Combined lesions of direct and indirect basal ganglia pathways but not changes in dopamine levels explain learning deficits in patients with Huntington's disease

The European Journal of Neuroscience
Henning SchrollFred H Hamker

Abstract

Huntington's disease (HD) is a hereditary neurodegenerative disease of the basal ganglia that causes severe motor, cognitive and emotional dysfunctions. 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-computational model to investigate which of these basal ganglia dysfunctions can explain patients' deficits in different stimulus-response 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 HD. We find that combined lesions of direct and indirect basal ganglia pathways, but none of these lesions alone, reproduce patients' learning impairments. Degeneration of medium spiny neurons of the direct pathway accounts for patients' 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...Continue Reading

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Citations

Jul 10, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Henning Schroll, Fred H Hamker
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Jul 28, 2021·Neural Networks : the Official Journal of the International Neural Network Society·Oliver MaithFred H Hamker

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