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Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Mild cognitive impairment in Parkinson's disease (PD-MCI) can affect several cognitive domains, including attention, working memory, executive functions, language, visuospatial skills, and episodic memory, resulting in a progressive reduction of autonomy and an increased risk of dementia. Cognitive training may help preserve cognitive abilities, especially when supported by innovative tools; nevertheless, standardized and engaging interventions are still lacking. The OPERA project aims to develop and evaluate the usability of PRoBio, a novel bio-cooperative platform that integrates virtual reality (VR), robotic assistance and physiological monitoring to deliver personalized cognitive rehabilitation for individuals with PD-MCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      The OPERA project is a 13-months non-profit, multicentre clinical investigation structured in four phases. Phase 1 (month 2): focus group, involving 23 participants (10 people with PD (PwPD), 5 caregivers, 8 healthcare professionals) to explore usability, expectations and rehabilitation needs. Phase 2 (months 2\u20137): development of the PRoBio platform, by integrating the \u201cVirtual Reality Rehabilitation System\u201d (VRRS, by Khymeia Group) with the TIAGo robot (by PAL Robotics) to deliver personalized exercises to patients' cognitive profiles, while also monitoring their emotional and physiological state. Phase 3 (month 6): two living labs involving a total of 21 healthy subjects (13 volunteers and 8 rehabilitation professionals) to assess PRoBio's usability in a real setting, with emotional data collection and standardized usability questionnaires completion after use. Phase 4 (months 8\u201312): usability study assessing PRoBio's usability as the primary objective, involving 10 PD-MCI patients completing a 4-week cognitive rehabilitation program with pre\/post clinical and neuropsychological assessments. Descriptive statistics and appropriate inferential tests (parametric or non-parametric) will be applied to usability data, pre\/post intervention clinical measures, and physiological and performance data registered by the PRoBio platform (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The present paper presents the methodological framework of the OPERA project, which brings together partners with complementary expertise to develop and evaluate the PRoBio platform, a novel bio-cooperative system for cognitive rehabilitation in patients with PD-MCI. By integrating VR, robotics and physiological feedback, PRoBio aims to enable personalized, adaptive interventions, offering a more engaging alternative to traditional rehabilitation approaches while advancing research in bidirectional human\u2013robot interaction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1680215","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T05:56:08Z","timestamp":1769406968000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated bio-cooperative robotic platform for virtual cognitive training in Parkinson's disease: design and methodology of the OPERA project"],"prefix":"10.3389","volume":"16","author":[{"given":"Cristina","family":"Polito","sequence":"first","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Don Carlo Gnocchi","place":["Florence, 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