BACKGROUND: THE ROLE OF EMOTION IS CRUCIAL TO THE LEARNING PROCESS, AS IT IS LINKED TO MOTIVATION, INTEREST, AND ATTENTION. AFFECTIVE STATES ARE EXPRESSED IN THE BRAIN AND IN OVERALL BIOLOGICAL ACTIVITY. BIOSIGNALS, LIKE HEART RATE (HR), ELECTRODERMAL ACTIVITY (EDA), AND ELECTROENCEPHALOGRAPHY (EEG) ARE PHYSIOLOGICAL EXPRESSIONS AFFECTED BY EMOTIONAL STATE. ANALYZING THESE BIOSIGNAL RECORDINGS CAN POINT TO A PERSON'S EMOTIONAL STATE. CONTEMPORARY MEDICAL EDUCATION HAS PROGRESSED EXTENSIVELY TOWARDS DIVERSE LEARNING RESOURCES USING VIRTUAL REALITY (VR) AND MIXED REALITY (MR) APPLICATIONS. OBJECTIVE: THIS PAPER AIMS TO STUDY THE EFFICACY OF WEARABLE BIOSENSORS FOR AFFECT DETECTION IN A LEARNING PROCESS INVOLVING A SERIOUS GAME IN THE MICROSOFT HOLOLENS VR/MR PLATFORM. METHODS: A WEARABLE ARRAY OF SENSORS RECORDING HR, EDA, AND EEG SIGNALS WAS DEPLOYED DURING 2 EDUCATIONAL ACTIVITIES CONDUCTED BY 11 PARTICIPANTS OF DIVERSE EDUCATIONAL LEVEL (UNDERGRADUATE, POSTGRADUATE, AND SPECIALIST NEUROSURGEON DOCTORS). THE FIRST SCENARIO WAS A CONVENTIONAL VIRTUAL PATIENT CASE USED FOR ESTABLISHING THE PERSONAL BIOSIGNAL BASELINES FOR THE PARTICIPANT. THE SECOND WAS A CASE IN A VR/MR ENVIRONMENT REGARDING NEUROANATOMY. THE AFFECTIVE MEASURES THAT WE RECORDED WERE EEG (THETA/BETA RATIO AND ALPHA RHYTHM), HR, AND EDA. RESULTS: RESULTS WERE RECORDED AND AGGREGATED ACROSS ALL 3 GROUPS. AVERAGE EEG RATIOS OF THE VIRTUAL PATIENT (VP) VERSUS THE MR SERIOUS GAME CASES WERE RECORDED AT 3.49 (SD 0.82) VERSUS 3.23 (SD 0.94) FOR STUDENTS, 2.59 (SD 0.96) VERSUS 2.90 (SD 1.78) FOR NEUROSURGEONS, AND 2.33 (SD 0.26) VERSUS 2.56 (SD 0.62) FOR POSTGRADUATE MEDICAL STUDENTS. AVERAGE ALPHA RHYTHM OF THE VP VERSUS THE MR SERIOUS GAME CASES WERE RECORDED AT 7.77 (SD 1.62) MU V VERSUS 8.42 (SD 2.56) MU V FOR STUDENTS, 7.03 (SD 2.19) MU V VERSUS 7.15 (SD 1.86) MU V FOR NEUROSURGEONS, AND 11.84 (SD 6.15) MU V VERSUS 9.55 (SD 3.12) MU V FOR POSTGRADUATE MEDICAL STUDENTS. AVERAGE HR OF THE VP VERSUS THE MR SERIOUS GAME CASES WERE RECORDED AT 87 (SD 13) VERSUS 86 (SD 12) BPM FOR STUDENTS, 81 (SD 7) VERSUS 83 (SD 7) BPM FOR NEUROSURGEONS, AND 81 (SD 7) VERSUS 77 (SD 6) BPM FOR POSTGRADUATE MEDICAL STUDENTS. AVERAGE EDA OF THE VP VERSUS THE MR SERIOUS GAME CASES WERE RECORDED AT 1.198 (SD 1.467) MU S VERSUS 4.097 (SD 2.79) MU S FOR STUDENTS, 1.890 (SD 2.269) MU S VERSUS 5.407 (SD 5.391) MU S FOR NEUROSURGEONS, AND 0.739 (SD 0.509) MU S VERSUS 2.498 (SD 1.72) MU S FOR POSTGRADUATE MEDICAL STUDENTS. THE VARIATIONS OF THESE METRICS HAVE BEEN CORRELATED WITH EXISTING THEORETICAL INTERPRETATIONS REGARDING EDUCATIONALLY RELEVANT AFFECTIVE ANALYTICS, SUCH AS ENGAGEMENT AND EDUCATIONAL FOCUS. CONCLUSIONS: THESE RESULTS DEMONSTRATE THAT THIS NOVEL SENSOR CONFIGURATION CAN LEAD TO CREDIBLE AFFECTIVE STATE DETECTION AND CAN BE USED IN PLATFORMS LIKE INTELLIGENT TUTORING SYSTEMS FOR PROVIDING REAL-TIME, EVIDENCE-BASED, AFFECTIVE LEARNING ANALYTICS USING VR/MR-DEPLOYED MEDICAL EDUCATION RESOURCES.