Reversal learning reveals cognitive deficits and altered prediction error encoding in the ventral striatum in Huntington’s disease
Huntington’s disease (HD) is an autosomal dominant neurodegenerative condition characterized by a triad of movement disorder, neuropsychiatric symptoms and cognitive deficits. The striatum is particularly vulnerable to the effects of mutant huntingtin, and cell loss can already be found in presymptomatic stages. Since the striatum is well known for its role in reinforcement learning, we hypothesized to find altered behavioral and neural responses in HD patients in a probabilistic reinforcement learning task performed during functional magnetic resonance imaging. We studied 24 HD patients without central nervous system (CNS)-active medication and 25 healthy controls. Twenty HD patients and 24 healthy controls were able to complete the task. Computational modeling was used to calculate prediction error values and estimate individual parameters. We observed that gray matter density and prediction error signals during the learning task were related to disease stage. HD patients in advanced disease stages appear to use a less complex strategy in the reversal learning task. In contrast, HD patients in early disease stages show intact encoding of learning signals in the degenerating left ventral striatum. This effect appears to be lost with disease progression.
KeywordsHuntington’s disease Reinforcement learning Ventral striatum Gray matter density
We wish to thank Dirk Lang for help with pilot experiments. This work was supported by grants from the Cluster of Excellence NeuroCure (to J.P.). R.B. received funding by the Deutsche Forschungsgemeinschaft (GRK-1123). The funding sources were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Compliance with ethical standards
Conflict of interest
Katharina Nickchen, Rebecca Boehme, Maria del Mar Amador, Thomas D. Hälbig, Katharina Dehnicke, Patricia Panneck, Joachim Behr, Konstantin Prass, Andreas Heinz, Lorenz Deserno, Florian Schlagenhauf and Josef Priller declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all participants for being included in the study.
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