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In the human basal ganglia, these dysfunctions are accompanied by a loss of striatal medium spiny neurons, dysfunctions of the subthalamic nucleus and globus pallidus, and changes in dopamine receptor binding. Here, we used a neuro\u2010computational model to investigate which of these basal ganglia dysfunctions can explain patients\u2019 deficits in different stimulus\u2013response learning paradigms. We show that these paradigms are particularly suitable for scrutinising the effects of potential changes in dopamine signaling and of potential basal ganglia lesions on overt behavior in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>. We find that combined lesions of direct and indirect basal ganglia pathways, but none of these lesions alone, reproduce patients\u2019 learning impairments. Degeneration of medium spiny neurons of the direct pathway accounts for patients\u2019 deficits in facilitating correct responses, whereas degeneration of indirect pathway medium spiny neurons explains their impairments in inhibiting dominant but incorrect responses. The empirical results cannot be explained by lesions of the subthalamic nucleus, which is part of the hyperdirect pathway, or by changes in dopamine levels. Overall, our simulations suggest combined lesions of direct and indirect pathways as a major source of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> patients\u2019 learning impairments and, tentatively, also their motor and cognitive deficits in general, whereas changes in dopamine levels are suggested to not be causally related to patients\u2019 impairments.<\/jats:p>","DOI":"10.1111\/ejn.12868","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T10:49:34Z","timestamp":1426502974000},"page":"1227-1244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Combined lesions of direct and indirect basal ganglia pathways but not changes in dopamine levels explain learning deficits in patients with Huntington's disease"],"prefix":"10.1111","volume":"41","author":[{"given":"Henning","family":"Schroll","sequence":"first","affiliation":[{"name":"Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Bernstein Center for Computational Neuroscience Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Psychology Humboldt Universit\u00e4t zu Berlin Berlin Germany"},{"name":"Computer Science Chemnitz University of Technology Stra\u00dfe der Nationen 62 09111 Chemnitz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beste","sequence":"additional","affiliation":[{"name":"Cognitive Neurophysiology Department of Child and Adolescent Psychiatry Faculty of Medicine of the TU Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred H.","family":"Hamker","sequence":"additional","affiliation":[{"name":"Bernstein Center for Computational Neuroscience Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Computer Science Chemnitz University of Technology Stra\u00dfe der Nationen 62 09111 Chemnitz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90074-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310412"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)62678-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2010.00134.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2011.00046"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.6.2085"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.05.040"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.12.2207"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001263"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2007.12.008"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01152.2007"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"11695","DOI":"10.1523\/JNEUROSCI.2659-08.2008","article-title":"Increased cognitive functioning in symptomatic Huntington's disease as revealed by behavioral and event\u2010related potential indices of auditory sensory memory and attention","volume":"28","author":"Beste C.","year":"2008","journal-title":"J. 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