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bioRxiv · 10.1101/2025.11.17.688777

Prenatal valproic acid-exposed autism marmosets increase mutual gaze and reduce inter-individual distance during dyadic social interactions

Nakamura, M.·Sato, T.·Kurotani, T.·Sakai, K.·Hadjiev, A. M.·Sasai, S.·Mimura, K.·Kawai, N.·Shimmura, T.·Ichinohe, N.
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Abstract

Autism spectrum disorder (ASD) is associated with differences in social interaction, including alterations in gaze behavior and interpersonal distance. Although most assessments of ASD remain individual-centric, emerging human studies indicate that social difficulties may arise from atypical dyadic coordination rather than from reduced social interest alone. We examined dyadic coordination in a non-human primate model of ASD, focusing on gaze and inter-individual distance during minimally constrained first encounters between prenatal valproic acid-exposed marmosets (VPA) and unexposed conspecifics (UE). Markerless pose estimation quantified frame-by-frame gaze direction and spacing, comparing VPA-UE with UE-UE dyads. VPA-UE pairs exhibited a higher proportion of mutual-gaze events than UE-UE pairs. VPA individuals showed more rapid looks in response to the partners gaze, yet spent less time looking at the partner when unobserved. VPA-UE dyads maintained shorter inter-individual distances than UE-UE dyads, and closer spacing was associated with decreased stability of mutual gaze. These findings reveal a dyadic coordination pattern in VPA-UE pairs, with rapid responsiveness coupled with distance-dependent fragility, paralleling features reported in human ASD. Our dyad-centric, markerless framework yields ecologically grounded readouts and potential intervention targets that leverage intact social responsiveness while accommodating altered spatial coordination.

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Nakamura, M., Sato, T., Kurotani, T., Sakai, K., Hadjiev, A. M., Sasai, S., Mimura, K., Kawai, N., Shimmura, T., Ichinohe, N.. 2025-11-18. Prenatal valproic acid-exposed autism marmosets increase mutual gaze and reduce inter-individual distance during dyadic social interactions. https://doi.org/10.1101/2025.11.17.688777

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