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This experimental study focused on enriching practice-rooted teacher learning with artificial intelligence (AI)-powered virtual agents and learning support in virtual reality (VR) simulation-based learning. We investigated the impacts of model-based support (an integrative approach to designing learning support) and AI-powered virtual agents in simulation-based learning on preservice teachers’ teaching knowledge and skills and teaching self-efficacy. We collected pre- and post-intervention data from 57 preservice teacher participants. The results suggested that 1) there was a significant impact of model-based support and AI-powered virtual agents on preservice teachers’ teaching knowledge and skills; 2) there was no significant impact between experimental and control groups on preservice teachers’ self-efficacy; but model-based support group’s pre and post improvement was observed to be significant.