title: Reversal learning reveals cognitive deficits and altered prediction error encoding in the ventral striatum in Huntington's disease.
abstract: 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.
authors.affiliation: Department of Neuropsychiatry, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany.|Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.|Fliedner Klinik Berlin, 10117, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Nickchen
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.|Center for Social and Affective Neuroscience, Linköping University, 58245, Linköping, Sweden.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Boehme
authors.affiliation: Department of Neuropsychiatry, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Mar Amador
authors.affiliation: Department of Neuropsychiatry, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Hälbig
authors.affiliation: Department of Neuropsychiatry, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany.|Department of Neurology, Helios Klinikum Bad Saarow, 15526, Bad Saarow, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Dehnicke
authors.affiliation: Department of Neuropsychiatry, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany.|Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Panneck
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.|Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School Brandenburg - Campus Neuruppin, 16816, Neuruppin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Behr
authors.affiliation: Department of Neurology, Helios Klinikum Bad Saarow, 15526, Bad Saarow, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Prass
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.|Max-Planck-Fellow-Group Cognitive and Affective Control of Behavioral Adaptation, Max-Planck-Institute for Human Cognitive and Brain Sciences, 04103, Leipzig, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Deserno
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany.|Max-Planck-Fellow-Group Cognitive and Affective Control of Behavioral Adaptation, Max-Planck-Institute for Human Cognitive and Brain Sciences, 04103, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schlagenhauf
authors.affiliation: Department of Neuropsychiatry, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), Charitéplatz 1, 10117, Berlin, Germany. josef.priller@charite.de.|Department of Psychiatry and Psychotherapy, Charité -Universitätsmedizin Berlin (Charité Campus Mitte), 10117, Berlin, Germany. josef.priller@charite.de.|Cluster of Excellence NeuroCure, BIH and DZNE, 10117, Berlin, Germany. josef.priller@charite.de.
authors.forename: Josef
authors.identifier: http://orcid.org/0000-0001-7596-0979
authors.initials: J
authors.lastname: Priller
mesh_terms: D000328:Adult; D000465:Algorithms; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015331:Cohort Studies; D003198:Computer Simulation; D018450:Disease Progression; D005260:Female; D007839:Functional Laterality; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011337:Probability Learning; D012193:Reversal Learning / Q000502:physiology*; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology*
keywords: Gray matter density; Huntington’s disease; Reinforcement learning; Ventral striatum