsa ma neuropathology. Ngakhale kusokonezeka kwamphamvu kukuwoneka kofanana kwambiri pakati pa otchova njuga ndi odwala HD, kusintha kwamalingaliro ndikofanana. Ochita juga pazakuwonetseratu amawonetsa chidwi chochulukirapo cha mphotho, kuwalimbikitsa kuti ayambe ndikupitiliza kutchova juga. HD, kumbali ina, yalumikizidwa ndi kuchepa kwakumvera kwa zilango ndi malingaliro osalimbikitsa. Kusiyanaku kungakhale chifukwa chofunikira kwambiri choti odwala HD sikuwoneka kuti ali ndi chizolowezi chowonjezereka choyambira kutchova juga kapena kuchita zina zabwino.

Komabe, kusokonezeka mu gawo lamankhwala olimbitsa thupi a odwala a HD kungalimbikitse kupanga zisankho zowopsa pamavuto osatsimikizika, monga akuwonetsera ku IGT (Doya, 2008). Kuphatikiza apo, kuphatikizidwa kwa chidwi chakuchepa kwa kulangidwa, kulephera kuyimitsa mayankho okakamizidwa kumalipiro aposachedwa, komanso kulephera kulingalira mphotho zomwe zikuchedwa kuyambiranso kwakanthawi ndikupangitsa njira zabwino zikhalidwe moyenera, zimapangitsa kuti odwala HD akakhale ndi mavuto otchova njuga, akakumana ndi mkhalidwe womwe umalimbikitsa izi. Mavuto amtundu wa odwala HD omwe akusunthika kwazomwe zimachitika komanso zizindikiro za kusakhazikika kwa chidziwitso komanso kupirira kwake zimathandizira pakukula kwa zochita zamatenda munthawi zonsezi. Chifukwa chake, tikuganiza kuti odwala HD samakhala ndi chizolowezi choyambira kutchova njuga kapena zizolowezi zina zokhudzana ndi mitsempha yawo, koma kuti atha kukhala pachiwopsezo chokhala ndi chizolowezi akangoyamba kuchita njuga. Malinga ndi lingaliroli, zinaonedwa kuti odwala am'maso amadzala amakhala othamangitsidwa ndipo nthawi zambiri amasankha zosayenera, koma osawonetsa chikhalidwe chowopsa (Miller, 1992; Bechara et al., 2000). Izi zikusonyeza kuti kupanga zisankho mosavutikira kapena kuchitapo chiwerewere sizimachitika palimodzi, komanso kuti kusokonezeka kwa miyambo yolumikizana / yolumikizana / yolumikizana kungakhale ndi zotsatira zosiyana pakupanga zisankho zowopsa ndi machitidwe a njuga. Zongoganizira zathu zithandizanso kufotokozera chifukwa chake odwala HD sanaonedwe kuti azichita zoyipa kwambiri pa CGT. Popeza chidziwitso chonse chokhudzana ndi mwayi komanso phindu la kupambana ndi kutayika chikupezeka patsogolo pantchito imeneyi, odwala HD sangakhale ndi njira zowonongeka, chifukwa sakufunafuna zovuta. Komabe, izi zidzafunika kuyesedwa mwa odwala omwe ali ndi matenda opita patsogolo.

Ngati odwala HD alidi ndi chiwopsezo chowonjezereka cha kukhala ndi vuto la kutchova njuga akaperekedwe ndi zomwe zili zoyenera, kukwera kwa mwayi wotchova njuga kwa intaneti kungakhale pachiwopsezo cha gulu la odwala. Ngakhale sadzafunafuna machitidwe amenewa, odwala HD tsopano ali ndi mwayi wopeza njuga kuposa momwe adalili kale. Izi ndizofunikira kwambiri kwa odwala omwe amakhala nthawi yayitali kunyumba chifukwa cha zizindikiro zawo, komwe intaneti ingakhale njira yofunika kukhalira. Kuthekera kwakukulu kokuchita njuga kungayambitse kuchuluka kwakukuru mu zovuta za HD. Tikupangira kuti osamalira ayenera kudziwa za ngozi zomwe zingachitike, ndipo makamaka yesani kuletsa odwala HD kuchita nawo (pa intaneti) njuga. Komanso, tikuti azachipatala azisanthula pafupipafupi kuchuluka kwa zovuta zokhudzana ndi kutchova njuga kwa anthu a HD, kuti athe kupereka chithandizo choyenera ndi chitsogozo kwa odwala ndi osamalira.

Malangizo Otsogolera

Kuphatikiza pa maphunziro a miliri kuti ayese kufalikira kwa kutchova juga kwa matenda a m'magazi komanso zina mu HD, kafukufuku wazomwe angatithandizire kukulitsa kamvedwe kathu pazomwe tafotokozazi. Choyamba, zingakhale zosangalatsa kuphatikiza zoperewera pa IGT mwachindunji pakusokoneza zochitika za cortico-striatal mu HD odwala. Kufikira izi, ma ubongo a odwala omwe ali ndi HD amatha kuwerengera momwe mungagwiritsire ntchito zamagetsi pogwiritsa ntchito IGT, ndikufanizira zochitika zambiri. Zochita mu striatum, dorsolateral prefrontal cortex ndi orbitofrontal cortex zikuyembekezeka kuchepetsedwa mwa odwala HD posankha zochita pa IGT.

Kuti muwerenge zamachitidwe azinthu zamtundu wa njuga mu HD mwatsatanetsatane, zitsanzo za matenda omwe ali ndi makoswe zitha kugwiritsidwa ntchito. Pamakhalidwe, nyama izi zitha kuyembekezeredwa kuwonetsa kuchepa kwa IGT, yofanana ndi odwala. Mitundu ya Rodent ya IGT ikupezeka (onaninso: de Visser et al., 2011) komanso kuphatikizidwa kwa mitundu yosiyanasiyana ya ma neuronal m'mitundu iyi amadziwika bwino (de Visser et al., 2011; van den Bos et al., 2013a, 2014). Chifukwa chake, kuyesa koteroko ndi kotheka, ndipo kungaphatikizidwe ndikuwunika mozama kusinthika kwapakati pa kusintha kwa mitsempha mumitundu yapamwamba ya HD pogwiritsa ntchito njira zosiyanasiyana. Kuphatikiza apo, pofika njira zambiri zofufuzira zachilengedwe zatsopano komanso zida zowunikira zomwe zikuchitika, chiopsezo chakukula kwa njuga titha kuphunzitsidwa pansi pa (chilengedwe) cha anthu ndi nyama (van den Bos et al., 2013a). Pamodzi, maphunziro awa a zokhudzana ndi kutchova juga komanso ma neuropathology omwe ali m'magulu onse awanthu ndi nyama za HD atipatsa kumvetsetsa bwino za ngozi zomwe zili zokhudzana ndi kutchova juga komanso machitidwe ena osokoneza bongo mu HD, ndikuwongolera kuthekera kwathu kupereka chithandizo choyenera ndi chitsogozo.

Kutsutsana kwa Chidwi

Olembawo akunena kuti kufufuza kunkachitika popanda mgwirizano uliwonse wa zamalonda kapena zachuma zomwe zingatengedwe kuti zingatheke kukangana.

Zothandizira

Lolembedwa ndi:

Patrick Anselme, University of Liège, Belgium

Kuwunikira by:

Damien Brevers, Université Libre de Bruxelles, Belgium
Bryan F. Singer, University of Michigan, USA