A Computational Cognitive Biomarker for Early-Stage Huntington’s Disease

Abstract

Huntington's disease (HD) is genetically determined but with variability in symptom onset, leading to uncertainty as to when pharmacological intervention should be initiated. Here we take a computational approach based on neurocognitive phenotyping, computational modeling, and classification, in an effort to provide quantitative predictors of HD before symptom onset. A large sample of subjects-consisting of both pre-manifest individuals carrying the HD mutation (pre-HD), and early symptomatic-as well as healthy controls performed the antisaccade conflict task, which requires executive control and response inhibition. While symptomatic HD subjects differed substantially from controls in behavioral measures [reaction time (RT) and error rates], there was no such clear behavioral differences in pre-HD. RT distributions and error rates were fit with an accumulator-based model which summarizes the computational processes involved and which are related to identified mechanisms in more detailed neural models of prefrontal cortex and basal ganglia. Classification based on fitted model parameters revealed a key parameter related to executive control differentiated pre-HD from controls, whereas the response inhibition parameter declined only after symptom onset. These findings demonstrate the utility of computational approaches for classification and prediction of brain disorders, and provide clues as to the underlying neural mechanisms.

DOI: 10.1371/journal.pone.0148409

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@inproceedings{Wiecki2016ACC, title={A Computational Cognitive Biomarker for Early-Stage Huntington’s Disease}, author={Thomas V. Wiecki and Chrystalina A. Antoniades and Alexander Stevenson and Christopher Kennard and Beth Borowsky and Gail Owen and Blair R. Leavitt and Raymund Roos and Alexandra Durr and Sarah J. Tabrizi and Michael J. Frank and Daniel Durstewitz}, booktitle={PloS one}, year={2016} }