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Aberrant striatal value representation in Huntington’s disease gene carriers 25 years before onset

Nair, A; Johnson, EB; Gregory, S; Osborne-Crowley, K; Zeun, P; Scahill, RI; Lowe, J; ... Tabrizi, SJ; + view all (2021) Aberrant striatal value representation in Huntington’s disease gene carriers 25 years before onset. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 10.1016/j.bpsc.2020.12.015. (In press). Green open access

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Abstract

BACKGROUND: In this study, we asked whether differences in striatal activity during a reinforcement learning (RL) task with gain and loss domains could be one of the earliest functional imaging features associated with carrying the Huntington's disease (HD) gene. Based on previous work, we hypothesized that HD gene carriers would show either neural or behavioral asymmetry between gain and loss learning. METHODS: We recruited 35 HD gene carriers, expected to demonstrate onset of motor symptoms in an average of 26 years, and 35 well-matched gene-negative control subjects. Participants were placed in a functional magnetic resonance imaging scanner, where they completed an RL task in which they were required to learn to choose between abstract stimuli with the aim of gaining rewards and avoiding losses. Task behavior was modeled using an RL model, and variables from this model were used to probe functional magnetic resonance imaging data. RESULTS: In comparison with well-matched control subjects, gene carriers more than 25 years from motor onset showed exaggerated striatal responses to gain-predicting stimuli compared with loss-predicting stimuli (p = .002) in our RL task. Using computational analysis, we also found group differences in striatal representation of stimulus value (p = .0004). We found no group differences in behavior, cognitive scores, or caudate volumes. CONCLUSIONS: Behaviorally, gene carriers 9 years from predicted onset have been shown to learn better from gains than from losses. Our data suggest that a window exists in which HD-related functional neural changes are detectable long before associated behavioral change and 25 years before predicted motor onset. These represent the earliest functional imaging differences between HD gene carriers and control subjects.

Type: Article
Title: Aberrant striatal value representation in Huntington’s disease gene carriers 25 years before onset
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bpsc.2020.12.015
Publisher version: https://doi.org/10.1016/j.bpsc.2020.12.015
Language: English
Additional information: © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).
Keywords: computational psychiatry, Huntington’s, striatum, learning, value, neuroimaging
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10119249
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