Computer vision-aided locomotor behavioral analysis identifies therapeutic motor signatures in a mouse model of Huntington disease

Authors

Du, L., Wang, Z., Wu, Q., Liu, H., Bavkar, A., Zhou, Y., Shi, Y., Lim, L. A., Guo, J., Qin, Z., Ross, C. A., Duan, W.

Abstract

Huntington disease (HD) is a neurodegenerative disorder characterized by progressive motor dysfunction. Traditional open-field tests quantify spontaneous locomotor parameters; however, fine mouse motor signatures, particularly disease stage-specific changes in HD motor symptoms and pharmacodynamic responses to therapeutic treatments. Here, we employed a computer vision-aided behavioral flow analysis designed to quantify fine, HD-relevant motor dysfunction in the zQ175DN HD mouse model, ranging from early HD-like motor signatures to well-defined motor deficits. Markerless pose estimation and Keypoint-MoSeq segmented standard top-view open-field recordings into recurrent behavioral syllables, which were then organized into higher-order clusters and transition networks. Disease stage-dependent changes in syllable occurrence, syllable duration, behavioral-state composition, and transition structure were identified. These analyses are not possible with traditional open-field assays. Syllable-duration features provided the strongest genotype discrimination, and HD-like motor features were also characterized by hub remodeling and transition-network disorganization. These features were integrated into an HD motor dysfunction (HDMD) score based on age- or HD progress-matched wild-type (WT) -standardized absolute deviations. The HDMD score distinguished HD mice from WT across multiple symptomatic stages and correlated with HD pathology and disease severity. Effect-size and power analyses suggested improved efficiency for detecting potential therapeutic effects. This framework requires only standard top-view recordings and may also support retrospective analysis of existing open-field video datasets. Overall, the HDMD framework provides a practical strategy for identifying fine motor changes in HD mice, aiding study design and preclinical efficacy assessment in HD drug development.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Sep 2026.

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